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Utskriftsdato (5.12.2020)

Intraspinal tumors

The term spinal canal refers to the canal from the large skull opening (foramen magnum) to the tail bone (coccyx). The term intraspinal tumors refers to all tumors in the spinal canal that emanate from the spinal cord (medulla spinalis), spinal membranes (meninges), spinal nerves and the filamental end of the spinal cord (filum terminale). The three spinal membranes that surround the spinal cord are called pia mater, the arachnoid mater and dura mater.

The tumors are defined according to anatomical localization and histology.

The most common intramedullary (in the actual spinal cord) types of tumor are:

  • ependymoma 
  • astrocytoma 
  • capillary hemangioblastoma 

The most common intradural/extramedullary types of tumor are:

  • Schwannoma
  • meningioma
  • neurofibroma

The most common extradural types of tumor are:

  • metastases

The majority of extradural and intramedullary tumors are malignant, whereas over 90% of intradural/extramedullary tumors are benign.

Incidence

The incidence of primary intraspinal tumors is approximately 1.0 per 100,000 per year.

Extraspinal and intraspinal metastases from extraspinal cancers occur more frequently than primary tumors. Through the increased use of MR imaging more of these metastases are discovered and treated.

Etiology of intraspinal tumors

In the majority of cases the reasons for the development of primary intraspinal tumors are not known.

Risk factors

  • Receiving high doses of ionizing radiation is the only risk factor that can definitely be associated with the development of primary intraspinal tumors. 
  • There is no certain connection between primary intraspinal tumors and risk factors such as tobacco, alcohol and electromagnetic radiation (cell phones/microwave ovens), for example.

Histology of intraspinal tumors

Intramedullary tumors

Tumors emanating from the medulla spinalis make up around 20 % of intraspinal tumors in adults. Over 90 % of intramedullary tumors begin in glial cells, hence the term glioma. The majority of gliomas share a tendency for diffuse infiltration of the spinal cord. This limits the possibility for radical surgical treatment. It is extremely rare for these to metastasize to other organs. Ependymomas and astrocytomas are most common. Oligodendrogliomas are extremely rare in the spinal cord. Intramedullary gliomas are more common in patients with neurofibromatosis. Ependymomas are relatively common in patients with type 2 neurofibromatosis, whereas astrocytomas develop in those with type 1.

Ependymomas

The cells in the ependymomas resemble ependymal cells, and presumingly the ependymomas emanate from the ependymal cells in the central canal. These tumors make up around 60 % of intramedullary tumors, and are the most common type of intramedullary tumors in adults. The tumor is most common in the 20-30 year age group, but can occur at any age. Unlike astrocytomas, ependymomas in the spinal cord are relatively well-defined and are, therefore, more easily accessible for surgical resection.

Intramedullary ependymomas occur most often in the cervical region. 45 % affect this area only; whereas in 25 % of cases, the tumors are localized in both the cervical and upper part of the thoracic sections. In 25 % of the cases the tumor is localized in the thoracic and upper lumbar sections.

MRI of a patient with myxopapillary ependymoma. Click to enlarge the image. Optical light microscope image of a myxopapillary ependymoma. Click to enlarge the image.

In accordance with the WHO's classification, so-called myxopapillary ependymomas make up a separate entity. They differ in histological terms from ordinary ependymomas and are almost exclusively localized in the caudal cone/filum terminale region. Over 80 % of tumors in this region are myxopapillary ependymomas. These can often be radically operated.

Astrocytomas

The cells in the astrocytomas resemble astrocytes. These tumors make up around one third of all intramedullary gliomas.

Optical microscope image of pilocytic astrocytoma. Click to enlarge the image. MRI of patient with oligodendroglioma. Click to enlarge the image.

In accordance with the WHO, astrocytomas are graded from I-IV according to an increasing degree of malignancy. Grade I, so-called pilocytic astrocytomas, are often well-defined and the most low-grade variant. Grade II corresponds to low-grade astrocytomas of the fibrillary type. These two types make up around 75 % of intramedullary astrocytomas. Grade III, anaplastic astrocytomas, make up around 25 %. Only 0.2–1.5 % of astrocytomas of the spinal cord are classified as grade IV, i.e. glioblastomas. In the brain, glioblastomas make up half of all gliomas. Astrocytomas occur most often in the thoracic medulla.

Capillary hemangioblastomas

Capillary hemangioblastomas are the third most common type of intramedullary tumor.

MRI of patient with a capillary hemangioblastoma. Click to enlarge the image. Optical light microscope image of a capillary hemangioblastoma. Click to enlarge the image.

Even though such tumors are most often intramedullary (75 %), they can also be localized intradurally/extramedullarily and extradurally. The majority of capillary hemangioblastomas occur in persons under 40 years of age and are solitary.

In around 25 % of cases, this tumor is a stage of von Hippel-Lindau disease, an autosomal dominant hereditary disease. This condition should therefore be considered if the patient has multiple capillary hemangioblastomas or also has tumors in the retina, kidney, adrenal medulla, pancreas or in the inner ear.

Intradural/extramedullary tumors

Schwannomas 

Schwannomas are benign tumors that normally emanate from the sensory nerve roots. Schwannomas are the most common primary tumor in the spinal cord and make up 30 % of such cases. They can occur in all age groups, but are most common in the 30-50 year age group. Schwannomas occur equally often in men and women.

MRI of patient with Schwannoma.
Click to enlarge the image.
Optical microscope image of a Schwannoma. Click to enlarge the image.

Often the tumor emanates from parts of a sensory nerve root, and in some cases these tumors can be extirpated without destroying the entire root. Malignant transformation of Schwannomas is extremely rare. Schwannomas occur sporadically or as a stage of type 2 neurofibromatosis.

Meningiomas

11–12 % of all meningiomas occur in the spinal cord. Meningiomas are the second most common intraspinal tumor and make up 25 % of such cases. They occur in all age groups, but are most common in the 45-50 year age group. Meningiomas are more common in women than in men. This can partly be explained by the growth-stimulating effect of female hormones.

MRI of patient with meningioma.
Click to enlarge the image.
Optical microscope image of a meningioma. Click to enlarge the image.

Meningiomas emanate from arachnoidal cells. They are normally well-defined with regard to the spinal cord, surrounded by a capsule, and they push the spinal cord ahead of them during growth. The majority of meningiomas occur in the thoracic region and are found in a postereolateral location in the spinal canal. Meningiomas usually grow very slowly and 95 % of tumors are benign. Multiple mengingiomas can be a stage of type 2 neurofibromatosis. 

Neurofibromas

By definition, a neurofibroma is a benign tumor that emanates from nerves. As a rule the entire nerve root is diffusely affected and will be damaged in the event of an operation. Intraspinal neurofibromas are often a stage in type 1 neurofibromatosis (Von Recklinghausen disease). In contrast to Schwannomas, neurofibromas can undergo malignant transformation. 5–10 % of the neurofibromas that affect multiple nearby nerve roots, so-called plexiform neurofibromas, develop into a malignant peripheral nerve sheath tumor. Half of all malignant peripheral nerve sheath tumors are a stage in neurofibromatosis.

Extradural tumors

Metastases

5–15 % of all patients with cancer will experience symptom-producing spinal/epidural metastases. The primary tumor is generally localized in the chest, lungs, prostate or kidneys.

On the other hand, intradural metastases are extremely rare and make up just 1–4 % of all symptom-producing metastases in the spinal canal.

MRI of patient with a spinal/epidural metastasis. Click to enlarge the image.

Compression of the intraspinal area can occur in several ways:  intraspinal tumor growth, a compression fracture with pressure on the rear part of the vertebral body in the spinal canal, or luxation/subluxation secondary to tumor destruction. In very rare cases, intracranial tumors can metastasize into the spinal canal. In such cases the spreading has occurred through the flow of cerebrospinal fluid, and the secondary tumors are therefore located in the subarachnoidal space - so-called "drop metastases". Medullablastomas can metastasize in this manner, and one should therefore always examine the spinal canal in patients with an intracranial medullablastoma (posterior cranial fossa).

Multiple myeloma

Multiple myeloma is a malignant systemic disease that is generally localized in the bone marrow. The tumor consists of monoclonal myeloma cells that produce a pathological immunoglobulin. It is not unusual for this disease to present debut symptoms in the form of back pain and progressive neurological effects, secondary to compression of the spinal cord.

Lymphoma

The majority of spinal lymphomas affect the vertebrae or epidural space. However, intramedullary lymphomas do occur, and make up 3.3 % of all CNS lymphomas.

Staging of intraspinal tumors

The TNM classification is not used for primary intraspinal tumors. Intraspinal tumors are defined according to anatomical localization and histology.

Metastatic patterns of intraspinal tumors

Primary intraspinal tumors shows little or no tendency of hematogenous spreading. Distant metastases in other organs are therefore extremely rare.

Very occasionally, ependymomas can spread via cerebrospinal fluid and create remote metastases in the craniospinal space.

Around 5–15 % of all patients with cancer will experience symptom-producing spinal/epidural metastases. The spreading is hematogenous and the majority of spinal metastases originate from cancer of the:

  • chest
  • lung
  • prostate
  • kidney

In very rare cases, intracranial tumors can metastasize into the spinal canal. In such cases the spreading has occurred through the flow of cerebrospinal fluid, and the secondary tumors are located in the subarachnoidal space, known as "drop metastases". This applies to medullablastomas and germinomas, amongst others.

Symptoms of intraspinal tumors

The spinal canal is relatively narrow and has limited space. Thus even small intraspinal tumors can give rise to serious symptoms in the form of:
  • local spinal column pain (back pain or neck pain).
  • radiculopathy (pain radiating downward to the arms or legs that can be associated with reduced sensitivity and loss of power).
  • myelopathy (difficulty walking, motor-skill problems and reduced sensitivity in the lower extremities. Problems with urinating/emptying the bowels can also be present).
  • cauda equina syndrome (bladder and rectal paresis, impaired sexual function and reduced sensitivity in the perineal area).
  • metastatic epidural spinal cord compression (loss of power and loss of sensitivity below the level where the tumor pushes against the spinal cord).
Metastatic Epidural Spinal Cord Compression (MESCC) caused by extradural intraspinal metastases from primary tumors outside the central nervous system occur frequently, often on multiple spinal levels. Metastases will often compress the spinal cord or its terminal, and can thereby cause cauda equina syndrome and/or incomplete or complete spinal cord injury with paralysis and loss of sensitivity distal to the level of compression. Patients with MESCC require immediate examination and treatment with radiation therapy and/or surgery to prevent permanent neurological impairment.

Differential diagnoses of intraspinal tumors

  • Degenerative back problem
  • Infection (for example, tuberculosis)
  • Connective tissue disease (for example, rheumatoid arthritis)
  • Myelitis
  • Multiple sclerosis
  • Amyotrophic lateral sclerosis
  • Vascular diseases

Using advanced MR image diagnostics, it is usually possible to differentiate between the various conditions.

Prognosis of intraspinal tumors

Benign intraspinal tumors and tumors with a low grade of malignity usually have a good prognosis with prolonged survival if surgical treatment is successful.  

With regard to neurological function, the prognosis is generally better for patients with minor neurological impairment than for more pronounced spinal cord lesions.

Highly malignant tumors have a poor prognosis with rapid progression and an average survival of less than one year.

Intramedullary tumors

The majority of intramedullary tumors grow slowly, and it is normal that the patient lives for several decades after the tumor diagnosis. Patients who undergo a radical operation for ependymomas have a particularly good prognosis, whereas patients with aggressive astrocytomas in the spinal cord have a short life expectancy.

Intradural/extramedullary tumors

The prognosis after the surgical removal of meningiomas and Schwannomas is very good, and recurrence is rare.

Extradural tumors

The majority of extradural tumors are metastases. Patients, therefore, often have short life expectancy due to generalized cancer.

The aim of treatment is to maintain the patient's quality of life and neurological function.

References on intraspinal tumors

  1. Schellinger KA, Propp JM, Villano JL, McCarthy BJ. Descriptive epidemiology of primary spinal cord tumors. Neurooncol (2008) 87: 173-179
  2. Helseth E, Lied B, Lote K, Nakstad PH, Scheie D, Wester K. Intraspinale svulster i: Gjerstad L, Helseth E. Rootwelt T. Nevrologi og Nevrokirurgi. 5. utgave. Nesbru: Vett & Viten AS. 2010; 539-546.
  3. Parsa AT, Lee J, Parney IF, Weinstein P, McCormick PC, Ames C. Spinal cord and intradural-extraparenchymal spinal tumors:current best care practices and strategies. J Neuroocol. 2004;69(1–3):291–318.
  4. Conti P, Pansini G, Mouchaty H, Capuano C, Conti R. Spinal neurinomas: retrospective analysis and long-term outcome of 179 consecutively operated cases and review of the literature. Surg Neurol. 2004;61(1):34–43;discussion 44.
  5. Gottfried ON, Gluf W, Quinones-Hinojosa A, Kan P, Schmidt MH. Spinal meningeomas:surgical management and outcome. Neurosurg Focus 2003;14:Articel 2.
  6. Halvorsen CM et al. Long-term Outcome after resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases. Neurosurgery2010; 67:1622-1631
  7. Lilleeng B, Helseth E. Reseksjon av symptomatiske intraspinale meningeomer. Tidsskr Nor Legeforen. 2008;128:818-21.
  8. Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 2005;366:643–48.
  9. Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol 2008;7:459-66.
  10. Taylor JW, Schiff D. Metastatic Epidural Spinal Cord Compression. Semin Neurol 2010;30:245-253
  11. Chi JC et al. Selecting treatment for Patients With Malignant Epidural Spinal Cord Compression-Does Age Matter? Spine 2009;34:431-435
  12. Zaikova O et al. A Population-based Study of Spinal Metastatic disease in South-East Norway. Clinical Oncology 2009;21:753-759
  13. Dahlberg D et al. Minimally invasive microsurgical resection of primary, intradural spinal tumours using a tubular retraction system. Neurosurg, Early Online:1-4;DOI:10.3109/02688697.2011.644823
  14. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD

Diagnostics of intraspinal tumors

Clinical neurological examination

Findings made during clinical examination can provide indications of the localization of the tumor in the spinal canal. The examination of the somatosensory system motility, gait disturbances, coordination and reflexes must be systematically carried out.

As a rule, the clinical neurological examination also includes a general medical examination that can provide valuable additional information.

Image diagnosis

MR imaging is the most important diagnostic aid in identifying an intraspinal tumor. Examination should always include images taken before the injection of contrast fluid. Contrast fluid can result in an enhancement that may easily mask destruction of vertebrae.

CT has clear limitations in the identification of tumors in the spinal canal, as well as the fact that non-contrast enhancing tumors can easily be missed. CT scan images and skeletal X-rays are often useful for documenting the extent of skeletal destruction and possible instability.

Myelography is only carried out if the patient is unable to undergo an MRI or if paramagnetic implants make MRI dangerous.

Examination of blood, urine and cerebrospinal fluid

For the majority of intraspinal tumors, examinations of blood, urine and cerebrospinal fluid have little or no diagnostic significance.

In general patients with suspected spinal blockage should not undergo spinal puncture.

Treatment of intraspinal tumors

Relevant treatment principles

  • Surgical treatment
    • Resection/decompression
    • Internal stabilisation
  • Radiation therapy
  • Chemotherapy

Glucocorticoids

Glucocorticoids are a purely symptomatic treatment. The definitive treatment for edema around a tumor is to remove the tumor.

Intraspinal tumors are often surrounded by a significant edema in the nearby tissue which further obstructs the intraspinal space. This edema reacts well to glucocorticoids, which can lead to significant pain relief for the patient. If such an edema is present, the patient should be given glucocorticoids preoperatively.

Surgery of intraspinal tumors

Early diagnosis and treatment is of great significance for the functional result of surgical treatment.

To a great extent surgical treatment will aim for the total extirpation of the tumor. When this is not possible, one tries to achieve as comprehensive a resection as possible with regard to a good functional result.

What can be achieved by surgical treatment is determined by the degree of malignancy, the localization of the tumor and the preoperative damage that the tumor has already caused to the nerve tissue.

The spinal cord is extremely vulnerable to damage and has a limited ability to regain lost function.

Surgical access is determined by the localization of the tumor.

  • Posterior access (laminectomy, laminotomy) for tumors in posterior and lateral locations.
  • Anterior access (transabdominal, transthoracic, anterior neck) for tumors in anterior locations in the spinal canal.

If surgical access or the cancer itself cause destruction that results in a risk of axis deviation or instability, it may be necessary to use internal stabilization.

Metastatic epidural spinal cord compression

Metastatic epidural spinal cord compression (MESCC) caused by extradural intraspinal metastases from primary tumors outside the central nervous system occur frequently, often on multiple spinal levels. The metastases will often compress the spinal cord and for the cauda equina, and can thereby cause cauda equina syndrome and/or incomplete or complete spinal cord injury and loss of sensitivity distal to the level of compression. Such patients require immediate examination and treatment with radiation therapy and/or surgery to prevent permanent neurological impairment.

PROSEDYRER

Resection of intraspinal tumor

General

Before the operation, the patient should be informed of the risk of function loss in the form of reduced muscle power, loss of sensitivity and loss of natural functions.

What can be achieved by surgical treatment is determined by the degree of malignancy, the localization of the tumor and the preoperative damage that the tumor has already caused to the nerve tissue.

Surgical access is determined by the location of the tumor.

  • Posterior access (laminectomy, laminotomy) for tumors in posterior and lateral locations.
  • Anterior access (transabdominal, transthoracic, anterior neck) for tumors in anterior locations in the spinal canal.

If surgical access or the cancer itself cause destruction that results in a risk of axis deviation or instability, it may be necessary to use internal stabilization.

Ultrasound diagnosis is carried out during the operation to define the boundaries of the tumor.

Neurophysiological monitoring during the operation consists of testing nerve function in the surgical wound. This is done to prevent damage to the nerves during dissection. Through stimulation it is possible to monitor nerve function and thereby avoid dividing functional nerve structures.

Following the extirpation of the tumor, normal anatomy is reconstructed. The membranes around the spinal cord and the nerve roots are sutured to prevent leakage of spinal fluid, the spinal canal is closed and the muscles are fixed in place.

Indications

  • Tumor in the spinal canal

Goal 

  • Curative radical tumor resection
  • Relief of the nerve roots and spinal cord
  • Stabilization of the spinal column

Preparations

  • The patient is informed of the risk for function loss, both with regard to peripheral power and natural functions.
  • The patient's bowels are emptied (enema).
  • The patient is given general anesthesia.
  • The patient lies in the prone position. Pressure on the abdomen is reduced to minimize bleeding.
  • By means of radiation fluoroscopy, the skin incisions are marked.
  • Local anesthetic is injected in the skin.
  • The patient is connected for neurophysiological monitoration.

Implementation

  • An incision is made and the skin edges are pulled to the side so that the spine is revealed.
  • The paraspinal musculature is dissected from the spinal column.
  • The facet joints are dissected bilaterally.
  • A laminotomy is performed in the relevant region.
  • The processes and laminae are resected, but the lowest one is kept attached.
  • The boundaries of the tumor are defined using ultrasound techniques.
  • The dura is opened in the midline, from proximal to distal, and is then pulled to the side with sutures.
  • The function of the nerve structures is monitored during the operation to prevent nerve damage during dissection.
  • The tumor is opened in the center and decompressed using the Cavitron technique.
  • A frozen section is performed.
  • All visible tumor tissue is extirpated.
  • The operation cavity is flushed.
  • The dura is sutured. Glue is applied to the suture line to prevent CSF leak.
  • The laminae are fastened with osteosutures to normalize the anatomy.
  • A vacuum drain is inserted in the lower part of the operation area.
  • The muscles are adapted to the laminae and processes. The fascia is sutured.
  • The subcutis is sutured. The drain tube is sutured to the skin.
  • The wound edges of the skin are closed with sutures.

Follow-up

  • The patient will remain in bed for 3 days after the operation.
  • Steroids are not routinely given but this depends upon the type and localization of the tumor.
  • Antibiotics are given as infection prophylactics during the operation.
  • Postoperative thrombosis prophylactics with LMWH (low molecular weight heparin) are routinely given.
  • The sutures are removed after approximately 14 days.
  • An MRI scan is taken on the first postoperative day.
  • The patient is normally discharged to the local hospital about a week after the operation (depending on the clinical progress).
  • The patient is followed up with a clinical examination and MRI scan at 3 months and 1 year postoperatively at the hospital where the treatment was performed.

Complications in the form of neurological impairment depend on the size, location and degree of malignancy of the tumor. The duration and severity of the symptoms before the operation are also important. Therefore, there is varying need for and duration of postoperative physiotherapy.

Drug therapy of intraspinal tumors

Primary spinal tumors are minimally sensitive to cytostatic drugs. Besides preoperative symptom-relieving glucocorticoids, chemotherapy can also be appropriate for lymphomas or germinomas.

Chemotherapy directed at the primary tumor must always be considered for metastatic epidural spinal cord compression.

Radiation therapy of intraspinal tumors

Radiation therapy may supplement surgery for rare high-grade gliomas and for some subtypes of ependymoma. Radiation can also be the main treatment for spinal metastases to the subarachnoidal space from medullablastomas or germinomas. Radiation therapy for low-grade spinal astrocytomas is controversial.

In general the indication for radiation therapy for primary intraspinal tumors must be assessed on an individual basis depending on the type of tumor and expected tumor biology.

The radiation tolerance of the medulla most often limits the dose to 45–50 Gy, with a fractional dose of 1.8 Gy–2 Gy.

Metastatic epidural spinal cord compression

Metastatic epidural spinal cord compression (MESCC) caused by extradural intraspinal metastases from primary tumors outside the central nervous system occur frequently, often on multiple spinal levels. Such patients will almost always require radiation therapy, either as the only local treatment or as a supplement to primary surgery.

The total radiation dose and choice of fractional dose may vary depending on the type of tumor, but is limited by the medulla's radiation tolerance (vide supra). A normal fractional regime for radiation therapy to the extradural intraspinal metastases to the spinal column is 3 Gy x 10.

Complication treatment of intraspinal tumors

Surgery, drug therapy, and radiation therapy cause side effects to varying degrees.

It may be necessary to provide supportive care so that the patient is able to fulfill and achieve the full benefit of the planned treatment.

Supportive care can also be given to reduce side effects and improve the patient's quality of life during and after treatment.

PROSEDYRER

Treatment of Nausea Induced by Chemotherapy

General

The majorities of chemotherapy drugs are emetic to varying degrees and may cause nausea and vomiting. Today, there are efficient antiemetic drugs that can significantly reduce the side effects.

Other factors that can aggravate or prolong the presence of nausea and vomiting are: pain, anxiety, electrolyte disturbances, constipation, dyspepsia, and ulcers.

There is a distinction between acute nausea, which occurs within the first 24 hours, and late nausea, which occurs later than 24 hours after the treatment.

Acute nausea can be effectively treated with 5HT3-antagonists (ondansetron, tropisetron, palonosetron), and possibly combined with steroids. Dopamine antagonists (metoklopramid, metopimazine) also have some effect on acute nausea. If this treatment is not effective, it may be improved with aprepitant.

If standard prophylaxis and treatment of nausea is not satisfactory, other nausea regimens should be tried.

Indication

  • Nausea induced by chemotherapy drugs.

Goal

  • Prevention and treatment of nausea and vomiting.

Definitions

Chemotherapies according to emetic potential

High emetogenicity   

Group 1

Moderate emetogenicity   

 Group 2

Low/minimal emetogenicity

Group 3

All cisplatin-containing regimens (CiFu, GemCis, BEP, TIP, VIP, PV, AP, EDP, DHAP, ECX, weekly dose cisplatin, and others) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosfamide, vincristine, prokarbazine, prednisolone)
Doxorubicin/epirubicine weekly dose
Doxorubicin/ifosfamide Bendamustine
Docetaxel
FEC-60 og FEC-100
(fluorouracil, epirubicin, cyklophosfamide)
Carboplatin
ENAP (etoposide, mitoxsantrone, cytarabine, prednisolone)
ABVD (doxorubicin, bleomycin, vinblastine, dakarbazine Carboplatin/pemetrexed
FLv (fluorouracil)
FOLFIRINOX
Carboplatin/vinorelbine
FuMi (fluorouracil, mitomycin)

CHOP (cyclophosfamide, doxorubicin, vincristine, prednisolone)
Gemcitabine

CHOEP (cyclophosfamide, doxorubicin, vincristine, etoposide, prednisolone)
Methotrexate weekly dose
   Dakarbazine
Navelbine
      ECO/ACO (epirubicin/doxorubicin, cyclophosfamide, vincristine)
Paclitaxel
       EOX (epirubicin, oxaliplatin, capecitabine)
Pemetrexed
      EPOCH-F (etoposide, prednisolone, vincristine, cyclofosfamide, doxorubicin, fludarabine)

    EPOCH-F (etoposide, prednisolone, vincristine, cyclophosfamide, doxorubicin, fludarabine)
 
    FLIRI (fluorouracil, irinotecan)
 
    FLOX (fluorouracil, oxaliplatin)    
   Gemcitabine/carboplatin      
   HD-Cytarabine
   
    HD-Methotrexate    
  IGEV (ifosfamide, gemcitabine, vinorelbine)
  
   IME (ifosfamide, methotreksate, etoposide)  
   Irinotecan  
   Streptozocin  
   Vorphase (cyclophosfamide)
 

References

  1. Lehne G, Melien Ø, Bjordal K, Aas N, Mella O. Kvalme og oppkast ved cytostatikabehandling i: Dahl O, Christoffersen T, Kvaløy S, Baksaas. Cytostatic Medication cancer treatment. 7. edition. Oslo. Department of Pharmacotherapeutics and The Norwegian Cancer Society, 2009, p 119-130.

Preparation

Nausea regimens are selected according to the emetogenicity of the relevant drugs.

  • Inform about the risk for and treatment of nausea. 
  • In the event of anxiety or conditional nausea, give tranquilizers if necessary.

Implementation

  • Start with an optimal antiemetic regimen starting with the first cycle of chemotherapy in order to counteract the amplification of the nausea that often occurs with a new treatment.
  • Start the oral antiemetic regimen 1-2 hours before chemotherapy and approx. 15-30 minutes before an intravenous injection.
  • If the patient is already nauseous, the medication should be administered parenterally or rectally.

Antiemetic regimens

Mildly emetic chemotherapy

  • Metoclopramide 10 mg is given intravenously before treatment with cytostatic agents.
  • Metoclopramide 10 mg is given orally uptil 3 times.

Moderately emetic chemotherapy

Ondansetron 8 mg orally 2 x daily. In the event of nausea before treatment, give ondansetron intravenously. If this has little effect, try ondansetron 8 mg x 3 or change to a 5HT3-antagonist, for example, tropisetron 5 mg orally/intravenously or palonosetron 250 µg intravenously.

Highly emetic chemotherapy, or if other treatment does not help

For highly emetic chemotherapy drugs, or if other treatment is not adequate, a 5HT3-antagonist can be given orally or intravenously. It should be combined with dexamethasone 8-16 mg intravenously ½-1 hour before treatment, and further, 8 mg x 2 intravenously or orally on the first day.

In addition, dopamine antagonists may be given, for example, metoclopramide 10 mg x 3.

In some cases, traditional nausea treatment is not sufficient. In this case, the patient can be treated with aprepitant. Aprepitant is used for highly emetic regimens and for patients where the usual antiemetic treatment has failed during moderate emetogenic treatment. Aprepitant is given orally 1 hour before chemotherapy and is combined with dexamethasone and 5HT3-antagonists:  125 mg capsules orally on day 1, then 80 mg orally on days 2-5, depending on the duration of the treatment. Aprepitant can enhance the effect of taxane and etoposide, as well as vinorelbine, and can reduce the effect of warfarin.

The regimen is repeated daily if highly emetic treatment is given over a number of days.

Delayed nausea

Aprepitant in combination with dexamethasone and 5HT3-antagonists is preferable if there is a high risk of delayed nausea and vomiting. This is offered especially to patients who have previously experienced delayed nausea.

Conditional nausea

In the event of conditional nausea, diazepam or other tranquilizers may be considered. Diversion or desensitization can be tried in more serious cases.

Follow-up

Ondansetron can have a constipating effect. Use of a laxative for several days should be considered.

Febrile Neutropenia

General

Febrile neutropenia occurs in compromised immune systems due to a low number of leukocytes, especially granulocytes. Patients with a declining number of granulocytes after chemotherapy, can during bacterial sepsis, quickly develop extensive neutropenia and become critically ill. Febrile neutropenia can be a life-threatening condition.

A patient with neutropenia and simultaneous fever or clinical suspicion of systemic infection should be treated as quickly as possible with broad spectrum antibiotics including gram-negative and gram-positive coverage as soon as the required microbiological samples are taken.

The clinical situation is most critical in patients who have not yet started antibiotic treatment. When broad-spectrum antibiotic treatment is started, monitoring the fever may be permitted.

Fever is often the only symptom. Some have septicemia without fever. One should therefore also be aware of other symptoms such as lethargia, diarrhea, or visible sign of infection. The local clinical symptoms and signs (redness, pain, temperature increase, swelling (boil), and reduced organ function) are most often very much reduced or completely absent during neutropenia.

Indications

  • A patient with neutropenia and simultaneously fever or clinical suspicion of systemic infection

Goals

  • Avoid septicemia.
  • The patient is able follow the planned scheme of treatment.

Definitions

Fever is defined as:

  • a single (rectal) temperature ≥ 38.5 °C or
  • temperature ≥ 38 °C for more than 2 hours or
  • temperature ≥ 38 °C measured three times during 24 hours

There is a known increase of infections when neutrophil < 1.0 x 109/l.  The infection risk increases with degree and duration of neutropenia. The neutropenia is considered severe when granulocytes are ≤ 0.5 x 109/l.

Preparation

The following diagnostic tests should be performed:

  • Adequate microbiologic tests: blood culture x 2-3, throat/nasopharynx, urine, catheter opening any surgical incisions. All blood cultures should be taken simultaneously to avoid losing valuable time.
  • Blood culture and other microbiological samples should be taken before antibiotic treatment is started
  • Blood tests with differential count of leukocytes, thrombocytes, Hb, CRP, SR, creatinine
  • X-ray of chest

Information

Before initiation of chemotherapy, the patient should be extensively informed, both verbally and in writing, of febrile neutropenia and  its consequences.

A patient who can develop febrile neutropenia should obtain a written statement of the condition to present to other treatment providers.

Use of an isolated or private room

Patients with neutrophil granulocytes ≤ 0.3 x 109/l should have a private room if possible. Guidelines for protective isolation should be followed. Thorough washing of hands is especially important.

 

Implementation

  • Treatment is started as soon as possible.  Treatment may be postponed a maximum of 30 minutes to complete microbiological testing.
  • Start septicemia treatment for fever if neutropenia is expected, regardless of granulocyte value.

Antibiotic regimen

  • Benzylpenicillin sodium 5 mg IE x 4 tobramycin or gentamicin 5-10 mg/kg x1
  • Tazocin® 4 g x 3
  • Cefotaxime® 1 g x 4 if aminoglycoside should be avoided
  • Ceftazidim® 1 g x 4  with suspicion of pseudomonas infection
  • Meronem ® 0.5 g x 4 usually 2nd or 3rd choice

When using aminoglycoside, the first dose should be high. Keep in mind the following:

  • age
  • sex
  • kidney function
  • fat index   

Otherwise, the dose should be decided from concentration of aminoglycoside determined after the second day and thereafter monitored 2x per week. 

Serum concentration of tobramycin and gentamycin

For single dose in 24 hours

  • Trough concentration (0-test = 24 hour test) < 0.5 mg/l
  • Top concentration (30 minute after infusion is completed) > 12 mg/l

For multiple doses in 24 hours

  • Trough concentration < 2 mg/l, top concentration (30 minutes after the infusion is completed) preferably > 8-10 mg/l 
  • Avoid aminoglycoside :
    • If kidney function is reduced. Avoid aminoglycoside if cisplatin is used. If cisplatin has been previously used, many patients will have subclinically reduced kidney function. If necessary, use aminoglycoside for a short period and monitor kidney function closely.
    • If carboplatin is used, determine glomerulus filtration rate (GFR) for each new treatment. Penicillin/aminoglycoside can be used if GFR is stable (has not declined more than 15% if initial value is in the normal range)
    • With sarcoma: Protocols with very high doses methotrexate and ifosfamid (> 5 g/m2) should be used in sarcoma treatment. It is not abnormal for these patients to have an increase in creatinine.
    • with massive ascites
    • with suspicion of or documented myeloma kidney (myelomatosis)
    • If aminoglycoside has been used in the past two weeks
  • Suspicion of staphylococcus aureus as a cause of infection (relatively rare)
    • Give penicillinase-stable penicillin, cloxacillin, or dicloxacillin, possibly clindamycin instead of ordinary penicillin. Yellow staphylococci are also killed by cefotaxime and by merop
  • Gram-positive cocci in multiple blood cultures and if the patient has clinical signs of infection
    • Use vancomycin 500 mg x 4 until resistance determination is available
  • Poor patient condition and suspicion of gram-negative septicaemia
    • Use “double gram-negative” with for example ceftazidim or tobramycin
    • Other preparations with good effects against most gram-negative bacteria are meropenem and ciprofloxacin
  • Suspicion of anaerobic infection
    • Use an anaerobic drug: Metronidazol 500 mg x 3, clindamycin 600 mg x 4, piperacillin/tazobactam 2g x 4 or meronem 500 mg x 4.  This especially applies if there is suspicion of anaerobic infection under the diaphragm such as gallbladder, intestines, perforation, abscess.
    • penicillin is often adequate for anaerobic infections above the diaphragm.

With continuing clinical signs of infection, adjust the antibiotic treatment according to resistance determination in blood culture. Maintain gram-negative coverage.

Systemic fungal treatment

By persistent fever after multiple days with broad spectrum antibiotic treatment, one should consider empirical treatment of possible candida-sepsis, for example with fluconazole 600 mg the first 24 hours, and thereafter 400 mg x 1.

If candida is documented without adequate response to fluconazole, a fungicide drug should be used, for example amphotericin B.

If suspected infection with Aspergillus apply voriconazole, amphotericin B or caspofungin.

Follow-up

Observe for symptoms of a new infection.

Nutrition during Cancer Treatment

General

Monitoring the patient's nutritional status is an important part of cancer treatment. The goal is to identify malnutrition as early as possible in order to initiate treatment as quickly as possible.

Measures include diet according to symptoms and the nutritional condition. The patient should be offered nutrition-rich food, snacks, nutritional drinks, tube feeding and intravenous nutrition.

Because cancer treatment breaks down both cancer cells and normal cells, the body requires an adequate supply of nourishment to increase growth of new cells. 

In cancer patients, the sensation of hunger is not always present to the necessary degree. In these cases, it is important to take actions to improve the nutritional status of the patient. The nutritional condition is easiest followed by monitoring body weight over time.

Indication

  • Cancer treatment (chemotherapy, radiation, surgery).

Goal

  • Maintain nutritional status in order for the patient to have the best possible conditions for implementing treatment.

Definitions

Subjective Global Assessment (SGA)

Subjective Global Assessment (SGA) is a scheme for classifying the patient's nutritional status.

Other tables that are frequently used are Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA) and Nutrition Risk Score (NRS). In principle, these schemes are prepared in the same way as SGA, but they are not validated for patients with cancer.

Weight loss is one of the most important signs of change in nutritional status. A weight loss of more than 15% over the past 6 months or more than 5% over the last month is a significant and serious weight loss. If the weight loss occurs in combination with low BMI (body mass index) (< 20 kg/m2 for adults) and/or a food intake of less than 60% of the calculated requirement over the past 10 days, the patient will be malnourished or be at nutritional risk.

Calculation of nutrition and fluid requirements

  • Ambulatory patients:  30-35 kcal/kg/day
  • Bed-ridden patients:  25-30 kcal/kg/day
  • Elderly above 70 years:  Recommended amount is reduced by 10%
  • Fluid requirement:  30-35 ml/kg/day

Nutritionally enriched diet / enrichment of food and beverages

Nutritional beverages may be used as a meal in itself or between meals. Nutritional drinks can be a more valuable snack than "normal" food, because it is often easier for the patient to drink than to eat. It has been shown that if nutritional drinks are introduced as snacks, it does not affect the energy intake during the main meals.

There are a number of ready-made nutritional drinks on the market. Some of the products are of nutritionally complete. They contain carbohydrates, protein and fat and are supplemented with all the necessary vitamins, minerals and trace minerals and possibly fiber. Some of these products can be used as the sole source of nutrition. The energy content varies from 85-200 kcal/100 ml and some products have a high protein content. Other nutritional drinks are supplement drinks adjusted to individual needs such as allergies, intolerance and special conditions associated with illnesses.

The products are also adapted to age, and the dose is determined individually by a clinical dietician/doctor.

Many patients prefer homemade nutritional drinks based on full fat milk, cream, ice cream, fruit and possibly flavor supplements. These are free of additives and have a fresher taste. The energy and protein content is close to the commercial products and at the same time they are more sensibly priced.

Tube feeding

Tube feeding is preferable to total parenteral nutrition (TPN) when the digestive system is working. Nutrition supply to the intestine is more physiological. It protects against bacterial growth, maintains the intestine's mucous membrane structure and function, and promotes motility. Tube feeding involves less risk of metabolic complications.

Tube feeding is used in the event of

  • insufficient food intake (less than 60% of energy requirements) over the past 5-7 days despite oral intake
  • weight loss >2 % over the past week, >5 % over the past month or >10% over the past 6 months
  • danger of weight loss due to planned treatment
  • low albumin values (under 35 g/l, lower limit for normal area)
  • stenosis with feeding obstacles in pharynx/gullet

Tube feeding must not be used for the following conditions.

  • Paralysis or ileus of the alimentary tract
  • Short bowel syndrome
  • Serious diarrhea
  • Serious acute pancreatitis
  • Obstruction of the intestine
  • Serious fluid problems

Tube feeding solutions

The tube feeding solution must be nutritionally complete because they shall be used as the sole source of nourishment. The most frequently used are standard (1 kcal/ml), fiber-containing (1 kcal/ml) or energy-rich (1.5 kcal/ml). There are also tube feeding solutions which are adapted to patients with digestion and absorption problems, patients with diabetes or lactose allergy, and intensive care patients.

Tube feeding solutions, which are adapted to cancer patients are energy-rich (1.5 kcal/ml). They contain extra omega-3 fatty acids, rich in MCT acid and enriched with extra vitamins and minerals. Recommended dosage is 500 ml/day.

Parenteral nutrition

Parenteral nutrition should only be used if food by mouth or tube feeding cannot be maintained. Parenteral nutrition can also be used as a supplement to tube feeding or ordinary food. 

Precautions must be taken for kidney failure, heart failure, lung failure, large fluid and electrolyte loss, diabetes mellitus and liver failure.

Preparation

The patient is classified as well-nourished, somewhat malnourished or seriously malnourished on the basis of information about weight development, food intake, symptoms and physical functioning. This classification has been shown to correlate well with more objective measurements of nutritional status and morbidity, mortality and quality of life.

Actions include individual adjustment of diet according to symptoms and nutritional status.

Tube feeding

The end of the tube is often inserted into the stomach. In the event of poor gastric function, total gastrectomy or pancreatic resection, the feeding tube should be inserted in the duodenum or jejunum. The position of the feeding tube is vital for the choice of feeding-tube solution and mode of administration.

The most common solution is to insert the tube nasogastrically, but it can also be done through the abdominal wall (PEG).

Parenteral nutrition

It is preferable to use intravenous or parenteral nutrition as a supplement to oral/tube feeding instead of only TPN (total parenteral nutrition).

  • Central veins must be used for TPN with high osmolality.
  • Peripheral veins can be used for short-term parenteral nutrition. In this case, a large vein on the forearm is used and a small needle. Nutrition is then given as more diluted solutions.

Implementation

All patients are weighed regularly (1–2 times each week). This is a prerequisite to being able to register changes in the nutritional status.

Varied and healthy food contributes to the growth of new cells and enhances the immune system.

  • Fruit, berries and vegetables are rich in vitamins, minerals, antioxidants and fiber, which contribute to enhances the immune system and contributes to keeping the digestive system working.
  • Fish, shellfish, poultry, meat, eggs, cheese, milk, beans and nuts are rich in proteins, which are the building blocks of new cells.
  • Bread, rice, pasta, porridge and breakfast cereals supplement the diet with proteins, carbohydrates, fiber, vitamins and minerals.
  • Oil, margarine, butter, mayonnaise products, nuts, cream, heavy cream, desserts etc. are fat and energy rich products, which are important to maintain the energy intake at a satisfactory level.
  • Cancer patients also have a requirement for plenty of fluid, especially during treatment, to discharge waste.

Often, the patients must have an individually adjusted diet. In the event of lack of appetite, it is generally more important that you eat (enough food) than what you eat (the right food). It is beneficial to have small portions and for the food to be as abundant in energy as possible. These patients will often have a need for 6–8 small meals everyday to obtain their energy requirements.

Enrichment of food and drink is done in order to increase the energy content of the food product without increasing the volume. Full-fat products such as full-fat milk, cream, butter, heavy cream, mayonnaise, sugar, honey, eggs and cheese etc. are primarily used. Enrichment powders from pharmacies may also be used. Some powders are nutritionally complete, i.e. they contain everything the body requires in terms of energy and nutrients, while others only contain pure energy (carbohydrates, fat and/or protein). 

Tube feeding

Tube feeding is given continuously with a low drop rate or by interval/bolus administration (individually adapted meals with high drop rate).

When the patient's energy and fluid requirements are fulfilled, it will be decided whether the patient will be given bolus or continuous supply at night, in order to increase mobilization during the day. However, this requires that the patient does not have diarrhea, nausea or other complaints associated with the supply of nutrition.

For a running feeding tube:

  • Every 4-8 hours, it should be aspirated in order to monitor the gastric emptying. This applies especially to immobile and weak patients.
  • Weekly or more often, the nutrition program/fluid balance, evaluation, edema control, blood tests (albumin, K, Mg, P, blood glucose) should be monitored weekly or more often.
  • Every 4-6 weeks, the tube should be changed. Alternate the uses of nostrils avoid irritation in the nose through prolonged feeding.

Experience shows that the use of infusion pumps causes fewer side effects and ensures correct volume and rate.

Bolus supply

Initiation of tube feeding with bolus supply is only recommended

  • if the patient been taking any food until the last 24 hours
  • if the patient is taking some food and requires tube feeding for additional nourishment

It is recommended to use pumps for bolus supply for the first 1–2 days.

Continuous supply

If the patient cannot tolerate bolus supply (vomiting, abdominal discomfort, nausea, diarrhea), reverting to continuous supply should be considered.

Tube feeding should always be administered continuously to very malnourished patients or if the tube end is located distally to the pylorus.

Parenteral nutrition

If the patient has a satisfactory nourishment status, begin with 100% of the requirement. If the patient is seriously malnourished, start with 80 % of the requirement and increase slowly to 100% over the course of three days.

The patient must be monitored closely in relation to

  • electrolytes (potassium, phosphate and magnesium).
  • infusion rate.
  • twenty-four hour urine sample and fluid balance should be calculated daily.
  • glucose in the blood and urine, and electrolyte in the blood should be examined daily at the start.
  • liver tests, kidney function tests and triglycerides should be taken examined at least once every week.

For TPN treatment longer than 1 month, vitamins and trace elements should be examined.

Follow-up

The patient's nutrition status should be monitored at follow-up visits after the end of treatment.

Transfusions

General

Transfusions of blood components are often necessary for the patient to complete the planned cancer treatment.

Blood transfusions are appropriate for low hemoglobin (Hb) and thrombocyte transfusions for low thrombocytes (trc) which also poses a risk for serious bleeding.

Normal values

  • Hemoglobin 13.4–17 g/dl
  • Platelets 145–348 109/l

Indications

Blood transfusion

Assessment for a blood transfusion based on:

  • Hb/hct
  • symptoms/sign/function level
  • underlying disease (heart/lung, serious infection)
  • expected development of anemia (marrow function, current bleeding)
  • acute blood loss > 15% of total blood volume
  • Hb < 8.0 g/dl and symptom causing chronic anemia
  • Hb < 8.0 g/dl and reduced bone marrow production without sign of regeneration
  • Hb < 8.0 g/dl in perioperative period
  • Hb < 7.0 g/dl in patients without symptoms of other disease
  • Hb < 10.0 and receiving radiation therapy

Platelet transfusion

The patient is assessed for thrombocyte transfusion based on:

  • clinical status (bleeding, bleeding tendency, or fever/infection)
  • ongoing bleeding and thrombocytopenia < 50x19/l
  • degree of thrombocytopenia and cause of thrombocytopenia (reduced production or increased consumption)

Prophylactic platelet transfusion

  • For values < 10x109/l secondary to previous chemotherapy
  • Before invasive procedures
  • For spinal puncture and installation of central vein catheter, thrombocytes should be 30x109/l and 
  • Puncture biopsies (liver/kidney/tumor) > 40x109/l
  • For major surgeries, thrombocytes should be > 50x109/l. After surgery, thrombocytes should be monitored and transfusion repeated, if necessary.

Remember clinical evaluations: possible bleeding, other risk factors for bleeding, diagnosis, treatment, prognosis.

Goal

  • Complete the planned treatment
  • Ensure hemostasis 
  • Ensure adequate oxygen transport to peripheral tissue.
  • Maintain intravascular fluid volume for adequate circulations of vital organs

Definitions

Blood

For a blood transfusion for anemia, SAGMAN erythrocytes are used. One unit is obtained from 450 ml blood. Most of the plasma is removed and replaced with 100 ml SAGMAN solution (Saltwater-Adenine-Glucose-Mannitol). Hematocrit is about 0.60%.

Platelets

One unit contains 240-300 x 109 platelets and is prepared from blood donors with type O and A. In acute situations, the receiver's blood group is of minor importance.
Two kinds of platelet products are available:
  • Apheresis platelets produced from thrombophereses from one donor
  • Buffcoat platelets produced from buffy coat from 4 donors

All cellular blood products should be leukocyte filtered. Leukocyte filtration is done to remove antigen-presenting and virus-bearing cells. 99.99% of leukocytes in the unit are removed.

Radiation

Blood and thrombocytes are irradiated to a minimum of 25 Gy in the blood bank to eliminate T-lymphocytes.

This is done for:

  • Bone marrow transplant or stem cell transplant (1 month before or 3 months after HMAS until 1 year after allogeneic stem cell transplant)
  • For use of HLA-compatible platelet concentrations
  • For all transfusions from relatives
  • For use of fresh blood
  • For use of fludarabine

Preparation

Blood tests

Before the first blood transfusion, the following blood tests are performed:
  • Virus antigens
    • HCV
    • HBV
    • HIV
Every three days, and as needed, pre-transfusion tests are taken.

Compatibility

Erythrocyte concentration—Rh(D) negative products can usually be given to everyone while Rh(D) positive can only be given to Rh(D) positive receivers.

Thrombocyte concentration—Rh(D) negative girls and women in fertile ages who obtain Rh(D) positive thrombocyte products should be given a prophylaxis for Rh immunization. Boys/men and women who are over the fertile age may obtain thrombocytes regardless of Rh(D) type.

Implementation

Blood components should never be given together with other medications.
  • Premedication if the patient has reacted to previous transfusions.
  • Secure venous access
  • The blood product is checked to ensure the correct unit is given to the correct patient.
  • Use blood set with filter
  • Give SAGMAN over 1 hour and thrombocytes 20-30 minutes per unit.
  • Rinse the set with NaCl 9 mg/ml at the end of the infusion
  • Store the blood product bag for one day before discarding

Observations

The patient should be observed during the transfusion with emphasis on reactions. Most serious transfusion reactions occur within the first 20 minutes.

Symptoms of transfusion reaction:
  • chills
  • fever
  • feeling of heat in the face
  • breathing difficulty
  • itching
  • nervousness
  • fall in blood pressure
  • shock
Suspect/manifest blood transfusion reaction:
  • Stop transfusion immediately
  • Start treatment if necessary (intravenous fluid, adrenalin, steroids, oxygen, respirator)
  • Check blood bag and compatibility form. The residue should be sent to the blood bank.

Follow-up

Hemoglobin and thrombocytes are checked.

If poor effect of platelet transfusion, platelet value should be checked after approximately one hour. The value should have increased by approximately 30x109/l or more after a standard dose.

If the increase is drastically less, the cause may be:
  • Abnormally high consumption. This is an indication for more frequent transfusions.
  • Antigens against HLA or platelet-specific antigens. The patient must be examined in cooperation with the blood bank to find compatible donors.

Bone Marrow Stimulation with G-CSF

General

Bone marrow stimulation with G-CSF (Neupogen®, Granocyte®) is only recommended for febrile neutropenia which does not respond to antibiotic treatment, severe neutropenia (granulocytes < 0.5 x 109 /L for more than 1 week), and in cases where it is necessary to administer curative treatment with sufficient dosage intensity.

Indications 

  • To maintain dosage intensity for curative treatment; when a reduction in dosage will significantly reduce the chance of cure.
  • As prophylaxis for treatments associated with a high risk for febrile neutropenia (> 40 %)
  • Febrile neutropenia that does not respond quickly to antibiotic treatment
  • Long-lasting neutropenia

Goal

  • Maintain treatment intensity

Preparation

The patient should be adequately informed about the treatment.

Implementation

  • The dosage of Neupogen® is 5 µg/kg daily. The treatment is initiated, at the earliest, 48 hours after the treatment is completed. The treatment continues for 10 days.
  • The dosage of Neulasta® is 6 mg subcutaneously administered 24 hours after chemotherapy is completed. The neutrophil cells are counted on day 15.
  • The subsequent course is started on day 21, if the neutrophil count is 0.5 or higher, and the patient has not had febrile neutropenia.
  • It is important not to postpone the treatment if the neutrophil count is 0.5 or higher. The neutrophil count will compulsory decline after ending Neupogen® stimulation. Low values at the start of treatment should not be alarming if the values during hospitalization have been high enough to avoid febrile neutropenia.
  • Stimulation late in the cycle should only be performed for long-lasting, severe neutropenia. At least 48 hours should pass after completed stimulation treatment before the next chemotherapy course  is started. In these cases, it is always important to check that the doses are correct and to recalculate GFR etc. Continuation of chemotherapy will either require a drastic dosage reduction or secondary prophylaxis with G-CSF.

 

Follow-up Care

It is of utmost importance that the patient is informed of the risk of infections associated with a low neutrophil count.

Patients at risk for developing  very low values, must be  informed to take their temperature if they feel unwell or  febrile. In case of  a temperature above 38 °C they should contact their doctor immediately.

Intravenous Extravasation of Cytotoxic Drugs

General

Intravenous extravasation occurs when there is an accidental leak of intravenous cytotoxic fluid (chemotherapy drug) from the vein to surrounding tissue.  

If chemotherapy is given in a peripheral vein, a large vein should be used, which is preferably in the underarm. Before the infusion begins, the vein should be checked for leaks by injecting NaCl 9 mg/ml or glucose 50 mg/ml. Backflow should also be checked. The patient must be informed that pain or burning in the area is not normal and they must inform the doctor.

Cytotoxic chemotherapy drugs should always be given through a central vein catheter to reduce the risk of intravenous extravasation.

Risk factors for intravenous extravasation:

  • Small veins (infants and children)
  • Brittle veins (elderly patients)
  • Reduced physical health (cancer patients)
  • Sclerosizing veins
  • Rolling veins
  • Poor circulation (if the needle is placed in an arm with edema)
  • Obstructed vena cava (raised venous pressure may cause leakage)
  • Conditions such as diabetes and radiation damage
  • Obesity

Chemotherapeutic drugs are separated into three groups according to the degree of toxicity:

  • Non-cytotoxic/irritating
  • Tissue irritant
  • Cytotoxic

Cytotoxic drugs can cause blisters or ulcerations leading to skin necrosis if extravasation occurs. If intravenous extravasation is left untreated, it can lead to permanent tissue damage, necrosis, scar formation around ligaments, nerves and joints, infections, abscesses, contractures, and in the worst case, amputation.

Indication

  • Intravenous extravasation of cytotoxic drugs. 

Goal

  • Limit damage of tissue from intravenous extravasation.

Definitions

Non-cytotoxic drugs or non-irritants

Non-cytotoxic/non-irritant drugs normally do not cause skin necrosis.

Irritants

Drugs that are tissue irritants can cause pain in and around the injection site and along the vein. They can also cause inflammation. Some tissue irritating drugs cause ulceration if a large amount leak extravasally.

Cytotoxic drugs

Cytotoxic drugs are categorized into subgroups according to the mode of damage. This categorization is important for the choice of treatment.

DNA-binding

DNA binders absorb locally into the cells, bind to DNA, and cause cell death. After cell death, the drug molecule can be liberated from the dead cell and start killing healthy cells. This group is divided into these subgroups:  

  • Anthracycline
  • Alkylating drugs
  • Other

For doxorubicin and mitomycin, progrediating tissue damage has been reported over weeks, and in some cases, months after intravenous extravasal injection.

Non DNA-binding

This group of medications can lead to cell death through other mechanisms than DNA binding drugs. This group is divided into:

  • Vinca alkaloids
  • Taxanes

 

Chemotherapy cytotoxicity (1)
Cytotoxic, necrosis

Irritant, can cause flaking or inflammation

Non-cytotoxic or non-irritant
Amsacrine Cisplatin Aldesleukin
Decarbazine Doxorubicin liposomal Alemtuzumab
Dactinomycin Estramustine** Asparaginase
Docetaxel**** Etoposide Bleomycin
Doxorubicin* Floxuridine Bevacizumab
Epirubicin* Florouracil Bortezomib
Daunorubicin* Irinotecan Cetuximab
Idarubicin* Carboplatin Cyclophosphamide**
Irinotecan Carmustin** Cytarabine
Kloremtin** Oxaliplatin Fludarabine
Mitoguazon Pemetrexed Gemcitabine
Mitomycin-C Ralitrexed Ibritumomab tiuxetan
Mitoxanthrone Temoporfin Ifosfamide**
Paclitaxel**** Teniposide Interferon
Plicamycin Topotecan Cladribine
Streptozocin Methylene blue***** Clofarabine
Verteporphin   Melfalan**
Vinblastine***   Methotrexate
Vindesine***   Rituximab 
Vincristine***   Tiotepa**
Vinorelbine***   Trastuzumab

 * = Anthracycline

** = Alkylating agents

*** = Vinca alkaloids

**** = Taxanes

*****= Methylene blue is not a chemotherapy drug, but is used for ifosfamide-induced encephalopathy, and is therefore included on the list.  

All chemotherapy drugs can damage tissue in high concentrations.

References

 

  1. Allwood M, Stanley A WP. The Cytotoxics Handbook. Ed. 4th ed. 2002. 2001
  2. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726

Preparation

Identification of an extravasal injection

  • A burning, stinging pain or other acute change of the puncture site.
  • Local redness or inflammation of the skin around the puncture site.
  • The infusion rate slows/stops.
  • Swelling of the puncture site.

Extravasation has probably also occurred if blood cannot be aspirated, resistance is felt on the plunger when a syringe is used, and/or there is no current if the drug is infused. 

 

Implementation

Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

Emergency response:

  • Stop the infusion immediately.
  • Allow the needle to remain and aspirate with as much water as possible. Avoid applying direct pressure on the area of extravasation.  
  • The volume, type, and time of extravasation should be recorded.
  • A doctor/plastic surgeon should be called for to examine the patient.
  • The damaged area and skin manifestations should be marked/photographed.
  • The affected area should be kept elevated.
  • The remaining chemotherapy should not be discarded.
  • The patient should be informed about what is happening and what must be done. 
  • The needle is removed while aspirating.
  • Pain medication is administered if necessary.

Based on which medication has leaked extravasally, the doctor or plastic surgeon will decide whether conservative treatment or primary surgery is necessary.

Conservative treatment

Conservative treatment consists of two different treatment strategies to limit the damage by extravasation: localize/neutralize and spread/dilute (2).

Localize and neutralize:

  • Place an ice pack on the area for 15-20 minutes, at least 4 times daily for multiple days. A coldpack is used to limit spreading of the drug. Studies have indicated that there is reduced cellular uptake of drugs at lower temperatures (2).
  • The drug that has leaked extravasally is neutralized by a specific drug if the instructions are followed.
  • The affected area of the body should be kept elevated.

Spread and dilute (applies to vincristine, vinorelbine, vindesine, and vinblastine):

  • Warm compresses are placed on the area for 15–20 minutes, at least 4 times daily, for multiple days.
  • To dilute the drug that has leaked extravasally, many subcutaneous injections are given with hyaluronidase diluted with sterile water.

If the patient has lasting pain or blisters, surgical treatment should be considered by excising the area with direct sutures, skin transplant, or flap reconstruction.

Another type of reconstruction may be necessary at a later time. 

Treatment 

Dexrazoxan (Savene®)

Dexrazoxan is an EDTA analong used to treat extravasation of anthracycline (doxorubicin, daunorubicin, epirubicin, idarubicin). The mechanism of action is not fully understood, but it is believed that it may work through two mechanisms. By chelating iron, the formation of the iron-doxorubicin complex and  iron-mediated hydroxy radicals are hindered, which cause oxidative damage to cell membranes and proteins. Another possible mechanism is inhibition of topoisomerase II (3).

Treatment lasts for 3 days. In all cases of extravasation of anthracycline, this treatment should be assessed by an oncologist and surgeon/plastic surgeon.

  • The first infusion should start as soon as possible and within 6 hours after extravasation. 
  • On the following two days, the infusions should occur at the same time as the previous infusion (+/- 3 hours).
  • If possible, the infusion should be placed in a vein where there is no extravasation.
  • An ice pack or cooling element used on the area must be removed at least 15 minutes before the infusion starts to ensure sufficient blood circulation.

Cost

A package costs about NOK 100,000.-. If the expiration date runs out, the drug is replaced by the pharmaceutical company free of cost.

Dimethylsulfoxide (DMSO)

DMSO (70–90% solution) quenches free radicals and prevents formation of sores. The solution can be used after extravasation of cytotoxic drugs (anthracycline, mitomycin C, doxorubicin, idarubicin, epirubicin andactinomycin D) together with cooling of the area when other treatment methods cannot be used (5, 6). DMSO cannot be used in combination with dexrazoxan (3, 4).

  • An area twice as big as the affixed area is treated with the solution every 8 hours for one week.(6)

Hyaluronidase

Hyaluronidase is an enzyme that breaks down hyaluronic acid found in connective tissue. This leads to permeability and increased diffusion of the drug that is leaking extravasally, and is used only to spread the drug out into the tissue (spread and dilute).  

  • Hyaluronidase is administered subcutaneously or intradermally in 5-10 locations on the border of the area where the drug has leaked extravasally (7).

Surgical treatment

"Wash-out"

The washing out technique can be used with chemotherapy drugs when tissue damage is likely. When used with anthracycline, it is important that this is performed before the chemotherapy drug goes intracellularly.

In most cases, this is a very successful method if it is performed within 6 hours after the extravasation.

  • The patient receives regional anesthesia.
  • Multiple small incisions must be made to ensure sifficient access to the damaged subcutaneous tissue.
  • With an infiltration needle, which is usually used for liposuction, isotonic NaCl is flushed through the tissue and drains through the incisions.
  • The infiltrated fluid is then carefully removed by suction through a small needle used for liposuction.
  • The procedure is repeated until 300-500 ml fluid is used.

References

  1. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726
  2. Hasinoff BB. Dexrazoxane use in the prevention of anthracycline extravasation injury. Future Oncol 2008; 2006: 1–15.
  3. Statens legemiddelverk. Preparatomtale. 2008
  4. Langstein HN, Duman H, Seeling D, Butler CF, Evens GR. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plastic Surg 2002; 49: 369–74. 
  5. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M et al. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: A prospective clinical study. J Clin Oncol 1995; 13: 2851–5.
  6. Clinical Pharmacology© 2008 database. Hyaluronidase. 2008.

Follow-Up

For conservative treatment 

The damaged tissue should be observed for multiple weeks (with mitomycin at least 13 weeks) since necrosis can occur after months.

For emergency surgical treatment

Patients treated by a plastic surgeon should receive follow-up care by the surgeon until the wound has healed.

 

Intravenous extravasation of cytotoxic drugs.Intravenous extravasation of cytotoxic drugs.Extravasation of tissue toxic chemotherapy

Smoking cessation in connection with cancer treatment

General

In patients treated with surgery, radiation and/or chemotherapy, the treatment efficacy may be affected by smoking. Smoking has an impact on both metabolism and pharmacokinetics.

Smoking may inhibit wound healing after surgery and increase the probability of surgical site infections. Because smokers generally have more mucus in the airways and are less able to remove it, they also may have a increased risk of serious lung complications during anesthesia. However, it is disputed whether or not it is beneficial to quit smoking directly prior to surgery and this should be considered in each case individually. (28,30-33). Smokers are more prone to stagnation of bronchial secretion than non-smokers and rapid postoperative extubation is important. 

Patients who continue smoking during radiation therapy have a lower risk of complete respons, development of secondary cancer, increased toxicity and several other side effects compared to non-smokers and smokers that quit before treatment. Continued smoking during radiation therapy is also associated with oral mucositis, impaired ability to taste, dry mouth, reduced voice quality, weight loss, cachexia, fatigue, pneumonia, bone-and soft tissue necrosis.

Tobacco may have an effect the metabolism and the mechanisms of chemotherapy and in this way may make the treatment less effective. Smokers undergoing chemotherapy may also experience a weakened immune system, increased rates of infection, exacerbation of common side effects, weight loss, cachexia, fatigue and cardiac or pulmonary toxicity. Some findings suggest that it may also apply to monoclonal antibodies.

Cancer patients who quit smoking before chemo- and radiation therapy get a total symptom burden equal to that of non-smokers, but those who continue to smoke state a higher symptom burden. Targeted measures in smoking cessation may increase quality of life and lead to less treatment interruptions.

A lot of patients wonder if there is any point to quit smoking after receiving a cancer diagnosis. tudies show that continued smoking is associated with increased treatment-related toxicity, increased risk of second primary cancers, reduced quality of life, reduced treatment effect and reduced survival in patients with cancer. This applies to both cancer diagnoses where smoking is a known causal factor, as with lung- and head and neck cancers and in cases where smoking has no known correlation with the diagnosis. Studies conducted on smoking and cancer diagnoses such as breast cancer, prostate cancer, colorectal cancer, esophageal cancer, cervical and ovarian cancer as well as leukemia and lymphoma cancers show that to continuation of smoking after a proven cancer diagnosis is associated with increased risk of mortality.

Studies support that quitting smoking improves cancer, and emphasizing the potential importance of targeted smoking cessation in cancerpatients during and after treatment. The link between tobacco and impact on cancer and cancer treatment is a complex matter.

Regarding the significance of the various components much is still unkown. When it comes to tobacco use in cancer treatment research is primarily done on the link between cigarette smoking and efficacy of cancer treatment. Nevertheless, it cannot be excluded that using other smokeless tobacco products such as snuff and chewing tobacco, may also impact the cancer treatment. According to international guidelines all tobacco use should be stopped during cancer treatment.


Benefits of smoking cessation and risks of continued smoking in patients with cancer
Quitting smoking results in the following benefits: Continued smoking results in a risk of :
  • improved treatment results.
  • less side effects
  • fewer infections
  • improved respiration and circulation
  • increased survival
  • reduced efficacy of treatment.
  • postoperative complications and longer recovery.
  • cardiovascular and respiratory complications.
  • recurrence of cancer, and secondary cancer.
  • shortened life expectancy.

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

Healthcare providers should convey evidence-based information to patients about how smoking affects cancer treatment, the risk of side effects and prognosis and also provide guidance and relevant treatment for smoking cessation.

Preparation

Patients require clear, formalized and fact-based guidance and continuous follow-up. Many patients want encouragement for smoking cessation early in the disease. Being hospitalized is a good opportunity because patients have access to support and help to reduce nicotine withdrawal symptoms and discomfort.

A patient recently diagnosed with cancer is often motivated to quit smoking and also receptive to conversations about how to do this. Motivation or willingness to quit often changes during the treatment, and use of tobacco and motivation should therefore be discussed at every consultation.

Clarifying the patient´s smoking habit is important. The time of day the patient lights their first cigarette says something about the degree of addiction. Making the patient aware of the situations in which he or she smokes most; at work, at home or in social settings, can help break unwanted patterns of behavior.

Implementation

The best and most direct approach to motivate the patient is telling that tobacco use will decrease the effectiveness of treatment and the most important thing the patient can do himself is to stop using tobacco.

  • Speak directly to the patient about how tobacco use may decrease the effectiveness of treatment.
  • Discuss smoking cessation with the patient at each visit.
  • Clarify any misunderstandings about the risks of tobacco use. Point out the importance of quitting.

Sometimes there may be misunderstandings about what kind of health risk smoking during and after cancer treatment may entail.

Advice to those who are not ready for smoking cessation
The smokers statement The response of health care professionals
Justifications
The damage from smoking is already done.
Some damage is done, but continued smoking will still damage your health and reduce the effects of treatment. Quitting smoking is more important now than ever.
This response tells the patient that it is not too late to quit smoking, and the effect of treatment will be positive.

I have reduced smoking.
That is great, and now you need to focus on quitting completely. What do you think keeps you from quitting altogether?
This response tells the patient the importance of quitting completely, as the benefits of quitting at baseline are documented.
This is not a good time to quit smoking.
The benefits of quitting are greatest now, before treatment begins. What is needed to make you feel ready to quit smoking?
 
This response make the patient aware of the fact that quitting smoking optimizes the cancer treatment.

Health professionals must assist the patient identifying realistic expectations and goals for smoking cessation. For some, it may feel easier to scale down the number of cigarettes than to quit completely. The patient should know that every puff affects their health, and that the total health benefits can only be achieved through smoking cessation. For patients unable to stop completely, a gradual reduction may be a step in the right direction.

The probability of success for smoking cessation significantly increases for those who receive professional help in combination with nicotine replacement therapy (NRT) or non-nicotine based products. For the best possible effect of NRT the patient needs professional guidance to find the right product and dosage. For some patients combining two products or receiving a higher dosage than recommended will give the best effect. Sometimes the product must be replaced during the treatment.

Treatment with nicotine replacement therapy

Topical products are patches (Nicorette®, Nicotinell®), chewing gum (Nicorette®, Nicotinell®), lozenges (Nicorette®, Nicotinell®), inhalator (Nicorette®) or a combination of these. These products contain nicotine and therefore reduce the withdrawal symptoms experienced after smoking cessation.

  • Patch: Nicorette® 5 mg,10 mg and 15 mg/16 hours up to 6 months or Nicotinell® 7 mg,14 mg og 21 mg/24 hours up to 3 months.
  • Chewing gum: Nicorette®/Nicotinell® 2 mg and 4 mg, 8-12 pcs/day up to 12 months.
  • Lozenges: Nicorette® 2 mg and 4 mg, typically 8-12 pcs/day, maximum respectively 15 pcs/day up to 9 months or Nicotinell® 1 mg and 2 mg, typically 8-12 pcs/day, maximum is respectively
    25 and 15 pcs/day up to 12 months.
  • Inhalator: Nicorette® 10 mg/dosage container, 4-12 pcs/day up to 6 months.

Combination therapy means combining patches with chewing gum, lozenges or an inhalator.

  • Nicorette® patch15 mg/16h and Nicorette chewing gum 2 mg. 5-6 chewing gums daily. Maximum 24 pcs/day
  • Nicorette® patch 15 mg/16h and Nicorette® inhalator 10 mg: 4-5 dosage-container daily. Maximum 8 pcs/day

Nicotine replacement therapy increases the chance of smoking cessation by 50 to 70% after six months. Two products used in combination increase the chance of smoking cessation compared to the use of only one product.

Side effects

  • Headache, dizziness, nausea, flatulence and hiccup.
  • Irritation in the mouth and esophagus using chewing gum/ lozenges/inhalator
  • Skin irritations while using patches.

Precautions

  • Precaution in acute cardiovascular disease, peripheral arterial disease, cerebrovascular disease, hyperthyroidism, diabetes mellitus, kidney- and liver failure and peptic ulcers.
  • Should not be used during pregnancy, unless the potential benefit outweighs the potential risk.
  • The products should not be used during breastfeeding.

Treatment with non-nicotine medications

Bupropion (Zyban®) is a selective reuptake inhibitor of dopamine and norepinephrine. The mechanism behind why the ability to refrain from smoking increases by using bupropin is unknown. A should be set for smoking cessation for the second week of treatment.

Bupropion increases the chance of smoking cessation after 6 months by nearly 70%.

Side effects

  • Dry mouth, nausea, insomnia, hypersensitivity reactions and seizures (convulsions)

Precautions

  • Contraindicated in people with disease that can cause convulsions,  people with substance abuse or other circumstances lowering the seizure threshold.
  • Depression, which in rare cases includes suicidal thoughts and – behavior including  suicide attempt.
  • Safety and efficacy have not been established for people under 18 years.
  • Should not be used during pregnancy.

Varenicline (Champix®) is a partial agonist by a subtype of nicotinic receptors. It has both agonistic activity with lower intrinsic efficacy than nicotine and antagonistic activity in the presence of nicotine.

A date for smoking cessation should be set. Treatment should start 1-2 weeks, or up to 35 days, before that date. The starting dose is 0,5 mg one time daily on days 1-3, then 0,5 mg two times daily on days 4-7, then 1 mg two times daily on day 8 and until the end of treatment. The treatment should last for 12 weeks.

Side effects

  • Nausea, sleep disturbances, headache, constipation, flatulence and vomiting

Precations

  • Links have been reported between the use of varenicline and an increased risk of cardiovascular events, suicidal thoughts, depression and aggressive and erratic behavior
  • Safety and efficacy have not been established for people under 18 years of age
  • Should not be used during pregnancy

Follow-up

If the patient experiences a relapse, it is important to inform them that this is completely normal, and encourage them to continue. If the most common measures do not work,
consideration should be given both to increase the NRP and to provide closer follow-up by health care providers.

Guidance in smoking cessation is described in the literature as brief and clear advice and then further follow-up with a telephone helpline offering treatment for addiction and behavior change/issues. It is not necessary for the patient to have decided to quit smoking in order to be referred to a quitline. If the patient agrees to receive a call from quitline, he or she will be followed up by a supervisor. Supervisors are bound by confidentiality, are up-to-date professionally and offer free follow-up counseling calls for up to a year.

References

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Follow-up care after treatment of intraspinal tumors

Tumor follow-up

Meningioma/Schwannoma

  • The first MR scan is undertaken 3–6 months postoperatively by the operating surgeon.
  • The surgeon then recommends a further follow-up plan to be undertaken by the neurological department in the patient's home county.
  • If the MR image at the 3–6 month follow-up shows no sign of residue or relapse of the tumor then normally an MR follow-up is recommended after 2 and 5 years.
  • If the MR image at the 3–6 month follow-up shows residual tumor, annual examinations are recommended.
  • In the event of tumor recurrence or growth of residual tumor, the patient must be referred for a new neurosurgical evaluation to consider tumor resection. 

Low-grade gliomas (ependymomas, astrocytomas - WHO grade I/II and oligodendrogliomas)

  • The first MR scan is undertaken 3 months postoperatively by the operating surgeon.
  • The surgeon then recommends a further follow-up plan to be undertaken by the neurological department in the patient's home county:
    • If the MR image at the 3–6 month follow-up shows no sign of residue or recurrence of the tumor, then it is recommended that the next examination takes place after 6 months.
    • If the MR image at the 3–6 month follow-up shows signs of tumor residue or relapse of the tumor, an oncologist should be consulted. The neurosurgeon and oncologist will then decide if radiation therapy and/or chemotherapy should be given. If further observation is chosen in these cases, an individually-adapted follow-up plan will be prepared.

Extradural metastases and malignant gliomas

  • Surgical treatment for these patients is only one part of the primary treatment.
  • All patients will be referred by the neurosurgical department to radiation therapy and/or chemotherapy.
  • Follow-up is not planned at the neurosurgical department.
  • Around 4 weeks after being discharged from the neurosurgical department, the patient is followed-up for oncological treatment at at a cancer clinic.
  • After the end of the primary treatment (surgery, radiation treatment and, if applicable, chemotherapy), clinical follow-up is recommended every 3–6 months with an oncologist or neurologist.
  • In the majority of cases, MR imaging is most useful inpatients withfor new symptoms causing suspicion of recurrence of the tumor.
  • For the majority of malignant intraspinal tumors it is only symptom-producing relapse that is assessed for further treatment. The treatment possibilities for relapse are unfortunately often limited. 

Rehabilitation

All rehabilitation should take place under the care of the neurological department in the patient's home county.

The level of rehabilitation training is determined by the patient's potential of improvement. Rehabilitation consists of being able to learn how to master any function which has been reduced, i.e. the use of technical aids and techniques for managing natural functions (for example, bladder and rectal function).

PROSEDYRER

Fatigue before, during, and after Cancer Treatment

General

There are many reasons why cancer patients feel fatigued. In many patients, the causes are synergistic. Cancer patients are often very sick during treatment periods and may experience extreme fatigue during intensive chemotherapy. It is also very important to be aware that fatigue is a symptom of many other medical conditions, both physical and psychological, which also affects cancer patients. Some known causes of fatigue associated with cancer and cancer treatment are: 

  • Cancer itself
  • An operation
  • Current or recently concluded chemotherapy
  • Current or recently finished radiation therapy
  • Severe anemia
  • Other symptoms such as pain and nausea 
  • Fever or infection
  • Too little fluid or food intake
  • Reduced lung function
  • Changes in sleep
  • Worries, anxiety, stress, or depression

For some of these conditions, such as infections, there is medical treatment available. Fatigue that occurs after an operation or during chemotherapy and radiation therapy will, for most, gradually disappear when strength is regained. If a patient was feeling healthy after treatment and all of the sudden experiences fatigue, they should contact their doctor. If a patient feels fatigue and at the same time feels stressed, worried, or down, they may be reluctant to speak to their doctor or health personnel about it. It is still recommended to talk about these problems. Talking about it may be therapeutic, and provides room for discussing measures with a qualified person with experience with patients that have the same problems. For cured patients experiencing chronic fatigue, it may be difficult to pinpoint a specific cause. Many of these patients experience improvement by changing their lifestyle to a lower tempo than before the diagnosis.

Definition

Everyone knows what it feels like to be tired, fatigued, or lethargic when sick. This feeling is the most common side effect of cancer and cancer treatment. A symptom is a condition or state that something is not right in the body. Other frequent symptoms associated with cancer and cancer treatment are reduced appetite and nausea. Most patients who experience fatigue associated with cancer say that the feeling does not improve with rest, and many describe a lack of energy or exhaustion.  

If fatigue arises during chemotherapy or radiation therapy, most patients experience that it will gradually go away when treatment is over and their strength is regained. This type of fatigue is considered acute. Improvement may take time depending on the intensity of treatment. Some patients experience that fatigue lasts for months, or even years. This is considered chronic fatigue. The ability to carry out daily activities, a lack of humor, health-related worries, a reduced capacity to carry out work functions, or less energy for family, can also accompany chronic fatigue. Most patients will find it difficult to be told by their doctor that they are considered healthy, while their friends and family expect them to be normal again, despite having a lack of energy and ability to perform activities they want to.  

For many, feeling fatigued is often accompanied by having difficulty concentrating, poor memory, and an increased need for sleep. Most patients will need more sleep than before they became sick. For many, sleep is not restful, and it may take time to "get going" in the morning. Many also experience that they quickly become drained of strength if they exert themselves, and that it takes a long time before regaining strength after exertion. Exertion in this context can mean both physically and mentally such as working on a task that requires concentration.

Preparation

Fatigue can occur in all phases of cancer illness. Some patients feel it before the diagnosis, and almost all patients experience fatigue during radiation therapy or chemotherapy. A minority of patients experience long term fatigue after cancer treatment is over and the disease is cured. Patients who cannot be cured will almost always feel tired, worn-out, and exhausted. The degree of fatigue in these patients varies depending on the cancer type, spreading, and other symptoms of the disease.

The patient should be given necessary information on both causes of fatigue and measures he/she can take.

Implementation

General measures that can reduce feeling tired and fatigued

Following suggestions are meant as general advice that may not necessarily apply to everyone in all situations. This advice is based on results from studies, experiences from cancer patients, and recommendations from experts. Each patient should assess what works for them. It is recommended to express concerns and seek advice for what measures you can take and what you should avoid.

General advice
  • Try to live as "normal" as possible.
  • Try to plan your day to include time to rest.
  • Take many small breaks during the day instead of a few long ones.
  • Rest after strenuous activity.
  • Plan your daily activities and do those that are most important for you.
  • Set realistic goals for yourself and try to be happy with those you accomplish.
  • Try to recognize activities that make you especially tired/fatigued and limit them, or spread them out over longer intervals. 
  • Try to accept that you do not have the energy to do the things you could previously.
  • Assess what is important for you to do yourself and what you can allow others to do.
  • Assume you will be tired after something strenuous even if you experience the activity as positive.

Physical activity and exercise

Exercise and physical activity that is appropriate for you will reduce the feeling of fatigue. Regular exercise is the most effective measure against chronic fatigue in cancer patients. Nevertheless, both too much and too little exercise can worsen fatigue, therefore, it is important to find a level (frequency and intensity) that suits you. You should never exercise so intensely that you must stop a session or exercise period because you are exhausted. Remember that daily form varies for everyone and adjust your exercise routine accordingly. Make long-term goals (months) and gradually increase activity, and carefully for a period. 

  • Activities such as walking, biking, swimming, dance, and aerobics are recommended.
  • Light exercise periods at regular intervals are better than intense, sporadic periods.
  • Always start with a slow tempo and increase gradually before finishing with a slow tempo again.
  • Always sit down and rest after exercise but try not to lay down and sleep.
  • Physical therapists and sport pedagogs can provide advice on exercises that are right for you. The principles are the same for all exercise, but it should be adjusted for your energy level.  

Sleep

Many cancer patients with chronic fatigue have sleep pattern disturbances. It is important to maintain a normal rhythm even if you feel like sleeping during the day.

  • Try to wake up at the same time every day and keep a regular bedtime.
  • Avoid too much activity right before bedtime.
  • Try not to sleep during the day because this will disturb your biological rhythm.
  • But, a short afternoon nap may be energizing!
  • Rest during the day by relaxing in a good chair, but try not to fall asleep.
  • Speak to your doctor about lasting sleep disturbances.

Nutrition

Having a reduced appetite or intake of food can also result in a lack of strength and energy. We recommend eating healthy food regularly, and to follow the national guidelines on nutrition. Special diets or supplements do not improve fatigue unless there is a deficiency.

Work situation

Some patients do not have the strength to continue working, or they must reduce their hours because of chronic fatigue. Consulting with a social worker may be beneficial for guidance regarding your work situation, your welfare rights, and financial situation. 

Some adjustments that you and your employer can make:

  • Discuss the possibility for more simple or easier tasks, especially if you have a physically demanding profession.
  • Assess the possibility of reducing your hours.
  • Remember to take regular breaks also at work, if possible.
  • Assess the possibility of flexi-time to work during the hours you have energy, as well as the possibility of working from home.

Care for children

Caring for children or adolescents may be very difficult when you are fatigued or lack energy and strength. There are, however, some measures you can take:

  • Explain to your children that you are tired and are not able to do as much as you used to.
  • Discuss what the children can help you with and allow them to take part in household chores.
  • Try to establish permanent household chores for all family members.
  • Try to do activities that suit you that do not require too much energy, and can be performed without too much exertion. 
  • Ask and accept help from others for driving to and from activities, school, etc. if this relieves you.

Drug therapy

In Norway, there is currently no specific drug therapy for chronic fatigue associated with cancer. If the fatigue is due to specific conditions, this is of course treated with medication, if possible. Sometimes, such treatments improve the fatigue, but other times they do not. Examples of treatment that often reduce fatigue are treatment for infections and depression. 

Treatment with medications that stimulate production of red blood cells is not recommended for cancer patients due the the danger of serious side effects.

Follow-up

Information about fatigue

Healthcare workers in cancer care will often have knowledge about fatigue and cancer. Most general care physicians have general experience with fatigue but meet relatively few cancer patients. There is a lot of information available on the internet of varying quality. Below is a list of web adresses and some literature. Be aware that you may find opposing advice because knowledge on treatment especially, is limited.

Some articles/books:

  • Armes J., m.fl. (2004). Fatigue in cancer. Oxford University Press.
  • Berger A.M., m.fl. (2009). NCCN Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue. www.nccn.org
  • Patarca-Montero R. (2004). Handbook of cancer-related fatigue. Haworth Medical Press