Brain Stem Gliomas medical therapy: Difference between revisions

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==Overview==
==Overview==
The optimal therapy for brainstem gliomas depends on the subtype and whether it is newly diagnosed or a recurrent tumor. Patients with diffuse brainstem gliomas are treated with [[radiotherapy]] and [[chemotherapy]], whereas patients with focal brainstem gliomas are treated with [[surgical resection]] with or without [[radiation therapy]] and [[chemotherapy]].


==Medical therapy==
==Medical therapy==
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The overview of the treatment regime is as follows:
The overview of the treatment regime is as follows:
===A) '''''Newly diagnosed'''''  brainstem gliomas===
===1. Newly diagnosed brainstem gliomas===
====Diffuse brainstem gliomas====
:: A. '''Diffuse brainstem gliomas'''
*[[Radiation therapy]]
:::* [[Radiation therapy]]
*[[Chemotherapy]]
:::* [[Chemotherapy]]


====Focal brainstem gliomas====
:: B. '''Focal brainstem gliomas'''
*[[Surgical resection]] (with or without [[radiation therapy]] and [[chemotherapy]])
:::* [[Surgical resection]] (with or without [[radiation therapy]] and [[chemotherapy]])
*Observation (with or without [[cerebrospinal fluid]] diversion)
:::* Observation (with or without [[cerebrospinal fluid]] diversion)
*[[Radiation therapy]], [[chemotherapy]], and alternative approaches for inoperable focal or low-grade tumors
:::* [[Radiation therapy]], [[chemotherapy]], and alternative approaches for inoperable focal or low-grade tumors


===B) '''''Recurrent'''''  brainstem gliomas===
===2. Recurrent brainstem gliomas===
====Diffuse brainstem gliomas====
:: A. '''Diffuse brainstem gliomas'''
*[[Palliative care]]
:::* [[Palliative care]]
====Focal brainstem gliomas====
:: B. '''Focal brainstem gliomas'''
*Repeat [[surgical resection]]
:::* Repeat [[surgical resection]]
*[[Radiation therapy]]
:::* [[Radiation therapy]]
*[[Chemotherapy]]
:::* [[Chemotherapy]]


=='''''Newly diagnosed''''' brainstem gliomas==
==Newly Diagnosed Brainstem Gliomas==
===Diffuse brainstem gliomas===
===Diffuse brainstem gliomas===


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'''1) Radiation therapy'''.
'''1) Radiation therapy'''.
*Conventional treatment for children with diffuse brainstem glioma is ''radiation therapy''. The conventional dose of radiation ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions. Such treatment will result in transient benefit for most patients, but more than 90% of patients will die within 18 months of diagnosis. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.
*Radiation therapy is the treatment of choice for children suffering from brain stem gliomas. A radiation dose of 54 to 60 Gy is typically used for treatment. Prognosis after radiation therapy remains poor as > 90% of patients die after 18 months of initial diagnosis. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.
*The efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have '''not''' demonstrated improved outcomes using these radiation techniques.
*The efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have '''not''' demonstrated improved outcomes using these radiation techniques.
::*Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPGs, whether given alone or in combination with chemotherapy.
 
::*Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, a dose of 78 Gy has been used for treatment and it has been found that increasing the dose of radiation does not improve survival in these patients.
::*Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.
::*Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.
::*Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.
::*Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.


'''2) Chemotherapy only (infants)'''
'''2) Chemotherapy only (infants)'''
*Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with diffuse brainstem gliomas, and chemotherapy-only approaches are utilized.
*Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with diffuse brainstem gliomas, and [[chemotherapy]]-only approaches are utilized.


===Focal brainstem gliomas===
===Focal brainstem gliomas===
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'''2) Observation (with or without cerebrospinal fluid diversion)'''
'''2) Observation (with or without cerebrospinal fluid diversion)'''
*Patients with small tectal lesions and [[hydrocephalus]] but no other neurological deficits may be treated with [[cerebrospinal fluid]] diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease. As focal brainstem gliomas are low grade and often very slow growing, shunting is often the only required intervention for long term survival.
*Small tectal lesions and [[hydrocephalus]] without neurological deficits:
**Treat with [[cerebrospinal fluid]] diversion alone and follow-up with imaging.
**Shunting for favorable long-term outcomes
*In the minority of patients who progress, [[radiotherapy]] often leads to local control or even [[tumor]] regression. [[Surgical excision]] is sometimes necessary.
*In the minority of patients who progress, [[radiotherapy]] often leads to local control or even [[tumor]] regression. [[Surgical excision]] is sometimes necessary.
*Imaging predictors of patients who will need further treatment include a size greater than 2.5 cm and presence of contrast enhancement.
*Imaging predictors of patients who will need further treatment include a size greater than 2.5 cm and presence of contrast enhancement.
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*In selected circumstances, adjuvant therapy in the form of [[radiation therapy]] or [[chemotherapy]] can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma. Decisions regarding the need for such therapy depend on the ''age'' of the child, the ''extent of resection'' obtainable, and associated ''neurologic deficits''.
*In selected circumstances, adjuvant therapy in the form of [[radiation therapy]] or [[chemotherapy]] can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma. Decisions regarding the need for such therapy depend on the ''age'' of the child, the ''extent of resection'' obtainable, and associated ''neurologic deficits''.
*Alternative approaches for the treatment of inoperable brain stem gliomas include the following:
*Alternative approaches for the treatment of inoperable brain stem gliomas include the following:
::*[[Stereotactic]] iodine I-125 [[brachytherapy]] approaches, with or without adjuvant [[chemotherapy]].
::*[[Stereotactic]] iodine I-125 [[brachytherapy]] approaches, with or without adjuvant [[chemotherapy]]
::*The use of '''''[[BRAF]]''''' inhibitors for [[tumors]] harboring a '''''V600E''''' [[mutation]].[28]
::*The use of '''''[[BRAF]]''''' inhibitors for [[tumors]] harboring a '''''V600E''''' [[mutation]]


=='''''Recurrent''''' brainstem gliomas==
==Recurrent Brainstem Gliomas==


===Diffuse brainstem gliomas===
===Diffuse brainstem gliomas===
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'''1) Palliative care'''
'''1) Palliative care'''
 
*Given the dismal [[prognosis]] for patients with diffuse brainstem gliomas, progression of the pontine lesion is anticipated generally within 1 year of completing [[radiation therapy]]. In most cases, [[biopsy]] at the time of clinical or radiologic progression is not recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity.
Given the dismal [[prognosis]] for patients with diffuse brainstem gliomas, progression of the pontine lesion is anticipated generally within 1 year of completing [[radiation therapy]]. In most cases, [[biopsy]] at the time of clinical or radiologic progression is not recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity.
*[[Palliative care]] is provided for these patients whether or not disease-directed therapy is administered.
 
[[Palliative care]] is provided for these patients whether or not disease-directed therapy is administered.


===Focal brainstem gliomas===
===Focal brainstem gliomas===
The treatment considerations at the time of recurrence are dependent on prior treatment. The standard treatment option for ''recurrent focal'' brainstem gliomas include the following:
The treatment considerations at the time of recurrence are dependent on prior treatment. The standard treatment options for ''recurrent focal'' brainstem gliomas include the following:


'''1) Repeat surgical resection'''
'''1) Repeat surgical resection'''
 
*The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment, the appearance of the mass lesion, and the clinical picture.
The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment, the appearance of the mass lesion, and the clinical picture.


'''2) Radiation therapy'''
'''2) Radiation therapy'''
 
*The radiation therapy include 3-dimensional conformal [[radiation therapy]].
The radiation therapy include 3-dimensional conformal [[radiation therapy]].


'''3) Chemotherapy'''  
'''3) Chemotherapy'''  
 
*[[Carboplatin]] and [[vincristine]] may be effective in children with recurrent low-grade exophytic gliomas.
[[Carboplatin]] and [[vincristine]] may be effective in children with recurrent low-grade exophytic gliomas.
 
==Clinical trials==
*There are several new clinical trials in process.<ref> Rx of brainstem gliomas. National Cancer Institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_45</ref> One such trial is '''dendritic cell [[immunotherapy]]''' which uses the patient’s tumor cells and [[white blood cells]] to produce a chemotherapy that directly attacks the tumor. However, these treatments do produce side effects; most often including [[nausea]], the breakdown of the [[immune system]], and [[fatigue]]. [[Hair loss]] can occur from both [[chemotherapy]] and [[radiation]], but usually grows back after chemotherapy has ceased.
 
*[[Steroids]] such as '''[[decadron]]''' may be required to treat swelling in the brain. Decadron can lead to [[weight gain]] and [[infection]]. Patients may also experience [[seizures]], which need to be treated to avoid complications. For some patients there is a chance of a neurological break down, this can include, but is not limited to, [[confusion]] and [[memory loss]].
 
*The use of '''[[topotecan]]''' is being investigated.<ref> Rx of brainstem gliomas. National Cancer Institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_45</ref>


==References==
==References==
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Latest revision as of 19:39, 21 October 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

The optimal therapy for brainstem gliomas depends on the subtype and whether it is newly diagnosed or a recurrent tumor. Patients with diffuse brainstem gliomas are treated with radiotherapy and chemotherapy, whereas patients with focal brainstem gliomas are treated with surgical resection with or without radiation therapy and chemotherapy.

Medical therapy

The treatment is significantly influenced by tumor type, morphology and location. Radiation and chemotherapy are a key part of the treatment regime. For treatment purposes, patients are grouped as having newly diagnosed or recurrent disease.[1][2]

The overview of the treatment regime is as follows:

1. Newly diagnosed brainstem gliomas

A. Diffuse brainstem gliomas
B. Focal brainstem gliomas

2. Recurrent brainstem gliomas

A. Diffuse brainstem gliomas
B. Focal brainstem gliomas

Newly Diagnosed Brainstem Gliomas

Diffuse brainstem gliomas

The standard treatment options for newly diagnosed diffuse brainstem gliomas include the following:

1) Radiation therapy.

  • Radiation therapy is the treatment of choice for children suffering from brain stem gliomas. A radiation dose of 54 to 60 Gy is typically used for treatment. Prognosis after radiation therapy remains poor as > 90% of patients die after 18 months of initial diagnosis. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.
  • The efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have not demonstrated improved outcomes using these radiation techniques.
  • Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, a dose of 78 Gy has been used for treatment and it has been found that increasing the dose of radiation does not improve survival in these patients.
  • Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.
  • Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.

2) Chemotherapy only (infants)

  • Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with diffuse brainstem gliomas, and chemotherapy-only approaches are utilized.

Focal brainstem gliomas

The standard treatment options for newly diagnosed focal brainstem gliomas include the following:

1) Surgical resection (with or without radiation therapy and chemotherapy)

  • In general, maximal surgical resection is attempted. Patients with residual tumor may be candidates for additional therapy, including 3-dimensional conformal radiation therapy approaches, with or without adjuvant chemotherapy.

2) Observation (with or without cerebrospinal fluid diversion)

  • Small tectal lesions and hydrocephalus without neurological deficits:
    • Treat with cerebrospinal fluid diversion alone and follow-up with imaging.
    • Shunting for favorable long-term outcomes
  • In the minority of patients who progress, radiotherapy often leads to local control or even tumor regression. Surgical excision is sometimes necessary.
  • Imaging predictors of patients who will need further treatment include a size greater than 2.5 cm and presence of contrast enhancement.
  • A period of observation may be indicated before instituting any treatment for patients with neurofibromatosis type 1. Brain stem gliomas in these children may be indolent and may require no specific treatment for years.

3) Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors

  • In selected circumstances, adjuvant therapy in the form of radiation therapy or chemotherapy can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma. Decisions regarding the need for such therapy depend on the age of the child, the extent of resection obtainable, and associated neurologic deficits.
  • Alternative approaches for the treatment of inoperable brain stem gliomas include the following:

Recurrent Brainstem Gliomas

Diffuse brainstem gliomas

The standard treatment option for recurrent diffuse brainstem gliomas include the following:

1) Palliative care

  • Given the dismal prognosis for patients with diffuse brainstem gliomas, progression of the pontine lesion is anticipated generally within 1 year of completing radiation therapy. In most cases, biopsy at the time of clinical or radiologic progression is not recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity.
  • Palliative care is provided for these patients whether or not disease-directed therapy is administered.

Focal brainstem gliomas

The treatment considerations at the time of recurrence are dependent on prior treatment. The standard treatment options for recurrent focal brainstem gliomas include the following:

1) Repeat surgical resection

  • The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment, the appearance of the mass lesion, and the clinical picture.

2) Radiation therapy

3) Chemotherapy

References

  1. ↑ Treatment of brainstem gliomas. National Cancer Institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_45
  2. ↑ Rx of Brainstem gliomas. Dr Yuranga Weerakkody and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/brainstem-glioma


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