Glioma Treatment Guide

As a service to our community, BTSS medical advisors have compiled a summary of Treatments for Gliomas which list treatments that are clinically available in Singapore, including clinical trials and helpful treatments that are available overseas. The efficacy, as well as the potential adverse side effects of these treatments, are also highlighted.
This Glioma Treatment Guide will be updated once in 6 months to provide current information to guide our BTSS members who are researching and deciding on alternative treatment options.
As the information provided herein is not intended as medical advice for your specific medical conditions, BTSS and our medical advisors shall not be responsible or be liable for any matter arising from your pursuit of the treatments mentioned. You should always consult a suitably qualified doctor to decide and pursue the best course of treatment for your unique condition.

NeuroOncology treatments for Glioma that are available in Singapore

No.Name of treatmentLine of treatment/EfficacySome known adverse effectsApplicable patient programme
1Temozolomide 
Standard first-line treatment/ may also be used in the recurrent setting. Survival benefit in the first-line
setting when added to radiotherapy
 
Fatigue, hair loss, nausea, vomiting, constipation, suppression of immunity, low
platelet, liver toxicity, loss of fertility
MAF plus, Singapore Cancer Society (please approach your doctor for more information)
2Procarbazine, Lomustine, VincristineFirst-line treatment of oligodendrogliomas, Treatment in the recurrent settingFatigue, hair loss, nausea, vomiting, suppression of immunity, low platelet, liver toxicity, lung toxicity, loss of fertility, numbness
3Lomustine       Treatment in the recurrent settingFatigue, nausea, vomiting, suppression of immunity, low platelet, liver toxicity, lung toxicity, loss of fertility
4Bevacizumab (Avastin)Mainly used in the recurrence setting, in the first-line setting under special circumstancesHypertension, protein in the urine, blood clots, bleeding, wound healing issuesRoche ARISE program, Singapore Cancer Society (please approach your doctor for more information)
5Tumor Treating Fields (TTF, Optune)First-line treatment. May also be used in the recurrent setting.Scalp irritation, headaches.
6Platinum-based regimens (Carboplatin)Treatment in the recurrent settingFatigue, nausea, vomiting, suppression of immunity, low platelet count, renal toxicity, loss of fertility.
7EtoposideTreatment in the recurrent settingFatigue, alopecia. nausea, vomiting, suppression of immunity, low platelet count.
8LarotrectinibPresence of NTRK gene fusion tumours in recurrent settingFatigue, nausea, vomiting, anemia, suppression of immunity, liver toxicity.
9Dabrafenib/CobimetinibPresence of BRAF V600E activation mutation in recurrent settingHair loss, skin conditions, headache, constipation, joint aches, anemia, bleeding.
10Vemurafenib/CobimetinibPresence of BRAF V600E activation mutation in recurrent setting

Clinical trials available in Singapore

No.Name of treatmentRational of trialTarget populationStudy site(s)
1Entrectinib (STARTRK-2 study; NCT02568267)Evaluation of TRK inhibitor targeted therapy in
patients with NTRK gene fusion-positive solid
tumors (approximately 2% of gliomas)
NTRK fusion-positive recurrent glioma patientsNUH, NCC
2Pilot study for the optimisation of systemic therapy in recurrent glioblastoma multiformeTesting patient-derived organoids against a panel of therapies used to treat recurrent GBM, in order to determine the combination which would be most efficacious for the individual patient at the point of relapseGBM patients – patient-derived organoid is harvested at the time of first surgery or biopsyNUH (anticipated Q1 2022)
3Study of LY3410738 administered to patients with advanced solid tumors with IDH1 mutations (NCT04521686)Oral targeted therapy in patients with IDH1 R132-mutant tumors, including gliomasIDH1 R132-mutant recurrent glioma patientsNUH (anticipated Q4 2021)
4A trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma (GBM AGILE) (NCT03970447)Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed and recurrent GBM(in local arm) Patients with newly diagnosed/recurrent GBM harboring specific tumour signature and mutationsNNI (anticipated Q4 2022)

Treatments for gliomas that may be helpful but not available in Singapore

No.Name of treatmentEfficacySome known adverse effectsStudy site(s)
1ONC201H3 K27M-mutant recurrent gliomasFavourable toxicity profilePlease consult your oncologist for potential availability and clinical trials overseas

Novel treatment and summary evaluation (Trials that are available outside Singapore, efficacy pending confirmation)

No.Name of treatmentRational of trialTarget population
1VAL083Oral chemotherapy which can overcome resistance associated with MGMTMGMT unmethylated GBM patients
2Immunotherapy, mainly vaccine therapies– PVSRIPO (intratumoral delivery of recombinant poliovirus)
– CMV-targeted vaccines
– Personalised cancer vaccines
Mainly recurrent GBM populations

RadioOncology treatments for Glioma that are available in Singapore

No.Name of treatmentLine of treatment/EfficacySome known adverse effectsApplicable patient programme
1Image Guided Radiotherapy (IGRT)
Refers to the use of daily imaging to ensure that the tumour target is within the treatment volume. Most useful when anatomical changes are expected within the treatment volume or there are critical organs such as optic nerves in close proximity to the tumour target
– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas ) : Standard dose RT (59.4 to 60Gy) with concurrent temozolamide, over ~6 weeks

– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas) : Abbreviated RT 40Gy with concurrent temozolamide, over ~3 weeks

– Low grade glioma : RT 50 – 54 Gy with or without chemotherapy (TMZ or PCV), over ~6 weeks
Short term : lethargy, headache, nausea/vomiting, skin irritation, hair thinning/loss.

Medium-long term : increased risk of brain scarring (Radiation necrosis), possible cognitive changes , changes in vision/hearing (depending on location of tumour).

Risk of secondary malignancies in patients who survive > 10 years. Estimated risk
<1% every 10 years
 
MAF plus, Singapore Cancer Society (please approach your doctor for more information)
2Intensity modulated radiotherapy (IMRT)
Allows shaping of the radiation dose around the target. This allows better coverage of the tumour target while achieving improved sparing of the surrounding normal organs. IMRT can be delivered with or without image guidance (IGRT) depending on the level of precision required.
– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas ) : Standard dose RT (59.4 to 60Gy) with concurrent temozolamide, over ~6 weeks

– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas) : Abbreviated RT 40Gy with concurrent temozolamide, over ~3 weeks

– Low grade glioma : RT 50 – 54 Gy with or without chemotherapy (TMZ or PCV), over ~6 weeks
Short term : lethargy, headache, nausea/vomiting, skin irritation, hair thinning/loss.

Medium-long term : increased risk of brain scarring (Radiation necrosis), possible cognitive changes , changes in vision/hearing (depending on location of tumour).

Risk of secondary malignancies in patients who survive > 10 years. Estimated risk
<1% every 10 years
MAF plus, Singapore Cancer Society (please approach your doctor for more information)
3Volumetric modulated arc therapy (VMAT)
A different form of IMRT. The main advantage is the delivery of radiation doses continuously, as the treatment gantry rotates. This usually results in a shorter time spent on the treatment couch.
– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas ) : Standard dose RT (59.4 to 60Gy) with concurrent temozolamide, over ~6 weeks

– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas) : Abbreviated RT 40Gy with concurrent temozolamide, over ~3 weeks

– Low grade glioma : RT 50 – 54 Gy with or without chemotherapy (TMZ or PCV), over ~6 weeks
Short term : lethargy, headache, nausea/vomiting, skin irritation, hair thinning/loss.

Medium-long term : increased risk of brain scarring (Radiation necrosis), possible cognitive changes , changes in vision/hearing (depending on location of tumour).

Risk of secondary malignancies in patients who survive > 10 years. Estimated risk
<1% every 10 years
MAF plus, Singapore Cancer Society (please approach your doctor for more information)
4Tomotherapy
A different form of IMRT. Tomotherapy incorporates daily imaging with delivery of radiation doses ‘slice by slice’. Tomotherapy is most useful for treating lengthy volumes such as in craniospinal irradiation.
– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas ) : Standard dose RT (59.4 to 60Gy) with concurrent temozolamide, over ~6 weeks

– High grade glioma (e.g. Glioblastoma, WHO grade 3 astrocytomas) : Abbreviated RT 40Gy with concurrent temozolamide, over ~3 weeks

– Low grade glioma : RT 50 – 54 Gy with or without chemotherapy (TMZ or PCV), over ~6 weeks
Short term : lethargy, headache, nausea/vomiting, skin irritation, hair thinning/loss.

Medium-long term : increased risk of brain scarring (Radiation necrosis), possible cognitive changes , changes in vision/hearing (depending on location of tumour).

Risk of secondary malignancies in patients who survive > 10 years. Estimated risk
<1% every 10 years
MAF plus, Singapore Cancer Society (please approach your doctor for more information)
5Stereotactic radiotherapy/ radiosurgery (SRT/ SRS)
Stereotactic techniques allow delivery of radiotherapy doses with sub-millimetre precision. This improved precision is most useful for treating smaller tumour targets as it allows for dose intensification (the delivery of larger radiotherapy doses per day).
Recurrent tumoursSide effects are depdenent on the location of the target and prescribed dose.
Depending on the degree of dose intensification, there is a 10% risk of radiation necrosis resulting in symptoms (headaches, nausea, changes in power/
sensation/ vision

Treatments for gliomas that may be helpful but not available in Singapore

No.Name of treatmentEfficacySome known adverse effectsStudy sites(s)
1Proton beam therapy, in lieu of IMRT/VMAT, at the same doseConformal radiotherapy delivered using proton particles may potentially reduce the dose to normal tissue. The degree of benefit is dependent on factors such as tumour type, prescription dose and the proximity of the target to normal organs. Please consult your radiation oncologist for further details.Please consult your radiation oncologist for potential availability locally and overseas.

Clinical trials available overseas

No.Name of treatmentRational of trialTarget populationApplicable patient programme
1Proton beam therapyChildren/Adolescent
2Proton beam therapy
for benign conditions
Patients expected to survive > 10 years
3External beam RTPh 1/2 study studying the role of TLX101 as a radiosensitizer in combination with external beam RTRecurrent GBM in patients 18 years and aboveThis phase I/II trial of TLX101 in combination with RT in recurrent GBM (NCT03849105) has recently closed following encouraging safety and efficacy signals. A trial in the upfront setting is currently being planned
4Concurrent TTF with chemoradiotherapy (TMZ + 60Gy RT)Pilot study examining synergistic interactions between TTF and chemoradiotherapyAdult patients 18 years and above with newly diagnosed GBM following surgery and biopsyThis pilot study has now closed. Planning for a phase II study is currently underway

Neurosurgery for Glioma that are available in Singapore

No.Name of treatmentEfficacySome known adverse effectsApplicable patient programme
1Awake surgeryUseful for gliomas in eloquent areas of the brain
2Brain Mapping Surgery (with patient asleep)For patients who cannot tolerate awake conditions or with severe deficits
3Stereotactic biospyMinimally invasive surgery to obtain tissue sample
for histology
4Use of intra- operative MRI for Glioma resectionUseful to ensure maximum safe removal of tumours. Used in conjunction with the other modalities – awake surgery