General
- LGGs remain incurable
- Patient will over several years progress via serial anaplastic transformations towards the unequivocal endpoint, mortality.
- Disease volume will increase
- Distorting and invading the surrounding brain
- Gradually interfere more and more with brain’s normal function.
- The 2016 WHO grading on its own may not correlate with the prognosis in patients with LGG
- Evidence supports maximal safe resection for patients with presumptive diagnosis of a LGG
- Sequential Radiotherapy-Chemotherapy seems to be beneficial for patients with resections other than GTR or SM/ST Resection
- Early low dose RT
- Better at controlling seizure
- RT has significant cognitive side effects
- Even though no head-to-head trial PCV versus TMZ has been performed, the evidence seems to support PCV over TMZ
- However, PCV side effects and compliance are a significant concern
- Careful with one size fit them all approach based on RTOG 9802 Trial
- Only of GTR in this Trial
- Best treatment after GTR or SM/ST Resections?
- Current matter of debate
Aim
- Maximize the patient’s survival
- By reducing tumour load → malignant transformation potential
- Preserving quality of life (QoL)
- Prevent neurological deficits
- Reduce seizure
- Gross total resection was found to be predictive of seizure freedom in two institutional studies
- Englot et al., 2011
- You et al., 2012
- Pallud et al., 2014: In a large series (N = 1509)
- By the French glioma network not only total, but also subtotal resections were found to be predictive of postoperative seizure control
Algorithm
NICE Guidelines
- Centres should have access to
- Access to awake craniotomy with language and other appropriate functional monitoring
- Expertise in intraoperative neurophysiological monitoring
- Access to neuroradiological support
- Access to intraoperative image guidance
- Consider surgical resection as part of initial management (within 6 months of radiological diagnosis to
- Obtain a histological and molecular diagnosis
- Remove as much of the tumour as safely possible after discussion of the possible extent of resection at MDT meeting and with pt + relatives
Other Guidelines
Duffau
Surgery
General
- Resection avoid misdiagnosis that can occur with biopsy
- Early and maximal surgical resection is the first therapeutic option to consider in DLGG, as recommended by the European guidelines published in 2010 (Soffietti et al., 2010).
- The role of needle biopsy is limited to patients who do not want or who are not able to undergo resection for medical reasons.
- Biopsy can be mainly considered for diffuse lesions, such as gliomatosis, when a subtotal resection is not a priori possible.
- Once histological diagnosis has been established, certain clinical parameters need to be taken into account to decide whether adjuvant therapy should be instituted.
- The following clinical characteristics would make recommendation of adjuvant treatment more likely:
- Aged more than 40
- Partial resection/ residual more than 10 ml
- Astrocytoma histology
- Triple negative, or TERT mutation status
- Rapid growth
- Difficult to control seizures
- The threshold for radiotherapy will probably be lower in the case of astrocytoma, TERT, and triple negative tumours, considering their poorer OS and the poor response to ChT.
- However, the significance of the molecular markers ought to be considered with a degree of caution, especially as they await wider validation.
Indication for surgery
- Seizure control
- To reduce tumour bulk
- To prevent malignant progression
- Prevent progression of tumour to eloquent areas of the brain
Extent of resection (extent of resection (EOR)
- Measured based on volumetric assessment of FLAIR MRI
Theory
- OS outcome: Better (Complete resection > small residual > large residual) Worse
- Due to either
- ‘Histological upgrading’: When you resect all tumour and it is found that some parts have high grade foci then it is removed from studies of LGG
- True biological downgrading of the tumour: because the volume of residual tumour serves as a predictor of anaplastic transformation
Surgery vs Observation
- Aghi 2015: Surgical resection is recommended over observation to improve overall survival for patients with diffuse low-grade glioma (Level III) although observation has no negative impact on cognitive performance and quality of life (Level II)
Biopsy vs Resection
- Aghi 2015: surgical resection should be carried out to maximize the chance of accurate diagnosis.
- Jakola 2012
- Two centres
- B do resection
- A do Biopsy
- Outcome
- Overall survival was significantly better with early surgical resection (P=.01).
- Median survival was 5.9 years (95% CI, 4.5-7.3) with the approach favouring biopsy only while median survival was not reached with the approach favouring early resection.
- 5-year survival
- Biopsy: 60%(95% CI, 48%-72%)
- Early resection: 74% (95% CI, 64%-84%)
- Adjusted multivariable analysis the relative hazard ratio was 1.8 (95% CI, 1.1-2.9, P=.03) when treated at the centre favouring biopsy and watchful waiting.
- Downside
- Biopsy alone was carried out in 47 (71%) patients served by the centre favouring biopsy and watchful waiting and in 12 (14%) patients served by the centre favouring early resection (P⬍.001).
- Retrospective study
- More oligos in the resected group (19vs9%) than biopsy group
- Early post- operative radiation therapy was administered more commonly at the centre favouring resection (43%) vs the center preferring biopsy alone (29%).
Evidence
- GTR vs STR
- Survival benefits with extent of resection in low-grade gliomas (WHO grade I and II) using volumetric analyses
- LGG, low-grade glioma; EOR, extent of resection; OS, overall survival; PFS, progression-free survival; MPFS, malignant progression-free survival.
- Claus et al. 2005: N=156 LGG
- Incomplete resection had 4.9 x the risk of death compared with those who underwent total resection.
Study | Year | Tumor Type (n) | Number of Patients | Extent of Resection (%) | Conclusions |
Claus et al. | 2005 | Oligodendroglioma (95) Astrocytoma (35) Mixed (26) | 156 | 100 <100 | Patients who underwent subtotal resection were at 1.4× the risk of disease recurrence and 4.9× the risk of death relative to patients undergoing gross total resection. There is a possible association between resection and survival for LGG using intraoperative magnetic resonance imaging. |
Smith et al. | 2008 | Astrocytoma (93) Oligodendroglioma (91) Mixed (32) | 216 | 100 90–99 70–89 41–69 0–40 | Patients with at least 90% EOR had 5-year and 8-year OS of 97% and 91%, respectively OS was predicted by EOR, preoperative and postoperative tumor volume on multivariate analysis. PFS was predicted by preoperative and postoperative tumor volume. MPFS was predicted by EOR and preoperative tumor volume. Improved outcome in adults with LGG was predicted by greater EOR. |
Snyder et al. | 2014 | Oligodendroglioma (93) | 93 | 0–100 | A greater EOR was associated with improved OS, but did not prolong MPFS |
- Yeh et al. 2005 N=93 LGG
- EOR and postoperative KPS showed independent prognostic significance for OS using multivariate analysis
- Duffau et al. 2005 N=222 LGG
- 20.6% of patients with > 10 cc of residue died,
- 8% of patients with < 10 cc of residue died
- 0% of patients with complete resection died
- Smith et al. 2008 N=216 LGG
- After adjusting for the effects of
- Age
- KPS
- Tumour location
- Tumour subtype
- EOR remained a significant predictor of
- Malignant PFS
- OS
- 8- year OS of 98% of patients who underwent complete resection.
- Survival was significantly better with > 90% EOR vs < 90% EOR
- EOR of at least 80% also remained a significant predictor of OS.
- McGirt et al. 2008 N=170 LGG
- Observed that gross total resection (complete resection of the preoperative FLAIR signal abnormality) versus subtotal resection was independently associated with increased OS (P = 0.017).
- Chaichana et al. 2010 N=191 LGG
- Gross total resection was an independent factor associated with anaplastic transformation
- Ahmadi et al. 2009 N=130 LGG
- > 90% resection to be associated with prolonged OS.
- Schomas et al. 2009 N= 314 LGG
- 13.6- year follow-up
- < Subtotal resection was an adverse prognostic factor for OS.
- Youland et al., 2013 N=852 LGG
- Gross total resection and subtotal resection were factors associated with improved OS
- Lus et al. 2012 N=190 LGG
EOR | 5 year OS |
> 90% | 93% |
70% - 89% | 84% |
<70% | 41% |
- French Glioma Network (FGN) (Capelle et al., 2013) N=1097 LGG
- EOR and postsurgical residual volume were independent prognostic factors significantly associated with longer OS .
- Pallud et al., 2014 N=1509 LGG
- Surgical resection being an independent prognostic factor associated with increased
- Malignant PFS (P = 0.001)
- OS = almost 15 years
Drawbacks to maximum resection
- McGirt 2009:
- For GBM → extend to LGG. surgical morbidities (motor or language deficits ) may also affect survival despite similar extent of resection and adjuvant therapy.
- Patients with a new postoperative motor deficit (P < 0.05) or a new postoperative language deficit (P < 0.05) experienced decreased overall survival compared with patients without a new-onset perioperative neurological deficit.
- Median and 2-year survival in patients who acquired a new perioperative motor deficit, a new perioperative language deficit, or did not acquire a new operative-induced neurological deficit
ㅤ | Median survival (mo) | 2-year survival (%) |
New perioperative motor deficit | 9.0 | 8 |
New perioperative language deficit | 9.6 | 0 |
No new perioperative deficit | 12.8 | 23 |
Supra maximal resection
- Goal
- Reduction of permanent neurological deficit to below 5%
- The limit of resection should not be the ‘tumour boundary’ but rather brain functional boundary.
- Resection extending beyond the MRI signal abnormalities
- Leeuw 2019 - Meta-analysis
- New studies support supratotal resection in both low- and high-grade glioma, but evidence is poor.
- Only 88 out of 492 patients across reviewed studies had supratotal resections.
- Evidence quality is low, showing some promise, but widespread application is not yet justified.
- Definition of supratotal resection is variable and not standardised
- Yordanova 2011
- Supratotal resection performed in patients with a DLGG within non-eloquent brain regions avoided AT at a mean follow- up of 35.7 months and maximum follow- up of 135 months
- This series was compared with a control group having only complete resection for a DLGG.
- Anaplastic transformation was observed in seven patients in the control group but not in any of the patients who underwent supratotal resection (P = 0.037).
- Furthermore, adjuvant treatment was administrated to ten patients in the control group versus only one patient with supracomplete resection (P = 0.043).
- Duffau 2015
- 11 year follow up of 16 patients with LGG who had supratotal resection
- There was no relapse in eight cases. Eight patients experienced tumor recurrence, with an average time to relapse of 70.3 months (range, 32–105 months), but without malignant transformation.
- Five of them have been re-treated, with a reoperation (two cases), chemotherapy (three cases) and radiotherapy (two cases).
- Rossi 2019
- Supratotal resection was possible in approximately half the cases the others were gross total resection
- Post op at 3 months neurocognition improves to baseline but is worse initially post op
- Supratotal resection is safe in terms of preserving memory, language, praxis, executive functions, and fluid intelligence
Adjuncts
- Intraoperative MRI
- Evidence
- Aghi 2015.pdf:
- Intraoperative MRI should be considered as a method of increasing the extent of resection of LGGs.
- Black et al., 1999
- Intraoperative MRI has been shown to increase both the extent of the resection and survival in patients with low- or high- grade glioma
- Lo 2021
- IMRI use improved GTR in gliomas, including LGGs.
- No PFS and OS benefit was shown in the meta-analysis.
- Coburger 2016
- GTR was an independent positive prognostic factor for PFS in LGG surgery.
- Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors.
- Use of high-field iMRI was significantly associated with GTR.
- Pros
- To fix the issues with brain shift due to CSF loss and tissue oedema (Nimsky et al., 2002).
- Cons
- Foreign environment
- Takes 40mins to do scan
- Preoperative imaging
- Aghi 2015.pdf: It is recommended that preoperative fMRI and DTI be utilized in the appropriate clinical setting to improve functional outcome after surgery for LGG.
- iKnife
- Uses mass spectroscopy from smoke
- Raman spectroscopy
- Uses light spectroscopy
- Neuronavigation
- Awake craniotomy
- Brain mapping
- Direct cortical electrocorticography
- Visualising tumour: Fluorophores
- 5-ALA
Reoperation
- Indicated
- Recurrence/regrowth of tumour
- For Gross total resection
- For Subtotal resection
- Debulk to allow radiotherapy to prevent radiotherapy induced focal symptomatic mass effect or raised intracranial pressure
- Part of initially planned treatment (Duffau)
- Initial surgery to help remap the brain then when the portion of the cortex is non functional perform further resection
- If the relationship between the growth of DLGG and brain adaptation are taken into account
- Cerebral rehabilitation
- Regular neurocognitive assessments and serial functional neuroimaging can provide helpful data for predicting EOR of a second or even third or fourth surgery.
- Management of intractable epilepsy
- Because even partial resection may result in a relief of seizures.
- Esp if tumours located within the insula or mesiotemporal structures.
- In cases with intractable epilepsy, chemotherapy (ChT) and/ or radiation therapy (RT) should also be considered.
- French Glioma Network Capelle et al., 2013
- Subsequent surgical resection was an independent prognostic factor significantly associated with longer OS
- As with primary surgery the degree of resection influences OS (Ramakrishna et al., 2015).
- Reoperation should be considered in all recurrent tumours, including those located in eloquent areas as greater degree of resection can be achieved.
- Martino et al., 2009
- Total or subtotal resection was achieved in 73.7% of patients during the reoperation, despite involvement of functional areas ().
- Median time between surgeries was 4.1 years.
- Early vs Late
- Aim to catch tumour cell before the transform
- Such a multistage surgical approach— beginning with initial function- guided resection, followed by a period of several years, and then a second surgery with optimization of EOR while preserving QoL— is possible, thanks to brain plasticity (Duffau, 2005; Duffau, 2014).
- However, a significant oncological benefit of surgery was demonstrated only when the resections were at least subtotal.
- So if glioma is very diffuse just do subtotal resection
Incidental LGG
- Compared to symptomatic LGG are
- Less likely to be located in eloquent areas of the brain,
- Have lower preoperative volume,
- Greater likelihood of total resection
- Longer OS
- As EOR is a major predictor of OS, PFS, and AT, and because of gross total and supratotal resections are more likely achievable in incidental DLGGs,
- Early and radical surgical resection has been proposed (Duffau, 2012b)
- Arguments are now being put forward for screening for DLGGs (Mandonnet et al., 2014).
Outcome
- Shaw 2008
- Prognostic Factors in RTOG 9802:
- Size of initial tumor (>4 cm)
- Size of residual tumor (>1 cm)
- Histology: Astrocytoma
- Study Details:
- Recruitment Period: 1998 to 2002
- Study Population: 111 patients included
- Criticism:
- Main criticism: Extent of resection assessed by the surgeon
- Survival Outcomes:
- OS (Overall Survival) rates at 2 and 5 years: 99% and 93%, respectively
- PFS (Progression-Free Survival) rate at 5 years: 48%
- Prognostic Factor Impact:
- In patients without unfavorable prognostic factors, 2- and 5-year PFS rates were 100% and 70%, respectively
- Patients with unfavorable prognostic factors had a PFS less than 50% at 5 years
- Recommendation:
- Close follow-up and adjuvant treatment should be considered in the high-risk group
- Aghi 2015.pdf: After taking into account the patient’s clinical status and tumour location, gross total resection is recommended for patients with diffuse LGG as a way to achieve more favourable seizure control.
Chemotherapy
Aims
- Improvement of QoL via
- Reduction of seizures
- Reduction neurological deficits. (Quinn et al., 2003; Koekkoek et al., 2015).
- Cytoreduction
- For
- Incomplete resection
- Rapid progression on follow- up MRIs
- Can take 24 - 30 months to see radiological reduction in tumour
- May persist once chemotherapy has been terminated, even though this is not the case for the majority of patients.
Options
PCV
- Made up of
- Procarbazine
- Lomustine (also known as CCNU)
- Vincristine
- Toxic
- Constitutional symptoms
- Fatigue
- Weight loss
- Blood or bone marrow disorder
- Hemoglobin decreased
- Packed red-cell transfusion required
- Platelet count decreased
- Platelet transfusion
- Neutropenia
- Febrile neutropenia
- Infection
- Lymphopenia
- Gastrointestinal disorder
- Anorexia
- Constipation
- Nausea
- Vomiting
- Hepatic disorder
- Alanine aminotransferase increased
- Aspartate aminotransferase increased
- Oligodendrogliomas
- PCV can lead to 50% complete resolution
- Non oligodendroglioma: 25% response
Temozolomide (TMZ)
- Better toxicity profile
- Better tolerability (especially reduced myelotoxicity) → better QoL (Soffietti et al., 1998; van den Bent et al., 1998; Quinn et al., 2003; van den Bent et al., 2003; van den Bent et al., 2012; Fisher et al., 2015).
Vorasidenib
- Indicated for
- IDH1- or IDH2-Mutant Low-Grade Glioma
- Mellinghoff 2023
- Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes
- Inclusion:
- Residual or recurrent grade 2 IDH-mutant glioma
- No previous treatment other than surgery
- Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival,
- 27.7 months vs. 11.1 months: 16 months
- Hazard ratio for disease progression or death, 0.39
Outcome
- Similar objective response rates on MRI (45– 62%)
- Duration of response (10– 24 months)
Evidence
TMZ
- Koekkoek et al., 2015 N=104 LGG
- For TMZ
- Most patients with seizures have clinical benefit, even in the absence of a radiological change
- ≥50% reduction in seizure frequency after 6 months occurred in 43.9% patients.
- Oligodendroglial tumours are more likely to respond, but those with mixed or astrocytic tumours also may respond
- Kaloshi et al., 2007; Kesari et al., 2009
- All LGGs exhibit some response to TMZ treatment
- Response rate is significantly higher and the duration of response is longer and resulted in longer PFS and OS for patients with
- 1p/ 19q loss than for those with 1p/ 19q intact
- Methylated MGMT promoter
- Protracted low doses of TMZ when compared with standard TMZ regimen
- Have resulted in prolonged OS and PFS even in patients with unmethylated MGMT promoters (Kesari et al., 2009).
- Protracted low doses of TMZ was associated with increase in TMZ- related toxicity.
- Johnson et al. (2014)
- Occurrence of multiple mutations in LGG patients treated with TMZ.
- 6/10 patients treated with TMZ recurred as high- grade gliomas.
- However, the study cohort (N = 23) is not representative of DLGGs as a whole as only one case was an oligodendroglioma with all samples having either ATRX or p53 or both genes mutated and nearly three- quarters of the tumours recurred as high- grade gliomas.
- At present it is unclear whether this TMZ- induced hypermutation genotype found in this study is a phenomenon occurring in LGGs across the board and it is even less clear whether the hypermutation genotype influences outcome in LGGs. As such these findings should be regarded only as a laboratory finding (van den Bent, 2014).
- Baumert 2016 EORTC III for high-risk low-grade glioma: RT (RED) vs TMZ (BLUE): no diff
- Low-grade glioma (astrocytoma, oligoastrocytoma, oligodendroglioma, WHO grade II) with at least one high-risk feature:
- Age > 40 years
- Progressive disease
- Tumor > 5 cm or crossing the midline
- Neurological symptoms (focal or mental deficits, increased intracranial pressure or intractable seizures)
PCV vs TMZ
- Hafazalla 2018
- Adjuvant therapy with PCV results in prolonged PFS and OS in patients with newly diagnosed high-risk LGG.
- Age over 40 years
- Astrocytic histology
- Tumour diameter >= 6cm or crossing the midline
- Neurological deficit prior to surgery
- There is not enough evidence to say RT and TMZ are an inferior option, as this is primarily due to lack of trials investigating this subject matter.
- Some evidence to say that PCV is better than TMZ for oligodendrogliomas.
- Temozolomide is associated with lower toxicity than therapy with PCV
- PCV grade 3/4 toxicity occured in 40-70% of patients
- Intact 1p/19q and wildtype IDH1, RT/TMZ plus adjuvant TMZ may be the best option.
Radiotherapy
General
- Not as a first therapeutic option (Youland et al., 2013)
- Because of its potentially delayed neurotoxicity and the equivalent results in terms of OS whatever the timing of treatment (early or late), RT is being increasingly reserved to high risk patients with
- Unresectable tumours or tumours that cannot be reoperated and
- In cases of progression after ChT
Indication
- Size >6cm
- Age >40
- Young patients with GTR can be observed due to cognitive deficits risk
- Tumour crossing midline
- Astrocytoma
- Neurological deficits
- Patient with high risk of transformation
Dose
- 45-54Gy in fractions of 1.8-2.0Gy
Side effect of radiotherapy
- Malignant transformation
- In situ tumour formation
- Cognitive deficit
- Douw et al., 2009 N=65 LGG
- Neuropsychological follow-up at 12 years
- No radiation group
- Were free of tumour progression maintained their cognitive status
- Radiation group
- Worsening of their
- Attentional and executive functioning
- Information- processing speed
- 50% will develop long term cognitive deficits from radiotherapy at 12 yrs
- It is nonetheless important to acknowledge some limitations in this study:
- The lack of baseline testing,
- The inherent selection bias of patients who received radiotherapy having more aggressive disease,
- The use of out- dated techniques such as whole brain radiotherapy.
- Lawrie 2019 Cochrane Meta analysis
- All outcomes at best had low certainty of evidence
- Radiotherapy versus no adjuvant treatment
- Radiotherapy patient possibly had greater cognitive impairment
- High‐dose radiotherapy versus low‐dose radiotherapy
- No difference in terms of cognitive side effect
- The study later will show no OS or PFS benefit for high dose
- Conventional radiotherapy versus stereotactic conformal radiotherapy
- Stereotactic had fewer cognitive side effect than conventional radiotherapy
- Chemoradiotherapy versus radiotherapy
- No difference in MMSE scores between the two study arms
- Forest plot of comparison A (exploratory with totals):
- Radiotherapy versus no RT, outcome: Neurocognitive impairment at 2 or more years after RT.
- Reijneveld 2016
- N=477 LGG
- radiotherapy vs temozolomide
- No difference in QOL
- No difference in Neuro-cognition (MMSE)
Evidence
EORTC II (Karim 2002)
- Early RT prolongs progression free survival but does not change overall survival
- PFS: 4.8 yrs vs 3.4 yrs (RT vs no RT)
- OS: 5 year survival rate: 63% vs 66% (RT vs no RT)
High vs low dose
- Two phase III randomized trials have demonstrated no advantage for high versus low radiation doses and reported increased toxicity in higher doses
- EORTC I: Karim et al., 1996
- Showed no benefit (5 year OS and 5 year PFS) high dose RT (59Gy) vs low dose RT (45Gy)
- At 74 months median follow up
- Shaw et al., 2002: North central cancer treatment group
- No differences in 2- and 5-year overall survival (OS) between low dose (94% and 75%) and high dose (85% and 64%), p = 0.48
- Higher rates of severe radionecrosis seen in high dose group (5% versus 2.5%)
RT dose | High | low |
Over all survival | 59% | 58% |
Progression free survival | 47% | 50% |
Early or late RT
- van den bent 2005
- EORTC 22845 phase III randomised trial
- Progression-Free Survival (PFS): Early RT improved median PFS (5.3 vs 3.4 years; HR 0.59, p<0.0001)
- Overall Survival (OS): No significant difference in median OS (7.4 vs 7.2 years; HR 0.97, p=0.872)
- At 1 year, irradiated pt had better seizure control
- Irradiated: 25% had seizure
- Non-irradiated: 41% had seizure
Combination
RT vs TMZ
- Baumert 2016 EORTC III N=707 LGG Grade 2/3 astrocytoma & Grade 2/3 Oligodendroglioma
- 48 months f/u: Median overall survival has not been reached.
- No significant difference in PFS in patients with all types of LGG
- Median PSF
- TMZ: 39 months
- RT: 46 months
- G2/3 Astrocytoma RT>TMZ
- G2/3 oligodendroglioma No significant difference in PFS
- Regardless of whether they have MGMT hypermethylation
- All IDHmt/codel and 90% of the IDHmt/non-codel tumors have a methylated MGMT promoter → MGMT testing does not provide additional prognostic or predictive value in the IDHmt subgroup
- IDHwt tumors, MGMT may be of a predictive value
RT + TMZ vs RT
- Fisher 2015
- RT+TMZ vs RT (historical data) for high-risk low-grade glioma
- High risk definition
- Age ≥ 40 years
- Preoperative tumor diameter ≥ 6 cm
- Bihemispherical tumor (crosses the midline)
- Astrocytoma histology
- Preoperative neurological function status > 1 (moderate–severe impairment)
- RT+TMZ
- 3-year Overall Survival Rate
- 73.1% for RTOG 0424 high-risk patients, which was significantly higher than both historical controls (p<0.001) and the study hypothesized rate of 65%
- Progression-Free Survival (PFS): 3-year PFS was 59.2%
- Van den Bent 2017 (EORTC study 26053-22054) n=745
- Grade 2 Astrocytoma: RT + TMZ vs RT
- HR for overall survival with use of adjuvant temozolomide was 0·65.
- 5 years OS
- 55·9% with adjuvant temozolomide
- 44·1% without adjuvant temozolomide
RT + PCV vs RT
- Buckner 2016
- Critique
- How it change in practice, but 50% were only biopsy, therefore does not applicable to us who do more total resection
- This study is frequently misinterpreted as demonstrating benefit of early use of radio- and chemotherapy. Instead, it demonstrates benefit of early use of chemotherapy.
Radio | Radio + PCV | |
Median overall survival | 7.8yrs | 13.3 yrs |
Overall survival at 10 yrs | 40% | 60% |
Progression free survival at 10 yrs | 21% | 51% |
- Van den Bent 2012
- Grade 3 Oligodendrogliomas RT + PCV > RT N=80 (Rest of the study had 369)
- Median OS for grade 3 oligodendrogliomas
- RT 111.8
- RT+PCV not reached
- Cairncross 2013 RTOG 9402 RT +PCV> RT grade 2/3 oligodendroglioma
- The hazard ratio (HR) for overall survival of patients with codeleted AO/AOA treated with procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) compared with those treated with RT alone was 0.59 (95% CI, 0.37 to 0.95; P = .03).
Outcome
- Five- and ten-year survival rates for diffuse gliomas grades 2-4
- Oligodendroglioma: 80,50
- Astrocytoma: 50,25,5
- Glioblastoma 5%
Diffuse glioma (WHO grade) | 5-year relative survival rate (%) | 10-year relative survival rate (%) |
Oligodendroglioma (2) | 79.5 | 62.8 |
Anaplastic oligodendroglioma (3) | 52.2 | 39.3 |
Astrocytoma (2) | 47.4 | 37.0 |
Anaplastic astrocytoma (3) | 27.3 | 19.0 |
Glioblastoma (4) | 5.0 | 2.6 |
- Baumert 2016:
- for PFS as OS not reached in 48 months
- Median Overall survival
- Oligodendroglioma: 10 years
- Astrocytoma: 4 years
- Gliomas: 1.5 years
- Low grade to High grade malignant transformation (MT)
- Tom 2019:
- MT occurred in 84 (17%) patients,
- 5-year freedom from MT of 86%
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