Publications by authors named "Luis Souhami"

139 Publications

BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort.

Oncology 2021 May 6:1-9. Epub 2021 May 6.

Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA.

Purpose: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA).

Methods And Materials: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test.

Results: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months.

Conclusions: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment.
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http://dx.doi.org/10.1159/000516168DOI Listing
May 2021

OPTIMIZING TREATMENT IN INTERMEDIATE RISK PROSTATE CANCER: SECONDARY ANALYSIS OF A RANDOMIZED PHASE III TRIAL.

Int J Radiat Oncol Biol Phys 2021 Apr 23. Epub 2021 Apr 23.

McGill University Health Centre, CA.

Purpose: To identify patients with intermediate risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiotherapy (DERT), we performed a secondary analysis of a phase III trial by measuring biochemical failure (BF), distant metastases (DM), prostate cancer specific mortality (PCSM), overall survival (OS) and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF).

Methods: The initial trial randomized 600 patients with IRPC to a three-arm trial with 200 patients per arm consisting of 6 months of ADT plus RT 70Gy (ADT+RT70) vs. ADT plus a DERT of 76Gy (ADT+DERT76) vs. DERT of 76Gy alone (DERT76). We performed an analysis based on IRF present: clinical stage, PSA level, Gleason score, percentage of positive biopsy cores (PBC) ≥50% and Gleason pattern. Patients were allocated into two groups: favorable intermediate risk (FIR), defined as patients with only one IRF without Gleason pattern 4+3 or PBC ≥50% and unfavorable intermediate risk (UIR) all other patients. BF, DM, PCSM, OS and DMFS were compared between FIR and UIR.

Results: The median follow-up is 11.3 years (interquartile range: 10.9-11.7). In the FIR cohort, BF and OS were not significantly different between arms. UIR patients had significantly worse DMFS [Hazard ratio (95% confidence interval) = 1.61 (1.20-2.15), p=0.026] and OS [HR=1.51 (1.12 - 2.04), p=0.0495] and a non-significant higher cumulative incidence of BF rate [1.55 (0.98-2.47), p=0.08]. In UIR patients a significant improvement in BF was seen in the arms receiving ADT compared to DERT76 alone. On multivariable analysis, Gleason pattern 4+3 and PSA >10 ng/ml independently impacted on BF and OS, regardless of the treatment arm.

Conclusions: In IRPC, therapeutic optimization appears possible. To avoid ADT side effects, DERT76 alone appears sufficient in patients harboring only one RF without Gleason pattern 4+3 and PBC ≥50% (FIR). All other UIR patients seem to benefit from ADT + DERT76.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.013DOI Listing
April 2021

Bladder-sparing protocols in the treatment of muscle-invasive bladder cancer.

Transl Androl Urol 2020 Dec;9(6):2920-2937

Department of Surgery, Division of Urology, McGill University, McGill University Health Centre, Montréal, Québec, Canada.

Bladder-sparing protocols (BSP) have been gaining widespread popularity as an attractive alternative to radical cystectomy (RC) for muscle-invasive bladder cancer. Unimodal therapies are inferior to multimodal regimens. The most promising regimen is trimodal therapy (TMT), which is a combination of maximal transurethral resection of bladder tumor (TURBT), radiotherapy, and chemotherapy. In appropriately selected patients (low volume unifocal T2 disease, complete TURBT, no hydronephrosis and no carcinoma-in-situ), comparable oncological outcomes to RC have been reported in large retrospective studies, with a potential improvement in overall quality of life (QOL). TMT also offers the possibility for definitive therapy for patients who are not surgically fit to undergo RC. Routine biopsy of previous tumor resection is recommended to assess response. Prompt salvage RC is required in non-responders and for recurrent muscle-invasive disease, while non-muscle-invasive recurrence can be managed conservatively with TURBT +/- intravesical BCG. Long-term follow-up consisting of routine cystoscopy, urine cytology, and cross-section imaging is required. Further studies are warranted to better define the role of neoadjuvant or adjuvant chemotherapy in the setting of TMT. Finally, future research on predictive markers of response to TMT and on the integration of immunotherapy in bladder sparing protocols is ongoing and is highly promising.
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http://dx.doi.org/10.21037/tau.2020.02.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807363PMC
December 2020

Phase I Trial of Atezolizumab plus Trimodal Therapy in Patients with localized Muscle-Invasive Bladder Cancer.

Int J Radiat Oncol Biol Phys 2021 Jan 6. Epub 2021 Jan 6.

Division of Urology, McGill University Health Centre, McGill University, 1001 Decarie Blvd, D02.7210, Montreal, QC H4A 3J1, Canada. Electronic address:

Purpose: Immune checkpoint programmed death-ligand 1 (PDL-1) inhibitor therapy has shown response in metastatic muscle invasive bladder cancer (MIBC). We evaluated the safety and tolerability of atezolizumab (anti-PDL-1) in combination with trimodal therapy (TMT) in patients with localized MIBC.

Methods: A prospective non-randomized phase I study using a 3+3 design was conducted in patients with localized MIBC (T2-T4a N0M0) treated on a bladder preservation program. Following trans-urethral resection of bladder tumor, patients received concurrent radiotherapy at a fixed dose of 50 Gy/20 fractions, gemcitabine (100 mg/m, IV once weekly x 4) and atezolizumab (1200 mg IV every 3 weeks x 16 cycles). Primary endpoint was safety/toxicity profile.

Results: Between May 2018 and March 2019, 8 patients (6 males and 2 females) were enrolled. The first 5 patients received atezolizumab at 1200 mg, three of whom developed grade 3 side effects (2 of them dose limiting toxicity). Atezolizumab dose was reduced to 840 mg for 3 additional patients. The study was terminated due to the presence of three grade 3 adverse events (2 of them dose limiting toxicity) despite the reduced atezolizumab dose. Gastro-intestinal (GI) events were the main toxicity. No grade 4-5 adverse effects were observed.

Conclusion: Concurrent administration of atezolizumab with concomitant hypofractionated radiotherapy and gemcitabine appears to be associated with unacceptable GI toxicity. While numbers studied are small, our results suggest considerable caution with its concurrent use with trimodal therapy for MIBC.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.033DOI Listing
January 2021

Refining assessment of response to radiation-based therapy for muscle-invasive bladder cancer: Is post-treatment tumor bed biopsy always necessary?

Urol Oncol 2020 Oct 23. Epub 2020 Oct 23.

Department of Urology, McGill University Health Centre, McGill University, Montreal, QC, Canada. Electronic address:

Introduction: Radiation-based therapy (RT) has emerged as a suitable alternative to radical cystectomy (RC) and pelvic lymph node dissection for muscle-invasive bladder cancer (MIBC) patients. Routine biopsy after RT to rule out residual disease remains inconsistent across guidelines. Our objective was to review the significance of a bladder biopsy in terms of assessment of response post-RT and its potential impact on survival.

Patients And Methods: This was a single-center retrospective study on patients with MIBC (cT2-4aN0-2M0) treated with curative intent RT. A total of 169 patients with primary urothelial carcinoma were analyzed. Patients' demographic, clinical and pathological variables, imaging, cystoscopy, urine cytology, and biopsy reports after RT were collected and compiled. Whenever urine cytology was positive or cystoscopy showed any malignant-appearing lesion, the first assessment post-RT was considered suspicious for residual disease. A descriptive population analysis was reported. Cox regression multivariable analysis was performed to identify independent variables associated with survival outcomes.

Results: Median age was 75 years (interquartile range 66-82) and clinical staging was cT2 in 152 (90%) patients. Cytology and cystoscopy were normal in 140 (83%) after RT. Of patients with a control biopsy, residual MIBC was present in 3 (5%) and non-MIBC in another 6 (11%). On the contrary, a for-cause biopsy due to a suspicious assessment post-RT did not yield residual cancer in 45% of patients. Multivariable analysis showed that age (hazard ratio [HR] 1.04, P< 0.001), lymphovascular invasion (HR 1.68, P = 0.03) and a suspicious assessment after RT (HR 3.21; P< 0.001) were significantly associated with worse OS. This study was limited by its retrospective design.

Conclusions: A routine biopsy after RT may be warranted to assess treatment response. This might be particularly important for patients who may benefit from early surgical intervention for residual MIBC. Further prospective studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.001DOI Listing
October 2020

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial.

Eur J Cancer 2021 01 3;143:64-74. Epub 2020 Dec 3.

McGill University Health Centre, CA, Canada.

Background: The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone.

Methods: From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria.

Findings: With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity.

Interpretation: In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.
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http://dx.doi.org/10.1016/j.ejca.2020.10.023DOI Listing
January 2021

Current topics in radiotherapy for genitourinary cancers: Consensus statements of the Genitourinary Radiation Oncologists of Canada.

Can Urol Assoc J 2020 Nov;14(11):E588-E593

Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada.

Introduction: The biennial meeting of the Genitourinary Radiation Oncologists of Canada (GUROC) took place November 22-23, 2019. A consensus-building session was held during the meeting addressing topics of emerging interest or controversy in the management of genitourinary malignancies.

Methods: Draft statements were debated among all meeting attendees in an open forum with anonymous live voting. Statements for which there was at least 75% agreement among attendees were adopted as GUROC consensus.

Results: Four evidence-based consensus statements were developed. First, the use of prostate radiotherapy is recommended in the setting of de novo low-volume metastatic hormone-sensitive prostate cancer to improve overall survival. Second, the support of ongoing randomized trials evaluating metastasis-directed ablative local therapy in oligometastatic prostate cancer is recommended; where such trials are available, off-trial use of oligometastasis-directed ablative radiotherapy at this time is strongly discouraged. Third, routine use of prostate-rectal hydrogel spacer devices in patients with localized prostate cancer planned to receive external beam radiotherapy is not recommended; instead, selective use in patients at highest risk of rectal toxicity may be considered. Finally, multidisciplinary consultation is recommended for all patients with newly diagnosed localized muscle-invasive bladder cancer.

Conclusions: The GUROC consensus statements provide practical guidance to clinicians in areas of current controversy in the management of prostate and bladder cancer, and it is hoped that their implementation will contribute to improved outcomes in real-world practice and greater support of clinical trials.
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http://dx.doi.org/10.5489/cuaj.6649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673835PMC
November 2020

Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.

World J Urol 2020 Sep 11. Epub 2020 Sep 11.

Department of Radiation Oncology, Jewish General Hospital, Montreal, QC, Canada.

Purpose: Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer.

Methods: Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu/ retrieved ongoing clinical trials on the topic as well.

Results: Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes.

Conclusion: RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.
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http://dx.doi.org/10.1007/s00345-020-03440-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484608PMC
September 2020

Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e514-e520. Epub 2020 Jul 29.

Department of Radiation Oncology, McGill University, Quebec, Canada.

Purpose: Moderate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique.

Methods And Materials: Patients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan-Meier from the date of last radiation treatment until date of event.

Results: We report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively.

Conclusions: The longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.
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http://dx.doi.org/10.1016/j.prro.2020.06.012DOI Listing
July 2020

Combined Long-Term Androgen Deprivation and Pelvic Radiotherapy in the Post-operative Management of Pathologically Defined High-Risk Prostate Cancer Patients: Results of the Prospective Phase II McGill 0913 Study.

Front Oncol 2020 12;10:312. Epub 2020 Mar 12.

Department of Radiation Oncology, Jewish General Hospital, Montreal, QC, Canada.

Following radical prostatectomy, prostate bed radiotherapy (PBRT) has been combined with either long-term androgen deprivation therapy (LT-ADT) or short-term ADT with pelvic lymph node radiotherapy (PLNRT) to provide an oncological benefit in randomized trials. McGill 0913 was designed to characterize the efficacy of combining PBRT, PLNRT, and LT-ADT. It is the first study to do so prospectively. In a single arm phase II trial conduced from 2010 to 2016, 46 post-prostatectomy prostate cancer patients at a high-risk for relapse (pathological Gleason 8+ or T3) were assessed for treatment with combined LT-ADT (24 months), PBRT, and PLNRT. Patients received PLNRT and PBRT (44 Gy in 22 fractions) followed by a PBRT boost (22 Gy in 11 fractions). The primary endpoint was progression-free survival (PFS). Toxicity and quality of life (QoL) were evaluated using CTCAE V3.0 and EQ-5D-3L questionnaires, respectively. Among the 43 patients were treated as per protocol, median PSA was 0.30 μg/L. On surgical pathology, 51% had positive margins, 40% had Gleason 8+ disease, 42% had seminal vesicle involvement, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there were no deaths or clinical progression. At 5 years, PFS was 78.0% (95% Confidence Interval 63.7-95.5%). Not including erectile dysfunction, patients experienced: 14% grade 2 endocrine toxicity while on ADT, one incident of long-term gynecomastia, 5% grade 2 acute urinary toxicity, 5% grade 2 late Urinary toxicity, and 24% long-term hypogonadism. No comparison between the average or minimum self-reported QoL at baseline, during ADT, nor after ADT demonstrated a statistically significant difference. Combining PBRT, PLNRT, and LT-ADT had an acceptable PFS in patients with significant post-operative risk factors for recurrence. While therapy was well-tolerated, long-term hypogonadism was a substantial risk. Further investigations are needed to determine if this combination is beneficial. NCT01255891.
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http://dx.doi.org/10.3389/fonc.2020.00312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080953PMC
March 2020

The association between BMI and BSA-temozolomide-induced myelosuppression toxicities: a correlative analysis of NRG oncology RTOG 0525.

Neurooncol Pract 2019 Dec 6;6(6):473-478. Epub 2019 Apr 6.

Baptist Hospital of Miami, FL.

Background: Fearing increased myelotoxicity, many practitioners adjust the body surface area (BSA)-calculated doses in obese patients. Regarding temozolomide (TMZ), a prior study suggested men with a BSA >2 m may experience increased toxicity; however, surprisingly, the inverse observation was noted in women, ie, BSA <2 m was associated with higher toxicity. To further clarify this issue, data derived from a large clinical trial were analyzed.

Methods: The incidence of grade 3 and 4 myelotoxicity in a newly diagnosed glioblastoma phase 3 trial (RTOG 0525) was statistically correlated with BMI and separately with BSA. All patients received radiation and TMZ followed by adjuvant standard dose TMZ vs dose-dense TMZ; dosing regimen-associated myelotoxicity and BMI/BSA were analyzed separately. was defined as a BMI ≥30.

Results: There was no statistically significant correlation between gender and BSA and the occurrence of myotoxicities. For the standard arm, surprisingly the incidence of grade 3/4 myotoxicities in patients with a BMI <30 was significantly higher than in patients with a BMI ≥30 (12% vs 1%, odds ratio [OR] 12.5, < .001). There was no significant difference between obese and nonobese patients (BMI "cut-point" of 30) in the dose-dense arm (OR = 0.9, 95% confidence interval: 0.4-1.6). The grade hematological 3/4 toxicity rate was significantly higher in women vs men (14% vs 8%) = .009 in spite of the lack of association between gender and BSA or BMI.

Conclusion: TMZ dosing based on actual BSA is recommended with the caveat that woman are likely at higher toxicity risk.
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http://dx.doi.org/10.1093/nop/npz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899045PMC
December 2019

Novel knowledge-based treatment planning model for hypofractionated radiotherapy of prostate cancer patients.

Phys Med 2020 Jan 6;69:36-43. Epub 2019 Dec 6.

McGill University Health Centre, Montreal, QC, Canada.

Purpose: To demonstrate the strength of an innovative knowledge-based model-building method for radiotherapy planning using hypofractionated, multi-target prostate patients.

Material And Methods: An initial RapidPlan model was trained using 48 patients who received 60 Gy to prostate (PTV60) and 44 Gy to pelvic nodes (PTV44) in 20 fractions. To improve the model's goodness-of-fit, an intermediate model was generated using the dose-volume histograms of best-spared organs-at-risk (OARs) of the initial model. Using the intermediate model and manual tweaking, all 48 cases were re-planned. The final model, trained using these re-plans, was validated on 50 additional patients. The validated final model was used to determine any planning advantage of using three arcs instead of two on 16 VMAT cases and tested on 25 additional cases to determine efficacy for single-PTV (PTV60-only) treatment planning.

Results: For model validation, PTV V of 99.9% was obtained by both clinical and knowledge-based planning. D was lower for model plans: by 1.23 Gy (PTV60, CI = [1.00, 1.45]), and by 2.44 Gy (PTV44, CI = [1.72, 3.16]). OAR sparing was superior for knowledge-based planning: ΔD = 3.70 Gy (bladder, CI = [2.83, 4.57]), and 3.22 Gy (rectum, CI = [2.48, 3.95]); ΔD = 1.17 Gy (bowel bag, CI = [0.64, 1.69]), and 4.78 Gy (femoral heads, CI = [3.90, 5.66]). Using three arcs instead of two, improvements in OAR sparing and PTV coverage were statistically significant, but of magnitudes < 1 Gy. The model failed at reliable DVH predictions for single PTV plans.

Conclusions: Our knowledge-based model delivers efficient, consistent plans with excellent PTV coverage and improved OAR sparing compared to clinical plans.
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http://dx.doi.org/10.1016/j.ejmp.2019.11.023DOI Listing
January 2020

Gleason pattern 5 is associated with an increased risk for metastasis following androgen deprivation therapy and radiation: An analysis of RTOG 9202 and 9902.

Radiother Oncol 2019 12 17;141:137-143. Epub 2019 Sep 17.

Cedars-Sinai Medical Center, Department of Radiation Oncology, Los Angeles, USA. Electronic address:

Background/purpose: Stratification of Gleason score (GS) into three categories (2-6, 7, and 8-10) may not fully utilize its prognostic discrimination, with Gleason pattern 5 (GP5) previously identified as an independent adverse factor.

Materials/methods: Patients treated on RTOG 9202 (n = 1292) or RTOG 9902 (n = 378) were pooled and assessed for association of GS and GP5 on biochemical failure (BF), local failure (LF), distant metastasis (DM), and overall survival (OS). Fine and Gray's regression and cumulative incidence methods were used for univariate and multivariate analyses.

Results: With median follow-up of 9.4 years, patients with GS 8-10 with GP5 had worse outcome than GS 4 + 4 for DM on both RTOG9202 (p = 0.038) and RTOG9902 (p < 0.001) with a trend toward worse OS (p = 0.059 and p = 0.089, respectively), but without differences in BF or LF. At 10-years DM was higher by 11% (RTOG 9202) and 18% (RTOG 9902) with GP5 compared to GS 4 + 4. On multivariate analysis restricted to long-term androgen deprivation therapy the presence of GP5 substantially increased distant metastasis (HR = 0.43, 95%CI: 0.24-0.76, p = 0.0039) with a trend toward worse OS (HR:0.74, 95% CI:0.54-1.0, p = 0.052) without association with LF (HR:0.55, 95%CI:0.28-1.09, p = 0.085) or BF (HR:1.15, 95%CI:0.84-1.59, p = 0.39). We did not observed substantial differences between Gleason 3 + 5, 5 + 3, or Gleason 9-10.

Conclusions: These results validate GP5 as an independent prognostic factor which is strongest for DM. As a result GP5 should be considered when stratifying patients with GS 8 and may be a patient population in which to evaluate newly approved systemic therapies or additional local treatments.
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http://dx.doi.org/10.1016/j.radonc.2019.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912855PMC
December 2019

Growth of Pituitary Macroadenomas Postpartial Resection: Implications for Adjuvant Radiotherapy.

J Neurol Surg B Skull Base 2019 Jun 10;80(3):323-326. Epub 2018 Oct 10.

Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec, Canada.

 To determine the volumetric growth in macroadenomas (MAs) patients with residual postoperative disease and to identify subpopulations with rapid postoperative growth rate that may benefit from early salvage radiotherapy (RT).  Patients who had undergone a partial resection for MAs and did not receive immediate postoperative RT were eligible. Residual tissue was contoured on serial magnetic resonance imaging and planimetric and volumetric changes in size were measured. Growth rates were established by a single observer using serial volumetric measurements. Data were analyzed to find a relationship among growth rate, adjuvant treatment, and patient and tumor characteristics.  Thirty-one patients met the eligibility criteria. Nine patients (29%) required adjuvant treatment because of tumor growth. Volumetric growth was identified 95% of the time compared with 64% planimetrically. Planimetric growth could not be established in 10% of patients showing volumetric changes. Median growth rate was 0.4464 mL/y. Growth rate positively correlated with size of residual postoperative volume (  < 0.001). Receiving salvage treatment positively correlated with growth rate (  = 0.001), particularly at a rate above 2.19 mL/y (  = 0.0064). Five patients (16%) had a growth rate above this level, all of which required salvage treatment. Patients with postoperative residual volume > 3.95 mL were most likely to experience rapid growth rate and require salvage treatment (  = 0.007).  Volumetric measurement was found to be superior to planimetric measurement in detecting changes in patients with residual tumors. Patients with postoperative residual volume > 3.95 mL should be considered for early treatment with RT.
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http://dx.doi.org/10.1055/s-0038-1670686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534728PMC
June 2019

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

Int J Radiat Oncol Biol Phys 2019 08 6;104(5):1057-1065. Epub 2019 Apr 6.

Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer.

Methods And Materials: This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs >0.1 ng/mL) groupings, and clinical outcomes.

Results: The median follow-up for surviving patients was 9.4 years. The median post-neoAS, pre-RT PSA level was 0.3 ng/mL, with 32% of patients having levels ≤0.1 ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and >0.1 ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1 ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P < .0001); local failure (HR, 2.51; P < .0001); distant metastases (HR, 1.73; P = .0006); cause-specific mortality (HR, 2.36; P < .0001); and all-cause mortality (HR, 1.24; P = .005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1 ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P < .0001); local failure (HR, 2.33; P < .0001); and cause-specific mortality (HR, 1.75; P = .03).

Conclusions: Patients with a PSA level >0.1 ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1 ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.
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http://dx.doi.org/10.1016/j.ijrobp.2019.03.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646073PMC
August 2019

Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial.

J Clin Oncol 2019 05 12;37(14):1159-1168. Epub 2019 Mar 12.

6 Cedars-Sinai Medical Center, Los Angeles, CA.

Purpose: Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer.

Patients And Methods: The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT.

Results: A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided = .043).

Conclusion: For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.
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http://dx.doi.org/10.1200/JCO.18.02158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506419PMC
May 2019

Adjuvant therapy in stage III endometrial cancer confined to the pelvis.

Gynecol Oncol 2019 01 22;152(1):26-30. Epub 2018 Nov 22.

Department of Radiation Oncology, McGill University Health Centre, Cedars Cancer Centre, Canada. Electronic address:

Objective: To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT).

Methods: Between 1990 and 2012, 144 patients diagnosed with stage IIIA, B or C1 endometrial cancer were treated in our institution. All were treated with total hysterectomy, bilateral salpingo-oophorectomy ± lymph node dissection. Post-operatively, 67 patients received adjuvant RT alone, 37 CRT, 21 chemotherapy alone and 19 had no adjuvant therapy. This analysis focuses on the 104 patients treated with RT or CRT.

Results: The median follow-up was 61 months. Forty-six patients (44%) were stage IIIA, 6 (6%) were stage IIIB and 52 (50%) stage IIIC1. The 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) for patients treated by RT alone vs. CRT were, respectively, 67% vs. 61% (p = 0.55); 67% vs. 51% (p = 0.35); and 76% vs. 65% (p = 0.21). Grade 3 disease was an independent predictor for worse OS (HR = 6.01, p = 0.001), DFS (HR = 3.16, p = 0.03), and DSS (HR = 3.77, p = 0.02). In patients with grade 3 disease (n = 49), the 5-year OS was superior for the CRT (42% vs. 56%, p = 0.007).

Conclusions: In patients with stage III endometrial cancer confined to the pelvis, the addition of adjuvant chemotherapy with RT significantly improved OS in grade 3 disease. Grade 3 histology is a strong predictor for poor outcome. Further randomized studies aiming specifically at stage III disease are warranted.
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http://dx.doi.org/10.1016/j.ygyno.2018.11.002DOI Listing
January 2019

Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712-A Randomized Phase II Trial.

J Clin Oncol 2019 01 15;37(1):44-51. Epub 2018 Nov 15.

3 Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Purpose: Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive bladder cancer. Gemcitabine and once daily radiation (GD) is a well-supported alternative. The current trial evaluates these regimens.

Methods: Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT or GD. Patients underwent transurethral resection and induction CRT to 40 Gy. Patients who achieved a complete response (CR) received consolidation CRT to 64 Gy and others underwent cystectomy. We administered adjuvant gemcitabine/cisplatin chemotherapy. The primary end point was the rate of freedom from distant metastasis at 3 years (DMF3). The trial was not statistically powered to compare regimens, but to assess whether either regimen exceeded a DMF3 benchmark of 75%. Toxicity and efficacy end points, including CR and bladder-intact distant metastasis free survival at 3 years (BI-DMFS3), were assessed.

Results: From December 2008 to April 2014, 70 patients were enrolled, of which 66 were eligible for analysis, 33 per arm. Median follow-up was 5.1 years (range, 0.4 to 7.8 years) for eligible living patients. DMF3 was 78% and 84% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. Postinduction CR rates were 88% and 78%, respectively. Of 33 patients in the FCT arm, 21 (64%) experienced treatment-related grade 3 and 4 toxicities during protocol treatment, with 18 (55%), two (6%), and two patients (6%) experiencing grade 3 and 4 hematologic, GI, and genitourinary toxicity, respectively. For the 33 patients in the GD arm, these figures were 18 (55%) overall and 14 (42%), three (9%) and two patients (6%), respectively.

Conclusion: Both regimens demonstrated DMF3 greater than 75%. There were fewer toxicities observed in the GD arm. Either gemcitabine and once daily radiation or a cisplatin-based regimen could serve as a base for future trials of systemic therapy.
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http://dx.doi.org/10.1200/JCO.18.00537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354769PMC
January 2019

Bladder Preservation Therapy: Review of Literature and Future Directions of Trimodal Therapy.

Curr Urol Rep 2018 Nov 3;19(12):108. Epub 2018 Nov 3.

Department of Surgery, McGill University Health Center, McGill University, 1001 Decarie Blvd, D02.7210, Montreal, QC, H4A 3J1, Canada.

Purpose Of The Review: This review targets the latest literature on bladder preservation therapy with emphasis on trimodal therapy (TMT), highlighting its role in the management of muscle invasive bladder cancer (MIBC) and outlining future directions in bladder preservation research.

Recent Findings: TMT is the most promising bladder preservation treatment modality. Comparable results to contemporary radical cystectomy series are seen in properly selected patients. A multidisciplinary team approach is critical in the management of these patients. Future research is directed at the integration of immunotherapy into the treatment protocol. TMT, involving maximal transurethral resection followed by chemoradiation, is an attractive alternative to radical cystectomy with urinary diversion in carefully selected patients with muscle invasive disease. In the absence of randomized trial (RCT), comparison between TMT and cystectomy, based on retrospective data from large centers, suggests comparable oncological outcomes, with a favorable impact on quality of life.
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http://dx.doi.org/10.1007/s11934-018-0859-zDOI Listing
November 2018

Clinical significance of isolated tumor cells and micrometastasis in low-grade, stage I endometrial cancer.

J Surg Oncol 2018 Dec 24;118(7):1194-1198. Epub 2018 Oct 24.

Department of Obstetrics and Gynecology, McGill University Health Center, Montreal, Canada.

Introduction: Ultrastaging in endometrial cancer (EC) led to increased detection of isolated tumor cells (ITC, ≤0.2 mm) and micrometastases (MM, 0.2-2 mm), with unclear effect on prognosis. Our aim was to characterize the impact of ITC and MM on the outcome of these patients.

Methods: Grade 1 to 2 stage I endometrioid EC patients with nodal ITC (n = 11) or MM (n = 12) between 2012 and 2018 were retrospectively compared to a matched group of lymph node negative (n = 18) patients based on age, body mass index, grade, myometrial invasion, and lymphovascular space invasion (LVI) status using propensity score analysis (1:1). Mann-Whitney U tests were performed on continuous variables and χ tests on categorical variables. Progression-free survival (PFS) was the main endpoint.

Results: All MM and 81% of ITC had LVI. More ITC/MM patients received RT and chemotherapy (91.7% vs 18.4%; 70.8% vs 4.5%, respectively; P < 0.01) without significant difference in treatment-related toxicities (25% vs 27.3% grade 1%-2% and 20.8% vs 9.1% grade 2-3; P = 0.538) or PFS (29.2 vs 25 months; P = 0.828). Two distant recurrences occurred in MM patients after 2.5 years; one lung and one para-aortic lymph node.

Conclusion: With adjuvant treatment, ITC/MM in otherwise well-differentiated stage I endometrial cancer have similar outcomes to matched LN- patients.
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http://dx.doi.org/10.1002/jso.25259DOI Listing
December 2018

Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy.

Pract Radiat Oncol 2019 Jan 7;9(1):24-28. Epub 2018 Aug 7.

Division of Radiation Oncology, Cedars Cancer Centre, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Purpose: This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.

Methods And Materials: The study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT.

Results: For the purpose of this study, we considered an arbitrary 5 cm of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively.

Conclusions: The anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.
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http://dx.doi.org/10.1016/j.prro.2018.07.006DOI Listing
January 2019

Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial.

Eur Urol 2018 10 3;74(4):432-441. Epub 2018 Jul 3.

McGill University Health Centre, Montréal, QC, Canada.

Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with localized high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined.

Objective: The aim of this superiority randomized trial was to compare outcomes of RT combined with either 36 or 18 mo of ADT.

Design, Setting And Participants: From October 2000 to January 2008, 630 patients with HRPC were randomized, 310 to pelvic and prostate RT combined with 36 mo (long arm) and 320 to the same RT with 18 mo (short arm) of ADT.

Outcome Measurements And Statistical Analysis: Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model.

Results And Limitations: With a median follow-up of 9.4 yr, 290 patients had died (147 long arm vs 143 short arm). The 5-yr OS rates (95% confidence interval) were 91% for long arm (88-95%) and 86% for short arm (83-90%), p=0.07. QoL analysis showed a significant difference (p<0.001) in six scales and 13 items favoring 18 mo ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points.

Conclusions: In localized HRPC, our results support that 36 mo is not superior to 18 mo of ADT. ADT combined with RT can potentially be reduced to 18 mo in selected men without compromising survival or QoL. Thus, 18 mo of ADT appears to represent a valid option in HRPC.

Patient Summary: In this study, we report outcomes from high-risk prostate cancer patients treated with radiotherapy and either 36 or 18 mo of androgen deprivation therapy. There was no difference in survival between the two groups, with the 18-mo group experiencing a better quality of life.
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http://dx.doi.org/10.1016/j.eururo.2018.06.018DOI Listing
October 2018

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials.

J Neurooncol 2018 Aug 4;139(1):195-203. Epub 2018 Jun 4.

Department of Radiation Oncology, Hospital Sírio-Libânes, São Paulo, Brazil.

Propose: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT).

Methods: MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics.

Results: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant.

Conclusions: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.
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http://dx.doi.org/10.1007/s11060-018-2860-2DOI Listing
August 2018

Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial.

Neurosurgery 2019 01;84(1):41-49

Department of Radiation Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Background: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes.

Objective: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective.

Methods: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin.

Results: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT.

Conclusion: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.
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http://dx.doi.org/10.1093/neuros/nyy018DOI Listing
January 2019

Short delay in initiation of radiotherapy for patients with glioblastoma-effect of concurrent chemotherapy: a secondary analysis from the NRG Oncology/Radiation Therapy Oncology Group database.

Neuro Oncol 2018 06;20(7):966-974

Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Background: We previously reported the unexpected finding of significantly improved survival for newly diagnosed glioblastoma in patients when radiation therapy (RT) was initiated later (>4 wk post-op) compared with earlier (≤2 wk post-op). In that analysis, data were analyzed from 2855 patients from 16 NRG Oncology/Radiotherapy Oncology Group (RTOG) trials conducted prior to the era of concurrent temozolomide (TMZ) with RT. We now report on 1395 newly diagnosed glioblastomas from 2 studies, treated with RT and concurrent TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant.

Methods: Data from patients treated with TMZ-based chemoradiation from NRG Oncology/RTOG 0525 and 0825 were analyzed. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT. Overall survival (OS) was investigated using the Kaplan-Meier method and Cox proportional hazards model. Early progression (during time of diagnosis to 30 days after RT completion) was analyzed using the chi-square test.

Results: Given the small number of patients who started RT early following surgery, comparisons were made between >4 and ≤4 weeks delay of radiation from time of operation. There was no statistically significant difference in OS (hazard ratio = 0.93; P = 0.29; 95% CI: 0.80-1.07) after adjusting for known prognostic factors (recursive partitioning analysis and O6-methylguanine-DNA methyltransferase methylation status). Similarly, the rate of early progression did not differ significantly (P = 0.63).

Conclusions: We did not observe a significant prognostic influence of delaying radiation when given concurrently with TMZ for newly diagnosed glioblastoma. The effects of early (1-3 wk post-op) or late (>5 wk) initiation of radiation tested in our prior study could not be replicated.
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http://dx.doi.org/10.1093/neuonc/noy017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007748PMC
June 2018

Prognostic factors for progression in atypical meningioma.

J Neurosurg 2018 11;129(5):1240-1248

5Neuropathology, Cedars Cancer Centre, McGill University Health Centre, Montreal, Quebec, Canada.

In patients with postoperative residual atypical meningiomas, by using volumetric instead of linear measurements in follow-up imaging studies, the authors detected disease progression earlier. By using this approach, treatment for recurrent disease can be instituted promptly with potentially better tumor control and less toxicity due to smaller volume of residual disease.
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http://dx.doi.org/10.3171/2017.6.JNS17120DOI Listing
November 2018