Publications by authors named "George Shenouda"

49 Publications

Examination of the Dose-Effect Relationship of Radiation-Induced Hypopituitarism: Results of a Case-Control Study.

Adv Radiat Oncol 2021 Jul-Aug;6(4):100693. Epub 2021 Apr 15.

Department of Radiation Oncology.

Purpose: Previous reports have documented a dose-effect relationship for radiation-induced hypopituitarism in patients receiving therapy near or at the base of the skull. We aimed to characterize this long-term endocrinopathy further by examining the effect of dose on both the incidence and severity of toxicity, as well as exploring a possible dose threshold for this effect.

Methods And Materials: Out of an initial 346 patients who had received radiation therapy to the base of the skull, 53 patients with adequate endocrine evaluation were found. Of these, 19 patients who subsequently developed at least 1 endocrinopathy (cases) as well as 17 patients who did not (controls) were identified, for a total of 36. Patients' charts were reviewed, and endocrinologic laboratory tests recorded. Treatment plans were reviewed and doses to the hypothalamus and pituitary gland were calculated. One-way analysis of variance was used to determine differences between cases and controls, and Pearson's correlation coefficient was used to relate mean pituitary dose to serum free thyroxine, insulin-like growth factor 1, prolactin, cortisol, and luteinizing hormone.

Results: There were 20 men and 16 women, with a median age of 58. Median follow-up was 32 months (range, 18- 85 months). Median total plan dose delivered was 54 Gy (range, 50.4-70 Gy). Independent sample tests as well as univariate analysis showed a significantly greater dose to the hypothalamus and pituitary of the cases compared with the controls, while other factors were not significantly different between the 2 groups. There was a statistically significant negative correlation (Pearson's correlation coefficient = -0.65,  = .001) between the mean dose to the pituitary gland and the serum free thyroxine. No case of endocrine toxicity was observed at a mean dose to the pituitary below 30 Gy.

Conclusions: Our results suggest that late endocrinopathy is a true deterministic effect, with a dose threshold, and with both the incidence and severity of toxicity being related to the dose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.adro.2021.100693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184512PMC
April 2021

Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: A GORTEC internationally-reviewed HNCIG-endorsed consensus.

Radiother Oncol 2021 07 11;160:140-147. Epub 2021 May 11.

Department of Radiation Oncology, Hospital Clinic, Barcelona, Spain.

Introduction: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps.

Material And Methods: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance.

Results: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown.

Conclusion: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2021.04.026DOI Listing
July 2021

The impact of age on outcome in phase III NRG Oncology/RTOG trials of radiotherapy (XRT) +/- systemic therapy in locally advanced head and neck cancer.

J Geriatr Oncol 2021 Jul 2;12(6):937-944. Epub 2021 Apr 2.

Stanford University, United States of America.

Purpose: To examine the role age plays in the treatment and prognosis of locally advanced head and neck cancer (LAHNC) treated definitively with radiation alone or combined modality therapy.

Methods: A retrospective analysis was performed of three NRG/RTOG trials examining either radiation alone or combined radiation and systemic therapy for LAHNC. The effect of age (≥70 yrs.) on cause-specific survival (CSS), overall survival (OS), and toxicity was evaluated.

Results: A total of 2688 patients were analyzed, of whom 309 patients (11.5%) were ≥ 70. For all studies combined, the hazard ratio (HR) for CSS for patients age ≥ 70 vs. those <70 was 1.33 (95%CI: 1.14-1.55, p < 0.001). For OS, the HR for patients age ≥ 70 vs. those <70 for all studies combined was 1.55 (95% CI 1.35-1.77, p < 0.001). After adjustment for all covariates, age ≥ 70 was associated with worse OS regardless of adjustment for smoking and p16 status. The survival difference was more pronounced in those receiving combined radiation and systemic therapy. Hematologic and renal toxicities were increased in combined modality trials in patients ≥70 years old.

Conclusions: Patients age ≥ 70 with LAHNC were underrepresented in these clinical trials. Their CSS and OS proved inferior to patients <70 years old.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgo.2021.03.011DOI Listing
July 2021

Risk groups of laryngeal cancer treated with chemoradiation according to nomogram scores - A pooled analysis of RTOG 0129 and 0522.

Oral Oncol 2021 May 25;116:105241. Epub 2021 Feb 25.

Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH, United States.

Objectives: To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC).

Material And Methods: Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively.

Results: The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome.

Conclusions: We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2021.105241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144062PMC
May 2021

Magnetic Resonance Imaging Texture Analysis Predicts Recurrence in Patients With Nasopharyngeal Carcinoma.

Can Assoc Radiol J 2019 Nov 11;70(4):394-402. Epub 2019 Sep 11.

Department of Radiology, McGill University Health Centre, Montreal, Quebec, Canada.

Background: The personalization of oncologic treatment using radiomic signatures is mounting in nasopharyngeal carcinoma (NPC). We ascertain the predictive ability of 3D volumetric magnetic resonance imaging (MRI) texture features on NPC disease recurrence.

Methods: A retrospective study of 58 patients with NPC undergoing primary curative-intent treatment was performed. Forty-two image texture features were extracted from pre-treatment MRI in addition to clinical factors. A multivariate logistic regression was used to model the texture features. A receiver operating characteristic curve on 100 bootstrap samples was used to maximize generalizability to out-of-sample data. A Cox proportional model was used to predict disease recurrence in the final model.

Results: A total of 58 patients were included in the study. MRI texture features predicted disease recurrence with an area under the curve (AUC), sensitivity, and specificity of 0.79, 0.73, and 0.71, respectively. Loco-regional recurrence was predicted with AUC, sensitivity, and specificity of 0.82, 0.73 and 0.74 respectively while prediction for distant metastasis had an AUC, sensitivity, and specificity of 0.92, 0.79 and 0.84, respectively. Texture features on MRI had a hazard ratio of 4.37 (95% confidence interval 1.72-20.2) for disease recurrence when adjusting for age, sex, smoking, and TNM staging.

Conclusion: Texture features on MRI are independent predictors of NPC recurrence in patients undergoing curative-intent treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carj.2019.06.009DOI Listing
November 2019

Changing functional status within 6 months posttreatment is prognostic of overall survival in patients with head and neck cancer: NRG Oncology Study.

Head Neck 2019 11 22;41(11):3924-3932. Epub 2019 Aug 22.

Emory University/Winship Cancer Center, Atlanta, Georgia.

Background: Is posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC).

Methods: In an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality.

Results: Across all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31).

Conclusions: Posttreatment functional status is a strong prognostic marker of survival in patients with HNC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865821PMC
November 2019

Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer.

Clin Cancer Res 2019 12 16;25(23):7078-7088. Epub 2019 Aug 16.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.

Purpose: Previous studies indicate that the benefit of therapy depends on patients' risk for cancer recurrence relative to noncancer mortality (ω ratio). We sought to test the hypothesis that patients with head and neck cancer (HNC) with a higher ω ratio selectively benefit from intensive therapy.

Experimental Design: We analyzed 2,688 patients with stage III-IVB HNC undergoing primary radiotherapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to ω ratio and compared the effectiveness of intensive therapy as a function of predicted ω ratio (i.e., ω score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' ω score on the basis of tumor, demographic, and health factors. Analysis was by intention to treat.

Results: Decreasing age, improved performance status, higher body mass index, node-positive status, P16-negative status, and oral cavity primary predicted a higher ω ratio. Patients with ω score ≥0.80 were more likely to benefit from intensive treatment [5-year overall survival (OS), 70.0% vs. 56.6%; HR of 0.73, 95% confidence interval (CI): 0.57-0.94; = 0.016] than those with ω score <0.80 (5-year OS, 46.7% vs. 45.3%; HR of 1.02, 95% CI: 0.92-1.14; = 0.69; = 0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression.

Conclusions: Patients with HNC with a higher ω score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-19-1832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028339PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1670686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534728PMC
June 2019

Deep learning in head & neck cancer outcome prediction.

Sci Rep 2019 02 26;9(1):2764. Epub 2019 Feb 26.

Medical Physics Unit, McGill University and Cedars Cancer Center, 1001 Décarie Blvd, Montréal, QC, H4A 3J1, Canada.

Traditional radiomics involves the extraction of quantitative texture features from medical images in an attempt to determine correlations with clinical endpoints. We hypothesize that convolutional neural networks (CNNs) could enhance the performance of traditional radiomics, by detecting image patterns that may not be covered by a traditional radiomic framework. We test this hypothesis by training a CNN to predict treatment outcomes of patients with head and neck squamous cell carcinoma, based solely on their pre-treatment computed tomography image. The training (194 patients) and validation sets (106 patients), which are mutually independent and include 4 institutions, come from The Cancer Imaging Archive. When compared to a traditional radiomic framework applied to the same patient cohort, our method results in a AUC of 0.88 in predicting distant metastasis. When combining our model with the previous model, the AUC improves to 0.92. Our framework yields models that are shown to explicitly recognize traditional radiomic features, be directly visualized and perform accurate outcome prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-39206-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391436PMC
February 2019

Evaluation of supportive and barrier-protective skin care products in the daily prevention and treatment of cutaneous toxicity during systemic chemotherapy.

Onco Targets Ther 2018 17;11:5865-5872. Epub 2018 Sep 17.

La Roche-Posay Dermatological Laboratory, Levallois-Perret, France,

Introduction: The purpose of this multicenter, prospective, observational, open-label study was to evaluate the use and tolerability of dermo-cosmetic products in preventing skin reactions associated with cancer treatments.

Patients And Methods: A 12-product kit was supplied to patients before chemotherapy began and was to be used throughout the treatment phase. Cutaneous adverse events were evaluated at each treatment session. Physicians evaluated skin reactions (edema, erythema, dryness, desquamation, pigmentation disorders, and cracks) and gave their opinion on the skin benefit for patients at the end of the study. Patients also evaluated the product benefit using the Patient Benefit Index (PBI) questionnaire. Results were analyzed by subgroups of casual and regular users, based on number and frequency of products used.

Results: A total of 147 patients were enrolled in cancer services in Germany, France, Italy, Spain, and Canada. Mean age was 59 years with 71% being female. Product tolerance on whole body was rated good to excellent for at least 89% of the patients for each product. Aggravated skin reactions during the study were reported more frequently by casual users than regular users (39.5% versus 22%; =0.029). Similarly, casual users reported more erythema aggravation (=0.02) and desquamation (=0.03) than regular users. PBI >1 was reported for 95.5% of patients and regular users had significantly higher scores than casual users (=0.049).

Discussion: Overall, the 12-product kit was very well tolerated, with regular users reporting benefits more frequently than casual users. Results support international recommendations to use appropriate skin care products to minimize the impact of cutaneous reactions associated with chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S155438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149940PMC
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2017.6.JNS17120DOI Listing
November 2018

Performance of Knowledge-Based Radiation Therapy Planning for the Glioblastoma Disease Site.

Int J Radiat Oncol Biol Phys 2017 11 14;99(4):1021-1028. Epub 2017 Jul 14.

McGill University Health Centre, Montreal, Quebec, Canada.

Purpose: The presence of multiple serial organs at risk (OARs) in close proximity to the tumor makes treatment planning for glioblastoma (GBM) complex and time consuming. The present study aimed to create a knowledge-based (KB) radiation therapy model for GBM patients using RapidPlan.

Methods And Materials: An initial model was trained using 82 glioblastoma patients treated with 60 Gy in 30 fractions. Plans were created using either volumetric modulated arc therapy (VMAT) or intensity modulated radiation therapy (IMRT). To improve the goodness-of-fit of the model, an intermediate model was generated by using the dose-volume histograms (DVHs) of best spared OARs of the initial model. Using the intermediate model and manual refinement, all 82 cases were replanned, resulting in the final model. The final model was validated on an independent set of 45 patients with GBM, astrocytoma, oligodendroglioma, and meningioma.

Results: The plans created by the final model exhibited superior planning target volume (PTV) dose metrics compared with manual clinical plans: ΔD=-0.52 ± 0.20 Gy, and ΔD=0.80 ± 0.13 Gy (differences are computed as clinical-model). OAR maximum doses were statistically similar, with improved optic apparatus sparing (ΔD=2.78 ± 0.82 Gy). Stated improvements correspond to P<.05. The KB planning time is typically 7 minutes for IMRT and 13 minutes for VMAT, compared with a typical 4 hours for manual planning.

Conclusions: The KB approach results in significant improvement in planning efficiency and in superior PTV coverage and better normal tissue sparing irrespective of tumor size and location within the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2017.07.012DOI Listing
November 2017

A Phase 2 Trial of Neoadjuvant Temozolomide Followed by Hypofractionated Accelerated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Patients With Glioblastoma.

Int J Radiat Oncol Biol Phys 2017 03 15;97(3):487-494. Epub 2016 Nov 15.

Department of Radiation Oncology, McGill University Health Centre, Montréal, Québec, Canada.

Purpose: We performed a phase 2 trial of neoadjuvant temozolomide (TMZ), followed by hypofractionated accelerated radiation therapy (HART) with concurrent TMZ, and adjuvant TMZ in patients with newly diagnosed glioblastoma to determine whether neoadjuvant TMZ would safely improve outcomes in this group of patients prior to subsequent cytotoxic therapy.

Methods And Materials: Adult patients with newly diagnosed glioblastoma and a Karnofsky Performance Status >60 were eligible. Neoadjuvant TMZ administration started 2 to 3 weeks from surgery at a daily dose of 75 mg/m for 2 weeks prior to delivery of HART (60 Gy in 20 daily fractions) with concurrent and adjuvant TMZ. The primary endpoints were feasibility and toxicity. The secondary endpoints included overall survival (OS) and progression-free survival.

Results: Fifty patients were accrued. The median follow-up period was 44.0 months for patients at risk and 22.3 months for all 50 patients. Except for 1 patient in whom infection developed and another patient with progression during HART, all patients completed protocol therapy as planned. The median OS and progression-free survival were 22.3 months (95% confidence interval, 14.6-42.7 months) and 13.7 months (95% confidence interval, 8.0-33.3 months), respectively. The 4-year OS rates were 30.4% for the entire cohort and 53.3% and 14.0% for patients with methylated (n=21) and unmethylated (n=27) MGMT gene promoter tumors, respectively. One patient had grade 5 pancytopenia during HART, and another patient had transient grade 4 hepatotoxicity. A second surgical procedure was performed in 13 patients: 2 had intracranial infection, 3 had recurrences, 4 had recurrences and radiation-induced damage, and 4 had only radiation-induced damage.

Conclusions: This novel approach of neoadjuvant TMZ is associated with an encouraging favorable long-term survival with acceptable toxicity. A future comparative trial of the efficacy of this regimen is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2016.11.006DOI Listing
March 2017

Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial.

JAMA Oncol 2017 Feb;3(2):220-226

Canadian Cancer Trials Group, Kingston, Ontario, Canada.

Importance: The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).

Objective: To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab.

Design, Setting, And Participants: A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011.

Interventions: Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B).

Main Outcomes And Measures: Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety.

Results: Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25).

Conclusions And Relevance: With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies.

Trial Registration: clinicaltrials.gov Identifier: NCT00820248.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2016.4510DOI Listing
February 2017

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Locally Advanced Head and Neck Carcinoma: NRG Oncology Radiation Therapy Oncology Group 0522.

Int J Radiat Oncol Biol Phys 2017 03 12;97(4):687-699. Epub 2016 Aug 12.

Emory University, Atlanta, GA.

Purpose: To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year.

Methods And Materials: Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years. The pretreatment QOL/PS scores were correlated with outcome and p16 status in patients with oropharyngeal cancer (OPC).

Results: Of 818 analyzable patients, the 1-year change from baseline score for FACT-HN total was -0.41 (CIS arm) and -5.11 (CET/CIS arm) (P=.016), representing a 3.2% between-arm change of the FACT-HN total score. The mean EQ-5D index and PSS-HN scores were not significantly different between arms. The p16-positive OPC patients had significantly higher baseline and 1-year scores for PSS-HN, FACT-HN total, physical and functional subscales, and 2-years for the EQ-5D index compared with p16-negative OPC patients. Higher pretreatment PSS-HN diet, PSS-HN eating, FACT-HN, and EQ-5D index scores were associated with better overall survival (OS) and progression-free (PFS) survival on multivariate analysis. Higher baseline FACT-HN total, functional, physical subscale, and EQ-5D index scores were associated with improved OS and PFS in p16-positive OPC patients but not in p16-negative and non-OPC patients.

Conclusion: There was no clinically meaningful difference in QOL/PS between arms. The p16-positive OPC patients had significantly higher QOL/PS than did p16-negative patients. Pretreatment QOL/PS is a significant independent predictor of outcome in locally advanced HNC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2016.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303682PMC
March 2017

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience.

Int J Radiat Oncol Biol Phys 2016 08 26;95(5):1346-1354. Epub 2016 Mar 26.

Stanford University Medical Center, Stanford, California.

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab.

Methods And Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin).

Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002).

Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2016.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199017PMC
August 2016

Moderate hypofractionated external beam radiotherapy alone for intermediate risk prostate cancer: long term outcomes.

Can J Urol 2016 Apr;23(2):8209-14

Division of Radiation Oncology and Medical Physics, McGill University Health Center, Montreal, Quebec, Canada.

Introduction: To report long term toxicity and efficacy of patients with intermediate risk prostate cancer treated with moderate hypofractionated radiotherapy (HypoRT).

Materials And Methods: We studied the first consecutive 100 men with intermediate risk (stage T2b-T2c, or PSA = 10-20 ug/L, or Gleason score = 7) adenocarcinoma of the prostate treated between October 2002 and May 2010 in our institution with moderate HypoRT. Patients were treated using three-dimensional conformal HypoRT to a dose of 66 Gy in 22 daily fractions prescribed to the isocenter. Androgen suppression was not given to any patient. A uniform 7 mm margin was created around the prostate for the planning target volume. Daily ultrasound was used to guide the radiotherapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir PSA level plus 2 ng/m.

Results: After a median follow up time of 80 months (range: 7-152), the 8 year actuarial freedom from biochemical relapse survival rate was 90%. The 8 year cancer specific survival and overall survival rates were 96% and 84%, respectively. Only 2 patients died from prostate cancer. The worst grade ≥ 2 late genitourinary (GU) or gastrointestinal (GI) toxicities ever documented were 19% and 20%, respectively. At the last follow up the incidence of grade ≥ 2 late GI or GU toxicity was of only 2% and 3%, respectively. No grade 4 or 5 late toxicity was seen.

Conclusion: Our long term experience with HypoRT delivering 66 Gy/22 fractions prescribed to the isocenter using three-dimensional conformal radiotherapy shows excellent tumor control with acceptable toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2016

A retrospective study of head and neck re-irradiation for patients with recurrent or second primary head and neck cancer: the McGill University experience.

J Otolaryngol Head Neck Surg 2015 Sep 2;44:31. Epub 2015 Sep 2.

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

Background: We report our experience with patients who received re-irradiation to the head and neck area for locoregional recurrences (LRR) or second primaries (SP) in a previously irradiated field.

Methods: We reviewed 27 consecutive patients with a diagnosis of LRR or SP head and neck carcinoma treated with a second course of radiotherapy between April 2004 and July 2012. The main outcome measures were local control, overall survival, and complications. The results are expressed as actuarial values using the Kaplan-Meier estimates.

Results: The median follow-up time was 24.7 months (range: 11 days-79.3 months). There were 23 males and four females with a median age of 61 years (range: 40-87 years). The actuarial overall survival rates at 1, 2, and 5 years were 77, 59, and 57%, respectively. The actuarial local control rate was 80, 52, and 52% at 1, 2, and 5 years, respectively. Three patients developed systemic metastases. The rate of grade 3 toxicity was 26%, and that of grade 4 toxicity was 3%. There were two treatment-related deaths (grade 5 toxicity).

Conclusions: Continuous course re-irradiation in patients with LRR or SP head and neck cancer is feasible with acceptable toxicity. With current encouraging rates of local control and overall survival, this option should be discussed with patients who have few alternative therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40463-015-0084-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557220PMC
September 2015

Comparison of radiation regimens in the treatment of Glioblastoma multiforme: results from a single institution.

Radiat Oncol 2015 Apr 26;10:106. Epub 2015 Apr 26.

Department of Oncology, Division of Radiation Oncology, McGill University, Montreal General Hospital, 1650 Avenue Cedar, H3G 1A4, Montréal, QC, Canada.

Background: The optimal fractionation schedule of radiotherapy (RT) for Glioblastoma multiforme (GBM) is yet to be determined. We aim to compare different fractionation regimens and identify prognostic factors to better tailor RT for newly diagnosed GBM patients.

Methods: All data for patients who underwent surgery for GBM between January 2005 and December 2012 were compiled. Clinical information was collected using patient charts and government registry. Cox analysis was used to identify variables affecting survival and treatment outcome.

Results: The median follow-up time was 13.2 months. Two hundred and seventy-six patients met the inclusion criteria, including 147 patients in the 60 Gy in 30 fractions (ConvRT) group, 86 patients in the 60 Gy in 20 fractions (HF60) group, and 43 patients in the 40 Gy in 15 fractions (HF40) group. Median survival (MS) was 16.0 months with a median progression-free survival (PFS) of 9.23 months in the ConvRT group. This was comparable to outcome in the HF60 group with MS 15.0 months and a median PFS of 9.1 months. Patients in the HF40 group had MS of 8 months, with a median PFS 5.4 months. Cox analysis showed no significant difference in OS between the ConvRT and HF60 groups but worse outcome in the HF40 group (HR 2.22, P=0.04). MGMT methylation, extent of resection, use of chemotherapy, and repeat surgery were found to be significant independent prognostic factors for survival.

Conclusions: HF60 constitutes a safe RT approach that shows survival comparable to standard RT while allowing for a shorter treatment time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-015-0396-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422039PMC
April 2015

Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.

Int J Radiat Oncol Biol Phys 2015 Apr 7;91(5):907-15. Epub 2015 Feb 7.

Stanford University Medical Center, Stanford, California.

Purpose: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).

Methods And Materials: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.

Results: A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.

Conclusions: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2014.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657552PMC
April 2015

p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma.

J Clin Oncol 2014 Dec 29;32(35):3930-8. Epub 2014 Sep 29.

Christine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.

Purpose: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx.

Patients And Methods: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics.

Results: p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes.

Conclusion: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2013.54.5228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251957PMC
December 2014

A case of recurrent anaplastic meningioma of the skull base with radiologic response to hydroxyurea.

J Neurol Surg Rep 2014 Aug 17;75(1):e52-5. Epub 2014 Apr 17.

Department of Otolaryngology-Head and Neck Surgery, Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec, Canada.

Anaplastic meningiomas are rare and aggressive tumors with a high propensity for local recurrence. Surgical resection and postoperative radiotherapy are the standard of care for primary disease and local recurrences. Refractory disease is managed with chemotherapy with limited success. A highly efficacious, well-tolerated chemotherapeutic agent has yet to be found for this disease entity. Hydroxyurea is currently receiving renewed attention because of its efficacy in inducing apoptosis of meningioma cells in vitro and its favorable side-effect profile. Thus far, in humans, this agent has only induced stable disease. We describe the first patient showing a near complete/partial clinical and radiological regression after 5 months of 25 mg/kg of hydroxyurea once daily, given within 1 month after stereotactic fractionated reirradiation of a previously irradiated and operated anaplastic meningioma of the skull base. Magnetic resonance imaging showed a significant and sustained response with tumor shrinkage and cavitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0033-1359300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110141PMC
August 2014

Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer.

Int J Radiat Oncol Biol Phys 2014 May 7;89(1):13-20. Epub 2014 Mar 7.

MD Anderson Cancer Center, University of Texas, Houston, Texas.

Purpose: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy.

Methods And Materials: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX.

Results: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09).

Conclusions: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2013.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664465PMC
May 2014

Intraoperative sonographically assisted radioactive iodine 125 plaque brachytherapy for choroidal melanoma: visual acuity outcome.

J Ultrasound Med 2013 Jun;32(6):995-1001

Department of Ophthalmology, McGill University, Montreal, Canada.

Objectives: The purpose of this study was to present a retrospective series of cases from a single Canadian academic center assessing visual acuity outcomes after intraoperative sonographically assisted iodine 125 ((125)I) plaque brachytherapy treatment.

Methods: The cases of 28 patients (16 male and 12 female; mean age ± SD diagnosis, 62.3 ± 15 years) with choroidal melanoma treated with (125)I plaque brachytherapy using intraoperative sonography between 1997 and 2002 were reviewed.

Results: The mean longitudinal, transverse, and depth dimensions were 11.4, 10.6, and 4.7, respectively. The median follow-up was 48 months (range, 3-102 months) for our cohort of patients. The prescribed dose was 85 Gy to a height of 5 mm (for an apex height ≤5 mm) or to the tumor apex (for an apex height >5 mm). Five years after (125)I plaque brachytherapy, all tumors had regressed in their longitudinal, transverse, and depth dimensions. The prebrachytherapy tumor depth (P = .023) and sclera dose (P = .036) were found to significantly affect visual acuity after plaque brachytherapy at 24 months. One recurrence was recorded 6 years after plaque brachytherapy.

Conclusions: This study supports (125)I plaque brachytherapy as an efficacious treatment for patients with choroidal melanoma, and intraoperative sonography may help with optimizing tumor control. In addition, to our knowledge, this study is the first to report the sclera dose as a significant predictor of visual acuity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7863/ultra.32.6.995DOI Listing
June 2013

Hypofractionated radiation therapy (66 Gy in 22 fractions at 3 Gy per fraction) for favorable-risk prostate cancer: long-term outcomes.

Int J Radiat Oncol Biol Phys 2013 Jul 15;86(3):534-9. Epub 2013 Apr 15.

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

Purpose: To report long-term outcomes of low- and intermediate-risk prostate cancer patients treated with high-dose hypofractionated radiation therapy (HypoRT).

Methods And Materials: Patients with low- and intermediate-risk prostate cancer were treated using 3-dimensional conformal radiation therapy to a dose of 66 Gy in 22 daily fractions of 3 Gy without hormonal therapy. A uniform 7-mm margin was created around the prostate for the planning target volume, and treatment was prescribed to the isocenter. Treatment was delivered using daily ultrasound image-guided radiation therapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir prostate-specific antigen level plus 2 ng/mL.

Results: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rates were 97% and 92%, respectively. The 5- and 8-year actuarial overall survival rates were 92% and 88%, respectively. Only 1 patient died from prostate cancer at 92 months after treatment, giving an 8-year actuarial cancer-specific survival of 98%. Radiation therapy was well tolerated, with 57% of patients not experiencing any acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33%, respectively. There was no grade >3 toxicity. At last follow-up, the rate of grade ≥2 for both GI and GU toxicity was only 1.5%.

Conclusions: Hypofractionation with 66 Gy in 22 fractions prescribed to the isocenter using 3-dimensional conformal radiation therapy produces excellent biochemical control rates, with moderate toxicity. However, this regimen cannot be extrapolated to the intensity modulated radiation therapy technique.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2013.02.010DOI Listing
July 2013

Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment of intermediate-risk prostate cancer - long term results.

Int J Radiat Oncol Biol Phys 2012 Mar 23;82(4):1417-23. Epub 2011 Jul 23.

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

Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT).

Methods And Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control.

Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively.

Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2011.05.025DOI Listing
March 2012

Stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma: the McGill University experience.

Int J Radiat Oncol Biol Phys 2011 Nov 25;81(4):e455-62. Epub 2011 Jun 25.

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

Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma.

Methods And Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates.

Results: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma.

Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2011.05.012DOI Listing
November 2011

Hypofractionated radiotherapy for favorable risk prostate cancer.

Int J Radiat Oncol Biol Phys 2010 Jul;77(3):805-10

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

Purpose: Since the recognition that prostate cancer probably has a low alpha/beta ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy.

Material And Methods: A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version 3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL.

Results: With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade >or=2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade >or=2 late GU and GI toxicity were 2% and 1.5%, respectively.

Conclusions: This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2009.05.047DOI Listing
July 2010

Iodine-125 radiotherapy for choroidal melanoma.

Ann N Y Acad Sci 2008 Sep;1138:15-8

Department of Ophthalmology, McGill University, Montréal, Québec, Canada.

The objective was to evaluate the effect of the gender, size, and tumor location at the time of the diagnosis on the regression response of choroidal melanoma following plaque radiotherapy treatment. The paper is a longitudinal prospective study of 28 patients diagnosed with choroidal melanoma at McGill University Health Centre from 1997 to 2002. All patients were treated with episcleral iodine-125 (I(125)) plaque radiotherapy. Plaques were inserted at the tumor site under echographic visualization. All patients had medium-size tumors, except for three. Patients had periodic ophthalmic evaluation at 3 and 6 months post radiation treatment, followed by 6-month intervals thereafter. Patients' mean age was 62 +/- 15 years, 16 males and 12 females. Fifty percent of the tumors were located posterior to the equator with significant reduction in size at 12 months post plaque radiotherapy treatment. Significant regression was observed in all the tumor diameters at 5 years post treatment follow-up. Reduction in the depth diameter was significant (P < 0.01) in both male and female groups post treatment. There was a 25% (P < 0.001) reduction in the medium size of tumors at 5-year follow-up. Tumors located posterior to the equator responded best to I(125) plaque radiotherapy. Male patients responded better than females to treatment. Medium-size melanoma responded well to plaque radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1196/annals.1414.003DOI Listing
September 2008

Intra-operative echographic localization for radioactive ophthalmic plaques in choroidal melanoma.

Ann N Y Acad Sci 2008 Sep;1138:10-4

Department of Ophthalmology, Notre Dame Hospital, Montréal, Québec, Canada.

The objectives were to evaluate the beneficial effect of intra-operative echographic plaque site localization and to assess the rate of complications of postplaque insertion. This paper is a descriptive study of 48 patients with choroidal melanoma who underwent iodine-125 (I(125)) or ruthenium-106 (Ru(106)) plaque radiotherapy with intra-operative echographic confirmation of plaque placement with the aid of a nonradioactive plaque (dummy) at McGill University Health Centre from 1997 to 2003. Patients' mean age was 63.7 years; 52% (25/48) male, 48% (23/48) female. Twenty-seven percent (13/48) of the tumors were confined to the right eye and 73% (35/48) to the left eye. Forty-eight percent (23/48) of the tumors were located posterior to the equator, 14.6% (7/48) were anterior to the equator, 18.7% (9/48) in posterior pole, and 18.7% (9/48) at equator. Sixty-nine percent (33/48) received I(125) and 31% (15/48) had Ru(106) treatment. Ninety percent of the dummy plaques were initially positioned suboptimally and required repositioning under echographic guidance. At mean follow-up of 18.8 months, there was no tumor-related death or metastasis, but one patient required enucleation. The dummy plaque technique under echographic visualization resulted in reduction of radioactive exposure time during surgery of up to 50%. Intra-operative echographic utilization has the ability to localize precisely the tumor-plaque relationship, thereby optimizing the radiation delivered to the choroidal melanoma, while minimizing the surgeon's exposure time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1196/annals.1414.002DOI Listing
September 2008
-->