Publications by authors named "Khalil Sultanem"

27 Publications

  • Page 1 of 1

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

The role of brachytherapy for margin control in oral tongue squamous cell carcinoma.

J Otolaryngol Head Neck Surg 2020 Oct 14;49(1):74. Epub 2020 Oct 14.

Department of Otolaryngology - Head & Neck Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

Background: The aim of this study is to assess the feasibility and effectiveness of using peri-operative brachytherapy (BRTx) for positive/narrow margins present post primary surgical resection of oral tongue squamous cell carcinoma (OTSCC).

Methods: Prospective single-centre study of patients with OTSCC (T1-3, N0-3, M0) treated with resection of primary tumour ± regional nodal resection and intra-operative insertion of BRTx catheters. BRTx was administered twice daily at 40.8Gy/12Fr for 'Positive' (≤2 mm) margins, at 34Gy/10Fr for 'Narrow' (2.1-5 mm) margins, and not given for 'Clear' (> 5 mm) margins over the course of 5-6 days, 3-5 days post operatively.

Results: Out of 55 patients recruited 41 patients (74.6%) were treated with BRTx, as 12 patients had clear margins and 2 patients had unfavourable tumour anatomy for catheter insertion. EBRTx was avoided in 64.3% of patients. Overall Survival (OS) at 3 and 5 years was 75.6 and 59.1% respectively, while Disease Specific Survival (DSS) was 82.3 and 68.6% at 3 and 5 years respectively. Recurrence and survival outcomes were not associated with margin status or the use of or specific dose of BRTx on Cox regression analysis. Acute and late toxicity secondary to BRTx was minimal.

Conclusions: The use of BRTx after primary OTSCC resection with positive/narrow margins ± EBRTx to the neck ± CTx achieves outcomes comparable to traditional treatment of surgery followed by re-resection or EBRTx ± CTx. Morbidity associated with oral cavity EBRTx or secondary resection and reconstruction is thus avoided. Both acute and late toxicity rates are low and compare favourably with other BRTx OTSCC studies.

Trial Registration: Retrospectively registered. https://www.mcgill.ca/rcr-rcn/files/rcr-rcn/2017.06.05_rcn_hn.pdf .

Level Of Evidence: 4.
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http://dx.doi.org/10.1186/s40463-020-00467-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556952PMC
October 2020

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BMC Cancer 2020 Feb 14;20(1):125. Epub 2020 Feb 14.

Department of Radiation Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E, London, Ontario, N6A 5W9, Canada.

Background: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches.

Methods: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity.

Discussion: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials.

Trial Registration: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.
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http://dx.doi.org/10.1186/s12885-020-6607-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023689PMC
February 2020

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

Lancet Oncol 2019 10 12;20(10):1349-1359. Epub 2019 Aug 12.

Department of Audiology, London Health Sciences Centre, London, ON, Canada.

Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment.

Methods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting.

Findings: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS.

Interpretation: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options.

Funding: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
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http://dx.doi.org/10.1016/S1470-2045(19)30410-3DOI Listing
October 2019

Local Failure Rate in Oropharyngeal Carcinoma Patients Treated with Intensity-modulated Radiotherapy Without High-dose Clinical Target Volume.

Cureus 2018 Jul 10;10(7):e2958. Epub 2018 Jul 10.

Oncology, Jewish General Hospital, Montreal, CAN.

Purpose: Our purpose was to evaluate whether omitting high-dose clinical target volume radiation (CTV-HD) around the gross tumor volume (GTV) in patients with oropharyngeal squamous cell carcinoma (OSCC) treated with intensity-modulated radiotherapy (IMRT) was associated with increased local failure.

Methods And Materials: Patients diagnosed with stage I to stage IV OSCC between December 2004 and April 2017 were retrospectively reviewed. All patients were treated with radical radiotherapy using IMRT, with or without neoadjuvant or concurrent chemotherapy. In accordance with institution guidelines, CTV-HD was not used. Local failure was defined as disease persistence or reappearance at the primary tumor site. When primary failure was documented, the computed tomography/positron emission tomography (CT/PET) scan that showed primary failure was fused with the original treatment scan. Each recurrent tumor was contoured to evaluate the pattern of recurrence. Recurrences were categorized as in-field, marginal, or out-of-field if >95%, 20%-95%, or <20% of the recurrent tumor volume, respectively, was encompassed by the 95% high-dose prescription isodose line of the original treatment plan. We then determined whether omitting CTV-HD was associated with increased locoregional failure.

Results: A total of 272 patients with OSCC were assessed. The median follow-up from initial treatment was 43 months (range: 3-194 months). Seven patients were lost to follow-up. The overall five-year survival rate was 87%. The three- and five-year disease-free survival rates were 86% and 83%, respectively. Forty-one patients had 53 treatment failures (16 were local, eight were regional, and 29 were distant; some patients had treatment failures in multiple locations). Fourteen (87.5%) of the local recurrences were in-field, one (6.25%) was marginal, and one (6.25%) was out-of-field.

Conclusion: Our analysis of patients with oropharyngeal cancer suggests that local failure is mostly in-field and potentially due to radioresistance, rather than a marginal miss of the tumor. It suggests that omitting CTV-HD is feasible and safe.
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http://dx.doi.org/10.7759/cureus.2958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132597PMC
July 2018

Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer.

Sci Rep 2017 08 31;7(1):10117. Epub 2017 Aug 31.

Department of Radiation Oncology, Physics Division, University of Michigan, 519 W. Williman St, Argus Bldg, Ann Arbor, Michigan, 48103-4943, USA.

Quantitative extraction of high-dimensional mineable data from medical images is a process known as radiomics. Radiomics is foreseen as an essential prognostic tool for cancer risk assessment and the quantification of intratumoural heterogeneity. In this work, 1615 radiomic features (quantifying tumour image intensity, shape, texture) extracted from pre-treatment FDG-PET and CT images of 300 patients from four different cohorts were analyzed for the risk assessment of locoregional recurrences (LR) and distant metastases (DM) in head-and-neck cancer. Prediction models combining radiomic and clinical variables were constructed via random forests and imbalance-adjustment strategies using two of the four cohorts. Independent validation of the prediction and prognostic performance of the models was carried out on the other two cohorts (LR: AUC = 0.69 and CI = 0.67; DM: AUC = 0.86 and CI = 0.88). Furthermore, the results obtained via Kaplan-Meier analysis demonstrated the potential of radiomics for assessing the risk of specific tumour outcomes using multiple stratification groups. This could have important clinical impact, notably by allowing for a better personalization of chemo-radiation treatments for head-and-neck cancer patients from different risk groups.
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http://dx.doi.org/10.1038/s41598-017-10371-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579274PMC
August 2017

Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer.

J Comput Assist Tomogr 2017 Nov/Dec;41(6):931-936

From the *Department of Radiology, †Division of Radiation Oncology and Medical Physics, ‡Segal Cancer Centre, §Lady Davis Institute for Medical Research, and ∥Department of Oncology, Division of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada H3T 1E2.

Objective: Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction.

Methods: The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated.

Results: The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV.

Conclusions: High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.
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http://dx.doi.org/10.1097/RCT.0000000000000617DOI Listing
December 2017

Pattern of Local Recurrence and Distant Metastasis in Breast Cancer By Molecular Subtype.

Cureus 2016 Dec 9;8(12):e924. Epub 2016 Dec 9.

Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.

Background And Purpose:  No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting.

Material And Methods:  The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-).  Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype.

Conclusions:  Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates. The TN and HER2 subtypes of breast cancer were associated with significantly poorer overall survival and prone to earlier recurrence and metastases. Our results demonstrate a significant association between molecular subtype and survival. The risk of death and relapse/metastases increases fewfold in TN compared to LA. Future prospective studies are warranted and could ultimately lead to the tailoring of adjuvant radiotherapy treatment fields based on both molecular subtype and the more conventional clinicopathologic characteristics.
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http://dx.doi.org/10.7759/cureus.924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222631PMC
December 2016

Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6).

Eur J Cancer 2017 02 29;72:192-199. Epub 2016 Dec 29.

Canadian Cancer Trials Group, Kingston, ON, Canada.

Aim: To compare quality of life (QOL) between standard (SFX) chemoradiotherapy (arm A) and altered fractionation radiotherapy (AFX) with panitumumab (PMab; arm B).

Methods: Patients with T any N + M0 or T3-4N0M0 squamous cell head-neck carcinoma were randomised to SFX (70 Gy/35/7 wks) plus cisplatin (100 mg/m IV × 3) versus AFX (70 Gy/35/6 wks) plus PMab (9 mg/kg IV × 3). QOL was collected at baseline, end of radiation therapy (RT) and 2, 4, 6, 12, 24 and 36 months post-RT using the Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N), MD Anderson Dysphagia Index (MDADI) and SWAL-QOL. We hypothesised a 6-point more favourable change in FACT-H&N score from baseline to 1 year in arm B over arm A.

Results: Among 320 patients, median follow-up was 46 (range: 0.1-64.3) months, median age 56, 84% male, Eastern Cooperative Oncology Group PS 0 (71%), 1 (29%). Primary site was oropharynx in 81% (p16+ 68%, p16- 16%, missing 16%). Baseline scores did not differ by arm (A/B): FACT-H&N 116.5/115, MDADI Global 83/77, SWAL-QOL General 67/68. At 1 year, no difference was seen between arms in FACT-H&N change from baseline: A -1.70, B -4.81, p = 0.194. Subscale change scores by arm were (A/B): last week RT, FACT-Physical (-11.6, -10, p = 0.049), MDADI Physical (-40.4, -33.9, p = 0.045), and SWAL-QOL Eating Duration (-61.2, -51.2, p = 0.02), Eating Desire (-53.3, -43.9, p = 0.031) and Mental Health (-42, -32.6, p = 0.009); 4 months, HN subscale (-7.7, -10, p = 0.014). No clinically important differences by arm were seen post-treatment.

Conclusions: PMab with AFX did not durably improve QOL or swallowing as compared with SFX with cisplatin.

Trial Registration: ClinicalTrials.gov: NCT00820248.
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http://dx.doi.org/10.1016/j.ejca.2016.11.008DOI Listing
February 2017

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.

J Pain Symptom Manage 2017 01 27;53(1):139-145.e2. Epub 2016 Nov 27.

Emory University/Winship Cancer Institute, Atlanta, Georgia, USA.

Context: The 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537.

Objectives: This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales.

Methods: EFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability.

Results: The 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ ≥ 0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ > 0.65).

Conclusion: The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.
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http://dx.doi.org/10.1016/j.jpainsymman.2016.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191964PMC
January 2017

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

Qual Life Res 2016 09 25;25(9):2323-33. Epub 2016 Feb 25.

University of South Florida H. Lee Moffitt Cancer Center, Tampa, FL, USA.

Purpose: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS).

Methods: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization.

Results: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm.

Conclusion: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.
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http://dx.doi.org/10.1007/s11136-016-1255-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982852PMC
September 2016

Clinical parameters predicting development of pulmonary malignancies in patients treated for head and neck squamous cell carcinoma.

Head Neck 2016 04 30;38 Suppl 1:E1277-80. Epub 2015 Oct 30.

Department of Otolaryngology - Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

Background: As the locoregional control rates in head and neck squamous cell carcinoma (HNSCC) have increased, these patients may suffer distant metastasis in a higher proportion of cases. Clinicopathological characteristics allowing prediction of high-risk profile would allow adapting posttreatment surveillance to individual risk.

Methods: A retrospective review of all patients with HNSCC treated at the Jewish General Hospital, McGill University, Montreal, Quebec, Canada, between 1999 and 2008 was conducted for this study.

Results: The study included 428 patients with a mean follow-up of 65 months (±SEM 1.7). Eighty patients (18.6%) developed pulmonary malignancy during follow-up. In multivariate Cox-regression analysis, locoregional failure and current smoking were associated with higher risk of pulmonary malignancy (p < .001 and p = .008, respectively).

Conclusion: Locoregional failure and smoking persistence are predictors of pulmonary malignancy in patients with HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1277-E1280, 2016.
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http://dx.doi.org/10.1002/hed.24210DOI Listing
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.
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http://dx.doi.org/10.1186/s40463-015-0084-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557220PMC
September 2015

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

Int J Radiat Oncol Biol Phys 2015 Jun 1;92(2):220-7. Epub 2015 Apr 1.

University of South Florida H. Lee Moffitt Cancer Center, Tampa, Florida.

Purpose And Objectives: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia.

Methods And Materials: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted.

Results: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group.

Conclusions: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.
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http://dx.doi.org/10.1016/j.ijrobp.2015.01.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431932PMC
June 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.
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http://dx.doi.org/10.1016/j.ijrobp.2014.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657552PMC
April 2015

Use of three-dimensional ultrasound in the detection of breast tumor bed displacement during radiotherapy.

Int J Radiat Oncol Biol Phys 2011 Jan 10;79(1):39-45. Epub 2010 Jul 10.

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

Purpose: To evaluate the feasibility and usefulness of a three-dimensional ultrasound (3D-US) image-guided system in identifying and tracking the tumor bed (TB) for planning and daily localization before radiation delivery for breast cancer.

Methods And Materials: Twenty breast cancer patients underwent two CT scans at the time of simulation and just before their boost. Three-dimensional ultrasound images were acquired immediately after the CT scans, to which the images were automatically fused. Three-dimensional ultrasound images were also acquired immediately before treatment. Spatial and temporal TB differences between CT and US were evaluated.

Results: The TB was not visible on US and CT in 1 subject who had and 1 subject who had not received chemotherapy before whole-breast radiotherapy. The mean (SD) TB volume overlap was 78% (14%). The mean centroid position of the TB on CT vs. US differed by 0.1, 0.2, and 0.4 mm in the anterior-posterior, left-right, and superior-inferior directions. The mean (SD) absolute radial displacement of the TB on each fraction from the treatment plan was 10.8 (6.3) mm.

Conclusions: The TB was well visualized by US for the majority of patients. Clinically insignificant differences in the displacements calculated by paired CT vs. paired US demonstrate the feasibility of using 3D-US. The present study suggests that a 10-mm planning target volume margin could result in undercoverage of the clinical target volumes in 50% of treatments. Multimodality planning and image-guided radiotherapy with US potentially offers an accurate and non-ionizing solution for the daily definition of the TB position during partial-breast irradiation and boost treatments.
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http://dx.doi.org/10.1016/j.ijrobp.2009.10.023DOI Listing
January 2011

Dosimetric evolution of the breast electron boost target using 3D ultrasound imaging.

Radiother Oncol 2010 Aug 28;96(2):185-91. Epub 2010 Jun 28.

Medical Physics Unit, McGill University, Montréal, Canada.

Purpose: To investigate the effect of treatment planning, patient setup, and interfraction motion errors on the delivered dose for external beam electron boosts for postoperative early stage breast cancer patients.

Methods And Materials: For 5 patients, 10-15 Gy was prescribed and administered via a conventionally defined electron boost treatment field - no dose distribution was calculated. Two computed tomography (CT) data sets were acquired on an average of 47 days apart. Using Monte Carlo techniques the clinically defined electron beams were reconstructed on CT1 and CT2, and a dosimetric comparison between the two data sets was made. Additionally, 3D ultrasound (US) imaging was performed to monitor interfraction motion. 3D US images were acquired concurrently with the CT images, as well as prior to each boost fraction in the treatment room. Taking into account interfraction motion, the dose to the clinical target volume (CTV) was calculated.

Results: Based on conventionally determined treatment fields the CT1-based CTV D95 averaged 49% (range 12-89%) of the prescribed dose. Representing setup errors, the CT2-based CTV D95 averaged 47% (range 16-91%) of the prescribed dose. Considering interfraction motion, the average radial displacement was 11 mm, and the resulting CTV D95 was further reduced in 2/5 patients.

Conclusions: Poor initial coverage at the time of planning is exacerbated by breast mobility and interfraction tumour bed motion, increasing the uncertainty in the delivered dose.
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http://dx.doi.org/10.1016/j.radonc.2010.05.017DOI Listing
August 2010

Phase III randomized study: oral pilocarpine versus submandibular salivary gland transfer protocol for the management of radiation-induced xerostomia.

Head Neck 2009 Feb;31(2):234-43

Department of Radiation Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.

Background: Xerostomia is a serious morbidity of radiation treatment in head and neck cancer.

Methods: We conducted a prospective phase III multicenter randomized study comparing submandibular salivary gland transfer (SGT) procedure with pilocarpine during and for 3 months after XRT. Salivary flow (baseline, stimulated) and University of Washington Quality of Life Questionnaire (U of W QOL) scores were measured. RESULTS.: An interim intent to treat analysis (120 patients) at 6 months shows superior results in SGT arm: median baseline salivary flow for SGT (0.04 mL/minute) versus pilocarpine (0.01 mL/minute), p = .001; median stimulated salivary flow (0.18 mL/minute) for SGT versus (0.05 mL/minute) for pilocarpine, p = .003. Scores (U of W QOL) for amount (p = .017) and consistency of saliva (p = .005) in favor of SGT leading to premature closure of study.

Conclusions: Submandibular SGT procedure is superior to pilocarpine in management of radiation-induced xerostomia.
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http://dx.doi.org/10.1002/hed.20961DOI Listing
February 2009

Descriptive study of patients receiving excision and radiotherapy for keloids.

Int J Radiat Oncol Biol Phys 2008 Aug 4;71(5):1465-9. Epub 2008 Feb 4.

Department of Medical Oncology, Jewish General Hospital, McGill University, 3755 rue de la Côte Ste. Catherine, Montreal, Quebec, Canada.

Purpose: To review and describe our institution's outcomes in patients treated with external beam radiotherapy after keloid excision.

Methods And Materials: This was a retrospective study. Patients who received radiotherapy between July 1994 and January 2004 after keloid excision were identified. A questionnaire was mailed regarding sociodemographic factors, early and late radiation toxicities, the need for additional therapy, and satisfaction level. All patients had received a total of 15 Gy in three daily 5-Gy fractions. Treatment started within 24 h after surgery and was delivered on a Siemens orthovoltage machine. The data were analyzed using the STATA statistical package.

Results: A total of 234 patients were approached. The response rate was 41%, and 75% were female. The mean age was 36.5 years (range, 16-69 years). The patients were mainly of European (53.1%) or African (19.8%) descent. For early toxicity outcomes, 54.2% reported skin redness and 24% reported skin peeling. For late toxicity outcomes, 27% reported telangiectasia and 62% reported permanent skin color changes. No association was found with gender, skin color, or age for the late toxicity outcomes. Of the patients responding, 14.6% required adjuvant treatment. On a visual scale of 1-10 for the satisfaction level, 60% reported a satisfaction level of > or =8. Telangiectasia was the most significant predictor of a low satisfaction level (< or =3, p < 0.005).

Conclusion: The results of our study have shown that orthovoltage-based radiotherapy after surgical excision for keloids is a good method for the prevention of relapse. It is well tolerated, causes little toxicity, and leads to a high patient satisfaction level.
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http://dx.doi.org/10.1016/j.ijrobp.2007.12.015DOI Listing
August 2008

Comparison of repositioning accuracy of two commercially available immobilization systems for treatment of head-and-neck tumors using simulation computed tomography imaging.

Int J Radiat Oncol Biol Phys 2008 Apr 22;70(5):1389-96. Epub 2008 Jan 22.

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

Purpose: To compare the setup accuracy, comfort level, and setup time of two immobilization systems used in head-and-neck radiotherapy.

Methods And Materials: Between February 2004 and January 2005, 21 patients undergoing radiotherapy for head-and-neck tumors were assigned to one of two immobilization devices: a standard thermoplastic head-and-shoulder mask fixed to a carbon fiber base (Type S) or a thermoplastic head mask fixed to the Accufix cantilever board equipped with the shoulder depression system. All patients underwent planning computed tomography (CT) followed by repeated control CT under simulation conditions during the course of therapy. The CT images were subsequently co-registered and setup accuracy was examined by recording displacement in the three cartesian planes at six anatomic landmarks and calculating the three-dimensional vector errors. In addition, the setup time and comfort of the two systems were compared.

Results: A total of 64 CT data sets were analyzed. No difference was found in the cartesian total displacement errors or total vector displacement errors between the two populations at any landmark considered. A trend was noted toward a smaller mean systemic error for the upper landmarks favoring the Accufix system. No difference was noted in the setup time or comfort level between the two systems.

Conclusion: No significant difference in the three-dimensional setup accuracy was identified between the two immobilization systems compared. The data from this study reassure us that our technique provides accurate patient immobilization, allowing us to limit our planning target volume to <4 mm when treating head-and-neck tumors.
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http://dx.doi.org/10.1016/j.ijrobp.2007.08.035DOI Listing
April 2008

A treatment planning analysis of inverse-planned and forward-planned intensity-modulated radiation therapy in nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2007 Dec;69(5):1625-33

Department of Radiation Oncology, Toronto-Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: To compare dose-volume histograms of target volumes and organs at risk in 57 patients with nasopharyngeal carcinoma (NPC) with inverse- (IP) or forward-planned (FP) intensity-modulated radiation treatment (IMRT).

Methods And Materials: The DVHs of 57 patients with NPC with IMRT with or without chemotherapy were reviewed. Thirty-one patients underwent IP IMRT, and 26 patients underwent FP IMRT. Treatment goals were to prescribe a minimum dose of 66-70 Gy for gross tumor volume and 59.4 Gy for planning target volume to greater than 95% of the volume. Multiple selected end points were used to compare dose-volume histograms of the targets, including minimum, mean, and maximum doses; percentage of target volume receiving less than 90% (1-V90%), less than 95% (1-V95%), and greater than 105% (1-V105%). Dose-volume histograms of organs at risk were evaluated with characteristic end points.

Results: Both planning methods provided excellent target coverage with no statistically significant differences found, although a trend was suggested in favor of improved target coverage with IP IMRT in patients with T3/T4 NPC (p = 0.10). Overall, IP IMRT statistically decreased the dose to the parotid gland, temporomandibular joint, brain stem, and spinal cord overall, whereas IP led to a dose decrease to the middle/inner ear in only the T1/T2 subgroup.

Conclusions: Use of IP and FP IMRT can lead to good target coverage while maintaining critical structures within tolerance. The IP IMRT selectively spared these critical organs to a greater degree and should be considered the standard of treatment in patients with NPC, particularly those with T3/T4. The FP IMRT is an effective second option in centers with limited IP IMRT capacity. As a modification of conformal techniques, the human/departmental resources to incorporate FP-IMRT should be nominal.
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http://dx.doi.org/10.1016/j.ijrobp.2007.08.028DOI Listing
December 2007

Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: Is there a need for neck dissection?

Head Neck 2007 Jun;29(6):585-90

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

Background: The aim of the study was to evaluate the outcomes and patterns of failure in patients with metastatic carcinoma to cervical lymph nodes from an unknown head and neck primary origin, who were treated curatively with radiotherapy, with or without neck dissection.

Methods: The study included 61 patients referred to the McGill University Hospital Centers from 1987 to 2002. The median age was 57 years, with male to female ratio of 4:1. Distribution of patients by N status was as follows: N1, 16 patients (26%); N2a, 18 (30%); N2b, 13 (22%); N2c, 7 (11%); and N3, 7 (11%). Twenty patients underwent neck dissection (11 radical, 9 functional) and 41 patients had biopsy (9 fine-needle aspiration and 32 excisional biopsy). All patients received radiotherapy. The median dose to the involved node(s) was 64 Gy, and 60 Gy to the rest of the neck. Treatment of the neck was bilateral in 50 patients (82%) and ipsilateral in 11 (18%). The minimum duration of the follow-up was 12 months, with the median of 32 months.

Results: The 5- and 8-year overall survival for the whole population was 79% and 67%, respectively. There was no statistically significant difference in the 8-year actuarial overall survival (64.8% and 67.6%, respectively, p = .64) and local relapse-free survival (75% vs 74.5%, respectively, p = .57), among patients who had biopsy versus those who had neck dissection.

Conclusion: In our experience, definitive radiotherapy to the neck and the potential mucosal sites, whether preceded by neck dissection or not, is effective to achieve a good local control rate in the unknown primary cancer of the head and neck. The indication for neck dissection, in particular for early nodal stage, is controversial.
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http://dx.doi.org/10.1002/hed.20581DOI Listing
June 2007

Long-term results of para-aortic irradiation for patients with stage I seminoma of the testis.

Int J Radiat Oncol Biol Phys 2005 Mar;61(3):741-4

Department of Oncology, Division of Radiation Oncology, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

Purpose: Adjuvant postoperative para-aortic lymph nodal irradiation is an acceptable alternative to para-aortic and ipsilateral pelvic irradiation postorchiectomy for patients with Stage I seminoma of the testis. In this article, we report the long-term results of our prospective evaluation of para-aortic irradiation only for such patients.

Methods And Materials: Between March 1991 and September 2000, 71 patients with Stage I seminoma were treated with adjuvant irradiation to the para-aortic region only after radical inguinal orchiectomy. Radiotherapy was delivered using parallel-opposed fields extending from T11 to L5. A total dose of 25 Gy in 15 fractions was prescribed to midpoint. Follow-up was performed every 3 months for the first year, every 4 months for the second and third years, every 6 months for the fourth and fifth years, and annually thereafter. Chest X-ray, tumor markers, and computed tomography scan of the pelvis were performed routinely as part of the follow-up investigation.

Results: At a median follow-up of 75 months, 68 of 71 patients are alive and free of relapse. Only 1 patient (1.4%) experienced failure in the ipsilateral inguinal nodal region. Two patients (2.8%) died of unrelated causes. The actuarial 10-year relapse free survival is 98.5% and the actuarial 10-year overall survival is 92%. No late toxicity has been encountered.

Conclusion: Patients with Stage I seminoma of the testis may be safely treated with para-aortic radiotherapy only. Risk of pelvic failure is very low and treatment toxicity minimal.
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http://dx.doi.org/10.1016/j.ijrobp.2004.06.247DOI Listing
March 2005

Double-blind randomized, placebo-controlled study of pilocarpine to salvage salivary gland function during radiotherapy of patients with head and neck cancer.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004 Jul;98(1):45-52

Department of Dentistry, Sir Mortimer B. Davis-Jewish General Hospital and McGill University, 3755 Cote Ste Catherine Road, Room A024, Montreal, Quebec, Canada H3T 1E2.

Objective: The efficacy of pilocarpine given during radiotherapy for head-neck cancer to reduce xerostomia was assessed.

Study Design: 58 patients receiving 5000 cGy radiotherapy (RT) involving salivary glands bilaterally were selected at the Jewish General Hospital, Montreal, Canada. Patients were randomly assigned to pilocarpine (5 mg, PILO, n=29) or placebo group (PLA, n=29). These drugs were taken 5 times daily during radiotherapy (first study phase) and 4 times daily for 5 weeks thereafter (second study phase). Saliva was collected and estimated for not stimulated and stimulated patients using the SAXON method.

Results: At the conclusion of the first phase, PILO patients reported a better global quality of life (P=.02) and less oral discomfort (P=.001) when compared to PLA. No significant difference was noted in the level of saliva, xerostomia, and other symptoms between patients in PILO and PLA. At the end of the second phase, a difference between groups was observed only for xerostomia and mucosal pain; both were significantly higher in PILO when compared to PLA (P <.05).

Conclusion: Pilocarpine 5mg given 5 times daily did not appear to improve the production of saliva and global quality of life assessments, nor to decrease the symptoms of xerostomia 5 weeks after completion of RT in patients who were taking pilocarpine post-RT. There was a slight improvement in the quality of life and a decrease in the level of discomfort noted only after the first study phase. The limitations of this study are discussed.
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http://dx.doi.org/10.1016/j.tripleo.2004.04.009DOI Listing
July 2004

The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial.

Int J Radiat Oncol Biol Phys 2004 Jan;58(1):247-52

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

Purpose: Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM.

Methods And Materials: Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume < or =110 cm3 were treated with a hypofractionated accelerated course of radiotherapy. The gross tumor volume (GTV) was defined as the contrast-enhancing lesion on the postoperative MRI T1-weighted images with the latter fused with computed tomography images for treatment planning. The planning target volume was defined as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases.

Results: Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival rate was 40%, and the median progression-free survival was 5.2 months (range: 1.9-12.8 months).

Conclusion: This hypofractionated accelerated irradiation schedule using forward planning (step-and-shoot) hypofractionated, intensity-modulated accelerated radiotherapy is feasible and seems to be a safe treatment for patients with GBM. A 2-week reduction in the treatment time may be of valuable benefit for this group of patients. However, despite this accelerated regimen, no survival advantage has been observed.
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http://dx.doi.org/10.1016/s0360-3016(03)00819-8DOI Listing
January 2004

Safety of a simple asymmetric jaw technique in the treatment of head and neck cancer.

Radiother Oncol 2003 Aug;68(2):149-52

Department of Oncology (Division of Radiation Oncology), McGill University, Montreal, Canada.

We reviewed our experience treating head and neck malignancies junctioning over the spinal cord using asymmetric collimation. The mean dose delivered to the cord was 43.28 Gy above to the junction, 40.36 Gy below it. With a median follow-up of 20 months, none of our 32 patients developed radiation myelitis.
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http://dx.doi.org/10.1016/s0167-8140(03)00188-9DOI Listing
August 2003

Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience.

Int J Radiat Oncol Biol Phys 2002 May;53(1):12-22

Department of Radiation Oncology, University of California-San Francisco, 505 Parnassus Avenue, L-08, San Francisco, CA 94143, USA.

Purpose: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC).

Methods And Materials: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17-82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50-60 Gy to the clinically negative neck, and 5-7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method.

Results: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose.

Conclusion: Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.
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http://dx.doi.org/10.1016/s0360-3016(02)02724-4DOI Listing
May 2002
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