54 results on '"Nguyen-Tan PF"'
Search Results
2. P67 L'incidence de récidive sus-claviculaire chez les patientes atteintes de néoplasie du sein de stade Tl-2, ayant quatre ganglions atteints ou plus, traitées par chirurgie conservatrice et irradiation par champs tangentiels sans irradiation ganglionnaire
- Author
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Nguyen-Tân, PF, Vincent, L, Méthot, F, Rousseau, P, and Bahary, JP
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- 1998
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3. Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma.
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Hes C, Desilets A, Tonneau M, El Ouarzadi O, De Figueiredo Sousa M, Bahig H, Filion É, Nguyen-Tan PF, Christopoulos A, Benlaïfaoui M, Derosa L, Alves Costa Silva C, Ponce M, Malo J, Belkad W, Charpentier D, Aubin F, Hamilou Z, Jamal R, Messaoudene M, Soulières D, and Routy B
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- Male, Humans, Female, Squamous Cell Carcinoma of Head and Neck complications, Prospective Studies, Chemoradiotherapy adverse effects, Head and Neck Neoplasms complications, Mucositis etiology, Gastrointestinal Microbiome
- Abstract
Objectives: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis., Materials and Methods: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients., Results: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding., Conclusion: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2024
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4. Predictors of prolonged treatment time intervals in oral cavity cancer.
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Dayan G, Bahig H, Fortin B, Filion É, Nguyen-Tan PF, O'Sullivan B, Charpentier D, Soulières D, Gologan O, Nelson K, Létourneau L, Schmittbuhl M, Ayad T, Bissada E, Guertin L, Tabet P, and Christopoulos A
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- Humans, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Mouth Neoplasms pathology, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms
- Abstract
Objectives: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals., Material and Methods: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics., Results: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult., Conclusions: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gabriel Dayan: none declared. Houda Bahig: grants from Varian Medical Systems and personal fees from AstraZeneca outside the submitted work. Bernard Fortin: none declared. Édith Filion: none declared. Phuc-Felix Nguyen Tan: none declared. Brian O’Sullivan: none declared. Danielle Charpentier: none declared. Denis Soulières: none declared. Olga Gologan: none declared. Kristoff Nelson: none declared. Laurent Létourneau: none declared. Matthieu Schmittbuhl: none declared. Tareck Ayad: none declared. Eric Bissada: none declared. Louis Guertin: none declared. Apostolos Christopoulos: personal fees from Sanofi (advisory board) and Merck (presenter) outside the submitted work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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5. Long-Term Update of NRG/RTOG 0522: A Randomized Phase 3 Trial of Concurrent Radiation and Cisplatin With or Without Cetuximab in Locoregionally Advanced Head and Neck Cancer.
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Caudell JJ, Torres-Saavedra PA, Rosenthal DI, Axelrod RS, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, El-Naggar AK, Konski AA, Echevarria MI, Dunlap NE, Shenouda G, Singh AK, Beitler JJ, Garsa A, Bonner JA, Garden AS, Algan O, Harris J, and Le QT
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- Humans, Cetuximab adverse effects, Treatment Outcome, Chemoradiotherapy methods, Cisplatin adverse effects, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy
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Purpose: The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS)., Methods and Materials: Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3)., Results: Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P = .74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P = .94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P = .10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P = .36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P = .26)., Conclusions: With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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6. Magnetic Resonance-Guided Radiation Therapy for Head and Neck Cancers.
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Lavigne D, Ng SP, O'Sullivan B, Nguyen-Tan PF, Filion E, Létourneau-Guillon L, Fuller CD, and Bahig H
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- Humans, Radiotherapy Planning, Computer-Assisted methods, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy, Radiotherapy, Image-Guided methods, Head and Neck Neoplasms diagnostic imaging, Head and Neck Neoplasms radiotherapy
- Abstract
Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including enhanced baseline and planning evaluations, anatomical and functional treatment adaptation, potential for hypofractionation, and multiparametric assessment of response. This article offers a structured review of the current literature on these established and upcoming roles of MRI for patients with head and neck cancer undergoing RT.
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- 2022
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7. Combining dense elements with attention mechanisms for 3D radiotherapy dose prediction on head and neck cancers.
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Cros S, Bouttier H, Nguyen-Tan PF, Vorontsov E, and Kadoury S
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- Humans, Organs at Risk, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Head and Neck Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: External radiation therapy planning is a highly complex and tedious process as it involves treating large target volumes, prescribing several levels of doses, as well as avoiding irradiating critical structures such as organs at risk close to the tumor target. This requires highly trained dosimetrists and physicists to generate a personalized plan and adapt it as treatment evolves, thus affecting the overall tumor control and patient outcomes. Our aim is to achieve accurate dose predictions for head and neck (H&N) cancer patients on a challenging in-house dataset that reflects realistic variability and to further compare and validate the method on a public dataset., Methods: We propose a three-dimensional (3D) deep neural network that combines a hierarchically dense architecture with an attention U-net (HDA U-net). We investigate a domain knowledge objective, incorporating a weighted mean squared error (MSE) with a dose-volume histogram (DVH) loss function. The proposed HDA U-net using the MSE-DVH loss function is compared with two state-of-the-art U-net variants on two radiotherapy datasets of H&N cases. These include reference dose plans, computed tomography (CT) information, organs at risk (OARs), and planning target volume (PTV) delineations. All models were evaluated using coverage, homogeneity, and conformity metrics as well as mean dose error and DVH curves., Results: Overall, the proposed architecture outperformed the comparative state-of-the-art methods, reaching 0.95 (0.98) on D95 coverage, 1.06 (1.07) on the maximum dose value, 0.10 (0.08) on homogeneity, 0.53 (0.79) on conformity index, and attaining the lowest mean dose error on PTVs of 1.7% (1.4%) for the in-house (public) dataset. The improvements are statistically significant ( p < 0.05 $p<0.05$ ) for the homogeneity and maximum dose value compared with the closest baseline. All models offer a near real-time prediction, measured between 0.43 and 0.88 s per volume., Conclusion: The proposed method achieved similar performance on both realistic in-house data and public data compared to the attention U-net with a DVH loss, and outperformed other methods such as HD U-net and HDA U-net with standard MSE losses. The use of the DVH objective for training showed consistent improvements to the baselines on most metrics, supporting its added benefit in H&N cancer cases. The quick prediction time of the proposed method allows for real-time applications, providing physicians a method to generate an objective end goal for the dosimetrist to use as reference for planning. This could considerably reduce the number of iterations between the two expert physicians thus reducing the overall treatment planning time., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)
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- 2022
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8. Cross-institutional outcome prediction for head and neck cancer patients using self-attention neural networks.
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Le WT, Vorontsov E, Romero FP, Seddik L, Elsharief MM, Nguyen-Tan PF, Roberge D, Bahig H, and Kadoury S
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- Adult, Aged, Aged, 80 and over, Attention, Biomarkers, Tumor, Carcinoma, Squamous Cell therapy, Deep Learning, Female, Head and Neck Neoplasms therapy, Humans, Male, Middle Aged, Neoplasm Recurrence, Local diagnostic imaging, Positron Emission Tomography Computed Tomography, Prognosis, Quality of Life, Retrospective Studies, Carcinoma, Squamous Cell diagnostic imaging, Diagnosis, Computer-Assisted methods, Head and Neck Neoplasms diagnostic imaging, Image Processing, Computer-Assisted methods, Neural Networks, Computer
- Abstract
In radiation oncology, predicting patient risk stratification allows specialization of therapy intensification as well as selecting between systemic and regional treatments, all of which helps to improve patient outcome and quality of life. Deep learning offers an advantage over traditional radiomics for medical image processing by learning salient features from training data originating from multiple datasets. However, while their large capacity allows to combine high-level medical imaging data for outcome prediction, they lack generalization to be used across institutions. In this work, a pseudo-volumetric convolutional neural network with a deep preprocessor module and self-attention (PreSANet) is proposed for the prediction of distant metastasis, locoregional recurrence, and overall survival occurrence probabilities within the 10 year follow-up time frame for head and neck cancer patients with squamous cell carcinoma. The model is capable of processing multi-modal inputs of variable scan length, as well as integrating patient data in the prediction model. These proposed architectural features and additional modalities all serve to extract additional information from the available data when availability to additional samples is limited. This model was trained on the public Cancer Imaging Archive Head-Neck-PET-CT dataset consisting of 298 patients undergoing curative radio/chemo-radiotherapy and acquired from 4 different institutions. The model was further validated on an internal retrospective dataset with 371 patients acquired from one of the institutions in the training dataset. An extensive set of ablation experiments were performed to test the utility of the proposed model characteristics, achieving an AUROC of [Formula: see text], [Formula: see text] and [Formula: see text] for DM, LR and OS respectively on the public TCIA Head-Neck-PET-CT dataset. External validation was performed on a retrospective dataset with 371 patients, achieving [Formula: see text] AUROC in all outcomes. To test for model generalization across sites, a validation scheme consisting of single site-holdout and cross-validation combining both datasets was used. The mean accuracy across 4 institutions obtained was [Formula: see text], [Formula: see text] and [Formula: see text] for DM, LR and OS respectively. The proposed model demonstrates an effective method for tumor outcome prediction for multi-site, multi-modal combining both volumetric data and structured patient clinical data., (© 2022. The Author(s).)
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- 2022
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9. The rs6942067 genotype is associated with a worse overall survival in young or non-smoking HPV-negative patients with positive nodal status in head and neck squamous cell carcinoma.
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Cardin GB, Bernard M, Bourbonnais J, Bahig H, Nguyen-Tan PF, Filion E, Soulieres D, Gologan O, Ayad T, Guertin L, Bissada E, Rodier F, and Christopoulos A
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- Genotype, Humans, Squamous Cell Carcinoma of Head and Neck genetics, Head and Neck Neoplasms genetics, Oropharyngeal Neoplasms pathology, Papillomavirus Infections complications, Papillomavirus Infections genetics
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- 2022
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10. Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress.
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Desilets A, McCarvill W, Aubin F, Bahig H, Ballivy O, Charpentier D, Filion É, Jamal R, Lambert L, Nguyen-Tan PF, Vadnais C, Weng X, and Soulières D
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- Chemoradiotherapy adverse effects, Genotype, Humans, Retrospective Studies, Carcinoma, Dihydrouracil Dehydrogenase (NADP) genetics
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Background : 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods : The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results : 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% ( n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% ( n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A -negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping ( p = 0.18). When retrospectively analyzing additional non- DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39-2.13], p = 0.0063), dysphagia (RR 2.89 [1.20-5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42-61.5)], p = 0.00065) were all significantly increased. Conclusion : The DPYD*2A , c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided.
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- 2022
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11. Risk groups of laryngeal cancer treated with chemoradiation according to nomogram scores - A pooled analysis of RTOG 0129 and 0522.
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Awan MJ, Gittleman H, Barnholtz-Sloan J, Machtay M, Nguyen-Tan PF, Rosenthal DI, Schultz C, Huth BJ, Thorstad WL, Frank SJ, Kim H, Foote RL, Lango MN, Shenouda G, Suntharalingam M, Harris J, Zhang Q, Le QT, and Yao M
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- Chemoradiotherapy, Cisplatin administration & dosage, Humans, Neoplasm Recurrence, Local, Neoplasm Staging, Prospective Studies, Squamous Cell Carcinoma of Head and Neck diagnosis, Squamous Cell Carcinoma of Head and Neck therapy, Laryngeal Neoplasms diagnosis, Laryngeal Neoplasms therapy, Nomograms, Prognosis
- Abstract
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., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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12. Phase II study of de-intensified intensity-modulated radiotherapy and concurrent carboplatin/5-fluorouracil in lateralized p16-associated oropharyngeal carcinoma.
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Bahig H, Lambert L, Filion E, Soulières D, Guertin L, Ayad T, Christopoulos A, Bissada E, Alizadeh M, Bélair M, and Nguyen-Tan PF
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- Carboplatin, Fluorouracil therapeutic use, Humans, Radiotherapy Dosage, Carcinoma, Squamous Cell, Oropharyngeal Neoplasms therapy, Radiotherapy, Intensity-Modulated
- Abstract
Purpose: To assess cancer control and patient-reported outcomes (PROs) after de-intensified intensity-modulated radiotherapy (IMRT) in lateralized p16-associated oropharyngeal cancer (p16-OPC)., Methods: Lateralized p16-OPC treated with radiotherapy and concurrent Carboplatin/5-fluorouracil between 2011 and 2014 were enrolled. De-intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC-C30 and QLQ-HN35 scales., Results: Twenty-nine patients were included. Median follow-up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5-year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post-treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post-treatment., Conclusion: De-intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16-OPC., (© 2020 Wiley Periodicals LLC.)
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- 2020
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13. Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma.
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Bernard M, Cardin GB, Cahuzac M, Ayad T, Bissada E, Guertin L, Bahig H, Nguyen-Tan PF, Filion E, Ballivy O, Soulieres D, Rodier F, and Christopoulos A
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Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentially increase autophagy in HNSCC and indirectly support cancer cell survival. Here, we sought to understand the relationship between the PI3K signaling pathway and autophagy during their dual inhibition in a panel of HNSCC cell lines. We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors. Using the Bliss independence model, we determined that the combination of chloroquine with PI3K inhibitors works in synergy to decrease cancer cell proliferation, independent of the PIK3CA status of the cell line. Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies.
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- 2020
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14. Single Nucleotide Polymorphism rs6942067 Is a Risk Factor in Young and in Non-Smoking Patients with HPV Negative Head and Neck Squamous Cell Carcinoma.
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Cardin GB, Bernard M, Bahig H, Nguyen-Tan PF, Ballivy O, Filion E, Soulieres D, Philouze P, Ayad T, Guertin L, Bissada E, Rodier F, and Christopoulos A
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Genetic factors behind the increasing incidence of human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) in young non-smokers are suspected, but have not been identified. Recently, rs6942067, a single nucleotide polymorphism (SNP) located upstream of the DCBLD1 gene, was found associated with non-smoking lung adenocarcinoma. To validate if this SNP is also implicated in HNSCC, participants of The Cancer Genome Atlas HNSCC cohort were investigated for rs6942067 status, associated DCBLD1 expression, and clinical characteristics. Occurrence of the rs6942067 GG genotype is significantly higher in young and in HPV negative non-smoking HNSCC than in other HNSCC. Additionally, rs6942067 GG is associated with higher DCBLD1 expression in HNSCC and patients with high DCBLD1 expression have a worse overall survival at three years, both in univariate and multivariate analysis. Furthermore, high DCBLD1 expression is associated with activation of the integrin signaling pathway and its phosphorylation with EGFR and MET. Collectively, these findings suggest that DCBLD1 plays a critical role in HNSCC and demonstrate an association between rs6942067 and clinical characteristics of young age and HPV negative non-smoking status in HNSCC patients.
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- 2019
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15. Cystic masses of the lateral neck: Diagnostic value comparison between fine-needle aspiration, core-needle biopsy, and frozen section.
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Tabet P, Saydy N, Letourneau-Guillon L, Gologan O, Bissada É, Ayad T, Tabet JC, Guertin L, Nguyen-Tan PF, and Christopoulos A
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- Adult, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Biopsy, Fine-Needle, Biopsy, Large-Core Needle, Cysts pathology, Frozen Sections, Head and Neck Neoplasms pathology, Neck pathology
- Abstract
Background: The usefulness of fine-needle aspiration (FNA), core-needle biopsy (CNB), and frozen section (FS) for assessing lateral cystic neck masses (LCNM) remains unclear., Methods: A retrospective review of patients presenting with a LCNM was undertaken., Results: In total, 135 patients were included. FNA had a lower sensitivity then CNB (59% vs 83%; P = .036) and FS (59% vs 93%; P = .01). FS had a better negative predictive value (NPV) when compared to FNA (92% vs 40%; P < .001) and CNB (92% vs 50%; P = .062). Positive predictive values (PPV) and sensitivities were similar among all groups., Conclusion: Given its adequate PPV (92%), FNA should be used initially on LCNM. Because of its high sensitivity, CNB should be considered if FNA is not diagnostic of malignancy. FS should always follow a CNB indicative of malignancy, because of low NPV. A diagnosis of malignancy on FNA, CNB, or FS strongly indicates presence of malignancy., (© 2019 Wiley Periodicals, Inc.)
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- 2019
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16. Increased risk of oropharyngeal cancers mediated by oral human papillomavirus infection: Results from a Canadian study.
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Laprise C, Madathil SA, Schlecht NF, Castonguay G, Soulières D, Nguyen-Tan PF, Allison P, Coutlée F, Hier M, Rousseau MC, Franco EL, and Nicolau B
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- Aged, Canada, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell psychology, Case-Control Studies, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Oropharyngeal Neoplasms psychology, Papillomavirus Infections pathology, Papillomavirus Infections psychology, Risk Factors, Carcinoma, Squamous Cell virology, Oropharyngeal Neoplasms epidemiology, Oropharyngeal Neoplasms virology, Papillomaviridae, Papillomavirus Infections epidemiology, Sexual Behavior
- Abstract
Background: This study aimed to estimate the extent to which oral sex behavior is associated with an increased risk of oropharyngeal cancers (OPCs), and how much of the association is mediated by oral human papillomavirus (HPV) infection., Methods: We used data from a hospital-based case-control study conducted in Montreal, Canada. Information on oral sex behaviors was collected. Oral rinse and oral brush specimens were analyzed for HPV positivity and genotyping. Logistic regression estimated the odds ratios (OR) and 95% confidence intervals (CI) for the association between oral sex behaviors and OPC., Results: Onset of oral sex practice at age 16 years or younger had an increased risk of OPCs relative to those with onset after age 30 years (OR = 2.98; 95% CI 1.37-6.47). This association decreased (OR = 1.09; 95% CI 0.25-4.71) when restricted to those positive for HPV., Conclusions: Our results suggest that the association between oral sex and OPC seems mediated by oral HPV infection., (© 2019 Wiley Periodicals, Inc.)
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- 2019
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17. Dual-energy computed tomography for prediction of loco-regional recurrence after radiotherapy in larynx and hypopharynx squamous cell carcinoma.
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Bahig H, Lapointe A, Bedwani S, de Guise J, Lambert L, Filion E, Roberge D, Létourneau-Guillon L, Blais D, Ng SP, and Nguyen-Tan PF
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- Adult, Aged, Contrast Media, Female, Humans, Hypopharyngeal Neoplasms diagnostic imaging, Hypopharyngeal Neoplasms mortality, Hypopharynx diagnostic imaging, Iodine, Kaplan-Meier Estimate, Laryngeal Neoplasms diagnostic imaging, Laryngeal Neoplasms mortality, Larynx diagnostic imaging, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck diagnostic imaging, Tomography, X-Ray Computed methods, Hypopharyngeal Neoplasms radiotherapy, Laryngeal Neoplasms radiotherapy, Neoplasm Recurrence, Local diagnostic imaging, Squamous Cell Carcinoma of Head and Neck radiotherapy
- Abstract
Purpose: To investigate the role of quantitative pre-treatment dual-energy computed tomography (DECT) for prediction of loco-regional recurrence (LRR) in patients with larynx/hypopharynx squamous cell cancer (L/H SCC)., Methods: Patients with L/H SCC treated with curative intent loco-regional radiotherapy and that underwent treatment planning with contrast-enhanced DECT of the neck were included. Primary and nodal gross tumor volumes (GTVp and GTVn) were contoured and transferred into a Matlab® workspace. Using a two-material decomposition, GTV iodine concentration (IC) maps were obtained. Quantitative histogram statistics (maximum, mean, standard deviation, kurtosis and skewness) were retrieved from the IC maps. Cox regression analysis was conducted to determine potential predictive factors of LRR., Results: Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed. Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively; 44% had concurrent chemo-radiotherapy and 28% had neodjuvant chemotherapy. Median follow-up was 21 months. Locoregional control at 1 and 2 years were 75% and 69%, respectively. For the entire cohort, GTVn volume (HR 1.177 [1.001-1.392], p = 0.05), voxel-based maximum IC of GTVp (HR 1.099 [95% CI: 1.001-1.209], p = 0.05) and IC standard deviation of GTVn (HR 9.300 [95% CI: 1.113-77.725] p = 0.04) were predictive of LRR. On subgroup analysis of patients treated with upfront radiotherapy +/- chemotherapy, both voxel-based maximum IC of GTVp (HR 1.127 [95% CI: 1.010-1.258], p = 0.05) and IC kurtosis of GTVp (HR 1.088 [95% CI: 1.014-1.166], p = 0.02) were predictive of LRR., Conclusion: This exploratory study suggests that pre-radiotherapy DECT-derived IC quantitative analysis of tumoral volume may help predict LRR in L/H SCC., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2019
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18. Pre-irradiation dental care: Ready-to-use templates for oropharyngeal cancers.
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Jumeau R, Nguyen-Tan PF, Bahig H, Liem X, Lambert L, Schmittbuhl M, Simard D, and Filion E
- Abstract
Aim: To develop a tool in order to guide pre-irradiation dental care (PIDC) for patients with oropharyngeal cancers., Background: Osteoradionecrosis of the jaws is a potential complication of radiotherapy (RT) for head and neck cancers. To prevent this complication, PIDC can involve multiple dental extractions as a preventative measure to avoid post-RT complications. However, there is no standardized tool to guide PIDC., Materials and Methods: From January 2005 to October 2015, 120 head and neck cancer patients were prospectively included in a study investigating dysgeusia after RT. From this cohort, patients were enrolled according to the following inclusion criteria: histopathological confirmation of oropharyngeal squamous cell carcinoma; stage T1-4 N1-3 M0; ≤10 missing teeth. Individual teeth were retrospectively delineated on planning computed tomography and doses to dentition were assessed to generate templates., Results: Thirty-three patients were included. Molars received highest doses with a mean dose of 50 Gy (range; 19-75 Gy). Ipsi-lateral and contralateral wisdom teeth received RT dose superior to 50 Gy in 92% and 56% of cases, respectively. Patients with advanced disease (T4 or N2c-3) received higher mean doses on inferior and ipsi-lateral dental arches compared to other patients (T1-3 N0-2b): 42 Gy vs. 39 Gy and 44 Gy vs. 39 Gy ( p < 0.05), respectively., Conclusion: Pre-RT dose distribution templates are an objective way to prepare PIDC. Further studies with a larger cohort are needed to validate these templates.
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- 2018
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19. Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol.
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Farsi NJ, Rousseau MC, Schlecht N, Castonguay G, Allison P, Nguyen-Tan PF, Souliéres D, Coutlée F, Hier M, Madathil S, Franco EL, and Nicolau B
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- Adult, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Odds Ratio, Risk Factors, Squamous Cell Carcinoma of Head and Neck, Alcohol Drinking adverse effects, Carcinoma, Squamous Cell etiology, Head and Neck Neoplasms etiology, Papillomavirus Infections complications, Smoking adverse effects
- Abstract
Tobacco and alcohol consumption are the main risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV) infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC. We assessed the independent effects of tobacco, alcohol and HPV infection on OPC risk in the head and neck cancer (HeNCe) Life study, a hospital-based case-control study of HNSCC with frequency-matched controls by age and sex from four Montreal hospitals. Interviewers collected information on socio-demographic and behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427) without missing values for HPV, smoking or alcohol. We examined associations by estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI) using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45) and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and 18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants who were HPV negative, respectively. Moreover, the combined effect of heavy smoking and alcohol comsumption with HPV 16 infection substantially increased OPC risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40), respectively. Our results support the independent roles of smoking, alcohol and HPV infection in OPC risk and a possible combined effect. Efforts should be made to tackle these major risk factors simultaneously., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2017
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20. Four PTEN-targeting co-expressed miRNAs and ACTN4- targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue.
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Berania I, Cardin GB, Clément I, Guertin L, Ayad T, Bissada E, Nguyen-Tan PF, Filion E, Guilmette J, Gologan O, Soulieres D, Rodier F, Wong P, and Christopoulos A
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- Actinin metabolism, Aged, Area Under Curve, Biomarkers, Tumor analysis, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell mortality, Female, Fluorescent Antibody Technique, Head and Neck Neoplasms genetics, Head and Neck Neoplasms mortality, Humans, Kaplan-Meier Estimate, Male, Middle Aged, PTEN Phosphohydrolase metabolism, Prognosis, ROC Curve, Real-Time Polymerase Chain Reaction, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms genetics, Tongue Neoplasms mortality, Biomarkers, Tumor genetics, Carcinoma, Squamous Cell pathology, Gene Expression Regulation, Neoplastic genetics, Head and Neck Neoplasms pathology, MicroRNAs genetics, Tongue Neoplasms pathology
- Abstract
The purpose of this study was to determine the prognostic value and oncogenic pathways associated to miRNA expression in squamous cell carcinoma of the oral tongue and to link these miRNA candidates with potential gene targets. We performed a miRNA screening within our institutional cohort (n = 58 patients) and reported five prognostic targets including a cluster of four co-expressed miRNAs (miR-18a, miR-92a, miR-103, and miR-205). Multivariate analysis showed that expression of miR-548b (p = 0.007) and miR-18a (p = 0.004, representative of co-expressed miRNAs) are independent prognostic markers for squamous cell carcinoma of the oral tongue. These findings were validated in The Cancer Genome Atlas (TCGA) cohort (n = 131) for both miRNAs (miR-548b: p = 0.027; miR-18a: p = 0.001). Bioinformatics analysis identified PTEN and ACTN4 as direct targets of the four co-expressed miRNAs and miR-548b, respectively. Correlations between the five identified miRNAs and their respective targeted genes were validated in the two merged cohorts and were concordantly significant (miR-18a/PTEN: p < 0.0001; miR-92a/PTEN: p = 0.0008; miR-103/PTEN: p = 0.008; miR-203/PTEN: p = 0.019; miR-548b/ACTN4: p = 0.009)., (© 2017 UICC.)
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- 2017
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21. Larynx motion considerations in partial larynx volumetric modulated arc therapy for early glottic cancer.
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Bahig H, Nguyen-Tan PF, Filion É, Roberge D, Thanomsack P, de Guise J, Blais D, Doucet R, Létourneau-Guillon L, and Lambert L
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- Aged, Deglutition, Female, Humans, Laryngeal Neoplasms pathology, Male, Middle Aged, Motion, Neoplasm Staging, Prospective Studies, Radiotherapy Dosage, Treatment Outcome, Four-Dimensional Computed Tomography methods, Glottis, Laryngeal Neoplasms radiotherapy, Magnetic Resonance Imaging methods, Radiotherapy Planning, Computer-Assisted methods
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Introduction: To assess laryngeal motion in early glottic cancer in order to determine safe margins for partial larynx volumetric modulated arc therapy (PL-VMAT), and to quantify dosimetric advantages of PL-VMAT., Methods: This prospective study included T1-2N0 glottic cancers treated with whole larynx VMAT (WL-VMAT). Pre- and mid-treatment 4D-computed tomography (4D-CT) and dynamic magnetic resonance imaging (MRI) allowed for assessment of larynx swallowing and respiratory motion. For 10 patients with lateralized lesions, PL-VMAT plans were calculated using margins derived from 4D-CT analysis., Results: Twenty patients were accrued from 2014 to 2016. Mean amplitude of larynx swallowing excursion was 23 mm and 6 mm in the superior and anterior directions, respectively. Mean respiratory motion reached 4 mm and 2 mm in superior-inferior and antero-posterior directions, respectively. Pre-treatment 4D-CT analysis identified one patient with planning CT acquired during swallowing. Mid-treatment 4D-CT revealed larynx shift relative to vertebrae in 30% of cases. PL-VMAT allowed for significant reduction of mean doses to ipsilateral carotid, contralateral carotid, thyroid gland, contralateral arytenoid and larynx. Using 8 mm internal margin for PL-VMAT, swallowing resulted in clinical target volume excursion beyond 95% isodose line during ≤1.5% of total treatment time in all patients., Conclusion: Although swallowing motion is rare, rapid and easily suppressed by patients, there is a risk of systematic miss-targeting if planning CT is acquired during swallowing. Larynx position shift relative to vertebrae occurs in 1/3 of patients over the course of radiotherapy. With soft-tissue image guidance and margins accounting for respiratory motion, PL-VMAT allows safe reduction of dose to organs at risk., (© 2017 The Royal Australian and New Zealand College of Radiologists.)
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- 2017
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22. Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer.
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Vallières M, Kay-Rivest E, Perrin LJ, Liem X, Furstoss C, Aerts HJWL, Khaouam N, Nguyen-Tan PF, Wang CS, Sultanem K, Seuntjens J, and El Naqa I
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- Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms pathology, Humans, Risk Assessment, Carcinoma, Squamous Cell diagnostic imaging, Head and Neck Neoplasms diagnostic imaging, Positron-Emission Tomography methods, Precision Medicine methods, Tomography, X-Ray Computed methods
- Abstract
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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- 2017
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23. Human papillomavirus genotypes and risk of head and neck cancers: Results from the HeNCe Life case-control study.
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Laprise C, Madathil SA, Schlecht NF, Castonguay G, Soulières D, Nguyen-Tan PF, Allison P, Coutlée F, Hier M, Rousseau MC, Franco EL, and Nicolau B
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- Aged, Canada, Case-Control Studies, Female, Genes, Viral, Humans, Male, Middle Aged, Risk Factors, Squamous Cell Carcinoma of Head and Neck, Alphapapillomavirus genetics, Carcinoma, Squamous Cell virology, Genotype, Head and Neck Neoplasms virology
- Abstract
Objective: Human papillomaviruses (HPV) are changing dramatically the epidemiologic landscape of head and neck cancers (HNCs). Their role in the aetiology of these cancers varies widely among HNCs subsites, sex and geographical regions worldwide. We describe HPV prevalence and its association with HNCs risk overall and by anatomical subsite in a sample of Canadians., Materials and Methods: The HeNCe Life study recruited 460 incident HNCs cases and 458 controls frequency-matched by age and sex from four Montreal hospitals in 2005-2013. We tested oral rinse and oral brush specimens for mucosal HPV genotypes. HPV positivity was categorized hierarchically as either negative, exclusively non-α-9 species types, α-9 types other than HPV16, and HPV16. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV and HNCs using unconditional logistic regression, controlling for confounders., Results: The prevalence of HPV infection among controls and cases was 14.5% and 41.2% in oral rinse and 3.1% and 24.4% in oral brush samples, respectively. HPV16 was the predominant genotype with an oral rinse and oral brush prevalence of 26.3% and 16.2% among cases and 2.4% and 0.2% among controls, respectively. HPV infection was associated with an increased risk of HNCs overall (OR=4.18; 95% CI, 2.94-5.95) and oropharyngeal cancer only (OR=10.3; 95% CI, 6.8-15.7). HNCs and oropharyngeal cancer were strongly associated with HPV16 (OR=18.1; 95% CI, 9.1-35.8, and OR=47.2; 95% CI, 23.1-96.6, respectively)., Conclusion: HPV infection, particularly HPV16, was associated with an increased HNCs risk, most strongly for oropharyngeal cancers., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
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- 2017
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24. The KRAS-Variant and Cetuximab Response in Head and Neck Squamous Cell Cancer: A Secondary Analysis of a Randomized Clinical Trial.
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Weidhaas JB, Harris J, Schaue D, Chen AM, Chin R, Axelrod R, El-Naggar AK, Singh AK, Galloway TJ, Raben D, Wang D, Matthiesen C, Avizonis VN, Manon RR, Yumen O, Nguyen-Tan PF, Trotti A, Skinner H, Zhang Q, Ferris RL, Sidransky D, and Chung CH
- Subjects
- Adult, Aged, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Carcinoma, Squamous Cell drug therapy, Chemoradiotherapy methods, Cisplatin administration & dosage, Disease-Free Survival, Female, Head and Neck Neoplasms drug therapy, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Squamous Cell Carcinoma of Head and Neck, Antineoplastic Agents administration & dosage, Carcinoma, Squamous Cell genetics, Cetuximab administration & dosage, Head and Neck Neoplasms genetics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Importance: There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment., Objectives: To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based transforming growth factor β1 (TGF-β1)., Design, Setting, and Participants: A total of 891 patients with advanced HNSCC from a phase 3 trial of cisplatin plus radiotherapy with or without cetuximab (NRG Oncology RTOG 0522) were included in this study, and 413 patients with available samples were genotyped for the KRAS-variant. Genomic DNA was tested for the KRAS-variant in a CLIA-certified laboratory. Correlation of the KRAS-variant, p16 positivity, outcome, and TGF-β1 levels was evaluated. Hazard ratios (HRs) were estimated with the Cox proportional hazards model., Main Outcomes and Measures: The correlation of KRAS-variant status with cetuximab response and outcome, p16 status, and plasma TGF-β1 levels was tested., Results: Of 891 patients eligible for protocol analyses (786 male [88.2%], 105 [11.2%] female, 810 white [90.9%], 81 nonwhite [9.1%]), 413 had biological samples for KRAS-variant testing, and 376 had plasma samples for TGF-β1 measurement. Seventy patients (16.9%) had the KRAS-variant. Overall, for patients with the KRAS-variant, cetuximab improved both progression-free survival (PFS) for the first year (HR, 0.31; 95% CI, 0.10-0.94; P = .04) and overall survival (OS) in years 1 to 2 (HR, 0.19; 95% CI, 0.04-0.86; P = .03). There was a significant interaction of the KRAS-variant with p16 status for PFS in patients treated without cetuximab. The p16-positive patients with the KRAS-variant treated without cetuximab had worse PFS than patients without the KRAS-variant (HR, 2.59; 95% CI, 0.91-7.33; P = .07). There was a significant 3-way interaction among the KRAS-variant, p16 status, and treatment for OS (HR, for KRAS-variant, cetuximab and p16 positive, 0.22; 95% CI, 0.03-1.66; HR for KRAS-variant, cetuximab and p16 negative, 1.43; 95% CI, 0.48-4.26; HR for KRAS-variant, no cetuximab and p16 positive, 2.48; 95% CI, 0.64-9.65; and HR for KRAS-variant, no cetuximab and p16 negative, 0.61; 95% CI, 0.23-1.59; P = .02). Patients with the KRAS-variant had significantly elevated TGF-β1 plasma levels (median, 23 376.49 vs 18 476.52 pg/mL; P = .03) and worse treatment-related toxic effects., Conclusions and Relevance: Patients with the KRAS-variant with HNSCC significantly benefit from the addition of cetuximab to radiotherapy and cisplatin, and there is a significant interaction between the KRAS-variant and p16 status. Elevated TGF-β1 levels in patients with the KRAS-variant suggests that cetuximab may help these patients by overcoming TGF-β1-induced suppression of antitumor immunity., Trial Registration: clinicaltrials.gov Identifier: NCT00265941.
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- 2017
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25. Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.
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Pugh SL, Wyatt G, Wong RK, Sagar SM, Yueh B, Singh AK, Yao M, Nguyen-Tan PF, Yom SS, Cardinale FS, Sultanem K, Hodson DI, Krempl GA, Chavez A, Yeh AM, and Bruner DW
- Subjects
- Aged, Factor Analysis, Statistical, Female, Head and Neck Neoplasms complications, Humans, Male, Middle Aged, Pain etiology, Activities of Daily Living psychology, Eating psychology, Head and Neck Neoplasms psychology, Pain psychology, Quality of Life psychology, Surveys and Questionnaires
- Abstract
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., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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26. Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.
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Galloway TJ, Zhang QE, Nguyen-Tan PF, Rosenthal DI, Soulieres D, Fortin A, Silverman CL, Daly ME, Ridge JA, Hammond JA, and Le QT
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- Antineoplastic Agents therapeutic use, Biomarkers, Tumor metabolism, Chemoradiotherapy mortality, Chemoradiotherapy statistics & numerical data, Combined Modality Therapy methods, Combined Modality Therapy mortality, Combined Modality Therapy statistics & numerical data, Female, Humans, Internationality, Lymph Nodes metabolism, Lymph Nodes pathology, Male, Neck, Neck Dissection statistics & numerical data, Prevalence, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Survival Rate, Treatment Outcome, Cisplatin therapeutic use, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Neck Dissection mortality, Oropharyngeal Neoplasms metabolism, Oropharyngeal Neoplasms mortality, Oropharyngeal Neoplasms therapy
- Abstract
Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129., Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection., Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection., Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors., Competing Interests: none., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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27. Palliative Radiation Therapy for Advanced Head and Neck Carcinomas: A Phase 2 Study.
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Fortin B, Khaouam N, Filion E, Nguyen-Tan PF, Bujold A, and Lambert L
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- Adult, Aged, Aged, 80 and over, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms psychology, Humans, Male, Middle Aged, Quality of Life, Head and Neck Neoplasms radiotherapy, Palliative Care, Radiotherapy, Conformal adverse effects
- Abstract
Purpose: Incurable head and neck cancer is hard to manage with usual palliative care. Radiation therapy (RT) in this setting is sometimes omitted because there is an apprehension that the side effects in the head and neck region might counterbalance the benefits. The objective of this phase 2 study was to evaluate whether highly conformal RT could improve the therapeutic ratio with this comprehensive Quality of Life (QOL) and toxicity evaluation., Methods and Materials: Patients from 2 academic centers, deemed unfit for radical treatment because of their poor medical condition or advanced cancer stage by an experienced tumor board, were offered 25 Gy in 5 daily intensity modulated RT fractions over 1 week to the symptomatic tumor volume. QOL was evaluated with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL and QLQ-H&N35 questionnaires, and toxicities with the Common Terminology Criteria for Adverse Events version 4.0. Survival and time to tumor progression were calculated with the Kaplan-Meier method., Results: Thirty-two patients were recruited, of whom 66% had at least T4, N3, or M1 disease. The QOL questionnaires completion rate was 86%. Eighty-eight percent of patients received the planned dose. The median overall survival and progression-free survival times were, respectively, 6.5 and 3.2 months. No grade 4 or 5 toxicity was seen. Only 13% of patients had any grade 3 toxicities, and 17% of patients reported no toxicity at all. The QOL was equal or improved, and head and neck symptoms remained equal to or lower than the baseline values for most patients at up to 6 months. Eighty-five percent of patients would have chosen to receive this RT regimen again when asked., Conclusions: This palliative RT regimen was highly tolerable and effective in preserving or improving self-reported QOL in most patients for up to 6 months, which corresponds to this population's median overall survival. Given the minimal side effects, intensification could be considered to achieve longer locoregional control., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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28. Reply to B. O'Sullivan et Al.
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Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar AK, Garden AS, Soulieres D, Trotti A, Avizonis VN, Ridge JA, Harris J, Le QT, and Gillison M
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- Female, Humans, Male, Carcinoma, Squamous Cell virology, Neoplasm Proteins analysis, Oropharyngeal Neoplasms virology, Papillomaviridae isolation & purification
- Published
- 2015
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29. Predictive factors of survival and treatment tolerance in older patients treated with chemotherapy and radiotherapy for locally advanced head and neck cancer.
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Bahig H, Fortin B, Alizadeh M, Lambert L, Filion E, Guertin L, Ayad T, Christopoulos A, Bissada E, Soulières D, Gaba Idiamey F, and Nguyen-Tan PF
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- Aged, Antineoplastic Agents adverse effects, Combined Modality Therapy, Female, Humans, Male, Radiotherapy adverse effects, Retrospective Studies, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy, Survival Analysis
- Abstract
Purpose: To report outcomes and predictive factors of overall survival, hospitalization and treatment completion rates in elderly patients with locally advanced head and neck cancer treated with concurrent chemoradiotherapy (CRT)., Material and Methods: A retrospective analysis of patients aged 70years or older treated with concurrent CRT for locally advanced head and neck cancer was conducted. Univariate and multivariate analysis as well as competing risk survival analysis were used to determine predictors of mortality. Logistic regression was used to predict for hospitalization and treatment completion rates., Results: In total, 129 patients were included. Median follow-up was 27months (range: 1.7-125months). Completion rate of combined CRT was 84%. Actuarial OS and DSS at 4years were 56% and 75%. Hospitalization rate was 36%. On multivariate analysis, a Karnofsky performance status (KPS) ⩽80 was predictive of mortality. Using competing risks, KPS ⩽80 and weight loss >5% were predictive of cancer mortality whereas Charlson score ⩾3 was predictive of mortality due to other causes. On logistic regression, patients with abnormal renal function and lower body mass index were more likely to be hospitalized during their treatment course. Charlson score and chemotherapy regimen were predictive of treatment completion., Conclusion: Concurrent CRT may be a feasible treatment option for healthier older patients at the cost of high hospitalization rates. Pre-treatment factors linked to physiological age such as KPS ⩽80, Charlson score ⩾3, abnormal renal function should be considered at the time of treatment decision., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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30. Reply to D. Adkins et al.
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Axelrod RS, Sherman E, Garden A, Nguyen-Tan PF, Trotti A, Yom SS, and Zhang Q
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- Female, Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Squamous Cell therapy, Chemoradiotherapy, Head and Neck Neoplasms therapy
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- 2015
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31. Institutional clinical trial accrual volume and survival of patients with head and neck cancer.
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Wuthrick EJ, Zhang Q, Machtay M, Rosenthal DI, Nguyen-Tan PF, Fortin A, Silverman CL, Raben A, Kim HE, Horwitz EM, Read NE, Harris J, Wu Q, Le QT, and Gillison ML
- Subjects
- Adult, Aged, Carcinoma, Squamous Cell pathology, Disease-Free Survival, Female, Head and Neck Neoplasms pathology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Prospective Studies, Antineoplastic Agents therapeutic use, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell therapy, Chemoradiotherapy, Cisplatin therapeutic use, Dose Fractionation, Radiation, Head and Neck Neoplasms mortality, Head and Neck Neoplasms therapy, Patient Selection
- Abstract
Purpose: National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer (HNC) receive treatment at centers with expertise, but whether provider experience affects survival is unknown., Patients and Methods: The effect of institutional experience on overall survival (OS) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group (RTOG 0129), which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy. As a surrogate for experience, institutions were classified as historically low- (HLACs) or high-accruing centers (HHACs) based on accrual to 21 RTOG HNC trials (1997 to 2002). The effect of accrual volume on OS was estimated by Cox proportional hazards models., Results: Median RTOG accrual (1997 to 2002) at HLACs was four versus 65 patients at HHACs. Analysis included 471 patients in RTOG 0129 (2002 to 2005) with known human papillomavirus and smoking status. Patients at HLACs versus HHACs had better performance status (0: 62% v 52%; P = .04) and lower T stage (T4: 26.5% v 35.3%; P = .002) but were otherwise similar. Radiotherapy protocol deviations were higher at HLACs versus HHACs (18% v 6%; P < .001). When compared with HHACs, patients at HLACs had worse OS (5 years: 51.0% v 69.1%; P = .002). Treatment at HLACs was associated with increased death risk of 91% (hazard ratio [HR], 1.91; 95% CI, 1.37 to 2.65) after adjustment for prognostic factors and 72% (HR, 1.72; 95% CI, 1.23 to 2.40) after radiotherapy compliance adjustment., Conclusion: OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations. Institutional experience substantially influences survival in locally advanced HNC., (© 2014 by American Society of Clinical Oncology.)
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- 2015
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32. Predicting depression and quality of life among long-term head and neck cancer survivors.
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Moubayed SP, Sampalis JS, Ayad T, Guertin L, Bissada E, Gologan OE, Soulières D, Lambert L, Filion E, Nguyen-Tan PF, and Christopoulos A
- Subjects
- Cohort Studies, Female, Humans, Male, Prognosis, Squamous Cell Carcinoma of Head and Neck, Survivors, Carcinoma, Squamous Cell complications, Depression etiology, Head and Neck Neoplasms complications, Quality of Life
- Abstract
Objective: The aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long-term survivors of head and neck squamous cell carcinoma and to develop predictive scores using these factors., Study Design: Cohort study, Setting: Tertiary referral center., Subjects and Methods: A total of 209 posttreatment (median follow-up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient-related, tumor-related, and treatment-related predictors were identified using chart review. Bivariate (χ(2) and t test) and multivariate (linear regression) analyses were used to construct predictive models., Results: Significant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3 medications (P < .001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified., Conclusion: Pretreatment predictors of long-term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long-term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at-risk patients., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)
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- 2015
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33. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity.
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Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, Kim H, Silverman C, Raben A, Galloway TJ, Fortin A, Gore E, Westra WH, Chung CH, Jordan RC, Gillison ML, List M, and Le QT
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Carcinoma mortality, Carcinoma pathology, Cisplatin adverse effects, Disease Progression, Disease-Free Survival, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Risk Factors, Time Factors, Treatment Outcome, Antineoplastic Agents administration & dosage, Carcinoma therapy, Chemoradiotherapy adverse effects, Chemoradiotherapy mortality, Cisplatin administration & dosage, Dose Fractionation, Radiation, Head and Neck Neoplasms therapy
- Abstract
Purpose: We tested the efficacy and toxicity of cisplatin plus accelerated fractionation with a concomitant boost (AFX-C) versus standard fractionation (SFX) in locally advanced head and neck carcinoma (LA-HNC)., Patients and Methods: Patients had stage III to IV carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Radiation therapy schedules were 70 Gy in 35 fractions over 7 weeks (SFX) or 72 Gy in 42 fractions over 6 weeks (AFX-C). Cisplatin doses were 100 mg/m(2) once every 3 weeks for two (AFX-C) or three (SFX) cycles. Toxicities were scored by using National Cancer Institute Common Toxicity Criteria 2.0 and the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. Overall survival (OS) and progression-free survival (PFS) rates were estimated by using the Kaplan-Meier method and were compared by using the one-sided log-rank test. Locoregional failure (LRF) and distant metastasis (DM) rates were estimated by using the cumulative incidence method and Gray's test., Results: In all, 721 of 743 patients were analyzable (361, SFX; 360, AFX-C). At a median follow-up of 7.9 years (range, 0.3 to 10.1 years) for 355 surviving patients, no differences were observed in OS (hazard ratio [HR], 0.96; 95% CI, 0.79 to 1.18; P = .37; 8-year survival, 48% v 48%), PFS (HR, 1.02; 95% CI, 0.84 to 1.24; P = .52; 8-year estimate, 42% v 41%), LRF (HR, 1.08; 95% CI, 0.84 to 1.38; P = .78; 8-year estimate, 37% v 39%), or DM (HR, 0.83; 95% CI, 0.56 to 1.24; P = .16; 8-year estimate, 15% v 13%). For oropharyngeal cancer, p16-positive patients had better OS than p16-negative patients (HR, 0.30; 95% CI, 0.21 to 0.42; P < .001; 8-year survival, 70.9% v 30.2%). There were no statistically significant differences in the grade 3 to 5 acute or late toxicities between the two arms and p-16 status., Conclusion: When combined with cisplatin, AFX-C neither improved outcome nor increased late toxicity in patients with LA-HNC. Long-term high survival rates in p16-positive patients with oropharyngeal cancer support the ongoing efforts to explore deintensification., (© 2014 by American Society of Clinical Oncology.)
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- 2014
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34. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma.
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Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, Soulieres D, Trotti A, Avizonis V, Ridge JA, Harris J, Le QT, and Gillison M
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- Adult, Aged, Carcinoma, Squamous Cell mortality, Cyclin-Dependent Kinase Inhibitor p16, Disease Progression, Female, Humans, Male, Middle Aged, Oropharyngeal Neoplasms mortality, Proportional Hazards Models, Carcinoma, Squamous Cell virology, Neoplasm Proteins analysis, Oropharyngeal Neoplasms virology, Papillomaviridae isolation & purification
- Abstract
Purpose: Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced., Patients and Methods: Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol., Results: A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment., Conclusion: Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC., (© 2014 by American Society of Clinical Oncology.)
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- 2014
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35. North-American survey on HPV-DNA and p16 testing for head and neck squamous cell carcinoma.
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Maniakas A, Moubayed SP, Ayad T, Guertin L, Nguyen-Tan PF, Gologan O, Soulieres D, and Christopoulos A
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- Alphapapillomavirus genetics, Canada, Data Collection, Humans, In Situ Hybridization, Polymerase Chain Reaction, Alphapapillomavirus isolation & purification, Carcinoma, Squamous Cell virology, DNA, Viral genetics, Genes, p16, Head and Neck Neoplasms virology
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Objectives: Human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) have been shown to have a significantly better prognosis and response to current treatment modalities. Current guidelines recommend systematic HPV-DNA and/or p16 testing on HNSCCs, although treatment approach should not be directed by test results. The objectives of this study were to (1) assess whether HPV-DNA and/or p16 status are systematically evaluated across North American otolaryngologists-head and neck surgeons and (2) whether the status is used to direct treatment approach., Materials and Methods: A 15-question online survey was sent to three associations: the Association of Oto-rhino-laryngology-Head and Neck Surgery of Quebec, the Canadian Society of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society., Results: Sixty-seven percent of respondents systematically test for HPV-DNA and/or p16 on HNSCC sites, while 58.3% report using test results to direct treatment for oropharyngeal cancers. A lack of official guidelines was the primary reason (81.8%) physicians did not use test results to direct treatment. Academic centre physicians (83.3%) and physicians with ⩾50% oncologic practice (87.6%) were more likely to test for HPV-DNA and/or p16 in HNSCC compared to non-academic centre physicians (39.7%) and physicians with <50% oncologic practices (51.4%) (p<0.001). Cost of the tests (69.2%), lack of relevance (46.1%) and time constraints (30.8%) were the primary reasons HPV-DNA and/or p16 were not tested., Conclusion: The majority of North American respondents in this survey systematically test for HPV-DNA and/or p16 in HNSCC sites, and most indicate that test results influence their treatment approach for oropharyngeal cancers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
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- 2014
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36. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.
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Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, and Axelrod RS
- Subjects
- Adult, Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Cetuximab, Cisplatin administration & dosage, Cisplatin adverse effects, Drug Administration Schedule, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mucositis chemically induced, Neoplasm Staging, Patient Selection, Radiation-Sensitizing Agents administration & dosage, Risk Factors, Smoking adverse effects, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Squamous Cell therapy, Chemoradiotherapy adverse effects, Head and Neck Neoplasms therapy
- Abstract
Purpose: Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS)., Patients and Methods: Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers., Results: Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome., Conclusion: Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.
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- 2014
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37. Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.
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Fortin I, Fortin B, Lambert L, Clavel S, Alizadeh M, Filion EJ, Soulières D, Bélair M, Guertin L, and Nguyen-Tan PF
- Subjects
- Antineoplastic Agents therapeutic use, Carcinoma pathology, Combined Modality Therapy, Dose-Response Relationship, Radiation, Female, Humans, Incidence, Male, Middle Aged, Oropharyngeal Neoplasms pathology, Particle Accelerators, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated adverse effects, Retrospective Studies, Xerostomia epidemiology, Carcinoma therapy, Oropharyngeal Neoplasms therapy, Radiotherapy, Intensity-Modulated methods, Xerostomia prevention & control
- Abstract
Background: In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction., Methods: The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60)., Results: Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months., Conclusion: This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria., (Copyright © 2013 Wiley Periodicals, Inc.)
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- 2014
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38. Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129.
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Xiao C, Hanlon A, Zhang Q, Movsas B, Ang K, Rosenthal DI, Nguyen-Tan PF, Kim H, Le Q, and Bruner DW
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- Dose Fractionation, Radiation, Female, Humans, Male, Middle Aged, Racial Groups, Radiation-Sensitizing Agents therapeutic use, Radiotherapy Dosage, Risk Factors, Sex Factors, Smoking, Syndrome, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell therapy, Chemoradiotherapy, Laryngeal Neoplasms diagnosis, Laryngeal Neoplasms therapy, Oropharyngeal Neoplasms diagnosis, Oropharyngeal Neoplasms therapy
- Abstract
Background: Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters., Methods: Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters., Results: Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy., Conclusions: Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies., (© 2013 American Cancer Society.)
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- 2014
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39. Symptom clusters in patients with head and neck cancer receiving concurrent chemoradiotherapy.
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Xiao C, Hanlon A, Zhang Q, Ang K, Rosenthal DI, Nguyen-Tan PF, Kim H, Movsas B, and Bruner DW
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- Combined Modality Therapy, Female, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy, Humans, Male, Middle Aged, Head and Neck Neoplasms physiopathology, Head and Neck Neoplasms therapy
- Abstract
Objectives: This study is to identify symptom clusters for head and neck (HNC) patients treated with concurrent chemoradiotherapy., Patients and Methods: A secondary data analysis of 684 HNC patients treated on the Radiation Therapy Oncology Group (RTOG) 0129 trial comparing different RT fractionation schedules with concurrent chemotherapy was used to examine clusters. Treatment-related symptoms were measured by clinicians at three time-points during and after chemoradiotherapy using the National Cancer Institute Common Toxicity Criteria v2.0. Exploratory factor analysis was applied to identify symptom clusters, which was further verified by confirmatory factor analysis. Coefficients of congruence and alpha coefficients were employed to examine generalizability of cluster structures over different time-points and in different subgroups., Results: Two clusters were identified. The HNC specific cluster is composed of radiodermatitis, dysphagia, radiomucositis, dry mouth, pain, taste disturbance, and fatigue. The gastrointestinal (GI) cluster involves nausea, vomiting, and dehydration. With the exception of patients 65years old or older, diagnosed with larynx cancer, or with stage III cancer, the two clusters were generalizable to different subgroups defined by age, gender, race, education, marital status, history of tobacco use, treatments, primary sites, disease stages, and tube feedings, as well as to the three symptom assessment time-points., Conclusions: The data provides preliminary support for two stable clusters in patients with HNC. These findings may serve to inform the symptom management in clinical practice. Moreover, the findings necessitate future research to examine the generalizability of identified clusters in the late symptom phase or other treatment modalities, and to understand the underlying biological mechanism., (Published by Elsevier Ltd.)
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- 2013
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40. A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck.
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Abdul Razak AR, Soulières D, Laurie SA, Hotte SJ, Singh S, Winquist E, Chia S, Le Tourneau C, Nguyen-Tan PF, Chen EX, Chan KK, Wang T, Giri N, Mormont C, Quinn S, and Siu LL
- Subjects
- Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell secondary, Diarrhea chemically induced, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Induction Chemotherapy, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Quinazolinones adverse effects, Quinazolinones pharmacokinetics, Treatment Outcome, Antineoplastic Agents administration & dosage, Carcinoma, Squamous Cell drug therapy, ErbB Receptors antagonists & inhibitors, Head and Neck Neoplasms drug therapy, Neoplasm Recurrence, Local drug therapy, Quinazolinones administration & dosage
- Abstract
Background: An open-label, multicenter, single-arm phase II trial was conducted to investigate the clinical activity of dacomitinib in recurrent/metastatic squamous-cell carcinoma of the head and neck (RM-SCCHN)., Patients and Methods: Eligible patients were administered dacomitinib at 45 mg orally daily, in 21-day cycles. Primary end point was objective response rate., Results: Sixty-nine patients were enrolled with a median age of 62 years. Among response-evaluable patients, 8 [12.7%, 95% confidence interval (CI) 5.6% to 23.5%] achieved a partial response and 36 (57.1%) had stable disease, lasting ≥24 weeks in 9 patients (14.3%). The median progression-free survival (PFS) was 12.1 weeks and the median overall survival (OS) was 34.6 weeks. Most adverse events (AEs) were tolerable. The most common grade 3 or higher treatment-related AEs were diarrhea (15.9%), acneiform dermatitis (8.7%), and fatigue (8.7%). Treatment-related AEs led to at least one dose interruption in 28 (40.6%) patients and dose reductions in 26 (37.7%). Permanent treatment discontinuation occurred in 8 (11.6%) patients due to treatment-related AEs., Conclusions: Dacomitinib demonstrated clinical activity in RM-SCCHN, and the primary end point of this study was met. The toxicity profile of this agent was generally manageable with dose interruptions and adjustments.
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- 2013
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41. Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes.
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Bissada E, Abboud O, Abou Chacra Z, Guertin L, Weng X, Nguyen-Tan PF, Tabet JC, Thibaudeau E, Lambert L, Audet ML, Fortin B, and Soulières D
- Abstract
Background. RAS gene mutations have an impact on treatment response and overall prognosis for certain types of cancer. Objectives. To determine the prevalence and impact of K-RAS codons 12 and 13 mutations in patients with locally advanced HNSCC treated with primary or adjuvant chemo-radiation. Methods. 428 consecutive patients were treated with chemo-radiation therapy and followed for a median of 37 months. From these, 199 paraffin embedded biopsy or surgical specimens were retrieved. DNA was isolated and analyzed for K-RAS mutational status. Results. DNA extraction was successful in 197 samples. Of the 197 specimens, 3.5% presented K-RAS codon 12 mutations. For mutated cases and non-mutated cases, complete initial response to chemoradiation therapy was 71 and 73% (P = 0.32). LRC was respectively 32 and 83% (P = 0.03), DFS was 27 and 68% (P = 0.12), distant metastasis-free survival was 100 and 81% (P = 0.30) and OS was 57 and 65% (P = 0.14) at three years. K-Ras codon 13 analysis revealed no mutation. Conclusion. K-RAS codon 12 mutational status, although not associated with a difference in response rate, may influence the failure pattern and the type of therapy offered to patients with HNSCC. Our study did not reveal any mutation of K-RAS codon 13.
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- 2013
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42. Prognostic value of cartilage sclerosis in laryngeal cancer treated with primary radiation therapy.
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Moubayed SP, Bélair M, Saliba J, Bibeau-Poirier J, Christopoulos A, Nguyen-Tan PF, Guertin L, Lambert L, Olivier MJ, and Ayad T
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- Cohort Studies, Female, Humans, Laryngeal Cartilages diagnostic imaging, Laryngeal Neoplasms complications, Laryngeal Neoplasms mortality, Male, Middle Aged, Prognosis, Retrospective Studies, Sclerosis diagnostic imaging, Sclerosis etiology, Survival Rate, Tomography, X-Ray Computed, Laryngeal Cartilages pathology, Laryngeal Neoplasms radiotherapy
- Abstract
Objective: In patients with laryngeal cancer, pretreatment diagnosis of cartilage invasion often warrants a surgical or a bimodal treatment. Controversy exists on whether laryngeal cartilage sclerosis on computed tomography (CT) scan is a sign of tumor invasion. Our objective is to evaluate locoregional, laryngectomy-free, disease-specific, and overall survival in patients with laryngeal cancer with or without laryngeal cartilage sclerosis treated with primary radiation therapy., Study Design: Historical cohort study., Setting: Tertiary referral university center., Subjects and Methods: All laryngeal cancer patients treated with primary radiation therapy between 2002 and 2007 were included. Patients with and without laryngeal cartilage sclerosis on CT scan were identified. Patient, tumor, and treatment data were collected. Univariate and multivariate analyses were conducted using Kaplan-Meier survival analyses and Cox proportional-hazards regression., Results: One hundred eleven patients were included for analysis. Seventy-nine patients were classified as T1 or T2, and 32 patients were classified as T3 or T4. Twenty-three percent of patients had any laryngeal cartilage sclerosis, and 77% of patients had no sclerosis. On univariate and multivariate analyses, there was no statistically significant difference between patients with or without sclerosis. Results did not vary when studying each cartilage separately., Conclusion: Laryngeal cancer patients with cartilage sclerosis on CT scan do not have significantly different survival than patients without sclerosis. Validation of these results prospectively is warranted.
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- 2012
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43. Cervical lymph node metastases from unknown primary cancer: a single-institution experience with intensity-modulated radiotherapy.
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Villeneuve H, Després P, Fortin B, Filion E, Donath D, Soulières D, Guertin L, Ayad T, Christopoulos A, and Nguyen-Tan PF
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- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Adenosquamous drug therapy, Carcinoma, Adenosquamous mortality, Carcinoma, Adenosquamous pathology, Carcinoma, Adenosquamous secondary, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell secondary, Chemoradiotherapy methods, Female, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Head and Neck Neoplasms secondary, Humans, Lymphatic Metastasis, Male, Middle Aged, Neck, Neoplasm Staging, Neoplasms, Unknown Primary drug therapy, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated adverse effects, Retrospective Studies, Survival Analysis, Xerostomia etiology, Xerostomia pathology, Carcinoma, Adenosquamous radiotherapy, Carcinoma, Squamous Cell radiotherapy, Head and Neck Neoplasms radiotherapy, Lymphatic Irradiation methods, Neoplasms, Unknown Primary pathology, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer., Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method., Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up., Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities., (Copyright © 2012 Elsevier Inc. All rights reserved.)
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- 2012
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44. The role of computed tomography in the management of the neck after chemoradiotherapy in patients with head-and-neck cancer.
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Clavel S, Charron MP, Bélair M, Delouya G, Fortin B, Després P, Soulières D, Filion E, Guertin L, and Nguyen-Tan PF
- Subjects
- Antineoplastic Agents therapeutic use, Carboplatin administration & dosage, Cisplatin administration & dosage, Decision Making, Dose Fractionation, Radiation, Female, Fluorouracil administration & dosage, Follow-Up Studies, Humans, Lymph Nodes pathology, Lymphatic Metastasis, Male, Middle Aged, Neck, Neoplasm Staging, Neoplasm, Residual, Remission Induction, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Tumor Burden, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell secondary, Carcinoma, Squamous Cell therapy, Chemoradiotherapy methods, Head and Neck Neoplasms diagnostic imaging, Head and Neck Neoplasms pathology, Head and Neck Neoplasms secondary, Head and Neck Neoplasms therapy, Lymph Nodes diagnostic imaging, Neck Dissection, Tomography, X-Ray Computed
- Abstract
Purpose: The aim of this study was to describe the outcome in patients with head-and neck-squamous cell carcinoma (HNSCC) followed up without neck dissection (ND) after concomitant chemoradiotherapy (CRT) based on computed tomography (CT) response. The second objective was to establish CT characteristics that can predict which patients can safely avoid ND., Methods and Materials: Between 1998 and 2007, 369 patients with node-positive HNSCC were treated with primary CRT at our institution. After a clinical and a radiologic evaluation based on CT done 6 to 8 weeks after CRT, patients were labeled with a complete neck response (CR) or with a partial neck response (PR)., Results: The median follow-up was 44 months. The number of patients presenting with N3, N2, or N1 disease were 54 (15%), 268 (72%), and 47 (13%), respectively. After CRT, 263 (71%) patients reached a CR, and 253 of them did not undergo ND. Ninety-six patients reached a PR and underwent ND. Of those, 34 (35%) had residual disease on pathologic evaluation. A regression of the diameter of ≥ 80% and a residual largest diameter of 15 mm of nodes had negative pathologic predictive values of 100% and 86%, respectively. The 3-year regional control and survival rates were not different between patients with CR who had no ND and patients with PR followed by ND., Conclusion: Node-positive patients presenting a CR as determined by CT evaluation 6 to 8 weeks after CRT had a low rate of regional recurrence without ND. This study also suggests that lymph node residual size and percentage of regression on CT after CRT may be useful criteria to guide clinical decisions regarding neck surgery. Those results can help diminish the number of ND procedures with negative results and their associated surgical complications., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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45. Simultaneous integrated boost using intensity-modulated radiotherapy compared with conventional radiotherapy in patients treated with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma.
- Author
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Clavel S, Nguyen DH, Fortin B, Després P, Khaouam N, Donath D, Soulières D, Guertin L, and Nguyen-Tan PF
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carboplatin administration & dosage, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Chemoradiotherapy adverse effects, Chemoradiotherapy methods, Disease-Free Survival, Dose Fractionation, Radiation, Female, Fluorouracil administration & dosage, Humans, Male, Middle Aged, Neoplasm Staging, Oropharyngeal Neoplasms drug therapy, Oropharyngeal Neoplasms mortality, Oropharyngeal Neoplasms pathology, Radiotherapy, Intensity-Modulated adverse effects, Retrospective Studies, Carcinoma, Squamous Cell radiotherapy, Oropharyngeal Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer., Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method., Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months., Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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46. ¹⁸F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head and neck cancer.
- Author
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Delouya G, Igidbashian L, Houle A, Bélair M, Boucher L, Cohade C, Beaulieu S, Filion EJ, Coulombe G, Hinse M, Martel C, Després P, and Nguyen-Tan PF
- Subjects
- Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell pathology, Female, Head and Neck Neoplasms diagnostic imaging, Head and Neck Neoplasms pathology, Humans, Lymphatic Metastasis, Male, Middle Aged, Radiotherapy, Image-Guided, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Tomography, X-Ray Computed, Carcinoma, Squamous Cell radiotherapy, Fluorodeoxyglucose F18, Head and Neck Neoplasms radiotherapy, Multimodal Imaging methods, Positron-Emission Tomography, Radiopharmaceuticals
- Abstract
Purpose: To determine the impact of (18)F-fluorodeoxyglucose positron emission tomography (PET) in radiotherapy target delineation and patient management for head and neck squamous cell carcinoma (HNSCC) compared to computed tomography (CT) alone., Materials and Methods: Twenty-nine patients with HNSCC were included. CT and PET/CT obtained for treatment planning purposes were reviewed respectively by a neuroradiologist and a nuclear medicine specialist who were blinded to the findings from each other. The attending radiation oncologist together with the neuroradiologist initially defined all gross tumor volume of the primary (GTVp) and the suspicious lymph nodes (GTVn) on CT. Subsequently, the same radiation oncologist and the nuclear medicine specialist defined the GTVp and GTVn on (18)F-FDG-PET/CT. Upon disagreement between CT and (18)F-FDG-PET on the status of a particular lymph node, an ultrasound-guided fine needle aspiration was performed. Volumes based on CT and (18)F-FDG-PET were compared with a paired Student's t-test., Results: For the primary disease, four patients had previous diagnostic tonsillectomy and therefore, FDG uptake occurred in 25 patients. For these patients, GTVp contoured on (18)F-FDG-PET (GTVp-PET) were smaller than the GTVp contoured on CT (GTVp-CT) in 80% of the cases, leading to a statistically significant volume difference (p=0.001). Of the 60 lymph nodes suspicious on PET, 55 were also detected on CT. No volume change was observed (p=0.08). Ten biopsies were performed for lymph nodes that were discordant between modalities and all were of benign histology. Distant metastases were found in two patients and one had a newly diagnosed lung adenocarcinoma., Conclusions: GTVp-CT was significantly larger when compared to GTVp-PET. No such change was observed for the lymph nodes. (18)F-FDG-PET modified treatment management in three patients, including two for which no curative radiotherapy was attempted. Larger multicenter studies are needed to ascertain whether combined (18)F-FDG-PET/CT in target delineation can influence the main clinical outcomes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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47. Enteral feeding during chemoradiotherapy for advanced head-and-neck cancer: a single-institution experience using a reactive approach.
- Author
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Clavel S, Fortin B, Després P, Donath D, Soulières D, Khaouam N, Charpentier D, Bélair M, Guertin L, and Nguyen-Tan PF
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carboplatin administration & dosage, Carcinoma complications, Carcinoma drug therapy, Carcinoma pathology, Carcinoma radiotherapy, Carcinoma, Squamous Cell, Combined Modality Therapy methods, Disease-Free Survival, Female, Fluorouracil administration & dosage, Follow-Up Studies, Head and Neck Neoplasms complications, Head and Neck Neoplasms pathology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mucositis, Neoplasms, Squamous Cell complications, Neoplasms, Squamous Cell drug therapy, Neoplasms, Squamous Cell pathology, Neoplasms, Squamous Cell radiotherapy, Patient Care Team, Radiodermatitis etiology, Radiotherapy Dosage, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Stomatitis etiology, Weight Loss, Enteral Nutrition methods, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy, Malnutrition therapy
- Abstract
Purpose: The optimal method for providing enteral nutrition to patients with head-and-neck cancer is unclear. The purpose of the present study was to evaluate the safety and efficacy of our reactive policy, which consists of the installation of a nasogastric (NG) feeding tube only when required by the patient's nutritional status., Methods and Materials: The records of all patients with Stage III and IV head-and-neck cancer treated with concomitant chemotherapy and radiotherapy between January 2003 and December 2006 were reviewed. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test., Results: The present study included 253 patients, and the median follow-up was 33 months. At 3 years, the estimated overall survival and disease-free survival rate was 82.8% and 77.8%, respectively, for the whole population. No survival difference was observed when the patients were compared according to the presence and absence of a NG tube or stratified by weight loss quartile. The mean weight loss during treatment for all patients was 10.4%. The proportion of patients requiring a NG tube was 49.8%, and the NG tube remained in place for a median duration of 40 days. No major complications were associated with NG tube installation. Only 3% of the patients were still dependent on enteral feeding at 6 months., Conclusion: These results suggest that the use of a reactive NG tube with an interdisciplinary team approach is a safe and effective method to manage malnutrition in patients treated with concomitant chemotherapy and radiotherapy for head-and-neck cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)
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- 2011
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48. Outcome with neck dissection after chemoradiation for N3 head-and-neck squamous cell carcinoma.
- Author
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Igidbashian L, Fortin B, Guertin L, Soulières D, Coulombe G, Belair M, Charpentier D, Tabet JC, and Nguyen-Tan PF
- Subjects
- Adult, Aged, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Combined Modality Therapy methods, Disease-Free Survival, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Radiotherapy, Intensity-Modulated, Remission Induction, Retrospective Studies, Statistics, Nonparametric, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy, Neck Dissection methods
- Abstract
Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease., Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND after partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests., Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%)., Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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49. Organ preservation with concurrent chemoradiation for advanced laryngeal cancer: are we succeeding?
- Author
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Lambert L, Fortin B, Soulières D, Guertin L, Coulombe G, Charpentier D, Tabet JC, Bélair M, Khaouam N, and Nguyen-Tan PF
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Carboplatin therapeutic use, Cisplatin therapeutic use, Combined Modality Therapy adverse effects, Combined Modality Therapy methods, Combined Modality Therapy mortality, Disease-Free Survival, Female, Gastrostomy statistics & numerical data, Humans, Hypopharyngeal Neoplasms mortality, Hypopharyngeal Neoplasms pathology, Laryngeal Neoplasms mortality, Laryngeal Neoplasms pathology, Male, Middle Aged, Radiotherapy Dosage, Tracheostomy statistics & numerical data, Hypopharyngeal Neoplasms drug therapy, Hypopharyngeal Neoplasms radiotherapy, Laryngeal Neoplasms drug therapy, Laryngeal Neoplasms radiotherapy
- Abstract
Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT)., Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years., Results: Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications., Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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50. Neck dissection following concurrent chemoradiation for advanced head and neck carcinoma: pathologic findings and complications.
- Author
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Christopoulos A, Nguyen-Tan PF, Tabet JC, Fortin B, Souliàres D, Charpentier D, and Guertin L
- Subjects
- Adult, Aged, Algorithms, Antineoplastic Agents therapeutic use, Blood Loss, Surgical statistics & numerical data, Combined Modality Therapy, Female, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Neck Dissection methods, Neoplasm, Residual, Postoperative Complications, Radiotherapy Dosage, Treatment Outcome, Head and Neck Neoplasms pathology, Head and Neck Neoplasms therapy
- Abstract
Objective: To assess the rate of pathologic residual neck disease and complication rates following selective neck dissection in patients with advanced head and neck carcinoma after concurrent chemotherapy (CT) and radiation therapy (RT)., Patients and Methods: Two hundred sixty-four patients with advanced-stage head and neck carcinoma underwent concurrent CT and RT from 1998 to 2004 at Notre-Dame Hospital. We describe the outcome of 32 of these patients who underwent neck dissections at our institution. The median age was 56 years (35-73 years). The primary sites were the oropharynx (n = 25), followed by the larynx (n = 3), hypopharynx (n = 1), and oral cavity (n = 1), and there were two unknown primary sites. The initial neck stages were 2 N1, 19 N2, and 11 N3. The known primary sites were staged 2 T1, 10 T2, 8 T3, 10 T4, and 2 Tx. All patients received conventional RT to a dose of 70 Gy in 35 fractions concurrent with a platinum-based CT regimen, Results: The median follow-up was 20 months. The mean operative blood loss for neck dissections alone was 170 mL (SD = 158.3 mL), the mean operative time was 128 minutes (SD = 41.6 minutes), and the mean hospital stay was 3.6 days (SD = 1.7 days). There were no major surgical complications. Five minor complications were noted in four patients (12.5%). Twelve patients (38%) had pathologic evidence of persistent disease (1 of 2 N1, 7 of 19 N2, and 4 of 11 N3)., Conclusions: Cervical neck dissection is a safe procedure following concurrent CT and RT and is still indicated if there is clinical or radiologic evidence of disease persistence in the neck. We experienced no major surgical complications and few minor complications. The pathologic residual rate was 38%.
- Published
- 2008
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