International Journal of Otorhinolaryngology and Head and Neck Surgery, 2018
Background: Dysphagia is a serious sequel of head and neck cancer (HNC) and its treatment. This d... more Background: Dysphagia is a serious sequel of head and neck cancer (HNC) and its treatment. This dysfunction is frequent and likely underreported by clinical exam. It seems necessary to assess its global burden during the pre, per and post treatment periods (up to 18 months), regardless of the treatment received.Methods: This was a prospective cohort study assessing the rate of dysphagia in first-time treated HNC patients, using the deglutition handicap index questionnaire (DHI) and the clinician reporting. Time to occurrence, severity and length of the dysfunction were recorded. The benefit of an evaluation by the patient himself was investigated. Results: Of 134 evaluable patients: 22 were treated by surgery alone (16.4%), 16 by radiotherapy (RT) alone (11.9%), 3 by chemotherapy (CT) alone (2.2%), 28 by RTCT (20.9%), 31 by induction chemotherapy followed by RTCT (23.1%), 11 by surgery+RT (8.2%) and 23 by surgery+RTCT (17.2%). Patients completed 87.9% of the expected DHI. The dysph...
COVER LETTER This manuscript entitled : Recommendations for postoperative radiotherapy in head & ... more COVER LETTER This manuscript entitled : Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: a GORTEC internationally reviewed consensus This timely article provides a consensus recommendations reviewed by international experts to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Best regards.
The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of ... more The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50 kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50 TM machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.
Background Cost-effectiveness is a pivotal consideration for clinical decision making of high-tec... more Background Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. Methods A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective...
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
au nom du Gortec et de trois centres franç ais abcefgh a Département d'oncologie-radiothérapie, i... more au nom du Gortec et de trois centres franç ais abcefgh a Département d'oncologie-radiothérapie, institut Curie,
Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachy... more Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC). Material and methods: This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed. Results: From May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1-13 pts (21.7%), T2-34 pts (73.9%), T3-2 pts (4.3%), N+-6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%. Conclusions: In ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.
Objective: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine... more Objective: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction. Methods: Patients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis. Results: A total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores. Conclusions: Psychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.
Purposes: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosim... more Purposes: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). Material and methods: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. Results: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. Conclusion: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.
European journal of cancer (Oxford, England : 1990), Nov 8, 2016
Providing head and neck cancer patients with adequate information is essential to their confidenc... more Providing head and neck cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate patient perceptions of the information received, the predictive factors of such perceptions and their potential correlation with patient quality of life (QoL). We conducted a prospective multicentric study using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-INFO25 and QLQ-C30 questionnaires before and after surgery. This study enrolled 200 patients, 149 men and 51 women, mean age 63.5 ± 10.3 years. Before and after treatment, global QLQ-INFO25 scores were 39.3 and 42.5, respectively, whereas satisfaction with the information received scores were 69.9 and 58.1, respectively. Regarding EORTC QLQ-INFO25 scores, between the pre- and post-treatment periods, we observed a significant increase in three scales/items (information about other services, information about different places ...
The aims of this study were to evaluate clinical outcomes and to determine their predictive facto... more The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status. Keywords Oral cavity Á Head neck cancer Á Mandible Á Reconstruction Á Free-flap Á Fibula & Alexandre Bozec
This study reports outcome of a homogenous cohort of oligometastatic patients treated with stereo... more This study reports outcome of a homogenous cohort of oligometastatic patients treated with stereotactic body radiotherapy for lung lesions arising from colorectal cancer. This study demonstrated lower local control with rectal lesions, which may have a more aggressive biological behavior, as suggested by a different KRAS mutation profile. Introduction: Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. Material and Methods: This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014. Results: We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1-and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site (P ¼ .001) and > 2 metastases (P ¼ .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P ¼ .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P ¼ .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P ¼ .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume ! 3266 mm 3 (P ¼ .03) and > 2 metastases (P ¼ .04). Conclusion: In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome.
International Journal of Radiation Oncology*Biology*Physics, 2015
mutation rate was not significantly different between primary and recurrent tumors (4.0 vs 3.1 mu... more mutation rate was not significantly different between primary and recurrent tumors (4.0 vs 3.1 mutations/Mb, P Z .77). Several genes were mutated in multiple tumors, including recurrent hotspot mutations in FBXW7 (8/17 tumors), as well as known oncogenic mutations in NFE2L2 (3 tumors) and PIK3CA (3 tumors). Copy number analysis revealed focal amplifications of chromosome 3p. In many cases, comparison of primary and recurrent tumors from the same patient demonstrated significant mutational heterogeneity, including the presence of distinct clonal driver mutations in some pairs. Human Papillomavirus status was determined by p16 immunohistochemistry (IHC) and by in situ hybridization (ISH) using a probe set for high-risk HPV subtypes. Fifteen of the 17 tumors were HPV positive (88%) by both p16 IHC and HPV ISH. Conclusion: To our knowledge, this study represents the first exome-level genomic analysis in anal carcinoma. In our pilot cohort, we identified recurrent mutations in several known cancer genes, with tumors sharing some mutational features with HPV-associated squamous cell carcinomas of other sites. Comparative analysis of paired primary and recurrent tumors reveals surprising mutational heterogeneity, indicating selective outgrowth of a treatment-resistant clone or development of a genetically distinct second tumor. Analyses of additional cases are underway to extend and validate these findings.
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont r... more Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont ressentis par le patient.
Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (O... more Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes. To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors. This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses. A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of...
Materials and Methods: Between June 2009 and January 2014, 100 consecutive patients (pts) (90 men... more Materials and Methods: Between June 2009 and January 2014, 100 consecutive patients (pts) (90 men, 10 women; mean age 60 years, range: 36-80) with HNC, were included in the study. The primary tumor sites were: 18% oral cavity, 20% oropharynx, 12% hypopharynx, 11% nasopharynx, 37% larynx, 2% paranasal sinuses. 5% were stage I, 7% stage II, 14% stage III, 61% stage IVa, 7% stage IVb and 6% stage IVc. All patients were staged according to the American Joint Committee of Cancer 7 th edition. We performed a contrast-enhanced CT and a contrast-enhanced 18 FDG PET-CT which was done in the specific radiotherapy patient positioning. Both exams were compared to analyze a change in the detection of the primary tumor or nodal disease by 18 FDG PET-CT and therefore a modification in the target volume planning (PTV). Results: In 6 pts, distance metastases were detected so that the intent of the treatment changed into palliative. Synchronous tumors were detected in 8 pts. When we analyzed he primary tumor defined by the CT and compared to the 18 FDG PET-CT, it varied in 27% of cases due to differences in extension: 16 % increased; 11 % decreased which implies a variation in the delineation of tumor-GTV (T-GTV). Referring to the nodal detection, it globally varied in 42% cases: 5% pts were down-staged (pts staged as N2c changed to N2a, N2b or N1) and 3% (Nx to N0) were in fact false positive. This implies a reduction in the size of the nodal GTV (N-GTV). On the other hand, there were 17% pts affected by nodal disease detected thanks to the 18 FDG PET-CT but not diagnosed by the basal CT. 3% pts were staged as N+ (N1, N2a or N2b) but turned out into N2c. Those findings required to enlarge the nodal GTV. Conclusions: Target volume delineation is crucial in the radiotherapy treatment. The detection of metastases, additional nodal disease or larger extension in primary tumor has a great impact on patient management. The modification of the T-GTV and N-GTV implies a variation in the prescribed dose that could be related with the disease outcome and the final quality of life. PO-0642 Nomograms to assess the parotid gland dose in head and neck IMRT based on anatomical markers
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
The primary objective of this study was to determine the clinical and pathological prognostic fac... more The primary objective of this study was to determine the clinical and pathological prognostic factors in locally advanced oral cavity cancers treated by primary surgery. Methods: All patients treated by primary surgery with free-flap reconstruction for locally advanced oral cavity squamous cell carcinoma in our institution between 2000 and 2010 were included in this retrospective study. Overall, cause-specific and locoregional disease-free survivals were determined by Kaplan-Meier analyses. Clinical and histological prognostic factors were assessed by univariate (Log Rank tests) and multivariate (Cox models) analyses. Results: A total of 149 patients (102 men and 47 women; mean age = 61.3 ± 12.1 years) were included in the study. Five-year overall, cause-specific and locoregional disease-free survivals were 55%, 68% and 71%, respectively. Age, comorbidity and tumour size (histological evaluation) were significantly correlated with overall survival (P < 0.05). Age, tumour size, bone invasion and surgical margins were significantly correlated with locoregional disease-free survival (P < 0.05).
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2011
Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont r... more Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont ressentis par le patient.
International Journal of Otorhinolaryngology and Head and Neck Surgery, 2018
Background: Dysphagia is a serious sequel of head and neck cancer (HNC) and its treatment. This d... more Background: Dysphagia is a serious sequel of head and neck cancer (HNC) and its treatment. This dysfunction is frequent and likely underreported by clinical exam. It seems necessary to assess its global burden during the pre, per and post treatment periods (up to 18 months), regardless of the treatment received.Methods: This was a prospective cohort study assessing the rate of dysphagia in first-time treated HNC patients, using the deglutition handicap index questionnaire (DHI) and the clinician reporting. Time to occurrence, severity and length of the dysfunction were recorded. The benefit of an evaluation by the patient himself was investigated. Results: Of 134 evaluable patients: 22 were treated by surgery alone (16.4%), 16 by radiotherapy (RT) alone (11.9%), 3 by chemotherapy (CT) alone (2.2%), 28 by RTCT (20.9%), 31 by induction chemotherapy followed by RTCT (23.1%), 11 by surgery+RT (8.2%) and 23 by surgery+RTCT (17.2%). Patients completed 87.9% of the expected DHI. The dysph...
COVER LETTER This manuscript entitled : Recommendations for postoperative radiotherapy in head & ... more COVER LETTER This manuscript entitled : Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: a GORTEC internationally reviewed consensus This timely article provides a consensus recommendations reviewed by international experts to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Best regards.
The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of ... more The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50 kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50 TM machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.
Background Cost-effectiveness is a pivotal consideration for clinical decision making of high-tec... more Background Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. Methods A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective...
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
au nom du Gortec et de trois centres franç ais abcefgh a Département d'oncologie-radiothérapie, i... more au nom du Gortec et de trois centres franç ais abcefgh a Département d'oncologie-radiothérapie, institut Curie,
Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachy... more Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC). Material and methods: This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed. Results: From May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1-13 pts (21.7%), T2-34 pts (73.9%), T3-2 pts (4.3%), N+-6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%. Conclusions: In ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.
Objective: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine... more Objective: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction. Methods: Patients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis. Results: A total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores. Conclusions: Psychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.
Purposes: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosim... more Purposes: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). Material and methods: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. Results: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. Conclusion: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.
European journal of cancer (Oxford, England : 1990), Nov 8, 2016
Providing head and neck cancer patients with adequate information is essential to their confidenc... more Providing head and neck cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate patient perceptions of the information received, the predictive factors of such perceptions and their potential correlation with patient quality of life (QoL). We conducted a prospective multicentric study using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-INFO25 and QLQ-C30 questionnaires before and after surgery. This study enrolled 200 patients, 149 men and 51 women, mean age 63.5 ± 10.3 years. Before and after treatment, global QLQ-INFO25 scores were 39.3 and 42.5, respectively, whereas satisfaction with the information received scores were 69.9 and 58.1, respectively. Regarding EORTC QLQ-INFO25 scores, between the pre- and post-treatment periods, we observed a significant increase in three scales/items (information about other services, information about different places ...
The aims of this study were to evaluate clinical outcomes and to determine their predictive facto... more The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status. Keywords Oral cavity Á Head neck cancer Á Mandible Á Reconstruction Á Free-flap Á Fibula & Alexandre Bozec
This study reports outcome of a homogenous cohort of oligometastatic patients treated with stereo... more This study reports outcome of a homogenous cohort of oligometastatic patients treated with stereotactic body radiotherapy for lung lesions arising from colorectal cancer. This study demonstrated lower local control with rectal lesions, which may have a more aggressive biological behavior, as suggested by a different KRAS mutation profile. Introduction: Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. Material and Methods: This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014. Results: We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1-and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site (P ¼ .001) and > 2 metastases (P ¼ .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P ¼ .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P ¼ .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P ¼ .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume ! 3266 mm 3 (P ¼ .03) and > 2 metastases (P ¼ .04). Conclusion: In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome.
International Journal of Radiation Oncology*Biology*Physics, 2015
mutation rate was not significantly different between primary and recurrent tumors (4.0 vs 3.1 mu... more mutation rate was not significantly different between primary and recurrent tumors (4.0 vs 3.1 mutations/Mb, P Z .77). Several genes were mutated in multiple tumors, including recurrent hotspot mutations in FBXW7 (8/17 tumors), as well as known oncogenic mutations in NFE2L2 (3 tumors) and PIK3CA (3 tumors). Copy number analysis revealed focal amplifications of chromosome 3p. In many cases, comparison of primary and recurrent tumors from the same patient demonstrated significant mutational heterogeneity, including the presence of distinct clonal driver mutations in some pairs. Human Papillomavirus status was determined by p16 immunohistochemistry (IHC) and by in situ hybridization (ISH) using a probe set for high-risk HPV subtypes. Fifteen of the 17 tumors were HPV positive (88%) by both p16 IHC and HPV ISH. Conclusion: To our knowledge, this study represents the first exome-level genomic analysis in anal carcinoma. In our pilot cohort, we identified recurrent mutations in several known cancer genes, with tumors sharing some mutational features with HPV-associated squamous cell carcinomas of other sites. Comparative analysis of paired primary and recurrent tumors reveals surprising mutational heterogeneity, indicating selective outgrowth of a treatment-resistant clone or development of a genetically distinct second tumor. Analyses of additional cases are underway to extend and validate these findings.
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont r... more Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont ressentis par le patient.
Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (O... more Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes. To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors. This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses. A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of...
Materials and Methods: Between June 2009 and January 2014, 100 consecutive patients (pts) (90 men... more Materials and Methods: Between June 2009 and January 2014, 100 consecutive patients (pts) (90 men, 10 women; mean age 60 years, range: 36-80) with HNC, were included in the study. The primary tumor sites were: 18% oral cavity, 20% oropharynx, 12% hypopharynx, 11% nasopharynx, 37% larynx, 2% paranasal sinuses. 5% were stage I, 7% stage II, 14% stage III, 61% stage IVa, 7% stage IVb and 6% stage IVc. All patients were staged according to the American Joint Committee of Cancer 7 th edition. We performed a contrast-enhanced CT and a contrast-enhanced 18 FDG PET-CT which was done in the specific radiotherapy patient positioning. Both exams were compared to analyze a change in the detection of the primary tumor or nodal disease by 18 FDG PET-CT and therefore a modification in the target volume planning (PTV). Results: In 6 pts, distance metastases were detected so that the intent of the treatment changed into palliative. Synchronous tumors were detected in 8 pts. When we analyzed he primary tumor defined by the CT and compared to the 18 FDG PET-CT, it varied in 27% of cases due to differences in extension: 16 % increased; 11 % decreased which implies a variation in the delineation of tumor-GTV (T-GTV). Referring to the nodal detection, it globally varied in 42% cases: 5% pts were down-staged (pts staged as N2c changed to N2a, N2b or N1) and 3% (Nx to N0) were in fact false positive. This implies a reduction in the size of the nodal GTV (N-GTV). On the other hand, there were 17% pts affected by nodal disease detected thanks to the 18 FDG PET-CT but not diagnosed by the basal CT. 3% pts were staged as N+ (N1, N2a or N2b) but turned out into N2c. Those findings required to enlarge the nodal GTV. Conclusions: Target volume delineation is crucial in the radiotherapy treatment. The detection of metastases, additional nodal disease or larger extension in primary tumor has a great impact on patient management. The modification of the T-GTV and N-GTV implies a variation in the prescribed dose that could be related with the disease outcome and the final quality of life. PO-0642 Nomograms to assess the parotid gland dose in head and neck IMRT based on anatomical markers
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012
The primary objective of this study was to determine the clinical and pathological prognostic fac... more The primary objective of this study was to determine the clinical and pathological prognostic factors in locally advanced oral cavity cancers treated by primary surgery. Methods: All patients treated by primary surgery with free-flap reconstruction for locally advanced oral cavity squamous cell carcinoma in our institution between 2000 and 2010 were included in this retrospective study. Overall, cause-specific and locoregional disease-free survivals were determined by Kaplan-Meier analyses. Clinical and histological prognostic factors were assessed by univariate (Log Rank tests) and multivariate (Cox models) analyses. Results: A total of 149 patients (102 men and 47 women; mean age = 61.3 ± 12.1 years) were included in the study. Five-year overall, cause-specific and locoregional disease-free survivals were 55%, 68% and 71%, respectively. Age, comorbidity and tumour size (histological evaluation) were significantly correlated with overall survival (P < 0.05). Age, tumour size, bone invasion and surgical margins were significantly correlated with locoregional disease-free survival (P < 0.05).
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2011
Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont r... more Communications orales du samedi 13 octobre A15 mieux les troubles fonctionnels tels qu'ils sont ressentis par le patient.
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