Mahmut Ozsahin - Academia.edu (original) (raw)
Papers by Mahmut Ozsahin
Swiss Medical Weekly
Tr ansitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several ... more Tr ansitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several risk factors are smoking, occupational carcinogens, analgesic abuse or Balkan nephropathy.T he grade and stage of the disease have the most significant impact on the outcome. The treatment of renal pelvis and ureter tumours is open or laparoscopic surgery varying from conservative to more extensive surgical procedures, i.e. radical nephroureterectomy including removal of the contents of Gerota's fascia with ipsilateral ureter and a cuff of bladder at its distal extent. Most available data are from retrospective studies and surgery is the mainstay of treatment. Chemotherapy and/or radiation therapy are possible adjuvant or primary treatment for selected patients; however, prospective studies are needed to confirm their use.
Clinical and Translational Radiation Oncology
Introduction: Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment re... more Introduction: Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment remains a challenge due to limited surgical options. We report a case series of 5 patients treated by stereotactic lung salvage reirradiation for local relapse after a previous lung SBRT. Material and methods: Included patients presented an isolated primary lung relapse within at least the 50% isodose of the previous SBRT treatment. Typical reirradiation schedule was 60 Gy in 8 fractions at isodose 80% and was delivered by Cyberknife Ò using Synchrony Ò fiducial tracking system. Dose summations were performed to evaluate the safety of the reirradiation. Results: We identified 5 patients presenting peripheral lesions. All reirradiated lesions were locally controlled after a median follow-up of 11.1 months (6,7-12,2), while PFS at 6 months was 60% (n = 3). We did not notice any Grade 3 or more acute or late adverse event. Conclusion: We observed encouraging short-term outcome of lung SBRT reirradiation in patients presenting isolated local relapse of an early-stage NSCLC. Further studies are necessary to confirm the safety and efficiency of this salvage treatment approach.
Cancers
Personalized treatment and precision medicine have become the new standard of care in oncology an... more Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decisio...
Research article Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-... more Research article Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer
Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurren... more Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer.
Translational Lung Cancer Research, 2021
Background: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease assoc... more Background: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex. Methods: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations. Results: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as
International Journal of Radiation Oncology*Biology*Physics, 2020
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Radiotherapy and Oncology, 2019
The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. Howev... more The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. However, only limited data are currently available for its precise contouring, although this is absolutely necessary in the era of intensity-modulated radiation therapy (IMRT). The purpose of this article is to present practical clinical guidelines for contouring the trigeminal nerve (V) in head and neck cancers at risk of spread along this nerve. Method: The main types of head and neck cancers associated with risks of spread along the trigeminal nerve (V) and its branches were comprehensively reviewed based on clinical experience, literaturebased patterns of failure, anatomy and radio-anatomy. A consensus for contouring was proposed based on a multidisciplinary approach among head and neck oncology experts including radiation oncologists (JBi, ML, MO, VG and JB), a radiologist (VD) and a surgeon (CS). These practical clinical guidelines have been endorsed by the GORTEC (Head and Neck Radiation Oncology Group). Results: We provided contouring and treatment guidelines, supported by detailed figures and tables to help, for the trigeminal nerve and its branches: the ophthalmic nerve (V1), the maxillary nerve (V2) and the manidibular nerve (V3). A CT-and MRI-based atlas was proposed to illustrate the whole trigeminal nerve pathway with its main branches. Conclusion: Trigeminal nerve (V) invasion is an important component of the natural history of various head and neck cancers. Recognizing the radio-anatomy and potential routes of invasion is essential for optimal contouring, as presented in these guidelines.
Expert Opinion on Investigational Drugs, 2019
Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates hetero... more Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors. Areas Covered: This systematic review covers recent advancements in "patient-specific" treatment modalities, which can be only administered to a given patient. Expert Opinion: Currently, patient-specific treatment modalities in HNC mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. Despite the slow pace of development, the interest continues in these treatment modalities. The future of HNC treatment is expected to be guided by biomarkers and personalized approaches with tailored combinations of local treatments (radiotherapy, surgery), systemic agents and immune system modulation. Systematic research is required to generate robust data and obtain a high-level of evidence for the effectiveness of such treatment modalities. A c c e p t e d M a n u s c r i p t Article Highlights • HNC is caused by exposure to carcinogenic substances (tobacco, alcohol, industrial chemicals) or oncogenic viruses (HPV, EBV) with distinct pathophysiology, biologic and immune profiles. • The head and neck squamous-cell carcinoma tumor microenvironment is strongly immunosuppressive • Currently, all patient-specific treatment modalities in HNC are under development and mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. • Despite of the emergence of advanced techniques, the current data suggest, that it is unlikely to find the ultimate cure for HNC using off-the-shelf or patient-specific immunotherapy in the coming years. • The future of HNC treatment is expected to be guided by biomarkers and personalized with tailored combinations of local treatments (radiotherapy, surgery), systemic agents, and modulation of patients' immune system. • An ideal personalized and patient-specific treatment with 100% on-target action, efficacy and reproducibility, but 0% off-target action and toxicity is not expected in the near future.
Acta oncologica (Stockholm, Sweden), 2016
Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated a... more Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques, has been only recently introduced for treating anal cancer patients. We report efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer. Materials and methods We retrospectively analyzed efficacy and toxicity of HT with or without chemotherapy for anal cancer patients. Local control (LC) and grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported. Results Between October 2007 and May 2014, 78 patients were treated. Fifty patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3 disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8 Gy/fraction) delivered to the anal and to nodal gross tumor volumes...
Radiotherapy and Oncology, 2012
Cancer Research, 2015
Objective: Predicting the outcome of breast cancer (BC) patients based on sentinel lymph node (SL... more Objective: Predicting the outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is a matter of debate, especially when it comes to the definition of regional nodal irradiation (RNI). This is even unclear in the framework of primary systemic therapy (PST). The aim of the NORA (NOdal RAdiotherapy) Survey was to examine the patterns of RNI practiced by European Radiation Oncology centers. Methods: A web questionnaire was distributed to EORTC centers, and responses were received during the period between July 2013-January 2014. Results: A total of 81 European and 3 non-European answers were analyzed. While 3D planning is performed in 81 (96%) of the centers for breast irradiation, nodal areas are delineated in only 51 (61%) of the centers. After breast conserving surgery (BCS), only 14 (17%) centers declared to treat systematically the internal mammary chain (IMC), when supraclavicular node RT (SCN-RT) is indicated. Extra-capsular extension (ECE) is the main factor impacting decision-making regarding IMC and axillary nodal RT (ALN-RT). Only half of the centers advocate SCN-RT for intermediate risk patients (1-3N+). For macro-metastatic SLN involvement, there was a significant impact of ECE on decision-making independently from the number of positive LNs. In the PST setting, only 49 (58%) centers take into account the histologic fibrotic changes of the axillary LNs in post-PST ypN0 patients with unknown pre-PST status. In ypN0 patients with inner and central BC, 32 (39%) and 23 (27%) centers centers indicate SCN-RT and IMC-RT, respectively. SCN-RT is delivered by 30, 44, 58, 67 centers in patients with ypN(i+), ypN(mi), 1-2N+ and > 3-4N+ disease, respectively. ALN-RT is indicated by in 25% of the centers in patients with ypN(mi) or 1-2N+. Older age > 70y was not considered as a limited factor for RNI. Discussion: The term of RNI is not uniformly defined in the literature. In the historic studies, RNI was dedicated to wide RT including whole lymphatic pathways of the breast. ALN and IMC RT indications have declined with the time during the last decades because of the risk of morbidity. However this practice is challenged by the recent RT trials that reported and increase of overall and distant metastatic survival with RNI and IMC delivery in high-risk N0 and inner-central tumors. In addition, AMAROS trial showed equivalence between axillary RT and ALND in SLN (mi+) patients. Taking these data altogether in the context of increased avoidance of ALND, future challenges should concern the multidisciplinary patients’ selection for RNI and better personalization of the lymphatic pathways RT according to the risk of locoregional and distant recurrences. Conclusions: The NORA Survey is unique by evaluating the impact of SLN status and PST on RNI decision-making. IMC RT is not frequently coupled to SCN-RT. ECE is the main factor impacting decision-making for RNI. Only 58% of the centers take fibrotic changes in the LNs into consideration in decision-making for RNI indications. Age is not considered as a limiting factor for prescribing RNI in Europe. Citation Format: Yazid Belkacemi, Orit Kaidar-Person, Philippe Poortmans, Mahmut Ozsahin, Maria-Clara Valli, Nicola Russell, Ian Kunkler, Julie Hermans, Abraham Kuten, Geertjan van Tienhoven, Helen Westenberg. Patterns of practice of regional node irradiation in the sentinel node biopsy era: Results of the nodal radiotherapy (NORA) survey. On behalf of the EORTC Breast Working Party of the Radiation Oncology Group (ROG) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-09.
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique, Jan 11, 2015
The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal... more The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45Gy in 1.8Gy per fraction in the prophylactic planning target volume and additional 14 to 20Gy in the boost planning target volume (5days per week) with a possibility of 15days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment brea...
Revue médicale suisse, Jan 21, 2008
Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of al... more Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of all patients present with metastatic disease at diagnosis and need systemic treatment. Since the introduction of irinotecan and oxaliplatin as part of standard chemotherapy, and recently the new targeted agents bevacizumab, cetuximab and panitumumab, the overall survival for patients suffering from metastatic colorectal cancer (mCRC) has increased significantly and nearly reaches 2 years nowadays. Surgery or radiofrequency ablation has become central in the care of metastatic disease. This article resumes recent therapeutic advances in the field and emphasizes the multidisciplinary concertation between specialists to obtain the best outcome.
International Journal of Radiation Oncology*Biology*Physics, 1994
'~661 lsn%ny ZI uo!lt?x[qnd .IOJ paldaxy .aXIE?J~ 'S&Ed 'S~J+N?ll~ S2Jn?JI1V Sap aJ?ls!U!m 2ql PU... more '~661 lsn%ny ZI uo!lt?x[qnd .IOJ paldaxy .aXIE?J~ 'S&Ed 'S~J+N?ll~ S2Jn?JI1V Sap aJ?ls!U!m 2ql PUS S!Jt?d apxnel!doH sapaupap?~ apa%?llo3aqliCq papoddnss! u!qUs-ZO 'la 'LWIl?J~ 'Sued 'UO!SS!LULUO~ 6&X3 +.UOlV q3UaJd aq] pu~?sap!unu~u~o~ueado.~ngaqlI(qpal~oddns SBM lCpnlss!ql EPE '266 I JavaAw El-6 'V3'O%a!a UES '~~O~OXIO PUE ii8OlO$X?~ 3!lIladEJaq~ 'OJ iclapos ue3~awyaql~o%u~laa~ynui~~qlp~aqllepalu~~d i3.guanUt.y S.IO~I?J snof.wA %u~z@u~ uey~ lay)w 'vodal Ino '(9) paysgqnd L[sno!.taJd uaaq sey J_JAI$J %U!MO[~OJ luaurdolahap SI! ql!~ pay3osst2 s.10w.g pue s~3s~e~e3~0 muammo ayl %u!ulamo3 Lpnls palyap v .papIays iou s! I! 'syaynal .IOJ a$ts awal.nvaJ alqissod I? s! t!qlo ayl axns wauxdolalzap ~3e.1~~~3 01 speal uoy3pe~ %u!z!uo! lql WJ UMOuy f! s! 11 '(L 1 '5 1 ' 11 'p 'z ' I) qommd ~~~~o%u!uo!~!puo~aq)u~a~o~ineuodw! uestCe[d(~~~) uo!wpwy Lpoq-Iet?loL *(z 1 'p ' 1) ~iomxu auoq aq3 %U!A~OA-u! sa~swuilgeur le3~%olo~suray Jo luaurjt?a.xl aql u! 'In3-ssaxms aq 01 pallold sey y3!ym'r~~~~epou1 luauwa.u.yn-dod6~urst?al3ursr(~~V8)uop"lileIdsueqMolreur-auoa. . NOIJ3naOWLNI wo!lWNqdSuttJl MOJJUUI-aUOs 'uo!~auop3B~~ 'alal asop SnoautrluqsuI 'UO!~E!~EJJ! 6poq-p?lo~ 'aauap!xq 13~13113~ TIOpt?lU~~dSUtZJl MOJJEIU-aUOq %I!AtO[[OJ Sl3I3JBl~3~0 lUaIUdOIaAap aql UO a3Uan~U! III3 adttq hU (UO+UIO!l3tnJ JO/pUIT alEJ aSOp SllOaUt3lU~lSU~) UalU!%aJ UO!~B!~BJJ! bpOq-18101 aql lSq1 apn[JUOJ aM :UO!Sn[JUO~ '(PO'0 = d)S!SaUa%olXW3183 aql%l~Xlan~U~ JOlXjluapuadapu! 6[UO aql SBM alar asop snoauwnzlsu! aql laql pa[SaAaJ sasrEIsurr altqnmyn~ *(zz-0 = d 'QSZ 'SA %oc) lou as:oql purr sp!oJals au!A!aaaJ slua!isd aql uaamlaq a3uappui lx~w3 palsuqlsa Jsabj JO smJa1 u! a3uaJagp
Gynecologic Oncology, 2008
Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characteriz... more Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.
Archives of Otolaryngology–Head & Neck Surgery, 2006
To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head a... more To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated radiotherapy (RT).
Annals of Surgical Oncology, 2014
Background. We retrospectively reviewed the long-term outcome and late side effects of endometria... more Background. We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). Methods. Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. Results. After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT ? VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT ? VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT ? VB (P = 0.002 and P = 0.01), respectively. Conclusions. Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.
Swiss Medical Weekly
Tr ansitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several ... more Tr ansitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several risk factors are smoking, occupational carcinogens, analgesic abuse or Balkan nephropathy.T he grade and stage of the disease have the most significant impact on the outcome. The treatment of renal pelvis and ureter tumours is open or laparoscopic surgery varying from conservative to more extensive surgical procedures, i.e. radical nephroureterectomy including removal of the contents of Gerota's fascia with ipsilateral ureter and a cuff of bladder at its distal extent. Most available data are from retrospective studies and surgery is the mainstay of treatment. Chemotherapy and/or radiation therapy are possible adjuvant or primary treatment for selected patients; however, prospective studies are needed to confirm their use.
Clinical and Translational Radiation Oncology
Introduction: Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment re... more Introduction: Local recurrence after lung SBRT for early stage NSCLC is rare but its treatment remains a challenge due to limited surgical options. We report a case series of 5 patients treated by stereotactic lung salvage reirradiation for local relapse after a previous lung SBRT. Material and methods: Included patients presented an isolated primary lung relapse within at least the 50% isodose of the previous SBRT treatment. Typical reirradiation schedule was 60 Gy in 8 fractions at isodose 80% and was delivered by Cyberknife Ò using Synchrony Ò fiducial tracking system. Dose summations were performed to evaluate the safety of the reirradiation. Results: We identified 5 patients presenting peripheral lesions. All reirradiated lesions were locally controlled after a median follow-up of 11.1 months (6,7-12,2), while PFS at 6 months was 60% (n = 3). We did not notice any Grade 3 or more acute or late adverse event. Conclusion: We observed encouraging short-term outcome of lung SBRT reirradiation in patients presenting isolated local relapse of an early-stage NSCLC. Further studies are necessary to confirm the safety and efficiency of this salvage treatment approach.
Cancers
Personalized treatment and precision medicine have become the new standard of care in oncology an... more Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decisio...
Research article Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-... more Research article Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer
Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurren... more Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer.
Translational Lung Cancer Research, 2021
Background: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease assoc... more Background: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex. Methods: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations. Results: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as
International Journal of Radiation Oncology*Biology*Physics, 2020
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Radiotherapy and Oncology, 2019
The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. Howev... more The trigeminal nerve (V) is a major route of tumor spread in several head and neck cancers. However, only limited data are currently available for its precise contouring, although this is absolutely necessary in the era of intensity-modulated radiation therapy (IMRT). The purpose of this article is to present practical clinical guidelines for contouring the trigeminal nerve (V) in head and neck cancers at risk of spread along this nerve. Method: The main types of head and neck cancers associated with risks of spread along the trigeminal nerve (V) and its branches were comprehensively reviewed based on clinical experience, literaturebased patterns of failure, anatomy and radio-anatomy. A consensus for contouring was proposed based on a multidisciplinary approach among head and neck oncology experts including radiation oncologists (JBi, ML, MO, VG and JB), a radiologist (VD) and a surgeon (CS). These practical clinical guidelines have been endorsed by the GORTEC (Head and Neck Radiation Oncology Group). Results: We provided contouring and treatment guidelines, supported by detailed figures and tables to help, for the trigeminal nerve and its branches: the ophthalmic nerve (V1), the maxillary nerve (V2) and the manidibular nerve (V3). A CT-and MRI-based atlas was proposed to illustrate the whole trigeminal nerve pathway with its main branches. Conclusion: Trigeminal nerve (V) invasion is an important component of the natural history of various head and neck cancers. Recognizing the radio-anatomy and potential routes of invasion is essential for optimal contouring, as presented in these guidelines.
Expert Opinion on Investigational Drugs, 2019
Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates hetero... more Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors. Areas Covered: This systematic review covers recent advancements in "patient-specific" treatment modalities, which can be only administered to a given patient. Expert Opinion: Currently, patient-specific treatment modalities in HNC mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. Despite the slow pace of development, the interest continues in these treatment modalities. The future of HNC treatment is expected to be guided by biomarkers and personalized approaches with tailored combinations of local treatments (radiotherapy, surgery), systemic agents and immune system modulation. Systematic research is required to generate robust data and obtain a high-level of evidence for the effectiveness of such treatment modalities. A c c e p t e d M a n u s c r i p t Article Highlights • HNC is caused by exposure to carcinogenic substances (tobacco, alcohol, industrial chemicals) or oncogenic viruses (HPV, EBV) with distinct pathophysiology, biologic and immune profiles. • The head and neck squamous-cell carcinoma tumor microenvironment is strongly immunosuppressive • Currently, all patient-specific treatment modalities in HNC are under development and mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. • Despite of the emergence of advanced techniques, the current data suggest, that it is unlikely to find the ultimate cure for HNC using off-the-shelf or patient-specific immunotherapy in the coming years. • The future of HNC treatment is expected to be guided by biomarkers and personalized with tailored combinations of local treatments (radiotherapy, surgery), systemic agents, and modulation of patients' immune system. • An ideal personalized and patient-specific treatment with 100% on-target action, efficacy and reproducibility, but 0% off-target action and toxicity is not expected in the near future.
Acta oncologica (Stockholm, Sweden), 2016
Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated a... more Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques, has been only recently introduced for treating anal cancer patients. We report efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer. Materials and methods We retrospectively analyzed efficacy and toxicity of HT with or without chemotherapy for anal cancer patients. Local control (LC) and grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported. Results Between October 2007 and May 2014, 78 patients were treated. Fifty patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3 disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8 Gy/fraction) delivered to the anal and to nodal gross tumor volumes...
Radiotherapy and Oncology, 2012
Cancer Research, 2015
Objective: Predicting the outcome of breast cancer (BC) patients based on sentinel lymph node (SL... more Objective: Predicting the outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is a matter of debate, especially when it comes to the definition of regional nodal irradiation (RNI). This is even unclear in the framework of primary systemic therapy (PST). The aim of the NORA (NOdal RAdiotherapy) Survey was to examine the patterns of RNI practiced by European Radiation Oncology centers. Methods: A web questionnaire was distributed to EORTC centers, and responses were received during the period between July 2013-January 2014. Results: A total of 81 European and 3 non-European answers were analyzed. While 3D planning is performed in 81 (96%) of the centers for breast irradiation, nodal areas are delineated in only 51 (61%) of the centers. After breast conserving surgery (BCS), only 14 (17%) centers declared to treat systematically the internal mammary chain (IMC), when supraclavicular node RT (SCN-RT) is indicated. Extra-capsular extension (ECE) is the main factor impacting decision-making regarding IMC and axillary nodal RT (ALN-RT). Only half of the centers advocate SCN-RT for intermediate risk patients (1-3N+). For macro-metastatic SLN involvement, there was a significant impact of ECE on decision-making independently from the number of positive LNs. In the PST setting, only 49 (58%) centers take into account the histologic fibrotic changes of the axillary LNs in post-PST ypN0 patients with unknown pre-PST status. In ypN0 patients with inner and central BC, 32 (39%) and 23 (27%) centers centers indicate SCN-RT and IMC-RT, respectively. SCN-RT is delivered by 30, 44, 58, 67 centers in patients with ypN(i+), ypN(mi), 1-2N+ and > 3-4N+ disease, respectively. ALN-RT is indicated by in 25% of the centers in patients with ypN(mi) or 1-2N+. Older age > 70y was not considered as a limited factor for RNI. Discussion: The term of RNI is not uniformly defined in the literature. In the historic studies, RNI was dedicated to wide RT including whole lymphatic pathways of the breast. ALN and IMC RT indications have declined with the time during the last decades because of the risk of morbidity. However this practice is challenged by the recent RT trials that reported and increase of overall and distant metastatic survival with RNI and IMC delivery in high-risk N0 and inner-central tumors. In addition, AMAROS trial showed equivalence between axillary RT and ALND in SLN (mi+) patients. Taking these data altogether in the context of increased avoidance of ALND, future challenges should concern the multidisciplinary patients’ selection for RNI and better personalization of the lymphatic pathways RT according to the risk of locoregional and distant recurrences. Conclusions: The NORA Survey is unique by evaluating the impact of SLN status and PST on RNI decision-making. IMC RT is not frequently coupled to SCN-RT. ECE is the main factor impacting decision-making for RNI. Only 58% of the centers take fibrotic changes in the LNs into consideration in decision-making for RNI indications. Age is not considered as a limiting factor for prescribing RNI in Europe. Citation Format: Yazid Belkacemi, Orit Kaidar-Person, Philippe Poortmans, Mahmut Ozsahin, Maria-Clara Valli, Nicola Russell, Ian Kunkler, Julie Hermans, Abraham Kuten, Geertjan van Tienhoven, Helen Westenberg. Patterns of practice of regional node irradiation in the sentinel node biopsy era: Results of the nodal radiotherapy (NORA) survey. On behalf of the EORTC Breast Working Party of the Radiation Oncology Group (ROG) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-09.
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique, Jan 11, 2015
The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal... more The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45Gy in 1.8Gy per fraction in the prophylactic planning target volume and additional 14 to 20Gy in the boost planning target volume (5days per week) with a possibility of 15days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment brea...
Revue médicale suisse, Jan 21, 2008
Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of al... more Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of all patients present with metastatic disease at diagnosis and need systemic treatment. Since the introduction of irinotecan and oxaliplatin as part of standard chemotherapy, and recently the new targeted agents bevacizumab, cetuximab and panitumumab, the overall survival for patients suffering from metastatic colorectal cancer (mCRC) has increased significantly and nearly reaches 2 years nowadays. Surgery or radiofrequency ablation has become central in the care of metastatic disease. This article resumes recent therapeutic advances in the field and emphasizes the multidisciplinary concertation between specialists to obtain the best outcome.
International Journal of Radiation Oncology*Biology*Physics, 1994
'~661 lsn%ny ZI uo!lt?x[qnd .IOJ paldaxy .aXIE?J~ 'S&Ed 'S~J+N?ll~ S2Jn?JI1V Sap aJ?ls!U!m 2ql PU... more '~661 lsn%ny ZI uo!lt?x[qnd .IOJ paldaxy .aXIE?J~ 'S&Ed 'S~J+N?ll~ S2Jn?JI1V Sap aJ?ls!U!m 2ql PUS S!Jt?d apxnel!doH sapaupap?~ apa%?llo3aqliCq papoddnss! u!qUs-ZO 'la 'LWIl?J~ 'Sued 'UO!SS!LULUO~ 6&X3 +.UOlV q3UaJd aq] pu~?sap!unu~u~o~ueado.~ngaqlI(qpal~oddns SBM lCpnlss!ql EPE '266 I JavaAw El-6 'V3'O%a!a UES '~~O~OXIO PUE ii8OlO$X?~ 3!lIladEJaq~ 'OJ iclapos ue3~awyaql~o%u~laa~ynui~~qlp~aqllepalu~~d i3.guanUt.y S.IO~I?J snof.wA %u~z@u~ uey~ lay)w 'vodal Ino '(9) paysgqnd L[sno!.taJd uaaq sey J_JAI$J %U!MO[~OJ luaurdolahap SI! ql!~ pay3osst2 s.10w.g pue s~3s~e~e3~0 muammo ayl %u!ulamo3 Lpnls palyap v .papIays iou s! I! 'syaynal .IOJ a$ts awal.nvaJ alqissod I? s! t!qlo ayl axns wauxdolalzap ~3e.1~~~3 01 speal uoy3pe~ %u!z!uo! lql WJ UMOuy f! s! 11 '(L 1 '5 1 ' 11 'p 'z ' I) qommd ~~~~o%u!uo!~!puo~aq)u~a~o~ineuodw! uestCe[d(~~~) uo!wpwy Lpoq-Iet?loL *(z 1 'p ' 1) ~iomxu auoq aq3 %U!A~OA-u! sa~swuilgeur le3~%olo~suray Jo luaurjt?a.xl aql u! 'In3-ssaxms aq 01 pallold sey y3!ym'r~~~~epou1 luauwa.u.yn-dod6~urst?al3ursr(~~V8)uop"lileIdsueqMolreur-auoa. . NOIJ3naOWLNI wo!lWNqdSuttJl MOJJUUI-aUOs 'uo!~auop3B~~ 'alal asop SnoautrluqsuI 'UO!~E!~EJJ! 6poq-p?lo~ 'aauap!xq 13~13113~ TIOpt?lU~~dSUtZJl MOJJEIU-aUOq %I!AtO[[OJ Sl3I3JBl~3~0 lUaIUdOIaAap aql UO a3Uan~U! III3 adttq hU (UO+UIO!l3tnJ JO/pUIT alEJ aSOp SllOaUt3lU~lSU~) UalU!%aJ UO!~B!~BJJ! bpOq-18101 aql lSq1 apn[JUOJ aM :UO!Sn[JUO~ '(PO'0 = d)S!SaUa%olXW3183 aql%l~Xlan~U~ JOlXjluapuadapu! 6[UO aql SBM alar asop snoauwnzlsu! aql laql pa[SaAaJ sasrEIsurr altqnmyn~ *(zz-0 = d 'QSZ 'SA %oc) lou as:oql purr sp!oJals au!A!aaaJ slua!isd aql uaamlaq a3uappui lx~w3 palsuqlsa Jsabj JO smJa1 u! a3uaJagp
Gynecologic Oncology, 2008
Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characteriz... more Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.
Archives of Otolaryngology–Head & Neck Surgery, 2006
To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head a... more To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated radiotherapy (RT).
Annals of Surgical Oncology, 2014
Background. We retrospectively reviewed the long-term outcome and late side effects of endometria... more Background. We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). Methods. Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. Results. After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT ? VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT ? VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT ? VB (P = 0.002 and P = 0.01), respectively. Conclusions. Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.