Less is more? Imaging-based target volume reduction – Authors’ reply.
Ursula Nestle, Tanja Schimek-Jasc, Jochem König
Abstract
We thank Eivind Blais and Idriss Troussier for their constructive comments on the interpretation of the results of the PET-Plan trial,1 posing the crucial question: is the potential benefit seen after radiotherapy target volume reduction because of a higher dose or a smaller volume?The target volume reduction done in PET-Plan goes beyond the move from elective nodal irradiation to involved-field irradiation. By design, in both study groups, all macroscopic (fluorodeoxyglucose [FDG]-positive) tumour was safely included but, in the experimental group (ie, target volumes informed by PET alone), the volumes (eg, concerning FDG-negative nodes and atelectasis) were further reduced compared with historic trials of involved-field irradiation. We, therefore, see here the results after focusing irradiation on macroscopic tumour (therefore, reducing irradiation of uninvolved tissue) with a consecutive moderate dose increment.The PET-Plan trial was powered to show non-inferiority of target volume reduction, and it clearly did. It was not powered to show a benefit of dose escalation, and it did not. In none of the secondary analyses did radiotherapy dose predict local or overall outcome, but a dose-effect cannot be excluded. We, therefore, agree that no recommendation about radiotherapy dose escalation can be deduced.The actual subjects of randomisation were target volumes; the results could, therefore, just be related to those and, if so, we can only speculate why. Beyond (hidden) toxicity,2 antitumour immunology might have a major role. Although this topic could not be investigated in the PET-Plan trial, we agree with Blais and Toussier that lymphopenia (as also shown for oesophageal cancer)3 might be relevant, and this deserves further discussion. Draining lymph nodes, which could have been somewhat protected in the experimental group of the PET-Plan trial, might also play a part in radiation-induced tumour immunoreactions.4 After stereotactic body radiotherapy, it has been shown that the irradiation of the macroscopically unaffected mediastinum had negative immunological effects.5The PET-Plan results pose new questions and highlight the importance of target volumes beyond treatment doses. We agree that this is very important for the combination of radiotherapy with immunotherapy, not just for non-small-cell lung cancer.UN, TS-J, and JK report grants from the German Cancer Aid (Deutsche Krebshilfe).
From bunker construction to patient treatment: quality controls applied to modern radiotherapy techniques.
Klausner G, Blais E, Martin C, Biau J, Jumeau R, Canova CH, Lyothier A, Slama Y, Jenny C, Chéa M, Zilli T, Miralbell R, Thariat J, Maingon P, Troussier I.
Cancer Radiother. 2019 Jun;23(3):248-254. doi: 10.1016/j.canrad.2018.07.142. Epub 2019 May 24. Review. French.
PMID: 31133513
Abstract
Installation and use of a new radiotherapy device require an adequate quality and safety policy. The process leading to the commissioning of an accelerator following the construction of a bunker includes, among other tasks, the installation of the accelerator, the verification of compliance with the specifications, the signature of the acceptance specification as well as the process of characterization and modeling of the accelerator before its clinical use. The emergence of modern radiotherapy techniques, such as intensity modulated conformational radiotherapy and stereotactic radiotherapy, has resulted in more complex quality controls. The purpose of this article is to explain the different stages of the implementation of innovative radiotherapy techniques and to specify their features.
Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 Update.
Biau J, Lapeyre M, Troussier I, Budach W, Giralt J, Grau C, Kazmierska J, Langendijk JA, Ozsahin M, O’Sullivan B, Bourhis J, Grégoire V.
Radiother Oncol. 2019 May;134:1-9. doi: 10.1016/j.radonc.2019.01.018. Epub 2019 Jan 30.
PMID: 31005201
Abstract
BACKGROUND AND PURPOSE:
In 2000, a panel of experts published a proposal for the selection of lymph node target volumes for definitive head and neck radiation therapy (Radiother Oncol, 2000; 56: 135-150). Hereunder, this selection is updated and extended to also cover primary sites not previously covered.
PATIENTS AND METHODS:
The lymphatic spread of head and neck cancers into neck lymph nodes was comprehensively reviewed based on radiological, surgical and pathological literature regarding both initial involvement and patterns of failure. Then a panel of worldwide head and neck radiotherapy experts agreed on a consensus for the selection of both high- and low-risk lymph node target volumes for the node negative and the node positive neck.
RESULTS:
An updated selection of lymph node target volumes is reported for oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity and carcinoma of unknown primary as a function of the nodal staging (UICC 8th edition).
CONCLUSIONS:
The selection of lymph node target volumes for head and neck cancers treated with IMRT/VMAT or other highly conformal techniques (e.g. proton therapy) requires a rigorous approach. This updated proposal of selection should help clinicians for the selection of lymph nodes target volumes and contribute to increase consistency.
Copyright © 2019 Elsevier B.V. All rights reserved.
Stereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients.
Klausner G, Troussier I, Biau J, Jacob J, Schernberg A, Canova CH, Simon JM, Borius PY, Malouf G, Spano JP, Roupret M, Cornu P, Mazeron JJ, Valéry C, Feuvret L, Maingon P.
Clin Genitourin Cancer. 2019 Jun;17(3):191-200. doi: 10.1016/j.clgc.2019.02.007. Epub 2019 Feb 28.
PMID: 30926219
Abstract
BACKGROUND:
The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era.
PATIENTS AND METHODS:
From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%).
RESULTS:
The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age ≥65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis ≤4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis.
CONCLUSION:
SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.
Copyright © 2019 Elsevier Inc. All rights reserved.
Neck management in head and neck squamous cell carcinomas: where do we stand?
Klausner G, Troussier I, Blais E, Carsuzaa F, Zilli T, Miralbell R, Caparrotti F, Thariat J.
Med Oncol. 2019 Mar 27;36(5):40. doi: 10.1007/s12032-019-1265-1. Review.PMID: 30919135
Abstract
Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/- followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms ‘neck management’ OR ‘cervical lymphadenopathies’ AND ‘head and neck neoplasms’. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV- or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna’s trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers’ experience, in the context of limited data, especially for N2-3 HPV- HNSCC.
Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study.
Pflumio C, Troussier I, Sun XS, Salleron J, Petit C, Caubet M, Beddok A, Calugaru V, Servagi-Vernat S, Castelli J, Miroir J, Krengli M, Giraud P, Romano E, Khalifa J, Doré M, Blanchard N, Coutte A, Dupin C, Sumodhee S, Pointreau Y, Patel S, Rehailia-Blanchard A, Catteau L, Bensadoun RJ, Tao Y, Roth V, Geoffrois L, Faivre JC, Thariat J.
Eur J Cancer. 2019 Apr;111:69-81. doi: 10.1016/j.ejca.2019.01.004. Epub 2019 Feb 28.
PMID: 30826659
Abstract
INTRODUCTION:
Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.
METHODS:
This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.
RESULTS:
Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.
CONCLUSION:
Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Chemoradiation for oesophageal cancer: A critical review of the literature.
Blais E, Vendrely V, Sargos P, Créhange G, Huguet F, Maingon P, Simon JM, Bourdais R, Ozsahin M, Bourhis J, Clément-Colmou K, Belghith B, Proudhom Briois MA, Gilliot O, Dujols JP, Peyras A, Dupin C, Riet FG, Canova CH, Huertas A, Troussier I.
Cancer Radiother. 2019 Feb;23(1):62-72. doi: 10.1016/j.canrad.2018.05.003. Epub 2019 Jan 11. Review. French.
PMID: 30639379
Abstract
Locally advanced oesophageal cancer treatment requires a multidisciplinary approach with the combination of chemotherapy and radiotherapy for preoperative and definitive strategy. Preoperative chemoradiation improves the locoregional control and overall survival after surgery for locally advanced oesophageal cancer. Definitive chemoradiation can also be proposed for non-resectable tumours or medically inoperable patients. Besides, definitive chemoradiation is considered as an alternative option to surgery for locally advanced squamous cell carcinomas. Chemotherapy regimen associated to radiotherapy consists of a combination of platinum derived drugs (cisplatinum or oxaliplatin) and 5-fluorouracil or a weekly scheme combination of carboplatin and paclitaxel according to CROSS protocol in a neoadjuvant strategy. Radiation doses vary from 41.4Gy to 45Gy for a preoperative strategy or 50 to 50.4Gy for a definitive treatment. The high risk of lymphatic spread due to anatomical features could justify the use of an elective nodal irradiation when the estimated risk of microscopic involvement is higher than 15% to 20%. An appropriate delineation of the gross tumour volume requires an exhaustive and up-to-date evaluation of the disease. Intensity-modulated radiation therapy represents a promising approach to spare organs-at-risk. This critical review of the literature underlines the roles of radiotherapy for locally advanced oesophageal cancers and describes doses, volumes of treatment, technical aspects and dose constraints to organs-at-risk.
Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
Quality and safety policy implementation for a new radiotherapy device.
Martin C, Jumeau R, Blais E, Canova CH, Klausner G, Dumas R, Rouger A, Pariente F, Lyothier A, Slama Y, Dol J, Perret J, Jenny C, Chea M, Pasdeloup F, Maingon P, Troussier I.
Cancer Radiother. 2019 Feb;23(1):50-57. doi: 10.1016/j.canrad.2018.04.002. Epub 2018 Dec 14. Review. French.
PMID: 30558863
Abstract
Modern radiotherapy techniques (intensity-modulated radiotherapy, volumetric-modulated arctherapy, image-guided radiotherapy) or stereotactic radiotherapy are in expansion in most French cancer centres. The arrival of such techniques requires updates of existing equipment or implementation of new radiotherapy devices with adapted options. With the arrival of these new devices, there is a need to develop a quality and safety policy. This is necessary to ease the process from the setup to the first treated patient. The quality and safety policy is maintained to ensure the quality assurance of the radiotherapy equipment. We conducted a review of the literature on the quality and safety policy in the French legal framework that can be proposed when implementing a new radiotherapy device.
Copyright © 2018. Published by Elsevier Masson SAS.
Management of locally advanced anal canal carcinoma with intensity-modulated radiotherapy and concurrent chemotherapy.
Klausner G, Blais E, Jumeau R, Biau J, de Meric de Bellefon M, Ozsahin M, Zilli T, Miralbell R, Thariat J, Troussier I.
Med Oncol. 2018 Aug 20;35(10):134. doi: 10.1007/s12032-018-1197-1. Review.
PMID: 30128811
Abstract
The best curative option for locally advanced (stages II-III) squamous-cell carcinomas of the anal canal (SCCAC) is concurrent chemo-radiotherapy delivering 36-45 Gy to the prophylactic planning target volume with an additional boost of 14-20 Gy to the gross tumor volume with or without a gap-period between these two sequences. Although 3-dimensional conformal radiotherapy led to suboptimal tumor coverage because of field junctions, this modality remains a standard of care. Recently, intensity-modulated radiotherapy (IMRT) techniques improved tumor coverage while decreasing doses delivered to organs at risk. Sparing healthy tissues results in fewer severe acute toxicities. Consequently, IMRT could potentially avoid a gap-period that may increase the risk of local failure. Furthermore, these modalities reduce severe late toxicities of the gastrointestinal tract as well as better functional conservation of anorectal sphincter. This report aims to critically review contemporary trends in the management of locally advanced SCCAC using IMRT and concurrent chemotherapy.
Advances in the management of cervical lymphadenopathies of unknown primary with intensity modulated radiotherapy: Doses and target volumes.
Troussier I, Klausner G, Blais E, Giraud P, Lahmi L, Pflumio C, Faivre JC, Geoffrois L, Babin E, Morinière S, Maingon P, Thariat J.
Cancer Radiother. 2018 Sep;22(5):438-446. doi: 10.1016/j.canrad.2017.10.008. Epub 2018 May 3. Review. French.
PMID: 29731331
Abstract
The definition of nodal and/or mucosal target volumes for radiation therapy for lymphadenopathies of unknown primary is controversial. Target volumes may include all nodal areas bilaterraly and be pan-mucosal or unilateral, selective, including the sole oropharyngeal mucosa. This review presents current recommendations in light of changes in the TNM classification, Human papillomavirus status and therapeutic advances. We conducted a systematic review of the literature with the following keywords: lymphadenopathy; head and neck; unknown primary and radiation therapy. There are no direct comparative studies between unilateral or bilateral nodal irradiation or pan-mucosal and selective mucosal irradiation. Contralateral lymph node failure rates range from 0 to 6% after unilateral nodal irradiation and 0 and 31% after bilateral irradiation. Occurrence of a mucosal primary varies between 0 and 19.2%. Initial clinical presentation and Human papillomavirus status are critical to define mucosal target volumes. Intensity-modulated radiotherapy is recommended (rather than three-dimensional irradiation) to avoid toxicities. Systemic treatments have similar indications as for identified primary head and neck cancers. Failures do not appear superior in case of unilateral nodal irradiation but comparative studies are warranted due to major biases hampering direct comparisons. Human papillomavirus status should be incorporated into the therapeutic strategy and practice-changing TNM staging changes will need to be evaluated.
Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
Advances in the management of cervical lymphadenopathies of unknown primary: advances in diagnostic imaging and surgical modalities and new international staging system.
Troussier I, Klausner G, Morinière S, Blais E, Jean-Christophe Faivre, Champion A, Geoffrois L, Pflumio C, Babin E, Maingon P, Thariat J.
Bull Cancer. 2018 Feb;105(2):181-192. doi: 10.1016/j.bulcan.2017.11.009. Epub 2017 Dec 21. Review. French.
PMID: 29275831
Abstract
INTRODUCTION:
Cervical lymphadenopathies of unknown primary represent 3 % of head and neck cancers. Their diagnostic work up has largely changed in recent years. This review provides an update on diagnostic developments and their potential therapeutic impact.
MATERIALS AND METHODS:
This is a systematic review of the literature.
RESULTS:
In recent years, changes in epidemiology-based prognostic factors such as human papilloma virus (HPV) cancers, advances in imaging and minimally invasive surgery have been integrated in the management of cervical lymphadenopathies of unknown primary. In particular, systematic use of PET scanner and increasing practice of robotic or laser surgery have contributed to increasing detection rate of primary cancers. These allow more adapted and personalized treatments. The impact of changes in the eighth TNM staging system is discussed.
CONCLUSION:
The management of cervical lymphadenopathies of unknown primary cancer has changed significantly in the last 10 years. On the other hand, practice changes will have to be assessed.
Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Clinical research for rectal carcinoma: State of the art and objectives.
Maingon P, Simon JM, Canova CH, Troussier I, Besson N, Caillot É, Huguet F.
Cancer Radiother. 2017 Oct;21(6-7):533-535. doi: 10.1016/j.canrad.2017.07.019. Epub 2017 Sep 7. French.
PMID: 28890092
Abstract
The treatment of rectal carcinoma is based on multidisciplinary strategy and multimodal approaches including gastrointestinal tract specialists, medical oncologists, radiation oncologists and surgery. The different objectives should be declined according to the characteristics of the tumours. The aim of the therapist would be to select the best strategy offering to the patient to be cured with as less as possible late adverse toxicity. The challenge of the treatment of small tumours is to maintain a functional anal sphincter while minimizing the risk of local recurrence. The standard treatment of locally advanced disease is aiming firstly to cure the patient and secondly to prevent late complications. Each of these clinical presentations of the disease has to be considered as a whole taking into account the new surgical techniques and a personalized approach adapted to the tumour. Nowadays they should be studied with dedicated clinical trials.
Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
Lung dose constraints for normo-fractionated radiotherapy and for stereotactic body radiation therapy.
Blais E, Pichon B, Mampuya A, Antoine M, Lagarde P, Kantor G, Breton-Callu C, Lefebvre C, Gerard M, Aamarcha A, Ozsahin M, Bourhis J, Maingon P, Troussier I, Pourel N.
Cancer Radiother. 2017 Oct;21(6-7):584-596. doi: 10.1016/j.canrad.2017.07.046. Epub 2017 Sep 5. Review. French.
PMID: 28886981
Abstract
Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15-20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.
Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
Adaptive radiation therapy in head and neck cancer for clinical practice: state of the art and practical challenges.
Veresezan O, Troussier I, Lacout A, Kreps S, Maillard S, Toulemonde A, Marcy PY, Huguet F, Thariat J.
Jpn J Radiol. 2017 Feb;35(2):43-52. doi: 10.1007/s11604-016-0604-9. Epub 2016 Dec 1. Review.
PMID: 27909957
Abstract
Modern radiation therapy techniques are characterized by high conformality to tumor volumes and steep dose gradients to spare normal organs. These techniques require accurate clinical target volume definitions and rigorous assessment of set up uncertainties using image guidance, a concept called image-guided radiation therapy. Due to alteration of patient anatomy, changes in tissue density/volumes and tumor shrinkage over the course of treatment, treatment accuracy may be challenged. This may result in excessive irradiation of organs at risk/healthy tissues and undercoverage of target volumes with a significant risk of locoregional failure. Adaptive radiation therapy (ART) is a concept allowing the clinician to reconsider the planned dose based on potential changes to accurately delivering the remaining radiation dose to the tumor while optimally minimizing irradiation of healthy tissues. There is little consensus on how to apply this concept in clinical practice. The current review investigates the current ART issues, including patient selection, clinical/dosimetric criteria and timing for re-planning, and practical technical issues. A practical algorithm is proposed for patient management in cases where ART is required.
Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study.
Bracci S, Laigle-Donadey F, Hitchcock K, Duran-Peña A, Navarro S, Chevalier A, Jacob J, Troussier I, Delattre JY, Mazeron JJ, Hoang-Xuan K, Feuvret L.
J Neurooncol. 2016 Sep;129(2):347-53. doi: 10.1007/s11060-016-2182-1. Epub 2016 Jun 16.
PMID: 27311728
Abstract
To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among “very elderly” patients affected by GBM. Patients 80 and older should be considered for management based on RT.
Efficacy and safety of helical tomotherapy with daily image guidance in anal canal cancer patients.
De Bari B, Jumeau R, Bouchaab H, Vallet V, Matzinger O, Troussier I, Mirimanoff RO, Wagner AD, Hanhloser D, Bourhis J, Ozsahin EM.
Acta Oncol. 2016 Jun;55(6):767-73. doi: 10.3109/0284186X.2015.1120886. Epub 2016 Apr 1.
PMID: 27034083
Abstract
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. Concomitant chemotherapy was delivered in 73 patients, mainly using mitomycin C and 5-fluorouracil (n = 30) or mitomycin C and capecitabine combination (n = 37). After a median follow-up period of 47 months (range 3-75), the five-year LC rate was 83.8% (95% CI 76.2-91.4%). Seven patients underwent a colostomy because of local recurrence (n = 5) or pretreatment dysfunction (n = 2). Overall incidence of grade 3 acute toxicity was 24%, mainly as erythema (n = 15/19) or diarrhea (n = 7/19). Two patients presented a late grade 3 gastrointestinal toxicity (anal incontinence). No grade 4 acute or late toxicity was recorded. Conclusions HT with daily IGRT is efficacious and safe in the treatment of anal canal cancer patients, and is considered in our department standard of care in this clinical setting.
Clinical and paraclinical follow-up after radiotherapy for head and neck cancer.
Clément-Colmou K, Troussier I, Bardet É, Lapeyre M.
Cancer Radiother. 2015 Oct;19(6-7):597-602. doi: 10.1016/j.canrad.2015.05.017. Epub 2015 Aug 13. French.
PMID: 26278985
Abstract
Head and neck cancer management often involves heavy multimodal treatments including radiotherapy. Despite the improvement of intensity-modulated radiation therapy, acute and late toxicities remain important. After such treatment, patients have to face different potential problems, depending on the post-therapeutic delay. In this way, short-term follow-up permits to appreciate the healing of acute toxicities and response to treatment. Long-term follow-up aims to recognize second primitive tumours and distant failure, and to detect and manage late toxicities. Medical and psychosocial supportive cares are essential, even after several years of complete remission. The objective of this article is to review the modalities of short-term and long-term follow-up of patients who receive a radiotherapy for head and neck cancer.
Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
Mucosal melanomas of the head and neck: State of the art and current controversies.
Troussier I, Baglin AC, Marcy PY, Even C, Moya-Plana A, Krengli M, Thariat J.
Bull Cancer. 2015 Jun;102(6):559-67. doi: 10.1016/j.bulcan.2015.04.013. Epub 2015 May 26. French.
PMID: 26022288
Abstract
Mucosal melanomas of the head and neck (sinonasal and oral cavity) account for 1% of neoplasms, 4% of all melanomas and over 50% of all mucosal melanomas. They have a high metastatic potential. Five-year overall survival does not exceed 30%. Diagnosis may be difficult and includes adequate immunohistochemical staining. Risk factors, presentation and molecular biology are different from those of cutaneous melanomas. The mainstay of treatment is surgery and postoperative radiotherapy. Endoscopic surgery should be evaluated prospectively. Neck dissection is recommended for N0 oral cavity melanomas, while it can generally be omitted for sinonasal melanomas. Inoperable tumors can be treated with exclusive radiotherapy. Molecular guidance for metastatic cases is a relevant option despite low level of evidence, based on the rarity of disease and low response rates to chemotherapy. c-KIT inhibitors and immunotherapy appear promising.
Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy.
Troussier I, Huguet F, Servagi-Vernat S, Benahim C, Khalifa J, Darmon I, Ortholan C, Krebs L, Dejean C, Fenoglietto P, Vieillot S, Bensadoun RJ, Thariat J.
Cancer Radiother. 2015 Apr;19(2):127-38. doi: 10.1016/j.canrad.2014.12.005. Epub 2015 Mar 12. French.
PMID: 25770884
Abstract
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 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days 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 break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.
Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
Lymph node metastases from squamous cell carcinoma of unknown primary site. Is it time to change of paradigm?
Hamoir M, Troussier I, Machiels JP, Reychler H, Schmitz S, Thariat J, Grégoire V.
Bull Cancer. 2014 May 1;101(5):455-60. doi: 10.1684/bdc.2014.1965. Review. French.
PMID: 24886896
Abstract
The diagnosis of carcinoma of unknown primary (CUP) is made after exclusion of the presence of a mucosal primary. There are two mains options for the primary treatment of CUP, either a neck node dissection followed by postoperative radiotherapy or chemo-radiotherapy, or a primary radiotherapy or chemo-radiotherapy depending on the nodal stage followed in case of residual neck disease by a selective neck dissection. There is no data to suggest the superiority of one over the other. For radiotherapy, unilateral neck or bilateral neck, including the upper aerodigestive tract mucosa are possible options. There is no definite data to demonstrate the superiority of one over the other, but owing the reduced toxicity of unilateral irradiation, and the possibility of salvage treatment in case of emergence of a mucosal primary and/or a contralateral neck node development, the former may be the preferred option. Advances in radiotherapy such as intensity modulated radiation therapy have the potential to spare organs at risk and reduce late toxicity rates. A selective irradiation approach customized on “major” criteria, such as nodal stage and level, HPV and EBV status and accessory criteria, such as histological variants, is under investigation.
Cervical node of unknown primary: patterns of care and factors influencing the choice of clinical target volumes.
Troussier I, Bensadoun RJ, Chamorey E, Lapeyre M, Baujat B, Leysalle A, Sun XS, Pointreau Y, Calugaru V, Pan Q, Ovidiu V, Schultz P, Malard O, Bujor L, Morinière S, Chamois J, Coutte A, Michel X, Huguet F, Fouillet B, Roth V, Vernat SS, Meert N, Gallocher O, Drouet F, Lang P, Thariat J.
Oral Oncol. 2014 May;50(5):e25-6. doi: 10.1016/j.oraloncology.2014.02.010. Epub 2014 Mar 11. No abstract available.
PMID: 24630259
Target volumes in cervical lympadenopathies of unknown primary: toward a selective customized approach? On behalf of REFCOR.
Troussier I, Barry B, Baglin AC, Leysalle A, Janot F, Baujat B, Fakhry N, Sun XS, Marcy PY, Dufour X, Bensadoun RJ, Thariat J.
Cancer Radiother. 2013 Nov;17(7):686-94. doi: 10.1016/j.canrad.2013.07.132. Epub 2013 Oct 4. Review. French.
PMID: 24095636
Abstract
The treatment of carcinomas of unknown primary revealed by cervical lymphadenopathy is based on neck dissection and nodal and pan-mucosal irradiation to control the neck and avoid the emergence of a metachronous primary. The aim of this review was to assess diagnostic and therapeutic approaches and criteria that may be used for a customized selective approach to avoid severe toxicities of pan-mucosal irradiation. A literature search was performed with the following keywords: cervical lymphadenopathy, unknown primary, upper aerodigestive tract, cancer, radiotherapy, squamous cell carcinoma, variants. The diagnostic workup includes a head and neck scanner or MRI, ((18)F)-FDG PET CT, a panendoscopy and tonsillectomy. Squamous cell carcinoma represents over two thirds of cases. The number of metastatic cervical nodes, nodal level, and histological variant (associated with HPV/EBV status) may determine the primary site origin and might be weighted for the determination of radiation target volumes on a multidisciplinary basis. A selective customized approach is relevant to decrease radiation toxicity only if neck and mucosal control is not impaired. Although no recommendation can yet be made in the absence of sufficient level of evidence, the relevance of systematic pan-mucosal irradiation appears questionable in a number of clinical situations. Accordingly, a customized selective redefinition of target volumes may be discussed and be prospectively evaluated in relation to the therapeutic index obtained.
Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
