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Because of the physical properties of proton beam radiation therapy (PT), which allows energy to be deposited at a specific depth with a rapid energy fall-off beyond that depth, PT has several theoretical advantages over photon radiation therapy for esophageal cancer (EC). Protons have the potential to reduce the dose to healthy tissue and to more safely allow treatment of tumors near critical organs, dose escalation, trimodal treatment, and re-irradiation. In recent years, larger multicenter retrospective studies have been published showing excellent survival rates, lower than expected toxicities and even better outcomes with PT than with photon radiotherapy even using IMRT or VMAT techniques. Although PT was associated with reduced toxicities, postoperative complications, and hospital stays compared to photon radiation therapy, these studies all had inherent biases in relation with patient selection for PT. These observations were recently confirmed by a randomized phase II study in locally advanced EC that showed significantly reduced toxicities with protons compared with IMRT. Currently, two randomized phase III trials (NRG-GI006 in the US and PROTECT in Europe) are being conducted to confirm whether protons could become the standard of care in locally advanced and resectable esophageal cancers.

Purpose Breast protontherapy efficiently limits cardiac, lung and contralateral breast exposure, which may clinically translate into better late tolerance profile compared with classic photon techniques. While breast protontherapy is already implemented in the United States and in some European countries, clinical experience of breast cancer protontherapy is currently limited in France. The aim of this study is to evaluate the clinical practice of breast cancer protontherapy at the Institut Curie in order to implement this technique at a larger scale. Materials and methods Data from all breast cancer patients that have been addressed to the protontherapy centre of Orsay (CPO, Institut Curie) for adjuvant breast protontherapy were retrieved. We analysed why these patients were ultimately treated with protontherapy or not. Results Between November 2019 and November 2020, eleven breast cancer patients have been evaluated for adjuvant protontherapy at the CPO. Two of them were ultimately treated with proton beams; adjuvant breast protontherapy therapy was well tolerated. The nine other patients were not treated with protontherapy due to lack of availability of protontherapy treatment rooms in acceptable time limits, at the time of patient evaluation. Conclusion Despite dosimetric advantages and excellent clinical tolerance, lack of availability of protontherapy machines currently limits wider implementation of breast protontherapy.

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7Gy vs. 8.4Gy) and median dose (0.002Gy vs. 6.9Gy), heart mean dose (2.6Gy vs. 3.7Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4Gy vs. 4.4Gy) and left (1.9Gy vs. 4.6Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.

Because of the physical properties of proton beam radiation therapy (PT), which allows energy to be deposited at a specific depth with a rapid energy fall-off beyond that depth, PT has several theoretical advantages over photon radiation therapy for esophageal cancer (EC). Protons have the potential to reduce the dose to healthy tissue and to more safely allow treatment of tumors near critical organs, dose escalation, trimodal treatment, and re-irradiation. In recent years, larger multicenter retrospective studies have been published showing excellent survival rates, lower than expected toxicities and even better outcomes with PT than with photon radiotherapy even using IMRT or VMAT techniques. Although PT was associated with reduced toxicities, postoperative complications, and hospital stays compared to photon radiation therapy, these studies all had inherent biases in relation with patient selection for PT. These observations were recently confirmed by a randomized phase II study in locally advanced EC that showed significantly reduced toxicities with protons compared with IMRT. Currently, two randomized phase III trials (NRG-GI006 in the US and PROTECT in Europe) are being conducted to confirm whether protons could become the standard of care in locally advanced and resectable esophageal cancers.

Purpose Protontherapy for mediastinal Hodgkin lymphoma reduces cardiac, lung and breast exposure, which may limit radiation-induced adverse events. While this technique is already widely implemented in the United-States, clinical experience is still limited in France. This study analyses the practice of mediastinal Hodgkin lymphoma protontherapy at the Institut Curie to implement this technique at a larger scale. Materials and Methods Data from all mediastinal Hodgkin lymphoma patients from the hematology department of the Institut Curie who were subsequently evaluated at the Protontherapy Center of Orsay (CPO) of Institut Curie for adjuvant protontherapy were retrieved. We analyzed why these patients were ultimately treated with protontherapy or not. Results Between January 2018 and January 2021, twenty mediastinal Hodgkin lymphoma patients from the hematology department of the Institut Curie have been screened for protontherapy at the CPO. Four of them (20%) were ultimately treated with proton beams. Treatment was well tolerated without grade 3–4 adverse events. With a median follow-up of two years, none of these patients relapsed. The others sixteen patients were not treated with protontherapy due to multiple reasons including: lack of treatment room disponibility, accessibility difficulties, psychiatric disorder, and anatomic or dosimetric considerations. Conclusion Despite notable dosimetric superiority over photon radiotherapy and excellent clinical tolerance, lack of availability of protontherapy facilities limit implementation of mediastinal Hodgkin lymphoma protontherapy. Additionally, strict selection criteria must be defined.

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France.

Summary Introduction The treatment of conjunctival melanoma is most often conservative, but exenteration is sometimes necessary in order to achieve local control of the disease. It can be performed as a primary procedure in cases of locally advanced disease or as a secondary procedure after one or more recurrences. No benefit to secondary exenteration on patient survival has been demonstrated to date for conjunctival melanoma, and it is generally considered a palliative procedure. Patients and methods Single-center retrospective study performed in the ocular oncology department of the Institut Curie (Paris, France). We included all patients who underwent secondary orbital exenteration for conjunctival melanoma between January 2008 and January 2016. Results Twenty-five patients underwent secondary exenteration for conjunctival melanoma. The maximum number of local recurrences prior to exenteration was six. Metastases occurred in 11 patients after exenteration and were more common when there was a greater tumor thickness on histology, if the tumor had not been treated initially in an ocular oncology center, or if there had been a greater number of local recurrences before the secondary exenteration was performed. Seventy-five percent of patients developed metastases when the exenteration was performed after 5 or 6 local recurrences. Conclusion This study suggests that early secondary exenteration (i.e. after a number of local recurrences less than or equal to 4) may reduce the occurrence of metastases (and therefore improve patient survival) in conjunctival melanoma. Thus, secondary exenteration might be a curative surgery in some patients with recurrent disease.

Purpose The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues. Patients and methods Ten patients with a paraganglioma of the head and neck were treated from 2001 to 2014 with image-guided proton therapy. Neurological and ear nose throat symptoms were collected in addition to audiometric testing, before and after the treatment. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4. Results Median age at diagnosis was 52.6 years (range: 18.2–65.8 years). Proton therapy was the exclusive treatment in six patients and four patients had a postoperative radiotherapy. Median dose was 50.4 Gy relative biological effectiveness (RBE; range: 45.0–67.0 Gy). With a median follow-up of 24.6 months (range: 6.7–46.2 months), local tumour control rate was 100% (stable, n = 10). No upper grade 2 acute toxicity was reported. To the latest news, seven patients had controlled symptoms (improved, n = 1, stabilized, n = 6). One patient out of seven with initial tinnitus had a decrease in his symptoms, while the six other patients had a sustained stabilization. Conclusion Proton beam therapy is an effective and well-tolerated treatment modality of skull base paragangliomas, with documented functional benefit. A longer follow-up is planned in order to assess local control and long-term toxicities.

Purpose/Objective(s) Proton therapy (PT) is being increasingly used for craniopharyngioma. Most series focus on pediatric population. Real therapeutic gain of PT in adults has yet to be demonstrated. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using PT to report outcomes for disease control, tumor response and treatment-related toxicity. Materials/Methods We reviewed medical records from 93 histological proven adult craniopharyngioma patients treated with PT at our institution from December 2006 to November 2018. Endpoints were overall survival, disease control and toxicity. The median age at PT was 36.5 years (18-82). Ninety patients were treated after at least one tumor resection prior PT (20 patients as adjuvant treatment after incomplete surgery, 70 for recurrent disease) and 3 as exclusive PT. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2–54 GyRBE). Toxicity was collected according CTCAE v5. Results With median clinical and radiographic follow-up of 37 and 31 months, respectively, the 3-year local control and overall survival rates were 100% and 93.5%, respectively. At last follow up, 16 patients remained in complete remission, 47 in partial remission, 24 with stable disease and 6 patients had a local relapse. Six patients required treatment replanning due to tumor changes during radiotherapy. There were two acute grade 3 toxicity events (one visual field decline and one headache). Two late grade 2 side-effects occurred (one visual field decline and one visual acuity deterioration) and one grade 3 neurocognitive dysfunction following radiotherapy. One patient with pre-existing visual field declines experienced grade 4 visual loss five months after PT and after receiving bevacizumab. Conclusion Fractionated PT appears as an effective and safe treatment for adult craniopharyngioma compared to IMRT and 3DRT. Although the integral dose in normal tissues decreases drastically, the benefit of PT remains uncertain in adult patients. Prospective quality-of-life and neurocognitive studies are needed to better define late toxicity. Only prospective trials in adult population should define the role of RT in terms of techniques, prescribed doses, fractionation and sparing of organs at risk. Author Disclosure N. Scher: None. G. Bentahila: None. A. Beddok: None. C. Alapetite: None. S. Helfre: None. S. Bolle: None. H. Mammar: None. R. Dendale: None. V. Calugaru: None. L. Feuvret: None.

Resume Objectif de l’etude L’objectif de cette etude etait d’evaluer l’efficacite et la tolerance d’un complement de dose de protons pour les patients atteints d’un cancer du nasopharynx localement evolue. Patients et methodes De novembre 1999 a septembre 2016, 17 patients atteints d’un cancer du nasopharynx de stade III–IVa ont ete pris en charge au centre de protontherapie d’Orsay de l’institut Curie. Les aires ganglionnaires cervicales bilaterales ont ete traitees par des photons a la dose de 40–54 Gy. La tumeur et ses extensions microscopiques ont recu une dose complementaire de protons pour atteindre la dose de 70–78 Gy. Tous les patients ont recu une chimiotherapie concomitante. Le controle local, la survie sans recidive et la survie globale ont ete determines, ainsi que la toxicite aigue et tardive. Resultats Les caracteristiques des patients etaient : un âge median de 49 ans, le sexe masculin pour 71 % des cas, 88 % des cancers etaient de stade IVa avec une majorite T4N0M0 (82 %). La mediane de suivi etait de 99 mois. Les probabilites de controle local et de survie globale actuarielle ont ete respectivement 94 % et 88 % a 2 ans, 86 % et 74 % a 5 ans, 86 % et 66 % a 10 ans. La toxicite tardive de grade ≥ 3 a ete la perte auditive (23,5 %) et une osteo-radio-necrose de l’os sphenoide (5,9 %). Conclusion Le complement de dose de protons semble donc une bonne alternative pour le traitement des cancers du nasopharynx localement evolues, en particulier pour ceux de stade T4N0M0.

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France.

Summary Purpose Our objective was to assess the results of surgical management of palpebral basal cell carcinomas (BCC) followed by a second line treatment discussed during a Multidisciplinary Team Meeting (MTM). Materials and Methods This retrospective single-centred study includes all surgically-treated basal cell carcinomas of the eyelids between January 2005 and January 2015. After initial surgery, the cases were systematically discussed during a multidisciplinary team meeting in order to assess the need for additional treatment. Data relative to the patient, tumor and management were pulled from the medical record. Results A total of 171 patients were included, with a mean age of 74 years. Among the patients, 151 underwent pentagonal resection of the tumor, and 20 patients had a superficial excision. After surgical management, 120 patients (70.2%) were considered to have sufficient free margins. The other 51 patients (29.8%) had insufficient margins due to remaining tumor cells (38 patients) or free margins less than 1 mm. Among these 51 patients with insufficient margins, 19 received a second surgical treatment, 17 patients received adjuvant radiotherapy, and 15 were followed closely with an intensive biannual follow-up program. No patients were lost to follow-up. With a mean follow-up of 42 months (min. 6 months–max. 128 months), 7 out of 171 patients (4.1%) developed a local recurrence. The mean time between surgical management and recurrence was 24 months. The recurrence rate was higher for the group of patients with a recurrent tumor (11.6%) than for the group of patients referred for initial management (2.8%). Incomplete resection was also associated with a higher recurrence rate (3 recurrences out of 51 patients). Discussion The management of basal cell carcinomas of the eyelid is first and foremost surgical with the goal of complete resection confirmed by histopathological analysis. The histological analyses (Mohs micrographic surgery, frozen section technic, paraffin fixation) and recommended sizes of the margins can vary in the literature, with recurrence rates from 1.8% to 9.5%. Conclusion In our experience, multidisciplinary management of BCC of the eyelid, including initial macroscopic surgery, histopathological analysis stating the histological type and size of the margins, along with additional treatment discussed in a MTM, allows for a recurrence rate of 4.1%.

The aim of this study was to assess the treatment outcome and toxicity for patients with locally advanced nasopharyngeal carcinoma treated with a complementary dose with proton.Between November 1999 and September 2016, 17 patients have been treated for a stage III-IVa nasopharyngeal carcinoma in the proton therapy centre of Curie Institute. Bilateral lymph node in the neck (I-V levels) received from 40 to 54Gy with photon beam. The primary tumor volume including microscopically extensions received a complementary dose with proton in order to reach the dose of 70 to 78Gy. All the patients received a concomitant chemotherapy. The end-points of the study were loco-regional control, survival, and treatment-related toxicity.Patients characteristics were: median age 49, 71 % male, 88% stage IVa, with a majority (82%) of T4N0M0. The median follow-up was 99 months. The 2-, 5- and 10-year actuarial locoregional free survival and overall survival were 94% and 88%, 86% and 74%, and 86% and 66%, respectively. The grade≥3 late adverse events were sphenoid bone radionecrosis (5.9%) and hearing loss (23.5%).This study showed that a complementary dose with proton seems to be a good option for the treatment of locally advanced nasopharyngeal carcinoma, particularly for T4N0M0.

Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy.Fourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy.Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy.Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.

Purpose: To report the results of a randomised study comparing the efficacy of Hydrosorb® versus control (water based spray) in the topical treatment of grade 1 and 2 radiation dermatitis in population of patients treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). Patients and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during normo fractionated postoperative radiotherapy were eligible (according to the CTCAE v3 scale). They were randomised to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of radiotherapy because of skin radiotoxicity or and/or change of local cares for skin alteration. Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Pain was assessed according to two classes with a VAS cut-off of 2. Results: Two-hundred seventy eight patients were enrolled (A = 142, B = 136). There were 186 successfully treated patients (82 in Hydrosorb® arm, and 74 in the control arm). There were 60 "failures" in the Hydrosorb® arm, and 62 in the control arm (p = 0.72), but mostly without interruption of the radiotherapy. Twenty-four patients stopped the radiotherapy treatment for local cares (16 in Hydrosorb®, arm and 8 in control arm). No risk factors were associated with failure to local treatment. The average absolute reduction of colorimetric levels between day 28 and day 0 was 4 in the Hydrosorb®, and 4.2 in the water spray groups, respectively (p = 0.36). Forty-eight patients in the Hydrosorb® arm had a VAS > 2 versus 51 patients in the placebo arm, i.e. 34% and 38%, respectively (p = 0.45). A significant reduction of pain was observed on D7 (p = 0.04) and D21 (p = 0.01) in the Hydrosorb® arm. Sixty patients in the Hydrosorb® arm and 55 patients in the placebo arm had moderately to severely altered quality of life (p = 0.76). Conclusions: The present study showed no significant difference between Hydrosorb® and simple water spray in the treatment of acute radio-induced dermatitis even if there was a trend to an improvement in pain at the first weeks after the treatment. Systematic prevention measures and modern breast cancer radiotherapy techniques now allow excellent tolerability, but the place of topical treatment to optimize this tolerability has yet to be defined. Citation Format: Bazire L, Fromentin I, Diallo A, de Lalande B, Pernin V, Dendale R, Fourquet A, Savignoni A, Kirova Y. Hydrosorb® versus control (water based spray) in the management of radio-induced skin toxicity: Results of multicentre controlled randomized trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-16.

Introduction et but de l’etude Les lymphomes de Hodgkin mediastinaux sont un defi dosimetrique chez des sujets jeunes avec une longue esperance de vie. La protontherapie presente un avantage dosimetrique, mais sa disponibilite est limitee. Nous presentons une demarche de selection des patients eligibles a une comparaison dosimetrique de la protontherapie contre la radiotherapie conformationnelle avec modulation d’intensite (RCMI) rotationnelle (arctherapie volumetrique modulee) et rotationnelle helicoidale (tomotherapie). Materiel et methodes La premiere etape etait la discussion systematique des dossiers par des oncologues-radiotherapeutes et des physiciens pour selectionner les patients pouvant tirer un benefice de la protontherapie. Apres une analyse de la comparaison dosimetrique, le choix de la technique d’irradiation a ete fait par deux medecins seniors. Nous presentons les resultats obtenus pour les deux premiers patients traites en France par protons pour un lymphome de Hodgkin mediastinal. Resultats et analyse statistique Les patients etaient des femmes jeunes (23 et 29 ans), avec une atteinte initiale mediastinale isolee (cas 1) ou associee a une atteinte sus-claviculaire bilaterale et cervicale gauche (cas 2), en reponse complete apres la chimiotherapie. La couverture des volumes cibles etait excellente : 95 % du volume cible previsionnel etaient couverte par 98 % contre 99 % de la dose prescrite en protontherapie au lieu de la tomotherapie et 83,9 % contre 94,3 % en protontherapie au lieu de l’arctherapie volumetrique modulee, respectivement. L’epargne des organes a risque etait meilleure avec la protontherapie qu’avec la tomotherapie (cas 1) et qu’avec l’arctherapie volumetrique modulee (cas 2) pour le cœur (dose moyenne 2,6 Gy contre 3,7 Gy et 1,2 Gy contre 1,5 Gy respectivement) et les seins (2,4 Gy et 1,9 Gy contre 4,4 Gy et 4,6 Gy et 1,2 Gy et 2,5 Gy contre 2,1 Gy et 2,9 Gy). L’epargne pulmonaire etait plus marquee (V20 Gy [VxGy : volume recevant x Gy] de 8,5 % contre 11,4 % et 3,8 % contre 4,4 %), en particulier pour les doses faibles (V5 Gy de 16 % contre 56,3 % et 11,4 % contre 23,2 %, respectivement). Nous avons choisi la protontherapie avec un faisceau direct anterieur par pencil-beam scanning a la dose de 30 Gy en 15 fractions. Aucune toxicite autre qu’une epitheliite grade 1 n’a ete observee pendant ou apres le traitement. Conclusion La protontherapie presente un avantage dosimetrique important dans la prise en charge des lymphomes de Hodgkin mediastinaux. La selection des patients est la cle, compte-tenu de la faible disponibilite de cette technique.

Summary Introduction To describe the results of retinoblastoma treatment from 1995–2009 in a single institution. Material and methods Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. Results During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P Discussion Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. Conclusions Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.

Summary Iris tumors include congenital benign cyst, naevi, melanocytomas malignant melanomas, benign adenoma,leiomyomas, metastatic tumors, iris location of leukemia or lymphomas and histiocytic proliferations like iris xanthogranuloma. Patients with metastatic disease rarely develop a bilateral diffuse melanocytic uveal proliferation (BDUMP) which can cause retinal detachment and blindness. The diagnosis of an iris tumor is made by careful medical history, slit lamp examination, UBM ultrasonography and OCT of the iris. In rare instances fine needle aspiration biopsy can be useful but follow up is often the more important test to differentiate stable naevus versus malignant melanoma of the iris. Treatment can be a simple observation for naevi or melanocytoma..Surgery is still the best option for adenomas and leiomyomas. Metastatic disease can be treated by chemotherapy and external beam radiation. Xanthogranulomas of the iris usually respond well to steroids. For melanoma of the iris a lot of centers do not use surgery and prefer radiotherapy most often proton beam radiotherapy. Results of proton beam therapy of iris melanoma will be presented.

Summary Introduction Surgical excision of large malignant lower eyelid tumors may cause important full-thickness eyelid defects. The reconstruction of such defects must restore the physiologic function of the eyelid and also re-establish an acceptable aesthetic result. Materials and methods We report the outcomes of full-thickness excision of tumors extending over half of the horizontal lid length, followed by reconstruction using a nasal chondromucosal graft (coming from the ipsilateral ala of the nose) and an upper eyelid myocutaneous flap . Histological analysis of the specimen identified the tumor type and surgical margins for each patient. Results A total of 25 patients were operated using this reconstruction technique between March 2009 and June 2015: 17 basal cell carcinomas , 3 spindle cell carcinomas and 5 conjunctival melanomas (out of which 2 were associated with lentigo maligna). Mean duration of follow-up after surgery was respectively 36, 41 and 17 months for each of these 3 tumor types. We found a single local tumor recurrence and this was a basal cell carcinoma in a xeroderma pigmentosum patient. After surgery, none of the patients had lagophthalmos or ocular surface complications. Only 4 patients had a 1 mm scleral show postoperatively; 3 other patients developed a small retraction of the eyelid after adjuvant radiotherapy and a 1 mm scleral show occurred. Conclusion In malignant tumors, complete surgical excision with histological margins adapted to tumor type prevents local recurrence in most cases. Our repair strategy of nasal chondromucosal graft and skin-muscle flap for large inferior eyelid defects provides good functional and aesthetic results.

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55 %. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0–126.0). Median age at diagnosis was 52 years (25–83). Internal mammary node (IMN) RT was performed in 227 patients (73.7 %). After completion of RT, 26 patients (8.4 %) presented an impaired LVEF: 17 (5.5 %) of grade 1, 7 (2.3 %) of grade 2, and 2 (0.6 %) of grade 3. At 48 months, locoregional control rate was 95 % [95 % CI 92; 98], and overall survival rate was 98 % [95 % CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

Resume L’hadrontherapie, radiotherapie par les particules lourdes chargees, beneficie depuis une dizaine d’annees d’un engouement sans precedent, tant sur le plan technologique que clinique. Le premier est lie au developpement commercial d’installations de protons compactes, relativement bon marche, et equipees de source rotatives isocentriques. L’arrivee du pencil beam scanning devrait simplifier et accelerer les procedures de traitement. Le second est lie aux succes rapportes dans, premierement, le traitement de tumeurs localement agressives, non ou peu resecables, et placees au voisinage immediat de structures saines radiosensibles : melanomes oculaires, sarcomes de bas grade de la base du crâne et du rachis, carcinomes de la sphere ORL evolues (cylindromes) ; secondement, la protection des tissus sains : a long terme, particulierement dans les tumeurs pediatriques, en raison de la grande radiosensibilite des tissus en croissance (incluant le risque carcinogene) ; immediate, sur la moelle osseuse, les muqueuses… notamment dans les associations concomitantes chimioradiotherapiques (etudiees dans les cancer du poumon et de l’œsophage). Les patients irradies par ions carbone ne representent qu’une minorite des 115 000 traites dans le monde mais, dans les mains des equipes japonaises, entrainent des resultats surprenants dans les formes les plus resistantes, telles que le melanome muqueux, les sarcomes de haut grade, le cancer du pancreas. Les modifications du fractionnement utilisees, posent d’interessantes questions biologiques et economiques. Une vive polemique s’est recemment developpee autour d’une expansion des indications vers des maladies communes (cancer de la prostate).

Resume Objectif Etude prospective monocentrique de la toxicite liee a l’administration concomitante du trastuzumab a la radiotherapie mammaire. Patientes et methodes Cent soixante-treize patientes ont ete traitees entre juin 2003 et mars 2009 par trastuzumab concomitant a une radiotherapie normofractionnee. Le trastuzumab etait delivre toutes les trois semaines (8 mg/kg a la premiere injection puis 6 mg/kg) pendant une duree mediane de 12 mois (2–62). La fraction d’ejection ventriculaire gauche a ete mesuree par echocardiographie ou scintigraphie cardiaque au moment du diagnostic, avant et apres la radiotherapie, tous les trois mois pendant un an puis annuellement. Une fraction d’ejection ventriculaire gauche strictement inferieure a 55 % etait consideree comme alteree. La toxicite a ete evaluee selon la Common Terminology Criteria for Adverse Effects version 3.0. Resultats Le suivi median etait de 52 mois (17–88). L’âge median etait de 52 ans (25–83). Cent trente-quatre patientes (77,5 %) ont recu une radiotherapie de la chaine mammaire interne. Une epitheliite aigue de grades 1, 2 et 3 a ete decrite chez respectivement 132 (76,3 %), 32 (18,5 %) et six patientes (3,4 %). Avec un recul median de 23 mois, une fibrose de grades 1 et 2 a ete observee chez respectivement 31 et huit patientes (18,8 et 4,6 %). La fraction d’ejection ventriculaire gauche etait normale pour 159 patientes (91,9 %) avant la radiotherapie. Elle etait alteree chez ces patientes 18 fois (11,3 %), dont huit (5,0 %) au terme de la radiotherapie. Une insuffisance cardiaque congestive symptomatique est survenue chez une patiente (0,6 %). Conclusion La toxicite en rapport avec l’association du trastuzumab a la radiotherapie mammaire s’est averee moderee. Un suivi prolonge est necessaire.

Purpose: To evaluate the early and late heart and skin toxicities, as well as the efficacy of concurrent adjuvant trastuzumab-radiotherapy (RT) for breast cancer (BC), with group with internal mammary chain (IMC) RT. Material and methods: Prospective study of 308 patients (pts) treated between 2000 and 2009 by concurrent trastuzumab with normofractionated RT for non-metastatic BC. Left ventricular ejection fraction (LVEF) was assessed by echocardiography or myocardial scintigraphy at baseline, before and after RT, every three months for one year, then annually. A LVEF strictly lower than 55%, was considered as altered. Trastuzumab was delivered every three weeks (8 mg/kg in the first infusion then 6 mg/kg) during a median time of 12 months (3–62). All toxicities were evaluated using the Common Terminology Criteria for Adverse Effects version 3.0. Survival data were defined as the time from the histological diagnosis of BC until occurrence of the event. Loco-regional recurrence free- and alive pts were censored at the date of their last known contact. Survival and interval rates as well as their confidence interval (CI) were calculated using the Kaplan–Meier method. Results: Median age was 52 years (25–83). Median follow-up was 50 months (13–126). The clinical tumour staging was: T0 or T1 in 131 pts (43.4%), T2 in 122 pts (40.4%), T3 or T4 in 49 pts (16.2%). The regional lymph nodes were histologically involved in 132 pts (43.0%). The left breast was treated in 155 pts (50.3%). The IMC was irradiated in 227 pts (73.7%), among them 114 (37.0%) in the left side. Before trastuzumab, anthracycline-based regimens were administered in 280 pts (90.9%). The median dose of trastuzumab was 6145 mg (1845–29180). Acute skin toxicity was acceptable with 226 (74.1%) grade 1, 67 (22.0%) grade 2 and 12 (3.9%) grade 3 skin reactions. Esophagitis was observed in 31 pts (10.0%): 26 (8.4%) grade 1; 4 (1.3%) grade 2, and 1 (0.3%) grade 3. Out of 286 pts with assessments at the median time of 23 months, late telangiectasia grade 1 occurred in 14 pts (4.9%) and grade 2 in 10 pts (3.5%), local pain grade 1 in 39 pts (13.7%) and grade 2 in 8 pts (2.8%), fibrosis grade 1 in 53 pts (18.6%) and grade 2 in 20 pts (7.0%). At the completion of RT, 11 pts (3.6%), whose cardiologic assessment at baseline was normal, presented a clinically silent LVEF alteration. During follow-up, 44 patients experienced cardio-vascular morbidity revealed by: asymptomatic LVEF alteration (50.0%), thrombo-embolic event (18.2%), tachycardia (15.9%), ischemic cardiomyopathy (6.8%), pericarditis (4.5%), hypertrophic cardiomyopathy (2.3%) or arterial hypertension (2.3%). The cumulative incidence of these events at 48 months was 13.3% CI95% [9.4; 17.2]. A symptomatic congestive heart failure was reported for 3 pts (1.0%). No death of cardiac origin was observed. At 48 months, loco-regional control was 95% CI95% [92; 98] and overall survival was 98% CI95% [96; 100]. Conclusions: In this prospective study of BC pts treated with trastuzumab and RT, both the rates of skin and esophageal toxicities were acceptable with excellent local control. Further follow-up is warranted to assess late cardiac toxicity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-21-03.

Summary Purpose Evisceration can be performed for blind, painful eyes. This surgery can promote the dissemination of tumor cells within the orbit if an ocular tumor has been missed preoperatively. Methods We reviewed the medical records of patients who were eviscerated for blind, painful eyes between 2009 and 2014 and who were referred after the surgery to the Institut Curie or the Rothschild Foundation in Paris. We included the patients with a histological diagnosis of ocular tumor or orbital recurrence. Cytogenetic analysis was performed whenever possible. Results Four patients turned out to have an ocular tumor after evisceration (two choroidal melanomas, a rhabdoid tumor and an adenocarcinoma of the retinal pigment epithelium); two had a history of prior ocular trauma. The tumors were diagnosed either on histological analysis of the intraocular contents (2 patients) or biopsy of orbital recurrence (2 patients). Prior to evisceration, fundus examination was not performed in 3 patients. One had preoperative imaging but no intraocular tumor was suspected. At the time of this study, 3 patients had had an orbital recurrence and died. We also found 2 patients who had an evisceration despite a past history of choroidal melanoma treated with proton beam therapy. Conclusion We showed that evisceration of eyes with unsuspected ocular malignancies was associated with a poor prognosis due to orbital recurrence and metastasis. The evisceration specimen should therefore always be sent for histological analysis in order to perform prompt adjuvant orbital radiotherapy if an ocular tumor is found.

In this chapter we present: I. The physical bases of proton therapy, going from microscopic concepts to macroscopic features II. The technology and the logistics, which evolve to more and more compact and cheaper facilities with the capability to perform adaptive radiation therapy III. The most usual clinical indications, moving toward (nearly) all indications of radiation therapy IV. Some research orientations, rediscovering physics, and radiation biology V. Basic elements to conceive and build a clinical center VI. Conclusions: The need to learn from others and also to innovate

Particle therapy provides an opportunity to study the human response to space radiation in ground-based facilities. On this basis, a study of light flashes analogous to astronauts' phosphenes reported by patients undergoing ocular proton therapy has been undertaken. The influence of treatment parameters on phosphene generation was investigated for 430 patients treated for a choroidal melanoma at the proton therapy centre of the Institut Curie (ICPO) in Orsay, France, between 2008 and 2011. 60% of them report light flashes, which are predominantly (74%) blue. An analysis of variables describing the patient's physiology, properties of the tumour and dose distribution shows that two groups of tumour and beam variables are correlated with phosphene occurrence. Physiology is found to have no influence on flash triggering. Detailed correlation study eventually suggests a possible twofold mechanism of phosphene generation based on (i) indirect Cerenkov light in the bulk of the eye due to nuclear interactions and radioactive decay and (ii) direct excitation of the nerve fibres in the back of the eye and/or radical excess near the retina.

Resume Objectif de l’etude Evaluer le benefice de la chirurgie mammaire chez les patientes traitees pour un cancer du sein inflammatoire. Patientes et methodes Cette etude retrospective a ete basee sur 232 patientes traitees pour des cancers du sein inflammatoire. Toutes les patientes ont recu une chimiotherapie premiere suivie soit de radiotherapie exclusive (118 patientes, 51 %) soit de chirurgie avec ou sans radiotherapie (114 patientes, 49 %). La duree mediane de surveillance etait de 11 ans. Resultats Les deux groupes etaient comparables en dehors de l’existence d’un plus petit nombre de tumeurs de moins de 70 mm (43 % contre 33 %, p = 0,003), un plus grand taux de tumeurs classees N2 cliniquement (15 % contre 5 %, p = 0,04) et un plus petit nombre de tumeurs de grade 3 (46 % contre 61 %, p Conclusion L’analyse des resultats indique que la chirurgie associee a la chimiotherapie et a la radiotherapie augmente le taux de controle local chez les patientes traitees pour un cancer du sein inflammatoire.

Resume Objectif de l’etude L’indication d’une radiotherapie externe est parfois posee chez des patients porteurs d’un stimulateur cardiaque. Ce traitement peut occasionner des dysfonctionnements lies soit a l’effet ionisant des rayons, soit a des interferences electromagnetiques. Nous avons repris le cas de patientes atteintes d’un cancer du sein traitees par une irradiation mammaire ou parietale, parfois aussi des aires ganglionnaires de drainage, pour evaluer la tolerance et les repercussions de la radiotherapie par rapport au stimulateur cardiaque. Patientes et methodes Plus de 900 patientes ont ete traitees par irradiation externe pour un cancer du sein de novembre 2008 a decembre 2009 dans notre departement par un accelerateur lineaire de haute energie (par photons X de 4 a 6 MV et electrons). Parmi ces dernieres, sept etaient porteuses d’un stimulateur cardiaque. Toutes les patientes ont ete irradiees dans le sein, la paroi thoracique ou les aires ganglionnaires. La dose totale prescrite etait de 50 Gy en 25 fractions dans le sein ou la paroi thoracique et de 46 Gy en 23 fractions dans les aires ganglionnaires. Un boost de 16 Gy en huit fractions etait indique chez certaines patientes traitees par chirurgie conservatrice. Le rythme cardiaque de toutes les patientes etait monitore pendant les seances et surveille par un medecin oncologue radiotherapeute. Tous les stimulateurs cardiaques ont ete controles par le cardiologue des patientes avant et apres l’irradiation. Resultats Sept patientes ont ete adressees dans notre departement pour radiotherapie postoperatoire dans le cadre d’un cancer du sein. Parmi ces sept patientes, seule une finalement s’est vue recuser la radiotherapie et a beneficie d’une mastectomie. Dans quatre cas, le stimulateur cardiaque a ete repositionne avant le debut de la radiotherapie. Six patientes âgees de 48 a 84 ans ont ete traitees par irradiation pour leur cancer du sein. Quatre patientes ont ete traitees par chirurgie conservatrice suivie d’une irradiation mammaire et deux par mastectomie suivie d’une irradiation de la paroi thoracique et des aires ganglionnaires sus- et sous-claviculaire et mammaire interne. La dose au stimulateur cardiaque a ete calculee et etait toujours inferieure a 2 Gy. Il n’a ete observe aucun dysfonctionnement des stimulateurs cardiaques pendant la radiotherapie. Conclusion La prise en charge multidisciplinaire incluant un eventuel changement de positionnement du stimulateur cardiaque avant radiotherapie et le monitoring quotidien ont permis le deroulement sans incident de la radiotherapie pour nos patientes. Il est neanmoins necessaire de mettre a jour des recommandations precisant la dose maximale tolerable aux differents constituants du stimulateur cardiaque.

Resume Objectif de l’etude Evaluer la radiotherapie exclusive comme option therapeutique apres reponse clinique complete a une chimiotherapie neoadjuvante pour des cancers du sein de stade II-IIIA. Patientes et methodes Entre 1985 et 1999, 1477 patients ont recu une chimiotherapie neoadjuvante pour un cancer du sein de stade II-IIIA considere trop volumineux pour etre opere de facon conservatrice. Parmi les 165 patientes en situation d’une reponse clinique complete apres la chimiotherapie neoadjuvante, 65 ont ete traitees par chirurgie mammaire et irradiation et 100 par irradiation exclusive. Resultats Les deux groupes etaient comparables en termes de caracteristiques initiales, excepte pour le diametre tumoral au diagnostic (plus grand dans le groupe exclusivement irradie). Aucune difference statistiquement significative n’a ete observee en termes de survie globale, de survie sans maladie ni de survie sans metastase. Les taux de survie globale a cinq et dix ans etaient respectivement de 91 et 77 % dans le groupe exclusivement irradie et de 82 et 79 % dans le groupe opere et irradie ( p = 0,9). Cependant, une tendance en faveur d’un taux plus eleve de recidive locoregionale a ete observee dans le groupe exclusivement irradie (31 contre 17 % a dix ans ; p = 0,06). Chez les patientes en situation de remission complete d’apres la mammographie et/ou l’echographie, il n’y avait pas de difference statistiquement significative de taux de recidive locoregionale (a dix ans : 21 dans le groupe opere et irradie contre 26 % dans le groupe exclusivement irradie, p = 0,45). Aucune difference n’a ete observee en termes de toxicite cutanee, cardiaque et pulmonaire. Conclusion La chirurgie est une etape incontournable du traitement locoregional des cancers du sein ayant repondu completement a une chimiotherapie neoadjuvante.

Proton beam therapy uses positively charged particles, protons, whose physical properties improve dose-distribution (Bragg peak characterized by a sharp distal and lateral penumbra) compared with conventional photon-based radiation therapy (X-ray). These ballistic advantages apply to the treatment of deep-sited tumours located close to critical structures and requiring high-dose levels. [60-250 MeV] proton-beam therapy is now widely accepted as the "gold standard" in specific indications in adults--ocular melanoma, chordoma and chondrosarcoma of the base of skull --and is regarded as a highly promising treatment modality in the treatment of paediatric malignancies (brain tumours, sarcomas…). This includes the relative sparing of surrounding normal organs from low and mid-doses that can cause deleterious side-effects such as radiation-induced secondary malignancies. Other clinical studies are currently testing proton beam in dose-escalation evaluations, in prostate, lung, hepatocellular cancers, etc. Clinical validation of these new indications appears necessary. To date, over 60,000 patients worldwide have received part or all of their radiation therapy program by proton beams, in approximately 30 treatment facilities.

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas “Help of delineation for breast cancer treatment”. In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

The radiation dose received by the eye depends on the pathology, tumour location (ocular globe, orbit, neighboring structures) and the radiation technique. The major complication is the complete loss of vision, which is often multifactorial. This article, based on a literature review, describes the radiation effects and the tolerance doses for all eye structures: cornea, lens, retina, optic nerves, orbit and ocular adnexa.

Poster-Abstract

Resume Avec l’amelioration considerable du pronostic global des tumeurs pediatriques au cours des 30 dernieres annees, la prise en charge et la prevention des complications et sequelles therapeutiques constituent un objectif prioritaire. La protontherapie qui a fait ses preuves comme traitement de tumeurs radioresistantes proches d’organes « critiques » chez l’adulte, devient maintenant essentielle chez l’enfant grâce a une meilleure epargne des tissus sains irradies. L’essentiel des donnees cliniques et dosimetriques publiees dans le domaine de la protontherapie pediatrique est aborde dans cet article ainsi qu’une mise a jour de l’experience du centre d’Orsay portant sur 108 enfants.