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A systematic review and meta-analysis were performed to better understand the benefits of particle beam therapy for nasopharyngeal cancer (NPC) treatment. The survival outcomes and toxicity of primary and recurrent NPC patients treated with proton or carbon ion beam therapy were investigated.PubMed, Scopus, and Embase were searched between 1 January 2007 to 3 November 2021. The inclusion and exclusion criteria included studies with either primary or recurrent NPC patients, sample size of ≥10 patients, and proton or carbon ion beam therapy as interventions. Twenty-six eligible studies with a total of 1502 patients were included. We used a random-effect meta-analysis to examine the impact of particle beam therapy on primary NPC patients and qualitatively described the results among recurrent patients. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), local control (LC) and toxicity.The pooled OS at 1-year, 2-year and 3-year and 5-year for primary NPC patients who received particle beam therapy were 96 % (95 % confidence interval (CI) = 92 %-98 %), 93 % (95 % CI = 83 %-97 %), 90 % (95 % CI = 73 %-97 %) and 73 % (95 % CI = 52 %-87 %) respectively. The pooled 1-year and 2-year PFS, and LC for these patients were above 90 %. For locally recurrent NPC patients, the 1-year OS rate ranged from 65 % to 92 %, while the 1-year LC rate ranged from 80 % to 88 %. Both proton and carbon ion beam therapy were generally safe among primary and recurrent patients, with ≥G3 late toxicity rates of 20 % or less. Approximately a 5 % mortality rate was reported among recurrent patients.This systematic review and meta-analysis demonstrated particle beam therapy has great potential in treating NPC, yielding excellent survival outcomes with low toxicity. However, further investigations are needed to assess the long-term outcomes and cost-effectiveness of this newer form of radiotherapy.

Oncology treatments are constantly and rapidly evolving. We aimed at highlighting the latest radiation therapy practice changing trials and emerging concepts, through an overview of recent randomised clinical trials (RCTs).Requests were performed in the Medline database to identify all publications reporting radiation therapy RCTs from 2018 to 2021.Recent RCTs sustained the role of newer combinatorial strategies through radioimmunotherapy for early stage or metastatic lung cancer, newer pro-apoptotic agents (e.g. debio 1143 in locoregionally advanced head and neck squamous cell carcinoma) or nanoparticles (e.g. NBTXR3 in locally advanced soft-tissue sarcoma). High-tech radiotherapy allows intensifying treatments and gaining ground in some indications through the development of stereotactic body radiotherapy for example. First randomised evidence on personalised radiation therapy through imaging-based (Radiation therapy is a dynamic field of research, and many RCTs have greatly impacted therapeutic standards over the last years. Investments in radiotherapy research should facilitate the transfer of innovation to clinic.

Our objective was to develop a predictive model using a machine learning signature to identify patients at high risk of relapse or death after treatment for HPV-positive oropharyngeal carcinoma.Pre-treatment variables of 450 patients with HPV-positive oropharyngeal carcinoma treated with a curative intent comprised clinical items, imaging parameters and histological findings. The events considered were progression or residual disease after treatment, the recurrent disease after a disease-free interval and death. The endpoints were the prediction of events and progression-free survival. After feature Z-score normalisation and selection, random forest classifier models were trained. The best models were evaluated on recall, the F-score, and the ROC AUC metric. The clinical relevance of the best prediction model was evaluated using Kaplan-Meier analysis with a log-rank test.The best random forest model predicted the 5-year risk of relapse-free survival with a recall of 79.1%, an F1-score of 81.08%, and an AUC of the ROC curve of 0.89. The models performed poorly for the prediction of specific events of progression only, recurrence only or death only. The clinical relevance of the model was validated with a 5-year relapse-free survival of high-risk patients versus low-risk patients of 23.5% and 80%, respectively (p 0.0001).Patients with HPV-driven oropharyngeal carcinoma at high risk of relapse-free survival could be identified with a predictive machine learning model using patient data before treatment.

The management of local relapse after prostate cancer radiotherapy is frequently based on androgen deprivation therapy. The aim of the study was to report Gustave Roussy's experience with salvage prostate brachytherapy.All cases of localized prostate cancer presenting in an irradiated area who received salvage high dose rate (HDR) brachytherapy from 2013 to 2020 were retrospectively reviewed.A total of 64 patients were included. Median follow up was 30.5 months. Median initial EBRT dose was 70 Gy [Q1-Q3: 70 - 74]. Median PSA at brachytherapy was 6.8 ng/mL [Q1-Q3: 4.4 - 8.7] with a median interval between first and salvage irradiation of 10 years [Q1-Q3: 6.9 - 12.6]. The modality of the first irradiation was an exclusive EBRT in 73% of the cases, mostly with a 3D technique (82%). Dose prescription was two fractions of 12 Gy or 13 Gy associated with androgen deprivation therapy for 63% of the patients. About 23% of the patients were castrate-resistant. Disease free survival at 2 years was 58% in the whole population and 66% in hormone sensitive patients. The only factors associated with disease free survival on multivariate analysis was a high-risk disease at initial diagnosis (HR = 3.59, IC95 [1.75; 7.39], p = 0.0005). Grade 3 urinary and rectal toxicities occurred in 1.5% and 1.5% of the patients, respectively.HDR salvage brachytherapy seems to be a safe option for patients presenting with an isolated local relapse of prostate cancer.

Resume Le cancer de la prostate oligometastatique est parmi les cancers oligometastatiques les plus etudies dans la litterature. Malgre cela, a ce jour, nous disposons de peu d’etudes prospectives ayant evalue la radiotherapie stereotaxique des oligometastases du cancer de la prostate. Deux essais randomises de phase II montrent un benefice en termes de survie sans progression en comparaison avec une surveillance simple. Les donnees de registres prospectifs montrent egalement un tres bon taux de controle local et une faible toxicite. L’inclusion dans les essais en cours doit etre fortement encouragee afin de preciser la place de cette irradiation stereotaxique en complement du traitement systemique. La radiotherapie de la tumeur primitive a fait l’objet d’essais randomises, elle apporte un benefice de survie globale chez les patients atteints d’un faible volume tumoral. Le benefice est inversement correle au nombre de lesions osseuses sur l’imagerie classique, jusqu’a trois lesions. La radiotherapie de la tumeur primitive est recommandee par les societes savantes chez les patients atteints d’un faible volume tumoral. Sa place en association avec les hormonotherapies de nouvelle generation doit etre precisee.

International audience; Purpose: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.Methods and materials: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.Results: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.Conclusion: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.

Purpose Stereotactic body radiotherapy (SBRT) of prostate cancer is associated with rectal toxicities, which can be reduced by using a hydrogel spacer. The object of this retrospective study was to show the feasibility of spacer placement under local anesthesia and utility of hydrogel spacer to reduce the dose to the rectal wall. Material and methods We collected data from all patients with localised prostate cancer treated with SBRT (40Gy in 5 fractions) between 2018 and 2020. A hydrogel spacer (SpaceOAR®) was placed depending on the availability of the product. We collected dosimetric data for target volumes and organs at risk. We calculated mean values, which were compared using non-parametric tests. Results Among 35 patients, mean age was 75 years. Seventeen had a spacer placed, with a mean space created of 10mm. No complication was reported during the intervention. High doses to the rectal wall were significantly lower in spacer group (V38: 0.39 cm3 vs. 0.72 cm3; P=0.02). PTV were better covered in spacer group (P=0.07). Doses to the bladder wall were similar in both groups. Conclusion Spacer procedure under local anesthesia was well tolerated. Hydrogel spacer allowed to reduce doses to the rectum while improving PTV coverage.

Resume Le recours a un ou plusieurs confreres est une pratique medicale habituelle et l’exercice solitaire de la cancerologie est revolu mais il doit encore evoluer pour mieux repondre aux attentes des patients. Le patient et eventuellement ses proches doivent etre associes aux demarches diagnostiques et therapeutiques. L’interet du patient et le secret medical sont toujours a respecter. Le praticien radiotherapeute, doit accepter et aider un patient pour la demande d’un second avis. Les reunions de concertation pluridisciplinaires (RCP) de recours, l’acces aux techniques innovantes, a des protocoles de recherches, a une prise en charge prenant en compte les specificites des patients telle que la population des adolescents et jeunes adultes sont autant d’outils qu’il faut savoir connaitre et manier en respectant les attentes des patients, la pluri-professionnalite et la confraternite. Parfois, lors d’un diagnostic initial, il ressort de tous les avis que l’abstention therapeutique est la meilleure option a proposer. L’information adaptee et une bonne communication sont alors les atouts pour faire comprendre et accepter au patient que la seule surveillance active ne lui fera pas courir de risque carcinologique tout en preservant sa qualite de vie. Dans le cas d’une recidive, une radiotherapie de rattrapage meme realisable doit etre profondement reflechie et toujours discutee si possible au sein de reseaux dit de tumeurs rares. Dans des situations peu frequentes ou complexes savoir passer la main a des centres experts peut aussi etre salutaire. Les modalites de la radiotherapie se sont diversifiees avec les avancees technologiques et ne sont a present plus qu’exceptionnellement disponibles sur un meme site. Parmi ces techniques de recours, on retrouve la protontherapie, la contactherapie, la radiotherapie stereotaxique avec tracking ou la curietherapie. Chaque radiotherapeute doit connaitre les benefices en survie, controle local ou preservation fonctionnelle de ces modalites ainsi que leurs organisations specifiques qui en facilitent l’adressage.

International audience; Background: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy.Methods: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP).Results: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found.Conclusion: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.

Purpose: To evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and Materials: OPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ≥2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. Results: In the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation.. .) and patient-related factors (comorbidities, sequelae of previous irradiation.. .), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques., Malgré les progrès dans la prise en charge des carcinomes épidermoïdes des voies aérodigestives supé-rieures (VADS), de nombreux patients vont développer une récidive en territoire irradié ou un second primitif. Devant la très grande hétérogénéité de ces patients, des facteurs liés à la maladie (localisa-tion, volume, récidive ou second primitif, intervalle depuis la première irradiation, etc.), des facteurs liés au patient (comorbidités, séquelles de la première irradiation.. .), les indications sont posées au cas par cas. Les données historiques de réirradiation, bien que rapportant des données d'efficacité parfois encourageantes, font état de taux de toxicité de grades 4 et 5 importants. Avec la généralisation récente des techniques de radiothérapie plus précises et mieux conformées comme la radiothérapie confor-mationnelle avec modulation d'intensité (RCMI) ou la radiothérapie stéréotaxique (SBRT), le rapport bénéfice/risque de la réirradiation a évolué ces dernières années. L'objectif de cette revue est de faire le point sur les réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures en termes de sélection de patients, et de techniques modernes de radiothérapie. © 2019 Société franç aise de radiothérapie oncologique (SFRO).

The risk of lymph node invasion, in case of prostate cancer, increases with the clinical stage of the disease, the Gleason score of prostate biopsies and the value of PSA at diagnosis. Historically, beyond 15% risk of lymph node involvement, irradiation of the pelvic areas was performed with prostate radiotherapy (RT) to take into account the risk of occult lymph node metastasis in patients at risk, but the benefit of this therapeutic approach remains to be demonstrated. The data from surgical lymph node dissection seem to question the risk levels, the escalation of the dose on the prostate increases the survival without relapse, the contribution of image-guided radiotherapy, (IGRT) and modulation of intensity (IMRT), decreases the toxicity of pelvic RT. This article reviews the principles of prophylactic ganglion irradiation for prostate cancer and discusses its relevance, current uncertainties, and prospective trials.

Post-therapeutic follow-up of patients with head and neck cancer involves numerous professionals. The radiation oncologist should play an active role in this process. His oncological knowledge and technical expertise position him as a cornerstone for the detection of recurrences from the treated tumor, the research of second primary cancers and the screening of potential side-effects induced by the different treatments administered. To improve the benefits/costs ratio and allow good patient-compliance, follow-up programs should be built through close collaboration between the different contributors and planned according to a feasible schedule. Paraclinical exams must be arranged to respond to accurate objectives. Patient-education is essential to ensure the patient's full understanding and active participation. Finally, the transfer of the long-term follow-up of cancer survivors from specialists to primary care physicians is relevant but would require a prospective evaluation of its efficiency for this specific population.

National audience; Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.

Resume Objectif de l’etude Pour faciliter la formation a la delineation, la Societe francaise de radiotherapie oncologique (SFRO) et l’association de formation continue en oncologie radiotherapie (Afcor) ont cree en 2008 un site Internet de radioanatomie et d’aide a la delineation. Materiel et methodes Entre 2015 et 2017, une mise a jour du site a ete entreprise, necessitant la mise en place de deux parties : des cours theoriques d’une part, et des ateliers de delineation en ligne d’autre part. Resultats Un nouveau site exploitant l’ensemble des nouvelles technologies numeriques a ete mis en ligne. Les cours ont ete realises sous forme de videos commentees et consultables a tout moment. La partie pratique offre une interface de delineation en ligne qui genere a la fin de l’exercice un rapport permettant de quantifier la qualite de sa delineation. Conclusion Siriade 2.0 est un outil numerique innovant qui s’inscrit en complement des formations initiales et continues deja disponibles.

Introduction et but de l’etude La question ethique est une thematique emergente et peu exploree dans le monde de la radiotherapie. L’objectif de notre travail etait de preciser le questionnement ethique en radiotherapie dans une approche multiprofessionnelle. Materiel et methodes Une etude multicentrique a ete realisee dans 22 departements de radiotherapie francais, a partir d’un questionnaire Google Form (dix questions) soumis aux oncologues radiotherapeutes, manipulateurs d’electroradiologie, physiciens medicaux, assistantes medicales et cadres. Le questionnaire visait a mieux comprendre la frequence et la nature du questionnement ethique dans les departements de radiotherapie, ainsi que le besoin de formation. Resultats et analyse statistique Un total de 200 personnes a repondu aux questionnaires, se repartissant en : oncologues radiotherapeutes (37 %), manipulateurs d’electroradiologie (37 %), physiciens medicaux (12,5 %), assistantes medicales (10 %) et cadres (3,5 %). Le nombre moyen d’annees d’experience en radiotherapie etait de 12 ans (extremes : 6 mois - 40 ans). En termes de frequence dans la pratique de radiotherapie, la question ethique se posait : frequemment (plus d’une fois par mois ; 52,5 %), rarement (entre trois et dix fois par an ; 35,5 %), exceptionnellement (moins de deux fois par an ; 9,5 %) et jamais (2,5 %). En termes de nature, la question ethique concernait : la comprehension et/ou l’acceptation du traitement par les patients (71 %), les objectifs attendus du traitement (65 %), la lourdeur technique et organisationnelle du traitement (62 %) et le cout du traitement (13 %). Une specificite de la question ethique en radiotherapie etait reconnue pour 64 % des personnels. Les questions ethiques etaient effectivement discutees dans les departements de radiotherapie : jamais (18,5 %), parfois (47,5 %), souvent (10,5 %) et ne se prononce pas (18,5 %). Les questions d’ethique etaient considerees comme suffisamment discutees dans ces departements : non (47,5 %), oui (14 %) et ne se prononce pas (38,5 %). Seuls 17 % des personnels ont deja eu une formation en ethique medicale. Le besoin de formation specifique etait ressenti par 83,5 % des personnels n’ayant jamais eu de formation. Conclusion La question ethique se pose effectivement assez frequemment et specifiquement en radiotherapie, avec un sentiment d’insuffisance a la fois de discussion dans les departements et de formation. Les questions principales d’ethique concernent la comprehension du traitement par les patients, ses objectifs et la lourdeur de ceux-ci.

Highlights • Treatment de-escalation in HPV+ oropharynx cancer is an active area of research. • A Bayesian phase II trial of MR-guided radiotherapy dose adaptation is proposed. • High dose volume will be adapted on weekly MRI based on tumor response. • The non-inferiority of dose adaptation compared to standard IMRT will be assessed., Background Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). Methods Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node

Nasopharyngeal carcinoma is a rare condition, with less than 300 cases occurring per year in France. Its treatment can be difficult due to the importance of side effects, but tumor control is usually excellent following a well conducted chemoradiotherapy. This article summarizes the recent advances in nasopharyngeal cancer diagnosis, classification, treatment, surveillance and management of recurrences. Chemotherapy timing is discussed, along with arguments in favor of induction chemotherapy in locally advanced cases. As a survival advantage has been suggested for when patients are treated in high volume center it seems reasonable to refer these young patients for treatment to tertiary expert centers, especially given the low incidence of the disease.

Prostate brachytherapy has been for a long time one of the standard treatments for low risk prostate cancer, with high rates of biochemical control and low levels of urinary and sexual late toxicity compared to other available techniques, namely external beam radiotherapy and radical prostatectomy. The aim of this article is to review the recent innovations of prostate brachytherapy, which suggest a bright future for the technique. We will discuss the extension of indications of permanent implant brachytherapy to favorable intermediate-risk patients, the use of novel isotopes such as Palladium 103 and Cesium 131, and the benefit of brachytherapy as a boost following external beam radiotherapy for intermediate and high-risk patients. We will also discuss the rise of high dose rate brachytherapy, as a boost or monotherapy, the increasing use of MRI for patient selection and treatment planning, as well as the development of brachytherapy as a means of focal therapy.

Highlights • The average dose to 95% of initial PTV volume was 70.7 Gy for standard plans vs. 58.5 Gy for adaptive plans. • MRI-guided adaptive approach resulted in decrease dose to normal tissue compared with standard plans. • NTCP of post-treatment dysphagia, feeding tube, and hypothyroidism were reduced using the adaptive approach., Purpose We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC). Materials/methods Patients with locally advanced HPV+ OPC underwent pre-treatment and in-treatment MRIs every two weeks using RT immobilization setup. For each patient, two IMRT plans were created (i.e. standard and adaptive). The prescription dose for the standard plans was 2.12 Gy/fx for 33 fractions to the initial PTV. For adaptive plans, a new PTVadaptive was generated based on serial MRIs in case of detectable tumor shrinkage. Prescription dose to PTVadaptive was 2.12 Gy/fx to allow for maximum dose to the residual disease. Any previously involved volumes received minimally a floor dose of 50.16 Gy. Uninvolved elective nodal volumes were prescribed 50.16 Gy in 1.52 Gy/fx. Dosimetric parameters of organs at risk (OARs) were recorded for standard vs. adaptive plans. Normal tissue complication probability (NTCP) for toxicity endpoints was calculated using literature-derived multivariate logistic regression models. Results Five patients were included in this pilot study, 3 men and 2 women. Median age was 58 years (range 45–69). Three tumors originated at the tonsillar fossa and two at the base of tongue. The average dose to 95% of initial PTV volume was 70.7 Gy (SD,0.3) for standard plans vs. 58.5 Gy (SD,2.0) for adaptive plans. The majority of OARs showed decrease in dosimetric parameters using adaptive plans vs. standard plans, particularly swallowing related structures. The average reduction in the probability of developing dysphagia ≥ grade2, feeding tube persistence at 6-month post-treatment and hypothyroidism at 1-year post-treatment was 11%, 4%, and 5%, respectively. The probability of xerostomia at 6-month was only reduced by 1% for adaptive plans vs. standard IMRT. Conclusion These in silico results showed that the proposed MRI-guided adaptive approach is technically feasible and advantageous in reducing dose to OARs, especially swallowing musculature.

Objectives: We investigated the prognostic value of pre-treatment hematological parameters in patients with p16-positive oropharyngeal squamous-cell carcinoma (OPSCC). Material and methods: Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and hemoglobin concentration measurement (Hb), were collected on day one of treatment. Endpoints were overall survival (OS) and progression-free survival (PFS). All patients were planned to receive concurrent chemoradiation. Staging were reviewed according to the recent AJCC 8th edition. Results: We included 167 patients in this study. In multivariate analyses, a smoking history > 30 packyears was associated with decreased OS (p = 0.009; HR, 3.4827) and PFS (p = 0.042; HR, 2.421); Hb < 12 g/dL was associated with impaired OS (p = 0.007; HR, 6.527) and PFS (p = 0.014; HR, 4.092); an NLR > 5 before treatment was associated with decreased OS (p = 0.042; HR, 2.945). Hemoglobin concentration and the NLR were not correlated (p = 0.577), nor anemia and an NLR > 5 (p = 0.167). Patients with an NLR > 5 had a significantly higher rate of disease recurrence (30.8% vs. 8.4%, p = 0.0299, RR = 3.922, 95% CI 1.351–11.386). Discussion: We found hemoglobin level and the NLR to be independent prognostic factors in p16-positive OPSCC patients. This approach is to be considered for further clinical investigations, and its significance in treatment decision-making should be further explored. Keywords: Oropharyngeal carcinoma, P16, Papillomavirus, Smoking, Hemoglobin, Neutrophil-to-lymphocyte ratio

Purpose To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. Methods and Materials Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. Results From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. Conclusions The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.

Highlights • HPV-driven cancers have significantly better survival than traditional head and neck cancers. • Current treatments are reassessed to develop less toxic strategies with good oncological outcomes. • Treatment de-escalation raises issues such as patient selection and the benefit/risk balance. • Rigorously constructed trials leading to specific management for HPV-driven OPSCCs are mandatory., HPV-driven oropharyngeal cancers have significantly better survival rates than tobacco and alcohol induced head and neck cancers. As HPV-positive patients are younger, healthier and far more likely to survive their disease, long-term treatment side effects are becoming a major issue. This has led the scientific and medical community to reassess the current treatment protocols in order to develop less toxic strategies while maintaining good oncological outcomes. In this article, we discuss the ongoing treatment de-escalation trials and highlight the issues raised by these studies.

Background and purpose The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab). Material and methods In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The correlations between biomarker expressions and clinicopathological characteristics and treatment outcomes were analyzed. Results We found a significant correlation of MVD with UICC stage (p = 0.02) and T classification (p = 0.05), of CA-IX with UICC stage (p = 0.03) and N classification (p = 0.04) and a significant inverse correlation of MVD with CA-IX expression (r = −0.22, p = 0.03). Multivariate analysis showed that low MVD combined with high CA IX-expression was a significant independent prognostic factor for worse loco-regional control (HR = 2.6, 95%CI 1.1–5.0, p = 0.02) in the whole population but not in the p16+ subgroup. Patients treated with CRT had a better LRC than those with BRT independent of MVD or CA-IX expression. Conclusions The combination of MVD and CA-IX expression might give additional prognostic information in HNSCC patients with known HPV status.

Highlights • The prognostic value of pretreatment blood counts is investigated. • This is also done for the nadir neutrophil & lymphocyte levels during radiotherapy. • The impact of treatment modality (IMPT and IMRT) on these nadir levels is examined. • Pretreatment neutrophilia and leukocytosis were associated with worse outcomes. • Treatment modality did not affect blood counts during radiotherapy., Introduction Peripheral blood count components are accessible and evidently predictive in other cancers but have not been explored in oropharyngeal carcinoma. We examine if there is an association between the use of intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) and lymphopenia, as well as if there is an association between baseline neutrophilia, baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Materials and Methods Analysis started with 150 patients from a previous case to case study design, which retrospectively identified adults with oropharyngeal carcinoma, 100 treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011–2014. Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels for associated analysis and 114 patients with recorded lymphocyte levels during radiation and associated analysis. Multivariate survival analyses were done with Cox regression. Results The radiotherapy type (IMRT vs. IMPT) was not associated with lymphopenia (grade 3 P > .99; grade 4 P = .55). In univariate analyses, poor overall survival was associated with pretreatment neutrophilia (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.99–15.7, P = .001), pretreatment leukocytosis (HR 4.85, 95% CI 1.73–13.6, P = .003), grade 4 lymphopenia during radiotherapy (HR 3.28, 95% CI 1.14–9.44, P = .03), and possibly smoking status >10 pack-years (HR 2.88, 95% CI 1.01–8.18, P = .05), but only T status was possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99–7.00, P = .05). Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis. Conclusions Treatment modality did not affect blood counts during radiotherapy. Pretreatment neutrophilia, pretreatment leukocytosis, and grade 4 lymphopenia during radiotherapy were associated with worse outcomes after, but establishing causality will require additional work with increased statistical power.

Introduction et but de l’etude Les rechutes intraprostatiques apres radiotherapie a visee radicale pour un adenocarcinome prostatique ne sont pas rares. Historiquement, l’unique option therapeutique etait la prostatectomie de rattrapage qui est grevee d’une morbidite importante, notamment urinaire. L’objectif de cette etude etait d’evaluer l’efficacite et la toxicite de la curietherapie de haut debit de dose en rattrapage. Materiel et methodes Les dossiers de tous les patients pris en charge dans notre institution par curietherapie prostatique de haut debit de dose pour une rechute locale isolee en zone irradiee (radiotherapie externe ou curietherapie) ont ete analyses retrospectivement. Resultats et analyse statistique Les dossiers de 64 patients pris en charge de 2013 a 2020 ont ete inclus. Le suivi median etait de 30,5 mois. Les patients avaient recu initialement pour 73 % d’entre eux une radiotherapie externe exclusive (dose mediane 70 Gy, [Q1–Q3 : 70–74]), essentiellement avec une technique conformationnelle tridimensionnelle (82 %) ; 27 % des patients avaient recu une curietherapie dans le cadre de leur irradiation initiale (curietherapie exclusive en grains d’iode pour 22 % et combinaison de radiocurietherapie pour 5 % des patients). Lors du diagnostic initial, 19 % des patients avaient une maladie de faible risque, 37 % une maladie de risque intermediaire et 44 % une maladie de haut risque ou evoluee. La concentration serique mediane d’antigene specifique de la prostate [PSA] au moment de la curietherapie de rattrapage etait de 6,8 ng/mL [Q1–Q3 : 4,36–8,73]. L’intervalle median entre l’irradiation initiale et la curietherapie de rattrapage etait de 10 ans [Q1–Q3 : 6,9–12,6]. La curietherapie de rattrapage consistait en deux fractions de 12 ou 13 Gy associee a une hormonotherapie dans 65 % des cas. Le volume traite etait la prostate en totalite pour 96 % des patients. Vingt-trois pour cent des patients etaient resistants a la castration au moment de la curietherapie de rattrapage. La survie sans rechute (biochimique, clinique ou deces) a 2 ans etait de 53 % dans la population globale et de 62 % dans le sous-groupe de patients hormonosensibles a la rechute. Le seul facteur associe a la survie sans rechute etait une maladie a haut risque au moment du diagnostic initial (≥ T3, Gleason ≥ 8, [PSA] ≥ 20 ng/mL), HR = 2,89, IC95 % [1,4 ; 6], p = 0,005. La toxicite tardive urinaire et digestive de grade 3 etait observee chez 1,5 % et 1,5 % des patients respectivement. Il n’y a eu aucune toxicite de grade 4 ni fistule. Conclusion Meme si le controle biochimique est moins bon qu’en primo irradiation, la curietherapie de haut debit de dose de rattrapage semble etre une option sure pour les patients atteints d’une rechute locale isolee d’un adenocarcinome prostatique.

Introduction et but de l’etude L’escalade de dose de radiotherapie dans les cancers de prostate de risque intermediaire ou haut risque ameliore le controle biochimique. Le complement en curietherapie qui permet de delivrer une dose elevee, a montre dans trois essais randomises un benefice superieur par rapport a la radiotherapie seule. Le groupe curietherapie de la Societe francaise de radiotherapie oncologique (SFRO) a conduit une etude retrospective multicentrique pour rapporter des donnees d’efficacite et de tolerance du complement en curietherapie en vie reelle. Materiel et methodes une etude retrospective multicentrique a ete conduite, incluant la totalite des patients consecutifs atteints de cancer de prostate de risque intermediaire ou haut risque pris en charge par association de radiotherapie externe et de boost par curietherapie, qu’elle soit par haut debit de dose ou par implants permanents de grains d’iode 125, de 2006 jusqu’en decembre 2019. Les caracteristiques des patients, de la maladie initiale, des traitements et du suivi ont ete recueillies. Resultats et analyse statistique Mille treize patients ont ete inclus (dont 960 pris en charge apres 2010) ; 914 patients ont ete suivis et leurs resultats analyses, dont 864 ayant recu une curietherapie de haut debit de dose (dose mediane 14 Gy en une fraction) et 50 par implants permanents de grains d’iode 125 (dose mediane 110 Gy). Quatre-cent-vingt-quatre cancers etaient de risque intermediaire et 490 de haut risque. La dose mediane de radiotherapie externe etait de 46 Gy. Apres un suivi median de 63 mois, le controle biochimique a 5 ans etait de 90 % pour la population globale, 94 % et 86 % pour les cancers de risque intermediaire ou haut risque, respectivement. A 5 ans, les taux de survie sans rechute biochimique ni clinique, survie sans metastase et controle local etaient respectivement de 67 %, 92 % et 97 %. Une toxicite tardive de grade 2 ou plus etait retrouvee chez 70 patients (soit 7,7 %) et 18 patients (soit 2 %) sur les plans urinaire et digestif. Conclusion Cette etude multicentrique montre l’efficacite de l’association de la curietherapie en complement de la radiotherapie externe et sa bonne tolerance. Cette base de donnees, en cours d’enrichissement, montre le dynamisme du groupe curietherapie de la SFRO et permettra de mieux etudier les facteurs influencant le controle du cancer de prostate et de contribuer a la diffusion de cette technique sur le territoire national.

The absence of exit dose and the sharp lateral penumbra are key assets for proton therapy, which are responsible for its dosimetric superiority over advanced photon radiotherapy. Dosimetric comparisons have consistently shown a reduction of the integral dose and the dose to organs at risk favouring intensity-modulated proton therapy (IMPT) over intensity-modulated radiotherapy (IMRT). The structures that benefit the most of these dosimetric improvements in head and neck cancers are the anterior oral cavity, the posterior fossa, the visual apparatus and swallowing structures. A number of publications have concluded that these dosimetric differences actually translate into reduced toxicities with IMPT, for example with regards to reduced weight loss or need for feeding tube. Patient survival is usually similar to IMRT series, except in base of skull or sinonasal malignancies, where a survival advantage of IMPT could exist. The goals of the present review is to describe the major characteristics of proton therapy, to analyse the clinical data with regards to head and neck cancer patients, and to highlight the issue of patient selection and physical and biological uncertainties.

The goal of treatment of metastatic prostate cancer remains palliation. The oligometastatic state could be the right time to intensify therapy by introducing metastases directed treatments. The aim of this trial was to evaluate the benefit of radiotherapy to all macroscopic metastatic sites and to the primary disease in patients with hormone sensitive oligometastatic prostate cancer.

To determine dosimetric parameters associated with osteoradionecrosis (ORN) in oropharyngeal cancer (OPC) patients in the IMRT era.Subsequent to institutional review board approval, we identified ORN in OPC patients treated with IMRT from 2002 to 2013. 1:2 case-control matching was implemented. Mandibular dose-volume histograms (DVH) were extracted. Dosimetric parameters were compared using non-parametric stats. Recursive partitioning analysis (RPA) was done to identify DVH correlates of ORN.68 ORN cases and 131 controls were matched. Median follow-up was 41months and median time to development of ORN was 16months. Mandibular mean dose was significantly higher in the ORN cohort (48.1 vs 43.6Gy, p0.0001). However, the maximum dose was not statistically different. DVH bins from V35 to V73 were all significantly higher in the ORN cohort compared with controls (p0.0006). Two DVH parameters were identified in RPA analysis, V43 and V58. The majority (81%) of ORN cases were observed with both V44≥42% and V58≥25%.Our data demonstrate that a wide range of DVH parameters in the intermediate and high beam path were all significantly higher in ORN patients. Mandibular V4442% and V5825% represent reasonable DVH constraints for IMRT plan acceptability, when tumor coverage is not compromised.

Purpose Permanent prostate brachytherapy dosimetry using computed tomography-magnetic resonance imaging (CT-MRI) fusion combines the anatomic detail of MRI with seed localization on CT but requires multimodality imaging acquisition and fusion. The purpose of this study was to compare the utility of MRI only postimplant dosimetry to standard CT-MRI fusion-based dosimetry. Methods and Materials Twenty-three patients undergoing permanent prostate brachytherapy with use of positive contrast MRI markers were included in this study. Dose calculation to the whole prostate, apex, mid-gland, and base was performed via standard CT-MRI fusion and MRI only dosimetry with prostate delineated on the same T2 MRI sequence. The 3-dimensional (3D) distances between seed positions of these two methods were also evaluated. Wilcoxon-matched-pair signed-rank test compared the D90 and V100 of the prostate and its sectors between methods. Results The day 0 D90 and V100 for the prostate were 98% versus 94% and 88% versus 86% for CT-MRI fusion and MRI only dosimetry. There were no differences in the D90 or V100 of the whole prostate, mid-gland, or base between dosimetric methods ( p > 0.19), but prostate apex D90 was high by 13% with MRI dosimetry ( p = 0.034). The average distance between seeds on CT-MRI fusion and MRI alone was 5.5 mm. After additional automated rigid registration of 3D seed positions, the average distance between seeds was 0.3 mm, and the previously observed differences in apex dose between methods was eliminated ( p > 0.11). Conclusions Permanent prostate brachytherapy dosimetry based only on MRI using positive contrast MRI markers is feasible, accurate, and reduces the uncertainties arising from CT-MRI fusion abating the need for postimplant multimodality imaging.

Magnetic resonance imaging (MRI) produces better soft tissue contrast than does ultrasonography (US) or computed tomography (CT) for visualizing male pelvic anatomy and prostate cancer. Better visualization of the tumor and organs at risk could allow better conformation of the dose to the target volumes while at the same time minimizing the dose to critical structures and the associated toxicity. Although the use of MRI for prostate brachytherapy would theoretically result in an improved therapeutic ratio, its implementation been slow, mostly because of technical challenges. In this review we describe the potential role of MRI at different steps in the treatment workflow for prostate brachytherapy: for patient selection, treatment planning, in the operating room, or for post-implant assessment. We further present the current clinical experience with MRI-guided prostate brachytherapy, both for permanent seed implantation and high-dose-rate brachytherapy.

Resume Introduction L’arrivee de nouveaux traitements du cancer de la prostate metastatique resistant a la castration (CPRCm) implique une surveillance rapprochee des patients pour adapter la strategie therapeutique en cas de progression. Dans ce contexte, une enquete nationale a ete proposee par un groupe d’experts afin d’identifier les modalites de la surveillance dans differentes situations cliniques. Methodologie Un questionnaire a ete diffusee aupres de 1464 urologues, oncologues medicaux et radiotherapeutes en France a propos d’un cas clinique de cancer de la prostate (CaP) avec recidive biologique apres prostatectomie totale jusqu’au stade de CPRCm. Les dix questions concernaient les motifs de changement de traitement lies a une progression et les modalites de surveillance de la maladie. Resultats Au total, 318 questionnaires ont ete analyses (taux de reponse de 22 %). Les resultats indiquaient des pratiques relativement homogenes entre les differentes specialites, meme si un rythme de surveillance plus frequent etait rapporte par les oncologues medicaux et radiotherapeutes. Le patient en progression apres une prostatectomie totale beneficiait d’une surveillance clinique et biologique tous les 3 ou 6 mois et les examens d’imagerie etaient faits a la demande. Au fur et a mesure de l’evolution de la maladie, la surveillance devenait plus rapprochee et systematique, avec des examens d’imagerie realises tous les 3 mois ou a la demande. Alors que la definition d’une progression de la maladie avec changement du traitement reposait essentiellement sur le taux de PSA au debut de la resistance a la castration, elle associait ensuite differents criteres, cliniques, biologiques et radiologiques. Conclusions Les recommandations disponibles sur les modalites et le rythme de surveillance du CPRCm sont peu nombreuses. Dans la communaute onco-urologique, le rythme de surveillance s’intensifiait au fur et a mesure de la progression de la maladie. Niveau de preuve 4.

Background High-risk human papillomaviruses (HR-HPV) are the cause of most ano-genital cancers and a fast growing subset of oropharyngeal cancer. As these malignancies occur as a result of an HPV- infection transmitted through intimate contact, many patients with HPV- induced cancer and their partners are concerned about HPV-transmission and the potential partners’ cancer risk. Few studies have addressed this issue and whether the HPV-related cancer risk of partners of patients with HPV-related cancers is comparable to or greater than that of the general population. Methods We performed a systematic review of the published literature addressing this issue. Out of 1055 references screened, 53 articles were found eligible for inclusion. Results Regarding the issue of coincidence of HPV-induced oropharyngeal and/or anogenital cancers in couples, 13 case-reports or case-series were reported and 9 larger studies based on population-registries. Four of these registry studies showed an increased risk of cervical cancer in the partner while four did not. Among the four positive studies, odds ratios for the development of HPV-related cancer among spouses were between 2.6 and 6.7. One study showed an increased risk of tongue or tonsil cancer among husbands of women with cervical dysplasia or cancer. Overall the absolute risk increase in all these studies was small, on the order of 1–3%, although potentially underestimated. Indeed, all these studies have assessed partner’s cancer risk at only one anatomical site whereas HPV- related malignancies can affect different locations. Conclusion This systematic review suggests a small trend of increase risk in HPV-associated cancers among spouses of patients with HPV-related cancer.