Importance:Postoperative radiotherapy (mainly fractionated intensity-modulated radiotherapy) is indicated after surgery for early-stage oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) in the presence of high-risk margins. Postoperative brachytherapy is a treatment option, but it is not always feasible; stereotactic body radiotherapy (SBRT) may offer a noninvasive alternative. Objective:To evaluate late toxic effects and 2-year local control after postoperative SBRT to the primary tumor bed in patients with early-stage OCSCC or OPSCC and high-risk resection margins. Design, Setting, and Participants:This national, multicenter, single-arm, phase 2 nonrandomized clinical trial was conducted across 18 academic centers in France in the Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC) network. Adults with pT1 to pT2 OCSCC or OPSCC and R1 or smaller than 5 mm margins, pN0 or pN1 without extracapsular extension, no indication for neck irradiation, and not planned for adjuvant chemotherapy were enrolled between April 2018 and August 2021. Final analysis was conducted from February to May 2024. Intervention:SBRT to the surgical bed, 36 Gy in 6 fractions over 2 weeks, using volumetric modulated arctherapy (VMAT) or CyberKnife, with image guidance and quality assurance protocols. Main Outcomes and Measures:The primary outcome was the 2-year rate of grade 3 or greater late toxic effects (>90 days after treatment), per Common Terminology Criteria for Adverse Events version 4.03. The key secondary end point was 2-year local control. Quality of life (QoL) was assessed using European Organization for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-HN35). Results:Among 90 patients (median [range] age, 64 [31-87] years; 51 [56.5%] male), at 2 years, 2 patients (2.2%) had grade 3 late toxic effects, while 13 patients (14.6%) experienced at least 1 grade 3 late toxic effect during the 2-year follow-up period, mainly soft-tissue necrosis and osteoradionecrosis, most of which were transitory. The 2-year local control rate was 92.0% (95% CI, 84.6%-96.4%). Acute grade 3 or greater toxic effects were limited to mucositis (28.9%; 95% CI, 19.8%-39.4%), mostly resolving by 3 months. Median follow-up was 25 months (range, 3-31 months). Disease-free and overall survival at 2 years were 73.3% (95% CI, 63.4%-81.7%) and 88.8% (95% CI, 80.9%-94.2%), respectively. QoL scores showed a transient decline at 1 month followed by recovery and improvement at 12 and 24 months. Conclusions and Relevance:In this phase 2 nonrandomized clinical trial, postoperative primary tumor bed SBRT for early-stage OCSCC and OPSCC with high-risk margins was associated with manageable toxic effects and high rates of local control. These findings support SBRT as a promising approach in carefully selected patients, but confirmatory randomized trials are needed. Trial Registration:ClinicalTrials.gov Identifier: NCT03401840.

Purpose. - Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histo surgical mapping by radiation oncologists (RO). A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. Results. - EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. Conclusions. - Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours. (c) 2021 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Background: To evaluate the patterns of failure in patients treated for head and neck carcinoma of unknown primary and to discuss treatment practices concerning radiotherapy target volumes definition and dose prescription. Methods: Eleven patients presenting a locoregional recurrence after head and neck carcinoma of unknown primary treatment with curative-intent radiochemotherapy performed between 2007 and 2017 in the departments of radiation oncology of 2 French cancer institutes. Images of the computed tomography scan or the magnetic resonance imaging performed at the time of the recurrence were fused with those of the simulation computed tomography scan to delimit a volume corresponding to the recurrence and to define the area of relapse compared to the volumes treated. Results: Irradiation was unilateral in 6 cases and bilateral in 5 cases. The median time to onset of recurrence was 7.24 months (extreme 3-67.7 months). Six patients had only a neck node recurrence, 3 had a neck node and subsequent primary recurrence, and 1 had only a median subsequent primary recurrence. Only 1 patient had synchronous distance progression to local recurrence. All neck node recurrences were solitary and ipsilateral. The subsequent primary recurrences were in the oropharynx in 3 cases and in the contralateral oral cavity in one case. All neck node recurrences were into the irradiated volume. The subsequent primary recurrences were either within or in border of the irradiated volumes. The median of the mean dose, received by neck node recurrences, was 69.9 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 66.7 Gy. For the primary relapses, the median of the mean dose was 52.1 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 39.9 Gy. Conclusions: All local nodal recurrences occurred at sites that received high radiotherapy doses and doses received by sites of eventual failure did not vary significantly from sites that remain in control.

Colorectal cancer (CRC) is the third most common cancer in western countries, but brain metastases only occur in 1% of CRC patients. Overall survival in CRC patients rises as new systemic drugs became available. Thus the incidence of brain metastases in CRC patients will likely increase. We conducted a multicentric analysis to evaluate and compare the outcomes of stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HFSRT) in CRC brain metastasis management. On behalf of the association of French-speaking neuro-oncologist (ANOCEF), we retrospectively collected individual data of patients treated with SRS or HFSRT for CRC brain metastases in 6 hospitals in France and Germany. The primary endpoint of the study was the radiological response rate defines as a complete response, partial response, or stability of the metastasis according to RANO BM criteria. The median follow-up from initial treatment was 31 months. The median response rate for metastasis treated was 65.9% (CI 95% [51.9% – 79.9%]) and was positively influenced by SRS whereas multiple brain metastases were related to poorest response rates as reported in the table below.Abstract 2188; Table 1ORSD2.5%97.5%p(OR<1)p(OR>1)Disease controlled0.730.510.172.050.790.21Multiple brain metastases0.720.520.162.050.800.20PTV volume (mL)0.990.030.941.040.700.30SRS3.274.120.3613.500.210.79 Open table in a new tab The median overall survival (OS) from initial treatment was ten months (CI 95% [5 – 22]). OS was negatively influenced by extra-cranial metastases, male gender, whereas it influenced positively by brain progression-free survival (BPFS). We report the results of one of the largest cohort of CRC brain metastasis treated with stereotactic radiotherapy. Our analysis suggests that age is associated with a higher response probability while the control of the disease is associated with a lower response probability. However, patients with a controlled disease are more likely to live longer and thus experience a progression of the treated metastasis. Finally, SRS seems to be associated with a higher response probability.

S669ESTRO 37 completion of RT due to an unrelated illness.All 8 skullbase patients are alive at last follow up with no clinical or radiological evidence of disease progression. ConclusionOur data shows that dose escalation utilising photons is safe and provides comparable local control rates to proton beam therapy.Longer follow up is needed but hopefully should support the efficacy and toxicity profile associated with dose escalation of photons with more modern planning techniques for this rare tumour.

The treatment of local recurrence of a previously irradiated cancer or a second cancer arising in-field remains challenging. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Reirradiation has historically been associated with unacceptable toxicity and a limited benefit. Brachytherapy offers the best dose distribution and a high radiation dose to the target volume while better protecting surrounding previously irradiated healthy tissues. The management of local cancer recurrence in irradiated areas should be planned through multidisciplinary discussions and patients should be selected carefully. This overview of the literature describes brachytherapy as a reirradiation treatment in local recurrences of previously irradiated prostate, breast, head and neck and rectal cancers, or second primary cancers occurring in-field. For these cancers, the prognosis and therapeutic challenges are quite different and depend on the type of primary cancer. However, current data confirm that brachytherapy reirradiation is feasible and has acceptable toxicity.

Background: Carcinomas of sinuses and salivary glands are rare and heterogeneous in terms of anatomical sites and histology subtypes. For these reasons and because of the absence of prospective study results, their treatment is still largely extrapolated from data of frequent carcinomas of the upper digestive tract. Treatment is based on surgery and radiotherapy (proof level grade C). Despite the advances, the 5-year overall survival does not exceed 65%, mainly due to locoregional recurrence. In this context, chemotherapy administered concomitantly with radiotherapy could increase the efficacy of locoregional treatment by radiosensitization, regardless of the histology. Trial design: The GORTEC launched a multicenter, phase III randomized, open-label, study evaluating in case of high-risk of locoregional relapse, the impact of the addition after surgery of cisplatin 100 mg/m2 (every 3 weeks; 3 cycles) to radiotherapy. The population is defined as patients with radioresistant histologies (e.g. cystic adenoids carcinomas) or patients with unfavorable histoprognostic critera (e.g. incomplete resection, T4 tumor, malignant lymph node(s) with capsular rupture, presence of emboli, …). The primary endpoint is the progression free survival. Secondary outcomes are: overall survival, quality of life, time to progression (locoregional and distant) and toxicities. Two hundred and sixty patients will be enrolled in 5 years. Eligible patients are adults, with a performance status ≤ 2 and an adequate hematological and renal function for cisplatin treatment. Recruitment is ongoing in France. The study comprises a quality insurance program in radiotherapy and surgery. Coordinating investigators are Drs Ferrand and Thariat. Clinical trial identification: NCT02998385. Legal entity responsible for the study: GORTEC (Groupe Oncologie Radiothérapie Tête et Cou) Funding: GORTEC Disclosure: All authors have declared no conflicts of interest.

to estimate deviations from stereotactic protocol in a randomized phase II trial assessing the possibility to avoid chemotherapy at diagnosis of oligometastatic squamous cell carcinomas of the head and neck and to perform stereotactic body radiation therapy (SBRT) only owing to hypofractionation, diversity and novelty of extracranial SBRT practice among centers, a benchmark case was submitted to all participating centers as a prerequisite for patient accrual. DICOMRT file exchange was performed on the secured GORTEC imaging platform Of 13 French centers completing QA (tertiary care hospitals 7, private clinics 3, others 3; CyberKnife 4, Truebeam 3, Novalis TX 2, linear accelerators 3, Tomotherapy 1), 11 had started intracranial SBRT and 12 extracranial SBRT after 2010. The benchmark case consisted of two 1.5 cm and 0.8cm metastases (1cm distant from each other) nodule in left superior lung lobe 2cm from mediastinal structures. Nine centers prescribed 5 fractions as recommended per protocol for central lesions. Fiducials were required by 2 centers. CT slices were 1-3mm thick 4DCT was available in 8 centers. Two arcs or 5-201 beams (median 10, non-coplanar beams in CyberKnife centers only). Type B dose calculation algorithm was used in 7 centers. Prescription isodose was 70-95% (median 80). GTV to CTV margins were 0-5mm (median 0). CTV to PTV margins were 1-5mm (median 3). Maximal PTV diameter was 25-50mm (median 40). Daily online IGRT was systematically used with 2D or 3D imaging in 5 and 7 cases. Constraints to organs at risk (OAR) were always fulfilled. Conformality and homogeneity indexes varied between 1.15-1.47 (median 1.19) and 1.11-1.35 (median 1.25) respectively, R50 and D2 between 1.00-12.50 (median 6.12) and 13.9-33.4 (median 28.35), respectively. Major deviation was noted in 3 centers (GTV delineation, CTV-PTV margins / inappropriate respiratory management, dose prescription) and corrected. Minor deviations were noted in 3 cases (OAR not delineated, minor deviation in dose prescription/delivery). QA prior to patient accrual shows a variety of SBRT techniques. It also reveals major deviations in a few centers but may result in better compliance with protocol guidelines, and aims at standardizing SBRT practice. QA will also be processed for all real cases within 6 months of completion of SBRT.

The Radiation Therapy Oncology Group-ASTRO Phoenix definition of biochemical failure (BF)(nadir+2ng/mL), based on several cohorts of patients receiving radiation therapy (RT) alone or RT+ androgen-deprivation therapy (ADT), is recommended worldwide for determining the effectiveness of RT alone or RT + short-term ADT. In the short term, this definition correlated strongly with a higher likelihood of freedom from BF when compared with the ASTRO definition but in the longer term, it tended to be worse. We aimed to evaluate the impact of several short-term PSA endpoints and EORTC, ASTRO, and Phoenix definitions of BF on disease-free survival (DFS) in a cohort of high-risk prostate cancer (PCa) patients treated with hormones (HT) combined with RT. Between 1997 and 2009, we selected 313 nonmetastatic PCa patients who underwent exclusive RT combined with HT. Three risk groups were determined using the National Comprehensive Cancer Network classification (NCCN): unfavorable intermediate-risk (UIR), high-risk (HR), and pelvic cN1/pN1 (N+). Prognostic factors of DFS were studied in a Cox model that included the occurrence of undetectable PSA under HT and different cut-offs for the PSA nadir (nPSA) from 0.1 to 0.5 ng/mL after completion of HT. Multiple definitions of BF were tested: ASTRO, EORTC (PSA value >1.5 ng/mL and 2 consecutive increasing PSA), and Phoenix. Median follow-up was 77.5 months (95% CI= 72.8-83.7). One hundred eighty-two patients were HR (58.2%), 96 were UIR (30.7%), and 35 N+ (11.2%). The median dose was 74 Gy (range, 60-80), and the median duration of HT was 12.2 months (range, 3-106). Seventy-nine patients relapsed, and of these 24 died of their cancer. In univariate analyses, the Phoenix definition correlated more strongly with DFS (HR=30.2) than did EORTC (HR=8.2) and ASTRO (HR=2.5) definitions. In multivariate analyses, HR and N+ groups had similar risks (HR=1.1, [95%CI: 0.5-2.4] for HR vs N+), while patients with UIR had a better prognosis (HR=0.3, [95%CI: 0.1-0.9] for UIR vs N+). Patients who did not achieve undetectable PSA under HT (HR=2.2, [95%CI: 1.2-4.0]), those who had BF according to the Phoenix definition (HR=37.1, [95%CI: 11.3-121.6]) and those who had HT <2 years (HR= 3.0, [95%CI: 1.2-7.7]) had a poorer prognosis. nPSA <0.5ng/mL after treatment was not associated with better DFS (HR=1.5, [95%CI: 0.8-2.8]). PCa patients with undetectable PSA under HT were more likely to live longer without disease, while a PSA nadir <0.5 after completion of HT was not associated with better outcomes. Unsurprisingly, the Phoenix definition was the most powerful prognostic factor for DFS. Nevertheless, the EORTC and ASTRO definitions also correlated significantly with worse DFS.

Comparer la réponse biochimique de deux modalités de radiothérapie de rattrapage pour des cancers de prostate en rechute ganglionnaire isolée identifiée par tomodensitométrie par émission de positons (TEP)-scanographie à la (18F)-fluorocholine. Entre 2009 et 2014, parmi les 102 patients ayant eu une TEP-scanographie à la (18F)-fluorocholine dans notre centre, 37 étaient atteints d’une rechute ganglionnaire isolée traitée par irradiation de rattrapage sans hormonothérapie : soit une radiothérapie stéréotaxique focale de 30–45 Gy en 3–6 fractions (n = 28), soit une radiothérapie ganglionnaire prophylactique avec un boost dans les ganglions atteints de 60–66 Gy en 25–33 fractions (n = 9). La progression était définie par une concentration d’antigène spécifique de la prostate (PSA) supérieure à celle avant la récidive sur deux dosages consécutifs ou le début d’un autre traitement de rattrapage. La concentration médiane de PSA au moment de la rechute ganglionnaire était de 5,9 ng/mL [1,3–17,3] dans le groupe traité par irradiation stéréotaxique et 6,9 ng/mL [0,5–13,8] dans celui traité par irradiation ganglionnaire prophylactique avec un boost dans les ganglions atteints (NS). Avec un suivi médian de 1,95 ans [0,54–1,52], respectivement 15 (51,7 %) et quatre (44,4 %) rechutes ont été observées. Le nadir médian du PSA était significativement plus bas après irradiation ganglionnaire prophylactique avec un boost dans les ganglions atteints qu’après irradiation stéréotaxique, 0,02 ng/mL [0,01–0,07] contre 0,57 ng/mL [0,01–4,52] (p = 0,0004), et le délai médian pour atteindre ce nadir était aussi significativement plus court, 8,46 mois [5,19–18,37] contre 17,61 mois [0,20–23,62] (p = 0,05). Les temps médians jusqu’à progression étaient respectivement de 2,89 ans [1,24–4,65] et 4,73 ans [0,40–ND] (NS). La radiothérapie ganglionnaire prophylactique avec un boost dans les ganglions atteints permet d’obtenir un nadir du PSA et un temps médian pour atteindre ce nadir significativement plus bas que la radiothérapie stéréotaxique. L’impact de ce traitement sur le contrôle biochimique et/ou clinique nécessite un suivi à plus long terme.

18F or 11C choline positron emission tomography–computed tomography (PET-CT) has significantly improved the detection of occult nodal relapse in prostate cancer patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy and/or external radiation therapy (RT). In parallel, focal hypofractionated stereotactic body RT (fSBRT) is an emerging salvage RT (sRT) for oligometastatic diseases. It allows delivery of a very high biologically effective dose (BED) in few fractions but to a small volume (e.g., involved node only). In this preliminary report, we aimed to assess short-term biochemical response of focal SBRT versus protracted ENI in node-positive recurrent prostate cancer on choline PET-CT. Between 2009 and 2014, 102 patients underwent choline PET-TDM in our center. Of these, 37 had sRT without hormones for nodal relapse only. Patients underwent either fSBRT (n=28) or protracted elective nodal irradiation (n= 9) combined with a protracted boost to positive nodes (pENI). Patients treated with fSBRT received 30 to 45 Gy in 3 to 6 fractions while patients treated with pENI had 60 to 66Gy in 25 to 33 fractions. Failure was defined as PSA rising higher than pre-sRT on 2 consecutive samples or the initiation of any second salvage therapy. PSA nadir (nPSA), time to nPSA, and time to failure (TTF) were assessed. The characteristics of patients and tumor at time of relapse were similar. The median PSA values at the time of sRT were 5.9 ng/mL (1.3; 17.3) with fSBRT and 6.9 ng/mL (0.5; 13.8) with pENI (P=NS); The median follow-up was 1.95 years (95% CI: 0.54-1.52). Fifteen failures occurred with fSBRT (51.7%) and 4 failures with pENI (44.4%). The median PSA nadir at 2 years was 0.57 (0.01-4.52) with fSBRT and 0.02 (0.01-0.07) with pENI (P=.0004). The time to nPSA at 2 years was 17.61 months (0.20-23.62) with fSBRT and 8.46 months (5.19-18.37) with pENI (P=.05). The median TTF was 2.89 years (95% CI: 1.24-4.65) with fSBRT and 4.73 years (95% CI: 0.40-ND) with pENI (P= NS). Patients with a nodal relapse on fluorocholine PET-CT who were treated with pENI experienced a lower nPSA and shorter time to nPSA 2 years following completion of sRT than with fSBRT, consistent with the eradication of micrometastatic disease in PET-negative nodes. Whether this translates into improved biochemical control and/or a clinical relapse needs longer follow-up.