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With the emergence of high-precision radiotherapy technologies such as stereotactic ablative radiotherapy (SABR), MR guided brachytherapy, image guided intensity modulated photon and proton radiotherapy and most recently daily adaptive radiotherapy, reirradiation is increasingly recognized as a viable treatment option for many patients. This includes those with recurrent, metastatic or new malignancies post initial radiotherapy. The primary challenge in reirradiation lies in balancing tumor control against the risk of severe toxicity from cumulative radiation doses to previously irradiated normal tissue.Although technology for precise delivery has advanced at a fast pace, clinical practice of reirradiation still mostly relies on individual expertise, as prospective evidence is scarce, the level of reporting in clinical studies is not standardized and of low quality − especially with respect to cumulative doses received by organs at risk.A recent ESTRO/EORTC initiative proposed a standardized definition of reirradiation and formulated general requirements for minimal reporting in clinical studies [1].As a consequence we found it timely to convene for an international and interdisciplinary meeting with experts in the field to summarize the current evidence, identify knowledge gaps and explore which best practices can be derived for safe reirradiation. The meeting was held on 15.06.2023 in Zurich and was endorsed by the scientific societies SASRO, DEGRO and ESTRO. Here, we report on available evidence and research priorities in the field of reirradiation, as discussed during the meeting.

BackgroundNodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes.Materials and methodsThis retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event–biochemical or imaging recurrence, or death.ResultsA total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score

Background and purpose: Extreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities. Materials and methods: This retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch–Prentice method. Results: Among the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61–81), 7 % (95 %CI: 3–14), and 82 % (95 %CI: 73–89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9–28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05–8.86; P = 0.04). Conclusion: Extreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP.

IntroductionStereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma.MethodsA retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment.ResultsA total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities.ConclusionSBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligoprogressive metastatic castration-resistant prostate cancer (omCRPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omCRPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local relapse (LR), distant (DP) and isolated biochemical (iBP) progressions were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 50 pts with omCRPC underwent SBRT. With a MFU of 23 months [3–––100], median STE-FS was 13.1 months (95 %CI 10.8 – 36.4). Median OS was not reached and PFS was 13 months (CI95% 10.1 – 20.8). Post-SBRT PSA remained stable or decreased in 19 pts (38 %). Progression events (LR, DP, iBP) were observed in 34 pts (68 %), among whom 6 relapsed in the irradiated area (local control rate: 88 %). DP and iBP were observed in 28 pts (56 %) and 4 pts (8 %) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 2 pts. Conclusion: With excellent local control and tolerance, SBRT for omCRPC patients represents an acceptable approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

Background: Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. Objective: To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Design, setting, and participants: Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. Outcome measurements and statistical analysis: GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. Results and limitations: The median follow-up period was 88 mo (range, 81–99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1–6.6%) and 11.0% (95% CI: 5.1–19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77–95%) and 76.9% (95% CI: 63.1–86.1), respectively. Conclusions: A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. Patient summary: We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.

Purpose: To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligometastatic hormone-sensitive prostate cancer (omHSPC) patients. Materials-Methods: In this retrospective, observational, multi-institutional study, omHSPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local (LR), distant (DR), prostatic (PR) and isolated biochemical (iBR) relapses were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. Results: From 01/07 to 09/19, 119 pts with omHSPC underwent SBRT. With a MFU of 34 months [12–97], median STE-FS was 33.4 months (95%CI 26.6–––40.1). Median OS was not reached and PFS was 22.7 months (CI95% 18.6–––32.3). Post-SBRT-PSA remained stable or decreased in 87 pts (73.1%). Progression events (LR, MR, PR, iBR) were observed in 72 pts (60.5%), among whom 6 relapsed in the irradiated area (local control rate: 95%). DR, BR, PR were observed in 44 pts (37%), 21pts (17.7%) and 2 pts (1.7%) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 1pt. Conclusion: With excellent local control and tolerance, SBRT for omHSPC patients represents an attractive approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

BackgroundIntensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation.ObjectiveThe objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses.MethodsPatients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan–Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test.ResultsSeventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity.ConclusionThe use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.

Abstract Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome. Therefore, the identification of mechanisms and biomarkers of NACT resistance is paramount for ameliorating the prognosis of patients with Stage IIIA NSCLC. Here, we investigated the miRNome and transcriptome of chemo-naïve LNmets collected from patients with Stage IIIA NSCLC (N = 64). We found that a microRNA signature accurately predicts NACT response. Mechanistically, we discovered a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance, hallmarks metastases with active IFN-γ response pathway (an inducer of PD-L1 expression), and impacts T cells viability and relative abundances in tumor microenvironment (TME). Our data provide new biomarkers to predict NACT response and add molecular insights relevant for improving the management of patients with locally advanced NSCLC.

Abstract Background Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. Methods We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. Results Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). Conclusion Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Backround and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive litterature review, 97 recommandation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65–74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Tweny-one out of 29 (72.4%) surveyed GETUG investigators responded to both rounds. Consensus was achieved for 91/97 statements (93.8%) allowing the edition of comprehensive guidelines encompassing all aspects of SBM and NSBM SBRT planning and delivery: patients selection (19 statements), treatment preparation (14 statements), target volume delineation (18 statements), dose and fractionation (11 statements), prescription and dose objectives (9 statements), organs at risk dose constraints (15 statements) and image guided radiation therapy (11 statements). Conclusion: GETUG guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocol recommendations in ongoing and further GETUG clinical trials.

PurposeRadiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence.Material and methodsData from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging.ResultsRILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03).ConclusionOur study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

BackgroundThe optimal modalities of radiotherapy when combining concurrent chemoradiation (CCRT) and immunotherapy (IO) for locally advanced non-small cell lung cancer (LA-NSCLC) remain to be determined. The aim of this study was to investigate the impact of radiation on different immune structures and immune cells in patients treated with CCRT followed by durvalumab.Material and methodsClinicopathologic data, pre- and post-treatment blood counts, and dosimetric data were collected in patients treated with CCRT and durvalumab consolidation for LA-NSCLC. Patients were divided into two groups according to the inclusion (NILN-R+) or not (NILN-R−) of at least one non-involved tumor-draining lymph node (NITDLN) in the clinical target volume (CTV). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method.ResultsFifty patients were included with a median follow-up of 23.2 months (95% CI 18.3–35.2). Two-year PFS and 2-year OS were 52.2% (95% CI 35.8–66.3) and 66.2% (95% CI 46.5–80.1), respectively. In univariable analysis, NILN-R+ (hazard ratio (HR) 2.60, p = 0.028), estimated dose of radiation to immune cells (EDRIC) >6.3 Gy (HR 3.19, p = 0.049), and lymphopenia ≤ 500/mm3 at IO initiation (HR 2.69, p = 0.021) were correlated with poorer PFS; lymphopenia ≤ 500/mm3 was also associated with poorer OS (HR 3.46, p = 0.024). In multivariable analysis, NILN-R+ was the strongest factor associated with PFS (HR 3.15, p = 0.017).ConclusionThe inclusion of at least one NITDLN station within the CTV was an independent factor for poorer PFS in the context of CCRT and durvalumab for LA-NSCLC. The optimal sparing of immune structures might help in achieving better synergy between radiotherapy and immunotherapy in this indication.

Abstract Background Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. Methods We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. Results: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. Conclusion: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Stage-I testicular germ-cell tumor (TGCT) has excellent cure rates. Surveillance is fully included in patient’s management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, mainly concerning imaging frequency and long-term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. First, an online survey on surveillance practice of stage-I TGCT based on clinical-cases was conducted among urologists, radiation-oncologists and medical-oncologists. These results were compared to ESMO/EAU and AFU guidelines. Then a panel of experts assessed surveillance proposals following a Delphi-CM. Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. The study was conducted between July 2018 and May 2019. Concerning the first step: 61 participated to the survey (69% medical-oncologists, 15% urologists, 16% radiation-oncologists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, but only 25% stopped surveillance after the 5th-year. No physician followed the EAU/ESMO guidelines of de-escalation chest imaging. Concerning the second step: 32 experts (78% medical-oncologists, 16% urologists, 6% radiation-oncologists) participated to the Delphi-CM. Thanks to Delphi-CM, a consensus was reached for 26 of the 38 statements. Experts agreed on clinico-biological surveillance modalities and end of surveillance after the 5th-year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th-year of follow-up. No consensus was reached regarding de-escalation of chest imaging. To conclude, the survey proved that French TGCT-specialists do not follow current guidelines. With Delphi-CM, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th-year, stop of AP scan on the 4th-year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.

Abstract Background About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR). Methods This investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed. Discussion The combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023. Trial registration ImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018–002583-11 ; Clinicaltrials.gov: NCT03705403 ; ISRCTN ID: ISRCTN49817477 ; Date of registration: 03-April-2019.

Background: As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations. Methods: We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used. Results: Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p

Recent evidence suggests that the chimeric protein SETMAR is a factor of interest in cancer, especially in glioblastoma. However, little is known about the expression of this protein in glioblastoma tissues, and no study has been done to assess if SETMAR could be a prognostic and/or diagnostic marker of glioblastoma. We analyzed protein extracts of 47 glioblastoma samples coming from a local and a national cohort of patients. From the local cohort, we obtained localized biopsies from the central necrosis area, the tumor, and the perilesional brain. From the French Glioblastoma Biobank (FGB), we obtained three types of samples: from the same tumors before and after treatment, from long survivors, and from very short survivors. We studied the correlations between SETMAR amounts, clinical profiles of patients and other associated proteins (PTN, snRNP70 and OLIG2). In glioblastoma tissues, the shorter isoform of SETMAR (S-SETMAR) was predominant over the full-length isoform (FL-SETMAR), and the expression of both SETMAR variants was higher in the tumor compared to the perilesional tissues. Data from the FGB showed that SETMAR amounts were not different between the initial tumors and tumor relapses after treatment. These data also showed a trend toward higher amounts of S-SETMAR in long survivors. In localized biopsies, we found a positive correlation between good prognosis and large amounts of S-SETMAR in the perilesional area. This is the main result presented here: survival in Glioblastoma is correlated with amounts of S-SETMAR in perilesional brain, which should be considered as a new relevant prognosis marker.

Background: Breast cancer (BC) in young women merits a specific approach given the associated fertility, genetic and psychosocial issues. De novo metastatic breast cancer (MBC) in young women is an even more serious condition, with limited data available. Methods: We evaluated management of women aged ⩽40 years with de novo MBC in a real-life national multicentre cohort of 22,463 patients treated between 2008 and 2016 (NCT0327531). Our primary objective was to compare overall survival (OS) in young women versus women aged 41–69 years. The secondary objectives were to compare first-line progression-free survival (PFS1) and to describe treatment patterns. Results: Of the 4524 women included, 598 (13%) were ⩽40 years. Median age at MBC diagnosis was 36 years (range = 20–40). Compared with women aged 41–69 years, young women had more grade III tumours (49% versus 35.7%, p

IntroductionStereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer.Materials and MethodsWe conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment.FindingsForty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 – 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported.ConclusionThe PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.

Background/purposeDose-escalated external beam radiotherapy (RT) is effective in the control of prostate cancer but is associated with a greater incidence of rectal adverse events. We assessed the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon.Materials/methodsPatients scheduled for image-guided, intensity-modulated RT for intermediate-risk prostate cancer were prospectively included in the French multicenter BioPro-RCMI-1505 study (NCT02478112). We evaluated the dosimetric gain, implantation feasibility, adverse events (AEs), and prostate-cancer-specific quality of life associated with use of the balloon spacer.ResultsAfter a scheduled review of the initial recruitment target of 50 patients by the study’s independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018. The interventional radiologist who implanted the balloons considered that 86% of the procedures were easy. 20 of the 24 patients (83.3%) received IMRT and 4 (16.7%) received volumetric modulated arc therapy (78-80 Gy delivered in 39 fractions). The dosimetric gains associated with spacer implantation were highly significant (p

BackgroundUnderstanding intra-fractional prostate motions is crucial for stereotactic body radiation therapy (SBRT). No studies have focused on the intra-fractional prostate motions during re-irradiation with SBRT. The objective was to evaluate these translational and rotational motions in primary treated patients and in the context of re-irradiation.MethodsFrom January 2011 to March 2020, 162 patients with histologically proven prostate cancer underwent prostate SBRT, including 58 as part of a re-irradiation treatment. We used the continuous coordinates of the fiducial markers collected by an orthogonal X-ray dual-image monitoring system. The translations and rotations of the prostate were calculated. Prostate deviations representing overall movement was defined as the length of the 3D-vectors.ResultsA total of 858 data files were analyzed. The deviations over time in the group of primary treated patients were significantly larger than that of the group of re-irradiation, leading to a mean deviation of 2.73 mm (SD =1.00) versus 1.90 mm (SD =0.79), P

PURPOSE: Low- and middle-income countries (LMICs) experience the burden of 80% of new childhood cancer cases worldwide, with cure rates as low as 10% in some countries. Metronomics combines frequent administrations of low-dose chemotherapy with drug repurposing, which consists of using already-approved drugs for new medical applications. With wide availability, limited costs, and little infrastructure needs, metronomics can be part of constraint-adapted regimens in these resource-limited settings—with the understanding that metronomics shall not be a substitute for standard treatments when available and doable. Our study aims to describe the experience, practices, opinions, and needs in metronomics of physicians working in LMICs. METHODS: An online questionnaire was sent to more than 1,200 physicians in pediatric oncology networks in LMICs. Items included the type of center, physician’s demographics, experience in pediatric oncology, and experience with current knowledge of metronomics. Opinions and perspectives were explored using multiple-answer and open questions. RESULTS: Of physicians, 17% responded. Of respondents, 54.9% declared that they had already used a metronomic regimen. The most frequently cited repositioned drugs were celecoxib (44%) followed by propranolol and valproic acid (17%). Respondents highlighted the advantages of outpatient use (20%) and expected low toxicity (24%). In considering the drawbacks of metronomics, 47% of responses highlighted the lack of scientific evidence or guidelines, 33% the availability or affordability of drugs, and 18% the problem of acceptance or compliance. Of physicians, 79% believed that use of metronomics will spread in LMICs in the near future and 98% of them were willing to participate in international metronomic protocols or registries. CONCLUSION: Metronomics is already used in LMICs and is a potential answer to unmet needs in pediatric oncology. There is room for improvement in the availability of drugs and a necessity to develop collaborative protocols and research to generate level A evidence.

IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and MethodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 – Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.

Background: Initial staging and assessment of treatment activity in metastatic prostate cancer (PCa) patients is controversial. Indications for the various available imaging modalities are not well-established due to rapid advancements in imaging and treatment.Methods: We conducted a critical literature review of the main imaging abnormalities that suggest a diagnosis of metastasis in localized and locally advanced PCa or in cases of biological relapse. We also assessed the role of the various imaging modalities available in routine clinical practice for the detection of metastases and response to treatment in metastatic PCa patients.Results: In published clinical trials, the most commonly used imaging modalities for the detection and evaluation of therapeutic response are bone scan, abdominopelvic computed tomography (CT), and pelvic and bone magnetic resonance imaging (MRI). For the detection and follow-up of metastases during treatment, modern imaging techniques i.e., choline-positron emission tomography (PET), fluciclovine-PET, or Prostate-specific membrane antigen (PSMA)-PET provide better sensitivity and specificity. This is particularly the case of fluciclovine-PET and PSMA-PET in cases of biochemical recurrence with low values of prostate specific antigen.Conclusions: In routine clinical practice, conventional imaging still have a role, and communication between imagers and clinicians should be encouraged. Present and future clinical trials should use modern imaging methods to clarify their usage.

Abstract Background Prospective trials have demonstrated the advantage of dose-escalated radiotherapy for the biochemical and clinical control of intermediate risk prostate cancer. Dose escalation improves outcomes but increases risks of urinary and bowel toxicity. Recently the contribution of “spacers” positioned in the septum between the rectum and the prostate could improve the functional results of intensity modulated radiation therapy (IMRT). To date most of the evaluated devices were polyethylen glycol (PEG) and hyaluronic acid (HA). Men on the Spacer arm had decreased bowel toxicity and less decline in both urinary and bowel quality of life as compared to Control men in a randomized trial. Methods This is an interventional, multi-center study to evaluate the use of biodegradable inflatable balloon for patients with intermediate risk prostate cancer treated by IMRT (74 to 80 Gy, 2 Gy/fraction) with daily image guided radiotherapy. Discussion This multicenter prospective study will yield new data regarding dosimetric gain and implantation stages of Bioprotect balloon. Acute and late toxicities and quality of life will be registered too. Trial registration NCT02478112, date of registration: 15/06/2015.

Abstract Background Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation. Methods We combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions. Results We demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation. Conclusions These findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.

Abstract Background Currently, there is no standard option for local salvage treatment for local prostate cancer recurrence after radiotherapy. Our objective was to investigate the feasibility and efficiency of Robotic Stereotactic Body Radiation Therapy (SBRT) in this clinical setting. Methods/materials We retrospectively reviewed patients who were treated at our institution with SBRT for local prostate cancer recurrence after External Beam Radiation Therapy (EBRT) or brachytherapy. Multidisciplinary staff approved the treatment, and recurrence was biopsy-proven when feasible. A dose of 36 Gy was prescribed in six fractions. Treatment was delivered every other day. Results Between August 2011 and February 2014, 23 patients were treated with SBRT for intra-prostate cancer recurrence with a median follow up of 22 months (6 to 40). Twenty patients had biopsy-proven recurrence. For 19 patients, EBRT was the initial treatment and in four patients, brachytherapy was the initial treatment; the median relapse-time from initial treatment was 65 months (28 to 150). At relapse, 10 patients had an extra-capsular extension. Fourteen patients were treated with androgen deprivation that could be stopped after a median of 1 month after SBRT (range 0–24). A PSA decrease occurred in 82.6% of the patients after SBRT. The 2-year disease-free survival and overall survival rates were 54 and 100%, respectively. Disease progression was observed for nine patients (39.1%) (five local, three metastatic and one nodal progression) after a median of 20 months (7–40 months). The median nadir PSA was 0.35 ng/ml and was achieved after a median of 8 months (1 to 30) after treatment. We observed no grade 4 or 5 toxicity. Two patients presented with grade 3 toxicities (two Cystitis and one neuralgia). Other toxicities included urinary toxicities (five grade 2 and nine grade 1) and rectal toxicities (two grade 2 and two grade 1). Conclusion SBRT for local prostate cancer recurrence seems feasible and well tolerated with a short follow up. Prospective evaluation is needed.

Purpose: PET/CT is a standard medical imaging used in the delineation of gross tumor volume (GTV) in case of radiation therapy for lung tumors. However, PET/CT could present some limitations such as resolution and standardized uptake value threshold. Moreover, chest MRI has shown good potential in diagnosis for thoracic oncology. Therefore, we investigated the influence of chest MRI on inter-observer variability of GTV delineation.Methods and Materials: Five observers contoured the GTV on CT for 14 poorly defined lung tumors during three contouring phases based on true daily clinical routine and acquisition: CT phase, with only CT images; PET phase, with PET/CT; and MRI phase, with both PET/CT and MRI. Observers waited at least 1 week between each phases to decrease memory bias. Contours were compared using descriptive statistics of volume, coefficient of variation (COV), and Dice similarity coefficient (DSC).Results: MRI phase volumes (median 4.8 cm3) were significantly smaller than PET phase volumes (median 6.4 cm3, p = 0.015), but not different from CT phase volumes (median 5.7 cm3, p = 0.30). The mean COV was improved for the MRI phase (0.38) compared to the CT (0.58, p = 0.024) and PET (0.53, p = 0.060) phases. The mean DSC of the MRI phase (0.67) was superior to those of the CT and PET phases (0.56 and 0.60, respectively; p < 0.001 for both).Conclusions: The addition of chest MRI seems to decrease inter-observer variability of GTV delineation for poorly defined lung tumors compared to PET/CT alone and should be explored in further prospective studies.

Purpose: This study aimed to describe our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the management of adrenal gland metastases from multiple primary cancers.Materials and Methods: We retrospectively reviewed 31 patients who underwent SBRT as treatment for 33 adrenal gland lesions in the academic radiotherapy department of Oscar Lambret cancer center between May 2011 and September 2018. The primary study endpoints were 1- and 2-year local control rates, defined as the absence of progression at the treatment site based on the response evaluation criteria in solid tumors (RECIST). Toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events version 4.03.Results: The average tumor volume was 33.5 cm3 (standard deviation: 51.7 cm3), and the prescribed dose ranged from 30 to 55 Gy given in 3–9 fractions. The median biological effective dose was 112.5 Gy (range: 45–115.5 Gy), assuming α/β = 10. Considering progression at distant sites or death as competing events, the 1- and 2-year actuarial local control rates were 96.5% (95% confidence interval: 84.9–99.7) and 92.6% (95% confidence interval: 79.2–98.7), respectively. According to RECIST, a complete response was achieved in 10 (32.3%) lesions, a partial response in 10 (32.3%) lesions, and stability in 8 (25.8%) lesions. Three patients presented with local relapse at 8.8, 14, and 49.4 months. After a median follow-up of 18 months (range: 4.4–66.4), the median overall survival was 33.5 months (95% confidence interval: 17–not reached), while the median progression-free survival was 7.4 months (95% confidence interval: 3.8–14.1). Treatment-related toxicity was grade 1 or 2 in 42.4% of patients, including nausea (27.3%), abdominal pain (18.2%), vomiting (15.2%), and asthenia (9.1%). None of the patients developed acute grade ≥3 or late toxicity.Conclusion: SBRT seems to be a safe and effective treatment for adrenal gland metastases in patients whose primary tumor and metastatic spread are controlled by systemic treatment. With a 2-year local control rate of 92.6%, SBRT may be considered as one of the first-line treatments in oligometastatic patients with adrenal metastases.

Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs).Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT.Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22–83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions (n = 52, 33%) and 30 Gy in 5 fractions (n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81–93%] and 81% [95%CI, 70–88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81–93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0–17.9 months] and the OS rate at 1 year was 58% [95% CI, 50–65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis.Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients.

Objectives: To report the preliminary results of salvage re-irradiation in the prostatic bed after radical prostatectomy and salvage external beam radiation therapy (EBRT) using robotic stereotactic body radiation therapy (SBRT) with Cyberknife® for local recurrence of prostate cancer.Materials and Methods: Retrospective monocentric analysis was performed on patients treated with SBRT for isolated macroscopic recurrence in the prostatic bed. All patients had radical prostatectomy and salvage or adjuvant EBRT. Local recurrence was documented using magnetic resonance imaging (MRI) and positron emission tomography (PET). Biochemical recurrence was defined as 2 rises in prostate-specific antigen (PSA) of ≥ 0.2 ng/mL above nadir. Internal gold fiducials were used for the tracking of tumor motion during SBRT. The prescription dose was 36 Gy in 6 fractions for all patients. Toxicity was scored according to the CTCAE v4.0.Results: Between July 2011 and November 2017, 12 patients were treated with SBRT for prostatic bed recurrence with a median follow-up of 34.2 (range, 3.5–64.4) months. Isolated non-metastatic recurrence in the prostatic bed was seen at MRI and PET imaging. Two patients were treated with 6 months androgen deprivation therapy (ADT) concomitant with re-irradiation. The median planning target volume was 4.5 cm3 (range, 1.2–13.3). A PSA decrease after SBRT was found in 10 (83%) patients. The 1 and 2 years biochemical recurrence-free survival rates were 79 and 56%, respectively. Biochemical recurrence was observed for 6 patients (50%) after a median time of 18 (4-42) months. Toxicity showed: 3 patients (25%) with grade 1 cystitis and 1 patient (8%) with acute grade 2 proctitis at 4 months. One patient (13%) had grade 1 cystitis at 12 months.Conclusion: Re-irradiation for local recurrence in the prostatic bed using Cyberknife® after surgery and salvage or adjuvant EBRT is well-tolerated and associated with 2 years biochemical recurrence-free survival rates of 56%. Longer follow-up and larger series are necessary.

Purpose: As many as 50% of patients with cancer develop acute skin reactions to some degree with radiotherapy. Proactive skin care is often recommended to minimise these skin reactions and maintain the integrity of the epidermal barrier; nevertheless, no consensual guidelines are systematically used. This multicentre, observational, prospective study evaluated the tolerability and benefit of supportive and barrier protective skin care products in preventing radiotherapy-induced skin reactions in 253 women initiating radiotherapy (exclusive or adjuvant) for breast cancer. Methods: Patients received a kit of 5 commercially available skin care products before the first radiotherapy treatment. The following variables were assessed: cutaneous adverse events, investigator-assessed skin reactions (oedema, erythema, dryness, desquamation) before and after radiotherapy course, investigator, and patient opinion on products benefit. Results were analysed by frequency of product use (heavy versus low). Results: Average age was 60 years (range: 34-85). Over 92% of patients reported good to excellent tolerance on irradiated skin for each product. During the 6-week radiotherapy period, we observed that heavy product users had less skin reactions than the low users, particularly within 10 days of radiotherapy initiation (8% versus 18%; p = .031). Positive physician’s opinion on product use was more frequent for high (66.6%) versus low (32%) users. Patient-assessed patient benefit index was generally >1, indicating relevant treatment benefit, with a tendency for better benefit in high versus low users. Conclusions: These results support recommendations to use skin care products to minimise the impact of secondary cutaneous reactions with radiotherapy cancer treatment.

Automated atlas-based segmentation algorithms present the potential to reduce the variability in volume delineation. Several vendors offer software that are mainly used for cranial, head and neck and prostate cases. The present study will compare the contours produced by a radiation oncologist to the contours computed by different automated atlas-based segmentation algorithms for prostate bed cases, including femoral heads, bladder and rectum. Contour comparison was evaluated by different metrics such as volume ratio, Dice coefficient and Hausdorff distance. Results depended on the volume of interest and showed some discrepancies between the different software. Automatic contours could be a good starting point for the delineation of organs since efficient editing tools are provided by different vendors. It should become an important help in the next few years for organ at risk delineation.

Recently, independent studies have shown that the expression of two integrin chains, β4 and α2, plus the epithelial cadherin are related to tumour progression in human bladder carcinomas. For the first time, we compare the expression of these three cell adhesion molecules using immunohistochemical analysis of consecutive cryosections from a series of 50 bladder tumours. E‐cadherin, β4, and α2 were strongly expressed in normal urothelium. A majority of non‐invasive bladder cancers stained positively for E‐cadherin (62%), whereas only 29% expressed normal positivity for α2, and only 35% for β4. However, most invasive tumours presented an aberrant expression of α2 (81%), β4 (100%), and E‐cadherin (75%). We studied the correlation of immunoreactivity with histological grade and stage. The α2 pattern was not correlated with stage and grade. In contrast, loss of normal β4 expression was significantly related to increasing tumour grade and deep invasion with a higher correlation for grade. Finally, E‐cadherin expression was highly correlated with stage, but not with grade. Thus our results indicate that, although many invasive bladder tumours presented a disorder in expression of the two integrins α2 and β4, E‐cadherin appeared to be a better marker of invasiveness in bladder carcinomas.