Purpose Stereotactic radiotherapy (SRT) is a highly effective approach and represents the current standard of treatment for patients with limited number of brain metastasis (BM). SRT is generally well tolerated but can sometimes lead to radionecrosis (RN). The aim of this study was to identify predictive factors of radionecrosis related to SRT for brain metastasis. Methods This retrospective observational cohort study included patients who underwent SRT in the Institut Sainte Catherine between January 1st, 2017 and December 31st, 2020 for the treatment of brain metastasis from any cancer. Individual data and particularly signs of radionecrosis (clinical, imaging, anatomopathological) were collected from electronic medical records. Radionecrosis was defined as the occurrence on MRI of contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 6 months after SRT and localized within fields of irradiation. Results 123 patients were included; median age was 66 years. 17 patients (11.8%) developed radionecrosis after a median follow up of 418.5 days [63;1498]. Predictive factors of radionecrosis in multivariate analysis were age under 66 years with a sensitivity of 77% and a specificity of 56%. No other factor as the presence of comorbidities, the number of irradiated metastases, the PTV volume or the volume of irradiated healthy brain were predictive of radionecrosis. Conclusion Age at treatment initiation and tumor location seems to be correlated with radionecrosis in patients with brain metastasis treated with SRT. These elements could be useful to adapted radiation therapy.
PURPOSE:/objective: Limited pelvic/para-aortic nodal relapse of prostate cancer after radical local treatment remains a major challenge for locoregional salvage strategies. Salvage Elective Nodes radiotherapy (ENRT) is an appealing option, but concerns persist regarding its toxicity. This study evaluates the 18-months toxicity profile of salvage ENRT combined with intermittent androgen deprivation therapy (iADT) in patients with pelvic and para-aortic oligometastatic disease, compared with iADT alone. MATERIAL:/Methods: OLIGOPELVIS-2/GETUG P12 was a prospective, multicenter, randomized phase III trial. Patients were randomized 1:1 to arm A (6-months iADT alone) or arm B (6-months iADT + ENRT: 54 Gy/1.8 Gy per fraction to the pelvic lymph nodes and 66 Gy/2.2 Gy per fraction to pathological nodes). ENRT started after three months of iADT. After analyzing relapse patterns in the OLIGOPELVIS GETUG P07 study, a December 22, 2021 amendment permitted the inclusion of para-aortic lymph nodes and extended irradiation fields up to the renal arteries. Toxicity was defined using NCI-CTCAE v4.0. RESULTS:A total of 256 patients were enrolled across 17 French centers between 12/2018 and 05/2023. The safety population included 127 patients in arm A and 121 in arm B. Eight patients in arm B were excluded as they did not ultimately receive radiotherapy. Prior prostate or prostatic bed irradiation was reported in 57% and 55% of patients, respectively. In arm B, 39 patients also received para-aortic irradiation. At 6 months, grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 2.4% vs 9.9% (p = 0.02) and 0% vs 19.8% (p < 0.001) of patients in arms A and B, respectively. At 18 months, grade ≥ 2 GU toxicity was 4.1% vs 10.7%, (p = 0.04) in arms A and B, respectively, while no difference in GI toxicity was observed. Prior prostate or prostatic bed irradiation did not increase toxicity at any time point. Among patients receiving para-aortic irradiation, compared to those without : grade ≥ 2 toxicity was similar at 6 months (GU: 12.8% vs 8.5%, p = 0.8; GI: 20.5% vs 19.5%, p = 0.9), or at 18 months (GU: 10.3% vs 11%, p = 1.0; GI: 0% vs 6.1%, p = 0.17), though 6 months upper grade ≥ 1 GI disorders were more frequent (25.6% vs 9.8%, p = 0.02). CONCLUSIONS:Eighteen-month toxicity of salvage ENRT with a simultaneous boost to the pathological lymph nodes, associated with 6-months iADT was acceptable, even among patients with prior prostate irradiation or additional para-aortic irradiation (NCT03630666- RCB 2018-A00551-54; FundingPHRC-K 16-129).
The first results of ASTER 70s were presented at the 2022 ASCO annual meeting and have been accepted for publication in the Lancet. After a median follow-up of 8 years, women aged 70 years and older who underwent surgery for luminal breast cancer did not derive any significant benefit in overall survival from adjuvant chemotherapy added to hormonotherapy when selected based on a high-risk genomic grade index (GGI) tumour. However, the acceptability of chemotherapy may vary with age. We report here the acceptability of chemotherapy in women randomized to receive chemotherapy (4 cycles of anthracycline- or taxane-based chemotherapy administered every 3 weeks) in addition to hormonotherapy, as assessed using a self-administered questionnaire designed based on a previous experience in a similar setting (GERICO 06 trial). After the last cycle of chemotherapy, patients were asked ‘to what extent the treatment was acceptable given the absolute additional benefit of 7.5% in terms of cure sought with chemotherapy”, as stated in the patient information sheet and informed consent form, and the main reason if they found the treatment unacceptable. They were also asked whether they would recommend such treatment to relatives or close friends facing a similar situation. The questionnaires were then administered then yearly for 4 years. Of the 1,969 women screened for tumour GGI between April 2012 and May 2016, 58 (2.9%) withdrew their consent before GGI results and randomisation, while 1,089 (55%) with high-risk GGI tumours were randomized between chemotherapy and no chemotherapy. Of the 541 (49.7%) assigned to chemotherapy, 111 (20.5%) did not receive it for the following reasons: 23 (20.7%) refused chemotherapy, 22 (19.8%) withdrew consent, 8 (7.2%) for medical reasons, and 58 (52.3%) for unknown reasons. Of the 430 patients (79.5%) who started chemotherapy [44 (10.2%) stopped before the fourth cycle], 299 (69.5%) completed the first acceptability questionnaire at the end of chemotherapy, with 266 (95.3%) and 13 (4.7%) rating the chemotherapy experience acceptable and unacceptable, respectively, an assessment that was strongly associated with the occurrence of a serious adverse event during chemotherapy (15% and 46%, respectively, p<0.05). In addition, 242 (94.2%) said they would recommend the treatment to relatives if they were in the same situation. These rates remained stable over time until the fourth year of follow-up. Patient and tumour characteristics, quality of life scores at baseline, overall survival and invasive disease-free survival did not differ between patients who completed the acceptability questionnaire and those who did not. Factors reducing the acceptability of chemotherapy over time (from acceptable à not acceptable versus stable acceptable since the first post-chemotherapy assessment) were advanced age, a high Lee score (4-year mortality estimation) and low IADL. At baseline, low role functioning, low cognitive or social functioning, pain, dyspnoea, and loss of appetite had some impact on the acceptability of chemotherapy. It is difficult to assess the acceptability of a treatment, which depends largely on its safety and, consequently, its intensity in relation to increasing frailty with age. The acceptability of chemotherapy appears also to be influenced by factors such as age and quality of life, which must be taken into account when developing hypotheses in clinical trials, especially in elderly subjects. E. Brain, J. Henriques, F. Rollot, O. Mir, E. Bourbouloux, O. Rigal, J. M. Ferrero, S. Kirscher, D. Allouache, V. d'Hondt, A. M. Savoye, X. Durando, F. P. Duhoux, L. Venat Bouvet, E. Blot, J. L. Canon, H. Bonnefoi, T. Roque, J. Lemonnier, A. Latouche, M. Lacroix-Triki, D. Vernerey. Acceptability of adjuvant chemotherapy in women aged 70 and older after surgery for ER-positive HER2-negative breast cancer selected with a high genomic grade index: results from the ASTER 70s/Unicancer trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-09-11.
Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). Epidermal growth factor receptor (EGFR) and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (ClinicalTrials.gov identifier: NCT06385080 ) evaluated subcutaneous amivantamab administered every 3 weeks in participants with non-human papillomavirus R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR therapy and p16-positive oropharyngeal cancer were exclusionary. The primary end point was RECIST v1.1 ORR. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review‑assessed ORR was 42% (95% CI, 32 to 52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9 to NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37 to 57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2 to 8.3) and 12.5 months (95% CI, 10.2 to 16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than has been reported for paclitaxel or cetuximab.
BACKGROUND:The management of oligorecurrent pelvic lymph nodes in patients with prostate cancer is debated. Intermittent androgen-deprivation therapy (ADT; IADT) is often proposed. Elective pelvis irradiation (ENRT) may prolong tumor control and decrease subsequent spread. OBJECTIVE:To assess the efficacy of a combination of 6 mo of IADT with or without ENRT to treat patients with oligorecurrent pelvic and para-aortic lymph nodes of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:The OLIGOPELVIS 2-GETUG P12 trial is a multicenter randomized phase 3 trial, randomizing patients with 1-5 oligorecurrent pelvic and/or para-aortic lymph nodes of prostate cancer between arm A (IADT alone for 6 mo) versus arm B (salvage pelvic image-guided intensity-modulated radiotherapy [IG-IMRT], 54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) combined with IADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcome is progression-free survival, defined as the time from randomization until a biochemical-clinical failure is detected or death from any cause. In total, 256 patients will be included. RESULTS AND LIMITATIONS:In this population of patients requiring ADT, ENRT may demonstrate antitumoral efficacy while achieving acceptable toxicity and maintaining quality of life. Limitations are mainly inherent to the open-label design of this study. CONCLUSIONS:This phase 3 study will explore the role of salvage pelvic IG-IMRT combined with IADT in patients with oligorecurrent pelvic lymph nodes of prostate cancer in prolonging the first failure-free interval between the first and the second IADT courses. PATIENT SUMMARY:The OLIGOPELVIS 2-GETUG P12 clinical trial assesses short-term (6 mo) androgen-deprivation therapy in association with external beam radiation therapy in men with prostate cancer relapsing to pelvic and para-aortic lymph nodes of prostate cancer. The trial investigates whether radiotherapy targeting pelvic and para-aortic lymph nodes can improve the biological response while maintaining a favorable tolerability profile. TRIAL REGISTRATION:NCT03630666, RCB 2018-A00551-54, date of registration: 2018-12-04.
