Early Toxicities After High Dose Rate Proton Therapy in Cancer Treatments

Background: The conventional dose rate of radiation therapy is 0.01-0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT). Materials and methods: A single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT. Results: There were 127 patients identified, with a median follow up of 14.8 months (3-42.9 months). The median age was 55 years (1.6-89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30-74 Gy), dose per fraction of 2 Gy (1-3 Gy), and CTV size of 47.6 ml (5.6-2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively. Conclusion: In this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit

Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome

Abstract Background To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose–rate brachytherapy (MIB). Methods A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician. Results Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65–92) with a median tumor size of 12 mm (range: 3–32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow–up of 40 months (range: 36–42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%. Conclusion We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed

Prognostic factors of colostomy free survival in patients presenting with locally advanced anal canal carcinoma: A pooled analysis of two prospective trials (KANAL 2 and ACCORD 03)

International audienc

High-dose-rate brachytherapy boost for prostate cancer: Comparison of three different fractionation schemes

International audiencePURPOSE:Dose escalation for prostate cancer can be achieved with a combination of external beam radiotherapy (EBRT) and brachytherapy (BT) boost to increase local control. For high-dose-rate (HDR)-BT, optimal fractionation remains under debate. The objective was to assess the clinical outcome of three schemes of HDR-BT boost.METHODS AND MATERIALS:Retrospective single institution data collection was performed. Patients received 46 Gy EBRT then an HDR-BT boost: 3 × 6 Gy, 2 × 9 Gy, or 1 × 14 Gy. HDR needles were placed under general anesthesia with endorectal ultrasonography guidance. CT-scan and treatment were performed postoperatively.RESULTS:Between 2009 and 2012, 159 patients were included. Nine patients (5.7%) were low, 32 (20.1%) intermediate, and 118 (74.2%) high risk (D'Amico classification) without significant difference between the three BT schemes. With a median followup of 61 months, 5-year biochemical relapse-free survival, 5-year local relapse-free survival, 5-year metastases-free survival, and 5-year overall survival rates were 86.6% (SE 2.7%), 98.3% (SE 1%), 95.3% (SE 1%), and 96.5% (SE 1.5%), respectively, with no significant difference between the BT schemes. The rates of acute ≥ G2 genitourinary and ≥G2 gastrointestinal toxicities were 11.3% and 6.3%, respectively (p = NS). The rates of late genitourinary ≥ G2 and gastrointestinal ≥ G2 toxicities (at last followup) were 9.4% and 0.6% with, respectively, 0.6% and 0% of G4 (p = NS).CONCLUSIONS:Hypofractionation up to a single-fraction HDR-BT boost for prostate cancer yields similar results in terms of biochemical control and late toxicity compared with two or three-fraction schemes. Single fraction HDR-BT appears acceptable for boosting prostate cancer after definitive EBRT

Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC)

International audiencePURPOSE: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer.MATERIALS AND METHODS: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up).RESULTS: After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented.CONCLUSION: For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose

French Recommendations for Osteoporosis Prevention and Treatment in Patients with Prostate Cancer Treated by Androgen Deprivation

International audienceAndrogen-deprivation therapy (ADT) in patients with prostate cancer can be achieved surgically or chemically, notably by prescribing LHRH analogs. Major bone loss occurs rapidly in both cases, due to the decrease in testosterone levels, and can increase the fracture risk. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on a literature review, about osteoporosis prevention and treatment in patients on ADT. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d’Information sur les Ostéoporoses (GRIO), Groupe Européen d’Etudes des Métastases Osseuses (GEMO), Association Francophone pour les SOins de Support (AFSOS), Association Française d’Urologie (AFU), Société Française de Radiothérapie Oncologique (SFRO). Medication prescription and reimbursement modalities in France were taken into account. The recommendations state that a fracture-risk evaluation and interventions targeting risk factors for fractures should be provided to all patients on ADT. Those patients with a history of severe osteoporotic fracture and/or a T-score &lt;-2.5 should receive osteoporosis therapy. Patients whose T-score is between -1.5 and -2.5 should be treated if they exhibit at least two other risk factors among the following: age ≥75 years, history of nonsevere fracture after 50 years of age, body mass index &lt;19 kg/m², at least three comorbidities (e.g., cardiovascular disease, depression, Parkinson’s disease, and dementia), current glucocorticoid therapy, and repeated falls. When the decision is difficult, FRAX® score determination and an assessment by a bone disease specialist may be helpful. When osteoporosis therapy is not indicated, general measures should be applied, and bone mineral density measured again after 12-24 months. The anti-tumor effects of bisphosphonates and denosumab fall outside the scope of these recommendations.</p