Stereotactic radiotherapy for brain metastases: predictive factors of radionecrosis.

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.

Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial.

INTRODUCTION: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). METHODS: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed. RESULTS: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms. CONCLUSIONS: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.

Pembrolizumab Treatment-Induced Liver Toxicity.

T cells play a critical role in immune responses against neoplasm. This finding contributed to the immunotherapy development, an effective treatment for many cancers nowadays. Programmed cell death protein 1 (PD1) is an inhibitory receptor on T cells which downregulate T-cell function per ligation with its ligands (PDL1 and PDL2). PD1 blockade is used to enhance antitumor immunity. Pembrolizumab is a humanized monoclonal anti-PD1 antibody currently used in the management of melanoma, non-small-cell lung cancer, and Hodgkin lymphoma. Most of the treatment toxicities are immune-related adverse events, but grade 3-4 toxicities occur in up to 5% of patients, mainly dermatologic. We present a case of grade 4 pembrolizumab-induced liver toxicity associated with an excellent treatment response in a Caucasian woman.

[The management of bone metastasis]. / Prise en charge des métastases osseuses.

Bone metastasis are the most common cause of pain related to cancer, reducing patients' quality of life, and sometimes threatening their life-expectancy. Their management has to be pluridisciplinary, because of all the therapeutic options and the diversity of bone metastasis locations. The aim of this work is to propose a rational decisional algorithm for the treatment strategy of these secondary locations. Anti-resorbtive drugs with systemic action, surgery, conventional or stereotactic radiation therapy, and new techniques of interventional radiology are options that could be used separately or combined. They have shown benefits on symptomatic treatment, improving quality of life. Their indications vary according to the tumor site (short vs. long bones, carrier vs. non-carrier bones), the symptomatology (pain, neurologic symptoms), and the presence of complications (most of all fractures). The diverse presentations lead us to define this decisional algorithm, to guide the practice, while giving the maximal benefit to each patient according to each metastasis.

Prognostic factors for ovarian epithelial cancer in the elderly: a case-control study.

OBJECTIVES: Ovarian cancer is the leading cause of mortality by gynecologic cancers in Western countries. Many publications have suggested that age may be an independent prognostic factor in ovarian carcinoma. There are only few data concerning the impact of treatments and geriatric features within the elderly population. METHODS/MATERIALS: We collected data of older (≥ 70 years old) patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. First we described usual clinical and pathological features for these patients, as well as their outcome. We compared these parameters with that of young (<70 years old) patients treated during the same period. We then observed geriatric features in our set: Eastern Cooperative Oncology Group performance status, number of medications, Charlson index, body mass index, hemoglobin, and glomerular filtration rate. We finally looked for prognostic factors specific of the elderly population. RESULTS: One hundred nine elderly patients were identified and compared with 488 younger cases. There was no difference concerning clinicopathologic data. Surgery was more frequently complete in young women (58% vs 41.7%), and older patients received less chemotherapy courses and less taxanes (38.4% vs 67.1%). Young patients had a longer overall survival (median, 65.2 vs 26.2 months, P = 8.5E-10, log-rank test). Multivariate analyses confirmed that age was an independent prognostic factor and that within the elderly set the International Federation of Gynecology and Obstetrics stage, surgery results, number of chemotherapy cycles administered and performance status had a significant prognostic value. No clear correlation could be observed between geriatric characteristics and treatments administration. CONCLUSIONS: Ovarian cancer prognosis is poorer for older women, but they are more frequently suboptimally treated. No correlation could be observed between geriatric factors and surgery or chemotherapy achievement. Treatment decision should be based on objective geriatric assessment in order to improve outcome in this population.

Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.