Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial.

AIM: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer. METHODS: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS. RESULTS: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo. CONCLUSIONS: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS). CLINICALTRIALS: govregistration: NCT01583322.

[Non-programmed hospitalization of elderly patients with cancer: Which care pathway?] / Hospitalisation non programmée des patients âgés atteints de cancer : quel parcours de soins ?

INTRODUCTION: Management of elderly patients with cancer is challenging worldwide. Improvement of their care pathway should focus on unplanned hospitalizations. This study aimed to compare the geriatric and oncologic profiles of elderly patients with cancer, hospitalized for an acute pathology either in medical oncology or acute geriatric medicine units. METHODS: Epidemiological, analytical, monocentric, transversal study performed in the geriatric and oncological short-stay units of the university hospital of Poitiers (France) from 07/01/2014 to 06/30/2015. Only patients with diagnosed cancer prior to hospitalization were included. The geriatric, oncological and hospitalization data were collected and analyzed. RESULTS: In total, 230 patients were included (156 in geriatrics, 74 in oncology). Alteration of the general condition was the most frequent reason for admission. In multivariate age-adjusted analyses, factors associated with admission to a geriatric unit were co-morbidities (OR=0.18 [95% CI: 0.07-0.46], P<0.01) and dependence (OR=0.07 [95% CI: 0.01-0.36], P<0.01). Ongoing antineoplastic treatment (OR=2.60 [95%CI: 1.14-5.89], P=0.02) and metastatic cancer (OR=2.63 [95%CI: 1.18-5.86], P=0.02) influenced hospitalization in the oncology unit. During the hospital stay there was more frequent psychological support in oncology (OR=45.59 [95%CI: 9.79-212.23], P<0.01) and social support in Geriatrics (OR=0.13 [95% CI: 0.04-0.40], P<0.01). CONCLUSION: This first comparative study showed a significant difference in profiles of elderly patients with cancer hospitalized for an acute problem, depending on the hospital unit. This finding paves the way of improvement of care pathway by formalizing links between these two departments to optimize care and referrals to the most appropriate care unit, according to patients condition, in case of unscheduled hospitalization.

Prevalence of cancer and management in elderly nursing home residents. A descriptive study in 45 French nursing homes.

This study aimed to determine cancer prevalence occurring after the age of 75 in 45 French nursing homes (NH), as well as residents' characteristics and parameters associated with cancer-specific management. Descriptive retrospective study including 214 residents (mean age, 89.7 years) with cancer diagnosed after age 75. The studied parameters were sociodemographic, functional, nutritional and cognitive data; comorbidity assessment; date of tumoral diagnosis; cancer type; tumoral stage; treatment plan; multidisciplinary staff decision and oncologic follow-up. Our results showed that cancer prevalence in NH was 8.4 ± 1.1%, diagnosed before admission in 63% of cases. The most common tumoral sites were skin (26%), digestive tract and breast (18% for both); 12% had metastasis. Cognitive impairment was the most common comorbidity (42%), and 44% of the residents were highly dependent. Multivariate analysis showed that therapeutic decisions were associated with age. Older patients had less staging exploration (odd ratios [ORs], 0.90, 95% confidence interval [CI], 0.85-0.97) and underwent less cancer-specific treatment (ORs, 0.92; 95%CI, 0.86-0.99). Oncologic follow-up was more frequent in younger patients (ORs, 0.90; 95%CI, 0.81-0.99) and those with recent diagnosis (ORs, 0.37; 95%CI, 0.23-0.61). This study identified factors associated with substandard neoplastic management in elderly NH residents. It highlights needs for information, education and training in cancer detection to improve cancer consideration and care in NH.

DNA-PKcs expression predicts response to radiotherapy in prostate cancer.

PURPOSE: Double-strand breaks, the most lethal DNA lesions induced by ionizing radiation, are mainly repaired by the nonhomologous end-joining system. The expression of the nonhomologous end-joining pathway has never been studied in prostate cancer, and its prognostic value for patients undergoing radiotherapy remains unknown. METHODS: Pretreatment biopsies from 238 patients treated with exclusive external beam radiotherapy for localized prostate cancer with ≥ 2 years of follow-up were reviewed to reassess the Gleason score. Of these 238 cases, 179 were suitable for in situ analysis and were included in the tissue microarrays. Expression of the nonhomologous end-joining proteins Ku70, Ku80, DNA-dependent protein kinase, catalytic subunits (DNA-PKcs), and X-ray repair cross complementing 4-like factor was studied by immunohistochemistry, together with the proliferation marker Ki67. RESULTS: The predictive value of the Gleason score for biochemical relapse (using the Phoenix criteria) was markedly improved after review (P<.0001) compared with the initial score (P=.003). The clinical stage, pretreatment prostate-specific antigen level, and perineural invasion status were also associated with progression-free survival (P=.005, P<.0001, and P=.03, respectively). High proliferation (>4%) tends to be associated with biochemical recurrence; however, the difference did not reach statistical significance (P=.06). Although the expression of Ku70, Ku80, and X-ray repair cross complementing 4-like factor was not predictive of relapse, positive DNA-PKcs nuclear staining was closely associated with biochemical recurrence (P=.0002). On multivariate analysis, only the Gleason score, prostate-specific antigen level, and DNA-PKcs status remained predictive of recurrence (P=.003, P=.002, and P=.01, respectively). CONCLUSIONS: The results of the present study highly suggest that DNA-PKcs could be a predictive marker of recurrence after radiotherapy, independently of the classic prognostic markers, including the Gleason score modified after review.