A strong vaccine-induced T cell response during standard-of-care chemotherapy correlates with survival in patients with advanced cervical cancer.

Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). Patients and Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). Results: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1–97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5–43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2–86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. Conclusions: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.

Background: Chemoradiation or bioradiation treatment (CRT/BRT) of locally advanced head and neck squamous cell carcinoma (LAHNSCC) comes with high toxicity rates, often leading to temporary tube feeding (TF) dependency. Cachexia is a common problem in LAHNSCC. Yet changes in body composition and muscle weakness during CRT/BRT are underexplored. Strong evidence on the effect of TF on body composition during treatment is lacking. The aim of this cohort study was to assess (i) the relationship of fat‐free mass index (FFMI) and handgrip strength (HGS) with CRT/BRT toxicity and outcome, (ii) body composition in patients treated with chemoradiation (cisplatin) vs. bioradiation (cetuximab), and (iii) the effect of the current TF regime on body composition and muscle strength.Methods: Locally advanced head and neck squamous cell carcinoma patients treated with CRT/BRT between January 2013 and December 2016 were included (n = 137). Baseline measurements of body composition (bioelectrical impedance analysis) and HGS were performed. Toxicity grades (Common Terminology Criteria for Adverse Events) were scored. In a subset of 69 patients, weight loss, body composition, and HGS were additionally assessed during and after CRT/BRT. TF was initiated according to the Dutch guidelines for malnutrition.Results: In this cohort (68% male, mean age 59 ± 8 years), the incidence of baseline muscle wasting, defined as FFMI < P₁₀, was 29%. Muscle wasting was present in 23 of 100 (23%) chemoradiation patients and 17 of 37 (46%) bioradiation patients (P = 0.009). Muscle‐wasted patients required more unplanned hospitalizations during CRT (P = 0.035). In the chemoradiation subset, dose‐limiting toxicity was significantly higher in wasted vs. non‐wasted patients (57% vs. 25%, P = 0.004). Median follow‐up was 32 months. Multivariate Cox regression analysis identified muscle wasting as independent unfavourable prognostic factor for overall survival [hazard ratio 2.1 (95% CI 1.1–4.1), P = 0.022] and cisplatin as favourable prognostic factor [hazard ratio 0.3 (95% CI 0.2–0.6), P = 0.001]. Weight and HGS significantly decreased during CRT/BRT, −3.7 ± 3.5 kg (P < 0.001) and −3.1 ± 6.0 kg (P < 0.001), respectively. Sixty‐four per cent of the patients required TF 21 days (range 0–59) after CRT/BRT initiation. Total weight loss during CRT/BRT was significantly (P = 0.007) higher in the total oral diet group (5.5 ± 3.7 kg) compared with the TF group (3.0 ± 3.2 kg). Loss of FFM and HGS was similar in both groups.Conclusions: In LAHNSCC patients undergoing CRT/BRT, FFMI < P₁₀ is an unfavourable prognostic factor for overall survival, treatment toxicity, and tolerance. Patients experience significant weight and FFM loss during treatment. Current TF regime attenuates weight loss but does not overcome loss of muscle mass and function during therapy. Future interventions should consider nutritional intake and additional strategies specifically targeting metabolism, loss of muscle mass, and function.

Background: Participation of Adolescents and Young Adults with cancer (AYAs: 18–39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long-term) physical and psychosocial health outcomes. We examined the representativeness of AYAs participating in the study, to observe the impact of various invitation methods on response rates and reasons for non-participation. Methods: A population-based, cross-sectional cohort study was performed among long-term (5–20 years) AYA cancer survivors. All participants were invited using various methods to fill in a questionnaire on their health outcomes, including enclosing a paper version of the questionnaire, and sending a reminder. Those who did not respond received a postcard in which they were asked to provide a reason for non-participation. Results: In total, 4.010 AYAs (response 36%) participated. Females, AYAs with a higher socio-economic status (SES), diagnosed more than 10 years ago, diagnosed with a central nervous system tumor, sarcoma, a lymphoid malignancy, stage III, or treated with systemic chemotherapy were more likely to participate. Including a paper questionnaire increased the response rate by 5% and sending a reminder by 13%. AYAs who did not participate were either not interested (47%) or did want to be reminded of their cancer (31%). Conclusions: Study participation was significantly lower among specific subgroups of AYA cancer survivors. Higher response rates were achieved when a paper questionnaire was included, and reminders were sent. To increase representativeness of future AYA study samples, recruitment strategies could focus on integrating patient-reported outcomes in clinical practice and involving AYA patients to promote participation in research.

Adolescent and young adult (AYA) cancer survivors (18–39 years at diagnosis) often experience negative body changes such as scars, amputation, and disfigurement. Understanding which factors influence body image among AYA survivors can improve age-specific care in the future. Therefore, we aim to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA cancer survivors (5–20 years after diagnosis). A population-based cross-sectional cohort study was conducted among AYA survivors (5–20 years after diagnosis) registered within the Netherlands Cancer Registry (NCR) (SURVAYA-study). Body image was examined via the EORTC QLQ-C30 and QLQ-SURV100. Multivariable logistic regression models were used. Among 3735 AYA survivors who responded, 14.5% (range: 2.6–44.2%), experienced a negative body image. Specifically, AYAs who are female, have a higher Body Mass Index (BMI) or tumor stage, diagnosed with breast cancer, cancer of the female genitalia, or germ cell tumors, treated with chemotherapy, using more maladaptive coping strategies, feeling sexually unattractive, and having lower scores of health-related Quality of Life (HRQoL), were more likely to experience a negative body image. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future research could help to identify when and how this support for AYA survivors can be best utilized.