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Background Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. Methods 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. Results The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5–13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5–13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%–24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. Conclusions This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

Background The COVID‐19 pandemic has challenged cancer care globally, introducing resource limitations and competing risks into clinical practice. Aims To describe the COVID‐19 impact on medical oncology care provision in an Australian setting. Methods Calvary Mater Newcastle and Newcastle Private Hospital medical oncology data from 1 February to 31 April 2019 versus 2020 were retrospectively analysed. Results Three hundred and sixty‐four inpatient admissions occurred in 2020, 21% less than in 2019. Total inpatient days decreased by 22% (2842 vs 2203). April was most impacted (36% and 44% fewer admissions and inpatient days respectively). Mean length of stay remained unchanged (6.4 vs 6.2 days, P = 0.7). In all, 5072 outpatient consultations were conducted, including 417 new‐patient consultations (4% and 6% increase on 2019 respectively). Telephone consultations (0 vs 1380) replaced one‐quarter of face‐to‐face consultations (4859 vs 3623, −25%), with minimal telehealth use (6 vs 69). Day Treatment Centre encounters remained stable (3751 vs 3444, −8%). The proportion of new patients planned for palliative treatment decreased (35% vs 28%, P = 0.04), observation increased (16% vs 23%, P = 0.04) and curative intent treatment was unchanged (both 41%). Recruiting clinical trials decreased by one‐third (45 vs 30), two trials were activated (vs 5 in 2019) and 45% fewer patients consented to trial participation (62 vs 34). Conclusion Our medical oncology teams adapted rapidly to COVID‐19 with significant changes to care provision, including fewer hospital admissions, a notable transition to telephone‐based outpatient clinics and reduced clinical trial activity. The continuum of care was largely defended despite pandemic considerations and growing service volumes.

Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse cardiovascular effects with bevacizumab have not been intensively studied. In this study, we determined factors associated with hospital admissions due to cardiovascular complications in patients who received bevacizumab for cancer treatment. Methods and Results: We retrospectively collected data for all patients treated with bevacizumab between the 1st January 2016 and the 31st December 2017 at the Hunter New England Local Health District. Patients&rsquo, characteristics and their medical history were obtained from hospital electronic medical records. Outcome data were sourced from the Institutional Cardiac and Stroke Outcomes Unit database. A total of n = 230 patients (mean age 65, males n = 124 (53.9%)) were treated with bevacizumab during the study period. N = 28 patients were admitted to hospital for a major cardiovascular-related event. Higher total treatment dose (p &lt, 0.05), concomitant hypertension (p = 0.005), diabetes (p = 0.04), atrial fibrillation (p = 0.03), and lack of use of statin therapy (p = 0.03) were key contributors to hospital admission. Conclusions: Results of our study highlight the fact that patients with concomitant baseline cardiovascular disease/risk factors are at an increased risk of cardiovascular hospitalization related to bevacizumab treatment. Careful baseline cardiovascular assessment may be an essential step to minimize cardiovascular complications.

BACKGROUND: The clinical benefit rate with aromatase inhibitors and the impact of treatment on quality of life (QOL) in endometrial cancer is unclear. We report the results of a phase 2 trial of anastrozole in endometrial cancer. METHODS: Investigator initiated single-arm, open label trial of anastrozole, 1 mg/d in patients with ER and/or PR positive hormonal therapy naive metastatic endometrial cancer. Patients were treated until progressive disease (PD) or unacceptable toxicity. The primary end-point was clinical benefit (response + stable disease) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life (QOL) and toxicity. RESULTS: Clinical benefit rate in 82 evaluable patients at 3 months was 44% (95% CI: 34-55%) with a best response by RECIST of partial response in 6 pts. (7%; 95% CI: 3-15%). The median PFS was 3.2 months (95% CI: 2.8-5.4). Median duration of clinical benefit was 5.6 months (95% CI: 3.0-13.7). Treatment was well tolerated. Patients who had clinical benefit at 3 months reported clinically significant improvements in several QOL domains compared to those with PD; this was evident by 2 months including improvements in: emotional functioning (39 vs 6%: p = 0.002), cognitive functioning (45 vs 19%: p = 0.021), fatigue (47 vs 19%: p = 0.015) and global health status (42 vs 9%: p = 0.003). CONCLUSION: Although the objective response rate to anastrozole was relatively low, clinical benefit was observed in 44% of patients with ER/PR positive metastatic endometrial cancer and associated with an improvement in QOL. ispartof: GYNECOLOGIC ONCOLOGY vol:154 issue:1 pages:29-37 ispartof: location:United States status: published

OBJECTIVE: Treatment options are limited for patients with recurrent/metastatic low-grade ovarian cancers (LGOCs) and serous borderline ovarian tumors (SBOTs) as response rates to chemotherapy are low. A subset of patients appears to derive clinical benefit from antiestrogens, but most studies have been retrospective and clinical benefit rates (CBR) remain uncertain. The primary aim of PARAGON was to prospectively investigate the CBR of anastrozole, an aromatase inhibitor, in patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive LGOC and SBOT. METHODS: Post-menopausal women with ER-positive and/or PR-positive recurrent/metastatic LGOCs and SBOTs and evaluable disease by RECIST v1.1 or GCIG CA125 criteria were treated with anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Thirty-six patients were enrolled. Clinical benefit at 3 months (primary endpoint) was observed in 23 patients (64%, 95% CI 48%-78%) and was similar at 6 months (61%, 95% CI 43%-75%). The median duration of clinical benefit was 9.5 months (95% CI 8.3-25.8). Best study response was partial response by RECIST in 5 patients (14%), stable disease in 18 patients (50%) with progressive disease in 13 patients (36%). Median PFS was 11.1 months (95% CI 3.2-11.9). Anastrozole was well-tolerated. Patients with evidence of clinical benefit at 3 months reported less pain, fatigue, and improved physical and role functioning as early as 1 month of commencing treatment. CONCLUSIONS: Anastrozole was associated with a CBR of 61% of patients with recurrent ER-positive and/or PR-positive LGOC or SBOT for at least 6 months with acceptable toxicity. ispartof: GYNECOLOGIC ONCOLOGY vol:154 issue:3 pages:531-538 ispartof: location:United States status: published

Background: There is strong interest in testing lifestyle interventions to improve cancer outcomes; however, the optimal methods for achieving behavior change in large-scale pragmatic trials are unknown. Here, we report the 1-year feasibility results for exercise behavior change in the Canadian Cancer Trials Group CO.21 (CHALLENGE) Trial. Methods: Between 2009 and 2014, 273 high-risk stage II and III colon cancer survivors from 42 centers in Canada and Australia were randomized to a structured exercise program (SEP; n = 136) or health education materials (HEM; n = 137). The primary feasibility outcome in a prespecified interim analysis was a difference between randomized groups of ≥5 metabolic equivalent task (MET)-hours/week in self-reported recreational physical activity (PA) after at least 250 participants reached the 1-year follow-up. Secondary outcomes included health-related fitness. Results: The SEP group reported an increase in recreational PA of 15.6 MET-hours/week compared with 5.1 MET-hours/week in the HEM group [mean difference = +10.5; 95% confidence interval (CI) = +3.1–+17.9; P = 0.002]. The SEP group also improved relative to the HEM group in predicted VO2max (P = 0.068), 6-minute walk (P < 0.001), 30-second chair stand (P < 0.001), 8-foot up-and-go (P = 0.004), and sit-and-reach (P = 0.08). Conclusions: The behavior change intervention in the CHALLENGE Trial produced a substantial increase in self-reported recreational PA that met the feasibility criterion for trial continuation, resulted in objective fitness improvements, and is consistent with the amount of PA associated with improved colon cancer outcomes in observational studies. Impact: The CHALLENGE Trial is poised to determine the causal effects of PA on colon cancer outcomes. Cancer Epidemiol Biomarkers Prev; 25(6); 969–77. ©2016 AACR.

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER⁺). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER⁺ and/or progesterone receptor (PR)-positive (PR⁺) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER⁺ and/or PR⁺ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%-48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1-3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8-11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER⁺ and/or PR⁺ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents. ispartof: JOURNAL OF GYNECOLOGIC ONCOLOGY vol:30 issue:5 ispartof: location:Korea (South) status: published

Purpose To explore the prostate-specific membrane antigen (PSMA)–avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. Methods and Materials A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. Results A total of 893 PSMA-avid lesions were identified; at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. Conclusions Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs.

Objective: To assess the impact of the systematic use of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease-Cancer (NAT: PD-C) on clinical assessment, response and service utilisation. Study setting: Three major oncology treatment centres in NSW, Australia. Study design: Between March 2007 and December 2009, 219 people with advanced cancer were recruited to complete bi-monthly telephone interviews. The intervention, introduced after at least two baseline interviews, involved training health professionals to complete the NAT: PD-C with patients approximately monthly. Data collection: Rates of service use and referrals were compared pre- and post-introduction of the NAT: PD-C. Rates of completion of the tool; its impact on consultation length; and the types of needs and follow-up care to address these were also assessed. Principal findings: The NAT: PD-C had a high rate of completion; identified needs consistent with those self-reported by patients in interviews; and did not alter consultation length. No changes in the number of health professionals seen by patients were found pre- and post-intervention. Conclusion: The NAT: PD-C is an efficient and acceptable strategy for supporting needs-based cancer care that can potentially be incorporated into standard routine care without increasing the burden on care providers. Copyright © 2011 John Wiley & Sons, Ltd.

5524Background: GCTs occur predominantly in postmenopausal women and arise from sex cord stromal cells of the ovary. They generally have a good prognosis but can metastasize / recur after surgery. ...

499 Background: Borderline resectable pancreas cancers (BRPC) often require vascular reconstruction, have higher rates of operative margin positivity and confer a poor prognosis. In 2014, our high-volume pancreatectomy, gastrointestinal tumor multidisciplinary treatment (GI MDT) group endorsed a consensus anatomical definition of BRPC consistent with NCCN criteria. Diagnostic and staging tests were standardized and a neoadjuvant chemoradiotherapy protocol adopted with the goals to (1) improve R0 resection rate and (2) prevent futile surgery in rapidly progressive disease. Methods: Neoadjuvant chemoradiotherapy (CRT) consisted of 50.4Gy in 28# and concurrent capecitabine 830mg/m2 bd. Pancreatectomy was planned 4-8 weeks later unless repeat imaging showed progressive disease. Comprehensive, prospectively defined data items were collected on all patients (pts) diagnosed with BRPC. Results: Nine pts have been diagnosed with BRPC by the GI MDT. Seven pts received full dose of CRT, one pt progressed during CRT hence stopped early and one pt didn’t receive CRT due to significant deterioration beforehand. CRT was tolerable in all eight pts who received it; there were no dose modifications for toxicity. Post-CRT, three pts underwent curative-intent resection and all are still alive (494, 319 and 172 days post-CRT). One was found to have a solitary liver metastasis during surgery (resected), R1 resection (SMV margin involvement) of T3N1 tumor and is receiving palliative chemotherapy. Two other pts underwent R0 resections (T3N0, T3N1) with histopathologic response to CRT. Four pts showed progressive disease on post-CRT imaging (all local & distant progression) and subsequently received palliative therapy. Median survival (first dose CRT to death) in the 5 CRT pts who have succumbed was 509 days (range 363-577). Conclusions: In this small prospective, unselected cohort the majority of pts diagnosed with BRPC demonstrated disease progression during/after neoadjuvant CRT and did not proceed to surgical resection, underscoring the poor prognosis of this pancreas cancer subset. Neoadjuvant CRT is well tolerated and did not preclude subsequent surgery in those patients with stable disease.

5520Background: Many endometrial cancers express hormone receptors and may respond to hormonal therapy, but the impact on quality of life (QOL) is unclear. The aim of PARAGON is to investigate anas...

To assess the impact of the systematic use of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease-Cancer (NAT: PD-C) on clinical assessment, response and service utilisation.Three major oncology treatment centres in NSW, Australia.Between March 2007 and December 2009, 219 people with advanced cancer were recruited to complete bi-monthly telephone interviews. The intervention, introduced after at least two baseline interviews, involved training health professionals to complete the NAT: PD-C with patients approximately monthly.Rates of service use and referrals were compared pre- and post-introduction of the NAT: PD-C. Rates of completion of the tool; its impact on consultation length; and the types of needs and follow-up care to address these were also assessed.The NAT: PD-C had a high rate of completion; identified needs consistent with those self-reported by patients in interviews; and did not alter consultation length. No changes in the number of health professionals seen by patients were found pre- and post-intervention.The NAT: PD-C is an efficient and acceptable strategy for supporting needs-based cancer care that can potentially be incorporated into standard routine care without increasing the burden on care providers.

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is similar to 4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.