Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy.

BACKGROUND: We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies. MATERIALS AND METHODS: We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). RESULTS: We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS. CONCLUSIONS: Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study.

PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

Beyond the median: Estimating survival times for patients starting endocrine therapy for estrogen receptor-positive, metastatic breast cancer from recent randomized trials.

AIM: To estimate scenarios for survival for patients with estrogen receptor (ER) positive, metastatic breast cancer (MBC) and to help communicate prognosis to patients starting endocrine therapy (ET) METHODS: We searched for randomized trials of ET for ER-positive MBC and extracted the following percentiles (representative survival scenarios) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We then assessed the accuracy of estimating these percentiles for each OS curve by multiplying the median OS by four simple multiples: 0.25 (to estimate the 90th percentile), 0.5 (75th), 2 (25th), and 3 (10th). Estimates were deemed accurate if it fell within 0.75-1.33 times the actual value. RESULTS: We identified 25 trials with 10,566 patients. The median OS (interquartile range) was: 61.3 months (53.4-64.8) for first-line ET with cyclin-dependant kinase 4/6 inhibitors (four treatment groups); 42.6 months (40.9-50.4) for first-line ET alone (21 treatment groups) and 29.2 months (24.8-33.4) for subsequent line ET (19 treatment groups). Simple multiples of the median OS accurately estimated the 90th percentile in 80%; 75th percentile in 93%; and 25th percentile in 76% of curves. The 10th percentile was only available for four OS curves and could not be evaluated. CONCLUSION: Simple multiples of the median OS are a helpful and accurate method to assist in estimating and discussing scenarios for survival for MBC patients starting ET. Longer follow-up of trials is required to help clinicians estimate the best-case scenario.

Case Series: "Silent" Spinal Epidural Metastases in Metastatic Castrate-Resistant Prostate Cancer.

Introduction: Spinal epidural metastases (SEM) are an uncommon phenomenon and traditionally occur as a preterminal event in heavily pre-treated patients. The introduction of novel anti-androgen therapies, such as enzalutamide and abiraterone acetate, has greatly improved the survival of patients with metastatic prostate cancer but may be changing the pattern of disease. Case Presentation: Four patients diagnosed with metastatic castrate-resistant prostate cancer (CRPC) were commenced on enzalutamide prior to chemotherapy. Baseline scans in all patients demonstrated extensive bony disease and lymph node involvement. All patients experienced a moderate initial PSA response to treatment (median PSA at baseline 53.5 ng/mL to median nadir 24.5 ng/mL). In all four cases, clinical presentation of spinal cord compression was unexpected with no prodromal neurological symptoms, PSA levels either stable or slowly rising, and CT scans and whole-body bone scans showing stable disease at other metastatic sites. Whole-spine MRI on presentation of neurological deficits showed epidural and dural metastases on the background of stable bone disease. Spinal cord compression occurred at a median of 11.4 months after starting enzalutamide. Conclusion: Clinicians should be aware of this change in the pattern of CRPC in patients treated with novel anti-androgen therapy. Onset of "silent" spinal cord compression due to SEM rather than bone metastases, can occur relatively early with minimal warning despite stable disease on PSA and standard imaging. Differential progression in nontraditional sites suggests that research into the androgen microenvironment in a wide range of tissue sites should be undertaken, and may explain why prostate cancer metastasizes preferentially to bone and lymph nodes.

Real world outcomes of neoadjuvant chemotherapy and radiotherapy for borderline resectable pancreatic cancer: a multicentre observational study.

BACKGROUND: Neoadjuvant therapy may increase the likelihood of complete (R0) resection for borderline resectable pancreatic cancer. The optimal approach is unknown and differs amongst treatment centres. METHODS: We identified patients with biopsy-proven borderline resectable pancreatic adenocarcinoma who commenced neoadjuvant therapy between January 2012 and June 2019 at three centres in Sydney, Australia. Patterns of care and outcomes of varying approaches were examined. RESULTS: Forty-eight patients were identified. Median age was 66 years (range: 41-84). Staging included endoscopic ultrasound in 98%, PET-CT scan in 77%, laparoscopy in 46%. Neoadjuvant regimens used were a combination of chemotherapy and chemo-radiation (58%), chemotherapy alone (13%) and chemoradiation alone (29%). Radiologic complete or partial response occurred in 33% and progression in 25%. Complete macroscopic surgical resection was achieved in 50%, and R0 resection in 38%. At median follow-up of 15 months, the 1-year and 2-year overall survival was 75% and 63% respectively, and the 1-year and 2-year progression-free survival was 50% and 29% respectively. Significant predictors of macroscopic resectability were radiologic response (p = 0.005) but not addition of radiotherapy to chemotherapy (OR 0.87, p = 0.81). Predictors of overall survival included baseline Ca19.9 level (p = 0.04) and a trend to the use of systemic chemotherapy (HR 0.51, p = 0.07), but not use of radiotherapy (HR 0.70, p = 0.47). CONCLUSION: There is high variability in staging and neoadjuvant approaches for borderline resectable pancreas cancer. Despite aggressive neoadjuvant therapies, R0 resection and prolonged survival are uncommon. The incremental benefit of neoadjuvant radiotherapy after neoadjuvant chemotherapy was not demonstrated in this observational study.

Patient satisfaction with telehealth consultations in medical oncology clinics: A cross-sectional study at a metropolitan centre during the COVID-19 pandemic.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a widespread adoption of telehealth (phone and video consultations) in cancer care worldwide. The aim of this study was to determine patient satisfaction with telehealth consultations with their medical oncologist at a tertiary cancer centre in Sydney, Australia. METHODS: Patients who attended a routine telehealth appointment at the medical oncology outpatient clinic were recruited to complete a questionnaire containing 16 items, each on a 5-point Likert scale regarding satisfaction levels in various aspects of telehealth and their willingness to continue telehealth after the pandemic. Patients were also invited to provide suggestions for improvement. RESULTS: In total, 150 patients were invited to participate, and 103 valid questionnaires were returned. Median age was 63 years (range: 25-90), 49% of patients were male, 63% of patients had advanced cancer and 81% were on active treatment. In total, 95% of participants indicated that they were satisfied (score ≥4) with telehealth. 82% of participants preferred to continue telehealth consultations after the coronavirus disease 2019 pandemic, but ideally with a mix of telehealth and in-person consultations. Phone appointments (vs. video, p < 0.002), patients with advanced cancer (vs. early, p < 0.036) and pre-chemotherapy/immunotherapy/targeted therapy treatment reviews (vs. follow-up appointments, p < 0.001) were significantly associated with a willingness to continue telehealth. DISCUSSION: Patients were overwhelmingly satisfied with telehealth during the study period and were willing to continue telehealth for some appointments beyond the coronavirus disease 2019 pandemic. More research into the effectiveness, safety and implementation of telehealth to compliment traditional face-to-face services for patient-centred cancer care is required.