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.

Measuring serum oestrogen levels in breast cancer survivors using vaginal oestrogens: a systematic review.

PURPOSE: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability. METHODS: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included. RESULTS: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported. CONCLUSIONS: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.

Timing of prognostic discussions in people with advanced cancer: a systematic review.

PURPOSE: Many people with cancer (patients) want to know their prognosis (a quantitative estimate of their life expectancy) but this is often not discussed or poorly communicated. The optimal timing of prognostic discussions with people with advanced cancer is highly personalised and complex. We aimed to find, organise, and summarise research regarding the timing of discussions of prognosis with people with advanced cancer. METHODS: We conducted a systematic review of publications from databases, clinical practice guidelines, and grey literature from inception to 2023. We also searched the reference lists of systematic reviews, editorials, and clinical trial registries. Eligibility criteria included publications regarding adults with advanced cancer that reported a timepoint when a discussion of prognosis occurred or should occur. RESULTS: We included 63 of 798 identified references; most of which were cross-sectional cohort studies with a range of 4-9105 participants. Doctors and patients agreed on several timepoints including at diagnosis of advanced cancer, when the patient asked, upon disease progression, when there were no further anti-cancer treatments, and when recommending palliative care. Most of these timepoints aligned with published guidelines and expert recommendations. Other recommended timepoints depended on the doctor's clinical judgement, such as when the patient 'needed to know' or when the patient 'seemed ready'. CONCLUSIONS: Prognostic discussions with people with advanced cancer need to be individualised, and there are several key timepoints when doctors should attempt to initiate these conversations. These recommended timepoints can inform clinical trial design and communication training for doctors to help improve prognostic understanding.

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.

Safety of vaginal oestrogens for genitourinary symptoms in women with breast cancer.

BACKGROUND: Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can significantly impair quality of life. Genitourinary symptoms are very common and although these symptoms can be effectively managed with vaginal oestrogens, concerns about their safety in women with breast cancer limits their use. OBJECTIVE: The aim of this review is to provide a summary of the data on the safety of vaginal oestrogens in women with breast cancer to help general practitioners advise their patients in this situation. DISCUSSION: Although there are no large randomised prospective studies to assess safety, the current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer considering vaginal oestrogens. Consultation with the oncology team is advised for women taking aromatase inhibitors, where the safety of vaginal oestrogens is less certain.

Estimating survival scenarios in advanced or metastatic gastric and oesophageal adenocarcinoma: a systematic review of randomized-controlled trials.

BACKGROUND: We aimed to summarize survival data from RCTs in patients with GO adenocarcinoma; estimate and explain worst-, typical-, and best-case-scenarios of survival time; and determine if simple multiples of median overall survival (mOS) could estimate these percentiles. METHODS: We systematically searched RCTs of systemic therapies for GO adenocarcinoma published 2000-2022. The following key percentiles were extracted from overall survival curves: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We tested if these percentiles could be estimated by simple multiples of mOS: 0.25 of the median for the 90th percentile, 0.5 for the 75th, 2 for the 25th, and 3 for the 10th. RESULTS: We identified 44 trials (22,447 participants). For first line chemotherapy and immunotherapy combined (CI) trials (n = 3) worst-to-best case survival time ranged from 4 months to not reached, compared to 3-30 months for other trials (n = 27) and 1-23 months for subsequent lines (n = 14). Simple multiples of mOS accurately estimated the following survival percentiles: 90th (n = 3/3 trials), 75th (n = 3/3), and 25th (n = 2/3) in first line CI trials. In other first line trials, the mOS accurately estimated the 90th survival percentile in n = 22/27 trials, 75th percentile in n = 26/27, 25th percentile in 27/27 trials, and 10th percentile in 22/27 trials. Simple multiples of the mOS accurately predicted the 90th, 75th, 25th, and 10th survival percentiles in the majority of trials of second and subsequent lines apart from chemotherapy and immunotherapy only trials. CONCLUSION: We provide realistic, evidence-based prognostic information as scenarios for survival time which can inform clinical decision-making. Simple multiples of the mOS accurately estimated the percentiles for most groups.

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.