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.

Coronary Flow Velocity Reserve Declines After Anthracycline Therapy in Breast Cancer Patients.

Anthracycline therapy (ANT) is associated with cancer therapy-related cardiac dysfunction. Coronary flow velocity reserve (CFVR) has shown prognostic utility in non-cancer cohorts, but no data have been obtained in a cardio-oncology setting. We investigated the acute effect of ANT on CFVR in breast cancer patients. A total of 12 female breast cancer patients undergoing ANT had pre- and post-ANT CFVR assessment. A significant decline in CFVR occurred (baseline: 2.66 ± 0.41 vs post-ANT: 2.47 ± 0.37, P = 0.016). This prospective study is the first to identify ANT-related coronary physiology changes in humans. Further studies are required to determine their clinical significance.

Le traitement par l'anthracycline est associé à une dysfonction cardiaque liée au traitement anticancéreux. La réserve de débit coronaire a démontré son utilité pronostique dans les cohortes sans cancer, mais aucune donnée n'a été obtenue dans un contexte de cardio-oncologie. Nous avons étudié l'effet aigu de l'anthracycline sur la réserve de débit coronaire chez des patientes atteintes d'un cancer du sein. La réserve de débit coronaire a été évaluée avant et après le traitement par l'anthracycline chez un total de 12 femmes atteintes d'un cancer du sein. Un déclin important de la réserve de débit coronaire est survenu (valeur initiale de 2,66 ± 0,41 par rapport à 2,47 ± 0,37 après le traitement par l'anthracycline, p = 0,016). Cette étude prospective est la première à déceler des changements dans la physiologie coronarienne liés à l'anthracycline chez les humains. D'autres études sont nécessaires pour en déterminer la portée clinique.

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.

Accuracy of oncologists' estimates of expected survival time in advanced cancer.

BACKGROUND: To evaluate the claim that oncologists overestimate expected survival time (EST) in advanced cancer. METHODS: We pooled 7 prospective studies in which observed survival time (OST) was compared with EST (median survival in a group of similar patients estimated at baseline by the treating oncologist). We hypothesized that EST would be well calibrated (approximately 50% of EST longer than OST) and imprecise (<30% of EST within 0.67 to 1.33 of OST), and that multiples of EST would provide well-calibrated scenarios for survival time: worst-case (approximately 10% of OST <1/4 of EST), typical (approximately 50% of OST within half to double EST), and best-case (approximately 10% of OST >3 times EST). Associations between baseline characteristics and calibration of EST were assessed. RESULTS: Characteristics of 1,211 patients: median age 66 years, male 61%, primary site lung (40%) and upper gastrointestinal (16%). The median OST was 8 months, and EST was 9 months. Oncologists' estimates of EST were well calibrated (50% longer than OST) and imprecise (28% within 0.67 to 1.33 of OST). Scenarios for survival time based on simple multiples of EST were well calibrated: 8% of patients had an OST less than 1/4 their EST (worst-case), 56% had an OST within half to double their EST (typical), and 11% had an OST greater than 3 times their EST (best-case). Calibration was independent of age, sex, and cancer type. CONCLUSIONS: Oncologists were no more likely to overestimate survival time than to underestimate it. Simple multiples of EST provide well-calibrated estimates of worst-case, typical, and best-case scenarios for survival.

Communicating prognostic information: what do oncologists think patients with incurable cancer should be told?

BACKGROUND: People with incurable cancer require information about their prognosis to make informed decisions about their future. AIMS: To determine the frequency, form and documentation of prognostic discussions between oncologists and their patients with incurable cancer. METHODS: We surveyed medical oncologists in Australia and New Zealand about their practices communicating prognosis. RESULTS: A total of 206 medical oncologists completed the survey. Respondent characteristics were: median age 40 years (range 27-75), female 51%, trainee 22%; and 71% had completed specific training on communicating prognosis. Respondents reported discussing prognosis with a patient a median of 10 times per month (interquartile range 4-15); 88% reported explaining that 'the cancer is incurable' to all their patients with incurable cancer and 84% reported always or usually providing a quantitative estimate of survival time. The preferred method for explaining expected survival time (EST) was providing 'multiple ranges of time with probabilities, for example best-case, typical and worst-case scenarios' (52% of respondents). The most frequently reported barriers to discussing EST were: 'family members requesting that prognostic information not be discussed' (57% of respondents), and 'not knowing the EST' (46% of respondents). Twenty percent reported always documenting prognostic discussions and the EST in the patient's medical record, and 11% reported always documenting this information in their letters to other doctors. CONCLUSIONS: Most oncologists reported providing quantitative estimates of EST to their patients with incurable cancer, but very few reported documenting this information. Methods to help oncologists estimate, explain and document survival time are needed to improve communication of prognosis.

Survival and cardiac toxicity in patients with HER2-positive, metastatic breast cancer treated with trastuzumab in routine clinical practice.

AIMS: We sought to describe survival outcomes and toxicities of trastuzumab in real-world patients with HER2-positive, metastatic breast cancer (MBC) and compare these to a recent systematic review of clinical trials. METHODS: We searched the medical records of three Sydney cancer centers for patients with HER2-positive, MBC starting trastuzumab from January 2001 to March 2017. We recorded patient, tumor, and treatment characteristics; survival times from start of palliative trastuzumab; and rates of cardiac toxicity. Survival distribution was summarized using the following percentiles (represented scenario): 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). Survival times were compared to recent review of HER2-positive MBC randomized trials. Factors associated with survival were assessed with Cox models. RESULTS: Characteristics of the 126 patients were: median age 53 years, ER positive cancer (50%), de-novo metastatic disease (23%), prior adjuvant trastuzumab (15%), liver metastases (37%), and brain metastases (23%). The median duration of first-line trastuzumab was 11 months (interquartile range, (IQR) 5-27). Survival times in months (vs the systematic review) were: 90th percentile 8 (9); 75th percentile 16 (19); and median 34 (33). Follow-up duration was insufficient to estimate the 25th and 10th percentiles, similar to the systematic review. Liver metastases were associated with shorter survival (HR = 1.74, 95% CI, 1.1-2.76, P = .02). Seventy percent of patients had a baseline cardiac assessment. Five patients (3.9%) developed symptomatic cardiac toxicity, similar to clinical trials. CONCLUSION: Survival and cardiac toxicity rates for women starting trastuzumab in routine practice were comparable to clinical trials. Oncologists can use clinical trial data as a reference point when explaining survival outcomes to women with HER2-positive MBC.

Accuracy and Prognostic Significance of Oncologists' Estimates and Scenarios for Survival Time in Advanced Gastric Cancer.

BACKGROUND: Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists' estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. MATERIALS AND METHODS: Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists' estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise (<33% within 0.67-1.33 times the OST); independently predictive of overall survival (OS); and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario). RESULTS: Oncologists' estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67-1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists' estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. CONCLUSION: Oncologists' estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. IMPLICATIONS FOR PRACTICE: Results of this study demonstrate that oncologists' estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.