Cardiopulmonary Substructure Doses are Not Correlated With Cardiorespiratory Fitness Among Breast Cancer Survivors Treated With Contemporary Radiation Therapy.

Purpose: Breast cancer radiation therapy (RT) techniques have historically delivered mean heart doses (MHDs) in the range of 5 Gy, which have been found to predispose patients to cardiopulmonary toxicities. The purpose of this study was to apply artificial intelligence (AI) cardiac substructure auto-segmentation to evaluate the corresponding substructure doses, whether there are laterality- and technique-specific differences in these doses, and if the doses are significantly associated with cardiorespiratory fitness after state-of-the-art RT planning and delivery for breast cancer.

Methods And Materials: Cardiopulmonary substructures were AI auto-segmented.

Prediction of breast cancer risk for adolescents and young adults with Hodgkin lymphoma.

Background: While female survivors of Hodgkin lymphoma (HL) have an increased risk of breast cancer (BC), no BC risk prediction model is available. We developed such models incorporating mean radiation dose to the breast or breast quadrant-specific radiation doses.

Methods: Relative risks and age-specific incidence for BC and competing events (mortality or other subsequent cancer) were estimated from 1194 Dutch five-year HL survivors, treated at ages 11-40 during 1965-2000.

A digital, decentralized trial of exercise therapy in patients with cancer.

We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient's homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response.

Effects of exercise therapy on chemotherapy delivery and response in primary breast cancer: A secondary analysis of a randomized trial.

Background: Whether structured exercise therapy improves chemotherapy delivery, tolerability, and tumor response is unclear.

Methods: This was a secondary analysis of a phase 2 trial investigating exercise therapy (n = 72) versus usual care (n = 72) in patients with primary breast cancer. Exercise therapy comprised individualized treadmill walking three times weekly for 20-50 minutes per session at 55%-100% of pretreatment exercise capacity.

Feasibility and acceptability of a parent-child intervention to improve step count in childhood cancer survivors exposed to cardiotoxic therapy: The STEP UP for FAMILIES Study.

Background: Late morbidity after childhood cancer may be mitigated by healthy lifestyle behaviors. We piloted a game-based, parent-child digital intervention to increase activity in sedentary survivors.

Methods: Survivors aged 10-16 treated with cardiotoxic therapy and not meeting US physical activity guidelines were enrolled in a single-arm study with a parent.

Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial.

Importance: Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known.

Objective: To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer.

Ovarian function in female survivors of high-risk neuroblastoma.

Introduction: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy.

Methods: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center.

Risk of increased mortality in underweight survivors: A brief report from the Childhood Cancer Survivor Study.

Background: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown.

Objective: To determine whether underweight status increases the risk of mortality.

Exercise and QUality Diet after Leukemia: A Randomized Weight Loss Trial among Adult Survivors of Childhood Leukemia in the Childhood Cancer Survivor Study.

Background: Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention trial that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity.

Methods: In this phase III efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with a body mass index ≥25 kg/m2 were randomized to a remotely delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy.

Use of Response Permutation to Measure an Imaging Dataset's Susceptibility to Overfitting by Selected Standard Analysis Pipelines.

Rationale And Objectives: This study demonstrates a method for quantifying the impact of overfitting on the receiving operator characteristic curve (AUC) when using standard analysis pipelines to develop imaging biomarkers. We illustrate the approach using two publicly available repositories of radiology and pathology images for breast cancer diagnosis.

Materials And Methods: For each dataset, we permuted the outcome (cancer diagnosis) values to eliminate any true association between imaging features and outcome.

Association of breast cancer with quantitative mammographic density measures for women receiving contrast-enhanced mammography.

Women with high mammographic density have an increased risk of breast cancer. They may be offered contrast-enhanced mammography to improve breast cancer screening performance. Using a cohort of women receiving contrast-enhanced mammography, we evaluated whether conventional and modified mammographic density measures were associated with breast cancer.

Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.

Purpose: The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease.

Methods: Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses.

Association of exercise with pan-cancer incidence and overall survival.

Lavery et al. show that the association between exercise and risk of cancer varied as a function of organ site and amount of exercise. Exercise was also associated with a longevity benefit regardless of a cancer diagnosis or not.

Peripheral Arterial Disease is Associated With Higher Rates of Hospital Encounters and Mortality in Cancer Patients: A Retrospective Study Conducted at a Tertiary Cancer Center.

Cancer and peripheral arterial disease (PAD) have overlapping risk factors and common genetic predispositions. The concomitant effects of PAD and cancer on patients have not been well studied. The objective of this retrospective study is to evaluate outcomes of cancer patients with PAD.

Modeling Tumor Growth Using Partly Conditional Survival Models: A Case Study in Colorectal Cancer.

Purpose: There are multiple approaches to modeling the relationship between longitudinal tumor measurements obtained from serial imaging and overall survival. Many require strong assumptions that are untestable and debatable. We illustrate how to apply a novel, more flexible approach, the partly conditional (PC) survival model, using images acquired during a phase III, randomized clinical trial in colorectal cancer as an example.

Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer.

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy.

Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality.

Purpose: The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear.

Methods: We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included.

Ethnic diversity in treatment response for colorectal cancer: proof of concept for radiomics-driven enrichment trials.

Background: Several barriers hamper recruitment of diverse patient populations in multicenter clinical trials which determine efficacy of new systemic cancer therapies.

Purpose: We assessed if quantitative analysis of computed tomography (CT) scans of metastatic colorectal cancer (mCRC) patients using imaging features that predict overall survival (OS) can unravel the association between ethnicity and efficacy.

Methods: We retrospectively analyzed CT images from 1584 mCRC patients in two phase III trials evaluating FOLFOX ± panitumumab (n = 331, 350) and FOLFIRI ± aflibercept (n = 437, 466) collected from August 2006 to March 2013.

Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer.

Importance: Cancer therapy-related cardiac dysfunction (CTRCD) is a potentially serious cardiotoxicity of treatments for ERBB2-positive breast cancer (formerly HER2). Identifying early biomarkers of cardiotoxicity could facilitate an individualized approach to cardiac surveillance and early pharmacologic intervention. Circulating cell-free DNA (cfDNA) of cardiomyocyte origin is present during acute cardiac injury but has not been established as a biomarker of CTRCD.

Benign and malignant pulmonary parenchymal findings on chest CT among adult survivors of childhood and young adult cancer with a history of chest radiotherapy.

Purpose: Childhood and young adult cancer survivors exposed to chest radiotherapy are at increased risk of lung cancer. In other high-risk populations, lung cancer screening has been recommended. Data is lacking on prevalence of benign and malignant pulmonary parenchymal abnormalities in this population.

Rationale and design of a cardiac safety study for reduced cardiotoxicity surveillance during HER2-targeted therapy.

Background: Echocardiograms are recommended every 3 months in patients receiving human epidermal growth factor 2 (HER2)-targeted therapy for surveillance of left ventricular ejection fraction (LVEF). Efforts to tailor treatment for HER2-positive breast cancer have led to greater use of non-anthracycline regimens that are associated with lower cardiotoxicity risk, raising into question the need for frequent cardiotoxicity surveillance for these patients. This study seeks to evaluate whether less frequent cardiotoxicity surveillance (every 6 months) is safe for patients receiving a non-anthracycline HER2-targeted treatment regimen.

Benign and Malignant Findings on Chest CT Among Adult Survivors of Childhood and Young Adult Cancer with a History of Chest Radiotherapy.

: Childhood and young adult cancer survivors exposed to chest radiotherapy are at increased risk of lung cancer. In other high-risk populations, lung cancer screening has been recommended. Data is lacking on prevalence of benign and malignant imaging abnormalities in this population.