bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized clinical trial on the effect of a supervised exercise program on quality of life, fatigue, and fitness following esophageal cancer treatment (PERFECT study).
Authors: May Anne Maria , van Vulpen Jonna , Hiensch Anouk E , Ruurda Jelle P. , Nieuwenhuijzen Grard , Kouwenhoven Ewout , Groenendijk Richard PR , Van der Peet Donald , Hazebroek Eric J , Rosman Camiel , Wijnhoven Bas P.L. , van Berge Henegouwen Mark I. , Van Laarhoven Hanneke W.M. , van Hillegersberg Richard , Siersema Peter
Published: May 2020

12055

Background: Patients with potentially curable esophageal cancer are often treated with chemoradiotherapy followed by surgery. This treatment might have a negative impact on physical fitness, fatigue and quality of life (QoL). In patients with other types of cancer, evidence suggests that physical exercise reduces treatment related side effects. We investigated whether a supervised exercise program also beneficially affects QoL, fatigue and cardiorespiratory fitness (CRF) in patients after treatment for esophageal cancer. Methods: The multicenter PERFECT study randomly assigned patients in the first year after esophagectomy to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate to high intensity aerobic and resistance exercise program supervised by a physiotherapist. UC patients were advised to maintain their physical activity levels. Attendance and compliance with the exercise intervention protocol were retrieved from exercise logs. QoL (primary outcome, EORTC-QLQ-30, range 0-100), fatigue (MFI-20, range 4-20) and CRF (cardiopulmonary exercise testing) were assessed at baseline and after 12 weeks (post-intervention). The outcomes were analyzed as between-group differences using either linear mixed effects models or ANCOVA adjusted for baseline and stratification factors (i.e. sex, time since surgery, center), according to the intention-to-treat principle. Results: A total of 120 patients (age 64±8) were included and randomized to EX (n = 61) or UC (n = 59). Patients in the EX group participated in 96% (IQR:92-100%) of the supervised exercise sessions and compliance with all parts of the exercise program was high ( > 90%). Post-intervention, global QoL was not statistically different between groups, but significant (p < 0.05) beneficial EX effects were found for QoL-Summary scores (between-group difference 3.5, 95% CI 0.2;6.8) and QoL-role functioning (9.4, 1.3;17.5). Physical fatigue wat non-significantly lower in the EX group (-1.2; -2.6;0.1, p = 0.08). CRF was significantly higher (VO2peak (1.8 mL/min/kg, 0.6;3.0) following the EX intervention. Conclusions: Patients were well capable to complete an intensive supervised exercise program after esophageal cancer treatment, which led to small but significant improvements in several aspects of QoL and cardiorespiratory fitness. Our results suggest that supervised exercise is a beneficial addition to routine care of patients with esophageal cancer. Clinical trial information: NTR5045 .
Panel-based methodology for assessing the impact of public policies on cancer patients and survivors.
Authors: Farner Amy , Smith Tenbroeck , Fleury Mark
Published: May 2020

12059

Background: Cancer interventions are subject to a range of regulations, but data from large, nationally representative surveys are not always available in time to inform the policy process and do not always address issues specific to cancer patients and survivors. Understanding their experiences is critical to achieving policy solutions to issues such as access to effective pain relief, reducing unexpected medical bills, and reducing the impact of high prescription drug costs on treatment for lower income cancer patients. This research intended to better understand patient experiences and opinions in a statistically valid manner specifically targeted to the policy process. Methods: 3057 panelists were identified from ACS contacts, health systems, and social media advertising through ACS/ACS CAN pages and paid Facebook ads, to participate in a series of surveys across a year. The panel included diverse survivors across age, gender, race, ethnicity, economic status, and cancer type. Online surveys deployed semi-monthly on cancer survivorship topics impacted by current policy, including access to/affordability of care, pain treatment, and prescription drug costs. Responses were analyzed for the entire population and across subgroups of cancer survivors. Results: Each survey achieved a response rate between 35% and 50% of all panel members, resulting in a margin of error +/- 3% and 95% confidence level. Insights from cancer patient and survivor experiences helped support public policies through findings such as (but not limited to): 41% of those prescribed opioids had trouble getting their medicine, creating difficulty participating in work, family, or social events; extra trips to the doctor or pharmacy; negative impact on treatment, and trips to the Emergency Room due to uncontrolled pain; 24% received a surprise medical bill, increasing their anxiety, reducing likelihood to see a specialist, and reducing likelihood to seek emergency care during a serious health issue; and 31% of those with household income less than $30,000 report trouble affording prescription drugs and 17% have delayed or not filled a prescription due to cost. Findings supported the policy process by helping craft policy positions aligned with cancer patient preferences, raising public awareness, and communicating to policymakers the impact of policies on cancer. Conclusions: The panel methodology illustrates the impact of policy decisions on cancer patients and survivors. Findings provide an unprecedented level of input to the policy process for cancer patients and survivors.
Efficacy of ear acupuncture on sleep quality in breast cancer survivors: A randomized controlled trial.
Authors: Hoextermann Melanie Désirée , Buner Katja , Haller Heidemarie , Kohl Wiebke , Reinisch Mattea , Dobos Gustav , Cramer Holger , Voiss Petra
Published: May 2020

12066

Background: Among females, breast cancer is the most commonly diagnosed cancer worldwide. Sleep problems impair 40 to 70 % of breast cancer survivors. The aim of this randomized controlled trial was to evaluate the effect of ear acupuncture on sleep quality in breast cancer survivors. Methods: Fifty-two female breast cancer survivors (mean age 55.73 ± 8.10) were randomized to either 10 treatments of ear acupuncture within five weeks (N = 26) or to a single session of psycho-education and given an advice booklet concerning insomnia (N = 26). Both interventions were delivered in a group setting. Primary outcome was sleep quality (measured by the Pittsburgh Sleep Quality Index) at week 5 corrected for treatment expectancies. Secondary outcomes were inflammation parameters (interleukin-6) at week 5, sleep quality at week 17, and stress, anxiety, depressive symptoms, quality of life and fatigue 5 weeks and 17 weeks after randomization. Results: Intention-to-treat analysis showed a significantly stronger increase of sleep quality in the ear acupuncture group compared to the psycho-education group ( p= .031; d = 0.64) at week 5. Furthermore, ear acupuncture improved stress ( p= .030; d = 0.64), anxiety ( p = .001; d = 0.97), and fatigue ( p = .012; d = 0.75) at week 5 compared to psycho-education. No significant group difference was found on any outcome at week 17. No serious adverse events occurred during the study period. Conclusions: Group ear acupuncture may be a helpful intervention in tackling sleep problems in breast cancer survivors in the short term and may reduce stress, anxiety and fatigue as well. Long-term effects remain questionable. Clinical trial information: NCT03874598 .
Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function.
Authors: Khoury Katia , Barac Ana , Lynce Filipa , Geng Xue , Dang Chau T. , Yu Anthony Francis , Smith Karen L. , Gallagher Christopher , Pohlmann Paula Raffin , Nunes Raquel , Herbolsheimer Pia Maarit , Warren Robert D. , Srichai M. Barbara , Hofmeyer Mark , Asch Federico M , Tan Ming Tony , Isaacs Claudine , Swain Sandra M.
Published: May 2020

12069

Background: HER2-targeted therapies are associated with cardiotoxicity, mostly asymptomatic and reversible. The impact of withholding these therapies on breast cancer outcomes is unknown. SAFE-HEaRt trial was the first study to evaluate the safety of HER2-targeted agents in patients with reduced left ventricular ejection fraction (LVEF) receiving concomitant cardioprotective medications and close cardiac monitoring. We report the 3-year follow-up (f/u) results. Methods: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with asymptomatic LVEF 40-49%, were started on beta blockers (ß-blockers) and/or ACE inhibitors/ARBs, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. Results: Patients were accrued from 10/2013 to 12/2017 and median f/u as of 2/7/20 is 37 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. 24 patients were reconsented for long-term f/u. There were 23 evaluable patients (1 lost for f/u). Off study, 2 patients continued treatment with trastuzumab, 3 with trastuzumab and pertuzumab, and 3 with TDM-1 for metastatic disease. 1 of the 2 patients who had developed a CE with symptomatic heart failure (HF) died of progressive oncological disease, and the second had LVEF recovery on cardiac medications after completion of adjuvant HER2-targeted therapy. Almost 5 years later, she had an asymptomatic decline in her LVEF to 35% after deciding to stop her ß-blocker and ARB. Of the remaining 21 patients, 15 had recovery of their LVEF to ≥50%, 9 of whom remain on cardiac medications. 5 patients had stable LVEF 40-49% and remain asymptomatic on cardiac medications. Only 1 patient had symptoms suggestive of HF, with last documented LVEF stable at 45-50%, but she has not sought medical care for the last 15 months since relocating to another country. There were no new CE and no cardiac deaths. Mean LVEF was 45% at baseline, 46% at end of treatment, and 51.5% at long term f/u. Conclusions: Long-term f/u of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is essential for improved patient outcomes. Clinical trial information: NCT04143594 .
Frequency and prediction of non-medical opioid use behaviors (NMOU) among advanced cancer patients referred to a supportive care center (SCC).
Authors: Yennu Sriram , Arthur Joseph Anthony , Reddy Suresh , Edwards Tonya , Lu Zhanni , Rozman de moraes Aline , Wilson Susamma M , Erdogan Elif , Joy Manju P , Ethridge Shirley Darlene , Kuriakose Leela , Malik Jimi S. , Najera John M , Rashid Saima , Qian Yu , Kubiak Michal J , Nguyen Kristy , Wu Jimin , Hui David , Bruera Eduardo
Published: May 2020

12086

Background: One of the methodological barriers to conducting research on interventions for NOMU (Aberrant Opioid Use Behaviors) among cancer patients is the lack of data on the frequency of this problem. Although the frequency of risk factors has been established by our group and others, not all the patients with risk factors will be diagnosed with having NMOU behaviors, and some patients with no previous risk factors will engage in NMOU. AIM: To characterize the overall frequency of NMOU for a duration of 3 months, as well independent predictors for NMOU. Methods: In this retrospective study, 1558 consecutive patients referred to supportive care clinic (SCC) from 3/18/2016 to 6/6/2018 were reviewed for development of NMOU using established diagnostic criteria. Patients were eligible if they were ≥18 years, had a diagnosis of cancer, and were on opioids for pain for at least a week. All patients were assessed with the Edmonton Symptom Assessment Scale (ESAS), SOAPP-14, and CAGE-AID. Descriptive statistics, spearman correlation coefficient, multivariate analysis were performed. Results: 299 patients (19%) had ≥1 NMOU behavior. The median (IQR) NMOU behavior was 1 (1-2); range 1-10. Most NMOU occurred at 1st and 2nd follow up visits. The most frequent NMOU behavior was unscheduled clinic visit for inappropriate refills. 29/299 (10%) NMOU patients received specialized care for high-risk for aberrant opioid misuse by interdisciplinary team. Results of multivariate logistic regression model showed Marital status (Divorced vs. Married, OR=1.47, 95% CI: 0.98, 2.22, p=0.654 (marginally significant); Single vs. Married, OR=1.68, 95% CI: 1.15, 2.46, p=0.0079), SOAPP (Positive vs. Negative, OR=1.42, 95% CI: 1.05, 1.93, p=0.0238), morphine equivalent daily dose (MEDD) (OR=1.004, 95% CI: (1.003, 1.006), p<0.0001) and ESAS pain (OR=1.11, 95% CI: 1.06, 1.17, p<0.0001) were independently associated with the presence of NMOU during follow-up visits. Conclusions: 19% cancer patients followed at SCC had detectable NMOU behaviors. Being single, SOAPP+, pain severity and high MEDD were independent predictors for NMOU. This information will assist clinicians and investigators designing clinical and research programs in this important field.
Feasibility of olanzapine at reduced dose in highly emetogenic chemotherapy: A randomised controlled trial against aprepitant in triple therapy (FORESIGHT).
Authors: Chen Michelle , Baron Isabelle , Beaulieu Stephanie , Dufour Annick , Letarte Nathalie , Prady Catherine C. M.
Published: May 2020

12087

Background: Olanzapine is used as an adjunct antiemetic in oncology as salvage therapy and in four-drug prophylaxis. Growing literature supports its effectiveness in initial three-drug prophylaxis in highly emetogenic chemotherapy (HEC). Methods: This prospective, multi-centre, open-label study evaluated the feasibility of a large-scale randomized controlled trial comparing the effectiveness and tolerability of 5 mg olanzapine once daily for four days (starting the night before chemotherapy) versus standard dose aprepitant (in tritherapy with standard ondansetron and dexamethasone) in treatment-naive patients receiving the first cycle of a HEC. Secondary outcomes included: complete response (no nausea, no emesis, no use of rescue medication), complete remission (no emesis, no rescue medication), intensity of patient-reported nausea and emesis on a visual analog scale, quality of life (scored with the Functional Living Index Emesis [FLIE]), and incidence of adverse events. Results: We randomized 30 patients in an intent-to-treat analysis. The large-scale trial was deemed not feasible without support from a research centre. Complete response rates were significantly higher in the olanzapine group in the delayed phase (24-120h post-chemotherapy) (86,7% v 21,4%, p < 0,001) and overall phase (0-120h post-chemotherapy) (60,0% v 21,4%, p = 0,04). Similar results were observed for complete remission. Intensity of patient-reported nausea was significantly lower in the olanzapine group in the delayed phase (p = 0,001). FLIE scores were significantly lower for the nausea domain (mean 62,3 v 60,9, p = 0,004) and overall score (124,3 v 108,8, p = 0,006). Depression on the ESAS-R was more common in the aprepitant group (0% v 38%, p = 0,01). Other adverse events were not significantly different. Conclusions: Support from a research centre must be ensured for study feasibility. Tritherapy olanzapine significantly improved complete response and remission in the delayed and overall phases post-chemotherapy among patients receiving HEC. It was also associated with higher quality of life and a reassuring safety profile. This feasibility trial, despite its small sample size, is one of the first prospective randomised trials to suggest similar efficacy of 5 mg olanzapine to aprepitant and to measure a difference in patient quality of life with this regimen. Clinical trial information: NCT04075955 .
A community oncology palliative care program: Pain-related inpatient utilization in oncology care model (OCM) patients.
Authors: Akhtar Adil Jamal , Margolis Jeffrey H. , Sheth Karna , Muskovitz Andrew A. , Maxwell Karma , Zekman Richard Philip , Howard George , Qamruzzaman Yusuf , Balaraman Savitha , Ballouz Samer , Ibrahim Mohammed , Folbe Mitchell , Ogaily Mohammed S. , Stortz Lexi , Fabbiano Maria , Pancholi Shehnaz , Tauquir Anoosha Maria
Published: May 2020

12094

Background: Oncology Division of Michigan Health Professionals (MHP) participates in OCM. A comprehensive community oncology program for early and timely involvement of palliative care (PC) was launched in September 2017 to help achieve the OCM program goals of high-quality, cost-effective, coordinated care. PC provides a single point of care for all-cause pain management. PC program included pre-program training and continuous education for early and timely involvement of PC. This study aims to assess the educative effect of PC to reduce pain-related inpatient admissions (Pain IP) in all MHP OCM patients, irrespective of PC-referral. Methods: This initiative was led by palliative care physicians and included continuous education and reinforcement of the benefits, every 2-4 weeks, by sharing PC outcomes data with MHP physicians. Physician feedback was part of the program enhancements that were regularly reviewed during monthly MHP physician meetings. Retrospective claims review was performed with OCM episodes from Oct 2016 – Mar 2019. Monthly Pain IP utilization (based on diagnosis code) per 1000 OCM patients (UPK) was analyzed within pre- and post- PC Program start (Sep 2017). Cost per Pain IP included mean of 30-day follow-up skilled nursing facility (SNF) stay and 30-day outpatient facility expenses. Monthly historical Pain IP (pre-PC UPK) was compared to post-PC Pain IP UPK to calculate OCM savings from PC education at MHP. Results: Pain IP peaked at 7.12 UPK in September 2017 when PC program training and education started, then fell as low as 0.87 UPK in January 2019. Unit cost per Pain IP was $12,473. Post-PC (Sep 2017 – Mar 2019), there were 40 fewer Pain IP admissions compared to Pre-PC Pain IP for a total cost savings of $498,920. Conclusions: After PC Program, Pain IP decreased in MHP OCM population (PC-referred and PC not referred). This trend suggests PC training and continuous education for OCM providers is reducing IP utilization. This also translated to a significant cost saving for OCM/Medicare of $498,920. Study was limited by OCM claims available as of December 2019. Results may be refreshed as more data becomes available.
Antiemetic prophylaxis with NEPA: Final results of the German AKYPRO study.
Authors: Schilling Joerg Peter , Busch Steffi , Hielscher Carsten , Holländer Martin , Klenske Julia , Zahn Mark-Oliver , Karthaus Meinolf
Published: May 2020

12095

Background: NEPA is a fixed combination antiemetic of the NK1-receptor-antagonist (RA) netupitant and the 5-HT3-RA palonosetron. Primary objective of this prospective non-interventional study in Germany was to assess quality of life of cancer patients (pts) undergoing moderately (MEC) or highly (HEC) emetogenic chemotherapy (CT) who received NEPA for prophylaxis of nausea and vomiting (CINV). Secondary objectives were patient reported outcomes as well as effectiveness and safety of NEPA. Here we report final data of the quality of life analysis. Methods: The study included 2.405 pts in 162 centers receiving 3 consecutive cycles of CT as one or two day MEC or HEC. Primary endpoint was impact of quality of life (QoL) due to vomiting or nausea, documented by Functional Living Index–Emesis (FLIE) questionnaires. Effectiveness was reported in patient diaries. Complete response (CR) was defined as no emesis and no rescue medication (RM). Non-significant nausea (NSN) was no or mild nausea. Adverse events (AEs) were reported on d1–21 of each cycle. Results: 2.173 patients were included in the final analysis (full analysis set; FAS). The majority of patients (n = 1976; 91%) received 1-day chemotherapy, 64% HEC, 36% MEC. Median age was 58 years and the majority (85%) was female. Cancer diagnoses: breast 66%, gastrointestinal 10%, ovarian 7% or lung 5%, other 12%. Chemotherapy: AC 57%, carboplatin 19%, cisplatin 8%, oxaliplatin 8% and other 8%. 84% of pts with HEC and 82% with MEC felt no impact on daily life due to vomiting in cycle 1 remaining constant in C2 and C3. 54% HEC patients and 59% MEC patients reported no impact on daily life due to nausea in cycle 1. CR rates ranged between 81-84% and were comparable between different HEC or MEC. NSN rates in MEC ranged from 75% (MEC) to 62% (HEC). Drug-related AEs were rare with constipation, fatigue, insomnia, and nausea as the most common (in > 1% pts). Conclusions: NEPA was highly effective in the prevention of CINV and maintenance of QoL in this real world study. Over 80% of pts reported that their daily live was not influenced by emesis while nausea was more difficult to control. Effectiveness was high and patients and physicians estimate was comparable.
The impact of the use of opioids among older breast cancer survivors and adverse events.
Authors: Winn Aaron N , Check Devon , Fergestrom Nicole , Neuner Joan Marie , Roberts Andrew
Published: May 2020

12098

Background: Older adults and cancer survivors are underrepresented in the literature underpinning recent opioid prescribing guidelines. As prevention of unnecessary persistent opioid use and inadvertent opioid-related harms gains importance in clinical practice, it is necessary to fully capture the risks of opioid related adverse events among patients with cancer pain. The objective of this study was to determine the association between opioid use after cancer diagnosis and comprehensive opioid-related adverse events among older adult breast cancer survivors. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results tumor registry data linked with Medicare administrative claims data from 2007-2016 of women with newly diagnosed non-metastatic breast cancer. The study observation period was the year following a patient’s end of active cancer treatment. The primary exposure was a daily measure of opioid exposure based on Part D prescription claims. The primary outcomes were daily indicators of all-cause hospitalization, substance use event and a composite of other opioid-related adverse events (infections, gastrointestinal events, falls/fractures, cardiovascular events) and each component of the composite adverse event. We estimated the association of current opioid use and the immediate risk of an outcome event the following day using modified Poisson generalized estimating equation models. We adjusted for patient demographics, cancer characteristics and cancer treatments received. Results: We found that opioid exposure more than doubled the immediate risk of all-cause hospitalization (aRR = 2.77; 95%CI = 2.57, 2.99; p < 0.001) and having a composite adverse event (aRR = 2.50; 95%CI = 2.18, 2.87; p < 0.001) and dramatically increases the immediate risk of a substance use event (aRR = 14.26; 95%CI = 7.11, 28.59; p < 0.001). We find consistent results when looking at individual components of the composite adverse event measure. Conclusions: Older adult breast cancer survivors with continued prescription opioid use in the year after completing active cancer treatment experienced an immediate increased risk of all-cause hospitalization, substance use events, and myriad opioid-related adverse effects.
Validity of patient-reported outcomes to describe the symptom experience of patients enrolled on phase I clinical trials.
Authors: Sedhom Ramy , Ferrell Betty R. , Ruel Nora , Koczywas Marianna , Chung Vincent , Smith Thomas J.
Published: May 2020

12107

Background: Symptoms are common among patients enrolled in phase I trials. To integrate the patient perspective, the National Cancer Institute developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic adverse events (AEs) directly from patients; however, the tool has not been used often in early phase trials or in palliative care studies. Our overall objective was to assess the validity of PRO-CTCAE items to previously validated assessments of quality of life (FACT-G) and psychological distress (Distress Thermometer). We utilized data from a randomized trial testing a palliative care intervention for patients with cancer enrolled on phase I trials. Methods: Patients (n = 481) were accrued to the parent study prior to initiating a Phase I clinical trial with data collected at baseline, 4, and 12 weeks. We determined the correlation of PRO-CTCAE with Distress Level, FACT-G total and subscale domain scores. Aggregate scores using PRO-CTCAE were calculated to explore the effect of overall symptom frequency, severity, and interference by calculating the total of all scored items classified within each of those domains. We used these metrics to identify associations between this and other validated tools. Results: Patients were predominantly female (56.8%), over age 60, and 30.7% were minority populations. Correlations between PRO-CTCAE items and corresponding FACT-G (total and subscales) and Distress levels reached statistical significance for all items (p < 0.001). Importantly, many of symptoms captured would have been missed using HRQOL assessment tools. Some of these symptoms affected nearly 50% of patients and were frequently rated as severe or very severe. The correlation coefficient for Distress Level for all PRO-CTCAE items was small to moderate (Pearson r = 0.33 to 0.46). Pearson’s correlation coefficient for FACT-G total was moderate ( r = -0.45 to -0.69). Mood items of the PRO-CTCAE had stronger associations (Pearson r > 0.5). PRO-CTCAE symptom interference scores had the strongest correlation with Distress (Pearson r = 0.46) and FACT-G Total (Pearson r = -0.69). Conclusions: Patients entering Phase I trials are willing to report on symptoms they experience as a result of advancing disease and adverse effects from experimental treatment. Evidence demonstrates favorable validity of PRO-CTCAE in a heterogeneous US sample of patients undergoing cancer treatment on phase I trials. The granular assessment of symptomatic AEs may be on increasing importance as we enter a new therapeutic era in oncology. Clinical trial information: NCT01828775 .
Relationship between caregiver burden and psychological distress among stem cell transplant (SCT) recipients prior to transplant.
Authors: Topping Carlisle , Nelson Ashley , Jacobs Jamie M. , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej
Published: May 2020

12120

Background: SCT is a potentially curative therapy for patients with hematologic malignancies that involves prolonged hospitalization, intensive follow-up, and a considerable risk of morbidity and mortality. Family and friends caring for SCT recipients experience substantial caregiving burden as they prepare for SCT. Previous research demonstrates caregiver distress is highest pre-transplant and is comparable to or higher than patient-reported distress. However, the extent of this distress and its relationship to certain domains of quality of life (QOL) and caregiving burden is currently unknown. Methods: We conducted a secondary analysis of cross-sectional data from two supportive care studies focused on caregivers of SCT recipients. Caregivers completed the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology QOL questionnaire to assess their psychological distress and QOL prior to SCT. Scores >8 on the HADS anxiety and depression subscales indicated clinically significant symptoms. We selected eight domains from the CareGiver Oncology QOL questionnaire including social support, physical wellbeing, self-efficacy, coping, leisure time, financial stability, private life concerns, and caregiving burden. Multivariate regression models adjusted for age, sex, caregiver relationship, and SCT type were used to examine associations between these domains and caregivers’ anxiety and depression symptoms. Results: A total of 193 caregivers (age M= 57 years, 70% female, 52% allogeneic transplant) were enrolled with a majority caring for their spouse (80%), parent (8%) or child (5%). Overall 47% and 16% of caregivers reported clinically significant anxiety and depression symptoms, respectively. Low social support, physical well-being, coping and leisure time as well as high caregiver burden, private life concerns and financial distress were associated with both caregiver anxiety and depression symptoms (p < .05). Low self-efficacy was associated with higher anxiety symptoms (p < .05). Conclusions: Caregivers of SCT recipients experience substantial anxiety and depression symptoms prior to SCT. Impairments across multiple QOL domains are associated with caregiver’s psychological distress. Psychosocial interventions designed to improve coping, reduce caregiving burden, and enhance QOL are needed for caregivers prior to transplant.
Tumor/normal genomic profiling in patients with metastatic solid tumors identifies pathogenic germline variants of therapeutic importance.
Authors: Cobain Erin Frances , Jacobs Michelle , Wu Yi-Mi , Robinson Dan R. , Vats Pankaj , Chugh Rashmi , Talpaz Moshe , Stoffel Elena Martinez , Chinnaiyan Arul
Published: May 2020

1501

Background: Tumor molecular profiling via next-generation sequencing (NGS) is routinely utilized to direct patients toward clinical trials of targeted therapeutics. NGS testing of paired tumor/normal samples identifies incidental pathogenic germline variants (PGVs), having potential implications for patients and their families. Methods: From 2011-2018, 1,015 patients with metastatic, refractory solid tumors underwent targeted (1700 genes) exome and transcriptome sequencing of matched tumor/normal samples through the Michigan Oncology Sequencing program. Identified PGVs that conferred increased cancer risk or were associated with certain autosomal recessive conditions were reported to the treating oncologist. Chart reviews were conducted every 3 months to assess whether PGV identification impacted treatment decision making. Results: 169 PGVs were identified in 160 unique patients (15.8% of cohort). 69 PGVs (41%) harbored a clear somatic second hit event in the tumor. PGVs associated with defects in double-strand DNA repair ( BRCA1, BRCA2, ATM, PALB2, BRIP1) or DNA mismatch repair ( MLH1, MSH2 and PMS2) were identified in 49 patients (5% of cohort, 31% of patients with PGVs), 37 of which had not previously been identified. 14 PGVs in DNA double-strand repair and 7 PGVs in DNA mismatch repair were identified in cancer types not commonly associated with hereditary breast ovarian cancer or Lynch syndromes, including cancers of unknown primary origin and sarcomas. 7 patients received a PARP inhibitor (PARPi), 3 patients received an immune checkpoint inhibitor (ICI) and 1 patient received both PARPi and ICI therapy on the basis of a PGV in DNA repair. 6 patients achieved clinical benefit, defined as time on treatment ≥ 6 months. A patient with cancer of unknown primary origin and PGV in MSH2 achieved exceptional response to ICI therapy, with complete response ongoing and lasting 23 months. Conclusions: Targeted NGS of matched tumor/normal samples identified PGVs in about 1 in every 6 patients with metastatic solid tumors. Approximately 40% of PGVs are associated with a somatic second hit in the tumor, supporting their role in tumor pathogenesis. Unexpected PGVs with therapeutic implications are identified in patients with diverse cancer types, providing opportunities to use targeted therapies with potential for significant clinical benefit. Given this finding, testing for PGVs in DNA repair genes should be considered in all patients with metastatic solid tumor malignancies.
Results from MAGENTA: A national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk.
Authors: Swisher Elizabeth M. , Rayes Nadine , Bowen Deborah , Peterson Christine B , Coffin Tara , Norquist Barbara , Gavin Kathleen , Polinsky Deborah , Crase Jamie , Bakkum-Gamez Jamie Nadine , Blank Stephanie V. , Munsell Mark F , Nebgen Denise R , Pradeep Harsha , Law Sherman , Olopade Olufunmilayo I. , Zhou Alicia , Levine Douglas A. , D'Andrea Alan D. , Lu Karen H.
Published: May 2020

1506

Background: Hereditary breast and ovarian cancer (HBOC) is preventable when genetic risk is identified. We aimed to test whether pre and/or post-test genetic counseling is needed to optimally deliver online accessible genetic testing. Methods: MAGENTA (Making GENetic Testing Accessible) is a four-arm non-inferiority trial evaluating electronic genetic education and results delivery alone or combined with pre-test only, or post-test only telephone genetic counseling compared to mandatory pre- and post-test counseling (control arm) in women at risk of HBOC (NCT02993068). Regardless of assigned arm, all subjects with a pathogenic mutation received post-test telephone counseling. All subjects were enrolled electronically as part of either a family history cohort (FHC) or a cascade cohort (CC, known familial mutation). The primary outcome was cancer risk distress at 3 months and the trial was powered for the FHC. Secondary outcomes included completion of testing (i.e., received results), anxiety, depression, quality of life, and decisional regret, all measured by standardized scales. Results: Enrollment is complete and a total of 3,822 participants were randomized, 3,111 in FHC and 711 in CC. Participants were enrolled from all 50 states, but most were white/non-Hispanic (88%). Among participants that completed genetic testing, 173 (7.2%) had a mutation in a breast or ovarian cancer gene, with 114 (5.7%) of FHC and 59 (14.2%) of CC. In the primary intention-to-treat analysis of FHC, each of the three experimental arms was non-inferior to the control arm for distress at 3 months (p < 0.025/3 = 0.0083). In the CC, no and pre-test only counseling were also non-inferior (p < 0.025/3 = 0.0083). Distress was lowest in the arm with neither pre nor post-test counseling. Overall, 318 (18%) participants had very high distress at three month follow-up, and this rate was not significantly different across arms. Anxiety, depression and decisional regret did not have statistically significant differences across arms at follow-up. Test completion was highest in the no counseling arm (86.4%) and lowest in the control arm (60.6%). Conclusions: Electronic genetic education and results release without genetic counseling was non-inferior with regard to patient distress and was associated with higher test completion and lower distress. These results support use of a genetic testing paradigm providing individualized genetic counseling only for patients with positive test results. Clinical trial information: NCT02993068.
Smoking cessation (SC) and lung cancer (LC) outcomes: A survival benefit for recent-quitters? A pooled analysis of 34,649 International Lung Cancer Consortium (ILCCO) patients.
Authors: Fares Aline Fusco , Jiang Mei , Yang Ping , Christiani David C. , Chen Chu , Brennan Paul , Zhang Jie , Schwartz Ann G. , Landi Maria Teresa , Shiraishi Kouya , Ryan Brid M , Shen Hongbing , Schabath Matthew B. , Adonina Garcia , Shete Sanjay , Le Marchand Loic , Cox Angela , Hung Rayjean , Xu Wei , Liu Geoffrey
Published: May 2020

1512

Background: Tobacco smoking profoundly impacts LC risk; however, data are limited as to what extent SC prior to diagnosis impacts LC overall survival (OS) and lung cancer specific survival (LCSS). LC screening offers a possible teachable moment, but there is uncertainty of SC benefits after a lifetime of smoking. We use the ILCCO database to answer if SC prior to LC dx is associated with better OS and LCSS, considering time since smoking cessation (TSSC). Methods: Using individual data, analysis was performed on 17 ILCCO studies with available TSSC to estimate survival using univariable analysis and models of stage-adjusted and cumulative smoking-adjusted multivariable analysis. Adjusted Hazard Ratios (aHR) from Cox models, cubic spline smooth curves and Kaplan-Meier curves were created. Sensitivity analysis was performed for TSSC and LCSS on 13 studies. Results: Of 34649 patients, 14322 (41%) were current smokers 14273 (41%) ex-smokers and 6054 (18%) never smokers at diagnosis. We confirmed that ex-smokers (aHR 0.88 CI 0.86-0.91) and never smokers (aHR 0.76 CI 0.73-0.8) improved OS compared to current smokers. Amongst ex-smokers, < 2y TSSC (aHR 0.88 CI 0.82-0.94), 2-5y TSSC (aHR 0.83 CI 0.77-0.90) and > 5y TSSC (aHR 0.8 CI 0.76-0.84) had improved OS compared to CS. Sensitivity analysis showed a trend towards improved LCSS survival for < 2y TSSC (aHR 0.95 CI 0.86-1.05) and 2-5y TSSC (aHR 0.93 CI 0.83-1.04), whereas > 5y TSSC significantly improved LCSS by 15% (aHR 0.85 CI 0.78-0.92). To mimic the LC screening participants, in analysis of > 30 pack-years individuals, associations were strikingly strong: < 2y TSSC had improved OS by 14% (aHR 0.86 CI 0.80-0.93); 2-5y TSSC by 17% (aHR 0.83 CI 0.76-0.90); and > 5 TSSC by 22% (aHR 0.78 CI 0.74-0.83), compared to current smokers; for < 30 packs-years, a trend towards better OS was observed for < 2y TSSC (aHR 0.95 CI 0.92-1.02) and 2-5y TSSC (aHR 0.86 CI 0.74-1.01), whereas > 5y TSSC improved OS by 23% (aHR 0.77 CI 0.72-0.82). Conclusions: Among ex-smokers, the risk of overall death was reduced by 12% on < 2y TSSC, 17% on 2-5y TSSC and 20% > 5y TSSC, whereas for LCSS, the benefit was significant only for > 5y TSCC, compared to current smokers at time of diagnosis. Here we demonstrate that convincing screening participants to quit smoking at any point of their trajectory, even just prior to dx such as < 2y TSSC, improved OS, and LCSS benefit was present beyond 5y of quitting. These relationships are independent of pack-years, age, across all stages and other prognostic variables.
Genetic counseling referrals after next generation sequencing testing.
Authors: Gonzalez Rafael , Ryan Emma , Watson Catherine , Broadwater Gloria , Kauff Noah D. , Havrilesky Laura J , Berchuck Andrew , Strickler John H. , Castellar Edgardo , Menendez Carolyn S. , Green Michelle , Strickland Kyle C , Previs Rebecca A.
Published: May 2020

1515

Background: Next generation sequencing (NGS) testing of tumor tissue or blood is performed to identify ‘actionable’ mutations that might guide patient care. NGS testing might incidentally identify germline mutations associated with cancer syndromes. No distinction is made between germline and somatic alterations on NGS reports, thus confirmatory germline testing is required. In this quality improvement (QI) initiative, we evaluated the frequency of referrals to genetic counseling (GC) for patients with potentially heritable germline mutations identified through NGS testing. Methods: We generated a list of high-risk mutations (HRMs) which merit GC referral based on NCCN guidelines. NGS test results for 3,400 consecutive patients with solid tumor malignancies were reviewed by the molecular tumor board from 1/2014-9/2019 and were screened for pathogenic HRMs. Basic demographic, oncologic, and GC data were retrospectively abstracted for each patient. The outcomes of interest were the frequency of HRMs identified through NGS testing, the proportion of patients subsequently referred to GC, and the proportion of patients ultimately diagnosed with a hereditary cancer syndrome. Results: 472 individual patients (14%) had NGS testing with one or more HRM identified; 465 patients were evaluable which corresponded to 519 HRMs that were included in the analysis (Table). Malignancies included were gastrointestinal 199 (42.8%), lung 83 (17.8%), genitourinary/renal 56 (12.0%), breast 49 (10.5%), gynecologic 35 (7.5%), and other 43 (9.2%). 75 (16.1%) patients had germline testing prior to NGS testing. Of those patients without prior germline genetic testing, 62 (15.9%) were referred to GC, and 19 (4.9%) patients were diagnosed with a hereditary cancer syndrome. Conclusions: Tumor NGS testing identifies HRMs that may represent an undiagnosed heritable germline mutation. Providers ordering NGS tests should review results for HRMs, refer to GC when appropriate, and offer confirmatory germline testing for patients and their families. [Table: see text]
Deep learning to identify high-risk smokers for lung cancer screening from chest radiographs.
Authors: Raghu Vineet , Mayrhofer Thomas , Aerts Hugo , Hoffmann Udo , Lu Michael T
Published: May 2020

1519

Background: Appearance on chest radiography may inform selection of high-risk smokers for lung cancer screening CT, beyond Centers for Medicare & Medicaid Services (CMS) eligibility criteria. Methods: A convolutional neural network (CXR-LC) predicting 12-year incident lung cancer from the chest radiograph image, age, sex, and smoking status (current/former) was developed in 41,856 persons aged 55-74 from the Prostate, Lung, Colorectal & Ovarian trial (PLCO). The final model was tested in held-out smokers from PLCO (n=5,615, 37.9% CMS eligible, 12-year follow-up), and externally in the National Lung Screening Trial (NLST, n=5,493, all CMS eligible, 6-year follow-up). Sensitivity was compared at a fixed screening population size defined by CMS eligibility. Ordinal CXR-LC risk score (low/indeterminate/high/very high) was based on development dataset 12-year probability thresholds (<2%/2-<3.3%/3.3-<8%/≥8%). Results are provided in test datasets only. Results: In the PLCO test dataset, CXR-LC was more sensitive than CMS eligibility at a fixed screening population size (74.9% vs. 63.8%, p=0.01) and missed 30.8% fewer lung cancers. CXR-LC risk groups were associated with incident lung cancer in PLCO test dataset smokers (very high vs. low CXR-LC risk: 12.4 vs 1.1 lung cancers/1,000 person-years) with external testing in NLST (all CMS eligible: 12.7 vs 2.3) (Table). This association was robust to adjustment for radiologist findings and the PLCOm2012 risk score. Conclusions: CXR-LC identified smokers at high risk of incident lung cancer, beyond CMS eligibility. [Table: see text]
Comparing and assessing the reported penetrance of cancer susceptibility genes for breast cancer.
Authors: Yin Kanhua , Braun Danielle , Tiwari Ankur , Wang Jin , Singh Preeti , Zhou Jingan , Parmigiani Giovanni , Hughes Kevin S.
Published: May 2020

1520

Background: It is critical for oncologists to be aware of unbiased and interpretable cancer risks (i.e., penetrance) in carriers with germline pathogenic variants in cancer susceptibility genes. However, relevant literature is large and varies significantly in study design, patient ascertainment, and types of risk estimates reported. This heterogeneity can cause inconsistent conclusions between studies and create barriers for clinicians to understand and apply them in practice. To further understand the current literature, we assessed penetrance studies associated with non-BRCA breast cancer susceptibility genes based on study design and ascertainment adjustment. Methods: We used a validated natural language processing-based abstract classifier to identify all penetrance studies regarding eleven genes: ATM, BARD1, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11, and TP53. Relevant studies were then manually annotated as “with ascertainment adjustment” if a study was based on: (1) a general population; (2) a pedigree analysis or a family-based study with appropriate ascertainment adjustment; or (3) a hospital-based study or a panel testing analysis with well-matched cases and controls. Results: A total of 49 penetrance studies were identified, with a median of nine studies for each gene (range: 4-16). The case-control study was the dominant study type, accounting for over 80% in five genes, 50% in two genes, and 18% to 43% in the other four genes. The proportion of studies with ascertainment adjustment was generally low (mean: 33%) and varied widely between different genes (7% to 80%). Contradictory breast cancer risks (no increased risk vs. significantly increased risk) were found in eight genes (73%) (Table). The most common ascertainment bias identified was a case-control study with cases (patients) who had a strong family history but using general population controls. Conclusions: Ascertainment bias is common in penetrance studies, but few studies adjust for it appropriately. Clinicians should be aware of this issue, and new methods are warranted to select unbiased risk estimates, synthesize them, and provide the accurate general-population penetrance. [Table: see text]
BRCA testing concordance with national guidelines for patients with breast cancer in community cancer programs.
Authors: Boehmer Leigh , Shivakumar Latha , Weldon Christine B. , Trosman Julia Rachel , Cohen Stephanie A. , Nixon Dawn , Ali-Khan Catts Zohra , Miesfeldt Susan , Wiryaman Stephanie , Tafra Lorraine , Muto Lisa , Fadrowski Natalie , Hulvat Melissa , Pallister Tiana , Shelton Charles Hendrix
Published: May 2020

1526

Background: Current National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment state that testing for highly penetrant breast/ovarian cancer genes is clinically indicated for women with early onset (≤ 45 years) or metastatic HER-2 negative breast cancer. A recent Association of Community Cancer Centers (ACCC) survey (N = 95) showed that > 80% of respondents reported ≤ 50% testing rate of patients with breast cancer who met guidelines. Given this disconnect, ACCC partnered with 15 community cancer programs to assess practice gaps and support interventions to improve access to genetic counseling (GC)/testing. Methods: Pre-intervention data from 9/15 partner programs for women diagnosed with stages 0-III breast cancer between 01/01/2017 and 06/30/2019 was collected. De-identified variables included: family history documentation, GC appointment/test results, and timing of results relative to treatment decisions. Results: There were 2691 women with stages 0-III breast cancer. Forty-eight percent (1284/2691) had a documented high-risk family history, 57% (729/1284) of whom had a GC appointment. This was a significantly higher rate of GC compared to the 23% (181/778) of women with no family history and 6% (35/629) of women with no documentation of family history (p < 0.0001). Patients ≤ 45 years old attended a GC appointment 72% (199/278) of the time and 49% (135/278) had genetic test results, with 84% (113/135) receiving results before surgery. For women with test results available before surgery, 37% (119/322) had breast conserving surgery, compared to 60% (144/240) with test results disclosed post-operatively (p < 0.0001). Conclusions: Genetic testing is underutilized in a community cohort of women with breast cancer. Further analysis is needed to understand the impact genetic test results have on surgical decisions. Opportunities exist to improve current rates of appropriate GC/testing. ACCC will share results of quality improvement projects to illuminate which strategies hold promise in reducing the hereditary breast cancer GC/testing practice gap.