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PURPOSE Women have more adverse events (AEs) from chemotherapy than men, but few studies have investigated sex differences in immune or targeted therapies. We examined AEs by sex across different treatment domains. METHODS We analyzed treatment-related AEs by sex in SWOG phase II and III clinical trials conducted between 1980 and 2019, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events. Symptomatic AEs were defined as those aligned with the National Cancer Institute's Patient-Reported Outcome–Common Terminology Criteria for Adverse Events; laboratory-based or observable/measurable AEs were designated as objective (hematologic v nonhematologic). Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 14 objective AE categories were examined. RESULTS In total, N = 23,296 patients (women, 8,838 [37.9%]; men, 14,458 [62.1%]) from 202 trials experiencing 274,688 AEs were analyzed; 17,417 received chemotherapy, 2,319 received immunotherapy, and 3,560 received targeted therapy. Overall, 64.6% (n = 15,051) experienced one or more severe (grade ≥ 3) AEs. Women had a 34% increased risk of severe AEs compared with men (odds ratio [OR] = 1.34; 95% CI, 1.27 to 1.42; P < .001), including a 49% increased risk among those receiving immunotherapy (OR = 1.49; 95% CI, 1.24 to 1.78; P < .001). Women experienced an increased risk of severe symptomatic AEs among all treatments, especially immunotherapy (OR = 1.66; 95% CI, 1.37 to 2.01; P < .001). Women receiving chemotherapy or immunotherapy experienced increased severe hematologic AE. No statistically significant sex differences in risk of nonhematologic AEs were found. CONCLUSION The greater severity of both symptomatic AEs and hematologic AEs in women across multiple treatment modalities indicates that broad-based sex differences exist. This could be due to differences in AE reported, pharmacogenomics of drug metabolism/disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving immunotherapy, suggesting that studying AEs from these agents is a priority.

Background Immune checkpoint inhibitors (ICI) are increasingly used across multiple cancer types and stages and little is known about real-world outcomes. This study sought to determine healthcare utilization, costs, immune-related adverse events (irAEs), and all-cause mortality of single-agent versus combination ICI in the USA. Materials and methods This is a retrospective study conducted with 2016–2018 data from the HealthCore Integrated Research Database, consisting of commercial and Medicare-insured adult patients with a cancer diagnosis using ICI in the USA. Outcomes were healthcare utilization, costs, and irAEs (FDA-recognized and others) up to 1-year post-index between patients using ICI monotherapy (mono, PD-1/PD-L1 inhibitor) and combination therapy (combo, PD-1/PD-L1 with CTLA-4 inhibitors). Results In total, 9084 patients received monotherapy and 904 patients received combo therapy. Mean age 65 years for mono and 58 years for combo. Overall, the combo arm had higher rates of FDA-recognized irAEs (67.4% vs. 45.9%), especially endocrinopathies (27.7% vs 14.7%) and dermatitis (25.9% vs. 12.4%). All-cause mortality over 1-year follow-up was similar, 30.7% in mono vs 30.8% in combo arms. The combo group had higher rates of all-cause inpatient hospitalizations (55.4% mono vs 65.6% combo) and emergency department (ED) visits (33.7% mono vs 41.4% combo). IrAE-related hospitalizations were higher in combo (55.2% vs 42.1%). IrAE-related ED visits were 15.7% mono vs 22.7% combo. This increased toxicity and health care utilization was reflected in significant differences in healthcare costs. Stark differences were seen in all-cause medical costs as well as costs related to inpatient and ED utilization and costs attributed to irAEs. Conclusions Higher rates of irAEs, healthcare utilization, and costs occur with combination immunotherapy. As further indications are approved for combination ICI, our study highlights the real-world tradeoffs involved with combination therapy regarding burdens of toxicity and increased healthcare utilization.

BackgroundLow-value services are common in cancer care. The onset of the COVID-19 pandemic caused a dramatic decrease in health care utilization, leading many to suspect that low-value cancer services may decrease.MethodsIn this retrospective cohort study, we used administrative claims from the HealthCore Integrated Research Environment, a repository of medical and pharmacy data from US health plans representing over 80 million members, to identify 204,581 patients diagnosed with breast, colorectal, and/or lung cancer between January 1, 2015, and March 31, 2021. We used linear probability models to investigate the relation between the onset of COVID-19 pandemic and 5 guideline-based metrics of low-value cancer care: 1) Positron Emission Tomography/Computed Tomography (PET/CT) instead of conventional CT imaging for initial staging; 2) conventional fractionation instead of hypofractionation for early-stage breast cancer; 3) non-guideline-based antiemetic use for minimal-, low-, or moderate-to-high-risk chemotherapies; 4) off-pathway systemic therapy; and 5) aggressive end-of-life care.ResultsAmong 204,581 patients, the mean [SD] age was 63.1 [13.2], 68.1% were female, 83,593 (40.8%) had breast cancer, 56,373 (27.5%) had colon cancer, and 64,615 (31.5%) had lung cancer. Rates of low-value cancer services did not exhibit meaningful declines during the pandemic: PET/CT imaging, adjusted percentage point difference 1.87 (95% CI −0.13 to 3.87); conventional radiotherapy, adjusted percentage point difference 3.93 (95% CI 1.50 to 6.36); off-pathway systemic therapy, adjusted percentage point difference 0.82 (95% CI −0.62 to 2.25); non-guideline-based antiemetics, adjusted percentage point difference −3.62 (95% CI −4.97 to −2.27); aggressive end-of-life care, adjusted percentage point difference 2.71 (95% CI −0.59 to 6.02).DiscussionLow-value cancer care remained prevalent through the pandemic. Policymakers should consider changes to payment and incentive design to turn the tide toward higher-value cancer care.

PURPOSE: The integration of pharmacies with oncology practices—known as medically integrated dispensing or in-office dispensing—could improve care coordination but may incentivize overprescribing or inappropriate prescribing. Because little is known about this emerging phenomenon, we analyzed historical trends in medically integrated dispensing. METHODS: Annual IQVIA data on oncologists were linked to 2010-2019 National Council for Prescription Drug Programs pharmacy data; data on commercially insured patients diagnosed with any of six common cancer types; and summary data on providers' Medicare billing. We calculated the national prevalence of medically integrated dispensing among community and hospital-based oncologists. We also analyzed the characteristics of the oncologists and patients affected by this care model. RESULTS: Between 2010 and 2019, the percentage of oncologists in practices with medically integrated dispensing increased from 12.8% to 32.1%. The share of community oncologists in dispensing practices increased from 7.6% to 28.3%, whereas the share of hospital-based oncologists in dispensing practices increased from 18.3% to 33.4%. Rates of medically integrated dispensing varied considerably across states. Oncologists who dispensed had higher patient volumes ( P < .001) and a smaller share of Medicare beneficiaries ( P < .001) than physicians who did not dispense. Patients treated by dispensing oncologists had higher risk and comorbidity scores ( P < .001) and lived in areas with a higher % Black population ( P < .001) than patients treated by nondispensing oncologists. CONCLUSION: Medically integrated dispensing has increased significantly among oncology practices over the past 10 years. The reach, clinical impact, and economic implications of medically integrated dispensing should be evaluated on an ongoing basis.

ImportancePayers use oncology clinical pathways programs to increase evidence-based drug prescribing and control drug spending. However, compliance with these programs has been low, which may decrease their efficacy, and factors associated with pathway compliance are unknown.ObjectiveTo determine extent of pathway compliance and identify factors associated with pathway compliance using characteristics of patients, practices, and the companies that develop cancer treatment pathways.Design, Setting, and ParticipantsThis cohort study comprised patients with claims and administrative data from a national insurer and a pathways health care professional between July 1, 2018, and October 31, 2021. Adult patients with metastatic breast, lung, colorectal, pancreatic, melanoma, kidney, bladder, gastric, and uterine cancer being treated in the first line were included. Six months of continuous insurance coverage prior to the date of treatment initiation was required for determination of baseline characteristics. Stepwise logistic regression was used to identify factors associated with pathway compliance.Main Outcomes and MeasuresUse of a pathway program–endorsed treatment regimen in the first-line setting for metastatic cancer.ResultsAmong 17 293 patients (mean [SD] age, 60.7 [11.2] years; 9183 [53.1%] women; mean [SD] Black patients per census block, 0.10 [0.20]), 11 071 patients (64.0%) were on-pathway, and 6222 (36.0%) were off-pathway. Factors associated with increased pathway compliance were higher health care utilization during the 6-month baseline period (measured in inpatient visits and emergency department visits) (5220 on-pathway inpatient visits [47.2%] vs 2797 off-pathway [45.0%]; emergency department visits, 3304 [27.1%] vs 1503 [24.2%]; adjusted odds ratio [aOR] for inpatient visits, 1.32; 95% CI, 1.22-1.43; P P = .002), and practice participation in the Oncology Care Model (on-pathway participation, 2601 [23.5%] vs 1305 [21.0%]; aOR, 1.13; 95% CI, 1.04-1.23; P = .004). Higher total medical cost during the 6-month baseline period were associated with decreased pathway compliance (mean [SD] costs: on-pathway, $55 990 [$69 706] vs $65 955 [$74 678]; aOR, 0.86; 95% CI, 0.83-0.88; P Conclusions and RelevanceIn this cohort study, despite generous financial incentives, compliance with payer-led pathways remained at historically reported low rates. Factors such as increasing exposure to the program due to the number of patients impacted and participation in other value-based payment programs, such as the Oncology Care Model, were positively associated with compliance; factors such as the type of cancer and patient complexity may have played a role, but the directionality of potential effects was unclear.

Background: Taxanes play an important role in the treatment of early-stage breast cancer. Chemotherapy induced peripheral neuropathy (CIPN) is a complication of taxane therapy and can lead to treatment dose reduction or discontinuation, which may ultimately affect overall survival, and can substantially impact quality of life and functional status in survivors. The trajectory of CIPN symptoms is not well described. Methods: SWOG S1714 enrolled participants 18 years or older with Stage I-III primary non-small cell lung, primary breast, or primary ovarian/fallopian tube/peritoneal cancer starting treatment with a taxane-based regimen. Participants with baseline neuropathy were eligible to enroll. Neuropathy was assessed with the patient-reported European Organization for Research and Treatment of Cancer QLQ-CIPN20 (CIPN-20). The occurrence of clinically meaningful sensory neuropathy was defined as an increase of 8 or more points (on a 0-100 scale, with a higher score indicating more severe symptoms) between baseline and follow-up in the sensory neuropathy subscale of the CIPN-20. Assessments occurred at baseline and at 4, 8, and 12 weeks +/- 14 days and 24, 52, 104, and 156 weeks +/- 28 days after registration. Results: Among N=1336 enrolled participants, 1321 were eligible (99%). Of the eligible participants, we will report on the 1198 (90.7%) with breast cancer. The median age was 55 years (range 23-84) and 99.3% were female. The breast cancer cohort included 72.2% White, 11.7% Black, 4.9% Asian, and 11.0% Hispanic/Latino participants. Paclitaxel (every week for 12 weeks or every 2 weeks for 8 weeks) was administered to 56.2% and docetaxel (every 3 weeks for 12-18 weeks) to 43.8%. The mean baseline patient-reported CIPN-20 sensory neuropathy subscale score was 6.2 (standard deviation 12.0). Through one full year of follow up, 1084 participants (90.5%) were evaluable for sensory neuropathy at any time point. At individual assessment times, clinically meaningful sensory neuropathy was reported by 18.7% of participants at week 4, 33.0% at week 8, 46.3% at week 12, 44.8% at week 24, and 47.4% at week 52. Clinically meaningful sensory neuropathy at one or more assessments was reported by 67.8% of participants. Conclusions: In this large prospective cohort of racially/ethnically diverse participants with breast cancer receiving taxane-based therapy, 2 out of every 3 experienced clinically meaningful sensory neuropathy symptoms during the first year of treatment and nearly 50% continue to experience clinically meaningful sensory neuropathy symptoms at the end of the first year. Given the high incidence of symptoms during taxane treatment and persistence of symptoms after treatment completion, it is critical to develop effective methods to predict, prevent, and treat this toxicity. Follow up of data at 104 and 156 weeks will further characterize the trajectory of long term CIPN symptoms. Funding: NIH/NCI/NCORP grant UG1CA189974 Citation Format: Meghna S. Trivedi, Joseph M. Unger, Dawn Hershman, Amy K. Darke, Daniel L. Hertz, Thomas H. Brannagan, Stephanie J. Smith, Bryan P. Schneider, William J. Irvin Jr, Amanda R. Hathaway, Amy C. Vander Woude, Vinay K. Gudena, N. Lynn Henry, Michael J. Fisch. Incidence of Acute and Persistent Clinically Meaningful Chemotherapy Induced Peripheral Neuropathy in Patients with Early-Stage Breast Cancer Receiving Taxane Therapy: SWOG S1714 (NCT# 03939481) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-06.

Background Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients’ health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status. Methods Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using the FACT-EGFRI 18 were completed prior to undergoing CTCAE assessment by trained clinicians at baseline, weekly × 6, and then monthly × 3. The psychometric properties of the FACT-EGFRI 14 (skin toxicity items only) and 18 (plus 2 nail and 2 hair items) were established based on criterion validity, known groups validity, internal consistency reliability, and responsiveness to change. Results Of the 146 registered patients, 124 were evaluable. High Cronbach’s alpha (> 0.70) for both FACT-EGFRI 14 and FACT-EGFRI 18 scores across assessment times were observed. Although agreement (i.e. criterion validity) between individual and summary scales of the FACT-EGFRI 18 for assessing skin toxicity was good, agreement with the clinician-reported CTCAE was only fair. The minimal important difference was determined to be 3 points. The results also demonstrated responsiveness to symptom change. Discussion Based on the results of this multi-center validation study, the FACT-EGFRI 18 patient-reported outcome instrument provided data from the patient’s perspective yielding unique information as well as complementing clinician-rated CTCAE grades, especially for the symptoms of pain, pruritus, and paronychia. Conclusions Good to excellent psychometric properties for the FACT-EGFRI 18 were demonstrated, supporting further use of this patient-reported outcomes measure. Additional validation with a more diverse group of patients should be conducted.

Objective Choosing chemotherapy for metastatic colorectal cancer (mCRC) requires balancing clinical effectiveness and risk of complications. This study characterized real-world inpatient/emergency department (ED) hospitalizations during first-line chemotherapy among individuals with mCRC. Methods This retrospective cohort study used data from medical and pharmacy claims. All patients had mCRC with ≥1 claim for ≥1 of the 5 most frequently utilized first-line chemotherapy agents (fluorouracil, oxaliplatin, bevacizumab, irinotecan, capecitabine). The main outcome was all-cause hospitalizations (inpatient or ED setting) identified from claims via ICD-9/10-CM coding from index date until 30 days after the end of first-line chemotherapy or last available data. Results A total of 717 individuals (mean age 55 years; 58% male; ECOG 0/1/2+/missing in 44%/39%/6%/11%; median follow-up 116 days) met study criteria. Thirty-four distinct chemotherapy regimens were used. Overall, 40% of patients had ≥1 hospitalization (n=285; total 415 hospitalizations); 12% (n=85) had ≥2 hospitalizations. The median time to first hospitalization was 52 days; median inpatient length of stay was 4 days; infections/neutropenia (21%) and bowel-related complications (17%) were the most common issues associated with inpatient hospitalizations. In univariate analyses, insurance plan type, geographical location, ECOG, and renal disease were associated with hospitalization. In multivariable analyses, ECOG ≥1 was associated with a 67% increase (p

Purpose Chemotherapy side effects diminish quality of life and can lead to treatment delay. Nausea and vomiting can occur prior to chemotherapy because of classical conditioning. We studied the effects of 20‐minute behavioral interventions, administered by oncology nurses, of higher intensity (mindfulness relaxation—MR) or lower intensity (relaxing music—RM), on anticipatory nausea and vomiting (ANV). Patients and methods Patients undergoing chemotherapy for solid tumors were randomized to MR (N = 160), RM (N = 159), or standard care SC (N = 155). Subjects were mostly female (91.8%) and white (86.1%) with breast cancer (85%). Most patients had early stage disease (Stage I: 26%; II: 52.9%; III: 19%; IV: 0.1%). Anticipatory nausea and vomiting were assessed at the midpoint and end of the chemotherapy course using the Morrow Assessment of Nausea and Emesis (MANE). Results Compared to SC, there was reduced anticipatory nausea at the midpoint of chemotherapy in those receiving MR (OR 0.44, 95% CI 0.20‐0.93) and RM (OR 0.40, 95% CI 0.20‐0.93), controlling for age, sex, cancer stage, and emetogenic level of chemotherapy. There was no difference between treatment groups in anticipatory nausea at the end of chemotherapy or in anticipatory vomiting and postchemotherapy nausea and vomiting at either time point. Conclusion A brief nurse‐delivered behavioral intervention can reduce midpoint ANV associated with chemotherapy., Chemotherapy administration can result in conditioned nausea and vomiting. This multi‐centred randomized controlled trial demonstrates the superiority of 2 preemptive behavioural interventions in reducing conditioned nausea.

BACKGROUND While women diagnosed with breast cancer have increased survival when compared with other cancers, survivorship may include residual symptom burden from treatment and continuing endocrine therapies. OBJECTIVE The objective of this study was to identify subgroups of breast cancer survivors experiencing similar symptom severity. METHODS Participants were 498 women with breast cancer, not on active treatment. Symptom severity was self-reported using the MD Anderson Symptom Inventory. Target symptoms were included in a latent profile analysis. Factors related to subgroup membership and differences in quality of life (QOL) and functioning were explored using logistic regression. RESULTS Mean age was 60.11 (SD, 11.32) years, 86.1% were white, and 79.1% were receiving endocrine therapy. Target symptoms included fatigue (reported at ≥5 by 22.8% of women), sleep disturbance (24.8%), and trouble remembering (17.2%). Two subgroups were identified: low symptom severity (77.0% of women) and high (23.0%). Older women (odds ratio [OR], 0.971; 95% confidence interval [CI], 0.952-0.989) and employed women (OR, 0.621; 95% CI, 0404-0.956) were less likely to be in the high subgroup; women with poorer performance status (OR, 1.653; 95% CI, 1.188-2.299) were more likely to be in the high subgroup. Women in the high subgroup reported lower QOL (P = .000) and greater interference with functioning (P = .000). CONCLUSIONS Two subgroups of women with distinct symptom severity were identified. IMPLICATIONS FOR PRACTICE Identification of women at risk for high symptoms during survivorship may allow clinicians to intensify their approach to symptom management, thereby mitigating poor outcomes and impairments in QOL.

Judith J Stephenson,1 Jonathon Colby Gable,2 Rebekah Zincavage,1 Gregory L Price,2 Collin Churchill,2 Emily Zhu,2 Keri Stenger,2 Mukul Singhal,1 Bal Nepal,1 Michael Grabner,1 Michael J Fisch,3 David Debono,4 Amy R Geschwender,5 Gebra Cuyun Carter2 1HealthCore, Inc., Wilmington, DE, USA; 2Eli Lilly and Company, Indianapolis, IN, USA; 3AIM Specialty Health, Chicago, IL, USA; 4Anthem, Inc., Indianapolis, IN, USA; 5SWOG Cancer Research Network, San Antonio, TX, USACorrespondence: Judith J Stephenson Tel +1 302-547-5770Email JStephenson@healthcore.comPurpose: To describe patients’ perspectives on the use of and potential challenges and barriers with adherence/persistence to cyclin-dependent kinase 4 and 6 inhibitors (CDK4& 6i’s) to treat metastatic breast cancer (MBC).Methods: This qualitative study consisted of 60-minute semi-structured telephone interviews with patients with MBC in the US who were either current or recent CDK4& 6i users, identified from administrative claims of survey-eligible commercial and Medicare Advantage patients in the HealthCore Integrated Research Database between November 1, 2018 and November 1, 2019. Patients were recruited by email and/or mailed letter. The 60-minute telephone interviews were conducted by a trained facilitator using a study-developed interview discussion guide that included topics impacting treatment choice and adherence/persistence. Interviews were audio-recorded, transcribed, and thematically analyzed.Results: All 462 eligible patients were sent a recruitment email and/or letter to which 36 patients responded, consented to participate, and met study inclusion criteria; 25 patients scheduled interviews, and 24 completed them. Study participants were predominately white, non-Hispanic (96%) with a mean age of 59.5 years. Participants reported a largely positive experience and mentioned very few adherence/persistence issues. They further reported appreciating the ease and convenience of oral oncolytics, coped with side effects, had strong medical and social support, and experienced few cost issues.Conclusion: The few adherence/persistence issues reported by participants contrasts with other findings of suboptimal oral oncolytic use. Interview themes indicated several factors that likely contributed to the lack of adherence/persistence issues: trusted relationship with oncologist, belief in importance of medication, positive medication views, strong medical and social support, and minimal personal drug cost. Future research should focus on whether and how much these factors impact adherence/persistence in more diverse populations. If adherence/persistence issues are identified in these populations, then it would be appropriate to study the development of interventions that target factors associated with better adherence/persistence.Keywords: oral oncolytics, patient perspective, semi-structured interviews, adherence, persistence, CDK4& 6i users

Immune checkpoint inhibitors (ICI) are increasingly used across multiple cancer types and stages and little is known about real-world outcomes. This study sought to determine healthcare utilization, costs, immune-related adverse events (irAEs), and all-cause mortality of single-agent versus combination ICI in the USA.This is a retrospective study conducted with 2016-2018 data from the HealthCore Integrated Research Database, consisting of commercial and Medicare-insured adult patients with a cancer diagnosis using ICI in the USA. Outcomes were healthcare utilization, costs, and irAEs (FDA-recognized and others) up to 1-year post-index between patients using ICI monotherapy (mono, PD-1/PD-L1 inhibitor) and combination therapy (combo, PD-1/PD-L1 with CTLA-4 inhibitors).In total, 9084 patients received monotherapy and 904 patients received combo therapy. Mean age 65 years for mono and 58 years for combo. Overall, the combo arm had higher rates of FDA-recognized irAEs (67.4% vs. 45.9%), especially endocrinopathies (27.7% vs 14.7%) and dermatitis (25.9% vs. 12.4%). All-cause mortality over 1-year follow-up was similar, 30.7% in mono vs 30.8% in combo arms. The combo group had higher rates of all-cause inpatient hospitalizations (55.4% mono vs 65.6% combo) and emergency department (ED) visits (33.7% mono vs 41.4% combo). IrAE-related hospitalizations were higher in combo (55.2% vs 42.1%). IrAE-related ED visits were 15.7% mono vs 22.7% combo. This increased toxicity and health care utilization was reflected in significant differences in healthcare costs. Stark differences were seen in all-cause medical costs as well as costs related to inpatient and ED utilization and costs attributed to irAEs.Higher rates of irAEs, healthcare utilization, and costs occur with combination immunotherapy. As further indications are approved for combination ICI, our study highlights the real-world tradeoffs involved with combination therapy regarding burdens of toxicity and increased healthcare utilization.

Background Almost one-half of aromatase inhibitor (AI)–treated breast cancer patients experience AI-associated musculoskeletal symptoms (AIMSS); 20%-30% discontinue treatment because of severe symptoms. We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from previously conducted trials. Methods We pooled patient-level data from 3 randomized trials testing interventions (omega-3 fatty acids, acupuncture, and duloxetine) for AIMSS that had similar eligibility criteria and the same patient-reported outcome measures. Only patients with a baseline Brief Pain Inventory average pain score of at least 4 of 10 were included. The primary outcome examined was 2-point reduction in average pain from baseline to week 12. Variable cut-point selection and logistic regression were used. Risk models were built by summing the number of factors statistically significantly associated with pain reduction. Analyses were stratified by study and adjusted for treatment arm. Results For the 583 analyzed patients, the 4 factors statistically significantly associated with pain reduction were Functional Assessment of Cancer Therapy Functional Well-Being greater than 24 and Physical Well-Being greater than 14 (higher scores reflect better function), and Western Ontario and McMaster Universities Osteoarthritis Index less than 50 and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands less than 33 (lower scores reflect less pain). Patients with all 4 factors were greater than 6 times more likely to experience at least a 2-point pain reduction (odds ratio = 6.37, 95% confidence interval = 2.31 to 17.53, 2-sided P < .001); similar results were found for secondary 30% and 50% pain reduction endpoints. Conclusions Patients with AIMSS who have lower symptom and functional distress at study entry on AIMSS intervention trials are more likely to experience meaningful pain reduction. Baseline symptom and functional status should be considered as stratification factors in future interventional trials.

ImportanceAromatase inhibitors (AIs) have proven efficacy for the treatment of hormone-sensitive breast cancer; however, arthralgias (pain and stiffness) contribute to nonadherence with therapy for more than 50% of patients.ObjectiveTo examine the effect of acupuncture in reducing AI-related joint pain through 52 weeks.Design, Setting, and ParticipantsA randomized clinical trial was conducted at 11 sites in the US from May 1, 2012, to February 29, 2016, with a scheduled final date of follow-up of September 5, 2017, to compare true acupuncture (TA) with sham acupuncture (SA) or waiting list control (WC). Women with early-stage breast cancer were eligible if they were taking an AI and scored 3 or higher on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Analysis was conducted for data received through May 3, 2021.InterventionsParticipants were randomized 2:1:1 to the TA (n = 110), SA (n = 59), or WC (n = 57) group. The TA and SA protocols were composed of 6 weeks of intervention at 2 sessions per week (12 sessions overall), followed by 6 additional weeks of intervention with 1 session per week. Participants randomized to WC received no intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52.Main Outcomes and MeasuresIn this long-term evaluation, the primary end point was the 52-week BPI-WP score, compared by study group using linear regression, adjusted for baseline pain and stratification factors.ResultsAmong 226 randomized women (mean [SD] age, 60.7 [8.6] years; 87.7% White; mean [SD] baseline BPI-WP score, 6.7 [1.5]), 191 (84.5%) completed the trial. In a linear regression, 52-week mean BPI-WP scores were 1.08 (95% CI, 0.24-1.91) points lower in the TA compared with the SA group (P = .01) and were 0.99 (95% CI, 0.12-1.86) points lower in the TA compared with the WC group (P = .03). In addition, 52-week BPI pain interference scores were statistically significantly lower in the TA compared with the SA group (difference, 0.58; 95% CI, 0.00-1.16; P = .05). Between 24 and 52 weeks, 12 (13.2%) of TA, 6 (11.3%) of SA, and 5 (10.6%) of WC patients reported receipt of acupuncture.Conclusions and RelevanceIn this randomized clinical trial, women with AI-related joint pain receiving 12 weeks of TA had reduced pain at 52 weeks compared with controls, suggesting long-term benefits of this therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT01535066

Background: AIMSS occurs often in women treated with AI therapy for early stage breast cancer and can negatively impact adherence and persistence with therapy. Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat mood disorders and chronic pain. In SWOG S1202, patients with AIMSS treated with duloxetine reported statistically significant improvement in pain by 12 weeks compared to placebo. Obesity is a predictor of increased likelihood of developing AIMSS, and a prior study of omega 3 fatty acid versus placebo for AIMSS showed a potential differential response to therapy by BMI. In this exploratory analysis of S1202, we investigated the association between baseline BMI and response to therapy. Methods: In S1202, 299 postmenopausal women with stage I-III hormone receptor-positive breast cancer on AI therapy who developed new or worsening average pain of 4-10 on a numerical rating scale were enrolled, randomized 1:1 to duloxetine or placebo with randomization stratified by baseline pain (4-6 vs. 7-10) and prior taxane therapy (yes vs. no). Patients were treated for 12 weeks. Patient-reported outcomes including Brief Pain Inventory (BPI) were obtained at baseline and weeks 2, 6, 12, and 24. Patients were categorized into BMI Results: 289 patients were eligible for the analysis, 54% of whom were obese. The cohorts were well balanced other than by race. The difference by intervention arm in the 12-week mean BPI scores between baseline and follow-up scores was substantially different for the obese versus non-obese cohorts. In the patients with BMI Conclusions: In the placebo-controlled S1202 trial, obese patients with AIMSS obtained more analgesic benefit from duloxetine. Additional studies are warranted to determine the biologic basis for these findings, such as a different mechanism underlying development of AIMSS or pain expression in patients with obesity, or other confounding variables related to analgesic response to duloxetine relative to placebo. Support: NIH/NCI grants CA189974, CA189821, CA180820; and in part by Damon Runyon-Lilly Clinical Investigator Award #CI-53-10 [to NLH], and in part by Lilly USA, LLC. Citation Format: Henry NL, Unger JM, Till C, Schott AF, Crew KD, Lew DL, Fisch MJ, Moinpour CM, Wade JL, Hershman DL. Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-04.

Progress toward improvement in cancer therapy relies on clinical trials. Yet, only a minority of eligible patients with cancer enroll as a result of multiple barriers at the patient, investigator, center, and national level. However, the rise of the Internet and mobile technology has created a slew of tools with medical applications, from Web sites to apps to social media platforms, all of which may aide clinicians in our quest to improve the clinical research enterprise. SWOG is one of five members in the National Cancer Institute’s National Clinical Trials Network—the nation’s oldest and largest publicly funded cancer research network—and is taking a leadership role in exploring and testing the promise of digital engagement through the empaneling of the Digital Engagement Committee. This article outlines the mission, principles, and priorities of the Digital Engagement Committee and proposes how this work may inform the use of digital tools for the cancer research community and, hopefully, translate to improved outcomes for our patients.

2016 Background: Efforts to standardize quality and control cost growth for cancer care have focused heavily on promoting evidence-based cancer drug prescribing. We evaluated the association between a national commercial insurer’s ongoing pay-for-performance (P4P) program for oncology and changes in prescribing of evidence-based cancer drugs and spending. Methods: Retrospective difference-in-differences quasi-experimental study utilizing administrative claims data from the insurer’s commercial health plans in 14 states covering 6.7% of US adults. We included patients 18 years of age or older with breast, colon, or lung cancer who were prescribed cancer drug regimens by 1,867 participating oncology physicians between 2013 and 2017. We leveraged the geographically staggered, time-varying rollout of the P4P program to simulate a stepped-wedge study design. Specifically, we estimated a patient-level model clustered by physician and used physician fixed-effects to examine pre- to post-intervention changes in evidence-based prescribing and spending for patients of participating physicians eligible earlier versus later in the period of P4P program rollout. We evaluated four categories of spending over a 6-month episode period: cancer drug spending; other (non-cancer drug) health care spending; total episode spending; and patient out-of-pocket spending. Results: The P4P program was associated with an increase in evidence-based regimen prescribing from 57.1% of patients in the pre-intervention periods to 62.2% in the post-intervention periods for a difference of +5.1 percentage points (pp) (95% CI 3.0 pp to 7.2 pp, P< 0.001). The P4P program was also associated with a differential $3,235 (95% CI $1,004 to $5,466, P= 0.005) increase in cancer drug spending, a differential $253 (95% CI $101 to $406, P= 0.001) increase in patient out-of-pocket spending, but no significant changes in other health care spending or total health care spending over the 6-month episode period. Conclusions: A national insurer’s oncology P4P program was associated with a 5.1 percentage point increase in prescribing of evidence-based cancer drug regimens. Our findings suggest that P4P programs may be effective in increasing evidence-based cancer drug prescribing at national scale -- enhancing cancer care quality. However, they may also increase out-of-pocket expenses and may not lead to savings in total health care spending during the 6-month episode.

PURPOSE: Symptom monitoring is attracting attention as a way to improve adherence to cancer therapy, reduce treatment-related toxicities, and possibly improve overall survival. How reporting thresholds affect symptom alert generation and clinical outcomes is poorly understood. PATIENTS AND METHODS: We analyzed data from 38 US health care institutions collected for the prospective Eastern Cooperative Oncology Group–American College of Radiology Imaging Network E2Z02 Symptom Outcomes and Practice Patterns study. Participants were outpatients receiving chemotherapy for breast (n = 642), colorectal (n = 486), or lung cancer (n = 340) who rated symptom severity using the MD Anderson Symptom Inventory at 2 assessment points 1 month apart. Percentages of patients with pain, dyspnea, fatigue, or distress at different thresholds (score of 4-7 on a 0-10 scale) were compared. The percentage of patients whose performance status had worsened at follow-up was used to estimate risk for missing clinically important symptom data by using higher severity thresholds RESULTS: At the guideline-recommended threshold of ≥ 4, suprathreshold rates were 60% for any of the 4 symptoms at the initial survey; performance status worsened at follow-up for 27% of all patients with any symptom rated ≥ 4 at the initiate survey. When the threshold was increased to ≥ 7, approximately half of patients (51%) with worsened performance status were not identified. CONCLUSION: The burden to clinicians from an alert threshold of ≥ 4 (per many current guidelines) would be substantial. However, setting higher alert thresholds may miss a large percentage of patients who need clinical intervention. These results may inform resource planning when implementing electronic symptom screening at an institutional or practice level.

PURPOSE: Although aromatase inhibitors (AIs) prolong survival in postmenopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. METHODS: We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I–III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0–10). RESULTS: Among the 249 participants, 139 had BMI

Introduction This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel. The primary end point was rate of objective or prostate-specific antigen (PSA) response at 16 weeks. A 50% response rate was considered of further interest. Results Eligible patients received a median of 3 cycles (range, 1-10 cycles). The response rate among patients with measurable disease was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95% CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression-free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was 17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities included lymphopenia (21%) and anemia (9%). There was one toxicity-related death. Quality-of-life scores improved by week 8, but the change was not statistically significant. Conclusion The combination has activity defined by PSA declines in CRPC but did not meet the protocol-specified end point for efficacy as defined by objective response rate. Since this study was conducted, more effective, better-tolerated regimens have been developed.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation. Patients were randomly assigned 1:1 to duloxetine or placebo for 13 weeks. The primary end point was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score of 4 to 6 v 7 to 10 and prior taxane use). Clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline. Results Of 299 enrolled patients, 127 patients treated with duloxetine and 128 who received placebo were evaluable for the primary analysis. By 12 weeks, the average joint pain score was 0.82 points lower for patients who received duloxetine compared with those who received placebo (95% CI, −1.24 to −0.40; P = .0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events of any grade were higher in the duloxetine-treated group (78% v 50%); rates of grade 3 adverse events were similar. Conclusion Results of treatment with duloxetine for AIMSS were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.

Background: Up to half of AI-treated breast cancer patients experience AIMSS, and 20-30% have severe symptoms that lead to treatment discontinuation. Multiple interventions have been examined in randomized clinical trials, including in SWOG S0927 (omega-3 fatty acids vs placebo), S1202 (duloxetine vs placebo), and S1200 (true acupuncture vs sham acupuncture vs wait list control). We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from these trials. Methods: The S0927, S1200, and S1202 clinical trials had similar eligibility criteria, and all used the same patient-reported outcomes measures to assess arthralgias and endocrine symptoms. The Brief Pain Inventory (BPI) examines average pain, worst pain, and pain interference; higher numbers reflect more symptoms. Endocrine symptoms were assessed with the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), which includes subscales for functional and physical well-being; higher scores reflect better function. We also used validated measures to assess joint symptoms in the knees/hips (WOMAC) and hands (M-SACRAH), where higher scores indicate greater symptom severity. We analyzed the subset of patients enrolled on these three trials who had a baseline BPI average pain score of at least 4/10 (S0927, n=185; S1200, n=158; S1202, n=240). The primary outcome was 50% reduction in BPI average pain from baseline to week 12. Variable cut-point selection was performed on each continuous variable to identify a binary cut-point that optimally distinguished high versus low levels of pain reduction. Logistic regression was performed for each variable. A risk model was built by summing the number of statistically significant baseline predictors and categorizing patients by low vs. medium vs. high likelihood of pain reduction. All analyses were stratified by study and adjusted for treatment arm. Results: Of the 583 analyzed patients, median age was 60 years (range 27-84), median body mass index was 30 kg/m2 (range 18-84), and 208 patients (35.7%) had at least a 50% reduction in BPI average pain. Factors significantly associated with at least a 50% reduction in pain included lower pain and pain interference and better physical and functional status at study enrollment (Table). Patients with 2-4 of the 7 statistically significant factors were twice as likely to experience pain reduction compared to those with fewer than 2 factors (37.8% vs. 22.5%; odds ratio [OR] 2.08, 95% CI 1.38-3.13, p Association of baseline characteristics with 50% reduction in average pain from baseline to 12 weeksFactorRates of pain reductionOdds Ratio (95% CI)P valueAge: Citation Format: N. Lynn Henry, Joseph M Unger, Cathee Till, Katherine D Crew, Michael J Fisch, Dawn L Hershman. Predictors of pain reduction in trials of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-03.

Twitter use by physicians, including those in the hematology – oncology field, is increasing. This microblogging platform provides a means to communicate and collaborate on a global scale. For the oncology professional, an active Twitter presence provides opportunities for continuing medical education, patient engagement and education, personal branding, and reputation management. However, because Twitter is an open, public forum, potential risks such as patient privacy violations, personal information disclosures, professionalism lapses, and time management need to be considered and managed. The authors have summarized the benefits and risks of Twitter use by the hematology – oncology physician. In addition, strategies to maximize benefit and minimize risk are discussed, and resources for additional learning are provided.

Background Anthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy. Methods We conducted a genome-wide association study (GWAS) of change in LV function after anthracycline exposure in 385 patients identified from BioVU, a resource linking DNA samples to de-identified electronic medical record data. Variants with P values less than 1×10 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospective clinical trial. Pathway analysis was performed to assess combined effects of multiple genetic variants. Results Both cohorts were middle-aged adults of predominantly European descent. Among 11 candidate loci identified in discovery GWAS, one single nucleotide polymorphism near PR domain containing 2, with ZNF domain (PRDM2), rs7542939, had a combined P value of 6.5×10 in meta-analysis. Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome. Identified pathways related to DNA repair, cellular metabolism, and cardiac remodeling. Conclusion Using genome-wide association we identified a novel candidate susceptibility locus near PRDM2. Variation in genes belonging to pathways related to DNA repair, metabolism, and cardiac remodeling may influence changes in LV function after anthracycline exposure.

BACKGROUND Cancer patients' symptom burden is commonly attributed to their cancer and treatment. Increasingly, cancer patients have many other chronic comorbid conditions. However, the degree to which these comorbid conditions may contribute to the patient-reported symptom burden is unclear. METHODS This study explored the relations between the presence of comorbid conditions, the symptom experience and burden, and the perceived bother from cancer or comorbid conditions in 3106 cancer patients. The associations between the number of comorbidities (identified from current medications), the patient-reported symptom burden (the number of symptoms scored as ≥7 on the 13-item MD Anderson Symptom Inventory physical scale), the patient-reported bother from comorbid conditions and from cancer (from “not at all” to “extremely”), and the clinician-reported difficulty in caring for patients' symptoms were examined. RESULTS According to medication lists, 19% of the patients had at least 5 of 12 comorbid conditions. Approximately 39% rated at least 1 symptom as ≥ 7, and this proportion increased with an increasing number of comorbid conditions (48% with ≥ 5 comorbid conditions vs 36% with 1 comorbid condition). One-third of the patients reported moderate or worse bother, and this was significantly associated with an increased number of comorbid conditions (odds ratio [OR], 2.4) and an increased symptom burden (OR, 1.22). Clinician ratings of difficulty in managing patients' symptoms were significantly associated with bother from cancer (OR, 2.0), comorbid conditions (OR, 1.6), and symptom burden (OR, 1.1). CONCLUSIONS Comorbidity is common in cancer patients and is associated with a greater symptom burden and clinician reports of difficulty in managing patients' symptoms. Greater attention to comorbid conditions is needed to optimize the symptom management of cancer patients with multimorbidity. Cancer 2017. © 2017 American Cancer Society.

Context Patients with cancer are bothered by its diagnosis, treatment, and associated uncertainty. Lack of concordance (LOC) of patients' reporting of their symptoms and quality of life (QOL) with that of their clinicians has been observed in cancer care. However, information regarding the reporting of patients' bother due to aspects of cancer experience and their clinicians' assessment is lacking. Objectives The objective was to describe cancer patients' bother due to aspects of their disease experience and explore the concordance (LOC) or a lack thereof between patients' and clinicians' reporting of patients' bother and factors associated with it. Methods Data from a prospective study of cancer patients' symptoms were analyzed. LOC was defined as any discrepancy between patient-clinician pairs in reporting patients' bother due to disease, cancer treatment, comorbidity, and side effects of symptom management. The relation of LOC to patients' QOL and distress was also explored. Results Of the 2597 patients analyzed, a perfect concordance was observed in 37%–42%. Clinicians underestimated the severity of bother in 62%–76% of discordant cases. LOC was significantly associated with patient-reported distress and poor QOL. Referral for symptom management was associated with the clinician's rating of patients' bother, and LOC was associated with likelihood of poor compliance with recommendations for symptom management. Conclusion Majority of clinicians tended to underestimate cancer patients' bother, and this was associated with poor QOL of cancer patients and their distress. Future studies should examine the LOC and its correlates to confirm the results of this study.

BACKGROUND Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]–positive/hepatitis B core antibody [anti-HBc]–positive) or past (HBsAg-negative/anti-HBc–positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017. © 2017 American Cancer Society.

This cohort study examines the association between billed advance care planning encounters and subsequent health care utilization among seriously ill patients near the end of life., Key Points Question Is advance care planning associated with health care utilization among seriously ill patients? Findings In this cohort study of 18 484 seriously ill Medicare Advantage beneficiaries, patients with billed advance care planning encounters were more likely than those without these encounters to require hospitalization, enroll in hospice, and die and less likely to receive intensive therapies, such as chemotherapy. Meaning Among seriously ill patients near the end of life, advance care planning may not be assoicated with reduced health care utilization., Importance Although advance care planning is known to increase patient and caregiver satisfaction, its association with health care utilization is not well understood. Objective To examine the association between billed advance care planning encounters and subsequent health care utilization among seriously ill patients. Design, Setting, and Participants This retrospective cohort study conducted from October 1, 2015, to May 31, 2018, used a national commercial insurance claims database to retrieve data from 18 484 Medicare Advantage members 65 years or older who had a claim that contained a serious illness diagnosis. Exposure A claim that contained an advance care planning billing code between October 1, 2016, and November 30, 2017. Main Outcomes and Measures Receipt of intensive therapies, hospitalization, emergency department use, hospice use, costs, and death during the 6-month follow-up period. Results The final study sample included 18 484 seriously ill patients (mean [SD] age, 79.7 [7.9] years; 10 033 [54.3%] female), 864 (4.7%) of whom had a billed advanced care planning encounter between October 1, 2016, and November 30, 2017. In analyses adjusted for patient characteristics and a propensity score for advance care planning, the presence of a billed advance care planning encounter was associated with a higher likelihood of hospice enrollment (incidence rate ratio [IRR], 2.52; 95% CI, 2.22-2.86) and mortality (hazard ratio, 2.27; 95% CI, 1.79-2.88) compared with no billed advance care planning encounter. Although patients with billed advance care planning encounters were also more likely to be hospitalized (IRR, 1.37; 95% CI, 1.26-1.49), including in the intensive care unit (IRR, 1.25; 95% CI, 1.08-1.45), they were less likely to receive any intensive therapies (IRR, 0.85; 95% CI, 0.78-0.92), such as chemotherapy (IRR, 0.65; 95% CI, 0.55-0.78). Similar results were observed in a propensity score–matched analysis (99% matched) and in a decedent analysis of patients who died during the 6-month follow-up period. Conclusions and Relevance Patients with billed advance care planning encounters were more likely than those without these encounters to receive hospice services and less likely to receive any intensive therapies, such as chemotherapy. However, they were also hospitalized more frequently than patients without billed advance care planning encounters. Although these findings were robust to multiple analytic methods, the results may be attributable to residual confounding because of a higher unmeasured severity of illness in the advance care planning group. Additional evidence appears to be needed to understand the effect of advance care planning on these outcomes.

Twitter use has increased among patients with cancer, advocates, and oncology professionals. Hashtags, a form of metadata, can be used to share content, organize health information, and create virtual communities of interest. Cancer-specific hashtags modeled on a breast cancer community, #bcsm, led to the development of a structured set of hashtags called the cancer tag ontology. In this article, we review how these hashtags have worked with the aim of describing our experience from 2011 to 2017. We discuss useful guidelines for the development and maintenance of health-oriented communities on Twitter, including possible challenges to community sustainability and opportunities for future improvement and research.

PURPOSE National hepatitis B virus (HBV) screening recommendations for patients with cancer anticipating systemic anticancer therapy range from universal screening to screening based on risk of HBV infection, cancer therapy–specific risk of HBV reactivation, or both. We conducted cost-effectiveness analyses to identify optimal HBV screening strategies. PATIENTS AND METHODS We constructed decision-analytic models to analyze three strategies (no screening, universal screening, and selective screening based on use of an HBV infection risk tool) for hypothetic cohorts of patients anticipating anticancer therapy at high or lower risk for HBV reactivation. Model parameters were drawn from previously published studies, the SEER-Medicare database, and other online resources. Outcomes included lifetime expected cost, quality-adjusted life expectancy, and incremental cost-effectiveness ratio, measured in US dollars required to gain an additional quality-adjusted life-year (QALY). RESULTS For patients at high reactivation risk, universal screening dominated (ie, was cheaper and more effective than) the other two strategies. Universal screening was associated with a gain in life expectancy of 0.01 QALY compared with no screening and cost $76.06 less than no screening and $4.34 less than selective screening. For those at lower reactivation risk, universal screening still dominated selective screening; however, the incremental cost-effectiveness ratio of the universal screening strategy compared with no screening was $186,917 per QALY gained. CONCLUSION Universal HBV screening is cost effective and cheaper for patients receiving anticancer therapy associated with a high reactivation risk. For patients receiving anticancer therapy associated with a lower reactivation risk, universal screening is not cost effective.

2625 Background: Immunotherapy is a fast growing class of cancer therapy. We evaluated the rates of immune-related adverse events (irAEs), healthcare utilization, and costs up to 1 year post-index among patients using monotherapy (PD-1/PD-L1 inhibitor) and combination therapy (PD-1/PD-L1 with CTLA-4 inhibitors). Methods: We reviewed claims from the HealthCore Integrated Research Database (HIRD), which contains commercially insured/Medicare Advantage members and captures clinical, utilization, and cost measures. We analyzed both the monotherapy (M) and combination therapy (C) cohorts focusing on members with ≥ 6 months of baseline continuous medical and pharmacy coverage. Descriptive and multi-variate analyses were performed. Results: The C cohort had 904 and M had 9,084 patients, with mean ages of 58 and 64 years, respectively. Prominent cancer types were melanoma for C and lung for M. The most common incident irAEs (%) for C vs. M were: endocrinopathies (27.7, 14.7), hepatitis (17.1, 7.7), nephritis (21.0, 14.0), neuropathy (6.6, 7.0), followed by colitis, dermatitis, and myocarditis. After adjustment, C therapy showed greater risk of all-cause inpatient admissions (OR 2.27, 95% CI 1.93, 2.66), all-cause emergency department (ED) visits (OR 1.55, 95% CI 1.33, 1.81) and irAE-related visits (See table). Mean adjusted all-cause cost difference for C vs M was +$43,747 (95% CI $38,440, $49,427). In age ≥65 subset, 222 received C and 4,208 received M. C therapy patients had more irAE-related hospitalizations (45.3% vs. 57.7%, p=0.0004). Costs were similar to the main cohort. Conclusions: C therapy showed greater incident irAE rates, increased utilization and medical costs compared to M therapy. Limitations include less precise ascertainment of irAEs in claims data and generalizability only to those with commercial or Medicare Advantage insurance. Our study highlights the increased toxicity and cost tradeoffs involved in choosing combination immunotherapy over monotherapy.[Table: see text]

12003 Background: AIMSS are common and frequently lead to early discontinuation of adjuvant AI therapy. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. The primary objective of E1Z11 was to validate previously identified associations between 10 specific SNPs in candidate genes and AI discontinuation due to AIMSS in a community-based, racially diverse cohort. Methods: Postmenopausal women with hormone receptor-positive stage I-III breast cancer enrolled onto a prospective multi-site cohort study, the majority through the NCI Community Oncology Research Program (NCORP). Participants received anastrozole 1 mg oral daily, and completed patient-reported outcomes (PROs) at baseline, 3, 6, 9, and 12 months. AIMSS was defined as >20% increase in Stanford Health Assessment Questionnaire (HAQ) score over baseline occurring within 1 year of AI therapy. We projected 40% would develop AIMSS and 25% would discontinue AI treatment within 1 year, informing a planned enrollment of 1000 women with a fixed number per strata (600 Caucasian, 200 African-American [AA] & 200 Asian) to provide 80% power to detect an effect size of 1.5-4. SNPs include ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). Hardy-Weinberg equilibrium (HWE) was evaluated within each racial subset. SNP genotypes were coded as additive effects on the log odds ratio by coding as 0, 1 or 2 for the count of the minor allele. A Cochran-Armitage trend test was used with a 1-sided alpha of 0.0025 (Bonferroni correction for 10 tests). Results: We enrolled 999 evaluable women (616 Caucasian, 184 AA, 199 Asian). Genotyping was successful in 974 (98%). AIMSS developed in 43%, and AI therapy was discontinued in 12% within 1 year. While more AA and Asians developed AIMSS compared to Caucasians (48% vs 38%, p=0.017; 50% vs 38%, p=0.004), AI discontinuation rates were similar across racial groups. HWE was satisfied for all SNPs at the 5% alpha level, except for TCL1A/rs11849538 (p=0.002) in the AA cohort. None of the 10 SNPs were significantly associated with AI discontinuation or development of AIMSS in the overall population, or in any of the 3 cohorts. Conclusions: Although AIMSS were more common in AA and Asians, AI discontinuation rates were similar in the 3 cohorts. We were unable to prospectively validate 10 SNPs in 4 genes previously associated with AI discontinuation due to AIMSS. Future analyses will include other predictors of AIMSS, PROs, and additional genetic markers for the entire cohort and by race. Support: NCI UG1CA189828, UG1CA233196, UG1CA233277, UG1CA233320, UG1CA233178, UG1CA233160, UG1CA232760, UG1CA233341, UG1CA233329, U10CA180821, UG1CA189821, UG1CA189830, U10CA180888, UG1CA189859, UG1CA189863, UG1CA189971. Clinical trial information: NCT01824836.

e18596 Background: Several oncology guidelines recommend using oral drugs vs. IV to minimize COVID-19 risk for patients with cancer. We examined the association between prescribing patterns of oral capecitabine vs. IV 5FU for GI cancers and social distancing, measured by the change in population mobility patterns in response to shelter-in place policies, during the pandemic. Methods: Using claims data for commercially insured members, we included patients 18 years of age or older with colorectal, gastroesophageal, or pancreatic cancer, who had continuous health plan coverage for at least 2 months before and 1 month after initiating chemotherapy with capecitabine or 5-FU from January 2017 to August 2020. We analyzed unadjusted trends in proportion of chemotherapy that was oral during pandemic (March 1st to August 31st, 2020) compared to previous years. Then, we conducted difference-in-differences analysis using COVID-19 Community Mobility Reports, by Google, and utilizing different levels of changes in mobility trends across states over time. In our main model, we used a 20% decrease in retail and recreation visits as our threshold and compared the prescribing rates in states below and above the threshold as well as before and after the pandemic began. We also used different thresholds and categories of places to check the sensitivity of our findings. Models are adjusted for age, gender, month of year, urban status, comorbidities, and state of residence at chemotherapy start date. Results: A total of 17,414 nationally distributed patients (69% colorectal, 13% gastroesophageal, 18% pancreatic) were included (mean age, 58.8 years; 41% female). During the pandemic, 1,875 patients (65% colorectal, 15% gastroesophageal, 20% pancreatic) were identified. The proportion of oral regimens did not change significantly for colorectal and gastroesophageal patients and decreased by 7.4 percentage points (pp) (p < 0.01) for pancreatic patients. In regression modelling with mobility data, oral prescribing rates for colorectal patients increased by 3.1 pp (p < 0.01), largely driven by increases for female patients (9.2 pp, p = 0.02). We observed a decrease in oral prescribing rates among pancreatic patients (-1.20 pp, p = 0.04) and did not observe a significant change for gastroesophageal patients. Our results are not sensitive to different social distancing specifications. Conclusions: We observed differential impact of the pandemic on oral prescribing rates by GI cancer type and gender. Oral prescribing increased among colorectal cancer patients driven mostly by higher oral prescribing in females. For pancreatic and gastroesophageal patients, oral prescriptions either remained unchanged or decreased. This observation may reflect a variable impact of the pandemic on women as compared to men and might involve heightened caregiving responsibilities for women.

Importance Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown. Objective To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm. Design, setting, and participants This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020. Interventions/exposures Cancer treatments, BMAs, and dental care were administered as clinically indicated. Main outcomes and measures Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined. Results The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P = .009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P = .006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P = .02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P = .02). Conclusions and relevance As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.

Background Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy. Methods and Results Patients were enrolled from a single medical center. Cardiac biomarkers (TnI, BNP) were measured before and within 24 hours after completion of anthracycline administration for each cycle of therapy. Cardiac imaging was obtained at baseline and at completion of chemotherapy (commonly at 6 or 12 months) or based on clinical suspicion of a cardiac event. Of the enrolled 109 patients, 11 (10.1%) experienced cardiac events; all of these patients had at least 1 BNP value >100 pg/mL before the cardiac event. Significant reduction in LV ejection fraction as defined for cardiotoxicity occurred in only 3 of 10 patients (30%) with a cardiac event. Conclusions The use of cardiac biomarkers, particularly BNP, may allow early detection of cardiotoxicity related to anthracycline chemotherapy.

Conversations about end-of-life (EOL) wishes are challenging for many clinicians. The Go Wish card game (GWG) was developed to facilitate these conversations. Little is known about the type and consistency of EOL wishes using the GWG in advanced cancer patients. We conducted a randomized controlled trial to assess the EOL wishes of 100 patients with advanced cancer treated at The University of Texas MD Anderson Cancer Center. The purpose of this study was to determine the EOL wishes of patients with advanced cancer and to compare patients’ preference between the GWG and List of wishes/statements (LOS) containing the same number of items. Patients were randomized into four groups and completed either the GWG or a checklist of 35 LOS and one opened statement found on the GWG cards; patients were asked to categorize these wishes as very, somewhat, or not important. After 4–24 h, the patients were asked to complete the same or other test. Group A (n = 25) received LOS-LOS, group B (n = 25) received GWG-GWG, group C (n = 26) received GWG-LOS, and group D (n = 24) received LOS-GWG. All patients completed the State-Trait Anxiety Inventory (STAI) for adults before and after the first test. Median age (interquartile range = IQR): 56 (27–83) years. Age, sex, ethnicity, marital status, religion, education, and cancer diagnosis did not differ significantly among the four groups. All patients were able to complete the GWG and/or LOS. The ten most common wishes identified as very important by patients in the first and second test were to be at peace with God (74 vs. 71 %); to pray (62 vs. 61 %); and to have family present (57 vs. 61 %). to be free from pain (54 vs. 60 %); not being a burden to my family (48 vs. 49 %); to trust my doctor (44 vs. 45 %); to keep my sense of humor (41 vs. 45 %); to say goodbye to important people in my life (41 vs. 37 %); to have my family prepared for my death (40 vs. 49 %); and to be able to help others (36 vs. 31 %). There was significant association among the frequency of responses of the study groups. Of the 50 patients exposed to both tests, 43 (86 %) agreed that the GWG instructions were clear, 45 (90 %) agreed that the GWG was easy to understand, 31 (62 %) preferred the GWG, 39 (78 %) agreed that the GWG did not increase their anxiety and 31 (62 %) agreed that having conversations about EOL priorities was beneficial. The median STAI score after GWG was 48 (interquartile range, 39–59) vs. 47 (interquartile range, 27–63) after LOS (p = 0.2952). Patients with advanced cancer assigned high importance to spirituality and the presence/relationships of family, and these wishes were consistent over the two tests. The GWG did not worsen anxiety.

BACKGROUND The aim of this study was to identify nurse factors (eg, knowledge, practices, and clinical habits regarding complementary and alternative medicine [CAM] as well as demographic factors) and patient characteristics (eg, age, sex, and treatment status) associated with nurses' CAM inquiry and referral patterns. METHODS Baseline data were collected with nurse/patient questionnaires about CAM use and knowledge as part of a multicenter CAM educational clinical trial. Frequencies and nested regression models were used to assess predictors of nurses' inquiries about and referral to CAM therapies. RESULTS Six hundred ninety-nine patients participated in the study. For patients, female sex (odds ratio [OR], 1.50; P = .019) and cancer recurrence (OR, 1.45; P = .05) were predictive of nurses' inquiries about and referral to CAM therapies. A total of 175 nurses with a mean age of 45 years and a mean experience of 20 years participated; 79% were staff nurses, and 11% were nurse practitioners. Fifty-three percent asked at least 1 of their last 5 patients about CAM use; 42% referred patients to CAM therapy. Nurses who reported being “somewhat comfortable” (OR, 2.70; P = .0001) or “very comfortable” (OR, 3.88; P < .0001) about discussing CAM, self-reported use of massage (OR, 2.20; P < .0001), and had formal CAM education (OR, 4.14; P = .0001) were more likely to ask about CAM use. Nurses who reported being “somewhat comfortable” (OR, 2.54; 95% confidence interval, 1.47-4.41; P = .0008) or “very comfortable” (OR, 7.46; P < .00001) and had formal CAM education (OR, 2.96; P < .0001) were also more likely to refer patients to CAM therapies. CONCLUSIONS Both patient and nurse characteristics were associated with discussions about CAM. Oncology institutions that prioritize evidence-based medicine should consider introducing CAM education to their nursing staff. Cancer 2016. © 2016 American Cancer Society.

BACKGROUND Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. A better understanding of how metastatic cancer affects employment is a necessary step toward the development of tools for assisting survivors in this important realm. METHODS The ECOG-ACRIN Symptom Outcomes and Practice Patterns study was analyzed to investigate what factors were associated with the employment of 680 metastatic cancer patients. Univariate and multivariate logistic regression analyses were conducted to compare patients stably working with patients no longer working. RESULTS There were 668 metastatic working-age participants in the analysis: 236 (35%) worked full- or part-time, whereas 302 (45%) had stopped working because of illness. Overall, 58% reported some change in employment due to illness. A better performance status and non-Hispanic white ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis in the multivariate analysis. The disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. CONCLUSIONS A significant percentage of the metastatic patients remained employed; increased symptom burden was associated with a change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working if this is desired. Improvements in symptom control and strategies developed to help address workplace difficulties have promise for improving this aspect of survivorship. Cancer 2016;122:438–446. © 2015 American Cancer Society.