Mazza, Gina L.

PURPOSE Financial toxicity (FT) affects 20% of cancer survivors and is associated with poor clinical outcomes. No large-scale programs have been implemented to mitigate FT. We evaluated the effect of monthly FT screening as part of a larger patient-reported outcomes (PROs) digital monitoring intervention. METHODS PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomly assigned 1:1 to digital symptom monitoring (PRO practices) or usual care (control practices). Digital monitoring consisted of between-visit online or automated telephone patient surveys about symptoms, functioning, and FT (single-item screening question from Functional Assessment of Chronic Illness Therapy-COmprehensive Score for financial Toxicity) for up to 1 year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this planned secondary analysis was development or worsening of financial difficulties, assessed via the European Organisation for Research and Treatment of Cancer QLQ-C30 financial difficulties measure, at any time compared with baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. RESULTS One thousand one hundred ninety-one patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the FT screening intervention developed, or experienced worsening of, financial difficulties, compared with 39.0% treated at control practices ( P = .004). Patients and nurses interviewed stated that FT screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. CONCLUSION In this report of a secondary outcome from a randomized clinical trial, FT screening as part of routine digital patient monitoring with PROs reduced the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy.

PURPOSE The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions. METHODS PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N–, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL). RESULTS From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point. CONCLUSION For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

Abstract Background: Historically, less than 10% of adult patients with cancer enroll in clinical trials, however, enrollment dropped further at the onset of the COVID-19 pandemic. Barriers to trial participation during the pandemic have not been reported. As part of the TBCRC 057 survey on the impact of the pandemic on willingness to participate in breast cancer trials, we assessed reasons for reluctance to participate in trials during the pandemic. Methods: US residents who self-reported a breast cancer diagnosis were eligible to complete the online survey 8/6/21-9/30/21. Respondents indicated whether they were current trial participants and, if not, their willingness to consider participating in a trial during the pandemic using a 5-point scale (0-not at all willing to 4-definitely willing). Respondents who were not current trial participants and who were not “definitely willing” to consider participation during the pandemic were characterized as “reluctant” and asked to select reasons for their reluctance from a checklist. Pandemic-related anxiety was assessed on an 11-point scale (0-no anxiety to 10-worst anxiety possible). Respondents indicated how the option to conduct trial activities online would affect their decision to participate in a trial (much less likely, somewhat less likely, would not affect my decision, somewhat more likely, or much more likely). In exploratory analyses, we evaluated whether pandemic-related anxiety and favorable reactions towards opportunities to conduct trial activities online were associated with reluctance to consider trial participation during the pandemic due to fear of SARS-CoV-2 exposure. Means were compared with two sample t-tests and proportions with Fisher’s exact tests. Results: Of 385 survey respondents, 185 (48%) were characterized as reluctant to consider trial participation during the pandemic. Among these 185, median age was 55 (range 25-80), 85.7% were non-Hispanic White, 48.1% had metastatic disease and 44.2% received care at academic centers. Reasons for reluctance to consider trial participation during the pandemic cited by ≥15% of the 185 reluctant respondents are shown in the Table. Respondents who selected fear of exposure to SARS-CoV-2 as a reason for their reluctance to consider participating in a trial during the pandemic had higher mean pandemic-related anxiety (7.0 vs 5.2, p&lt; 0.001). These respondents were more likely to indicate telemedicine doctor visits (p=0.01), virtual consents (p=0.001) and online study questionnaires (p=0.001) would make them somewhat or much more likely to participate in trials than respondents who did not select fear of exposure to SARS-CoV-2 as a reason for their reluctance. Conclusions: Reasons for reluctance of patients with breast cancer to consider participation in clinical trials during the pandemic are multifactorial. Although concerns about safety and efficacy remain prominent, fear of exposure to SARS-CoV-2 drives unwillingness to participate in &gt;25% of reluctant patients. Trial accrual may benefit from incorporation of electronic activities when possible. Table Citation Format: Karen L. Smith, Carolyn Mead-Harvey, Gina L. Mazza, Albert E. Holler, Eileen Shinn, Elizabeth Frank, Michelle Melisko, Cyd Eaton, Jeannine M. Salamone, Teri Pollastro, Patricia Spears, Antonio C. Wolff, Gabrielle B. Rocque. Reasons for Reduced Willingness to Participate in Clinical Trials During the COVID-19 Pandemic: The Translational Breast Cancer Research Consortium (TBCRC) 057 Survey [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 P6-08-07.

Abstract Background Pancreatic neuroendocrine tumors (pNETs) are rare cancers with outcomes determined by multiple factors including grade, stage, and clinical presentation. In this study, we aimed to determine the prognosis of patients with pNETs using a large population-based database. Materials and Methods In this population-based study, we identified patients with pNETs from the SEER 18 registry (2000-2016) using a combination of ICD-O-3 and histology codes. We calculated age-adjusted incidence rates using SEER*Stat 8.3.5. In addition, we analyzed overall survival (OS) using the Kaplan-Meier method, and investigated prognostic factors using a multivariable Cox proportional hazards model. Results A total of 8944 pNETs patients were identified. Annual incidence rates increased from 0.27 to 1.00 per 100 000. This was largely explained by an increase in number of patients diagnosed with localized disease in more recent years (2012-2016). Median OS was 68 months (95% CI [64, 73]) and 5-year OS rates in localized, regional, and metastatic disease were 83%, 67%, and 28%, respectively. There was a significant improvement in OS for patients diagnosed between 2009 and 2016 (median OS 85 months) compared with those diagnosed between 2000 and 2008 (median OS 46 months) (HR 0.66; 95% CI [0.62, 0.70]). This improvement in OS was consistent across all stages. Conclusions and Relevance This study shows a steady increase pNETs incidence with notable stage migration to earlier stages in recent years. This increase in incidence is accompanied by a significant improvement in survival across different disease stages.

e18612 Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling and color schemes, and (4) software to produce graphical displays. For consistency, considerations of tolerability relied on the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), which includes 124 items assessing the frequency, severity, interference, and/or presence of 78 symptomatic adverse events. Graphical displays were generated using simulated PRO-CTCAE data and summarized by composite score (range 0-3).Color schemes that were Section 508 compliant and color blindness accessible were created. Surveys were distributed to 68 consortium members to assess preferences and interpretability of the graphical displays. Results: The SWG created graphical displays for PRO-CTCAE data, including bar charts, butterfly plots, and Sankey diagrams and compiled SAS macros and R functions to do so. Graphical displays made available in the toolkit maximize the use of PRO-CTCAE data, incorporate missingness, support between-arm comparisons, and present data longitudinally over treatment cycles or study timepoints. Survey results for labeling and color schemes were summarized and informed a list of short labels for PRO-CTCAE items (e.g., “radiation burns” for “skin burns from radiation”) and standardized color schemes for use in graphical displays. Survey results were also summarized to provide insight into PRO researchers’ ability to accurately interpret the graphical displays. Conclusions: Standardizinggraphical displays is important for improving the communication and interpretation of tolerability data. The type of graphical display used depends on the purpose of the analysis and should be tailored to the intended audience, including patients. This toolkit will provide a comprehensive resource with best practice recommendations.

Background Patients with myeloproliferative neoplasms (MPNs) are faced with severe disease-related fatigue among a range of other constitutional and spleen-related symptoms. The MPN-Symptom Assessment Form (SAF) is recommended for use to characterize symptom burden (Scherber R, et al. Blood 2011). Within the SAF, a profile of 18 symptom items are evaluated ranging in severity from 0 (absent) to 10 (worst imaginable). The SAF is often summarized to the MPN-SAF Total Symptom Score (TSS) for analysis purposes - a single computed sum of the 10 most clinically meaningful symptom scores, including fatigue (Emanuel R, et al. J Clin Oncol 2012). Though the SAF includes a fatigue item, initial deployments of the MPN-SAF TSS incorporated a 0-10 scaled fatigue item taken from the Brief Fatigue Inventory (BFI; Mendoza T, et al. Cancer 1999). A subsequent version of the MPN-SAF TSS for use within myelofibrosis clinical trials (called the MFSAF v4; Gwaltney C, et al. Leuk Res 2017) employed a harmonized fatigue item. This analysis employing data from two studies was carried out to assess the use of the SAF fatigue item within the MPN-SAF TSS for consistency with the MFSAF v4. Methods Both BFI and SAF fatigue items were included in an initial online survey evaluating disease burden among patients with MPNs. Participants were assigned to survey variants as a function of their age. Survey variants included those to receive 1 instance of either the BFI or SAF fatigue item, instances of both BFI and SAF, or 2 instances of the same fatigue item. Surveying was aimed to assess the worst symptom experience in the patient's last 24 hours. Additionally, an independent survey assessing the impact of COVID-19 among MPN patients was deployed using the SAF fatigue item for the MPN-SAF TSS. This modified version was then used to test internal validity. Pearson correlation (r) and t-tests were used to assess association, Bland-Altman methods were used to evaluate systematic agreement between BFI and SAF fatigue scores, and Cronbach's alpha was used to measure internal consistency. Results There were 229 participants assigned both BFI and SAF fatigue items within the same survey. Among them, 51% (n=117) received the BFI item first and 49% (n=112) the SAF item first. No difference was seen between first and second fatigue scores (mean difference [first-second] = 0.00; 95%CI -0.18, 0.17). BFI and SAF fatigue scores were highly correlated (r=0.88, p&lt;0.001) and showed 88.7% agreement in categorizing severe versus non-severe fatigue (score ≥ 7 versus &lt; 7). Overall concordance in severity category was 73.4% (category [score range]: absent [0]; mild [1-3]; moderate [4-6]; severe [7-10]). Constructing the MPN-SAF TSS using the BFI and SAF fatigue components separately, the original and modified MPN-SAF TSS were nearly identical (r=0.997, p&lt;0.001), and had equivalent internal consistency (both Cronbach's alpha=0.88). The Bland-Altman plot further indicates the 2 fatigue measures have high agreement with no evidence of directional bias and negligible overall bias (Figure 1: regression slope = -0.04, p=0.25; mean difference=0.22; 95%CI 0.05, 0.39). Within the COVID-19 survey (n=1217), the modified version of the MPN-SAF TSS was consistent with known correlates among disease characteristics (Emanuel R, et al. J Clin Oncol 2012). For example, more severe MPN-SAF TSS scores were highly correlated with low quality-of-life (n=1156, r = -0.50, p&lt;0.001), and associated with those reporting spleen enlargement (n=301) versus not (n=617) (p&lt;0.001; mean difference=7.7; 95%CI 5.4, 10.1). Conclusion The BFI and SAF fatigue items are highly consistent in raw score, severity category, and in contribution to the MPN-SAF TSS. There was no order effect seen in which fatigue item was asked first. The independent COVID-19 survey using the modified MPN-SAF TSS was validated and shows high internal consistent. In the ongoing development to capture the symptom experience, this analysis shows disease-related fatigue is equivalently measured using the SAF fatigue survey item in harmonization with the MFSAF v4. Disclosures Mesa: Bristol Myers Squibb: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; Incyte: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy; Sierra Oncology: Consultancy.

Introduction Essential thrombocythemia (ET) and polycythemia vera (PV) patients suffer from various symptoms that worsen quality of life (QOL), yet serial data on symptom changes resulting from therapy are sparse in the literature. Patient questionnaires from 2 large multicenter trials (MPN-RC 111, 112) were used to assess change in symptom burden and QOL over 12 months and impact of baseline symptom burden on subsequent change in ET / PV patients on hydroxyurea (HU) or pegylated interferon alfa-2a (PEG). Methods Trials MPN-RC 111 was a single-arm, open-label, phase II trial evaluating response to PEG in high-risk ET / PV patients with HU resistance/intolerance or splanchnic vein thrombosis (SVT; NCT01259817). MPN-RC 112 was a randomized, open-label, phase III trial comparing response to PEG versus HU in cytoreductive therapy naïve high-risk ET / PV patients diagnosed &lt; 5 years ago (NCT01258856). Measures Patients reported disease-related symptoms via the validated Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF), QOL via the European Organisation for the Research and Treatment of Cancer Core QOL Questionnaire (EORTC QLQ-C30), and (if applicable) PEG-related symptoms (flu-like symptoms, injection site irritation, blurry vision, vision change, flushing) at baseline, 3, 6, 9, and 12 months. Analysis Mixed models assessed mean changes from baseline in the MPN-SAF Total Symptom Score (TSS), MPN-SAF items, QOL, and PEG-related symptoms in MPN-RC 111, 112 PEG, and 112 HU patients. Mixed models also assessed the impact of baseline symptom burden (high [TSS ≥ 20] versus low) on subsequent change in PEG (MPN-RC 111 and 112) and HU patients. Results Patients Of the 135 enrolled MPN-RC 111 patients, 20 with SVT and 1 with no questionnaires were excluded. Of the remaining 114, 64 (56%) / 50 (44%) had ET / PV. Patients were 51% / 48% female. Median age was 65 / 64 years, and median time since diagnosis was 38 / 55 months. 31% / 22% had prior thrombosis, and 19% / 56% had splenomegaly. Of the 168 enrolled MPN-RC 112 patients (82 PEG, 86 HU), 2 with no questionnaires were excluded. Of the remaining 166, 79 (48%) / 87 (52%) had ET / PV. Patients were 50% / 33% female. Median age was 60 / 62 years, and median time since diagnosis was 3 / 3 months. 25% / 29% had prior thrombosis, and 11% / 37% had splenomegaly. Symptoms Questionnaire completion rates ranged from 90 - 99%, 87 - 100%, and 75 - 96% for on-treatment MPN-RC 111, 112 PEG, and 112 HU patients. At baseline, TSS (0 [absent] - 100 [worst imaginable]) and QOL (0 [very poor] - 100 [excellent]) means (SDs) were 19.5 (18.4) and 71.6 (20.1) for MPN-RC 111, 17.0 (13.6) and 67.9 (24.3) for MPN-RC 112 PEG, and 14.6 (11.4) and 73.8 (18.8) for MPN-RC 112 HU patients. On average, MPN-RC 111 patients had significant improvement of TSS, fatigue, abdominal pain, abdominal discomfort, dizziness, numbness, night sweats, and fever; MPN-RC 112 PEG patients had significant worsening of fever; and MPN-RC 112 HU patients had significant worsening of inactivity (no mean changes indicating improvement were observed). PEG patients had significant worsening of PEG-related symptoms. The greatest improvements occurred in the 46 (40%), 27 (33%), and 23 (28%) MPN-RC 111, 112 PEG, and 112 HU patients with high baseline symptom burden. On average, PEG patients with high baseline symptom burden had significant improvement of TSS, fatigue, early satiety, abdominal pain, abdominal discomfort, inactivity, headache, concentration, dizziness, numbness, insomnia, cough, night sweats, itching, bone pain, fever, weight loss, and QOL, while those with low baseline symptom burden had significant worsening of TSS, early satiety, headache, itching, and bone pain. On average, HU patients with high baseline symptom burden had significant improvement of TSS, early satiety, abdominal discomfort, headache, dizziness, numbness, insomnia, itching, and weight loss, while those with low baseline symptom burden had significant worsening of TSS, early satiety, abdominal discomfort, inactivity, concentration, and sexual desire/function (Figures 1 and 2). Conclusions Although no statistical comparisons were made across trials, overall improvements were seen in MPN-RC 111 but not 112. Patients with high baseline symptom burden experienced the greatest improvements in symptom burden and QOL during treatment with PEG or HU, which may explain the improvements seen in the more advanced patients in MPN-RC 111 compared to 112. Disclosures Mascarenhas: Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution). Yacoub:Dynavax: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Cara Therapeutics: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in private company; Incyte: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support. Hoffman:Protagonist: Consultancy; Forbius: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Dompe: Research Funding. Silver:PharmaEssentia: Speakers Bureau. Mesa:Bristol Myers Squibb: Research Funding; Incyte: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy.

Background The COVID-19 pandemic continues to challenge effective treatment delivery to hematologically-compromised patients, including those with myeloproliferative neoplasms (MPNs). MPNs are characterized by clonal proliferation of hematopoietic cell lines in bone marrow. As such, increasing reports of COVID-19 related thrombotic events highlight how MPN patients are at an increased risk in navigating potential complications during this pandemic. Mitigation strategies to lesson MPN patient exposure to COVID-19 are vital. Though, such efforts come at an inherent cost to effective healthcare delivery. Restriction of regular in-clinic treatments and reported shortages of MPN pharmacotherapies present these patients with diminishing continued care. To understand how MPN patient care has been impacted by COVID-19, an internet-based questionnaire was deployed surveying a variety of disease and pandemic related items (reported elsewhere; Palmer J et al, ASH 2020 submitted). A single free-text response item instructed respondents to: "Please tell us anything else (bad or good) about how the COVID-19 outbreak has impacted your MPN care." This qualitative analysis evaluated first-hand comments directly from patients in order to form a richer understanding of how those with MPNs have been managing disease-related care amidst this pandemic. Methods This COVID-19 survey was hosted via Mayo Clinic's secured REDCap system for online surveys and posted on MPN organizational partner websites. Surveys were completely anonymous. The free-text responses describing impacts to MPN care were each independently reviewed by 2 individuals for overall sentiment (positive, negative, both, or neutral [no impact]) and categorized for themes. The 2 reviewers were assessed for agreement. Conflicting reviews were evaluated then adjudicated by an algorithm for cases meeting selected conditions or by lead author review for all remaining cases. Descriptive statistics are reported. Results Of the 1217 consenting adult patients participating in the overall COVID-19 study, 824 provided free-text responses. Of these, respondent MPN diagnoses included, essential thrombocythemia (n=324, 39%), polycythemia vera (n=251, 30%), myelofibrosis (n=153, 19%), and other/undisclosed (96, 12%); 69% (n=567) were female; median age was 63 (range 21-93); 38% (n=313) were from the US, 38% (n=313) UK, and 24% (n=198) other/unknown. There was 89% (n=734) sentiment agreement between reviewers. Free-text responses about the impact of COVID-19 on MPN care were 49% (n=400) negative, 21% (n=177) positive, 8% (n=65) both positive and negative, and 22% (n=182) neutral/no impact. Table 1 shows a selection of MPN patient free-text responses reflecting common negative and positive sentiment themes. Negative impact (n=400): The most common negative impact involved delays or cancellations of visits or perceived inaccessibility to regular providers (n=261, 65%). Primarily this sentiment was driven by lack of clinic availability and restrictions at treatment centers or by providers. However, some respondents reported delaying or canceling visits themselves due to fear of COVID-19 exposure. Perceived health consequences from this delay were also expressed. There were 129 (32%) respondents with concern regarding changes or access to medications, including explicit drug supply shortages. Some patients resorted to self-adjusting medications and reusing single-use supplies. General anxiety, stress, and isolation were also reported (n=98, 25%). Positive impact (n=177): Availability of telemedicine comprised the majority of positive impacts of the pandemic (n=95, 54%), with many noting the reduced travel time to visits. Routine local testing coupled with follow-up telemedicine was favorable. Despite general positivity towards telemedicine, some reported preferences for in-person visits; commenting that telemedicine was impersonal, difficult to schedule or receive virtual communication, and expressed concern for lack of spleen examinations during virtual visits. Conclusion Positive and negative aspects were reported including MPN-specific issues. Healthcare systems should use such data to emerge from the COVID-19 pandemic and retain the positive impacts such as telemedicine, while developing education materials and other resources to address the reported negative impacts where possible. Disclosures Mesa: CTI BioPharma: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Sierra Oncology: Consultancy; Samus Therapeutics: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Incyte: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Bristol Myers Squibb: Research Funding.