Effectiveness of Community-Engaged Research Strategies in Increasing COVID-19 Vaccinations in Targeted Communities: The Community Engagement Alliance (CEAL) Regional Teams.

Objectives. To explore a key outcome of interest for the Community Engagement Alliance (CEAL) Regional Teams by examining COVID-19 vaccinations over time in US counties where CEAL teams operated and comparing them to demographically similar counties in the same state. Methods. Our evaluation used a nonequivalent control group design. Each county where a CEAL team operated was matched to a unique non-CEAL county in the same state. Components of the Centers for Disease Control and Prevention's Social Vulnerability Index were used as the matching criteria. COVID-19 vaccinations (county-level percentage of residents aged 18 years or older who are fully vaccinated) for CEAL and matched counties were analyzed over time. Results. The mean percentage of vaccinated adults was significantly higher in CEAL counties than in matched non-CEAL counties. Sensitivity analyses confirmed conclusions did not change depending on the CEAL cohort or closeness of matches. Conclusions. Our findings support CEAL team efforts to increase COVID-19 vaccinations in target communities and employ community-engaged research more broadly within public health contexts. (Am J Public Health. 2024;114(S1):S124-S127. https://doi.org/10.2105/AJPH.2023.307517).

COVID-19 Information, Trust, and Risk Perception Across Diverse Communities in the United States: Initial Findings from a Multistate Community Engagement Alliance (CEAL).

Objectives. To provide initial findings from Community Engagement Alliance (CEAL), a multistate effort funded by the National Institutes of Health, to conduct urgent community-engaged research and outreach focused on COVID-19 awareness, education, and evidence-based response. Methods. We collected survey data (November 2020-November 2022) from 21 CEAL teams from 29 state and regional CEAL sites spanning 19 US states, the District of Columbia, and Puerto Rico, which covered priority populations served and trusted sources of information about COVID-19, including prevention behaviors, vaccination, and clinical trials. Results. A disproportionate number of respondents were Latino (45%) or Black (40%). There was considerable variability between CEAL sites regarding trusted sources of information, COVID-19 prevention, and COVID-19 vaccination. For example, more respondents (70%) reported health care providers as a trusted source of COVID-19 information than any other source (ranging from 6% to 87% by site). Conclusions. CEAL rapidly developed novel infrastructure to engage academic, public health, and community organizations to address COVID-19's impacts on underserved communities. CEAL provides an example of how to respond in future public health emergencies to quickly promote trustworthy, evidence-based information in ways that advance health equity. (Am J Public Health. 2024;114(S1):S112-S123. https://doi.org/10.2105/AJPH.2023.307504).

Do Editorialists With Industry-Related Conflicts of Interest Write Unduly Favorable Editorials for Cancer Drugs in Top Journals?

BACKGROUND: Editorials accompanying the publication of trials in major oncology journals can have a substantial influence on clinical practice. We describe the prevalence of financial conflicts of interest (FCOIs) of authors writing such editorials and the extent to which FCOIs may shape the interpretation of clinical trials. METHODS: We examined editorials published in 2018 alongside trial reports in the top 5 journals that publish cancer drug trials (New England Journal of Medicine, Lancet, Lancet Oncology, JAMA Oncology, and Journal of Clinical Oncology). An editorial was considered to have an FCOI if at least one of the editorialists had any disclosed FCOI. An FCOI with the same company whose drug was being discussed in the editorial was classified as a direct FCOI. Editorials were reviewed for their content and classified as being unduly favorable (defined as the presence of a positive spin without discussion of limitations) or not. Association of an FCOI and a direct FCOI with writing an unduly favorable editorial was assessed. RESULTS: Of the 90 editorials assessed, 74% (n=67) were classified as having an FCOI with the pharmaceutical industry, and 39% (n=35) had an FCOI with the same company whose product was being discussed in the editorial (direct FCOI). Editorials were classified as being unduly favorable toward the study drug in 12% (8 of 67) and 13% (3 of 23) (P=1.0) of those with and without FCOIs, respectively; corresponding rates with and without direct FCOI were 23% (8 of 35) and 5% (3 of 55), respectively (P=.009). CONCLUSIONS: Editorials in top oncology journals were frequently authored by experts with FCOIs, including direct FCOIs. Authoring an unduly favorable editorial for a new cancer drug was significantly associated with the author having a direct FCOI with the same company. These findings support the call for journals to ensure that authors of editorials have no direct FCOIs.

Mothers' Decisions About Donating Newborns' Blood Spots for Research: A Qualitative Study.

Residual dried blood spots from millions of newborns are being stored and used for research. The state of Michigan proactively developed a broad consent process for research use of newborns' blood spots. However, the extent to which mothers make informed choices about this research is unclear. A descriptive, qualitative study was conducted examining this issue. Twenty-nine observations of the consent process and 20 semistructured interviews were conducted with mothers on the postpartum unit of a large, academic hospital in Michigan. Content analysis of the transcripts was conducted. While most mothers agreed to donate the blood spots (n = 14/20; 70%), findings indicated that most decisions were uninformed (n = 16/20; 80%), as mothers lacked knowledge of biobanking research. Misunderstandings about anonymity, the consenter's credentials, and entity conducting the research seemed to influence decision making. Suggestions for improving the consent process include (1) changing the venue of blood spot education and consent from the postpartum period to the perinatal period, (2) strengthening the depth of information and delivery of information provided about the topic, including ethical and values clarification, and (3) increasing consenter education and training. Implementation may help increase the proportion of informed decisions.

A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer.

BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC). METHODS: Women with HER-2 positive MBC, Performance status (PS 0-2), and no limit on number of prior chemotherapies or lines of anti-HER-2 therapies were enrolled. A 3 + 3 dose escalation design was utilized. Four dose levels were intended with starting doses of foretinib 30 mg and lapatinib 750 mg orally once a day (OD) on a 4-weekly cycle. Assessment of c-MET status from the primary archival tissue was performed. RESULTS: We enrolled 19 patients, all evaluable for toxicity assessment and for response evaluation. Median age was 60 years (34-86 years), 95% were PS 0-1, 53% were estrogen receptor-positive and 95% had at least one prior anti-HER-2-based regimen. The fourth dose level was reached (foretinib 45 mg/lapatinib 1250 mg) with dose-limiting toxicities of grade-3 diarrhea and fatigue. There was only one grade-4 non-hematological toxicity across all dose levels. There were no PK interactions between the agents. A median of two cycles was delivered across the dose levels (range 1-20) with associated progression-free survival of 3.2 months (95% CI 1.61-4.34 months). By immunohistochemical assessment with a specified cutoff, none of the 17 samples tested were classified as positive for c-Met. CONCLUSIONS: The RP2D of the combined foretinib and lapatinib is 45 mg and 1000 mg PO OD, respectively. Limited activity was seen with this combination in a predominantly unselected cohort of HER-2-positive patients with MBC.

Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer. METHODS: In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase. Participants were randomly allocated (2:3:3), with five stratification factors and in alternating blocks, to receive placebo alongside chemotherapy and then placebo only maintenance (arm A; reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance). Patients continued treatment to progression or excessive toxic effects. The primary efficacy endpoint was progression-free survival between arms A and C. Efficacy analysis was by intention to treat. Safety was assessed in all patients who received the allocated study drug. This trial is registered with ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003. FINDINGS: We randomly assigned 486 [corrected] women between Nov 13, 2007, and Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent to the 30mg safety phase. During a median of 19·5 months (IQR 14-26) follow-up, 113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C had disease progression. Median progression-free survival was 11·0 months (95% CI 10·4-11·7) in arm C and 8·7 months (7·7-9·4) in arm A (hazard ratio 0·56, 0·44-0·72, p<0·0001). 156 (90%) of 174 patients in arm B had disease progression, and median progression-free survival was 9·9 months (95% CI 9·4-10·5). Diarrhoea, neutropenia, hypertension, and voice changes were significantly more common, during chemotherapy with cediranib, and diarrhoea, hypothyroidism and voice changes were more common during maintenance. Poor compliance with cediranib was noted during maintenance treatment with toxic effects being the most common cause for discontinuation. INTERPRETATION: Cediranib, when given orally with chemotherapy and continued as maintenance, yielded a meaningful improvement [corrected] in progression-free survival in women with recurrent platinum-sensitive ovarian cancer, albeit with added toxic effects. The positive results in ICON6 could provide women with a new therapeutic option for recurrent ovarian cancer. Assessment of the secondary endpoint of overall survival will need longer follow-up. FUNDING: Medical Research Council, Cancer Research UK, Canadian Cancer Society Research Institute, Cancer Australia, National Gynecological Cancer Centre, and AstraZeneca.

Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer.

In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7 % response evaluable cTNBC 5.4 %) with a median duration of 4.4 months (range 3.7-5 m) and 15 patients had stable disease (ITT 33 %, response evaluable cTNBC 40.5 %) with a median duration of 5.4 months (range 2.3-9.7 m). The most common toxicities (all grades/grade 3) were nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), and diarrhea (40/7 %). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46 % in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484).

Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel versus carboplatin-paclitaxel: effects on quality of life.

BACKGROUND: A recent phase III trial compared the efficacy of cisplatin-topotecan (a topoisomerase I inhibitor) followed by carboplatin-paclitaxel (Arm 1) versus paclitaxel-carboplatin (Arm 2) in women with newly diagnosed stage IIB or greater ovarian cancer. There was a significantly lower response rate in the experimental arm compared to standard treatment, and less likelihood of normalized CA125 within the first 3 months. At 43 months follow-up, there were no significant group differences in progression-free survival. There were also significantly more side effects in the experimental arm. METHODS: The current study examined quality of life (QoL) endpoints using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the ovarian cancer module, QLQ-OV28, administered prior to randomization, at day 1 of treatment cycles 3, 5, and 7, at completion of the last cycle, and at 3 and 6 months following completion of chemotherapy. RESULTS: Global QoL, physical symptoms, fatigue, and role, emotional, cognitive and social function (all from the EORTC QLQ-C30) significantly improved in both treatment arms, with no significant between-arm differences. Between-group differences in pain, insomnia, and peripheral neuropathy reported while on treatment did not differ at follow-up. Nausea and vomiting improved more with standard treatment both during and after treatment. Body image significantly differed between the groups only at cycle 5 (more deterioration in Arm 2) but group differences disappeared at follow-up. A stratified analysis of global QoL by debulking surgery status found no greater effect indicating that overall improvements in QoL were unrelated to surgical recovery. CONCLUSIONS: There was no significant QoL advantage of cisplatin-topotecan. This finding, combined with no progression-free survival conferred by this combination, reaffirms carboplatin-paclitaxel as the standard of care for women with newly diagnosed ovarian cancer.

Primary care providers' experiences with and perceptions of personalized genomic medicine.

OBJECTIVE: To assess primary care providers' (PCPs') experiences with, perceptions of, and desired role in personalized medicine, with a focus on cancer. DESIGN: Qualitative study involving focus groups. SETTING: Urban and rural interprofessional primary care team practices in Alberta and Ontario. PARTICIPANTS: Fifty-one PCPs. METHODS: Semistructured focus groups were conducted and audiorecorded. Recordings were transcribed and analyzed using techniques informed by grounded theory including coding, interpretations of patterns in the data, and constant comparison. MAIN FINDINGS: Five focus groups with the 51 participants were conducted; 2 took place in Alberta and 3 in Ontario. Primary care providers described limited experience with personalized medicine, citing breast cancer and prenatal care as main areas of involvement. They expressed concern over their lack of knowledge, in some circumstances relying on personal experiences to inform their attitudes and practice. Participants anticipated an inevitable role in personalized medicine primarily because patients seek and trust their advice; however, there was underlying concern about the magnitude of information and pace of discovery in this area, particularly in direct-to-consumer personal genomic testing. Increased knowledge, closer ties to genetics specialists, and relevant, reliable personalized medicine resources accessible at the point of care were reported as important for successful implementation of personalized medicine. CONCLUSION: Primary care providers are prepared to discuss personalized medicine, but they require better resources. Models of care that support a more meaningful relationship between PCPs and genetics specialists should be pursued. Continuing education strategies need to address knowledge gaps including direct-to-consumer genetic testing, a relatively new area provoking PCP concern. Primary care providers should be mindful of using personal experiences to guide care.

Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer.

BACKGROUND: Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is of increasing interest as a therapeutic strategy in many tumors. The aim of this study was to identify molecular markers associated with mTOR inhibitor activity in women with metastatic endometrial cancer. METHODS: Archival tumor samples were collected from 94 women with recurrent or metastatic endometrial cancer who participated in 3 National Cancer Insitute of Canada Clinical Trials Group phase 2 trials investigating single-agent mTOR inhibitors: IND160A and IND160B (temsirolimus) and IND192 (ridaforolimus). Analyses included mutational profiling using the OncoCarta Panel version 1.0 and immunohistochemical expression of the tumor suppressor gene PTEN (phosphatase and tensin homologue) and stathmin, a marker of PI3K activation. Associations between biomarker results and clinical outcomes were assessed. RESULTS: Mutations were found in 32 of 73 analyzed tumors, PIK3CA (21 patients) was the most common mutated gene. Co-mutations were seen in 8 tumors, most frequently KRAS and PIK3CA (4 cases). PTEN loss was observed in 46 of 85 samples analyzed and increased stathmin expression was observed in 15 of 65 analyzed samples. No correlation was observed between biomarkers and response or progression. In patients taking concurrent metformin, there was a trend toward lower progression, of 11.8% versus 32.5% (P = .14). CONCLUSIONS: No predictive biomarker or combination of biomarkers for mTOR inhibitor activity were identified in this study. Restriction and enrichment of study entry, especially based on archival tumor tissue, should be undertaken with caution in trials using these agents.

Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer.

OBJECTIVE: The phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study. METHODS: This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40mg for 5 consecutive days followed by a 2day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting. RESULTS: 31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status. CONCLUSION: Oral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.

Newborn Screening Has Moved Way Beyond PKU.

Nurses need to understand how clinical genetic and genomic applications affect newborn screening and advocate for parents and newborns.

Clinical and toxicity predictors of response and progression to temsirolimus in women with recurrent or metastatic endometrial cancer.

OBJECTIVE: Temsirolimus (TEM) has recently shown activity (NCIC CTG phase II trial) in endometrial cancer (EC). Despite EC having a high rate of PTEN mutation, in this trial activity was independent of PTEN and other molecular markers. We explored whether treatment related toxicity occurring in cycle one was predictive of outcomes. METHODS: Patients were those enrolled on two sequential phase II studies of the NCIC CTG that evaluated single agent TEM in women with recurrent or metastatic chemotherapy naïve or treated EC. An exploratory landmark analysis examined the relationship between early treatment related toxicities as well as prior chemotherapy and efficacy outcomes (response, progression, and tumor size shrinkage) in univariate and multivariate analyses. The relationship between molecular markers and outcomes was also reexamined in patients. RESULTS: Mucositis, diarrhea, decreased absolute neutrophil count, as well as elevated glucose, or cholesterol were not independent predictors of response or progression. Highest fasting triglyceride predicted for a 3.5% tumor shrinkage from baseline. Women previously treated with chemotherapy were at 7.37 times greater risk of progression and experienced 20.9% increased tumor growth compared to chemotherapy naïve women. Molecular markers were not predictors of response or progression. CONCLUSIONS: Except for elevation in fasting triglyceride being associated with minimal tumor shrinkage, no other relationship between efficacy and TEM induced adverse events was found. mTOR inhibition activity in EC seems greatest in chemo-naïve patients. Future studies of mTOR inhibitors in EC should focus on women without prior chemotherapy while continuing to explore molecular mechanisms of benefit.

A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium.

BACKGROUND: Pracinostat (SB939) is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDAC). The adult recommended phase II dose (RP2D) is 60 mg po three times per week (t.i.w.) for 3 weeks every 4 weeks. This study assessed the toxicities and pharmacokinetics of pracinostat and determined the RP2D in children with refractory solid tumors. METHODS: Pediatric patients with refractory solid tumors were treated with oral pracinostat t.i.w. for 3 consecutive weeks, followed by 1 week off dosing. Three dose levels-25, 35, and 45 mg/m(2) were evaluated using a standard 3 + 3 cohort design. Pharmacokinetic (PK) studies were optional. RESULTS: Twelve patients were enrolled. The most common diagnosis was Ewing sarcoma. Most adverse events (AEs) were hematological with five (40%) patients experiencing grade 3 neutropenia. Non-hematological AEs were generally grade 1. No dose limiting toxicities occurred. More hematological and non-hematological AEs occurred at 45 mg/m(2) : Two of five patients experienced Grade 3 neutropenia and one each Grade 3 thrombocytopenia and leucopenia, Grade 1 fatigue and anorexia occurred in three. The RP2D was declared to be 45 mg/m(2) (comparable to an adult dose of 80 mg). One patient had a best response of stable disease (duration of 2.9 months). Three patients on 25 mg/m(2) and one each on 35 and 45 mg/m(2) participated in the PK study. No dose related changes in Cmax or AUC occurred. CONCLUSIONS: Pracinostat is reasonably well tolerated in children with refractory solid tumors. The RP2D is 45 mg/m(2) .

Thoughts on Writing High-Quality Review Articles.

The Associate Editor provides useful suggestions for authors on writing review articles.

Characterizing Variability in Lung Cancer Outcomes and Influence of a Lung Diagnostic Assessment Program in Southeastern Ontario, Canada.

INTRODUCTION: Regional variability in lung cancer (LC) outcomes exists across Canada, including in the province of Ontario. The Lung Diagnostic Assessment Program (LDAP) in southeastern (SE) Ontario is a rapid-assessment clinic that expedites the management of patients with suspected LC. We evaluated the association of LDAP management with LC outcomes, including survival, and characterized the variability in LC outcomes across SE Ontario. METHODS: We conducted a population-based retrospective cohort study by identifying patients with newly diagnosed LC through the Ontario Cancer Registry (January 2017-December 2019) and linked to the LDAP database to identify LDAP-managed patients. Descriptive data were collected. Using a Cox model approach, we compared 2-year survival for patients managed through LDAP vs. non-LDAP. RESULTS: We identified 1832 patients, 1742 of whom met the inclusion criteria (47% LDAP-managed and 53% non-LDAP). LDAP management was associated with a lower probability of dying at 2 years (HR 0.76 vs. non-LDAP, p < 0.0001). Increasing distance from the LDAP was associated with a lower likelihood of LDAP management (OR 0.78 for every 20 km increase, p < 0.0001). LDAP-managed patients were more likely to receive specialist assessment and undergo treatments. CONCLUSIONS: In SE Ontario, initial diagnostic care provided via LDAP was independently associated with improved survival in patients with LC.

Patients' attitudes and preferences toward delayed disease progression in the absence of improved survival.

BACKGROUND: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences. METHODS: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings. RESULTS: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values. CONCLUSIONS: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed.