US Cancer Research Articles

Estimation of the Number of Individuals Living With Metastatic Cancer in the United States.

The purpose of this study was to estimate the number of individualsliving with metastatic breast, prostate, lung, colorectal, or bladder cancer or metastatic melanoma in the United States using population-based data. A back-calculation method was used to estimate the number of individuals living with metastatic cancer for each cancer type from US cancer mortality and survival statistics from the Surveillance, Epidemiology, and End Results registries. The percentages of those living with metastatic cancer who advanced to metastatic disease from early stage cancer vs who were diagnosed with metastatic cancer de novo were calculated. One- and 5-year relative survival rates for de novo metastatic cancer were compared by year of diagnosis to assess time trends in survival. It is estimated that, in 2018, 623 405 individuals were living with metastatic breast, prostate, lung, colorectal, or bladder cancer, or metastatic melanoma in the United States. This number is expected to increase to 693 452 in 2025. In 2018, the percentage of metastatic cancer survivors who were initially diagnosed with early stage cancer and advanced to metastatic cancer ranged from 30% for lung cancer to 72% for bladder cancer. This study demonstrates increasing numbers of individuals living with metastatic cancer of the 6 most common cancer types in the United States. This information is critical for informing the allocation of research efforts and healthcare infrastructure needed to address the needs of these individuals.

Combined lifestyle, mental health, and mortality in US cancer survivors: a national cohort study

BackgroundAdopting healthy lifestyles and staying mentally health are two cost-effective modifiable strategies that cancer survivors can implement in self-management. We aimed to evaluate the independent, mediation, interaction, and joint associations of combined lifestyle and mental health with mortality in cancer survivors.MethodsWe performed a cohort study including 3145 cancer survivors from National Health and Nutrition Examination Survey (2005–2018). A healthy lifestyle score was constructed based on post-diagnosis body mass index, physical activity, diet, smoking, and drinking. Post-diagnosis mental health was assessed by Patient Health Questionnaire (PHQ-9). Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and non-cancer mortality were computed using Cox proportional hazards regression models.ResultsAfter 20,900 person-years of follow-up (median, 6.3 years), cancer survivors with higher lifestyle score had decreased mortality, independent of mental health. Compared to participants with lower lifestyle score (0–1), HRs (95% CIs) for all-cause and non-cancer mortality among those with higher lifestyle score (3–5) were 0.68 (0.52–0.89) and 0.69 (0.56–0.85), respectively. 6.2–10.3% of the associations were mediated by mental health. Similar trends were observed among participants categorized by mental health, those with better mental health had lower mortality, independent of lifestyle. Participants with better mental health benefited more from adopting healthy lifestyles, and vice versa. Combinations of higher healthy lifestyle score and better mental health were associated with significant decreased mortality, the lowest mortality was seen in participants with highest healthy lifestyle score and concurrently with best mental health.ConclusionsFor the first time, in this cohort study with a nationally representative sample of US cancer survivors, we comprehensively explored the complex associations of lifestyle, mental health, and mortality. Evidence derived from this study may give much confidence to cancer survivors and healthcare providers that, changing one’s lifestyle and/or staying mentally healthy after cancer diagnosis can improve survival.

Adoption of Telemedicine in a Rural US Cancer Center Amid the COVID-19 Pandemic: Qualitative Study.

BackgroundThe COVID-19 pandemic necessitated a rapid shift to telemedicine to minimize patient and provider exposure risks. While telemedicine has been used in a variety of primary and specialty care settings for many years, it has been slow to be adopted in oncology care. Health care provider and administrator perspectives on factors affecting telemedicine use in oncology settings are not well understood, and the conditions associated with the COVID-19 pandemic offered the opportunity to study the adoption of telemedicine and the resulting provider and staff perspectives on its use.ObjectiveThe aim of this paper is to study the factors that influenced telemedicine uptake and sustained use in outpatient oncology clinics at a US cancer center to inform future telemedicine practices.MethodsWe used purposive sampling to recruit a mix of oncology specialty providers, practice managers, as well as nursing and administrative staff representing 5 outpatient oncology clinics affiliated with the Dartmouth Cancer Center, a large regional cancer center in the northeast of United States, to participate in semistructured interviews conducted over 6 weeks in spring 2021. The interview guide was informed by the 5 domains of the Consolidated Framework for Implementation Research, which include inner and outer setting factors, characteristics of the intervention (ie, telemedicine modality), individual-level factors (eg, provider and patient characteristics), and implementation processes. In total, 11 providers, 3 leaders, and 6 staff participated following verbal consent, and thematic saturation was reached across the full sample. We used a mixed deductive and inductive qualitative analysis approach to study the main influences on telemedicine uptake, implementation, and sustainability during the first year of the COVID-19 pandemic across the 5 settings.ResultsThe predominant influencers of telemedicine adoption in this study were individual provider experiences and assumptions about patient preference and accessibility. Providers’ early telemedicine experiences, especially if negative, influenced preferences for telephone over video and affected sustained use. Telemedicine was most favorably viewed for lower-acuity cancer care, visits less dependent on physical exam, and for patient and caregiver education. A lack of clinical champions, leadership guidance, and vision hindered the implementation of standardized practices and were cited as essential for telemedicine sustainability. Respondents expressed anxiety about sustaining telemedicine use if reimbursements for telephonic visits diminished or ceased. Opportunities to enhance future efforts include a need to provide additional guidance supporting telemedicine use cases and evidence of effectiveness in oncology care and to address provider concerns with communication quality.ConclusionsIn a setting of decentralized care processes, early challenges in telemedicine implementation had an outsized impact on the nature and amount of sustained use. Proactively designed telemedicine care processes with attention to patient needs will be essential to support a sustained role for telemedicine in cancer care.

Assessment of metal pollution and human health risks in road dust from mineral rich zone of East Singhbhum, India.

A detailed study of heavy metals in the road dust of a mineral rich zone of Jharkhand state, India is reported herein. Metal concentrations in the road dust exceeded the corresponding values in the average shale as well as world average of soil. Metal pollution due to the road dust and the possible health impact arising there from was appraised through a number of indices such as Geo-accumulation Index (Igeo), Pollution Load Index, Enrichment Factor (EF), Contamination Factor and US EPA Hazard Index and Cancer Risk. Cu contamination was highest as per EF and Igeo, followed by Pb and Zn. Aggravated heavy metal loading in the road dust was conspicuous in the proximity of copper mines and processing units. Both geogenic and anthropogenic sources were responsible for heavy metals in road dust according to principal component analysis. Hazard Quotient, Hazard Index and Cancer Risk were calculated to ascertain non-carcinogenic and carcinogenic health risks in adults and children. Local inhabitants, particularly children, were under appreciable cancer and non-cancer risk. Oral ingestion was the major pathway for risk to the local commuters followed by dermal pathway. Present study underscored the importance of regular heavy metal monitoring of road dust in this zone and administer proactive road dust management practices to reduce metal pollution.

Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor first-line maintenance among patients with newly diagnosed advanced ovarian cancer in a real-world database (351)

Objectives: With the advent of poly (adenosine diphosphate [ADP]- ribose) polymerase inhibitors (PARPi), first-line (1L) maintenance therapy in patients with ovarian cancer (OC) has evolved in recent years. This study described the use of 1L maintenance and assessed predictors of 1L PARPi maintenance therapy use among PARPi- eligible patients with OC in a real-world setting. Methods: This retrospective cohort study included patients with newly diagnosed stage III/IV epithelial OC who received the last dose of 1L platinum-based chemotherapy (PBC) between January 1, 2017, and February 28, 2021, from the nationwide Flatiron Health electronic health record-derived database. During the study period, the de-identified data originated from approximately 280 US cancer clinics. The end of the last cycle of 1L PBC was defined as the index date. Patients who started a second-line treatment within two months of the index date were excluded. Multivariable logistic regression was used to identify predictors of 1L PARPi monotherapy use versus active surveillance (AS). Variables included in the model were selected using the stepwise approach. Results: A total of 1010 patients were included in the study; 37.9% and 62.1% of patients received maintenance therapy and AS, respectively. A total of 162 (16.0%) patients received PARPi monotherapies (niraparib 6.3%, olaparib 8.7%, and rucaparib 1.0%), 122 (12.1%) received bevacizumab monotherapy, 33 (3.3%) received bevacizumab + PARPi combination therapies and 66 (6.5%) received other therapies. The median age was 68.0 years (Q1:58.0; Q3:75.0) for AS and 65.0 years (56.0; 71.8) for PARPi monotherapies. Other patient characteristics are shown in Table 1. Patients with BRCA mutation were significantly more likely to receive PARPi monotherapies (odds ratio [OR]: 7.49; 95% CI: 4.21-13.31) than patients with BRCA wild-type. Patients treated in 2019 (OR: 7.57; 95% CI: 3.86-14.86) and 2020 (OR: 14.99; 95% CI: 7.61-29.53) were significantly more likely to receive PARPi monotherapies than patients treated in 2017. Race, region of residence, practice type, FIGO stage at initial diagnosis, Eastern Cooperative Oncology Group (ECOG) score, residual disease status, and other disease characteristics were not selected into the model. Conclusions: Over the last four years, the use of 1L PARPi maintenance among ovarian cancer patients has increased significantly, mostly driven by biomarker status. However, stage and extent of residual disease after surgery were not associated with PARPi maintenance use. Objectives: With the advent of poly (adenosine diphosphate [ADP]- ribose) polymerase inhibitors (PARPi), first-line (1L) maintenance therapy in patients with ovarian cancer (OC) has evolved in recent years. This study described the use of 1L maintenance and assessed predictors of 1L PARPi maintenance therapy use among PARPi- eligible patients with OC in a real-world setting. Methods: This retrospective cohort study included patients with newly diagnosed stage III/IV epithelial OC who received the last dose of 1L platinum-based chemotherapy (PBC) between January 1, 2017, and February 28, 2021, from the nationwide Flatiron Health electronic health record-derived database. During the study period, the de-identified data originated from approximately 280 US cancer clinics. The end of the last cycle of 1L PBC was defined as the index date. Patients who started a second-line treatment within two months of the index date were excluded. Multivariable logistic regression was used to identify predictors of 1L PARPi monotherapy use versus active surveillance (AS). Variables included in the model were selected using the stepwise approach. Results: A total of 1010 patients were included in the study; 37.9% and 62.1% of patients received maintenance therapy and AS, respectively. A total of 162 (16.0%) patients received PARPi monotherapies (niraparib 6.3%, olaparib 8.7%, and rucaparib 1.0%), 122 (12.1%) received bevacizumab monotherapy, 33 (3.3%) received bevacizumab + PARPi combination therapies and 66 (6.5%) received other therapies. The median age was 68.0 years (Q1:58.0; Q3:75.0) for AS and 65.0 years (56.0; 71.8) for PARPi monotherapies. Other patient characteristics are shown in Table 1. Patients with BRCA mutation were significantly more likely to receive PARPi monotherapies (odds ratio [OR]: 7.49; 95% CI: 4.21-13.31) than patients with BRCA wild-type. Patients treated in 2019 (OR: 7.57; 95% CI: 3.86-14.86) and 2020 (OR: 14.99; 95% CI: 7.61-29.53) were significantly more likely to receive PARPi monotherapies than patients treated in 2017. Race, region of residence, practice type, FIGO stage at initial diagnosis, Eastern Cooperative Oncology Group (ECOG) score, residual disease status, and other disease characteristics were not selected into the model. Conclusions: Over the last four years, the use of 1L PARPi maintenance among ovarian cancer patients has increased significantly, mostly driven by biomarker status. However, stage and extent of residual disease after surgery were not associated with PARPi maintenance use.

Starting dose of niraparib as first-line maintenance among patients with newly diagnosed advanced ovarian cancer in a real- world database (352)

<b>Objectives:</b> Niraparib is the only poly (adenosine diphosphate [ADP]- ribose) polymerase inhibitor that is FDA-approved as monotherapy in first-line (1L) ovarian cancer (OC) maintenance regardless of biomarker status with an individualized starting dose (ISD). For patients weighing <77 kg (<170 lb) or with a platelet count <150,000/μL, the recommended starting dose is 200 mg taken orally once daily rather than the standard 300 mg dose. This study evaluated the uptake of the new ISD of niraparib using the Flatiron Health database in 1L OC maintenance. <b>Methods:</b> This retrospective cohort study included patients with newly diagnosed stage III/IV epithelial OC whose last 1L platinum-based chemotherapy (PBC) dose was between January 1, 2017, and February 28, 2021, from the nationwide Flatiron Health electronic health record- derived database. The de-identified data originated from approximately 280 US cancer clinics during the study period. Patients who started a second-line chemotherapy treatment within two months of the last 1L PBC dose were excluded. Starting doses of niraparib, according to weight and platelet count, were assessed among patients receiving niraparib monotherapy as 1L maintenance therapy. <b>Results:</b> Among patients with newly diagnosed advanced OC, 64 patients (median age: 66 years [Q1:60; Q3:74]) received niraparib monotherapy for 1L maintenance. The median time between initiation of maintenance therapy and the last 1L PBC dose was 49 days (Q1:38; Q3:77). The mean weight of patients receiving niraparib monotherapy was 70.2 kg (standard deviation [SD]: 15.3). In total, 40 patients (62.5%) had platelet counts ≥150,000/μL and 20 patients (31.3%) had platelet counts <150,000/μL. Median and mean platelet counts were 178,500/μL (Q1:127,500; Q3:252,000) and 209,296/μL (SD: 120,096), respectively. Platelet counts were missing for four patients. Among 45 patients who met the criteria for the lower dose, 25 (55.6%) initiated niraparib at the correct dose of 200 mg, and 16 (35.6%) initiated niraparib at 300 mg (Table 1). Dosing information was missing for four patients. Among 15 patients who weighed >77 kg and had a platelet count ≥150,000/μL, 12 (80.0%) initiated at the correct dose of 300 mg and two (13.3%) initiated at 200 mg. Dosing information was missing for one patient. After the ISD recommendation (April 29, 2021), the use of the 200 mg dose increased from 22.7% to 57.9% in the overall group. However, in those who met the weight and platelet criteria, it increased from 35.7% to 64.5%. Table 1 <b>Conclusions:</b> Despite the benefits of the individualized starting dose, over 25% of OC patients who were eligible were not receiving the lower dose. Further studies are needed to better understand and educate oncologists on the option of personalized dosing of PARP inhibitors.

Management of surgically inoperable muscle-invasive bladder cancer in a resource constraint setting at a tertiary care center by bladder preservation protocol: Case series.

Urinary bladder cancer is a major cause of morbidity and mortality worldwide. As per the data from the US cancer registry, it was diagnosed in nearly 71,000 patients and led to 14000 deaths in 2013. The Indian data in this regard are lacking with few case reports and epidemiological data only. The paucity of treatment data in this regard led us to undertake this prospective study at our radiation oncology canter. Carcinoma urinary bladder is a heterogeneous disease with variable natural history. Male preponderance and association with cigarette smoking appears to be the foremost in natural history of the disease. Our data analyzed the management of muscle-invasive medically and surgically inoperable carcinoma urinary bladder in a resource constraint setting at a tertiary care center by bladder preservation protocol (BPP). This prospective study was aimed to evaluate the treatment outcome in surgically inoperable muscle-invasive carcinoma urinary bladder in a resource constraint setting at a tertiary care center by BPP. All patients were treated with telecobalt 60 machine up to a dose of 60-66 Gy along with concurrent chemotherapy. Interim assessment was done at 40 Gy. A total of nine patients were taken up for treatment with BPP. All patients were evaluated with standard evaluation protocol. All patients were followed up till any event occurred and till 6 years. Out of nine patients treated, six patients are still alive without any progression of disease and are disease free with standard evaluation on follow-up. Two patients died during the 1st year of follow-up. One patient progressed with lung and abdominal metastases 5 months after the completion of treatment and one patient was lost to follow-up. BPP using trimodality therapy is a suitable alternative to radical cystectomy in medically and surgically inoperable carcinoma urinary bladder. These patients should be highly compliant for regular follow-up, and acute and long-term toxicity should be evaluated in detail at each visit. BPP gives a ray of hope in such settings and should be done with caution. In our study, we treated all these patients in our resource constraint settings with good results and high survival rates. Our integrated team of radiation oncologists, medical oncologists, and urologists closely followed up these patients in order to optimize outcomes.

Trends in Oropharyngeal Cancer Incidence Among Adult Men and Women in the United States From 2001 to 2018.

BackgroundThe human papillomavirus (HPV) vaccine was approved in 2006 and has been shown to decrease vaccine-related HPV types in the oropharynx. Its impact on the incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has not been examined. We investigated the impact of HPV vaccination on the incidence of HPV-related OPSCC in the US among male and female adults from different age groups.MethodsThe US Cancer Statistics 2001–2018 database and the National Cancer Institute (NCI)’s Surveillance Epidemiology and End Results (SEER) program were used in this study. OPSCC incidence was age-adjusted to the US standard population in 2000. Cause-specific 5-year survival probability was calculated using 60 monthly intervals in SEER*Stat software.ResultsIncidence of HPV-related OPSCC was much higher in males than in females. Age-adjusted annual incidence of OPSCC was significantly lower in 2014-2018 than in 2002-2006 among males 20-44 years old (11.4 vs 12.8 per 1,000,000, rate ratio 0.89, 95% confidence interval 0.84-0.93) and among females 20-44 years old (3.0 vs 3.6 per 1,000,000, rate ratio 0.86, 95% confidence interval 0.78-0.95), but increased in both 45-64 year old and 65+ year old males and females. Joinpoint regression revealed a significant joint in the HPV-OPSCC incidence trend for 20-44-year-old males in 2008 at which time the incidence began to decrease. Except for 20-44 year old females (74.8% in 2002-2006 vs. 75.7% in 2009-2013, p=0.84), cancer-specific 5-year survivals significantly improved for males and females of all age groups.ConclusionsHPV-related OPSCC was much more common in males. Incidence of HPV-related OPSCC declined among young adults during the vaccination era compared with pre-vaccination era. Cancer-specific 5-year survival was significantly improved in young males but not in young females.

Improving Cancer Care Delivery: Learnings for Oncology Nurses and Patient Navigation From a National Quality Survey.

Background:Although implementation of patient navigation programs in clinical practice is widespread, heterogeneity exists in the design and delivery of these services. Greater clarity is required on competencies of personnel, delineation of their roles in multidisciplinary cancer care teams, navigation service components that positively impact patient outcomes, and associated metrics.Methods:A national, double-blind, online survey was implemented between January 24, 2019, and April 25, 2019, to investigate care coordination for advanced (stage III/IV) non–small cell lung cancer (NSCLC). Respondents included multidisciplinary team (MDT) members, such as oncologists, pathologists, oncology nurses, advanced practice nurses, and patient navigators, from US cancer programs. Customized questions covered NSCLC screening, diagnosis, treatment, and care coordination, with a focus on oncology nurses, advanced practice nurses, and patient navigation. Descriptive statistics were computed. Subanalyses examined relationships between care delivery and outcomes such as shared decision-making (SDM) through statistical testing.Results:Across programs, there was a lack of patient (nurse or lay) navigators (22.3%, 101/452) to assist patients with NSCLC. Most respondents (90.1%, 100/111) worked in programs with no formal health literacy assessments. Significantly higher mean SDM scores (p < .05) were observed in programs with patient navigators compared with programs without these specialists.Conclusion:Patient navigation is pivotal to enhancing the patient experience along the lung cancer care continuum and should be strategically integrated within lung cancer MDTs. These findings, along with survey inputs from other MDT disciplines, can help support process improvement plans for patient-centered advanced NSCLC care delivery.

Abstract 4118: Brain metastases (BM) and next-generation sequencing (NGS) timing: Real-world (RW) outcomes for patients (pts) with advanced non-small cell lung cancer (aNSCLC) and MET exon 14 skipping mutations (METex14)

Abstract Background: Treatment (Tx) options for METex14 NSCLC have been limited to chemotherapy (Ctx), immunotherapy (IO), and multikinase inhibitors (MKi) until FDA approvals of selective MET inhibitors (METi) from 2020. BM are a further challenge to treat. We previously reported NGS timing in relation to start of first-line Tx (1L) for pts with METex14 NSCLC in the RW. Here we provide overall survival (OS) data, including subgroup analyses for pts with known BM prior to 1L initiation. Methods: Data originating from ~280 US cancer clinics (~800 sites of care) from the US electronic health record-derived de-identified Flatiron Health Foundation Medicine clinico-genomic database (FH-FMI CGDB) were evaluated. Pts were ≥18 yrs, diagnosed with advanced/metastatic NSCLC from Jan 1, 2011, with NGS-confirmed METex14, ≥1 line of Tx, and ≥90 days follow-up from 1L initiation to cutoff date (Dec 2020). Pts treated with capmatinib or tepotinib were excluded. We examined Tx patterns and OS for pts with and without known BM before starting 1L, and OS for pts with an NGS report before or on/after 1L initiation (time from 1L initiation to death or censoring, analyzed using Kaplan-Meier method with left truncation adjustment to mitigate bias due to the prerequisite for NGS testing). HRs were estimated using Cox regression models with covariates adjustment to estimate risk of death. Results: The analysis included 156 METex14 NSCLC pts: median age 75 yrs, 59% females, 85.3% non-squamous (NSQ), 9% squamous cell carcinoma (SQ), and 64% had history of smoking. A total of 31 pts (20%) had BM before 1L initiation: median age 73 yrs, 61% females, 94% NSQ, 0% SQ, and 71% had history of smoking. Overall, treatment patterns were similar for pts with and without known BM before 1L initiation (Ctx with or without IO, IO monotherapy, and MKi were all used in 1L). Median OS for pts with BM was 8.11 mo (95% CI, 6.0-19.8) and 14.39 mo (11.1-22.1) for pts without BM, corresponding to a 73% increase in risk of death for pts with BM vs pts without BM by univariate analysis (HR 1.73 [95% CI, 1.06-2.82]; P=0.03). Median OS for pts with an NGS report before and on/after 1L initiation was 13.3 mo (8.8-26.2) and 6.8 mo (0.03-19.8), respectively (P=0.45); HR by multivariate analysis was 0.78 (0.45-1.35) when comparing pts with NGS report before vs on/after 1L initiation. Conclusions: Tx patterns in 1L were similar for pts with or without BM at time of 1L initiation; presence of BM prior to 1L was associated with inferior outcomes. Numerically longer OS was observed in pts with NGS report prior to 1L initiation vs pts with NGS report on/after 1L, supporting further investigation of underlying causes. These data underline the ongoing unmet clinical need of METex14 NSCLC BM and the importance of investigating upfront comprehensive genomic testing in NSCLC. Citation Format: Xiuning Le, Stephen Robb, Nydia Caro, Simona Doria, Whitney C. Rhodes, Wen-Hsing Wu, Julia Kim, Vincent Prêtre, Fen Ye. Brain metastases (BM) and next-generation sequencing (NGS) timing: Real-world (RW) outcomes for patients (pts) with advanced non-small cell lung cancer (aNSCLC) and MET exon 14 skipping mutations (METex14) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4118.

Abstract 1249: Development of a pan-cancer algorithm to predict homologous recombination deficiency and sensitivity to PARPi therapy

Abstract Background: PARP inhibitors (PARPi) are approved for multiple indications with ongoing trials to explore broader utility. However, identifying the right patients for these therapies across multiple disease types remains a challenge. In ovarian cancer, genomic-scar based measures for homologous recombination deficiency (HRD) are approved diagnostics (genome-wide LOH [gLOH] and genomic instability score [GIS]); however, broader utility has not been established. Methods: A pan-cancer genomic profiling dataset (n = 202,472; Foundation Medicine, Cambridge, MA) was split 70:30 for training and validation of an HRD signature using an XGB machine learning model (mlHRD). A broad set of copy number (Macintyre 2018) and indel features (Alexandrov 2020) were used to identify signatures of HRD. gLOH (Coleman 2017) and GIS (Timms 2014) were calculated using copy number profiles. Biallelic alterations were predicted using a computational zygosity algorithm (Sun, 2018). The nationwide, de-identified Flatiron Health-Foundation Medicine ovarian and prostate clinico-genomic databases (FH-FMI CGDB) were utilized for outcomes analysis. The de-identified data originated from approximately 280 US cancer clinics (~800 sites of care). Time to therapy discontinuation (TTD) was estimated with Kaplan-Meier analysis. Hazard ratios were calculated using unadjusted Cox proportional Hazard models. Results: We developed an algorithm to predict HRD status using indel and copy number features (see methods). Across the pan-cancer dataset, the rate of mlHRD was 6.4% with the highest frequency in fallopian tube (30%), ovarian (30%), peritoneal (23%), breast (16%), and prostate cancers (15%). Sensitivity to detect biallelic BRCA1/2 alterations was high across tumors [ovary (93%), prostate (87%), breast (85%), pancreas (80%)]. Beyond BRCA1/2, mlHRD positivity was associated with biallelic alterations in RAD51D (OR = 24, p&amp;lt;1E-10), PALB2 (OR = 23, p&amp;lt;1E-10), BARD1 (OR = 23, p&amp;lt;1E-10), and RAD51C (OR = 19, p&amp;lt;1E-10). In the FH-FMI CGDB ovarian cancer cohort, 150 patients were treated with PARPi (mlHRD positive = 73; negative = 77); mlHRD positivity was associated with improved TTD (median 8.9 mo v 3.9 mo; HR = 0.49 [0.34-0.71], p &amp;lt; 0.001), with similar predictive power to gLOH &amp;gt;16% (HR = 0.55 [0.38-0.79], p = 0.001) and GIS &amp;gt;42 (HR = 0.59 [0.41-0.86], p = 0.006). For 62 patients with prostate cancer treated with PARPi (mlHRD positive = 27; negative = 35), mlHRD was associated with prolonged TTD on PARPi (median 6.8 mo v 3.4 mo; HR = 0.56 [0.30-1.03], p = 0.064), trending more predictive than gLOH &amp;gt;8.29% (Sokol 2020) and GIS &amp;gt;42 (HR = 0.64 [0.29-1.40] and 0.80 [0.37-1.73], respectively; p&amp;gt;0.05). Conclusion: These findings suggest that HRD is associated with genomic scarring beyond ovarian cancer. Additional retrospective and prospective analyses in clinical datasets are needed to explore the utility of this signature. Citation Format: Emmanuel Antonarakis, Jay Moore, Dexter Jin, Tim Chen, Justin Newberg, Zoe Fleischmann, Karthikeyan Murugesan, Garrett Frampton, David Fabrizio, Russell Madison, Ethan Sokol. Development of a pan-cancer algorithm to predict homologous recombination deficiency and sensitivity to PARPi therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1249.

Abstract 1243: Identification of aneuploidy biomarkers associated with response to first-line treatment of metastatic pancreatic cancer

Abstract Background: NCCN guidelines for first-line treatment of patients with metastatic pancreatic cancer includes either FOLFIRINOX or gemcitabine plus paclitaxel; however, these two treatment regimens have not been compared in a randomized clinical trial. In this study, we investigated genomic predictors of treatment response to guide this treatment decision. Methods: We selected 1,250 patients with metastatic pancreatic cancer who were treated with first-line FOLFIRINOX (FOLF, n = 588) or gemcitabine plus paclitaxel (G+P, n = 662) within the nationwide de-identified Flatiron Health-Foundation Medicine clinico-genomic database (CGDB). The de-identified data originated from approximately 280 US cancer clinics (~800 sites of care). Comprehensive genomic profiling was performed by Foundation Medicine on tumor samples from each patient as part of the standard of care. Gain/loss status as well as loss of heterozygosity (LOH) status of each chromosome arm was assessed using a custom research-use only algorithm that utilizes copy number model calls for each segment and SNP MAF information from sequencing data. Univariable Cox proportional hazards regression was used to identify chromosome arm-level aneuploidies associated with survival in patients treated with first-line FOLF or G+P. In each treatment cohort, a multivariable Cox model was built using the bidirectional stepwise regression procedure to select aneuploidy features associated with survival. A binary risk score was calculated based on the linear predictor of the multivariable Cox model and categorized as high vs low using a median threshold. Results: Among the FOLF-treated cohort, we identified six aneuploidy features associated with survival (Bonferroni adjusted p &amp;lt; 0.05). FOLF-treated patients with a low FOLF risk score had better survival compared to those with a high FOLF risk score (HR: 0.46, 95%CI: 0.34-0.61, p = &amp;lt;0.001). This association was not observed among G+P-treated patients (HR: 0.86, 95%CI: 0.66-1.11, p = 0.25). Among the G+P treated cohort; eight aneuploidy features were associated with survival (Bonferroni adjusted p &amp;lt; 0.05). G+P-treated patients with a low G+P risk score had better survival compared to patients with a high G+P risk score (HR: 0.43, 95%CI: 0.33-0.57, p = &amp;lt;0.001). This association was not observed among FOLF-treated patients (HR: 0.86, 95%CI: 0.66-1.12, p = 0.25). These findings remained after adjusting for clinical features including surgery and ECOG performance status (HRG+P: 0.52, p = &amp;lt;0.001; HRFOLF: 0.5, p = &amp;lt;0.001). Conclusions: In metastatic pancreatic cancer, we found different chromosome arm-level aneuploidies were associated with survival for FOLF and G+P regimens which suggests an aneuploidy-based risk score may have utility in choosing first-line treatment. Citation Format: Kuei-Ting Chen, Radwa Sharaf, Garrett Frampton, Lee Albacker, Ericka Ebot. Identification of aneuploidy biomarkers associated with response to first-line treatment of metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1243.

Associations of Obesity, Physical Activity, and Screening With State-Level Trends and Racial and Ethnic Disparities of Breast Cancer Incidence and Mortality in the US

Breast cancer causes disproportionate disease burden among various racial and ethnic groups in the US. However, state-level temporal trends and racial and ethnic disparities and whether metabolic and lifestyle factors and screening access are associated with temporal changes remain largely unknown. To investigate temporal trends and racial and ethnic variations at the state level and ecological correlations between obesity, physical activity, and mammography screening and breast cancer incidence and mortality trends among women in the US. A cross-sectional study was conducted to analyze breast cancer incidence and mortality trends among women in the US from January 1, 1999, to December 31, 2017, whereas an ecological analysis was performed to assess the associations. Data were analyzed from March 1, 2021, to September 30, 2021. Population-based cancer registry data were obtained from US Cancer Statistics incidence and mortality data. Prevalence of obesity, physical activity, and mammography screening were obtained from the Behavioral Risk Factor Surveillance System. Prevalence of obesity, physical activity, and mammography screening. Breast cancer incidence and mortality trends from 1999 to 2017 in the 50 US states and the District of Columbia. A total of 4 136 123 breast cancer cases and 782 454 deaths were included in the analysis, with a significant reduction in incidence (average annual percent change [AAPC], -0.4% [95% CI, -0.6% to -0.2%)]) and mortality (AAPC, -1.7% [95% CI, -1.8% to -1.5%]) during the study period. A significant state-level variation in breast cancer incidence and mortality between White women and those of other races and ethnicities was observed. A significant positive correlation was found between obesity and breast cancer incidence (r = 0.316; P = .02) and mortality (r = 0.400; P = .004) and an inverse correlation was found between physical activity and incidence (r = -0.577; P < .001) in women 55 years or older and mammography screening and mortality trends (r = -0.644; P < .001) in women 40 years or older. The findings of this cross-sectional study suggest that racial and ethnic disparities exist at the state level with regard to breast cancer incidence and mortality among women in the US. Metabolic and lifestyle factors and screening access were associated with the observed trends and racial and ethnic disparities. Interventions targeting these factors may help reduce the incidence of breast cancer and related deaths.

Financial payments from the pharmaceutical industry to U.S. cancer centers, 2014-2019.

1582 Background: Payments from the pharmaceutical industry to US health care providers were made public through Open Payments in 2013. Since then, industry payments to individual physicians have been studied extensively, but payments to hospitals remain uncharacterized. The goal of this study was to examine trends in industry payments to US cancer centers. Methods: We identified all US cancer centers that were National Comprehensive Cancer Network (NCCN) members or were National Cancer Institute (NCI) comprehensive cancer center as of 2019. Each institution was manually mapped to Open Payments, which contains industry payment data. Where applicable, subsidiary hospitals were included with the parent center. Among the NCCN centers, we used National Plan and Provider Enumeration System data to identify medical oncologists practicing there. Oncologists were linked to Open Payments by name and address. We analyzed “research payments” (RP), which include payments related to preclinical and clinical research, and “general payments” (GP), which include non-research-related payments in categories such as speaker fees, consulting fees, meals, grants, charitable contributions, and licensing fees. We ascertained public research support from NIH data, and included all research project grants. We used correlation analysis and linear regression models to assess the association between industry payments to a cancer center and to oncologists practicing at that center. All dollar values were inflation-adjusted to 2019 dollars using the Consumer Price Index for medical care from the US Bureau of Labor Statistics. Results: Overall industry RP to US cancer centers increased from $527 million in 2014 to $653 million in 2019, while GP increased from $346 million to $786 million. NCI research funding increased from $1,397 million in 2014 to $1,583 million in 2019 (13.3% increase) while overall industry payments (RP+GP) increased from $873 million to $1,439 million (64.8% increase). Industry payments were highest as a portion of total income (industry + NCI) at MD Anderson (64.2%) and lowest at St. Jude (0.1%). Among NCCN institutions, industry payments to cancer centers and the oncologists practicing at those centers were correlated (coefficient = 0.382). A $1,000 increase in GP to a cancer center from a given pharmaceutical company was associated with a $1.00 ($0.61 - $1.30) increase in GP from that company to oncologists at that cancer center. Conclusions: From 2014-2019, cancer center funding from industry sources grew quickly, driven by an increase in non-research payments, and now approaches the amount of public research funding cancer centers receive. Cancer center acceptance of industry payments is associated with increased industry payments to its employed physicians, which are known to sway prescribing practices. These trends raise concerns regarding the ability of these institutions to fulfill their public missions.

Prevalence of pain symptoms among U.S. adult cancer survivors.

12062 Background: Pain symptoms are common in cancer survivors. The life expectancy of US cancer survivors continues to raise. To date, the comprehensive pattern of pain symptoms in US cancer survivors by cancer history remains unknown. Methods: Data on pain symptoms and correlates were derived from a nationally representative sample of cancer survivors (n = 55,716, weighted population = 17,352,886) in the 1997-2018 National Health Interview Survey. Individuals who answered “yes” to the questions “During the past three months, did you have headache/facial/neck/low back pain/low back pain radiating to the leg” were considered as having pain symptoms at respective anatomical regions. The US national prevalence of pain overall and by anatomical regions were estimated. Correlates of pain symptoms were examined using multivariable logistic regression. Results: The prevalence of overall pain symptoms was persistently high (48.5%, 95% CI: 48.0-49.0) in cancer survivors from 1997-2018 ( P for trend =.58), driven by low back (37.6%, 95% CI: 37.1-38.0) and neck pain (20.9%, 95% CI: 20.5-21.3), and was leading in survivors of bone (63.1%, 95% CI: 57.9-68.4), soft tissue (58.1%, 95% CI: 50.6-65.6), and brain (58.2%, 95% CI: 52.3-64.0) cancers. Considerable pain symptoms were reported by survivors of commonly diagnosed cancers: lung (48.5%), breast (46.7%), colon (52.2%) and prostate (38.4%) cancers. The prevalence of pain is higher in females (52.9%) than males (42.6%) across all anatomical regions (OR, 1.50 [95% CI, 1.38-1.63]), particularly headache (19.8% vs. 8.6%) and facial pain (8.6% vs. 3.9%). Of note, females with reproductive system cancers, cervical (66.3%), uterine (60.0%) and ovarian (59.4%) cancers, have a higher prevalence in all types of pain than those with other cancers. Cancer survivors aged ≥65 years were less likely to report pain symptoms than younger survivors (OR, 0.71 [95% CI, 0.64-0.79]). Despite no racial disparity in the prevalence of overall pain, Non-Hispanic Blacks (18.6%, 95% CI: 17.2-20.0) and Hispanics (21.2%, 95% CI: 19.5-22.9) were more likely to report headache than Non-Hispanic Whites (14.4%, 95% CI: 14.0-14.8). A higher prevalence of pain symptoms was consistently observed in cancer survivors with low income, smoking history, low physical activity levels, diabetes, and cardiovascular diseases (all P &lt;.05). Age at cancer diagnosis ( P for trend &lt;.001), but not the time since, affected pain symptoms. Cancer survivors diagnosed at age 0-14 (53.0%, 95% CI: 49.1-56.9) and 15-39 years (58.6%, 95% CI: 57.5-59.7) had a significantly higher prevalence of pain across all anatomical regions than those at ≥40 years (45.5%, 95% CI: 44.9-46.1). Conclusions: Half of US cancer survivors experienced pain symptoms, driven by low back and neck pain. Higher prevalence of pain was noted in cancer survivors with younger age, female sex, low income and suboptimal lifestyle behaviors, calling for adequate pain management in cancer survivorship.

Improved overall survival of metastatic cancers in the United States across all age groups in the immunotherapy era: Implications for considering elderly patients (age ≥ 75) for immune checkpoint inhibitors (ICIs).

12039 Background: ICIs have changed the treatment paradigm in many cancer histologies. Population-level data regarding the impact of ICIs on the contemporary US cancer patients is scarce. In addition, elderly patients were underrepresented in the landmark trials. Methods: Metastatic cancers (melanoma, lung cancer, kidney cancer, head and neck cancer, Hodgkin’s lymphoma, and urothelial cancer) diagnosed between 2004-2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The year of the first FDA approved ICI in each cancer site was considered the commencement of the ICI era. The impact of metastatic cancers diagnosed in the ICI era was assessed in each age group (&lt;65, 65-75, and ≥75) using multivariable Cox regression after adjustment for age, sex, race, household income and residence status (metropolitan vs non-metropolitan) Results: There were 363,191 patients with metastatic cancers included in the analysis [lung cancer: 68%, head and neck cancer: 14%, Hodgkin Lymphoma: 7%, kidney cancer: 7%, urothelial cancer: 3%, and melanoma: 2%): 60% were male and 73% were non-Hispanic White. The median age was 66 (interquartile range: 57-75). After baseline adjustments for sociodemographic factors, metastatic cancers diagnosed in the ICI era had improved overall survival except urothelial cancer (Table). Results of overall survival and cancer-specific survival were consistent across all age groups (&lt;65, 65-75, and ≥75). Among patients with age ≥75, metastatic cancers diagnosed in the ICI era had improved overall survival in melanoma (AHR: 0.81, p-value&lt;.0001), lung cancer (AHR:0.91, p-value&lt;.0001), kidney cancer (AHR: 0.89, p-value: 0.0004), head and neck cancer (AHR:0.82, p-value&lt;.0001), Hodgkin lymphoma (AHR: 0.75, p-value:0.003) but not in urothelial cancer. Conclusions: Metastatic cancers diagnosed in the ICI era had improved overall survival and cancer-specific survival including the subgroup of age ≥ 75. ICIs should not be withheld in elderly patients solely due to chronological age. [Table: see text]

CtDNA shed as a tool to select immune checkpoint inhibitors (ICPI) with or without chemotherapy for patients (pts) with advanced non–small cell lung cancer (aNSCLC).

9045 Background: ICPI are compelling therapies for pts with aNSCLC given the potential for durable benefit and limited toxicity. Even in tumors with biomarkers associated with ICPI response, early progression (eP) can be seen, leading to chemotherapy combination approaches. We hypothesize that ctDNA tumor fraction (TF) may identify pts at risk of eP on ICPI, helping to select the optimal first-line regimen. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB). The de-identified data originated from ~280 US cancer clinics (~800 sites of care). Real-world overall survival (rwOS) accounting for delayed entry and real-world progression free survival (rwPFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional hazard models adjusting for relevant covariates. TF was calculated using an aneuploidy-based measure plus variant-based estimate and was categorized as follows: ≥10%: elevated, 1-10%: intermediate, &lt; 1%: low. eP was defined as rw progression within 8 weeks of starting therapy. Results: 426 pts with documented aNSCLC initiated 1st or 2nd line ICPI (128 ICPI, 298 ICPI+chemo) within 60 days of liquid biopsy. 88 (21%) pts had elevated TF, 193 (45%) had intermediate, and 145 (34%) had low. Pts with elevated TF had higher frequency of liver involvement (elevated: 27%; intermediate: 12%; low: 8%) and had worse performance status (ECOG 2+) near the start of therapy (elevated: 33%; intermediate 22%; low: 17%). PD-L1 was unknown for most pts (elevated: 44%; intermediate: 53%; low: 57%); elevated TF was associated with high PD-L1 positivity (elevated: 22%; intermediate: 17%; low: 12%). In pts with elevated TF, eP was more frequent (elevated: 26%, intermediate: 22%, low: 15%). Amongst all patients treated with either ICPI ± chemo, low TF was associated with better median rwPFS (low 6.7m [ref]; intermediate 5.1m, HR: 1.39 [1.11-1.74]; elevated 3.4m, HR: 1.74 [1.31-2.31]) and median rwOS: (low 14.2m [ref]; intermediate 8.4m, HR: 1.52 [1.10-2.09]; elevated 4.6m, HR: 2.17 [1.47-3.21]). In pts with elevated TF, the addition of chemo to ICPI was associated with favorable rwPFS and rwOS compared to pts who received ICPI alone (Table). Conclusions: ctDNA TF identifies pts with aNSCLC with an increased risk of eP on ICPI who may benefit from ICPI+chemo. In pts with low TF, outcomes on ICPI alone are favorable and similar to those receiving ICPI+chemo, suggesting low TF may be a non-invasive tool for identifying pts for single-agent ICPI. [Table: see text]

A real-world (rw) evidence study quantifying the clinical value of multi-gene testing in early-stage lung adenocarcinoma (LUAD).

8525 Background: Resected early-stage NSCLC has high risk of recurrence, and tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI), each requiring testing for precision biomarkers, have recently been approved in the adjuvant (adj) setting. We assessed the potential value of multi-gene testing in early NSCLC via enabling timely 1L therapy selection at recurrence and through avoidance of adj ICI in pts with driver alterations unlikely to benefit per current guidelines and the label for atezolizumab in first line (1L) NSCLC. Methods: Using the nationwide (̃280 US cancer clinics) de-identified EHR-derived rw Flatiron Health- Foundation Medicine clinico-genomic database, we selected 6,725 evaluable pts with LUAD who underwent tissue comprehensive genomic profiling (CGP) as part of routine cancer care (01/2011 – 06/2021). We focused on alterations in 4 drivers ( EGFR, ALK, ROS1, RET) and studied prevalence in early-stage specimens versus advanced (adv) specimens, as well as the rate of timely delivery of 1L therapy at recurrence for pts receiving CGP in early disease. We estimated the cost implications of adj ICI in pts with PD-L1+ LUAD and an ALK, ROS1, or RET fusion with a probabilistic decision tree. Results: CGP was performed on 1,490 specimens collected prior to adv disease (stage I 36%, II 27%, IIIA 37%) and ordered prior to adv diagnosis for 981 pts (15% of total, median 10 weeks after initial diagnosis). In specimens collected in early (n = 1,490) or adv (n = 5,130) stage LUAD, CGP identified drivers in EGFR (early/adv: 13%/16%), ALK (2.0%/4.2%), ROS1 (0.7%/1.1%), RET (1.0%/1.1%), and prevalence was similar when limiting to PD-L1+ cases. Studying 596 pts with recurrence and CGP on samples collected prior to recurrence, pts with CGP results obtained before (n = 196) vs after (n = 400) recurrence had less time between recurrence and start of any 1L therapy (median 3.1 vs 5.9 weeks, p &lt; 0.001). In the subset with a targetable driver detected, 32/42 (76%) with CGP before recurrence initiated matched 1L TKI while 43/67 (64%) with CGP after recurrence received matched 1L TKI (p = 0.2). Through avoidance of ICI in PD-L1+ early LUAD with an ALK/ ROS1/ RET driver, we estimate universal CGP (compared to EGFR single-gene testing) could reduce per pt expected costs by $875 (an average incremental $4,050 treatment cost reduction compared to a $3,175 increase in diagnostic cost per pt). Conclusions: CGP of early-stage LUAD can identify EGFR, ALK, ROS1 and RET drivers and enable appropriate selection of precision therapies and timely use of effective 1L therapy at recurrence. Assuming adj ICI maintains the lack of activity in RET/ ROS1 as seen for ALK, CGP could represent a cost-effective approach for avoiding futile adj ICI and reducing the risk of subsequent TKI-associated toxicity. Additional analysis of driver+ pts receiving adj ICI is needed to help balance the risk/benefit for these high risk pts.

Clinical and genomic characteristics of pts with durable benefit from immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (aNSCLC).

9048 Background: The 2-year mark has become a new milestone in pts with aNSCLC receiving immunotherapy. In pts who are progression free at that point, a subset experience ongoing disease control even after stopping active treatment. Some pts experience such impressive durability beyond 2 years, raising a question about potential cure. We queried a real-world (RW) clinico-genomic database (CGDB) to better understand these pts with durable benefit and their clinical and genomic features. Methods: Using the nationwide (̃280 US cancer clinics) de-identified EHR-derived Flatiron Health-Foundation Medicine aNSCLC CGDB linked to genomic data, pts treated with ICI (+/- chemotherapy) from 01/2011-06/2021 were selected. RW progression (rwP) was obtained via technology-enabled abstraction of EHR data. Durable benefit was classified as absence of rwP, death or treatment failure (indicated by switch to a new line of therapy) within 24 mos of beginning ICI therapy. Results: In a cohort of 4,030 evaluable aNSCLC pts, 184 (4.6%) were free of rwP or treatment failure at 24 mos. Of these 184 pts with durable benefit, 84% received ICI monotherapy and 16% received ICI with chemotherapy; ICI treatment was more often first line (1L, 43%) or 2L (38%). 59% with durable benefit were still on ICI at the 2-year mark, whereas 41% had stopped a median of 11.4 mos after therapy start. Of 109 pts remaining on ICI for 2-years, median time on ICI was 36.3 mos from therapy start. Overall, pts with durable benefit had a median rwPFS of 37.1 mos and median rwOS of 58.8 mos from start of ICI. Compared to pts with rwP on ICI before 24 mos, those with durable benefit were more likely to have history of smoking (94% vs 86%) and absence of liver, brain or bone metastases (all p &lt; 0.001). High tumor mutational burden (TMB ≥10) was more common (62% vs 35%, p &lt; 0.001) and STK11, CDKN2B, PIK3CA, and EGFR alterations were less common in pts with durable-benefit vs those with rwP on ICI before 24 mos. In a multivariate cox model of rwPFS beyond 24 mos in pts with durable benefit, TMB ≥20 was significantly associated with longer rwPFS (HR 0.45 95% CI 0.24-0.83, p = 0.01) while TMB ≥10 was marginally significant (HR 0.65 95% CI 0.40-1.03, p = 0.07); treatment with ICI with chemotherapy was significantly associated with worse rwPFS (HR 1.84 95% 1.093.12, p = 0.02). High PD-L1 &gt; 50% was noted in 728 (19%) of those without durable benefit and 38 (21%) of those with durable benefit, though many in the data set had unknown PD-L1 status. Conclusions: Pts with durable benefit &gt; 2 years after starting ICI therapy for aNSCLC represent a unique population of immune survivors with a median OS of almost 5 years; 41% of pts stopped ICI before the 2-year mark. Elevated TMB was associated with durable benefit on ICI as well as prolonged rwPFS after the 2-year mark and deserves further investigation as a biomarker for prolonged benefit to ICI in aNSCLC.

P-102 Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: A retrospective analysis using US claims data

Regorafenib is an oral multikinase inhibitor approved for advanced mCRC, advanced gastrointestinal stromal tumors, and advanced hepatocellular carcinoma. The phase 2 regorafenib dose-optimization study (ReDOS; Bekaii-Saab TS, et al., 2019) demonstrated that patients could initiate regorafenib at a dose of 80 mg/day and then subsequently escalate their dose depending on tolerability without compromising efficacy. In March 2018, the ReDOS strategy was included as a recommendation in US cancer guidelines.