Cancer-specific Outcomes Research Articles

MA14.13 Analysis of Lung Cancer-Specific Patient-Reported Outcome Measures (PROMs): Results from the PRO4All Project

MA14.13 Analysis of Lung Cancer-Specific Patient-Reported Outcome Measures (PROMs): Results from the PRO4All Project

Adaptation of a modified Elixhauser comorbidity index to isolate the impact of body mass index on survival outcomes in patients with cancer in a large integrated healthcare system.

124 Background: Variable impacts of body mass index (BMI) on overall survival (OS) and cancer-specific survival (CSS) have been described in patients with cancer, with existing data highlighting both detrimental effects and malignancy-specific benefits. Real-world data derived from integrated healthcare systems are underexplored in this context, and tight control of confounding using validated tools such as the Elixhauser Comorbidity Index (ECI) is rarely employed in pre-existing studies. Herein, we offer a highly refined description of the impact of BMI on cancer-specific outcomes in a large patient cohort using a targeted ECI model. Methods: 153,270 patient records were abstracted from an integrated healthcare system from 2010-2018, including descriptors of age, race/ethnicity, income, disease stage, and treatment regimens. Standardized derivation of BMI within one year prior to diagnosis was performed and categorized by World Health Organization definitions. A custom ECI was designed to exclude ICD codes for obesity to effectively isolate the impact of BMI on downstream analyses. Kaplan-Meier survival estimates of OS and CSS were constructed, and univariate and multivariate Cox proportional hazard (PH) modeling was performed to determine hazard ratios (HR). Results: When normalized to healthy BMI in multivariate modeling, we found a favorable dose-dependent relationship of overweight and obese BMI on OS and CSS independent of age, race/ethnicity, income, modified ECI score, cancer stage, or therapeutic regimen (Table). This advantage to OS and CSS was not as strongly reflected in severely obese patients, though still significant compared to healthy BMI counterparts. Being underweight was a negative prognostic indicator for OS and CSS in all patients compared to a healthy BMI. Conclusions: We demonstrate a beneficial impact of increased BMI on OS and CSS in a large cohort of patients treated in an integrated healthcare model independent of tightly controlled confounding. Specifically, we highlight the utility of isolating obesity using a targeted ECI model for comorbidity adjustment, which may provide a more robust measure of the influence of BMI on survival. Our findings raise questions regarding attention to adequate control of confounding in prior studies, as well as the potential benefit of removing variation in healthcare delivery in understanding these outcomes. Adjusted HR of OS and CSS stratified by BMI category (*95% Confidence Interval). BMI Category Adjusted OS Adjusted CSS Normal Weight(18.5 – 24.9) 1 (reference) 1 (reference) Underweight(< 18.5) 1.35 (1.25 – 1.45*) 1.28 (1.15 – 1.41) Overweight(25 – 29.9) 0.83 (0.81 – 0.85) 0.84 (0.81 – 0.87) Obese(30 – 39.9) 0.81 (0.79 – 0.83) 0.81 (0.78 – 0.84) Severe Obesity(≥ 40) 0.86 (0.82 – 0.90) 0.82 (0.77 – 0.87) Unknown 1.33 (1.24 – 1.43) 1.19 (1.07 – 1.31)

The time toxicity efficacy-effectiveness gap: A population-based study of stage III/IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

133 Background: While patients enrolled in clinical trials tend to have superior cancer-specific outcomes relative to those in routine practice (the ‘’efficacy-effectiveness gap’’), it is unknown if this gap extends to time toxicity. While trial protocols can impose additional contact days, trial participants also tend to be healthier, perhaps needing fewer contact days. We sought to evaluate the time toxicity efficacy-effectiveness gap among patients with stage III/IV NSCLC. Methods: We created a population-based, retrospective cohort with health administrative data covering the population of Ontario, Canada (15.5 million), of adults aged ≥20 years diagnosed with stage III/IV NSCLC in 2014-2017 and died in 2014-2019, receiving palliative systemic anti-cancer drug(s) as part of a trial. We matched patients 1:1 to those who received the same drug(s) in the real world (post-approval) in the same line of treatment, and received the same total lines of therapy. We calculated contact days (days with healthcare contact outside the home) from diagnosis to death and measured overall survival. We plotted, normalized, and fitted with cubic splines the weekly percentage of contact days to obtain trajectories over the disease course. Results: We identified and matched 55 trial participants to 55 patients in routine practice. Trial participants were younger (median age, 62 vs 66 years), had fewer co-morbidities (hypertension, 35% vs 53%), and more often had de novo metastatic disease (82% vs 67%). Median lines of therapy were 2. Systemic therapy regimens most commonly included immunotherapy (n=41, 75%). Trial participants initiated systemic therapy sooner than in routine practice (median 2.0 vs 2.4 months). Trial participants had a longer overall survival (median 13.8 vs 11.6 months) and a similar number of contact days (median 79 vs 78 days). The percentage of contact days was lower in trial participants due to longer survival (median 19% vs 22%). Trial participants had similar acute/assisted institutional care contact days (median 19 vs 18 days), but more days with laboratory tests (median 23 vs 17 days), systemic therapy (median 9 vs 6 days), and radiotherapy visits (median 15 vs 11 days). Normalized trajectories for both cohorts followed a ‘’U-shape’’; the difference between the maximal peak and trough was smaller in trial participants. Conclusions: We describe a novel efficacy-effectiveness gap in time toxicity, in addition to the previously established efficacy-effectiveness gap in overall survival. Encouragingly, trial participants did not experience delays in treatment, and initiated treatments sooner than in routine practice. Among trial participants, the higher number of contact days for tests, and the shallower U-shaped curve (indicating frequent visits even when relatively well) indicate potential opportunities to decrease trial-related time toxicity.

Abstract A004: Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients

Abstract PREDICT Breast v3 is the latest version of a prognostic tool designed to predict the treatment responses for early invasive breast cancer patients. It was developed using data from approximately 35,000 women diagnosed between 2000 and 2018 in the United Kingdom. However, its performance in the United States (US) population is unknown. This study aims to validate PREDICT Breast v3 using the newly released Surveillance, Epidemiology, and End Results (SEER) outcome data for US breast cancer patients and to address potential health disparities. We selected over 860,000 female patients diagnosed with primary breast cancer between 2000 and 2021 and followed for at least 5 years from the SEER database. The model’s performance was measured by calibration and discrimination; comparing predicted and observed 5-, 10- and 15-year breast cancer-specific survival outcomes and determining discrimination through the area under the receiver-operator curves (AUC). PREDICT Breast v3 demonstrated good calibration and discrimination for both short- and long-term up breast cancer-specific mortality in US populations. The predicted 10-year breast cancer-specific mortality differed from observed by 11% in ER-positive and 6 % in ER-negative patients. The AUCs for 15-year breast cancer-specific mortality were 0.81 for ER-positive patients and 0.76 for ER-negative patients. When stratified by race and ethnicity, the model showed strong performance in Non-Hispanic Asians ER-positive patients, despite being originally developed based on the UK population. These results are consistent with previous validations in Malaysia, Japan, and other Asian countries for PREDICT Breast v2. However, the model poorly estimated the number of deaths in Non-Hispanic Black individuals for both ER-positive and ER-negative. In conclusion, this study marks the first validation of PREDICT Breast v3 in the US and demonstrates that it is a reliable and generalizable tool, capable of providing longer term follow-up time up to 15 years for a wide and diverse population. Citation Format: Yi-Wen Hsiao, Paul Pharaoh, Pei-Chen Peng. Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A004.

Racial disparities in receipt of radiation and brachytherapy in cervical cancer patients: Do they exist in a SEER-Medicare population?

ObjectivesTo evaluate if race is associated with disparities in receipt of radiation (RT) and outcomes for Medicare patients with cervical cancer who are candidates for primary radiation-chemotherapy. MethodsThis SEER-Medicare retrospective study included White and Black patients with stage IB1 through IVA squamous cell carcinoma or adenocarcinoma diagnosed 2000–2017 who were candidates for primary radiation-chemotherapy. Receipt of treatment by race and associated cancer specific (CSS) and overall survival (OS) outcomes were analyzed using frequency distributions, chi squared, log rank, multivariable Cox proportional-hazards models, and multivariable logistic models. Results1038 patients (84.9 % White and 15.1 % Black) were included. 825 (79.5 %) received RT, and 601 (57.9 %) received brachytherapy (BT). Blacks were more likely to undergo RT than Whites (86.0 % vs. 78.3 %, p = 0.028) and had similar rates of BT (58.0 % vs. 57.9 %, p = 0.986). Median RT duration was 64.0 days (IQR 52.0, 75.0), and 276 (33.5 %) completed treatment in ≤ 56 days, with no differences by race (p = 0.488, 0.303, respectively). BT was more frequently provided at larger hospitals, National Cancer Institute-designated cancer centers, and teaching hospitals. When adjusted for covariates, no significant differences in RT, BT, or RT duration by race were identified. Median unadjusted OS was 3.58 years (95 % CI 2.92, 4.42) for White patients and 2.50 years (95 % CI 2.0, 5.25) for Black patients, with no differences in OS (HR 0.93, 95 % CI 0.75, 1.13) or CSS (HR 1.13, 95 %CI 0.86, 1.43). ConclusionsBlack Medicare patients with cervical cancer had greater receipt of RT than White patients, similar rates of BT, and no difference in survival.

Surgical Second Opinion for Pancreatic Cancer Patients

Background: Due to the complexity of pancreatic surgery, patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) may seek out the opinion of more than one surgeon. Little is known regarding how second surgical opinions impact the likelihood of pancreatectomy and perioperative outcomes. Our study aimed to determine the impact of obtaining second surgical opinions on pancreatectomy rates and to assess its impact on surgical outcomes. Study Design: Patients who were diagnosed with PDAC between 2013 and 2020 were identified using 100% Medicare Inpatient and Outpatient Standard Analytic Files (SAFs). Data collected included the number of surgeons consulted and geographic region. Receipt of pancreatectomy and perioperative outcomes were compared between patients who received more than one surgical consultation. Results: Of 116,072 patients diagnosed with PDAC, 10,640 (9.2%) underwent pancreatectomy. Among the 1,906 (17.9%) patients who underwent pancreatectomy after a second opinion, 39.7% (n=756) underwent resection with their initial surgeon. Patients receiving a second surgical opinion were more likely to undergo pancreatectomy (adjusted odds ratio [aOR] 6.17; 95% CI 5.78-6.59), with decreased odds among rural patients (aOR 5.57; 95% CI: 4.64-6.69). Patients who underwent surgery and received a second opinion had equivalent length of stay and complication rates compared to those who did not seek a second opinion (both p>0.05). Conclusions: Among Medicare patients who underwent pancreatectomy for pancreatic cancer, approximately 1 in 7 patients received a second surgical opinion. Additional research is needed on the impact of second opinions on long-term cancer-specific outcomes.

Wildfire-related PM2.5 and cause-specific cancer mortality

Wildfires have devastating effects on society and public health. However, little evidence from population-based cohort has been performed to analyze the relationship of wildfire-related PM2.5, an important component of wildfire smoke, with cancer-specific mortality. We aimed to explore this relationship and identify vulnerable populations in UK with lower levels of wildfire-related PM2.5 exposure. The study consisted of 492394 participants (age: 38–73 years) recruited by UK Biobank during 2004–2010. The cumulative wildfire-related PM2.5 within 10 kilometers of residence over three years was used as exposure, which was assessed by chemical transport and machine learning models. A time-varying Cox regression was utilized to explore the relationship of exposure with diverse cancer-specific mortality outcomes. Subgroup analyses of a range of potential modifiers were performed. Each 10 μg/m3 increment of 3-year cumulative exposure was related to a 0.4 % greater risk of total cancer (95 %CI: 1.001–1.007), a 1.1 % greater risk of lung cancer (95 %CI: 1.004–1.018), and a 2.7 % greater risk of lip, oral cavity and pharynx (LOP) cancer (95 %CI: 1.005–1.049). Higher vulnerability in the wildfire-related PM2.5-lung cancer relationship was found among participants being retired than those with other employment status. Even lower levels of exposure to PM2.5 from wildfires were related to elevated mortality risks for cancer from total, lung, LOP, highlighting the importance of wildfire prevention and control. Further investigations are warranted to enrich and extend existing knowledge in this field.

Patterns of care and outcomes for hepatocellular carcinoma and pancreatic cancer based on rurality of patient’s residence in a rural midwestern state

BackgroundAlthough advancements in surgical planning and multidisciplinary care have improved the survival of patients with hepatopancreatic cancers in recent years, the impact of the rurality of patient residence on care received and survival is not well known. We aimed to assess the association between the rurality of a patient’s residence and cancer-specific survival outcomes among patients with hepatocellular carcinoma (HCC) and pancreatic cancer (PC) in Iowa, hypothesizing that patients in rural areas would experience lower survival. MethodsAdult patients diagnosed with HCC or PC between 2010 and 2020 were identified using the Iowa Cancer Registry. Chi-square tests were used to compare categorical variables by rural/urban status. Logistic regression was used to examine factors associated with receiving surgery. Multivariable-adjusted Cox proportional hazards regression was used to determine associations with cancer-specific mortality. ResultsOf 1877 patients with HCC, 58%, 27%, and 16% resided in metropolitan, micropolitan, and rural areas, respectively. Approximately 70% of patients in rural areas traveled ≥50 miles for definitive care. Additionally, those residing in rural areas had the highest proportion of patients receiving definitive care at non-Commission on Cancer (CoC) centers (12.6% metro vs 14% micro vs 22.2% rural, P < .001). In a multivariable-adjusted analysis of patients with stage I to III disease, definitive care at a non-CoC center was independently associated with lower odds of surgery (odds ratio [OR] = 0.23; 95% CI, 0.12–0.45; P < .0001) and higher mortality risk (OR = 1.39; 95% CI, 1.07–1.79; P = .01), though rural residence was not. For PC, 5465 patients were diagnosed, and 51%, 28%, and 20% resided in metropolitan, micropolitan, and rural areas, respectively. Similar to HCC, although rural residence was neither associated with odds of surgery nor with mortality risk, receiving definitive care at non-CoC accredited centers was associated with significantly lower odds of receiving surgery (OR = 0.17; 95% CI, 0.11–0.26; P < .0001) and higher mortality risk (OR = 1.48; 95% CI, 1.23–1.77; P < .0001). ConclusionRural residents with hepatopancreatic cancer have the highest proportion of patients receiving definitive care at non-CoC centers, which is associated with lower odds of receiving surgery and higher odds of mortality. This highlights the importance of standardizing complex cancer care and the need to foster collaboration between specialized and non-specialized centers.

Blood cancer incidence, mortality and survival for Māori in New Zealand

BackgroundHaematological (‘blood’) cancers are a diverse group of non-solid cancers with varying incidence, mortality and survival. While there is some evidence that Māori experience disparities in blood cancer outcomes relative to New Zealand’s majority European population, there is a need for a comprehensive overview of the current state of evidence in this context. MethodsBlood cancer registrations were derived from the NZ Cancer Registry for the 2007–2019 period (combined blood cancers: 2653 Māori, 20,458 Europeans), and linked to Mortality records. We calculated age-sex-standardised incidence and mortality rates, and conducted cancer-specific survival analysis, for four main categories of blood cancers (leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and myeloma) as well as for sub-types of leukaemia non-Hodgkin lymphoma. ResultsWe found that Māori are more likely to be diagnosed with (incidence) and to die from (mortality) both leukaemia and myeloma, and similarly likely to be diagnosed or die from Hodgkin and non-Hodgkin lymphoma, compared to Europeans. Māori had demonstrably poorer cancer-specific survival outcomes across most blood cancer types (age-sex-adjusted hazard ratios [HRs], Māori vs European: leukaemia 1.77, 95 % CI 1.57–2.00; Hodgkin lymphoma 1.18, 95 % CI 0.65–2.16; non-Hodgkin lymphoma 1.71, 95 % CI 1.50–1.95; myeloma 1.40, 95 % CI 1.19–1.64). ConclusionBlood cancers are a common cancer type for Māori, and we found evidence of disparities in incidence, mortality and survival compared to Europeans. Further research is required to further pinpoint exactly where interventions should be aimed to reduce blood cancer incidence and address survival disparities for Māori.

A guide to large data sets for population-based cancer research: Strengths, limitations, and pitfalls.

With the proliferation of cancer research based on large databases, misalignment of research questions and data set capabilities is inevitable. Nationally maintained databases are appealing to cancer researchers because of the ease of access to large amounts of patient data available for analysis and risk estimation. Data sets that are commonly used in cancer research include the National Cancer Database, the SEER (Surveillance, Epidemiology, and End Results) program of the National Cancer Institute, the SEER-Medicare database, the American College of Surgeons National Surgical Quality Improvement Program, and the Healthcare Cost and Utilization Project databases, among others. Each data set has pros and cons with respect to variable availability and the ability to analyze cancer-specific outcomes. It is critical for researchers to understand the strengths and limitations of each database. Changing variable definitions, the length of postoperative data collection, and the availability of patient-reported outcomes or social determinants of health data are examples of factors that researchers must consider when selecting a data set for research purposes. For the current review, the authors summarized the advantages and disadvantages of various national data sets for cohort studies in cancer populations.

Gastrointestinal Cancer Therapy and Cardiotoxicity.

Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.

A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer.

While adjuvant bisphosphonate use in early breast cancer (EBC) is associated with improvements in breast cancer-specific outcomes, questions remain around optimal bisphosphonate type, dose and scheduling.We evaluated a single zoledronate infusion in a prospective randomised trial. Postmenopausalpatientswith EBC were randomised to receive a single infusion of zoledronate (4mg IV) or 6-monthly treatment for 3years. Outcomes measured were; Quality of Life (QoL; EQ-5D-5L), bisphosphonate-related toxicities, including acute phase reactions (APRs), recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS). 211 patients were randomized to either a single infusion (n = 107) or six-monthly treatment (n = 104).After 3years of follow up there were no significant differences between the arms for QoL and most toxicity endpoints. APRs following zoledronate occurred in 81% (171/211) of patients (77.6% in single infusion arm and 84.6% in the 6-monthly group).While the frequency of APRs decreased over 3years in the 6-monthly arm, they still remain common. Of 34/104 (32.7%) patients who discontinued zoledronateearlyin the 6-monthly treatment group, the most common reason was APRs (16/34, 47%). At the 3year follow up, there were no differences between arms for RFS, BMFS or OS. A single infusion of zoledronate was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation. Despite the common clinical impression that APRs decrease with time, this was not observed when patients were specifically questioned. While the study is not powered for non-inferiority, longer-term follow-up for confirmation of RFS and OS rates is ongoing.

Misuse of Prescribed and Nonprescribed Substances Among U.S. Cancer Survivors.

Substance misuse is common among cancer survivors and can negatively impact cancer outcomes. We conducted a cross-sectional study using National Survey on Drug Use and Health data for 2015 to 2020. We included adult respondents with a history of solid tumor cancer. We calculated the weighted prevalence and corresponding SEs (both expressed as percentages) of substance (alcohol, opioid, sedative, stimulant, other) misuse for respondents with any history of solid tumor cancer and, in secondary analyses, respondents diagnosed with cancer in the prior 12months. The study included 6,101 respondents with any history of cancer, 1,437 diagnosed in the prior 12months. Alcohol was the most commonly misused substance. The average prevalence of alcohol misuse was 14.4% (SE 0.60%) across cancer types; it was markedly more common among people with a history or cervical (24.2% [3.0%]) or head and neck cancer (27.4% [7.1%]). The next most common form of substance misuse was opioid misuse (average prevalence: 2.7% [0.25%]). As with alcohol misuse, the prevalence of opioid misuse was higher among those with a lifetime history of cervical cancer (5% [1%]) or head and neck cancer (5% [3%]). Results were generally consistent among cancer survivors diagnosed in the prior 12months. There is a clear opportunity to address substance misuse-particularly alcohol misuse-among cancer survivors. Such efforts should focus on populations with a high prevalence of substance misuse (e.g., cervical and head and neck cancer survivors) and have strong potential to improve cancer-specific and overall health outcomes.

21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial.

Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population. We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively. Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001). RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

Real-World Survival Comparisons Between Radiotherapy and Surgery for Metachronous Second Primary Lung Cancer and Predictions of Lung Cancer-Specific Outcomes Using Machine Learning: Population-Based Study.

Metachronous second primary lung cancer (MSPLC) is not that rare but is seldom studied. We aim to compare real-world survival outcomes between different surgery strategies and radiotherapy for MSPLC. This retrospective study analyzed data collected from patients with MSPLC between 1988 and 2012 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analyses and machine learning were performed to compare variables between patients with MSPLC. Survival curves were plotted using the Kaplan-Meier method and were compared using log-rank tests. A total of 2451 MSPLC patients were categorized into the following treatment groups: 864 (35.3%) received radiotherapy, 759 (31%) underwent surgery, 89 (3.6%) had surgery plus radiotherapy, and 739 (30.2%) had neither treatment. After PSM, 470 pairs each for radiotherapy and surgery were generated. The surgery group had significantly better survival than the radiotherapy group (P<.001) and the untreated group (563 pairs; P<.001). Further analysis revealed that both wedge resection (85 pairs; P=.004) and lobectomy (71 pairs; P=.002) outperformed radiotherapy in overall survival for MSPLC patients. Machine learning models (extreme gradient boosting, random forest classifier, adaptive boosting) demonstrated high predictive performance based on area under the curve (AUC) values. Least absolute shrinkage and selection operator (LASSO) regression analysis identified 9 significant variables impacting cancer-specific survival, emphasizing surgery's consistent influence across 1 year to 10 years. These variables encompassed age at diagnosis, sex, year of diagnosis, radiotherapy of initial primary lung cancer (IPLC), primary site, histology, surgery, chemotherapy, and radiotherapy of MPSLC. Competing risk analysis highlighted lower mortality for female MPSLC patients (hazard ratio [HR]=0.79, 95% CI 0.71-0.87) and recent IPLC diagnoses (HR=0.79, 95% CI 0.73-0.85), while radiotherapy for IPLC increased mortality (HR=1.31, 95% CI 1.16-1.50). Surgery alone had the lowest cancer-specific mortality (HR=0.83, 95% CI 0.81-0.85), with sublevel resection having the lowest mortality rate among the surgical approaches (HR=0.26, 95% CI 0.21-0.31). The findings provide valuable insights into the factors that influence cumulative cancer-specific mortality. Surgical resections such as wedge resection and lobectomy confer better survival than radiation therapy for MSPLC, but radiation can be a valid alternative for the treatment of MSPLC.

Association between comorbidity clusters and mortality in patients with cancer: A machine learning analysis of data from the US National Health and Nutrition Examination Survey 1999–2018.

11132 Background: Multimorbidity is common among patients with cancer; however, research on cancer prognosis has predominantly focused on cancers in isolation. This study identified comorbidity clusters among patients with cancer using machine learning and examine their associations with survival outcomes in a nationally representative sample of the US. Methods: This study used 10 survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2018. Participants aged ≥20 years with a self-reported history of cancer were included. Comorbidities were ascertained through self-reports and quantitative measurements. Machine learning techniques, including Bernoulli mixture model and partition-based methods, were used to identify comorbidity clusters. Cox proportional hazards models were used to analyze the associations between comorbidity clusters and mortality outcomes, including all-cause mortality and cause-specific mortality (cancer, cardiovascular disease [CVD], and respiratory diseases), adjusting for relevant covariates. Results: The study included 4,390 participants. Four comorbidity clusters were identified: Low Comorbidity, Metabolic, CVD, and Respiratory. After adjusting for confounders, participants in the Respiratory Cluster had the highest risk of all-cause mortality (adjusted hazard ratio[aHR]=1.62, 95% confidence interval [CI]=1.26-2.08, p&lt;0.001), followed by the CVD Cluster (aHR=1.50, 95%CI = 1.26-1.80, p&lt;0.001) and the Metabolic Cluster (aHR=1.15, 95%CI=1.02-1.29, p=0.03) compared to the Low Comorbidity Cluster. The Metabolic, CVD, and Respiratory clusters were associated with higher risks of cardiovascular disease-related mortality (aHR=1.48-3.05, p&lt;0.003), but no significant differences in cancer mortality were observed among the clusters. The effects of comorbidity clusters on all-cause mortality were modified by income-to-poverty ratio ( p for interaction=0.04), diet quality ( p for interaction=0.02), time since cancer diagnosis ( p for interaction=0.009), and cancer prognosis ( p for interaction=0.005). Conclusions: High comorbidity burden clusters showed increased all-cause and CVD-related mortality. Moreover, diet quality and socioeconomic status modified these associations. Machine learning approaches can provide valuable insights into complex multimorbidity profiles in patients with cancer. Further research is needed to deepen understanding of the relationships between multimorbidity, mortality, and cancer-specific outcomes.

The phase 3 INTerpath-002 study design: Individualized neoantigen therapy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non–small-cell lung cancer (NSCLC).

TPS8116 Background: Pembrolizumab (pembro; anti–PD-1) is indicated as adjuvant monotherapy following resection and adjuvant chemotherapy in patients (pts) with stage IB (T2a ≥4 cm), II, or IIIA NSCLC (per AJCC v7). However, many pts experience disease recurrence, and have limited treatment options available. V940 (mRNA-4157) is a novel individualized neoantigen therapy that encodes up to 34 neoantigens that is specifically tailored and manufactured for each pt derived from their tumor. V940 as monotherapy and in combination with pembro has shown preliminary antitumor activity in the phase 1 KEYNOTE-603 study in several solid tumor types, including NSCLC. Additionally, in pts with completely resected, high-risk stage IIIB/C/D and IV cutaneous melanoma in the KEYNOTE-942 primary analysis, V940 plus pembro demonstrated significant improvements in recurrence-free survival (HR, 0.561 [95% CI, 0.309–1.017]; P = 0.0266) and distant metastasis-free survival (HR, 0.347 [95% CI, 0.145–0.828]; P = 0.0063) vs pembro alone. Here we present the design of the phase 3, randomized, double-blind INTerpath-002 study (NCT06077760) of adjuvant V940 plus pembro vs placebo plus pembro in pts with completely resected and chemotherapy-treated stage II–IIIB (N2) NSCLC (AJCC v8). Methods: Eligible pts aged ≥18 years with completely resected stage II, IIIA, or IIIB (N2) squamous or nonsquamous NSCLC (per AJCC v8.0) where EGFR-directed therapy is not indicated as primary therapy (ie, absence of sensitizing EGFR mutations e.g. DEL19 or L858R), who have received 1–4 doses of adjuvant platinum-doublet chemotherapy, have ECOG PS 0 or 1, and have available tumor tissue for next-generation sequencing and PD-L1 testing will be enrolled. Pts must not have received previous neoadjuvant therapy for NSCLC and must not have received or be candidates for adjuvant radiotherapy. Pts will be randomized 1:1 to receive V940 1 mg IM or placebo Q3W for up to 9 doses plus pembro 400 mg IV Q6W for up to 9 cycles or until disease recurrence, pt withdrawal, unacceptable toxicity, or an additional malignancy requiring treatment. Randomization will be stratified by histology (squamous vs nonsquamous), PD-L1 TPS ( &lt; 1% vs 1%–49% vs ≥50%), disease stage (II vs III), and geographic location (North America/Western Europe/Australia vs rest of world). The primary endpoint is disease-free survival per investigator review. Secondary endpoints include distant metastasis-free survival per investigator assessment, OS, lung cancer‒specific survival, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, every 12 wk until wk 48, every 24 wk through year 3, and every 48 wk thereafter. Enrollment began in October 2023 and is ongoing globally (NCT06077760). The abstract was originally presented and published in: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT281. Clinical trial information: NCT06077760 .

Racial and elderly disparities in receipt of guideline-concordant care in stage I-III breast cancer.

e13688 Background: Elderly and non-Hispanic Black (NHB) patients have worse breast cancer specific survival outcomes. We evaluated whether guideline concordant care (GCC) and all-cause mortality in stage I-III breast cancer differed by race among patients ≥ 65 years old. Methods: We used the National Cancer Database (NCDB), to identify a cohort of 25174 NHB and 233357 non-Hispanic White patients (NHW), ≥65 years old, diagnosed with stage I-III breast cancer between 2010 and 2019. We used the National Comprehensive Cancer Network guidelines to define GCC, including surgery, radiation and systemic therapy. Specific systemic therapies and cause of death were unavailable. We used logistic regression models to assess the association between race and GCC. We used Cox proportional hazards models to estimate associations between race and all-cause mortality after adjusting for GCC. Both models adjusted for disease, demographics, income and educational attainment. We assessed the odds of not receiving timely GCC within 30, 60 and 90 days from diagnosis for NHB vs. NHW patients using logistic regression. Results: Overall, 15% of patients did not receive GCC. Being NHB compared to NHW was associated with increased odds of not receiving GCC in univariate (OR=1.24 95%CI: 1.20-1.28) and multivariate analysis (aOR=1.13, 95%CI: 1.08-1.17). Being NHB was associated with 26% increased risk of all-cause mortality in the univariate analysis (HR=1.26, p&lt;0.001), which decreased to 4% increased risk, after adjusting for GCC, age, clinical and sociodemographic factors (aHR=1.04, p=0.027). Non-receipt of GCC (aHR=1.75, p&lt;0.001) and lower educational attainment (aHR 1.18, p &lt;0.001) were independently associated with higher risk of all-cause mortality. Higher median income (aHR 0.91, p&lt;0.001) was independently associated with a decreased risk of mortality. Being NHW compared to NHB was associated with increased odds of initiating treatment within 30 (OR=1.65, 95% CI 1.6-1.69), 60 (OR=2.11, 95% CI 2.04-2.18), and 90 days of breast cancer diagnosis (OR=2.39, 95% CI 2.27-2.51). Conclusions: Among elderly patients with stage I-III BC, being NHB was associated with increased odds of not receiving GCC and less timely treatment initiation. Being NHB was associated with increased all-cause mortality, which was attenuated after adjusting for GCC. Optimizing timely receipt of GCC may reduce inferior survival outcomes among elderly NHB breast cancer patients. Identifying area-level determinants may help design targeted interventions. Limitations include lack of granular systemic therapy data, likely overestimating GCC receipt, biasing the analysis towards the null, and lack of cause-specific death among elderly patients with competing risks of death.

Evaluating the impact of depression on self-reported quality of life measurements for patients with a history of cancer: A 2022 behavioral risk factor surveillance system questionnaire study.

e23131 Background: Patients with cancer are known to have higher rates of depression than the general population. Depression is known to impact cancer-specific outcomes. We aimed to understand if a history of depression for patients with a history of cancer impacts self-reported quality of life measurements. Methods: We identified patients with a history of cancer and patients with a history of depression using the 2022 phone based Behavioral Risk Factor Surveillance System Questionnaire. The demographics and reported outcomes for several quality-of-life questions, including perceived emotional support, social isolation, cancer-related pain, memory, and ability to complete daily activities independently, were compared using a Chi-Square analysis. Results: Of the 441,339 patients over the age of 18 who completed the 2022 survey, 72,765 (16%) reported a history of cancer, and 90,489 (21%) reported a history of depression. Of those patients who reported a history of cancer 72,443 (99.6%) answered if they had ever been diagnosed with depression, and of these 14,987 (21%) reported a history of depression. Compared to patients with cancer alone, patients with a history of cancer and depression were younger (10% vs. 4% under the age of 45, p &lt; 0.001), less often married (45% vs.59%, p &lt; 0.001), more likely to be in the lowest income bracket (8% vs. 3%, p &lt; 0.001), more likely to be obese (36% vs. 26%, p &lt; 0.001), and more often active smokers (16% vs. 7%, p &lt; 0.001). Several quality-of-life questions were asked of the participants, although not everyone answered each question. Overall, among patients with cancer, patients with a history of depression were more likely to report &gt; 14 poor mental health or physical health days (35% vs. 6% and 34% vs. 14%, respectively, p &lt; 0.001) and more likely to report their general health as fair or poor (41% vs. 21%, p &lt; 0.001). Cancer patients with depression were less likely to report always having the social or emotional support that they need (33% vs. 55%, p &lt; 0.001) and more likely to report always or usually feeling socially isolated (17% vs. 5%, p &lt; 0.001). Cancer patients with depression were more likely to report pain associated with their cancer (16% vs. 7%, p &lt; 0.001) and five times as likely to report issues with making decisions and memory (31% vs. 6%, p &lt; 0.001). Finally, patients with depression were also more likely to report an inability to run errands alone (21% vs. 7%) and report difficulty getting dressed or bathing (12% vs. 4%, p &lt; 0.001). Conclusions: Among people with a history of cancer, those with a history of depression are more likely to report worse physical and mental health, report worse social and emotional support and report less independence in activities of daily living. Further work is needed to understand the complex interactions between depression and quality-of-life measures for cancer patients.

Does larger prostate size provide protection for cancer specific outcomes in localized prostate cancer.

Benign prostatic hyperplasia is common in the aging population and frequently comorbid with localized prostate cancer. Large prostate volume places significant challenges in robotic prostatectomy including reduced mobility and visualization. The goal of this study is to evaluate the effect of prostate volume as a continuous variable on cancer specific outcomes. Three thousand four hundred and twenty five patients with localized prostate cancer at a single institution who underwent robotic prostatectomy were retrospectively reviewed. A number of preoperative, operative, and postoperative variables were collected to evaluate cancer specific outcomes including pathologic stage, tissue margins, and biochemical recurrence (BCR). Logistic regression models and univariate and multivariate analyses were implemented for pathologic stage T3 and BCR respectively. The median follow up time was 52 months (IQR 18-95). 37.4% of the patients had a final pathologic stage of T3 or higher, 21.2% experienced positive surgical margins, and 24.7% of patients experienced BCR. Prostate size was a significant predictor of all three outcomes of interest. Increasing prostate size was protective against both higher pathologic stage and positive surgical margins (odds ratio = 0.989, 0.990 respectively, p < 0.001). There was a modest increase in the risk of BCR with increasing gland size (hazard ratio = 1.006, p < 0.001). These results were most significant for patients with Gleason Grade Groups 1 and 2 prostate cancer. Prostate size is a commonly determined clinical factor that effects both surgical planning and cancer specific outcomes. Increasing prostate size may offer protection against higher stage disease and positive surgical margins. While surgically challenging, favorable oncologic outcomes can be consistently achieved for patients with low-intermediate risk disease.