Multimodal AI-driven analysis in breast and lung cancer: insights from the OPTIMA prototyping workshop

Chemotherapy

Introduction to the Third Edition: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Wise Choices to Improve the Quality of Lung Cancer Care.

Cancer genomic medicine interprets genetic information for diagnosis and treatment. It requires an organized team of experts from various fields to discuss treatment recommendations at a molecular tumor board (MTB). It is also important to track patient outcomes based on these decisions and seamlessly incorporate them into future discussions at the MTB. We developed a system to manage the MTB efficiently. Using this system, we followed the outcome and prognosis of 1643 patients whose treatment was discussed at the MTB and evaluated the utility of a realistic comprehensive genomic profiling (CGP) test. Treatment recommendations were made for 240 patients (14% of the total cases). Of these, 118 (7% of the total) were treated with the drugs recommended by the MTB. The cancer type with the highest percentage of patients in which treatment recommendations were made and drugs were administered was thyroid cancer, followed by breast cancer, lung cancer, prostate cancer, and cholangiocarcinoma. While cancer-specific overall survival was inconclusive due to few cases, CGP-recommended treatment significantly extended patient survival from the CGP test date. This analysis, utilizing our patient follow-up system, suggests that CGP testing expands treatment options for a subset of patients and may improve treatment efficacy.

New American College of Chest Physicians Lung Cancer Guidelines*: An Important Addition to the Lung Cancer Guidelines Armamentarium

Lung Cancer in Belgium

Lung Cancer in Sudan

917P OPTIMA: Improve care for patients with prostate, breast, and lung cancer through artificial intelligence

e18582 Background: Lung, colorectal, and breast cancer account for the majority of cancer deaths in the U.S. Patients with late stage lung cancer have the shortest survival of the three, and lung cancer patients are more likely to be diagnosed at later stages. We undertook this study to compare social determinants of health in patients diagnosed with late stages of lung, breast, and colon cancer to assess the impact they have on health and mortality. Methods: Data from the National Cancer Database was used for this study. We compared factors including insurance, income, and residency among late stage cancer patients (Stage III and IV). We also compared baseline health status measured by comorbidity index. Descriptive statistics were used to compare patient characteristics. Statistical significance was determined on the basis of a two-sided p value < 0.05. All statistical analysis was performed using SAS, version 9.4. Results: Between 2004 - 2016, 3,005,513 patients were diagnosed with lung (1,004,999), breast (1,309,796), and colon (690,718) cancer. The racial make-up of the groups was similar. 72.5% of lung cancer patients were diagnosed at late stage compared to 48.8% of colon and 13.8% of breast cancer patients. Patients with late stage lung cancer were more likely to have income < $38,000, reside in rural locations, and less likely to have private insurance. Late stage lung cancer patients were 2 and 4 times more likely to have at least 2 comorbidities than patients with colon and breast cancer respectively. Conclusions: Patients with lung cancer are disproportionately affected by several negative social determinants of health. The association between smoking and lung cancer may help explain this because the highest smoking rates in the U.S. occur in populations with lower income, low education status, less insurance coverage, and significantly more comorbidities (e.g. COPD, Heart Disease). These patients are dealing with the complex interplay of negative social determinants of health and worse baseline health status causing delays in diagnosis and treatment when compared to other cancers. Recognizing this may allow systems to better support this disadvantaged population and improve access to screening, clinical trial inclusion, and personalized treatment options while working longitudinally to reverse the systemic factors affecting disproportionate tobacco use and lack of healthcare access in for this underserved population.

8094 Background: Patients with bone metastases of breast, lung, and prostate cancer often experience skeletal-related complications including pathological fracture, spinal cord compression, hypercalcemia, or pain requiring surgery, radiotherapy, or opioid analgesics (collectively, skeletal-related events [SREs]). Effects of SREs on total medical-care costs have not been compared across patients with different tumor types. Methods: We used a US health insurance claims database (7/94–6/02) to quantify the impact of SREs on total medical-care costs in patients with bone metastases of various solid tumors. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary breast, lung, or prostate cancer and ≥2 encounters with a diagnosis of metastases to bone. For each tumor type, Kaplan-Meier estimated medical-care costs were compared for propensity-matched samples of patients with SREs versus without SREs. Results: We identified 1702 patients with bone metastases of breast (n=617), lung (n=543), and prostate cancer (n=542), of whom 52% (breast and prostate) to 55% (lung) experienced at least one SRE during the observation period (mean 6.0 mos [lung] to 15 mos [breast]). After matching for age, gender, and comorbidities using propensity score, there were 201, 162 and 181 pairs of SRE/no SRE patients with breast, lung, and prostate cancer, respectively. In SRE patients, costs of SRE treatment ranged from $9,480 (95%CI $7,625-$11,374) in lung to $13,940 ($11,240-$16,856) in breast cancer. Differences (SRE vs no SRE) in total costs (SRE treatment and other care) ranged from $20,792 ($4,829-$36,475) in prostate to $48,173 ($19,068-$77,684) in breast cancer. Median survival was greater in SRE vs no SRE patients in lung cancer (p=.048); there was a similar trend in breast and prostate cancers. After adjusting for differences (SRE vs no SRE) in survival, differences (SRE vs no SRE) in total costs ranged from $18,051 in prostate to $43,548 in breast cancer. Conclusions: Costs of SREs in patients with solid tumors and bone metastases are substantial across tumor types and may be greatest in breast cancer. Treatments which prevent SREs, such as intravenous bisphosphonates, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Aventis

The era of precision oncology has fundamentally transformed cancer treatment from empirical cytotoxic approaches toward molecularly guided therapeutic strategies that exploit specific genetic vulnerabilities within individual tumors, representing a paradigm shift that has improved outcomes for patients with previously untreatable malignancies. This research characterized the landscape of actionable genetic mutations across multiple solid tumor types and evaluated treatment outcomes in patients receiving mutation-matched targeted therapies at Italian oncology centers between March 2019 and September 2022 to determine the clinical utility of comprehensive genomic profiling in routine practice. We conducted comprehensive molecular profiling using next-generation sequencing panels interrogating 161 cancer-associated genes on tumor specimens from 1,847 patients with advanced solid malignancies including lung cancer, colorectal cancer, breast cancer, melanoma, pancreatic cancer, and other tumor types, identifying driver mutations and correlating mutation status with response to targeted therapies administered according to national treatment guidelines. Actionable mutations were identified in 67.3% of analyzed specimens, with mutation frequencies varying substantially across tumor types ranging from 42.1% in prostate cancer to 89.7% in non-small cell lung cancer reflecting the differential genomic complexity characterizing different malignancies. The most frequently altered genes included TP53 (48.2%), KRAS (31.4%), PIK3CA (18.7%), EGFR (14.3%), and BRAF (11.8%), with distinct mutation patterns characterizing different malignancy types that inform tumor-specific testing strategies. Among 892 patients receiving mutation-matched targeted therapies, overall response rates reached 71.4% for EGFR-mutant lung cancers treated with third-generation tyrosine kinase inhibitors, 68.9% for BRAF-mutant melanomas receiving combination BRAF/MEK inhibition, 82.9% for ALK-rearranged tumors treated with second-generation inhibitors, and 42.3% for KRAS G12C-mutant tumors treated with recently approved covalent inhibitors. Progression-free survival correlated significantly with the presence of actionable mutations and with successful matching to approved targeted agents (hazard ratio 0.62, 95% CI 0.54-0.71), demonstrating the clinical value of molecular characterization. Patients with tumors harboring multiple concurrent driver mutations demonstrated inferior outcomes compared to those with single driver alterations, highlighting the complexity of resistance mechanisms requiring combination therapeutic strategies addressing concurrent oncogenic signaling. The research demonstrates that comprehensive genomic profiling enables identification of therapeutic targets in the majority of advanced solid tumors, with mutation-matched targeted therapies delivering superior outcomes compared to conventional chemotherapy, though the emergence of resistance mutations necessitates continued molecular monitoring and adaptive treatment approaches.

Stigma May Exacerbate Disproportionately Low Guideline-Concordant Treatment Rates for Patients With Advanced-Stage Lung Cancer in the United States

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Overall Survival From a Prospective Multi-Institutional Trial to Resolve Black-White Disparities in the Treatment of Early Stage Breast and Lung Cancer

Introduction: Family history of breast cancer has been shown to be a strong risk factor for breast cancer in all populations studied. However, there are limited data related to risk of estrogen receptor negative (ER-) breast cancer in African American women, who have a disproportionately high incidence of ER- and triple negative (ER-, progesterone receptor negative, and HER2 receptor negative; TN) breast cancer. Even less information is available on whether a family history of other cancers also affects risk of ER- and TN breast cancer. Methods: Questionnaire data from the Black Women's Health Study, the Carolina Breast Cancer Study, the Multiethnic Cohort Study, and the Women's Circle of Health Study were pooled as part of the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Breast cancer cases were classified as ER+, ER-, and TN based on pathology data from medical records and/or state cancer registries. Participants were asked about first degree relatives with a breast cancer diagnosis and the age at which the relative was diagnosed. Participants were also asked about first degree relatives with prostate, lung, colorectal, ovarian, or cervical cancer or with lymphoma or leukemia. Polytomous logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for various categories of positive family history relative to no first degree relative with breast cancer or no first degree relative with any of the cancers. Multivariable analyses controlled for age, study, time period, and other potential confounders. Results: The analysis included 3,023 African American women with ER+, 1,497 with ER-, and 696 with TN breast cancer and 17,420 controls. First degree family history of breast cancer, regardless of whether first degree relatives had cancers other than breast cancer, was associated with a 70% increased risk of ER+, ER- and TN breast cancer; the ORs were 1.7 (95% CI 1.6-2.0) for ER+, 1.7 (95% CI 1.4-1.9) for ER-, and 1.7 (95% CI 1.4-2.1) for TN breast cancer. The ORs were somewhat higher if the relative was diagnosed before age 50 (2.0 for ER+, 1.9 for ER-, and 1.8 for TN). Among the six other cancer sites examined, only family history of cervical cancer was significantly associated with risk; the ORs were 2.4 (1.4-4.2) for ER- and 2.9 (1.5-5.5) for TN breast cancer and there was no association with ER+ breast cancer. The OR for family history of ovarian cancer in relation to TN breast cancer was 1.6 (0.9-2.7), which is of interest because findings from The Cancer Genome Atlas (TCGA) indicate that serous ovarian cancers and basal-like breast cancers, which are mostly triple negative, have many molecular commonalities. The ORs for a family history of both breast and prostate cancer versus no family history of any of the cancers were 3.4 (2.4-4.7) for ER+ cancer, as compared with 1.6 for breast alone (p-interaction=0.01), and 2.1 (1.2-3.7) for ER- cancer, as compared with 1.5 for breast alone (p-interaction=0.08). The OR for a family history of both breast and lung cancer was 3.3 (1.9-5.9) for TN breast cancer, compared to 1.5 for breast alone (p-interaction=0.10). The ORs for family history of breast plus two other cancers were 2.4 (1.6-3.6) for ER+, 2.8 (1.6-4.7) for ER-, and 2.7 (1.3-5.7) for TN breast cancer. Conclusion: Our results confirm that having a first degree family history of breast cancer is a strong risk factor for ER+, ER-, and TN breast cancer. The findings also suggest that having relatives with other cancers in addition to a relative with breast cancer may further increase risk. Consideration of family history of other cancers may improve risk prediction models. The association observed for family history of cervical cancer and increased risk of ER- and TN breast cancer was unexpected and needs to be replicated by other studies. Citation Format: Traci N. Bethea, Lynn Rosenberg, Nelsy Castro-Webb, Kathryn L. Lunetta, Lara E. Sucheston, Edward A. Ruiz-Narvaez, Marjory Charlot, Song Y. Park, Elisa V. Bandera, Melissa A. Troester, Christine B. Ambrosone, Julie R. Palmer. Relation of family history of cancer to risk of ER+, ER-, and triple-negative breast cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C49.