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  • American Association for Cancer Research (AACR)  (4)
  • Bandlamudi, Chaitanya  (4)
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  • American Association for Cancer Research (AACR)  (4)
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  • 1
    Online Resource
    Online Resource
    Abstract IA04: COVID-19 in patients with lung cancers in New York City
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 18_Supplement ( 2020-09-15), p. IA04-IA04
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 18_Supplement ( 2020-09-15), p. IA04-IA04
    Abstract: Background: Patients with lung cancers may have distinct vulnerability to severe COVID-19. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. A key question is whether PD-1 blockade therapy impacts COVID-19 severity. Methods: We identified consecutive patients with lung cancer and a positive SARS-CoV-2 RT-PCR test seen at a single cancer center in New York City. We performed detailed manual review of the disease course, medical and oncologic history. COVID-19 severity outcomes were predefined, including need for hospitalization, ICU/intubation/transition to DNI-status, or death. We examined clinical features associated with severity using single and multivariable analyses. Regarding the impact of PD-1 blockade, we prespecified several bio-plausible comparisons of PD-1 exposure. HLA alleles were inferred from NGS and compared to controls with lung cancer and no known COVID-19. Results: We identified 102 patients with lung cancers and a SARS-CoV-2 positive swab between March 12, 2020 and May 6, 2020. Patients were followed until May 11, 2020. COVID-19 was severe in patients with lung cancers (62% hospitalized, 25% died), but accounted for only 11% of deaths among patients with lung cancer during the pandemic. Determinants of COVID-19 severity were largely patient specific, including smoking status and chronic obstructive pulmonary disease. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies, did not impact severity. Likelihood of severe COVID-19 was generally similar across HLA class I supertypes. We found no significant differences in the impact of PD-1 blockade on COVID-19 severity. Modest numerical increases in severity of COVID-19 associated with prior PD-1 blockade were diminished (Odds ratio 0.86-1.01) after adjusting for expected imbalances in prior smoking history. Most patients recovered from COVID-19, including 25% of patients initially requiring intubation. Conclusion: COVID-19 is associated with a high burden of severity in patients with lung cancers. Patient-specific features, rather than cancer-specific features or treatments, were the greatest determinants of severity. In particular, PD-1 blockade did not appear to impact severity of COVID-19 in patients with lung cancers. Citation Format: Jia Luo, Hira Rizvi, Isabel R. Preeshagul, Jacklynn V. Egger, David Hoyos, Chaitanya Bandlamudi, Mark T.A. Donoghue, Marta Łuksza, Benjamin D. Greenbaum, Jedd D. Wolchok, Mark G. Kris, Matthew D. Hellmann. COVID-19 in patients with lung cancers in New York City [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA04.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1557-3265.COVID-19-IA04
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 2
    Online Resource
    Online Resource
    Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 31, No. 7 ( 2022-07-01), p. 1450-1459
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 31, No. 7 ( 2022-07-01), p. 1450-1459
    Abstract: The genetic factors that modulate risk for developing lung cancer have not been fully defined. Here, we sought to determine the prevalence and clinical significance of germline pathogenic/likely pathogenic variants (PV) in patients with advanced lung cancer. Methods: We studied clinical and tumor characteristics of germline PV in 5,118 patients who underwent prospective genomic profiling using paired tumor–normal tissue samples in 468 cancer genes. Results: Germline PV in high/moderate-penetrance genes were observed in 222 (4.3%) patients; of these, 193 patients had PV in DNA damage repair (DDR) pathway genes including BRCA2 (n = 54), CHEK2 (n = 30), and ATM (n = 26) that showed high rate of biallelic inactivation in tumors. BRCA2 heterozygotes with lung adenocarcinoma were more likely to be never smokers and had improved survival compared with noncarriers. Fourteen patients with germline PV in lung cancer predisposing genes (TP53, EGFR, BAP1, and MEN1) were diagnosed at younger age compared with noncarriers, and of tumor suppressors, 75% demonstrated biallelic inactivation in tumors. A significantly higher proportion of germline PV in high/moderate-penetrance genes were detected in high-risk patients who had either a family history of any cancer, multiple primary tumors, or early age at diagnosis compared with unselected patients (10.5% vs. 4.1%; P = 1.7e−04). Conclusions: These data underscore the biological and clinical importance of germline mutations in highly penetrant DDR genes as a risk factor for lung cancer. Impact: The family members of lung cancer patients harboring PV in cancer predisposing genes should be referred for genetic counseling and may benefit from proactive surveillance.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-21-1287
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 3
    Online Resource
    Online Resource
    Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer
    American Association for Cancer Research (AACR) ; 2023
    In:  Clinical Cancer Research ( 2023-07-11)
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-07-11)
    Abstract: Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICIs), and how these might differ from features predictive of short-term response (STR). Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs over ten years. LTR and STR were defined as response ≥ 24 months and response & lt; 12 months, respectively. Tumor PD-L1 expression, mutational burden (TMB), next-generation sequencing, and whole exome sequencing data were analyzed to identify characteristics enriched in patients achieving LTR compared to STR and non-LTR. Results: Among 3118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival of 81% and 18% among LTR and STR patients respectively. High TMB (≥ 50th percentile) enriched for LTR compared to STR (P = 0.001) and non-LTR (P & lt; 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared to non-LTR (P & lt; 0.001); PD-L1 ≥ 50% did not enrich for LTR compared to STR (P = 0.181). Non-squamous histology (P = 0.040) and increasing depth of response (median best overall response [BOR] -65% vs -46%, P & lt; 0.001) also associated with LTR compared to STR; no individual genomic alterations were uniquely enriched among LTR patients. Conclusions: Among advanced NSCLC patients treated with ICIs, distinct features including high TMB, non-squamous histology, and depth of radiographic improvement distinguish patients poised to achieve long-term response compared to initial response followed by progression, whereas high PD-L1 does not.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-23-1207
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 4
    Online Resource
    Online Resource
    Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Discovery Vol. 12, No. 11 ( 2022-11-02), p. 2552-2565
    Details
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 12, No. 11 ( 2022-11-02), p. 2552-2565
    Abstract: Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions. Significance: We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including & gt;5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations. This article is highlighted in the In This Issue feature, p. 2483
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    URL: Article
    DOI: 10.1158/2159-8290.CD-22-0312
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2607892-2
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