Translational Research for the Near Future
Activity: 103rd Annual Meeting
Memorial Sloan Kettering Cancer Center
New York, NY
United States - Contact Me
Biography: David R. Jones, MD
Dr. Jones graduated Phi Beta Kappa from West Virginia University and received his medical degree from West Virginia University School of Medicine where he was AOA. He completed his Thoracic Surgery Residency at the University of North Carolina at Chapel Hill, NC. In 1999, Dr. Jones joined the faculty at the University of Virginia where he became Professor and Vice-Chairman of the Department. In 2013 Dr. Jones was recruited to Memorial Sloan Kettering Cancer Center as Chief of Thoracic Surgery.
Dr. Jones is Professor & Chief of Thoracic Surgery and Executive Vice-chair of the Department of Surgery at MSKCC. He is also the Co-Director of the Fiona and Stanly Druckenmiller Center for Lung Cancer Research. He is the current Secretary of the AATS and Chair of the AATS-MSKCC Thoracic Surgery Oncology Group (TSOG) for clinical trials. Dr. Jones is Associate Editor for the Journal of Thoracic and Cardiovascular Surgery. He is recent past Chair of the NIH/NCI Tumor Progression and Metastasis (TPM) study section and currently serves on the NCI Board of Scientific Advisors. He serves on numerous national and international committees related to thoracic surgical research and clinical care.
Dr. Jones’s research focuses on mechanisms and drivers of metastases in lung cancer. His research has been funded by the NIH/NCI, Department of Defense, and the AACR. He has been the Principal Investigator or Co-PI on over 35 funded grants and currently holds 2 R01 awards from the NCI. He has published over 380 papers and has written over 35 book chapters. He was an early adopter of VATS anatomic resections and minimally-invasive esophagectomies and performs the majority of his operations using these minimally-invasive approaches.
University of Maryland Medical System
Baltimore, MD
United States - Contact Me
Dr. Krupnick is the chief of thoracic surgery at the University of Maryland School of Medicine with an academic and clinical focus dedicated to the care of patients with end-stage lung failure and oncologic disease. He provides a full range of thoracic surgery services, including minimally invasive lung and esophageal resections, on the University of Maryland Medical School main campus as as affiliated hospitals. His laboratory has made seminal contributions toward the understanding lung transplant immunology, including the development of the world’s first model of vascularized orthotopic lung transplantation in the mouse (PMC3848695). He has also described numerous mechanistic aspects of lung allograft tolerance and rejection including the role of CD8+ T cells and eosinophils in mediating lung allograft tolerance (PMC3938255, PMC6629120). In addition to work on transplantation my laboratory has focused extensive efforts on understanding and reversing immunological dysfunction associated with cancer. His laboratory has made contributions in describing the role of natural killer cells in controlling lung cancer development and progression (PMID: 22751136), as well as advancing the understanding of immunological factors that limit natural killer cell function in malignancies (PMID: 30381460, 28123874). Based this understanding he has developed a rationally designed retargeted cytokine to activate natural killer cells and CD8+ cytotoxic lymphocytes (PMID: 27650575). These efforts are now being advanced toward human applications with an IND application in progress, GMP drug production initiated, and clinical trials planned for summer of 2022.
Sunday, May 7, 2023: 7:00 AM - 8:45 AM
Los Angeles Convention Center
Posted Room Name: 408B
Track
Thoracic
103rd Annual Meeting
Presentations
100. Pilot Study Demonstrating the Lung Microbiome as a Potential Marker for Lung Cancer
Total Time: 15 Minutes
Objectives: Lung cancer continues to be diagnosed at later stages limiting curative treatment options. The role of the lung microbiome in the proximal lung as a marker for a more peripheral cancer is not well understood. We hypothesized that the lung microbiome pattern could differentiate between tumor types and stages.
Methods: We collected central lobar bronchoalveolar lavage fluid (BALF) and brushing samples from early-stage lung cancer patients between July 2018 and May 2019 at a single academic center. Samples were collected from the affected lobe, ipsilateral non-affected lobe, and contralateral lobe. We performed microbial sequencing, untargeted metabolomics and cytokine analysis. We compared clinical and pathologic findings to microbiome signatures.
Results: Samples were collected from 28 patients with resectable lung cancer. Affected lobes displayed a different microbiome signature than contra-lateral lobes. In patents with adenocarcinoma (A), Microbiome diversity trended towards being less in patients with poor differentiated tumors vs those with well differentiated (p=0.08). The microbiome diversity in patients with A was similar to those with squamous cell cancer (SCC) (p=0.27). There were no differences in diversity or composition in the non-affected lobes of patients with A vs SCC. In evaluating the contralateral lobes, COPD patients trended towards having less diversity than those without COPD (p=0.1312).
Conclusions: The lung microbiome can potentially be used to differentiate between affected and non-affected lobes in the same patient. Further work is needed to understand the specific differences seen in the specific flora.
Methods: We collected central lobar bronchoalveolar lavage fluid (BALF) and brushing samples from early-stage lung cancer patients between July 2018 and May 2019 at a single academic center. Samples were collected from the affected lobe, ipsilateral non-affected lobe, and contralateral lobe. We performed microbial sequencing, untargeted metabolomics and cytokine analysis. We compared clinical and pathologic findings to microbiome signatures.
Results: Samples were collected from 28 patients with resectable lung cancer. Affected lobes displayed a different microbiome signature than contra-lateral lobes. In patents with adenocarcinoma (A), Microbiome diversity trended towards being less in patients with poor differentiated tumors vs those with well differentiated (p=0.08). The microbiome diversity in patients with A was similar to those with squamous cell cancer (SCC) (p=0.27). There were no differences in diversity or composition in the non-affected lobes of patients with A vs SCC. In evaluating the contralateral lobes, COPD patients trended towards having less diversity than those without COPD (p=0.1312).
Conclusions: The lung microbiome can potentially be used to differentiate between affected and non-affected lobes in the same patient. Further work is needed to understand the specific differences seen in the specific flora.
View Submission
Invited Discussant
*Sai Yendamuri, Roswell Park Comprehensive Cancer Center - Contact Me Amherst, NYUnited States
Abstract Presenter
*Rishindra Reddy, University of Michigan Medical Center - Contact Me Ann Arbor, MIUnited States
101. Targeting Loss of p19, not p16, Reprograms Tumor and Systemic Immunity in Pleural Mesothelioma
Total Time: 15 Minutes
Objective: Recently we reported that cyclin-dependent kinase inhibitor 2a (CDKN2A)-depleted malignant mesothelioma (MM) is resistant to immune checkpoint blockade (ICB) and CDK4/6 inhibitors (CDK4/6i) improved primary resistance to ICB. CDKN2A, which is the most altered genomic locus in MM, encodes p14 (p19 in mouse) and p16. P16-cyclin D-CDK4/6-Rb and p14-MDM2-p53 pathways inhibit cell cycle and apoptosis, respectively (Fig.1A). However, resistance to CDK4/6i is considered a near-inevitability in a real world. Thus, there are still unmet needs to decipher deeper mechanisms to overcome ICB resistance.
Methods: Given the synteny between human 9p21.3 and murine 4C4 (Fig.1B), p16- or p19-overexpressing mouse AB1 MM cell lines (AB1_p16OE vs. AB1_p19OE) were generated to investigate mechanisms to overcome Cdkn2a-related ICB resistance (Fig.1C). We performed mRNA sequencing for molecular characterization. Furthermore, we compared the alteration of the tumor ecosystems and systemic immunity between AB1_p16OE or AB1_p19OE in immunocompetent BALB/c mice by using imaging and time-of-flight mass cytometry (CyTOF). We also compared the efficacy of dual PD-1 and CTLA-4 blockade on these MM tumors.
Results: Transcriptome analysis showed that AB1_p19OE had a distinct gene expression pattern compared with AB1_p16OE and AB1_wild cell lines. Overexpression of p19 led to the increase of Cd80 and chemokines Cxcl10 and Ccl4, which are involved in lymphocyte recruitment. In contrast, cell cycle-related genes, Cdk2 and Ccne1, and the immunosuppressive cytokine Tgfb1 were markedly decreased in AB1_p19OE cells (Fig.1D). Our in vivo experiments showcased a novel molecular mechanism of regulation of the tumor ecosystems that AB1_p19OE tumors contained lymphocyte aggregates, but AB1_p16OE tumor did not (Fig.1E). We evaluated the topographical expansion of T cells from the tumor to circulation in AB1_p16OE and AB1_p19OE tumors. Mouse CyTOF data showed that PD-1(+)CTLA-4(+) T cells were abundant in tumors (Fig.1F). Interestingly, AB1_p19OE tumors revealed the topographical expansion of CD4 and CD8 effector memory T cells from the tumor to PBMC (Fig.1F) and had a better response to dual ICBs (Fig.1G).
Conclusions: We have identified a novel therapeutic target, p19 in mice or p14 in humans, to sensitize tumors to ICB. This finding could help provide a rationale for combination treatment of ICB with MDM2 inhibitors to restore the function of p14 to treat MM patients with CDKN2A loss.
Methods: Given the synteny between human 9p21.3 and murine 4C4 (Fig.1B), p16- or p19-overexpressing mouse AB1 MM cell lines (AB1_p16OE vs. AB1_p19OE) were generated to investigate mechanisms to overcome Cdkn2a-related ICB resistance (Fig.1C). We performed mRNA sequencing for molecular characterization. Furthermore, we compared the alteration of the tumor ecosystems and systemic immunity between AB1_p16OE or AB1_p19OE in immunocompetent BALB/c mice by using imaging and time-of-flight mass cytometry (CyTOF). We also compared the efficacy of dual PD-1 and CTLA-4 blockade on these MM tumors.
Results: Transcriptome analysis showed that AB1_p19OE had a distinct gene expression pattern compared with AB1_p16OE and AB1_wild cell lines. Overexpression of p19 led to the increase of Cd80 and chemokines Cxcl10 and Ccl4, which are involved in lymphocyte recruitment. In contrast, cell cycle-related genes, Cdk2 and Ccne1, and the immunosuppressive cytokine Tgfb1 were markedly decreased in AB1_p19OE cells (Fig.1D). Our in vivo experiments showcased a novel molecular mechanism of regulation of the tumor ecosystems that AB1_p19OE tumors contained lymphocyte aggregates, but AB1_p16OE tumor did not (Fig.1E). We evaluated the topographical expansion of T cells from the tumor to circulation in AB1_p16OE and AB1_p19OE tumors. Mouse CyTOF data showed that PD-1(+)CTLA-4(+) T cells were abundant in tumors (Fig.1F). Interestingly, AB1_p19OE tumors revealed the topographical expansion of CD4 and CD8 effector memory T cells from the tumor to PBMC (Fig.1F) and had a better response to dual ICBs (Fig.1G).
Conclusions: We have identified a novel therapeutic target, p19 in mice or p14 in humans, to sensitize tumors to ICB. This finding could help provide a rationale for combination treatment of ICB with MDM2 inhibitors to restore the function of p14 to treat MM patients with CDKN2A loss.
View Submission
- 101 - Targeting Loss of p19, not p16, Reprograms Tumor and Systemic Immunity in Pleural Mesothelioma
Invited Discussant
*Andrea Wolf, The Icahn School of Medicine at Mount Sinai - Contact Me New York, NYUnited States
Abstract Presenter
♦Hyun-Sung Lee, Baylor College of Medicine - Contact Me Houston, TXUnited States
102. Angiotensin System Inhibitors are Associated with Improved Survival in Locally Advanced NSCLC and Exhibit Anti-tumor Synergism with Chemotherapy in a Murine Model of NSCLC
Total Time: 15 Minutes
Objective: Several studies suggest that angiotensin system inhibitors can potentiate anti-tumor strategies in solid tumors. We investigated angiotensin system inhibitors (ASI) on outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) and performed translational studies to elucidate anti-tumor mechanism in a murine model of NSCLC.
Methods: Survival outcomes of patients (N=125) diagnosed with clinical stage IIIA NSCLC treated with chemoradiotherapy followed by surgery (2009-2015) were correlated with ASI use in a single institutional cohort. To assess anti-tumor efficacy of ASI's, cell culture models of lung cancer were treated with Losartan or combination Losartan and Cisplatin in vitro and then applied to in vivo models. Mechanism was assessed with markers of endothelial-mesenchymal transition (EMT) or surrogates of other signalling pathways.
Results: In a cohort of 125 patents treated stage IIIA NSCLC, overall survival of ASI users (n=99) were compared to ASI non users (n=26). On multivariate analysis ASI use was independently associated with improved overall survival (p =0.047, HR 0.324). Further exploration at the bench with Losartan (≥0.5μM) significantly inhibited proliferation and migration of multiple human lung cancer cells in vitro including H441, H358, H1299, SW1573 and also in a syngeneic murine lung cancer cell line, TC-1. The combination of Losartan and Cisplatin significantly improved the cytotoxic effect of cisplatin (H441 p 0.043, H358 p 0.044, H1299 p 0.046, SW1573 p 0.020, TC-1 p 0.012) and significantly reduced the tumor volume of implanted subcutaneous tumors (SW1573-Nude mice, p=0.045; TC-1-C57BL/6 mice, p=0.001) in a murine flank model. Combination treatment significantly inhibited EMT and down-regulated the expression of AKT, Stat3, and PD-L1.
Conclusions: ASI use was associated with improved overall survival in a cohort of stage IIIA NSCLC . Losartan enhances the cytotoxic effect of chemotherapy in a dose dependent fashion in a murine model of NSCLC by attenuating the EMT pathway. This study suggests an important role for ASI therapy as an adjunct in the multi-modality cytotoxic treatment of lung cancer.
Methods: Survival outcomes of patients (N=125) diagnosed with clinical stage IIIA NSCLC treated with chemoradiotherapy followed by surgery (2009-2015) were correlated with ASI use in a single institutional cohort. To assess anti-tumor efficacy of ASI's, cell culture models of lung cancer were treated with Losartan or combination Losartan and Cisplatin in vitro and then applied to in vivo models. Mechanism was assessed with markers of endothelial-mesenchymal transition (EMT) or surrogates of other signalling pathways.
Results: In a cohort of 125 patents treated stage IIIA NSCLC, overall survival of ASI users (n=99) were compared to ASI non users (n=26). On multivariate analysis ASI use was independently associated with improved overall survival (p =0.047, HR 0.324). Further exploration at the bench with Losartan (≥0.5μM) significantly inhibited proliferation and migration of multiple human lung cancer cells in vitro including H441, H358, H1299, SW1573 and also in a syngeneic murine lung cancer cell line, TC-1. The combination of Losartan and Cisplatin significantly improved the cytotoxic effect of cisplatin (H441 p 0.043, H358 p 0.044, H1299 p 0.046, SW1573 p 0.020, TC-1 p 0.012) and significantly reduced the tumor volume of implanted subcutaneous tumors (SW1573-Nude mice, p=0.045; TC-1-C57BL/6 mice, p=0.001) in a murine flank model. Combination treatment significantly inhibited EMT and down-regulated the expression of AKT, Stat3, and PD-L1.
Conclusions: ASI use was associated with improved overall survival in a cohort of stage IIIA NSCLC . Losartan enhances the cytotoxic effect of chemotherapy in a dose dependent fashion in a murine model of NSCLC by attenuating the EMT pathway. This study suggests an important role for ASI therapy as an adjunct in the multi-modality cytotoxic treatment of lung cancer.
View Submission
Invited Discussant
*Patricia Thistlethwaite, University of California, San Diego - Contact Me La Jolla, CAUnited States
Abstract Presenter
*Michael Lanuti, Harvard University - Contact Me Boston, MAUnited States
103. Early Real-World Experience Monitoring Circulating Tumor DNA in Resected Early-Stage Non-Small Cell Lung Cancer
Total Time: 15 Minutes
Objective: To evaluate the impact of circulating tumor DNA (ctDNA) on detection and management of recurrence in patients with resected early-stage non-small cell lung cancer (NSCLC).
Methods: In October 2021, post-operative ctDNA was monitored for all surgically resected lung cancer patients at a tertiary care referral center. Peripheral blood was collected for ctDNA at 3-month intervals utilizing a third-party company. Results were tracked prospectively and clinical data was retrospectively obtained from chart review. The primary outcome measure was an abnormal ctDNA result. The secondary outcome measure was changes in practice after abnormal ctDNA: (1) new referral for consideration of adjuvant therapy or (2) more aggressive radiographic surveillance. Patients with Stage III lung cancer, a history of other malignancies, and patients who had a known recurrence prior to initiation of ctDNA monitoring were excluded from this study.
Results: 76 patients were included for analysis with a mean age of 67.3 years. VATS accounted for 92.1% of cases with lobectomy accounting for 89.5% of cases. Adenocarcinoma was present in 75% of patients. 17.1% of patients received adjuvant chemotherapy for Stage II disease. 10.5% of patients (8/76) were positive for ctDNA. 75% (6/8) of ctDNA-positive patients had a biopsy-proven recurrence and were directed into therapy. 25% (2/8) have not demonstrated radiographic evidence of recurrence but were directed into earlier interval surveillance. 33% (2/6) of positive ctDNA patients with biopsy-proven recurrence received adjuvant chemotherapy after surgery (but before positive ctDNA) due to stage II disease. 1 patient was found to have recurrent disease (brain metastases) with a negative ctDNA level. Post-operative clinical care was altered in 87.5% (7/8) of ctDNA positive patients with 62.5% (5/8) receiving an earlier surveillance CT scan and 75% (6/8) receiving early PET-CT scan.
Conclusion: Serial monitoring of ctDNA following resection of early-stage NSCLC resulted in early detection of recurrent cancer leading to early surveillance and/or unexpected medical oncology referral in 87.5% (7/8) of patients with a positive ctDNA. One patient demonstrated recurrence (brain metastases) with a negative ctDNA level. Our study exemplifies real live utilization of ctDNA and its impact on surveillance and management in early-stage resected NSCLC. Further multicenter studies are required to determine protocol-specific best practices.
Methods: In October 2021, post-operative ctDNA was monitored for all surgically resected lung cancer patients at a tertiary care referral center. Peripheral blood was collected for ctDNA at 3-month intervals utilizing a third-party company. Results were tracked prospectively and clinical data was retrospectively obtained from chart review. The primary outcome measure was an abnormal ctDNA result. The secondary outcome measure was changes in practice after abnormal ctDNA: (1) new referral for consideration of adjuvant therapy or (2) more aggressive radiographic surveillance. Patients with Stage III lung cancer, a history of other malignancies, and patients who had a known recurrence prior to initiation of ctDNA monitoring were excluded from this study.
Results: 76 patients were included for analysis with a mean age of 67.3 years. VATS accounted for 92.1% of cases with lobectomy accounting for 89.5% of cases. Adenocarcinoma was present in 75% of patients. 17.1% of patients received adjuvant chemotherapy for Stage II disease. 10.5% of patients (8/76) were positive for ctDNA. 75% (6/8) of ctDNA-positive patients had a biopsy-proven recurrence and were directed into therapy. 25% (2/8) have not demonstrated radiographic evidence of recurrence but were directed into earlier interval surveillance. 33% (2/6) of positive ctDNA patients with biopsy-proven recurrence received adjuvant chemotherapy after surgery (but before positive ctDNA) due to stage II disease. 1 patient was found to have recurrent disease (brain metastases) with a negative ctDNA level. Post-operative clinical care was altered in 87.5% (7/8) of ctDNA positive patients with 62.5% (5/8) receiving an earlier surveillance CT scan and 75% (6/8) receiving early PET-CT scan.
Conclusion: Serial monitoring of ctDNA following resection of early-stage NSCLC resulted in early detection of recurrent cancer leading to early surveillance and/or unexpected medical oncology referral in 87.5% (7/8) of patients with a positive ctDNA. One patient demonstrated recurrence (brain metastases) with a negative ctDNA level. Our study exemplifies real live utilization of ctDNA and its impact on surveillance and management in early-stage resected NSCLC. Further multicenter studies are required to determine protocol-specific best practices.
View Submission
Invited Discussant
Uma Sachdeva, Massachusetts General Hospital - Contact Me Boston, MAUnited States
Abstract Presenter
Travis MArtin, UNTHSC - Contact Me Dallas, TXUnited States
104. Oncogenic Pathway Alterations Were Correlated with Tumor Progression and Survival Benefits from Immunotherapy in Lung Adenocarcinoma
Total Time: 15 Minutes
Objective: Oncogenic pathway alterations contribute to tumor progression in lung adenocarcinoma. The study aims to test whether number of oncogenic pathway alterations (NPA) could predict clinical outcomes in surgically-resected lung adenocarcinoma and efficacy of immunotherapy.
Methods: We calculated NPA for each patient with lung adenocarcinoma from our two prospective cohorts with available DNA sequencing data (250 patients receiving 520-gene target sequencing and 99 patients receiving whole-exome sequencing). Two public cohorts from MSKCC and POPLAR/OAK were utilized to explore the predictive value of NPA in the efficacy of immunotherapy. A pathway was considered to be "altered" if at least one nonsynonymous mutation from this pathway was discovered.
Results: Among patients having panel sequencing, the most prevalent pathway alteration was RTK/RAS, appearing in 98.4% of the whole cohort (Figure 1A). Increased NPA was associated with larger TMB (P < 0.001) and tumor size (P < 0.001). High-grade adenocarcinoma (P < 0.001), visceral pleural invasion (P = 0.063), advanced TNM stage (P < 0.001), and high expression of PD-L1 (P = 0.033) were more common in patients with higher NPA. Survival analyses of patients receiving whole-exome sequencing demonstrated patients with larger NPA had significantly worse recurrence-free survival (P = 0.007) and overall survival (P < 0.001). Furthermore, high NPA was associated improved survival in the MSKCC cohort receiving immunotherapy (Figure 1B). Combination of NPA and tumor mutation burden provided better performance in identifying patients benefitting from immunotherapy in the POPLAR&OAK cohort (Figure 1C).
Conclusions: Increased NPA was associated with advanced TNM stage and poor survival in lung adenocarcinoma. NPA was a novel predictor of efficacy to immunotherapy.
Methods: We calculated NPA for each patient with lung adenocarcinoma from our two prospective cohorts with available DNA sequencing data (250 patients receiving 520-gene target sequencing and 99 patients receiving whole-exome sequencing). Two public cohorts from MSKCC and POPLAR/OAK were utilized to explore the predictive value of NPA in the efficacy of immunotherapy. A pathway was considered to be "altered" if at least one nonsynonymous mutation from this pathway was discovered.
Results: Among patients having panel sequencing, the most prevalent pathway alteration was RTK/RAS, appearing in 98.4% of the whole cohort (Figure 1A). Increased NPA was associated with larger TMB (P < 0.001) and tumor size (P < 0.001). High-grade adenocarcinoma (P < 0.001), visceral pleural invasion (P = 0.063), advanced TNM stage (P < 0.001), and high expression of PD-L1 (P = 0.033) were more common in patients with higher NPA. Survival analyses of patients receiving whole-exome sequencing demonstrated patients with larger NPA had significantly worse recurrence-free survival (P = 0.007) and overall survival (P < 0.001). Furthermore, high NPA was associated improved survival in the MSKCC cohort receiving immunotherapy (Figure 1B). Combination of NPA and tumor mutation burden provided better performance in identifying patients benefitting from immunotherapy in the POPLAR&OAK cohort (Figure 1C).
Conclusions: Increased NPA was associated with advanced TNM stage and poor survival in lung adenocarcinoma. NPA was a novel predictor of efficacy to immunotherapy.
View Submission
Invited Discussant
David Jablons, UCSF Medical Center - Contact Me San Francisco, CAUnited States
Abstract Presenter
Fangqiu Fu, Fudan Shanghai Cancer Center - Contact Me Shanghai, ShanghaiChina
105. Patient Derived Xenograft Engraftment of Lung Adenocarcinoma is Associated with Preoperative Radiological Findings
Objective: Patient derived xenografts (PDXs) are patient tumors engrafted into immunodeficient mice. PDXs are useful for preclinical drug efficacy studies as they preserve many molecular and histological features of patient tumors. However, the engraftment rates of lung adenocarcinoma range from 20-40%, and this low engraftment rate limits the utility of PDX as models of clinical cancer.
Strong associations between CT imaging of lung nodules such as solid, part-solid, and ground grass opacity (GGO) and patient prognosis has been reported for non-small cell lung cancer (NSCLC). We hypothesized that radiological findings may predict PDX engraftments.
Methods: Fresh tumor tissues from surgical resections were implanted and grown in the subcutaneous pocket of NOD SCID gamma (NSG) mice; subsequent passages were grown in NOD SCID mice. FDG-PET and CT images were reviewed. The pulmonary nodules were classified into three categories such as solid / part-solid / GGO nodules. The data on total tumor size, solid tumor size, consolidation-tumor ratio (CTR), and maximum standardized uptake value (SUV max) were obtained from patient clinical records. We evaluated whether these radiological findings correlated with the PDXs engraftment.
Results: A total of 254 resected primary lung adenocarcinomas were implanted into NSG mice between 2006 and 2012. Engraftment was successful in 58 cases (22.8%). Among them, stable engraftment, which could be passaged serially at least 3 times was observed in 43 cases (16.9%), and unstable engraftment, which could not be passaged ≥3 times was observed in 15 cases (5.9%). There were 190 (74.8%) solid, 62 (24.4%) part-solid, and 2 (0.8%) GGO nodules. Stable engraftment rates from solid, part-solid, and GGO nodules were 22.1% (42 /190 cases), 1.6% (1 /62 cases), and 0% (0 /2 cases), respectively (Figure A). Tumor size (total and solid tumor size), CTR and SUVmax were also strongly associated with the PDXs stable engraftment (Figure B-E).
Conclusions: Large solid lung adenocarcinomas with high CTR and high SUVmax were more strongly associated with stable PDX engraftment. It may be cost-effective to avoid part-solid and GGO nodules for establishing PDXs in lung adenocarcinoma cases due to the low engraftment rate.
Strong associations between CT imaging of lung nodules such as solid, part-solid, and ground grass opacity (GGO) and patient prognosis has been reported for non-small cell lung cancer (NSCLC). We hypothesized that radiological findings may predict PDX engraftments.
Methods: Fresh tumor tissues from surgical resections were implanted and grown in the subcutaneous pocket of NOD SCID gamma (NSG) mice; subsequent passages were grown in NOD SCID mice. FDG-PET and CT images were reviewed. The pulmonary nodules were classified into three categories such as solid / part-solid / GGO nodules. The data on total tumor size, solid tumor size, consolidation-tumor ratio (CTR), and maximum standardized uptake value (SUV max) were obtained from patient clinical records. We evaluated whether these radiological findings correlated with the PDXs engraftment.
Results: A total of 254 resected primary lung adenocarcinomas were implanted into NSG mice between 2006 and 2012. Engraftment was successful in 58 cases (22.8%). Among them, stable engraftment, which could be passaged serially at least 3 times was observed in 43 cases (16.9%), and unstable engraftment, which could not be passaged ≥3 times was observed in 15 cases (5.9%). There were 190 (74.8%) solid, 62 (24.4%) part-solid, and 2 (0.8%) GGO nodules. Stable engraftment rates from solid, part-solid, and GGO nodules were 22.1% (42 /190 cases), 1.6% (1 /62 cases), and 0% (0 /2 cases), respectively (Figure A). Tumor size (total and solid tumor size), CTR and SUVmax were also strongly associated with the PDXs stable engraftment (Figure B-E).
Conclusions: Large solid lung adenocarcinomas with high CTR and high SUVmax were more strongly associated with stable PDX engraftment. It may be cost-effective to avoid part-solid and GGO nodules for establishing PDXs in lung adenocarcinoma cases due to the low engraftment rate.
View Submission
Invited Discussant
*Mark Onaitis, University of California San Diego - Contact Me La Jolla, CAUnited States
Abstract Presenter
Hiroyuki Ogawa, Latner Thoracic Research Laboratories, University Health Network - Contact Me Toronto, ONCanada
Locally Advanced Lung Cancer: Selected vs Universal NGS
Total Time: 15 Minutes