Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy

Pataer, Apar; Shao, Ruping; Correa, Arlene M.; Behrens, Carmen; Roth, Jack A.; Vaporciyan, Ara A.; Wistuba, Ignacio I.; Swisher, Stephen G.

doi:10.1002/cam4.1505

Cited by 25 publications

(23 citation statements)

References 35 publications

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“…[7][8][9][10] We also reported that combination of MPR with biomarker is a significant predictor of prognosis in patients with NSCLC who received neoadjuvant chemotherapy. 11 The purpose of this retrospective study was to confirm that MPR is predictive of long-term OS in patients with NSCLC treated with neoadjuvant chemotherapy and surgical resection. We also assessed interobserver agreement on MPR between 2 observers and determined the minimum number of slides needed to obtain an accurate determination of tumor response.…”

Section: Introductionmentioning

confidence: 96%

Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy

Weissferdt

Pataer

Vaporciyan

et al. 2020

Clinical Lung Cancer

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The assessment of MPR was reproducible between observers. We confirmed that MPR is associated with OS and can serve as an independent prognostic factor in NSCLC patients undergoing neoadjuvant chemotherapy. Our data suggest that at least 3 slides should be read to accurately determine tumor response. Our results clearly demonstrate that MPR is a significant predictor of OS. Introduction: We have suggested that major pathologic response (MPR) could serve as a surrogate endpoint for survival and provide rapid means of comparing different neoadjuvant treatment regimens. Here, we confirm that MPR is predictive of long-term overall survival (OS) in patients with nonesmall-cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy and surgical resection, to assess agreement on MPR between 2 observers, and to determine the minimum number of slides needed to obtain an accurate determination of MPR. Patients and Methods:We identified 151 patients with NSCLC who had been treated with neoadjuvant chemotherapy followed by complete surgical resection from 2008 to 2012. Tissue specimens were retrospectively evaluated by 2 pathologists who had been blinded to patients' treatment and outcome. We assessed the relationships between MPR and OS, the levels of agreement between the pathologists, and determined the number of slides needed to obtain an accurate determination of MPR. Results: Our results reveal that MPR examined by either observer 1 (experienced) or by observer 2 (trained) was significantly predictive of long-term OS after neoadjuvant chemotherapy. MPR was associated with longterm OS in patients with NSCLC undergoing neoadjuvant chemotherapy on multivariable analysis (hazard ratio 2.68; P ¼ .01). The levels of agreement between 2 pathologists were high after direct in-person training by one pathologist or the other (R 2 ¼ 0.994). Our data suggest that at least 3 slides should be read to accurately determine MPR. Conclusions: MPR is significantly predictive of long-term OS in neoadjuvant chemotherapyetreated patients with NSCLC. MPR may serve as a surrogate endpoint for evaluating novel chemotherapies and immunotherapy response in biomarker-driven translational clinical trials.

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Section: Introductionmentioning

confidence: 96%

Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy

Weissferdt

Pataer

Vaporciyan

et al. 2020

Clinical Lung Cancer

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“…The present study once again confirms that MPR predicts OS in patients with NSCLC receiving neoadjuvant chemotherapy by identifying a group of patients (PT-MPRþ/LN-MPRþ and PT-MPRþ/LN-MPRÀ) who experienced survival similar to that for patients with complete tumor responses. [13][14][15] These findings suggest that the use of PT-MPR, which was previously markedly correlated with OS in retrospective and prospective studies are applicable to all stages of NSCLC and various histologic tumor types. Furthermore, we found that LN-MPR status alone could predict outcome and that, by stratifying patients into three different groups on the basis of their combined PT-MPR and LN-MPR scores (PT-MPRþ/LN-MPRþ and PT-MPRþ/LN-MPRÀ versus PT-MPRÀ/LN-MPRþ versus PT-MPRÀ/LN-MPRÀ), statistically significant differences in outcome could be observed.…”

Section: Discussionmentioning

confidence: 58%

“…[5][6][7][8] We and others have previously reported that major pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, can be used as a surrogate end point for survival, thereby shortening the period needed to evaluate novel chemotherapies in clinical trials. [9][10][11][12][13][14][15][16] Currently, many lung cancer trials use MPR to predict drug efficacy after neoadjuvant treatment. In this context, evaluation of tumor viability is typically focused on the primary tumor and scoring of tumor in metastatic sites, such as lymph nodes, has not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Pathologic Response in Lymph Nodes of Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy

Pataer

Weissferdt

Vaporciyan

et al. 2021

Journal of Thoracic Oncology

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Introduction: Major pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome.Methods: A total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients' treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model.Results: LN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p ¼ 0.001).Conclusions: LN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population.

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“…Researches have investigated and indicated the correlation between complete pathological response and overall survival 9-12 . Other researches also have proved the validity of major pathological response as a surrogate of survival [13][14][15][16] . In this study, the complete response is different between IM and C group (37•5% vs. 7•69%).…”

Section: Clinical Analysismentioning

confidence: 99%

Neoadjuvant PD-1 Inhibitor combines with Chemotherapy in Resectable Squamous Cell Non-Small Cell Lung Cancer

Feng

Sun

Zhang

et al. 2020

Preprint

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Background Single agent of PD-1 or PD-L1 inhibitor has been explored recently for resectable patients before surgery. However, the effectiveness and safety of neoadjuvant PD-1 blockade combine with platinum-based doublet chemotherapy has not been fully investigated. Methods 21 patients with squamous cell lung cancer accepted neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were involved. 8 patients accepted two cycles of neoadjuvant platinum-based doublet chemotherapy combine with anti-PD-1 therapy, while 13 patients accepted two cycles of neoadjuvant platinum doublet chemotherapy. Besides baseline tumor staging, chest CT was repeated two to three weeks before surgery. Adverse events were monitored. Peripheral lymphocytes counting was tested during whole treatment. The residual viable tumor cells were counted after surgery to decide a major pathological response (MPR) rate. Selected specimen was sent for immunohistochemical, multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing. Results Comparing with neoadjuvant chemotherapy alone, combination with PD-1 blockade and chemotherapy increased the pathological complete response rate (37·5% Vs. 7·69%) and MPR rate (50% Vs. 38·46%). The pathological evaluation is not consistent with that of radiological evaluation. Although peripheral lymphocyte counting was influenced by neoadjuvant therapy, no unknown adverse effects were reported for all the patients. The tumor infiltrating lymphocytes were observed more in patients accepted PD-1 blockade, and seem infiltrated more in relative “non-responders”. No special pathological features associated with PD-1 blockade were found. Multiplexed immunofluorescence analyses revealed potential immune suppression status in the peritumoral spaces around the residual tumor cells. T-cell receptor DNA sequencing found although some amino acids were shared in primary tumor and lymph nodes in single patients, they are hardly shared among different patients. Conclusions Neoadjuvant chemotherapy combine with PD-1 blockade is safe and feasible for patients with potentially resectable squamous cell lung cancer, to improve the clinical and pathological outcome. Even with PD-1 blockade, the immune suppressive status around the residual tumor cells still exists. The squamous cell lung cancers, and corresponding immune responses are extremely highly individualized. The treatment needs to be designed accordingly. The combination strategy of traditional neoadjuvant chemotherapy with current anti-PD-1 inhibitor are still need further investigation.

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Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy

Cited by 25 publications

References 35 publications

Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy

Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy

Evaluation of Pathologic Response in Lymph Nodes of Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy

Neoadjuvant PD-1 Inhibitor combines with Chemotherapy in Resectable Squamous Cell Non-Small Cell Lung Cancer

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