Challenges in Predicting Recurrence After Resection of Node-Negative Non-Small Cell Lung Cancer

Thornblade, Lucas W.; Mulligan, Michael S.; Odem‐Davis, Katherine; Hwang, Billanna; Waworuntu, Rachel; Wolff, Erika M.; Kessler, Larry G.; Wood, Douglas E.; Farjah, Farhood

doi:10.1016/j.athoracsur.2018.06.022

Cited by 15 publications

(19 citation statements)

References 37 publications

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“…Among these clinical scenarios, primary pulmonary malignancy is a major concern, and tissue proof or resection is recommended if images change in the serial follow-up. In patients who underwent tumor resection and were confirmed with primary pulmonary malignancy, the risk of disease relapse was the major concern whereby the reported early relapse in patients with resectable non-small cell lung cancer is 10-19% [5,29]. Many prognostic factors have been identified but can only be used for surveillance planning [3][4][5], instead of relapse prediction [30].…”

Section: Discussionmentioning

confidence: 99%

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Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

Lee

et al. 2020

Diagnostics

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Background: The role of circulating tumor cells (CTCs) for predicting the recurrence of cancer in lung cancer patients after surgery remains unclear. Methods: A negatively selected protocol of CTC identification was applied. For all the enrolled patients, CTC testing was performed before and after surgery on the operation day (day 0), postoperative day 1, and day 3. The daily decline and trend of CTCs were analyzed to correlate with cancer relapse. The mixed model repeated measures (MMRM) adjusted by cancer characteristics was applied for statistical significance. Results: Fifty patients with lung mass undergoing surgery were enrolled. Among 41 primary lung cancers, 26 (63.4%) were pathological stage Tis and I. A total of 200 CTC tests were performed. MMRM analysis indicated that surgery could contribute to a CTC decline after surgery in all patients with statistical significance (p = 0.0005). The daily decrease of CTCs was statistically different between patients with and without recurrence (p = 0.0068). An early rebound of CTC counts on postoperative days 1 and 3 was associated with recurrence months later. Conclusion: CTC testing can potentially serve as a tool for minimal residual disease detection in early-staged lung cancer after curative surgery.

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Section: Discussionmentioning

confidence: 99%

“…CTCs were defined as cells that were negative for CD45 and positive for both EpCAM and Hoechst. We set the cutoff at 3.0 cells/mL as used in the literature to avoid false positives [29,30].…”

Section: Circulating Tumor Cell Sampling Identification and Qualitymentioning

confidence: 99%

Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

Lee

et al. 2020

Diagnostics

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“…Sandoval et al discovered a methylation signature based on 10 sites ( HOXA9, C1orf114, TRH, HIST1H4F, SP9, PCDHGB6, OTX2, NPBWR1, TRIM58 , and ALX1) that effectively distinguished stage I NSCLC patients with high recurrence risk and low risk 57 .Conventionally, molecular or epigenetic biomarkers are often identified by comparing the genomic or epigenomic landscapes of two groups with diverse outcomes. This identification method might be influenced by selection bias present in the groups due to the widespread interpatient and intra-patient heterogeneity 6 . Notably, our panel covers 7 of the 10 sites identified in Sandoval et al 2013 57 ( Table S3 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, although surveillance imaging is also recommended for all resected patients, the level of supportive evidences is low and adherence rates are limited 4 , 5 . Hence, stratifying patients according to the predicted recurrence risk may tailor adjuvant therapy and surveillance imaging to patients with a higher risk 6 . Tremendous efforts have been invested to identify clinical and molecular characteristics that might help predict recurrence risk in addition to TNM stage in resected lung cancers 7 - 11 .…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of a Methylome-based Malignancy Density Scoring System to predict recurrence risk in early-stage Lung Adenocarcinoma

et al. 2020

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Current NCCN guidelines do not recommend the use of adjuvant chemotherapy for stage IA lung adenocarcinoma patients with R0 surgery. However, 25% to 40% of patients with stage IA disease experience recurrence. Stratifying patients according to the recurrence risk may tailor adjuvant therapy and surveillance imaging for those with a higher risk. However, prognostic markers are often identified by comparing high-risk and low-risk cases which might introduce bias due to the widespread interpatient heterogeneity. Here, we developed a scoring system quantifying the degree of field cancerization in adjacent normal tissues and revealed its association with disease-free survival (DFS). Methods: We recruited a cohort of 44 patients with resected stage IA lung adenocarcinoma who did not receive adjuvant therapy. Both tumor and adjacent normal tissues were obtained from each patient and subjected to capture-based targeted genomic and epigenomic profiling. A novel methylome-based scoring system namely malignancy density ratio (MD ratio) was developed based on 39 patients by comparing tumor and corresponding adjacent normal tissues of each patient. A MD score was then obtained by Wald statistics. The correlations of MD ratio, MD score, and genomic features with clinical outcome were investigated. Results: Patients with a high-risk MD ratio showed a significantly shorter postsurgical DFS compared with those with a low-risk MD ratio (HR=4.47, P=0.01). The MD ratio was not associated with T stage (P=1), tumor cell fraction (P=0.748) nor inflammatory status (p=0.548). Patients with a high-risk MD score also demonstrated an inferior DFS (HR=4.69, P=0.039). In addition, multivariate analysis revealed EGFR 19 del (HR=5.39, P=0.012) and MD score (HR= 7.90, P=0.01) were independent prognostic markers. Conclusion: The novel methylome-based scoring system, developed by comparing the signatures between tumor and corresponding adjacent normal tissues of individual patients, largely minimizes the bias of interpatient heterogeneity and reveals a robust prognostic value in patients with resected lung adenocarcinoma.

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“…Risk stratification may facilitate a personalized approach to the use of adjuvant therapy [9]. Current evidence suggests that ACT can be considered as a treatment for those with high-risk stage IB disease [10,11].…”

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confidence: 99%

Adjuvant Chemotherapy Improves Survival in Surgically Resected Stage IB Squamous Lung Cancer

Wang

Zhang

et al. 2019

The Annals of Thoracic Surgery

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Background. At present there is a significant lack of clinical data for patients with surgically resected stage I squamous lung cancer. The purpose of this study was to investigate the impact of postoperative chemotherapy in this specific population.Methods. We retrospectively identified patients who had undergone complete squamous lung cancer resection at the Shanghai Chest Hospital between January 2008 and January 2014.Results. A total of 596 patients (236 stage IA, 360 stage IB) were included in this study. Results demonstrated that adjuvant chemotherapy (ACT) could provide longer overall survival for patients with p-stage IB disease (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.34-0.90; p [ 0.017). Among p-stage IB patients the ACTtreated cohort trended toward a benefit (HR, 0.69; 95% CI, 0.45-1.04) in recurrence-free survival but failed to reach statistical significance (p [ 0.076). After propensity score matching the HRs of recurrence-free survival and overall survival were 0.58 (95% CI, 0.35-0.96; p [ 0.033) and 0.49 (95% CI, 0.27-0.88; p [ 0.017), respectively. With regards to patients with p-stage IA disease, neither overall survival (HR, 0.87; 95% CI, 0.34-2.27; p [ 0.783) nor recurrence-free survival (HR, 0.79; 95% CI, 0.38-1.65; p [ 0.534) was significantly different when compared between patients receiving ACT and those who did not. Similar results were also achieved after propensity score matching.Conclusions. The data presented herein demonstrated that ACT might provide survival benefits for squamous lung cancer patients with p-stage IB disease.

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Challenges in Predicting Recurrence After Resection of Node-Negative Non-Small Cell Lung Cancer

Cited by 15 publications

References 37 publications

Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

The prognostic value of a Methylome-based Malignancy Density Scoring System to predict recurrence risk in early-stage Lung Adenocarcinoma

Adjuvant Chemotherapy Improves Survival in Surgically Resected Stage IB Squamous Lung Cancer

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