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H. Nakayama
Moderator of
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 14
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.01 - Clinical and Pathological Variables Influencing Noninvasive Detection of Early Stage Lung Cancer Using Circulating Tumor DNA (ID 8686)
15:45 - 15:50 | Presenting Author(s): Jacob John Chabon | Author(s): A.A. Chaudhuri, T.D. Azad, D.M. Kurtz, H. Stehr, C.L. Liu, J. Schroers Martin, D. Merriott, J. Carter, K. Ayers, Aaron S. Mansfield, J. Jen, H. Ren, R.B. West, V.S. Nair, J.B. Shrager, Joel W. Neal, Heather A Wakelee, Billy Loo, A.A. Alizadeh, M. Diehn
- Abstract
Background:
Analysis of circulating tumor DNA (ctDNA) represents a potential strategy for the early detection of lung cancer. Despite significant interest, few studies have evaluated ctDNA levels in early stage lung cancer patients and the feasibility of ctDNA-based screening remains unclear.
Method:
We applied lung cancer-focused Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) to assess ctDNA levels in 55 localized lung cancer patients treated with curative intent (stage I: n=22, stage II: n=7, stage III: n=26) and 50 healthy controls. Histological subtypes included: adenocarcinoma (n=30), squamous cell carcinoma (n=19), NSCLC NOS (n=4), and small cell lung cancer (n=2). Sensitivity and specificity of ctDNA detection were evaluated in all patients and in a subset of NSCLC patients with node negative (N0) stage I-II disease. Additionally, for patients with stage I adenocarcinoma in whom ctDNA was not detectable using the standard population-based CAPP-Seq approach, we designed personalized CAPP-Seq assays covering a median of 320 mutations/patient based on tumor exome sequencing from the respective patients.
Result:
We detected ctDNA in the pre-treatment plasma of 43/55 (78%) patients at a median allele fraction (AF) of 0.48% (range: 0.004%-26.1%). ROC analysis revealed an area under curve of 0.91, with sensitivity and specificity of 78% and 98%, respectively. Among patients with non-adenocarcinoma histologies, 92% (23/25) had detectable ctDNA (median AF: 0.90%), compared to 67% of patients with adenocarcinoma (20/30; median AF: 0.23%; P=0.046). However, tumor volumes were significantly smaller in adenocarcinomas (P=0.01) and in multivariate analysis ctDNA detection was significantly associated with tumor volume (P=0.01) but not histological subtype (P=0.16). In N0 stage I-II NSCLC patients (n=22), ctDNA was detected in 64% of patients (7/14 adeno vs 7/8 non-adeno) with a specificity of 98% and median AF of 0.022% (median AF of 0.018% vs 0.030% in adeno vs non-adeno patients, respectively). Using personalized CAPP-Seq assays, we detected ctDNA in 3/4 patients with stage I adenocarcinoma in whom ctDNA was not detected using our standard lung-cancer focused CAPP-Seq assay. In these 3 patients, tumor volumes ranged from 11.6-14.7 mL and the ctDNA AF ranged from 0.0014%-0.003%. Taken together, we detected ctDNA in 17/22 (77%) N0 stage I-II tumors.
Conclusion:
These data suggest tumor volume is a stronger determinant of ctDNA levels than histology in localized lung cancers. Additionally, our findings suggest that the majority of localized lung cancers shed ctDNA and that ultra-sensitive assays will be required for early detection of lung cancer using ctDNA
Information from this presentation has been removed upon request of the author.
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MA 13.02 - Comprehensive Genetic Analysis Related to PD-L1 Expression in Early-stage Lung Squamous Cell Carcinoma (ID 9077)
15:50 - 15:55 | Presenting Author(s): Hui Yu | Author(s): Z. Chen, K. Ballman, M. Watson, Ramaswamy Govindan, D. Beer, Raphael Bueno, L. Chirieac, M.H. Chui, W.A. Franklin, David R. Gandara, C. Genova, M. Joshi, D.T. Merrick, W.G. Richards, C.J. Rivard, Frances A Shepherd, T. Sporn, Ming Sound Tsao, K. Brovsky, A.V. Bokhoven, David Harpole, Fred R. Hirsch
- Abstract
- Presentation
Background:
Recently, anti PD-1/PD-L1 immunotherapies have yielded promising outcomes in advanced squamous NSCLC. Several studies have suggested that tumor PD-L1 protein expression status might correlate with outcome and response to treatment. The aim of this study is to identify mRNA gene signatures and microRNAs associated with tumor PD-L1 expression in early-stage lung squamous cell carcinoma (SCC).
Method:
Early stage (I-II) SCC resected patient tumors were collected from 6 cancer centers as part of the SPECS II program. Gene expression profiling was performed on the specimens. PD-L1 protein expression was evaluated by immunohistochemistry on SCC FFPE tissue using the Dako 22C3 PD-L1 antibody. The tumor proportion score (TPS) for PD-L1 protein expression was compared with comprehensive clinicopathological, mRNA and miRNA data.
Result:
The prevalence of PD-L1 expression in this cohort of 255 Stage I-II SCC patients was 46.7% with a TPS cutoff of ≥ 1%, and 9.8% with a cutoff of ≥ 50%. Among 202 cases with available clinical and expression data, no significant association was observed between PD-L1 expression and clinical outcome. We identified a 12-gene signature from mRNA microarray using the Minimax Concave Penalty (MCP) regression method with an AUC of 0.92 at ≥ 5% TPS cutoff. A subset of 138 miRNAs was shown to be significantly differentially expressed between PD-L1 positive and PD-L1 negative groups at false discovery rate (FDR) of 0.05 with TPS cutoffs of ≥ 1%, ≥ 5% and ≥ 10%. No miRNAs were found to be significantly differentially expressed between the groups using a TPS cutoff of ≥ 50%. Gene Set Enrichment Analysis (GSEA) identified two pathways with gene sets that were significantly enriched (FDR < 0.05) in the PD-L1 negative group. No significant association was found between tumor mutation burden and PD-L1 expression level.
Conclusion:
PD-L1 expression prevalence is lower in early-stage lung SCC than in advanced NSCLC. No significant association was found between PD-L1 expression and prognosis in this cohort. Both mRNA gene signatures and miRNAs were identified to be predictive of PD-L1 expression. Through GSEA, two distinct gene sets were identified with expression correlated to PD-L1, one comprising genes related to ovary and another related to collagens and extracellular matrix (ECM). No significant association was found between tumor mutation burden and PD-L1 expression level. Following validation, these predictive signatures could be used to select patients with positive PD-L1 expression who may benefit from immunotherapy.
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MA 13.03 - Quantitative Spatial Profiling of PD-1/PD-L1 Interaction Predicts Response to Adjuvant Chemotherapy Non–Small-Cell Lung Cancer (ID 8419)
15:55 - 16:00 | Presenting Author(s): Vamsidhar Velcheti | Author(s): J. Bordeaux, N. Dakappagari, N. Pennell, J.P. Stevenson, M. Khunger, J.Y. Kim, K.A. Schalper, David Rimm
- Abstract
- Presentation
Background:
Adjuvant chemotherapy (ACT) for ES-NSCLC has a modest improvement in survival but it is often associated with serious adverse effects. Thus, identifying subgroups of ES-NSCLC patients who may benefit from ACT is of high clinical relevance. We evaluated the prognostic and predictive role of quantitative spatial profiling of PD-1/PD-L1 interaction in the tumor cells of ES-NSCLC patients.
Method:
451 whole tissue sections of formalin-fixed, paraffin embedded surgical resection specimens from ES-NSCLC patients with/without ACT were tested with a multiplexed fluorescence immunohistochemistry assay to detect PD-1, PD-L1, cytokeratin and DAPI labeling. Fluorescence Images were acquired on the Perkin Elmer Vectra platform and analyzed with AQUA® algorithms to determine the percent positivity of each biomarker as well as the co-localization of PD-1 and PD-L1 (the Interaction Score).
Result:
High PD-1/PD-L1 Interaction Scores correlated with improved progression-free and overall survival for ES-NSCLC patients receiving ACT after surgery (p = 0.01) whereas no difference in survival was observed for patients who received surgery alone (p = 0.9) (Figure 1). Interestingly, the levels of PD-1 or PD-L1 alone did not demonstrate any difference in survival for surgery + ACT or surgery alone patient populations. Figure 1
Conclusion:
PD-1/PD-L1 Interaction Score is predictive of benefit from ACT in patients with ES-NSCLC. Future studies will determine if this tool can be used to select patients that may be spared chemotherapy without compromising outcome.
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MA 13.04 - Adjuvant Systemic Therapy in Patients with Early-Stage Non-Small Cell Lung Cancer (NSCLC) Treated with Stereotactic Body Radiation Therapy (ID 10216)
16:00 - 16:05 | Presenting Author(s): Vinicius Ernani | Author(s): A.K. Appiah, A. Marr, L.M. Smith, Apar Kishor Ganti
- Abstract
- Presentation
Background:
Stereotactic body radiation therapy (SBRT) is currently the standard of care for inoperable patients with early stage non-small cell lung cancer (NSCLC). Despite this, ≈20% will relapse at 2 years. While adjuvant chemotherapy is recommended for surgically resected patients with early stage NSCLC (IB-IIIA), data on the role of adjuvant systemic therapy following SBRT for early stage NSCLC are sparse. The goal of this study was to evaluate the role of adjuvant chemotherapy following SBRT in early-stage, inoperable NSCLC.
Method:
Adults diagnosed with early-stage (clinical stage I and II) between the years of 2004 and 2013 were identified from the National Cancer Database (NCDB). Variables abstracted included: age, gender, clinical stage, race, comorbidity, insurance status, treating facility, treatment received and survival. Chi-square tests were used to compare clinical characteristics by therapy type. Kaplan-Meier, Cox regression, and propensity score analyses were employed for survival analyses.
Result:
Data from 12,414 patients with early-stage NSCLC were analyzed. Of these, 75.6% and 25.4% had clinical stage I and II disease, respectively. A total of 9,164 (73.6%) patients received SBRT alone and 3,268 (26.4%) had SBRT followed by chemotherapy. Among patients with clinical stage I, 83.5% received SBRT alone and 16.5% received SBRT followed by chemotherapy. Among those with clinical stage II, 43% received SBRT alone while 57% received SBRT followed by systemic therapy. On multivariate analysis, increasing age, male gender and stage II disease were associated with worse overall survival (OS). There was evidence of a clinical stage by treatment interaction (p <0.001). When treatment effect was analyzed by stage after adjusting for age and gender, patients with stage I treated with SBRT alone had a better median OS, 26.2 months compared to 22.4 months in the combined arm (HR=0.78; p<0.001; CI: 0.73-0.83). In contrast, among patients with stage II NSCLC, median OS was 15 months in the SBRT compared to 20.2 months in the combined group (HR=1.3; p<0.001; CI: 1.22-1.44).
Conclusion:
SBRT should be the sole modality treatment for patients with inoperable stage I NSCLC. However, patients with stage II disease appear to benefit from adjuvant chemotherapy. Randomized trials are needed in this area to answer this question conclusively.
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MA 13.05 - Discussant - MA 13.01, MA 13.02, MA 13.03, MA 13.04 (ID 10784)
16:05 - 16:20 | Presenting Author(s): Shinichi Toyooka
- Abstract
- Presentation
Abstract not provided
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MA 13.06 - New Risk Factors for Overall Survival After SBRT in Early Stage NSCLC: A Role of RT Plan Optimization (ID 10428)
16:20 - 16:25 | Presenting Author(s): Feng-Ming (Spring) Kong | Author(s): Y. Liu, H. Zhang, H. Yao, A. Cerra-Franco, K. Shiue, D. Vile, W. Wang, M. Langer, G. Watson, G. Bartlett, K. Diab, T. Birdas, T. Lautenschlaeger, J. Jin
- Abstract
- Presentation
Background:
Stereotactic body radiation therapy (SBRT) provides over 90% local tumor control, is a treatment of choice in patients with early stage medically inoperable non-small cell lung cancer (NSCLC). However, long-term overall survival after SBRT remain suboptimal, with 5-year rates rendering less than 50%, which cannot be fully explained by comorbidity, distant tumor progression or commonly known toxicities. We hypothesize that doses of radiation to normal lung and heart contribute to poor survival in these patients.
Method:
Patients with T1-T2 NSCLC received more than 100 Gy BED and with retrievable RT plan were eligible. The primary endpoint was overall survival, calculated from the start of SBRT. Clinical factors included age, gender, race, tobacco history, respiratory and cardiovascular comorbidity, tumor lobar location, histology, T stage, gross tumor volume (GTV), planning target volume (PTV), and prescription dose. Heart and lung were contoured consistently by one radiation oncologist according to the RTOG atlas. Dosimetric factors of the total lung were computed with biocorrection of fractionation effect.
Result:
A total of 280 patients with T1-3N0 met criteria. The median follow-up were 47 months. The median survival time was 33 months (95% CI: 25-42 months). The 2-year, 3-year and 5-year survival rates were 63%, 53% and 45%, respectively. Univariate analysis demonstrated that age (HR=1.02, p=0.04), gender (HR=0.75 for female, p=0.07), tumor T stage (HR=1.3 for T2, 2.5 for T3, using T1 as the reference, p=0.10), GTV (HR=1.01, p<0.001), PTV (HR=1.01, p<0.001), mean lung dose (HR=1.2, p<0.001), V5 (HR=1.02, p=0.03), V10 (HR=1.03, p=0.01), V20 (HR=1.1, p<0.001) of total lung and mean heart dose (HR=1.001, p=0.029) were associated with survival probability. The median mean lung and heart doses were 4.1Gy (range 0.8-11.2) and 0.99 Gy (range 0.3-9.7), respectively. Presence of radiation pneumonitis was not significant (p>0.1). Multivariate analysis was not performed as the dosimetric factors were correlated with each other. Among the risk factors, lung dosimetric factors were most significant. Increase in dose or volume of lung was significantly associated with poorer overall survival. A 1 Gy increase in mean lung dose corresponded to a 12 % increase in the risk of death, or 5% reduction in 5-year survival.
Conclusion:
This study demonstrated at the first time that doses to lung and heart are significant for overall survival after SBRT, while radiation pneumonitis was not. This suggests that the suboptimal survival after SBRT may be improved with plan optimization. This data also challenges the current practice of toxicity based normal tissue dose tolerance policy.
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MA 13.08 - Long Term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a Randomized Phase II Study of 2 SBRT Schedules for Lung Cancer (ID 7390)
16:25 - 16:30 | Presenting Author(s): Gregory M.M. Videtic | Author(s): R. Paulus, A. Singh, Joe Y Chang, W. Parker, K. Olivier, R.D. Timmerman, Ritsuko Komaki, J. Urbanic, K. Stephans, Sue S Yom, C. Robinson, C.P. Belani, P. Iyengar, M. Ajlouni, D. Gopaul, S. Lele, R. McGarry, Hak Choy, Jeffrey Bradley
- Abstract
- Presentation
Background:
NRG Oncology RTOG 0915/NCCTG N0927 was a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction (arm 1) versus 48 Gy in 4 fractions (arm 2) designed to select the better of the 2 regimens by comparing them at 1 year (yr): first by rates of pre-specified protocol-specified adverse events (psAEs), then by primary tumor control for each arm. 34 Gy emerged as the least toxic yet equally efficacious regimen. Herein, we update those results with long-term follow-up.
Method:
This phase II North American multicenter study of patients aged 18 yrs or older with medically inoperable non-small cell lung cancer with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors was designed to detect 1-yr psAEs rates >17% as primary endpoint. Primary tumor failure (PTF) (either infield or marginal failure) and local failure (either infield, marginal, or involved lobe failure) [with death without failure considered as a competing event]; overall survival (OS); disease-free survival (DFS) and progression-free survival (PFS) were secondary endpoints, but the study was not designed for statistical comparisons of these outcomes. The study opened in September 2009 and closed in March 2011. Updated data were analyzed through November 14, 2016.
Result:
Ninety four patients were accrued, with 86 eligible for analysis: 41 in arm 1 and 45 in arm 2, after 8 cases were excluded. Median follow-up time was 3.8 yrs for all patients, and 5.1 yrs for those alive at analysis. The grade 3 and higher treatment-related toxicity profile was unchanged since previous report, with specifically no new high grade chest wall or grade 5 events. Four of 48 Gy patients had subsequent grade 3 changes in spirometry since meeting the primary endpoint. Medians (in yrs) for 34 Gy and 48 Gy were: 4.1 vs. 4.0 for OS, and 2.6 vs. 2.8 for DFS, respectively. Five-yr outcomes as % (95% CI) for 34 Gy and 48 Gy were: PTF rate of 7.9 (2.0, 19.5) vs. 6.8 (1.7, 16.9); OS of 28.8 (15.4, 43.8) vs. 40.2 (24.9, 55.0); PFS of 19.1 (8.5, 33.0) vs. 31.8 (18.6, 45.9); and second primary rate of 15.5 (6.1, 28.9) vs. 13.3 (5.3, 25.1), respectively. Distant failure as the sole failure or a component of first failure was numerically higher in the 34 Gy arm (7 (46.7%)), but in the 48 Gy arm, rate of second primary development was higher (7 (43.8%)). Approximately 1/3 of patients’ causes of death was unknown, and another 1/3 was related to causes other than cancer or treatment.
Conclusion:
No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 yrs were similar by arm. Median survival times of 4 yrs for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.
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MA 13.09 - Toxicity and Second Primary Lung Cancers in Late Survivors Following Lung SBRT (ID 8410)
16:30 - 16:35 | Presenting Author(s): Meredith Elana Giuliani | Author(s): A.J. Hope, M. Guckenberger, F. Mantel, J. Sonke, H. Peulen, J. Belderbos, M. Werner-Wasik, H. Ye, I. Grills
- Abstract
- Presentation
Background:
There is a paucity of data on the long-term outcomes following lung SBRT. This impacts our understanding of late toxicity, relapse patterns and rates of second lung cancers. We report our multi-institutional outcomes of those who survived ≥5 years from lung SBRT treatment.
Method:
1192 patients were treated for primary non-small cell lung cancer, T1/2N0 from 5 international institutions. For those who survived ≥5 years from lung SBRT treatment details of patient factors, treatment and outcome factors were extracted from the multi-institutional database. All events were calculated from the end of radiotherapy. Local (LR), regional (RR), and distant metastases (DM) and toxicity events after 5 years are reported. New cases of metachronous lung cancers after 5 years are reported. Univariable analyses was performed to determine factors associated with survival ≥5 years.
Result:
Of 1192 patients there were 182 (14%) ≥5 year survivors. Only 52 (8%) survived ≥ 7 years and 2 (0.2%) ≥10 years. Those surviving ≥5 years were younger (74.3 vs 71.5 years; p<0.01) and had better FEV1 (55% vs 65%; p<0.01) than those that did not survive 5 years. The Charleston Comorbidity Score was 1.4 (0-12) vs 2.1 (0-7) (p<0.001) in those who survived < vs ≥5 years. Those who survived <5 years had a trend to larger tumors (2.4cm vs 2.3 cm; p=0.07). Of the 182 patients 23 (13%) were operable, 67 (37%) were <70 years old at treatment, 115 (63%) were ECOG 0-1 and 156 (86%) had peripheral tumor location at time of initial diagnosis. 84 (46.2%) were T1a, 60 (33%) T1b, 33 (18.1%) T2a and 5 (2.7%) T2b. After 5 years there were 13 new events of grade ≥ 2 toxicity. These toxicities were 4 grade 2 fatigue, 1 grade 2 rib fracture, 7 grade 2 chronic myositis and 1 patient with grade 2 chronic myositis and fatigue. In this 182 patient cohort, after 5 years, there were 3 local recurrences, 2 regional failures and 5 distant failures. After 5 years follow-up there were 22 (12%) new primary lung tumors in the 182 patients (and 20 had a subsequent lung SBRT treatment).
Conclusion:
Late survivors after SBRT require dedicated follow-up as they remain at risk for second lung cancer, tumor recurrence and toxicity. Second cancers in these late survivors can be considered for SBRT treatments.
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MA 13.10 - Discussant - MA 13.06, MA 13.08, MA 13.09 (ID 10785)
16:35 - 16:50 | Presenting Author(s): Hong-Gyun Wu
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
The regularity of intrapulmonary lobar and segmental lymph node (LSN) metastasis in cT1N0M0 stage lung adenocarcinoma remains unclear. Thus, segmentectomy with uncertain LSNs metastatic status remains a potential oncological risk. We aimed to facilitate more accurate determination of N staging and identification of more suitable cases for segmentectomy.
Method:
A prospective study was performed from March 2014 to March 2016. A total of 156 patients diagnosed with cT1N0M0 stage lung adenocarcinoma received lobectomy and mediastinal lymph node dissection. The intrapulmonary LSNs were dissected and classified as adjacent LSNs or isolated LSNs. The metastatic status of the LSNs together with the TNM stage were analyzed. A comparison of the metastatic probability of isolated LSNs was carried out considering imaging features, serum carcinoembryonic (CEA) levels, pathological subtypes, size of the lesions, and metastatic status of adjacent LSNs.
Result:
Among the 156 cases enrolled, 129 were confirmed as pN0, 21 as pN1, 5 as pN1+N2, and 1 as skip pN2. When the LSNs had not been dissected, the false negative rate for N staging was 5.1% (7/136). Patients with a pure ground-glass-nodule had a lower isolated LSN metastasis rate (p = 0.027). Non-lepidic predominant invasive adenocarcinoma (p = 0.003), the cT1c group (p = 0.020), and those with adjacent LSN metastasis (p < 0.001) were detected with a higher isolated LSN metastasis rate. No significant difference in isolated LSN metastasis rate was found between groups with different serum CEA levels (p = 0.121).
Conclusion:
Dissection of intrapulmonary LSNs reduces the false negative rate of lymph node metastasis. Partial solid or solid lung adenocarcinoma, non-lepidic predominant invasive adenocarcinoma, and cT1c lung adenocarcinoma might not be suitable for segmentectomy. The lymph node sampling area during segmentectomy should include adjacent LSNs of the target segment. When metastasis to the adjacent LSNs is confirmed by fast frozen pathology, segmentectomy would not be suitable.
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MA 13.12 - Wedge Resection and Segmentectomy Are Associated with Comparable Outcomes for Patients with Less Than 2cm Non-Small Cell Lung Cancer (ID 10162)
16:55 - 17:00 | Presenting Author(s): Kamran Ali | Author(s): S. Cho, K. Kim, S. Jheon
- Abstract
- Presentation
Background:
Sublobar resection is widespread for selected patients with small sized non-small cell lung cancer (NSCLC). Segmentectomy has been considered superior to wedge resection, however well-balanced comparative studies are lacking. We compared oncologic outcomes between wedge resection and segmentectomy for patients with less than 2cm of NSCLC according to parenchymal safety margin
Method:
A retrospective review of a prospective database was performed (2003-2015), excluding patients with poor lung function (FEV~1~ or DLCO <50%), neoadjuvant therapy, previous lobar resection for primary lung cancer, and multiple primary other cancer. Demographic, clinical, and pathological data were reviewed. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Lymph nodes (LN) were evaluated preoperatively by PET/CT and EBUS-FNA if chest CT showed more than 1cm of LN short diameter
Result:
Two hundred nighty-six patients met our selection criteria, including wedge resection (W) in 188 and segmentectomy (S) in 108. There was no difference in smoking history, comorbidity, pulmonary reserve, cell type, and postoperative complication rate. All enrolled patients had clinically negative LN and 3 patients (1 in W, 2 in S) had pathologically node positive LN. The segmentectomy had more likely to have larger tumor (1.26 vs 1.36, p=0.045), more total nodes resected (1 vs 6, p<0.001), more distance of safety margin (median 0.5 vs 1.5, p<0.001). There was no statistical difference in OS (p=0.897), CSS (p=0.844), and RFS (p=0.763) between two groups. Patients were stratified by safety margin into ≤ 5mm in 118 (w101 vs s17), 5~10mm in 65 (w48 vs s17), 11~15mm in 45 (w23 vs s22), 16~20mm in 23 (w9 vs s14), and >20mm in 45 (w7 vs s38). Recurrence was developed in 8 (7%, w5 vs s3), 2 (3%, w2 vs s0), 1 (2%, s1), 0 (0%), 1 (2%, s1) of each safety margin. There was no significant difference of RFS between wedge resection and segmentectomy in each safety margin
Conclusion:
Wedge resection and segmentectomy showed comparable oncologic outcomes for carefully staged less than 2cm NSCLC patients. After thorough preoperative LN evaluation, wedge resection of sufficient safety margin is good surgical option
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MA 13.13 - Spread through Air Spaces Is a Prognostic Factor in Wedge Resection of Non-Small Cell Lung Cancer (ID 8439)
17:00 - 17:05 | Presenting Author(s): Satoshi Shiono | Author(s): N. Yanagawa, Katsuyuki Suzuki, K. Yarimizu, K. Hayasaka, M. Endo
- Abstract
- Presentation
Background:
Spread through air spaces (STAS), defined as “micropapillary clusters, solid nests, or single cells beyond the edge of the tumor into air spaces in the surrounding lung parenchyma” (Travis WD, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, 2015), has been recognized as a pattern of tumor invasiveness. Because complete lymph node dissection and sufficient surgical margin lengths are difficult to obtain, wedge resection is associated with worse surgical outcomes than those of lobectomy. Because of the insufficient margin length associated with wedge resection, we speculated that STAS has a prognostic impact in wedge resection cases compared with segmentectomy cases. The aim of this study was to clarify the prognostic impact of STAS in patients with non-small cell lung cancer (NSCLC) who underwent wedge resection.
Method:
This was a retrospective study using our prospectively collected institutional database, established in May 2004. From May 2004 to May 2017, 1071 patients with NSCLC underwent complete resection. After excluding patients with pure ground glass opacity or multiple lung cancers and those who underwent lobectomy or preoperative therapy, we evaluated 196 patients with clinical stage IA cancer who underwent segmentectomy or wedge resection. TNM staging was performed according to the seventh edition. We assessed the prognostic impact of STAS on stage IA lung cancer cases who underwent wedge resection compared with segmentectomy.
Result:
Segmentectomy was performed in 110 patients and wedge resection in 86. The wedge resection cases were older (p<0.001) and had a higher CEA level (p=0.023). The frequencies of STAS were 14.5% and 18.6% in the segmentectomy and wedge resection cases, respectively (p=0.447). STAS was a significant prognostic factor for overall survival in the wedge resection cases on univariate (p=0.003) and multivariate (p=0.013) analyses, but it was not significant in the segmentectomy cases (p=0.597). STAS was a significant prognostic factor for disease-free survival in the wedge resection cases on univariate (p<0.001) and multivariate (p<0.001) analyses, but this was not the case in the segmentectomy cases (p=0.108). STAS was a significant prognostic factor for the recurrence-free rate in the wedge resection cases on univariate (p<0.001) and multivariate (p<0.001) analyses, but it was not significant in the segmentectomy cases (p=0.205).
Conclusion:
STAS is a prognosticator of poor survival outcomes in NSCLC patients who underwent wedge resection, but not in those who underwent segmentectomy. We speculate that NSCLC with STAS tends to have invasive characteristics, and wedge resection is not sufficient to improve survival outcomes in such patients.
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MA 13.14 - Surgical Outcomes and Survival Analysis Following Second Pulmonary Resection for Non-Small Cell Lung Cancer (ID 9374)
17:05 - 17:10 | Presenting Author(s): Yusuke Takahashi | Author(s): J. Isbell, Takashi Eguchi, R. Vaghjiani, Kay See Tan, D. Jones, Prasad S. Adusumilli
- Abstract
- Presentation
Background:
The early detection and improved survival of resected non-small cell lung cancer (NSCLC) may increase the number of patients who eventually undergo subsequent pulmonary resection. We investigated the surgical outcomes and survival of patients following second and third pulmonary resections for NSCLC.
Method:
Patients who underwent second or third pulmonary resections without induction therapy for synchronous or metachronous NSCLC (511 patients, 535 procedures, 2000-2014) were included in the analysis.
Result:
Among 535 operations, 361 (67%) were sublobar resection and 103 (19%) were performed by minimally invasive approach, with the proportion of minimally-invasive procedures increasing in recent years (Fig. 1). The majority of re-resections were performed within 4 years of the previous resection (Fig. 2). Risk regression analysis demonstrated that predicted postoperative (ppo) FEV1 (p<0.001) and same side operation (p=0.002) were independent risk factors for severe complications (CTCAE grade ≧ 3; N=45). Multivariable Cox regression analysis revealed that age at subsequent surgery, male sex, ppoDLCO, interval from prior surgery, and tumor stage were independently associated with overall survival.
Conclusion:
In this large cohort of pulmonary re-resections for NSCLC, predicted postoperative pulmonary function tests were indictive of major complications and overall survival. Figure 1 Figure 2
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MA 13.15 - Discussant - MA 13.11, MA 13.12, MA 13.13, MA 13.14 (ID 10786)
17:10 - 17:25 | Presenting Author(s): Taichiro Goto
- Abstract
- Presentation
Abstract not provided
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P1.05 - Early Stage NSCLC (ID 691)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.05-011 - Comparison of Tumor Measurement Methods in Patients with Clinical Stage IA Non-Small Cell Lung Cancer (ID 10018)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
The consolidation size of tumor in early lung cancer is related to prognosis. However, the tumor area and volume can show the amount of tumor more precisely. The purpose of this study was to compare the prognostic impact of the tumor size, the area, and the volume in whole tumor and consolidation of it.
Method:
We retrospectively reviewed the clinicopathological characteristics of 160 patients with clinical stage IA NSCLC who received curative pulmonary lobectomy and mediastinal lymph node dissection between January 2008 and June 2011. We measured the size, the area and the volume in whole tumor and consolidation part respectively by using the volume analyzer SYNAPSE VINCENT by Fujifilm. We evaluated the relationships between these measurement methods and pathological upstage, tumor recurrence with receiver operating characteristics curve.
Result:
The median duration of follow up was 64.9 months. Thirty four percent of patients (n=55) were pathologically upstaged. Twenty three patients developed recurrence (14%). The mean whole tumor size, the area and the volume were 21 mm, 264 mm[2], 3741 mm[3], respectively. The mean consolidation tumor size, the area and the volume were 17 mm, 156 mm[2], 1861 mm[3], respectively. The receiver operating area under the curve for the consolidation tumor size, the area, and the volume used to predicting pathological upstage were 0.686, 0.692 and 0.687 respectively, and they all had significant correlations. The receiver operating area under the curve for the consolidation tumor size, the area, and the volume used to predicting tumor recurrence were 0.626, 0.649 and 0.623 respectively. The tumor area had significant correlation and the others had marginally significant correlations. On the other hand, there was no significant correlation between the whole tumor measurements and either pathological upstage or tumor recurrence.
Conclusion:
Each measurement method in consolidation of the tumor can be useful for predicting prognosis.
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P1.05-018 - Prognostic Impact of Tumor Shadow Disappearance Rate in Patients with Clinical IA Lung Adenocarcinoma (ID 8092)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
The aim of this study was to clarify whether tumor shadow disappearance rate (TDR) or consolidation to tumor diameter ratio (CTR) predict outcomes in patients with clinical stage IA lung adenocarcinoma.
Method:
We reviewed 250 patients with completely resected clinical stage IA lung adenocarcinoma between 2007 and 2014 and examined the prognostic impact of TDR and CTR. We classified all tumors into each two groups based on the TDR and CTR on high-resolution computed tomography: TDR >50% (Group A, n=77), TDR ≤50% (Group B, n=173), CTR <0.5 (Group C, n=33), and CTR ≥0.5 (Group D, n=217). TDR and CTR were calculated using the following formulas: TDR = 100 – (tumor size on mediastinal window/tumor size on lung window) ´ 100 and CTR = maximum diameter of consolidation/maximum tumor diameter.
Result:
The study group comprised 117 men (47%) and 133 women (53%), with a median age of 66 years (range, 36-83 years). The median follow-up was 50 months (range, 1 to 110 months). The disease-free survival rate at 5 years was 100%, 78.2%, 100%, and 82.5% in Groups A, B, C, and D, respectively. The lung cancer-specific survival rate at 5 years was 100%, 94.8%, 100%, and 95.9% in Groups A, B, C, and D, respectively. Multivariate analysis showed that the following factors were significant predictors of recurrence: lymph-node metastasis, lymphatic vessel invasion, blood vessel invasion, and TDR (TDR: hazard ratio=3.61, 95% confidence interval: 1.01-12.8, p=0.048). On the other hand, multivariate analysis revealed that lymph-node metastasis and TDR were significant predictors of lung cancer-specific mortality (TDR: hazard ratio=23.85, 95% confidence interval: 1.22-466.5, p=0.037).
Conclusion:
TDR is a significant predictor of not only recurrence but also lung cancer-specific mortality in patients with clinical stage IA lung adenocarcinoma.
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P1.05-021 - Are Prognostic Factors Different from That Which Predicts Recurrence in Completely Resected Pathological Stage IB Adenocarcinoma? (ID 9747)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
The 5-year survival rate of pathologic stage IB stage lung adenocarcinoma is reported to be 73%, and adjuvant chemotherapy is expected to improve prognosis about 10%. In Japan, UFT is the standard regimen as adjuvant chemotherapy for completely resected pathological stage IB. In addition to conventional clinicopathological factors, adenocarcinoma tissue subtype, EGFR mutation status and maxSUV of primary tumor like have also been found to have a large Impact as a recurrence / prognostic predictor. The purpose of this study is to investigate the factors which affect recurrence and prognosis in stage IB lung adenocarcinoma．
Method:
From 2008 to 2015 lung, completely resected 218 cases that undergo lobectomy with mediastinal lymph node dissection and diagnosed as pathological stage IB (7th UICC) . We examined the relationship between clinical pathologic factors including postoperative adjuvant therapy and, recurrence and prognosis.
Result:
Median follow-up period was 45.4 months. There were 122 male and 96 female. Mean age was 69.4 years old, BMI 22.2, smoking 122 cases (56.0%). CEA elevation was noted in 63 cases (28.9%). Median value of max SUV was 2.96. Median operative time was 166 minutes and blood loss was 45.7 g. Histological adenocarcinoma subtypes were followed; MIA 6, Lepidic 62, Acinar 79, Papillary 27, Solid 40 and Micopapillary 4. Lymph vessel invasion was noted in 35 (16.0%) and vascular vessel invasion was in 72 (33.0%) and pleural invasion was in102(46.8%), EGFR mutation was noted in 62 among 150 examined cases (41.3%)． Mean tumor diameter was 3.33 cm, collapse-fibrosis size was 2.18 cm. Adjuvant chemotherapy was performed in 90 cases (41.3%). The relapse-free survival rate (RFS) at 5-year was 77.1%, the factors influencing RFS were lymph vessel invasion, vascular vessel invasion, pleural invasion, histological adenocarcinoma subtypes, blood loss and maxSUV. In multivariate analysis, RFS was significantly affected by pleural invasion (HR=3.141 (95% CI 1.122 - 8.798)), blood loss (HR = 1.004 (1.000 - 1.007)) and maxSUV (HR = 1.083 (1.004 - 1.169)). However, the presence or absence of EGFR mutation did not contribute to relapse (p = 0.208). The overall survival rate (OS) at 5-year was 88.3%, the histological subtype and BMI statistically affected OS. In multivariate analysis, only histological subtype (lepidic vs. non-lepidic) (HR = 4.710 (95% CI = 1.097-20.218) was left, it was an independent prognostic factor. After matching the distribution of histological subtype to examine the effect of adjuvant chemotherapy, but no significant difference was observed. On the other hand, when focusing on prognosis based on the presence or absence of EGRF mutation in recurred cases (35 cases), the 5-year OS was 58.8% in wild type and 90.0% in mutant; it was not statistically significant difference (p = 0.165), but the mutant case seemed to have a high probability of long-term survival after relapse.
Conclusion:
Factors that contribute to recurrence were pathological malignancy (vascular invasion, histological subtype) and biological malignancy (high value of maxSUV). On the other hand, only histological subtypes contributed to prognosis. In addition, lepidic predominant was almost free from relapse and survived. Even if lepidic subtype was excluded, the effect of adjuvant UFT administration was not observed. Cytotoxic agent or EGFR-TKI should be examined in the future. On the other hand, the presence or absence of EGFR mutation seems to be an important OS predictor after recurrence.
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P1.13 - Radiology/Staging/Screening (ID 699)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.13-011a - Stratification Based on PET/CT Findings for Malignant Grade of Radiologically Pure Solid Small-Sized (≪ 2cm) Lung Cancer (ID 9372)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
Radiologically pure solid tumors are heterogeneity because of including various histological type, however, small-sized tumors are difficult to be preoperatively diagnosed histology. The aim of this study was to identify preoperative predictors for pathological malignant of pure solid lung cancer in clinical early stage.
Method:
The data from a multi-center database of 220 patients who underwent anatomical resection for radiologically pure solid, tumor size 2 cm or less, and clinical N0 lung cancer were retrospectively analysed. Factors affecting survival were assessed using Cox regression analysis. Predictors were found by drawing the receiver operating characteristic curves (ROC) and evaluated the possible cutoff value for independent prognostic factor.
Result:
Pure solid tumors included 164 (74%) adenocarcinoma, 33 (15%) squamous cell carcinoma, 16 (7%) neuroendocrine tumor, 5 (2%) pleomorphic carcinoma, and 3 (1%) adenosquamous cell carcinoma. In multivariate analyses, high malignant grade histology such as micropapillary and solid predominant adenocarcinoma, adenosquamous cell carcinoma, neuroendocrine tumor, or pleomorphic carcinoma and pathological lymph node metastasis were an independent prognostic factors for recurrence-free survival. The ROC showed that 3.55 in maximum standardized uptake value (SUV max) was cut-off value for detecting high malignant grade histology or lymph node metastasis (area under the curve, 0.71; 95% confidence interval, 0.63 – 0.78). Tumors with SUV max ≥ 3.55 had significantly more high-grade histology, the presence of lymphatic and vascular invasion, and lymph node metastasis and poorer recurrence-free survival rate than SUV max < 3.55 (Figure). Figure 1
Conclusion:
The prognosis of radiologically pure solid tumor with small size and clinical N0 lung cancer was stratified according to SUV max. SUV max could evaluate pathological malignant grade and help the decision of appropriate surgical procedure.
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P2.17 - Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies (ID 718)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.17-003 - Is Complete Resection Mandatory for Mediastinal Germ Cell Tumor Which Shows Severe Adhesion to Greater Vessels? (ID 9748)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
Surgical resection for mediastinal germ cell tumors is one of important modality to cure. But it sometimes shows severe adhesion to greater vessels, complete resection without vessel replacement is difficult. But, no viable cells are found in the resected specimen in many cases. Is vessel replacement really needed for this situation? The aim of this study is to confirm whether complete resection is really needed for mediastinal germ cell tumor.
Method:
The data of 13 patients with resected mediastinal germ cell tumor were retrospectively analyzed for recurrence.
Result:
Median follow up period was 72.2 months. All cases were male. Mean age was 33.1 years old. Pathological diagnosis was mature teratoma in 5 cases, seminoma in 5 and non-seminomatous malignant germ cell tumor in 3. Seven cases received preoperative chemotherapy. Mean tumor size before surgery was 7.1cm. Median sternotomy was performed in 10 cases and posterolateral approach in 3 cases. Mean operative time was 225 minutes and blood loss was 228 g. Mean postoperative in-hospital duration was 8.2 days. There were not any life-threatening postoperative complications. Macroscopic residual tumor (R2) was found in 5 cases; 2 mature teratoma and 2 seminomas and a germ cell tumor because of severe adhesion to aorta. Four cases received adjuvant therapy. But in R2 case; 2 of mature teratoma and a seminoma without viable cell did not receive adjuvant therapy. Only a case of non-seminoma with complete resection, which did not achieve negative tumor marker preoperatively, showed distant metastases 4 months later after surgery.
Conclusion:
The surgery for mediastinal germ cell tumor in selected situation can show good survivability without recurrence. To balance the invasiveness and curability, minimizing the extent of surgery; not performing greater vessel replacement is one of choice.
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P3.15 - SCLC/Neuroendocrine Tumors (ID 731)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.15-012 - Surgical Outcome in Early Stage Small Cell Lung Cancer (ID 10501)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
Chemo-radiation is considered to be the standard treatment for the management of limited disease of small cell lung cancer (SCLC). Even in this early stage, the role of surgery in SCLC is still controversial. We sought to examine the role of surgery; complete resection in terms of survival in SCLC.
Method:
A retrospective review was undertaken of patients who underwent surgery for SCLC between 2001 and 2015. Patients were staged according to the 7[th] edition of the Tumor, Node, Metastasis classification of lung cancer. Actuarial survival estimated with Kaplan Meier method and comparisons were undertaken using Cox regression hazard model. Clinicopathological factors and predictors of survival were analyzed.
Result:
We identified 49 patients who underwent complete resection. The mean follow up period was 1343 days. The mean age was 70.7 years. 40 patients were men and 9 were women. The number of patients of clinical stage was stage IA :21, IB: 15, IIA: 4, IIB: 6, IIIA:3. Operative procedure was lobectomy in 43, segmentectomy in 1, wedge resection in 5. The number of patients of pathological stage was stage IA :15, IB: 11, IIA: 14, IIB: 7, IIIA:2. Adjuvant chemotherapy was performed in 26 patients (53.1%). The 5-year overall survival (OS) rate in all patients was 58.8%. The 5-year OS was 61.3% in c-stage I, 54.5% in c-stage II, and 50% in c-stage III. The 5-year OS were 66.2% in p-stage I, 55.4% in p-stage II, and 50% in p-stage III. The 5-year OS of patients with adjuvant chemotherapy was significantly better than that of patients without adjuvant chemotherapy (77.8% vs. 39.8%, p=0.005). Multivariable Cox regression hazard model demonstrated that adjuvant chemotherapy was prognostic factor of overall survival (OS) (hazard ratio 0.255 (.095-.688), p=0.007)
Conclusion:
Surgical outcome for early stage SCLC was satisfied one. The role of surgery for this group seemed to be important. Adjuvant chemotherapy may improve prognosis and long-term survival will be expected.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-047 - Salvage Surgery for Locoregional Recurrence or Persistent Residual Tumor After Definitive Chemoradiation Therapy (ID 9886)
09:30 - 09:30 | Author(s): H. Nakayama
- Abstract
Background:
There are few treatment options with curative intent for locoregional recurrence or residual tumor of locally advanced lung cancer after definitive chemoradiation therapy. Lung resection; salvage surgery is likely to be one of the options for local control in this situation. However, perioperative complications and survival benefit of salvage surgery are not well-reported.
Method:
Patients who underwent lung resection after definitive chemoradiation therapy for the treatment of non-small cell lung cancer were selected. Frequency and content of perioperative complications, 5-y overall survival rate and disease free survival rate were retrospectively analyzed.
Result:
A total of 13 patients treated between January 2001 and December 2016 were eligible for evaluation. (12 men and 1 women, mean age 54 years, Median follow-up was 39.7 months.) The indication for surgery was primary tumor regrowth (69%) or tumor persistence (31%). The prior median radiation therapy dose was 60Gy (range 60-77Gy). The indication of for surgery were primary tumor regrowth (8 patients)or tumor persistence(5 patients). All patients underwent an anatomical resection, surgical procedure included lobectomy in 10 patients, pneumonectomy in 2 patients, bilobectomy in 1 patients. 2 patients underwent a bronchoplasty. Median estimated blood loss was 247ml, and median operative duration was 278 min. Compared with anatomical resection we usually perform, salvage surgery needs longer operative duration. Postoperative complications occurred in 4 patients(31%) without perioperative death within 90 days : arrhythmia, delayed pulmonary fistula, acute exacerbation of interstitial pneumonia and empyema. the 5-y overall survival and 5-y recurrence free survival rate were 73.3% and 55.0%,respectively.
Conclusion:
Salvage surgery for locoregional recurrence or residual tumor after definitive chemoradiotherapy was acceptable in safety. It should be considered as a treatment option for selected patients. However, the technique of salvage surgery is complicated, it needs an adequate experience.
