Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study.

BACKGROUND: Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. OBJECTIVE: To determine the most important prognostic factors for relapse in CSI-NS patients. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell's C-index) and calibration. RESULTS: Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from < 5% to > 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. CONCLUSION AND RELEVANCE: The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.

Excellent survival in relapsed stage I testicular cancer.

BACKGROUND: Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard management. However, 15-50% of patients eventually relapse with metastatic disease after AS. Relapses need to be detected early in order to achieve cure and avoid overtreatment. METHODS: We retrospectively analyzed consecutive GCC patients treated at two Swiss academic centers between 2010 and 2020. Patients with stage IS and extragonadal primaries were excluded. We compared disease characteristics and survival outcomes of patients relapsed from initial CSI to patients with de novo metastatic disease. Primary endpoint was the IGCCCG category at the time of relapse. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 360 GCC patients with initial CSI and 245 de novo metastatic patients. After a median follow-up of 47 months, 81 of 360 (22.5%) CSI patients relapsed: 41 seminoma (Sem) and 40 non-seminoma (NSem) patients. All Sems relapsed in the IGCCCG good prognosis group. NSem relapsed with good 29/40 (72.5%) and intermediate 11/40 (27.5%) prognostic features; 95.1% of relapses occurred within five years post-orchiectomy. Only 3 relapsed NSem patients died from metastatic disease. Five-year OS for relapsed CSI patients was 100% for Sem and 87% (95% CI: 61-96%) for NSem patients; five-year PFS was 92% (95% CI: 77-97) and 78% (95% CI: 56-90) for Sem and NSem, respectively. When stratified by IGCCCG prognostic groups, good risk relapsed patients had a trend towards better OS and PFS as compared to de novo metastatic patients. CONCLUSIONS: GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database

Objectives: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. Methods: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann–Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. Results: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01–12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. Conclusions: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk. (AU)

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

Testicular germ cell tumours' clinical stage I: comparison of surveillance with adjuvant treatment strategies regarding recurrence rates and overall survival-a systematic review.

PURPOSE: Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. METHODS/SYSTEMATIC REVIEW: We performed a systematic literature review confining the search to most recent studies published 2010-2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. RESULTS: Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7-100%, 91.7-100%, and 97-99.1%, respectively. In SE CSI, relapse rates were 0-22.3%, 0-5%, and 0-12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1-98.7%, 83.5-100%, and 92.3-100%, respectively. CONCLUSION: In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment.

Clinicopathologic predictors of outcomes in children with stage I testicular germ cell tumors: A pooled post hoc analysis of trials from the Children's Oncology Group.

BACKGROUND: Patients with clinical stage I (CS I: cN0M0) testicular germ cell tumors (TGCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I TGCT, we lack reliable means to predict relapse among pediatric and adolescent patients. OBJECTIVE: We sought to identify predictors of relapse in children with CS I TGCT. STUDY DESIGN: We performed a pooled post hoc analysis on pediatric and adolescent AJCC CS I TGCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of events, defined as relapse, secondary malignant neoplasm, or death. RESULTS: 106 patients were identified with outcomes data available. Most patients were pT1-2 stage. Among patients with evaluable histopathology, yolk sac tumor elements were present in all patients and lymphovascular invasion in 51% of patients. Over a median follow-up of 56 months, no patients died, and 25 patients (24%) experienced an event (median event-free survival not reached). Independent predictors of events on multivariable analysis included age ≥12 years at diagnosis (HR 8.87, p < 0.001) and higher pT stage (pT2 HR 7.31, p = 0.0017; pT3 HR 13.5, p = 0.0043). DISCUSSION: Although our study population reflects the largest pooled prospective cohort of CS I pediatric and adolescent TGCT to our knowledge, the relatively low event rate limits our multivariable analysis, and longer follow-up duration would help further characterize the natural history of these patients. Centralized pathologic review was also unable to be performed for several patients. CONCLUSION: Pediatric and adolescent CS I TGCT patients exhibit remarkable 5-year survival. Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and inform personalized treatment for these patients by potentially guiding surveillance versus adjuvant treatment strategies.

Wedge Resection vs. Stereotactic Body Radiation Therapy for Clinical Stage I Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Whether wedge resection or stereotactic body radiation therapy (SBRT) has better effectiveness in treatment of clinical stage I non-small cell lung cancer (NSCLC) patients remains unclear. Here we conducted the first meta-analysis to directly compare the survival outcomes of clinical stage I NSCLCs treated with wedge resection and SBRT. Methods: We systematically searched studies from PubMed, Embase, and Corchrane Library up to October 1, 2021. Data for analysis mainly included overall survival (OS) and disease-free survival (DFS), which were obtained directly from the text results or calculated from the Kaplan-Meier survival curve. We used the standard random-effect model test (DerSimonian and Laird method) to analyze the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The Q-test and I 2-test were used to assess heterogeneity. The stability of pooled HRs was examined by sensitivity analysis. Results: Six retrospective studies with a total of 11,813 clinical stage I NSCLCs who received wedge resection or SBRT were included. The results showed that patients receiving wedge resection had a significantly better OS (HR = 1.20, 95% CI = [1.07, 1.34], P = 0.002) than those with SBRT, but no significant difference of DFS (HR 1.53, 95% CI = [0.83-2.83], P = 0.17) was observed. There was no significant heterogeneity during our analysis, but there may be potential publication bias among these studies. Conclusions: Our meta-analysis showed that clinical stage I NSCLCs treated with wedge resection had superior OS than those treated with SBRT. However, more prospective clinical trials should be well-designed to evaluate the optimal treatment modality of early-stage NSCLCs.

Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry.

Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.

Selective Mediastinal Lymphadenectomy or Complete Mediastinal Lymphadenectomy for Clinical Stage I Non-Small Cell Lung Cancer: A Meta-Analysis.

INTRODUCTION: Selective mediastinal lymphadenectomy (SML) and complete mediastinal lymphadenectomy (CML) are two main types of surgery conducted for the treatment of non-small cell lung cancer (NSCLC) plus lobectomy or segmentectomy. It is not known whether stage I NSCLC can benefit from CML. Using the meta-analytical method, our research aimed to find out the worth of SML and CML for the therapy of clinical stage I NSCLC. METHODS: We searched PubMed, Ovid, MEDLINE, Cochrane Controlled Trial Register (CENTRAL), Embase, and Google Scholar for literature published up to June 2021 to evaluate the comparative research and to assess the post-operative complications, overall survival rate, disease-free survival rate, and local and distant recurrence. This meta-analysis was conducted by combining the results of the reported incidences of post-operative complications, local and distant recurrence, and short- and long-term mortality. The pooled odds ratios (OR) and the 95% confidence intervals were calculated by random or fixed effects models to compare the effectiveness between these two methods. RESULTS: Five retrospective studies and one randomized controlled trial study were included in our research. The six studies included a total of 5713 patients, of whom 1480 were assigned to the SML group and 4233 were assigned to the CML group. No statistically significant differences were found in the 1- and 5-year overall survival rates or the 1-, 3-, and 5-year disease-free survival rates between the two groups. However, the 3-year overall survival favored the SML group (P < 0.05). There were also no statistically significant differences between the local and distant metastasis. Among the postoperative complications, pneumonia, atelectasis, and prolonged air leak were more common in the CML group (P < 0.05). There were no differences in the prevalence of dysrhythmia, chylothorax, acute respiratory distress syndrome, or recurrent laryngeal nerve injury between the two groups, which may be due to the limited sample size. CONCLUSION: Considering the comparable survival rates, disease control, and fewer postoperative complications in the evaluated participants, SML is the preferred treatment with less invasiveness for clinical stage I NSCLC.

Minimally invasive open surgery (MIOS) for clinical stage I lung cancer: diversity in minimally invasive procedures.

BACKGROUND: Many thoracic surgeons have tried to make lung cancer surgery less invasive. Among the minimally invasive approaches that are currently available, it is controversial which is optimal. Minimally invasive open surgery, i.e. hybrid video-assisted thoracic surgery, has been adopted for lung cancer surgery at our institute. The objective of this study was to evaluate minimally invasive open surgery in terms of perioperative outcomes over the most recent 5 years. METHODS: Between 2015 and 2019, 2738 patients underwent pulmonary resection for lung cancer at National Cancer Center Hospital, Japan. Among them, 2174 patients with clinical stage I lung cancer who underwent minimally invasive open surgery were included. Several perioperative parameters were evaluated. RESULTS: The patients consisted of 1092 men (50.2%) and 1082 women (49.8%). Lobectomy was performed in 1255 patients (57.7%), segmentectomy in 603 (27.7%) and wide wedge resection in 316 (14.5%). Median blood loss was 30 ml (interquartile range: 15-57 ml) for lobectomy, 17 ml (interquartile range: 10-31 ml) for segmentectomy and 5 ml (interquartile range: 2-10 ml) for wide wedge resection. Median operative time was 120 min (interquartile range: 104-139 min) for lobectomy, 109 min (interquartile range: 98-123 min) for segmentectomy and 59 min (interquartile range: 48-76 min) for wide wedge resection. Median length of postoperative hospital stay was 4 days (interquartile range: 3-5 days). The 30-day mortality rate was 0.08% for lobectomy, 0.17% for segmentectomy and 0.00% for wide wedge resection. CONCLUSIONS: Minimally invasive open surgery for clinical stage I lung cancer is a feasible approach with a low mortality and a short hospital stay. Oncological outcomes need to be investigated.

Long-term outcomes of robotic gastrectomy for clinical stage I gastric cancer: a single-center prospective phase II study.

INTRODUCTION: The outcomes of robotic gastrectomy (RG) for gastric cancer remain unclear due to a lack of prospective studies. We had previously designed and conducted a prospective phase II study of RG that showed favorable short-term outcomes. Herein, we aimed to determine the long-term outcomes of RG for clinical stage I gastric cancer. PATIENTS AND METHODS: This single-center, prospective phase II study enrolled patients with clinical stage I gastric cancer undergoing RG. The survival outcomes, which were the secondary endpoints of the study, were evaluated. RESULTS: Between December 2012 and April 2015, 120 patients were enrolled in this study. The 5-year overall survival (OS) was 96.7% (95% confidence interval [CI] 91.5-98.7%). The 5-year recurrence-free (RFS) and disease-specific survival (DSS) rates were 96.7% (95% CI 91.5-98.7%) and 99.2% (95% CI 94.3-99.9%), respectively. When confining the analysis to distal and pylorus-preserving gastrectomy, the 5-year OS, RFS, and DSS were 98.1% (95% CI 92.7-99.5%), 98.1% (95% CI 92.7-99.5%), and 100%, respectively. Only one patient died due to relapse of gastric cancer, while three died from other causes. CONCLUSIONS: Long-term outcomes of RG was comparable to those of open and laparoscopic gastrectomy when the surgeries were performed by experienced surgeons in a high-volume center.

Clustered Circulating Tumor Cells in Lung Adenocarcinoma: Implications of Test Results of Continuous Variables.

BACKGROUND/AIM: We investigated the relationship between solid component size (SS), carcinoembryonic antigen (CEA), and standardized uptake value (SUVmax) as continuous variables and postoperative clustered circulating tumor cell (C-CTC) detection in patients with pulmonary adenocarcinoma who underwent surgery. PATIENTS AND METHODS: C-CTC detection was the main evaluation item, which was analyzed using the receiver operating characteristic curve to calculate areas under the curves (AUCs) for the variables. Additionally, the two-year recurrence-free survival rates (2Y-RFSRs) were analyzed. RESULTS: Among the 84 patients examined, SS, CEA, and SUVmax had AUCs>0.7, and were independent. Their thresholds were 2.1 cm, 7.5 ng/ml, and 2.9, respectively. The 2Y-RFSR were significantly better in the non-C-CTC group (n=58) and in the group of patients without high levels of these predictors (n=32). CONCLUSION: SS, CEA level, and SUVmax predicted postoperative CTC detection in pulmonary adenocarcinoma patients.

Long-term survival outcomes following laparoscopic surgery for clinical stage 0/I rectal carcinoma.

AIM: To clarify and evaluate the long-term outcomes of laparoscopic surgery for clinical stage 0/I rectal carcinoma patients. METHODS: This single-arm phase II trial involved accredited surgeons from 43 Japanese institutions. Patients were registered preoperatively. The planned sample size was 490. The primary endpoint was overall survival, and long-term outcomes were evaluated. RESULTS: A total of 495 patients were registered between February 2008 and August 2010. Eight patients (1.6%) required conversion to open surgery. Sphincter-preserving procedures were performed in 477 (97%) patients. Positive radial resection margin was found in two (0.4%) patients. Of 490 patients, 22, 314, 38, 115, and one patient had final pathological stages (p-stage) 0, I, II, III, and IV, respectively. Pathologically, 31.4% (154/490) of the patients did not have p-stage 0/I. The 5-year overall survival (OS) rates in p-stages 0, I, II, and III were 100%, 98%, 97%, and 94%, respectively. The 5-year OS of all patients at 96.6% (95% CI 94.6-97.9) was significantly better than the expected 5-year OS of 81.1% (P < .0001). The 5-year relapse-free survival in p-stages 0, I, II, and III were 100%, 93%, 81%, and 79%, respectively. The 5-year relapse-free survival of all patients was 90.1%. Fifty patients (10.2%) had recurrence; lung recurrence was found in 22 patients, local recurrence in 14, liver in seven, distant lymph node in nine, and bone in three. CONCLUSIONS: Laparoscopic surgery for clinical stage 0/I rectal carcinoma has feasible long-term outcomes. (ClinicalTrials.gov No.NCT00635466.).

Prognostic factors for relapse in patients with clinical stage I testicular cancer: protocol for a Danish nationwide cohort study.

INTRODUCTION: Approximately one-fourth of patients with clinical stage I testicular germ cell cancer will relapse within 5 years of follow-up. Certain histopathological features in the primary tumour have been associated with an increased risk of relapse. The available evidence on the prognostic value of the risk factors, however, is hampered by heterogeneity of the study populations included and variable reporting of the histopathological features. The aim of this study is to identify pathological risk factors for relapse in an unselected large nationwide cohort of patients with stage I disease. METHODS AND ANALYSIS: All incident cases of stage I testicular germ cell cancer diagnosed in Denmark between 2013 and 2018 will be identified using the nationwide prospective Danish Testicular Cancer (DaTeCa) database. Archived microscopic slides from the orchiectomy specimens will be retrieved through linkage to the Danish Pathology Data Bank and reviewed blinded to the clinical outcome. The DaTeCa database includes 960 stage I seminoma patients with expected 185 relapses and 480 patients with stage I non-seminoma with expected 150 relapses. A minimum follow-up period of 3 years of all patients will be ensured. Predefined prognostic variables will be investigated with regard to relapse in univariable and multivariable analysis using the Cox proportional hazards model. ETHICS AND DISSEMINATION: This study protocol has been approved by the Regional Ethics Committee (Region Zealand, Denmark) and the Danish Data Protection Agency. All data will be managed confidentially according to legislation. Study results will be presented at international conferences and published in peer-review journals.

Sublobar resection is associated with better perioperative outcomes in elderly patients with clinical stage I non-small cell lung cancer: a multicenter retrospective cohort study.

BACKGROUND: Sublobar resection has emerged as an alternative to lobectomy for management of early-stage non-small cell lung cancer (NSCLC). However, controversy remains as to whether it is adequate for elderly patients. The present study aimed to comparatively study the perioperative outcomes and overall survival of sublobar resection vs. lobectomy for management of elderly patients (≥65 years) with clinical stage I NSCLC. METHODS: This is a multicenter retrospective cohort study. Clinical stage I NSCLC patients who underwent lobar or sublobar resection (segmentectomy and wedge resection) at the Department of Thoracic Surgery of 10 tertiary hospitals between January 2014 and September 2017 were retrospectively reviewed from the national collaborative prospective lung cancer database (LinkDoc Technology Co, Ltd., Beijing, China). Clinical data on demographic and tumor characteristics, surgical details were collected. Perioperative outcomes and overall survival were analyzed by using propensity score matching to adjust for selection bias. Subgroup analysis was further carried out to explore the potential sources of heterogeneity. RESULTS: Among the 1,579 eligible patients, 1,164 (73.7%) underwent lobectomy and 415 (26.3%) underwent sublobar resection (106 segmentectomy and 309 wedge resection). Sublobar resection was more frequently performed in patients who were elder, had more comorbidities and smaller, left-sided adenocarcinoma (P<0.001). Propensity-matched analysis showed significant association of sublobar resection with less blood loss, shorter operation time, chest drainage and hospital stay, while with less lymph node removal when compared with lobectomy (P<0.001). Short term survival analysis showed comparable results even after adjusted in the matched analysis. Similar results were obtained when limiting patients to those aged >75 years, at pathologic stage I, and those who smoking or undergoing video-assisted thoracoscopic surgery (VATS) or segmentectomy and lobectomy. CONCLUSIONS: Sublobar resection was associated with significantly better perioperative outcomes without compromising short term survival in elderly patients with clinical stage I NSCLC. However, the importance of patient selection and management process, as well as accurate lymph node staging must be acknowledged when making the surgical decision (clinical registration number: NCT03429673).

Clinicopathologic characteristics of non-small cell lung cancer in patients with smoking-related chronic obstructive pulmonary disease.

BACKGROUND: The purpose of this study was to clarify the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) patients with smoking-related chronic obstructive pulmonary disease (COPD) and to evaluate the biological behavior of this disease. We investigated the association between smoking-related COPD, the recurrence-free proportion (RFP) and the clinicopathological features of clinical stage I NSCLC patients. METHODS: Between 2005 and 2014, 218 consecutive patients with clinical stage I NSCLC underwent complete resection with lobectomy or greater and systematic lymph node dissection. Differences in categorical outcomes were evaluated by the χ2 test. RFPs were estimated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. RESULTS: The 5-year RFP of clinical stage I NSCLC patients with smoking-related COPD was 55%, which was significantly lower than in those without smoking-related COPD (85%; p < 0.001). Postoperative pathological factors, including moderate or poor histological differentiation, intratumoral vascular invasion and lymph node metastasis, were detected more often in patients with smoking-related COPD. In adenocarcinoma patients, the 5-year RFP of patients with smoking-related COPD was 47%, which was significantly lower than in those without smoking-related COPD (87%; p < 0.001). The presence of a solid component was more frequently found in patients with smoking-related COPD (p = 0.007). CONCLUSION: Clinical stage I NSCLC patients with smoking-related COPD have histologically more invasive tumors than those without smoking-related COPD.

Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small cell lung cancer.

BACKGROUND: One of the known risk factors for non-small cell lung cancer (NSCLC) is somatic mutation in the Kirsten rat sarcoma (KRAS) gene. The relationship with smoking is well known. METHODS: We retrospectively studied the data of 92 patients who underwent pulmonary resection January 2003 and June 2012 and were diagnosed as KRAS-mutated pathological stage I adenocarcinoma. RESULTS: Among them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400) were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53-positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively). CONCLUSIONS: A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not affect survival in smokers harboring KRAS codon 12.

Clinical Outcomes of Stereotactic Body Radiotherapy for Patients With Stage I Small-Cell Lung Cancer: Analysis of a Subset of the Japanese Radiological Society Multi-Institutional SBRT Study Group Database.

Stereotactic body radiotherapy (SBRT) is widely used as a curative treatment option for stage I non-small-cell lung cancer, but for patients with stage I small-cell lung cancer, the role of stereotactic body radiotherapy is unclear. In this study, we retrospectively analyzed the outcomes of a subset of patients with stage I small-cell lung cancer treated with stereotactic body radiotherapy in the database of the Japanese Radiological Society-Multi-Institutional stereotactic body radiotherapy Study Group. The 43 patients treated with stereotactic body radiotherapy for stage I small-cell lung cancer between 2004 and 2012 at 11 Japanese institutions were studied: median age = 77 years; 32 (74%) males and 11 females; and 80% were medically inoperable. The clinical stage was IA in 31 and IB in 12. In all patients, the lung tumors were pathologically proven as small-cell lung cancer. A total dose of 48 to 60 Gy was administered in 4 to 8 fractions. The median biologically effective dose (α/ß = 10 Gy) was 105.6 Gy. Chemotherapy and prophylactic cranial irradiation were administered in only 8 patients, respectively. The median follow-up time was 23.2 months. The 2-year overall survival, progression-free survival, and distant metastasis-free survival rates were 72.3%, 44.6%, and 47.2%, respectively. The 2-year local control was 80.2%. Regarding the patterns of failure, distant metastasis, lymph node metastasis, and local recurrence were observed in 47%, 28%, and 16% of patients, respectively. No ≥grade 3 stereotactic body radiotherapy-related toxicities were observed. Although stereotactic body radiotherapy was thus revealed to be effective for the local control of stage I small-cell lung cancer, the incidence of distant metastases was high. Further investigations of larger cohorts are needed, including analyses of the effects of combined chemotherapy.