Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patiets were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG).

INTRODUCTION: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. METHODS: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. RESULTS: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. CONCLUSIONS: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

A multicenter propensity score-matched analysis of lymphadenectomy in N1-positve lung cancer.

OBJECTIVES: Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. METHODS: We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n = 150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n = 209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. RESULTS: The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P = 0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P = 0.37). CONCLUSIONS: The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Clinical results of carbon ion radiotherapy for inoperable stage I non-small cell lung cancer: A Japanese national registry study (J-CROS-LUNG).

BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for inoperable stage I non-small cell lung cancer (NSCLC), and carbon-ion radiation therapy (CIRT) may be used for such treatment. Although CIRT for stage I NSCLC has demonstrated favorable outcomes in previous reports, the reports covered only single-institution studies. We conducted a prospective nationwide registry study including all CIRT institutions in Japan. MATERIALS AND METHODS: Ninety-five patients with inoperable stage I NSCLC were treated by CIRT between May 2016 and June 2018. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. RESULTS: The median patient age was 77 years. Comorbidity rates for chronic obstructive pulmonary disease and interstitial pneumonia were 43% and 26%, respectively. The most common schedule for CIRT was 60 Gy (relative biological effectiveness (RBE)) in four fractions, and the second most common was 50 Gy (RBE) in one fraction. The 3-year overall survival, cause-specific survival, and local control rates were 59.3%, 77.1%, and 87.3%, respectively. Female sex and ECOG performance status of 0-1 were favorable prognostic factors for overall survival in a multivariate analysis. No grade 4 or higher adverse event was observed. The 3-year cumulative incidence of grade 2 or higher radiation pneumonitis was 3.2%. The risk factors for grade 2 or higher radiation pneumonitis were a force expiratory volume in 1 second (FEV1) of <0.9 L and a total does of ≥ 67 Gy(RBE). CONCLUSION: This study provides real-world treatment outcomes of CIRT for inoperable. stage I NSCLC in Japan.

Prognostic Significance of the Maximum Standardized Uptake Value on the Prognosis of Clinical Stage IA Lung Adenocarcinoma Based on the 8th Edition TNM Classification.

BACKGROUND: There are few reports on the utility of the maximum standardized uptake value (SUVmax) for predicting the prognosis of early-stage lung adenocarcinoma based on the latest tumor-node-metastasis (TNM) classification. This study aimed to determine whether clinicopathologic factors, including the SUVmax, affect prognosis in these patients. PATIENTS AND METHODS: We enrolled 527 patients with c-stage IA lung adenocarcinoma who underwent lobectomy or greater resection between 2011 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared using the log-rank test. Factors associated with RFS and OS were determined using the Cox proportional hazards model. RESULTS: RFS was significantly different based on tumor stage. In contrast, there was no significant difference in OS between patients with stage IA2 and IA3 disease (p = 0.794), although there were significant differences in OS between patients with stage IA1 and IA2 disease (p = 0.024) and between patients with stage IA1 and IA3 disease (p = 0.012). Multivariate analysis demonstrated that SUVmax was independently associated with both RFS and OS among patients with c-stage IA lung adenocarcinoma (RFS, p = 0.017; OS, p = 0.047). Further, even though there was no significant difference in OS between patients with stage IA2 and IA3 disease (n = 410), SUVmax was able to stratify patients with high and low RFS and OS among these patients (RFS, p < 0.001; OS, p < 0.001). CONCLUSION: SUVmax was an important preoperative factor to evaluate prognosis among patients with c-stage IA lung adenocarcinoma as well as the current TNM classification.

Segmentectomy for clinically early-stage primary squamous cell carcinoma of the lung.

BACKGROUND: Squamous cell carcinoma of the lung-the second most common subtype of lung cancer-has a poorer prognosis than lung adenocarcinoma. However, in contrast to lobectomy, the oncological outcomes after segmentectomy for primary squamous cell carcinomas remain unknown; hence, this study investigated these outcomes. METHODS: Patients who underwent lobectomy or segmentectomy for clinically node-negative primary lung squamous cell carcinoma with a whole tumor size of ≤ 30 mm on preoperative computed tomography scan during April 2010 to December 2020 were included in this study. The cumulative incidence of recurrence (CIR) among all included patients and propensity score-matched patients were compared using the Gray method. Multivariate analysis using propensity scores and surgical procedures was performed using the Fine and Gray method. RESULTS: Overall, 230 patients were included in this study; of these, 172 (74.8%) underwent lobectomy and 58 (25.2%) underwent segmentectomy. No significant differences were observed in the CIR between patients who underwent lobectomy and those who underwent segmentectomy (5-year rate 18.1% vs. 14.2%; p  = â€Š0.787). Moreover, no significant differences in CIR were observed between the propensity score-matched patients who underwent lobectomy (n = 43) and those who underwent segmentectomy (n   = â€Š43) (8.6% vs. 8.0%; p = 0.571). Multivariable analysis was performed for CIR using the propensity score; it revealed that segmentectomy was not a significant predictor of worse CIR (hazard ratio, 0.987; p = â€Š 0.980). CONCLUSIONS: Segmentectomy may be feasible for treating clinically early-stage lung squamous cell carcinoma; its oncological outcomes are similar to those of lobectomy.

Role of ground-glass opacity in pure invasive and lepidic component in pure solid lung adenocarcinoma for predicting aggressiveness.

Objective: Lung adenocarcinoma often includes noninvasive components with postoperative lepidic morphology on pathologic specimens that appear on preoperative high-resolution computed tomography (HRCT) images as ground-glass opacity (GGO). We aimed to disclose the role of GGO on the aggressiveness of pathologically confirmed pure invasive tumors in patients with early-stage lung adenocarcinoma. Methods: The prognosis of 932 patients with clinical stage 0-IA and pathologic node-negative lung adenocarcinoma who underwent lobectomy at 3 institutions between 2010 and 2016 was investigated according to the status of GGO and lepidic components. Results: The recurrence-free survival (RFS) of patients with pathologically confirmed pure invasive tumors was worse without (n = 81) than with (n = 43) GGO (69.7%; 95% confidence interval [CI], 57.3%-79.2% vs 90.5%; 95% CI, 76.6%-96.3%, P = .028). The RFS of patients with radiologically confirmed pure solid tumors was worse without (n = 81), than with (n = 173) a lepidic component (69.7%; 95% CI, 57.3%-79.2% vs 85.3%; 95% CI, 77.2%-90.7%, P = .0012). Multivariable Cox regression analysis of overall survival and RFS revealed that pure solid and pure invasive tumors, respectively, determined by HRCT and pathologic assessment together comprised an independent prognostic factor like vascular or pleural invasion for patients with early-stage lung adenocarcinoma. Conclusions: Tumors of non-small cell lung cancer with pure solid and pure invasive components were more aggressive than those with some GGO and lepidic components. Complementary HRCT and pathologic findings can predict the malignant aggressiveness of adenocarcinoma.

A Multicenter Study of Complex Segmentectomy Versus Wedge Resection in Clinical Stage 0-IA Non-Small Cell Lung Cancer.

BACKGROUND: Although sublobar resection is widely used for lung cancer treatment, very limited data are available comparing outcomes after complex segmentectomy and wedge resection. We compared the oncological outcomes of complex segmentectomy and wedge resection for clinical stage 0-IA lung cancer via a large cohort, multicenter database using propensity score-matched analysis. PATIENTS AND METHODS: We retrospectively analyzed data from 506 clinical stage 0-IA, solid component size ≤ 2.0 cm lung cancer patients who underwent surgical resection at three institutions between 2010 and 2018. Surgical results after complex segmentectomy (n = 222) and "location-adjusted" wedge resection (n = 284) were analyzed for all patients and their propensity score-matched pairs. RESULTS: In all cohort, the complex segmentectomy group tended to have a better prognosis than the wedge resection group (5 year cancer-specific survival rate, 97.4% vs. 93.7%; P = .065 and 5 year recurrence-free interval [RFI] rates, 96.9% vs. 86.1%; P = .0005). This trend was also identified in subanalyses for pure solid tumors. In 179 propensity score-matched pairs, the prognosis of patients with complex segmentectomy tended to be better than that of patients with wedge resection (5 year cancer-specific survival rates, 96.8% vs. 92.9%; 5 year RFI rates, 96.3% vs. 87.5%). Multivariable Cox regression analysis for RFI revealed that complex segmentectomy significantly reduced lung cancer recurrence compared with wedge resection (hazard ratio, 0.32; 95% confidence interval, 0.12-0.73; P = .0061). CONCLUSIONS: Complex segmentectomy can provide better oncological outcomes compared with wedge resection.

The prognostic impact of the ground-glass opacity component in nearly pure-solid stage IA non-small-cell lung cancer.

OBJECTIVES: The aim of this study was to assess the clinical effects of a small ground-glass opacity (GGO) component of a radiologically nearly pure-solid tumour on tumour aggressiveness in patients with clinical stage IA non-small-cell lung cancer (NSCLC). METHODS: Data of 988 patients with clinical stage IA NSCLC who had a consolidation-to-tumour ratio of ≥0.75 on high-resolution computed tomography were retrospectively analysed. The cumulative incidence of recurrence (CIR) was compared between patients with GGO (nearly pure-solid, n = 297) and those without GGO (pure-solid, n = 691). RESULTS: In patients with clinical T1mi + T1a and T1b, the CIR was significantly higher in the pure-solid group than in the nearly pure-solid group (5-year CIR, 15.2% and 19.3% vs 0% and 6.4%; P < 0.001); however, this was not the case for patients with clinical T1c (5-year CIR, 23.1% vs 26.5%; P = 0.580). In the multivariable analysis, pure-solid tumours were independently associated with a higher CIR than nearly pure-solid tumours in patients with clinical T1mi + T1a + T1b (solid tumour size ≤2 cm; subdistribution hazard ratio, 3.25; 95% confidence interval, 1.59-6.63; P = 0.001) but not in those with clinical T1c tumours (2-3 cm; subdistribution hazard ratio, 0.67; 95% confidence interval, 0.39-1.13; P = 0.130). CONCLUSIONS: Nearly pure-solid tumours with a small GGO component influence tumour aggressiveness based on solid tumour size, with a threshold of 2 cm in patients with clinical stage IA NSCLC. For tumours sized 2-3 cm, nearly pure-solid tumours had a similar tumour aggressiveness as pure-solid tumours.

Oncological outcome of segmentectomy for early-stage non-small-cell lung cancer with invasive characteristics: a multicentre study.

OBJECTIVES: Segmentectomy can provide oncologically acceptable results for small-sized non-small-cell lung cancer (NSCLC). However, in cases of NSCLC with pathological invasive characteristics such as lymphatic invasion (LY), vascular invasion (V), pleural invasion (PL) and/or lymph node metastasis, the feasibility of segmentectomy is not known. METHODS: The patients included in the study (i) underwent lobectomy or segmentectomy for NSCLC with invasive characteristics such as LY, V, PL or pathological lymph node metastasis; (ii) presented with a node-negative, solid component-predominant tumour (consolidation tumour ratio >50%) on preoperative computed tomography; (iii) had a whole-tumour size of 2 cm or less; and (iv) presented between January 2010 and December 2019 to one of the 3 institutions. Cumulative incidences of recurrence (CIRs) after segmentectomy and lobectomy were compared. RESULTS: A total of 321 patients were included. Segmentectomy and lobectomy were performed in 80 (24.9%) and 241 (75.1%) patients, respectively. There was no significant difference in CIR between segmentectomy (5-year CIR rate, 17.2%) and lobectomy patients (5-year CIR rate, 27.8%, P = 0.135). In the propensity score-matched cohort, there was no significant difference in CIR between segmentectomy (5-year CIR rate, 19.1%) and lobectomy patients (5-year CIR rate, 19.2%; P = 0.650). In the multivariable analysis using inverse probability of treatment weighting and surgical method, segmentectomy was not a significant predictor of worse CIR (P = 0.920). CONCLUSIONS: Segmentectomy is feasible for clinically early-stage NSCLC irrespective of the presence of LY, V, PL or lymph node metastasis.

The impact of epidermal growth factor receptor mutation status on adjuvant chemotherapy for patients with high-risk stage I lung adenocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on epidermal growth factor receptor mutation status in patients with stage I lung adenocarcinoma. METHODS: Between 2010 and 2016, of 1901 patients with pathologic stage I (8th edition) non-small cell lung cancer, we identified 475 with high-risk (pT1c/T2a or positive for lymphovascular invasion) stage I lung adenocarcinoma who underwent lobectomy. We estimated propensity scores to adjust for confounding variables, including age, sex, Brinkman index, pulmonary functions, comorbidities, surgical approach, invasive component tumor size, visceral pleural, lymphatic, and vascular invasion, adenocarcinoma subtype, epidermal growth factor receptor mutation status, postoperative complications, and institution associated with the administration of adjuvant chemotherapy. The primary end point was recurrence-free survival. RESULTS: Of 292 patients without/unknown epidermal growth factor receptor mutation, 105 (36.0%) received adjuvant chemotherapy and 187 (64.0%) did not. In 69 pairs of patients who were propensity score matched, the 5-year recurrence-free survival was significantly better in those who underwent adjuvant chemotherapy (88.4%) than in those who did not (63.6%; P = .001). Of 183 patients with epidermal growth factor receptor mutation, 78 (42.6%) received adjuvant chemotherapy and 105 (57.4%) did not. In 49 pairs of propensity score-matched patients, there was no significant difference in the 5-year recurrence-free survival between those who underwent adjuvant chemotherapy (74.3%) and those who did not (80.5%; P = .573). CONCLUSIONS: The effect of adjuvant chemotherapy for high-risk stage I lung adenocarcinoma varied by epidermal growth factor receptor mutation status. Epidermal growth factor receptor mutation status may help to identify patients with high-risk stage I lung adenocarcinoma who may benefit from adjuvant chemotherapy.

Complex Segmentectomy for Hypermetabolic Clinical Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Due to its invasiveness, the indications for "complex segmentectomy" for radiologically hypermetabolic (high maximum standard uptake value) non-small cell lung cancer (NSCLC) remain controversial. This study compared the outcomes after complex segmentectomy and lobectomy in these patients. METHODS: We retrospectively reviewed 717 patients with radiologically hypermetabolic (maximum standardized uptake value ≥2.5), clinical stage IA NSCLC who underwent complex segmentectomy (n = 61) or location-adjusted lobectomy (n = 656) at three institutions from 2010 to 2019. Postoperative outcomes were analyzed for all patients and their propensity score matched pairs. Factors affecting oncologic outcomes were assessed by Kaplan-Meier estimates and Cox proportional hazards regression analyses. RESULTS: The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival rate, 89.9% vs 91.1%, P = .98; and 5-year recurrence-free interval rate, 83% vs 77.5%, P = .62) in the nonadjusted cohort. In 55 propensity score matched pairs, oncologic outcomes were not significantly different between patients undergoing complex segmentectomy (5-year cancer-specific survival, 89.9%; 5-year recurrence-free interval, 83%) and lobectomy (5-year cancer-specific survival, 83.6%; 5-year recurrence-free interval, 82.5%). Multivariable Cox regression analysis for recurrence-free interval revealed no significant differences between oncologic outcomes associated with complex segmentectomy and lobectomy (hazard ratio, 0.84; 95% confidence interval, 0.25 to 2.14; P = .74). CONCLUSIONS: Oncologic outcomes of complex segmentectomy and lobectomy were not significantly different for patients with radiologically hypermetabolic, clinical stage IA NSCLC patients. Complex segmentectomy can treat high maximum standardized uptake value, clinical stage IA lung cancers without compromising oncologic results.

Impact of the initial site of recurrence on prognosis after curative surgery for primary lung cancer.

OBJECTIVES: This retrospective study aimed to elucidate the impact of the initial site of recurrence on relapse-free survival and post-recurrence survival (PRS) after the curative resection of primary lung cancer. METHODS: We enrolled 325 patients who developed recurrence after curative resection of pathological stage I-IIIA primary lung cancer between January 2006 and December 2018 at the Kanagawa Cancer Center. Cases were classified as follows based on the initial site of recurrence: cervicothoracic lymph node (n = 144), lung (n = 121), pleural dissemination (n = 52), bone (n = 59), brain and meningeal dissemination (n = 50) and abdominal organ (n = 34) cases. The relapse-free survival and PRS of patients with and without recurrence at each site were compared using the log-rank test. The impact of the initial site of recurrence on PRS was analysed using the Cox proportional hazards model. RESULTS: Relapse-free survival was significantly poorer in patients with abdominal organ recurrence than in patients without abdominal organ recurrence (11.5 vs 17.6 months, P = 0.024). The PRS of patients with bone and abdominal organ recurrences was worse than that of patients without bone (18.4 vs 31.1 months, P < 0.001) or abdominal organ (13.8 vs 30.6 months, P < 0.001) recurrence. Multiple recurrence sites were observed more frequently in patients with bone and abdominal organ recurrences. Bone [hazard ratio (HR) 2.13; P < 0.001] and abdominal organ metastasis (HR 1.71; P = 0.026) were independent poor prognostic factors for PRS. CONCLUSIONS: This study suggests surveillance for abdominal organ recurrence in the early postoperative period. Patients with bone and abdominal organ recurrence should receive multimodality treatment to improve their prognosis.

Adjuvant Chemotherapy for High-risk Pathologic Stage I Non-Small Cell Lung Cancer.

BACKGROUND: This study aimed to investigate the efficacy of adjuvant chemotherapy for pathologic stage I non-small cell lung cancer (NSCLC) with high risk for recurrence. METHODS: Prospectively collected data from 1278 patients with pathologic stage I NSCLC according to eighth edition staging guidelines who were undergoing lobectomy were retrospectively analyzed. Factors associated with high risk for recurrence were determined using the multivariable Cox proportional hazards model for recurrence-free survival (RFS). Survival was compared between patients who received adjuvant chemotherapy and those who did not. RESULTS: In multivariable analysis, age (≥70 years), invasive component size (>2 cm), visceral pleural invasion, lymphatic invasion, and vascular invasion were identified as independent factors for RFS. In patients with high-risk factors for recurrence such as pathologic T1c or T2a or lymphovascular invasion (high-risk group; n = 641), adjuvant chemotherapy resulted in significantly longer RFS and overall survival (n = 222; 5-year RFS, 81.4%; 5-year overall survival, 92.7%) than in patients who did not receive adjuvant chemotherapy (n = 418; 5-year RFS, 73.8%; P = .023; 5-year overall survival, 81.7%; P < .0001). In patients without any high-risk factors for recurrence (low-risk group; n = 637), RFS was not significantly different between those who received adjuvant chemotherapy (n = 83; 5-yeat RFS, 98.1%) and those who did not (n = 554; 5-year RFS, 95.7%; P = .30). CONCLUSIONS: Adjuvant chemotherapy may improve survival in patients with pathologic stage I NSCLC who have factors associated with high risk for recurrence, such as pathologic T1c or T2a or lymphovascular invasion.

Effect of epidermal growth factor receptor gene mutation on the prognosis of pathological stage II-IIIA (8th edition TNM classification) primary lung cancer after curative surgery.

OBJECTIVES: This retrospective study aimed to elucidate the effect of epidermal growth factor receptor (EGFR) gene mutations on the prognosis of patients with pathological stage II-IIIA primary lung cancer after curative surgery. MATERIALS AND METHODS: We enrolled 539 patients with p-stage II-IIIA (8th edition tumor-node-metastasis [TNM] classification) lung cancer who underwent curative resection at Kanagawa Cancer Center between January 2010 and December 2020 and whose tumors were tested for EGFR mutations. Relapse-free survival (RFS) and overall survival (OS) of patients with EGFR-mutant lung cancer (Mt, n = 126) including EGFR exon 21 L858R point mutation and EGFR exon 19 deletion mutation and EGFR mutation-wild lung cancer (Wt, n = 413) were analyzed using Kaplan-Meier curves and compared using a log-rank test. Cox regression analysis was performed to evaluate the effects of EGFR gene mutations on RFS and OS at each stage. RESULTS: There were 56/256 patients with p-stage II EGFR-Mt/Wt and 70/157 patients with p-stage IIIA EGFR-Mt/Wt. The 5-year RFS rate of patients with EGFR-Mt/Wt was 46.6%/52.0% (p = 0.787) for p-stage II and 17.4%/29.7% (p = 0.929) for p-stage IIIA. The 5-year OS rate was 92.0%/65.7% (p = 0.001) for p-stage II and 56.0%/39.3% (p = 0.016) for p-stage IIIA. EGFR-Mt was not an independent prognostic factor for OS of patients with p-stage IIIA lung cancer (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.51-1.76; p = 0.872); however, EGFR-Mt was an independent favorable prognostic factor for OS of patients with p-stage II lung cancer (HR, 0.59; 95% CI, 0.36-0.96; p = 0.034). CONCLUSION: The OS of lung cancer patients with p-stage II or IIIA, classified according to the 8th edition TNM classification, was remarkably favorable. Incorporating EGFR mutations to the anatomical TNM classification may lead to a more accurate prognosis prediction.

Anatomical location and number of metastatic lymph nodes for prognosis of non-small cell lung cancer.

BACKGROUND: The nodal classification of lung cancer is determined by the anatomical location of metastatic lymph nodes (mLNs). However, prognosis can be heterogeneous at the same nodal stage, and the current classification system requires improvement. Therefore, we investigated the correlation between the number of mLNs and prognosis in patients with non-small cell lung cancer. METHODS: Using a multicenter database in Japan, we retrospectively reviewed the records of patients who underwent complete resection for lung cancer between 2010 and 2016. Kaplan-Meier curves were used to determine recurrence-free and overall survival. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: We included 1,567 patients in this study. We could show a statistically significant difference in recurrence-free survival between pN2 patients with 1 mLN and pN2 patients with ≥2 mLNs (P=0.016). Patients with a combination of pN1 (≥4 mLNs) plus pN2 (1 mLN) had a poorer prognosis than pN1 patients (1-3 mLNs) (P=0.061) and a better prognosis than pN2 patients (≥2 mLNs) patients (P=0.007). Multivariate analysis showed that the number of mLNs was independently associated with cancer recurrence in patients with pN1 and pN2 disease (P=0.034 and 0.018, respectively). CONCLUSIONS: Nodal classification that combines anatomical location and the number of mLNs may predict prognosis more accurately than the current classification system. Our study provides the concept that supports the subdivision of nodal classification in the upcoming revision of the tumor, node, and metastasis staging system.