Maximum resistance pressure at the time of lung tissue rupture after porcine lung transection using automatic linear staplers with different reinforcement methods.

PURPOSES: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. METHODS: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. RESULTS: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. CONCLUSIONS: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Treatment-related adverse events of combination chemoimmunotherapy versus chemotherapy alone in first-line treatment for non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials.

Background: Numerous meta-analyses have examined immunotherapy-induced adverse events (AEs) in non-small cell lung cancer (NSCLC). However, there is limited research comparing AEs from combination chemoimmunotherapy versus chemotherapy alone in the first-line NSCLC treatment, particularly regarding specific toxic symptoms and hematological toxicities associated with the addition of immune checkpoint inhibitors (ICIs). Methods: We conducted a meta-analysis of randomized clinical trials (RCTs) comparing ICIs + non-ICIs versus non-ICIs alone as first-line therapy in NSCLC, sourced from PubMed and Scopus databases. Our objective was to assess treatment-related AEs in both regimens, focusing on identifying the more prevalent toxic symptoms and hematological toxicities with ICI treatment. We calculated the relative risks (RRs) and 95% confidence intervals (CIs), and estimated the pooled RRs and 95% CIs using common- or random-effects models. Results: Our analysis included 10 trials with 6,008 patients. Combination chemoimmunotherapy significantly increased the risk of grade 3 or higher treatment-related AEs, treatment discontinuation, and deaths due to treatment-related AEs. Moreover, patients receiving combination chemoimmunotherapy had a significantly higher risk of certain toxic symptoms (all-grade: vomiting, diarrhea, and constipation; high-grade: fatigue and diarrhea) and pneumonitis (both all-grade and high-grade). Conclusions: These findings offer crucial insights into the toxicity profile of combination chemoimmunotherapy, serving as a valuable resource for clinicians managing lung cancer care.

Usefulness of free subcutaneous fat pads for refractory secondary pneumothorax due to lung cancer.

Surgical treatment for a pneumothorax involves resection of the pulmonary pleural fistula, and closure of the fistula or coverage of the fistula using pericardial fat pads or an intercostal muscle flap. In some cases, however, these treatments are difficult because of thickened pleura or dense pleural adhesions in the thoracic cavity. We report two cases of refractory secondary pneumothorax due to lung cancer that were successfully treated using free subcutaneous fat pads to cover the pulmonary pleural fistulas. Both patients had advanced lung cancer, and each developed a pneumothorax after chemotherapy or the administration of osimertinib. Each had a prolonged air leak despite chest tube drainage. We harvested a free subcutaneous fat pad around the thoracotomy site and sutured it to cover the fistula. After the operation, the air leak disappeared immediately, and the chest tube was removed from each patient on postoperative day 2. Computed tomography at 2 or 4 months postoperatively demonstrated that the free subcutaneous fat pads were still present with no sign of pneumothorax. Application of free subcutaneous fat pads to cover a persistent pulmonary pleural fistula is useful for the treatment of secondary pneumothorax due to lung cancer.

Rare but clinically important salivary gland-type tumor of the lung: A review.

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.

Challenges in Robotic Lung Lobectomy through the Anterior Approach.

PURPOSE: Robot-assisted thoracic surgery (RATS) has become popular because of its minimally invasive nature and reduced burden on surgeons. The anterior approach (AA) is beneficial because it utilizes the same field of view and procedures as thoracotomy and video-assisted thoracic surgery, although the disadvantages are less well-known. METHODS: We retrospectively examined 35 consecutive patients who underwent RATS lobectomy via the AA, focusing on clinical factors and postoperative complications. RESULTS: The study included 12 males and 23 females with a median console time of 177 (120-346) min, median blood loss of 0 (0-100) mL, and median stapler usage of 5 (2-10) units. Postoperative complications, classified as Clavien-Dindo grade ≥III, included three cases of grade IIIa (prolonged air leakage) and one case each of grade IIIb and grade IVa (middle lobe torsion and ventricular arrhythmia). The influence of stapling device operation cannot be ruled out in prolonged air leakage and middle lobe torsion. A moderate correlation (correlation coefficient = 0.492, p = 0.003) was observed between console time and the number of staplers used. CONCLUSION: Although no severe incidence of vascular injury was observed with the AA, complications related to the use of stapling devices were noted.

Impact of Chronic Obstructive Pulmonary Disease on the Long-term Prognosis of Patients Undergoing Lobectomy for Non-small-cell Lung Cancer: A Propensity Score-matched Analysis.

BACKGROUND/AIM: Recent advances in surgery, such as thoracoscopic surgery, have made it possible to treat patients with chronic obstructive pulmonary disease (COPD) more safely than before. This study evaluated the short- and long-term prognosis of lobectomy in non-small cell lung cancer (NSCLC) patients with COPD. PATIENTS AND METHODS: This retrospective, propensity-matched, cohort analysis was conducted from January 2014 to December 2018. Among 441 patients who underwent lobectomy for NSCLC, 158 (35.8%) had a preoperative diagnosis of COPD. Propensity-matched analysis, incorporating preoperative variables, was used to compare postoperative hospital stay and complications, and long-term prognosis between the groups. RESULTS: Propensity matching estimated 145 patients in each group. There was no difference between the two groups for length of postoperative hospital stay (12 vs. 11 days, p=0.306). Postoperative complications were more frequent in the COPD group (24.1%) than in the non-COPD group (16.6%), but the difference was not significant (p=0.108). The 5-year overall survival rate was 86.2% in the COPD group and 82.1% in the non-COPD group after matching (p=0.580). The corresponding 5-year recurrence-free survival rate was 72.8% in the COPD group and 67.2% in the non-COPD group after matching (p=0.601). CONCLUSION: In case of Global Initiative for Chronic Obstructive Lung Disease (GOLD) I/II classification, COPD did not significantly worsen the prognosis of patients with NSCLC after lobectomy.

Lobectomy for Pulmonary Arteriovenous Fistula in a Patient With Rendu-Osler-Weber Disease: A Case Report.

BACKGROUND: Rendu-Osler-Weber disease (Osler's disease) is the most common cause of pulmonary arteriovenous fistula. We report a case of pulmonary arteriovenous fistula associated with Osler's disease that was treated by lobectomy. CASE REPORT: A 44-year-old man with Osler's disease presented with respiratory distress. Computed tomography showed a pulmonary arteriovenous fistula, which had a 26-mm-long diameter in S6 of the left lung. Transcatheter treatment had a high risk of recurrence, and surgery was indicated. The pulmonary arteriovenous fistula was found at the beginning of A6. A6 and the basilar artery were cut together with a stapler. The postoperative course was uneventful, and respiratory distress symptoms improved with no recurrence. CONCLUSION: We report a case of pulmonary arteriovenous fistula caused by Osler's disease treated by lobectomy. Although transcatheter treatment is the mainstream treatment for pulmonary arteriovenous fistulas, surgical resection may be effective depending on the size of the lesion.

Impact of Neoadjuvant Immune Checkpoint Inhibitors on Surgery and Perioperative Complications in Patients With Non-small-cell Lung Cancer: A Systematic Review.

Several clinical trials are currently underway to evaluate immune checkpoint inhibitors (ICIs) as neoadjuvant treatment for patients with early-stage non-small-cell lung cancer (NSCLC), and their use in clinical practice is expected to increase in the future. Therefore, a proper assessment of surgical outcomes and perioperative complications after neoadjuvant ICIs is essential to establish recommendations and guidelines. We performed a systematic literature review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), searching the PubMed and Scopus databases from the January 1, 2017, to the July 27, 2023, to identify potentially relevant published trials of neoadjuvant ICIs in patients with reseactable NSCLC with available information on surgical outcomes and perioperative complications. A total of 18 studies were included in the review. The rates of surgery cancellation ranged from 0% to 45.8%. Importantly, adverse events (AEs) were the least reported underlying cause, while disease progression caused from 0% to 75% of cancellations. Surgery delays ranged from 0% to 31.3% with AEs as the most frequently reported underlying cause. However, 6 out of 13 trials (46.2%) reported no surgery delays. Conversion rates from minimally invasive to open chest surgery were available for 7 trials and ranged from 0% to 53.8%. Thirty-day mortality rates ranged from 0% to 5.4%, with 11 out of 16 trials reporting 0%. A few reports described perioperative complications in detail. Considering the limited evidence available, we can preliminarily confirm that preoperative ICIs are safe and well tolerated even from the surgical perspective. Additional details on intraoperative findings from prospective controlled trials are needed to establish and disseminate guidelines and recommendations for thoracic surgeons.

Impact of Liver Metastasis on First-Line Immunotherapy in Stage IV Non-Small Cell Lung Cancer.

Background: Immunotherapy has become a key component of systemic therapy in stage IV non-small cell lung cancer (NSCLC). However, there have been conflicting reports of its efficacy in patients with liver metastasis (LM). Methods: Using National Cancer Database (NCDB), patients who have been diagnosed and treated at Commission on Cancer- participating US institutions were screened for analysis. Selection criteria included clinical stage IV NSCLC, available cTNM stage information, overall survival (OS) with at least 1 month, and diagnosis between 2015 and 2017. They were grouped based on status of LM as well as use of immunotherapy. Clinical characteristics were collected and their association with LM/immunotherapy was analyzed. Impact of immunotherapy on OS was examined according to LM status. Propensity score matching (PSM) analysis was also conducted. Results: A total of 83,479 including 18,497 LM-positive and 64,982 LM-negative patients met the study criteria. Presence of LM was associated with a number of clinical variables such as younger age, male sex, and chemotherapy. OS in patients with LM was significantly worse than that in those without LM (median OS, 5.0 vs. 8.8 months; hazard ratio (HR), 1.46; log-rank, P < 0.0001). Significant OS benefit from immunotherapy was observed in both LM-positive (median OS, 4.1 vs. 9.0 months; HR, 0.62; P < 0.0001) and negative groups (median OS, 7.2 vs. 15.6 months; HR, 0.64; P < 0.0001). Conclusion: Immunotherapy benefited similarly to the survival of metastatic NSCLC patients regardless of with or without LM. Further research to validate the result would be warranted.

Modulation of host glutamine anabolism enhances the sensitivity of small cell lung cancer to chemotherapy.

Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.

Efficacy of immune checkpoint inhibitors in younger patients with non-small cell lung cancer.

PURPOSE: Because patients younger than 40 years are rarely enrolled in clinical trials in non-small cell lung cancer (NSCLC), their survival benefit of immune checkpoint inhibitors (ICIs) needs to be clarified. METHODS: The National Cancer Database was queried for patients who were diagnosed with stage IV NSCLC between 2016 and 2018. ICIs were administered in the first-line setting. The overall survival (OS) of patients with stage IV NSCLC according to the receipt of ICIs was compared in different age groups (< 40, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years). Multivariate analyses identified the clinical characteristics predictive of OS. Propensity score matching (PSM) was conducted to reduce the biases arising from clinical characteristics. RESULTS: This study included 126,476 patients with stage IV NSCLC. In univariate analysis, ICI treatment was not associated with a survival benefit in patients younger than 40 years with stage IV NSCLC relative to their ICI-naïve counterparts after PSM (median OS: 24.2 months vs. 24.0 months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.81-1.27, P = 0.9031). Multivariate analysis revealed that ICI use was not an independent predictor of OS in patients with stage IV NSCLC < 40 years old (HR = 0.96, 95% CI = 0.76-1.21, P = 0.7230). Sequential improvement of the HR was observed with increasing age. CONCLUSION: Our study suggested a poor survival benefit of ICIs in stage IV NSCLC patients younger than 40 years old, which should be validated in prospective studies.

Comparison of radiological and pathological tumor sizes in resected non-small cell lung cancer.

OBJECTIVES: In non-small cell lung cancer (NSCLC), T factor plays an important role in determining staging. The present study aimed to determine the validity of preoperative evaluation of clinical T (cT) factor by comparing radiological and pathological tumor sizes. METHODS: Data for 1,799 patients with primary NSCLC who underwent curative surgery were investigated. The concordance between cT and pathological T (pT) factors was analyzed. Furthermore, we compared groups with an increase or decrease of ≥ 20% and groups with an increase or decrease of < 20% in the size change between preoperative radiological and pathological diameters. RESULTS: The mean sizes of the radiological solid components and the pathological invasive tumors were 1.90 cm and 1.99 cm, respectively, correlation degree = 0.782. The group with increased pathological invasive tumor size (≥ 20%) compared with the radiologic solid component was significantly more likely female, consolidation tumor ratio (CTR) ≤ 0.5, and within cT1. Multivariate logistic analysis identified CTR < 1, cT ≤ T1, and adenocarcinoma as independent risk factors for increased pT factor. CONCLUSION: The radiological invasive area of tumors with cT1, CTR < 1, or adenocarcinoma on preoperative CT may be underestimated compared with pathological invasive diameter.

Is radical local therapy effective in postoperative recurrent EGFR-mutated non-small cell lung cancer?

BACKGROUND: Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. METHODS: This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. RESULTS: From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. CONCLUSIONS: Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first-line ICI combined with or without chemotherapy. MATERIALS AND METHODS: Two-hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first-line therapy. Cutoff value of the pretreatment PNI was set as 42.17. RESULTS: Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression-free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51-0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32-0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively). CONCLUSION: The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first-line ICI therapy.

Conservative treatment for residual lung congestion after left upper trisegmentectomy: a case report.

Background: Currently, segmentectomy is the procedure of choice in approximately 10% of lung cancer surgeries in Japan. However, complications are often observed in that procedure. In particular, residual pulmonary congestion after segmentectomy often leads to surgical intervention. Case Description: We report a case of improved congestion in the residual lung after left upper trisegmentectomy (LUTS) with conservative treatment under careful observation. A 65-year-old man was diagnosed with bilateral lung cancer and initially underwent LUTS. On the next day after surgery, blood sputum was observed. Computed tomography (CT) showed consolidation in the lingual region of the left lung and stenosis of V4+5 in the left lung. The cause of the congestion was thought to be an isolated segment with part of the remaining S3 and a thin V4+5 with poor flow. Because pulmonary torsion or necrosis of the residual lung was not observed, conservative treatment with antibiotics under careful follow-up by CT was chosen. The pulmonary congestion and inflammatory reaction gradually improved, and the patient was discharged home on the 26th day after surgery. Conclusions: We experienced a case of residual pulmonary congestion after LUTS that resolved with conservative treatment. Careful follow-up of the patient's general condition and imaging studies are considered to be important.

Prognostic Impact of C-Reactive Protein-to-Lymphocyte Ratio in Non-small Cell Lung Cancer: A Propensity Score-Matching Analysis.

BACKGROUND: Many inflammatory and nutritional markers have been used to predict prognosis in lung cancer. The C-reactive protein (CRP)-to-lymphocyte ratio (CLR) is a useful prognostic factor in various cancers. However, the prognostic value of preoperative CLR in patients with non-small cell lung cancer (NSCLC) remains to be established. We examined the significance of the CLR compared with known markers. METHODS: A total of 1380 surgically resected NSCLC patients treated at two centers were recruited and divided into derivation and validation cohorts. After CLRs were calculated, patients were classified into high and low CLR groups based on the cutoff value determined by receiver operating characteristics curve analysis. Subsequently, we determined the statistical associations of the CLR with clinicopathological factors and prognosis and further analyzed its prognostic impact by propensity-score matching. RESULTS: Of all the inflammatory markers examined, CLR yielded the highest area-under-the-curve value. The prognostic impact of CLR remained significant after propensity-score matching. Prognosis was significantly worse in the high-CLR group than in the low-CLR group (5-year, disease-free survival [DFS]: 58.1% vs. 81.9%, P < 0.001; 5-year overall survival [OS]: 72.1% vs. 91.2%, P < 0.001). The results were confirmed in the validation cohorts. Multivariable analysis also showed high CLR as an independent factor for both DFS and OS (DFS: hazard ratio [HR] 1.42, P = 0.027; OS: HR 1.95, P = 0.0037). CONCLUSIONS: Preoperative CLR is a useful marker for predicting the prognosis of NSCLC patients who have undergone surgery.

Necitumumab plus gemcitabine and cisplatin in previously treated lung squamous cell carcinoma.

BACKGROUND: The efficacy and safety of the anti-EGFR antibody necitumumab combined with gemcitabine and cisplatin (N + GC) in the first-line treatment of advanced lung squamous cell carcinoma (LSCC) have been proven. However, the efficacy and safety of N + GC in the second line or later treatment remain unclear. METHODS: Eleven patients who received N + GC for advanced-stage or recurrent LSCC were enrolled. We retrospectively assessed the patients' clinical characteristics and efficacy and safety of treatment. RESULTS: The median patient age was 73 years (range, 63-77 years). The cohort included nine (81.8%) men and two (18.2%) women. Two (18.2%) patients had postoperative recurrence, and one (9.1%), three (27.3%), one (9.1%), and four (36.4%) patients were diagnosed with stage IIIA, IIIB, IVA, and IVB disease, respectively. Concerning the best overall response, partial response was achieved in five (45.5%) patients, four (36.4%) patients displayed stable disease, and two (18.2%) patients were not evaluable. Median progression-free survival was 6.8 months (range, 1.4-10.3 months). The grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in six (54.5%), three (27.3%), and two (18.2%) patients, respectively. Additionally, grade 3 skin reaction, rash, lung infection, duodenal ulcer, and febrile neutropenia were observed in one (9.1%) patient each. Two (18.2%) patients required treatment interruption because of adverse events. CONCLUSION: N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential.