Effects of tumor-infiltrating CD8+ T cells, PD1/PD-L1 axis, and expression patterns of HLA class I on the prognosis of patients with malignant pleural mesothelioma who underwent extra-pleural pneumonectomy.

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.

EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Predictive value of EGFR mutation in non-small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy.

The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non-small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).

[Clinicopathological Study of Small Intestinal Carcinoma].

We analyzed the clinicopathological characteristics, preoperative diagnosis, surgical operations, chemotherapy regimens, and prognoses of 6 patients with primary small intestinal carcinomas that were resected at our hospital between January 2004 and December 2014. The patients(3 men and 3 women)were 65 to 77 years old(mean: 70 years old). We were able to diagnose 3 patients pathologically before surgery via double balloon endoscopy and endoscopy of the large intestine. We performed partial resection of the jejunum in 3 patients, partial resection of the ileum in 1 patient, laparoscopic ileocecal resection in 1 patient, and right hemicolectomy in 1 patient. The histological type was well-differentiated adenocarcinoma in 2 patients, moderately differentiated adenocarcinoma in 2 patients, papillary adenocarcinoma in 1 patient, and poorly differentiated adenocarcinoma in 1 patient. The tumor depth was T2 in 1 patient, T3 in 2 patients, and T4 in 3 patients. The pathological stage was I in 1 patient, II A in 1 patients, II B in 2 patient, III A in 1 patient, and III B in 1 patient. The postoperative median duration of follow-up was 44 months(range: 10-127). Regarding prognosis, 5 patients are alive without recurrence, and 1 patient died of peritoneal dissemination. The overall 5-year survival rate was 75%. We suggest that it is very important to perform radical resection with lymph node dissection for patients without distant metastases.

[Clinicopathological Outcome of Perforated Colorectal Cancer].

We investigated the clinicopathological findings of 90 patients with colorectal perforation who underwent emergency surgery between January 2008 and July 2015.T he patients were divided into 2 groups, namely those with perforation due to colorectal cancer(colorectal cancer group, n=20)and those with perforation due to benign colorectal disease(non-colorectal cancer group, n=70).We investigated the clinicopathological findings of the 2 groups.The SOFA score was significantly lower in the colorectal cancer group than in the non-colorectal cancer group.Of the 20 cases of primary cancer, 11 were located in the sigmoid colon; 5, in the rectum; 2, in the transverse colon; 1, in the ascending colon; and 1, in the cecum.The perforation occurred at the tumor site in 8 patients and at the oral site of cancer in 12.Eleven patients had stage II cancer, 1 had stage IIIa, and 8 had stage IV.Ten patients underwent curability A resection; 1, curability B resection; and 8, curability C resection.Recurrence was observed in 6 of the 10 patients who had undergone curability A resection and in 1 patient who had undergone curability B resection.The initial recurrence site was the liver in 3 cases, the peritoneum in 2 cases, and a local site in 2 cases.Even if the patents underwent curative operation, the recurrence rate was high.Therefore, we conclude that adjuvant chemotherapy is required along with careful follow-up.

Intraoperative chylous leak diagnosis by preoperative oral administration of ice cream: a case report.

Background: Chylothorax is an intractable postoperative complication of thoracic surgery. Preventing postoperative chylothorax following initial surgery is important. Most cases of chylothorax are caused by injury to the thoracic duct or its branches. However, rare cases might result from injury to the lymphatic vessels in the chest wall. Preoperative oral administration of dairy products is widely recognized as a useful method for identifying the sites of chylous leaks during surgery for chylothoraces. Herein, we report a surgical case of a middle mediastinal tumor, wherein a chylous leak in the chest wall was intraoperatively detected due to scheduled preoperative oral administration of dairy products before the initial surgery, resulting in prevented postoperative chylothorax. Case Description: A 68-year-old male patient underwent computed tomography, revealing a cystic lesion in the middle mediastinum that was suspected to be a thoracic duct cyst or intrathoracic lymphangioma. A cup of ice cream was orally ingested 1 hour before entering the operating room to intraoperatively detect chylous leakage in case of injury to the lymphatic vessels, including the thoracic duct. The mediastinal tumor was removed via thoracoscopic surgery and histologically diagnosed as a schwannoma with cystic degeneration. Intraoperatively, chylous leakage was observed due to injury to a lymphatic vessel in the chest wall, which was repaired by clipping. The postoperative course was uneventful. Conclusions: Preoperative oral administration of dairy products was verified to be a useful method not only at the time of re-operation for postoperative chylothoraces but also at the time of initial surgery in cases where chylothorax is of high concern. Although relatively infrequent, chylothorax due to lymphatic vessel injury in the chest wall should be kept in mind.

Characterizing soluble immune checkpoint molecules and TGF-ß1,2,3 in pleural effusion of malignant pleural mesothelioma.

The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-ß isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-ß1, TGF-ß2, and TGF-ß3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-ß2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-ß1 and TGF-ß3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.

A case of primary lung adenocarcinoma mimicking metastatic papillary thyroid carcinoma.

A 61-year-old woman, who had a history of total thyroidectomy for follicular variant of papillary thyroid carcinoma (PTC), visited our hospital for assessment of an enlarging nodule which appeared in the lung with multiple metastatic lesions of PTC which had been stable for 17 years. Wedge resection of the lung was performed. Miliary nodules were confirmed to be metastatic PTCs based on their morphological as well as immunohistochemical findings. As for the main nodule, its morphological features suggested a diagnosis of metastatic PTC, while its immunohistochemical findings were identical with primary lung adenocarcinoma. Further genetic analysis provided no definitive information for the diagnosis of the main nodule. The present case shows the need of comprehensive analyses for differentiation between primary lung adenocarcinoma and metastatic PTCs.

NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.

[Left atrial myxoma with a coronary artery steal syndrome due to the coronary artery to left atrial fistula; report of a case].

A 73-year-old woman with dyspnea was diagnosed with a left atrial myxoma by echocardiography. Right and left circumflex coronary angiography showed neovascularity in the tumor and the blood flow jet extending from the tumor to the left atrial cavity, which led to the steal phenomenon in the left anterior descending artery. Surgical excision of the left atrial tumor and the maze procedure were performed with a cardiopulmonary circuit. To our knowledge, this is the 1st study to report the development of the coronary artery steal syndrome due to a cardiac myxoma. Exercise testing would involve risks such as embolism and left ventricular inflow disturbance; furthermore, the presence of concomitant chest symptoms with cardiac myxoma is not rare. Therefore, preoperative coronary angiography would be used for differential diagnosis and for detecting the coronary artery disease, which is reported to be common in patient with cardiac myxomas.

Preoperative neutrophil-to-lymphocyte ratio correlates with PD-L1 expression in immune cells of patients with malignant pleural mesothelioma and predicts prognosis.

We assessed the prognostic value of five complex inflammatory and nutritional parameters, namely neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), C-reactive protein-to-NLR ratio (C/NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) using data from patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP). Moreover, the correlation between these five parameters and programmed cell death protein 1 ligand-1 (PD-L1) expression in the tumor microenvironment was evaluated. This study included consecutive MPM patients who underwent EPP. The histological subtype of the eligible patients (n = 61) correlated with all five parameters. Moreover, the PD-L1 expression scores for immune cells correlated with NLR and PLR, and the PD-L1 expression scores for both tumor cells and immune cells were inversely correlated with both PNI and LMR. Univariate analysis elucidated that NLR, PNI, and C/NLR were predictors of 5-year overall survival (OS), and multivariate analysis revealed that NLR was an independent predictor of 5-year OS, suggesting that NLR is a preoperative, prognostic factor for patients with MPM who are scheduled for EPP. To the best of our knowledge, this is the first study to evaluate the prognostic potentials of NLR, PNI, C/NLR, PLR, and LMR simultaneously in patients with MPM who underwent EPP.

Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy.

OBJECTIVES: Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS: We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS: Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS: Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Prognostic values of preoperative C-reactive protein, albumin, and neutrophil ratios in patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy.

INTRODUCTION: A preoperative validation system for predicting the clinical outcome of extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is required, as EPP for MPM is one of the most invasive operation types. Recently, several inflammatory and nutritional parameters, such as C-reactive protein (CRP) and albumin, have been re-focused on as useful prognostic factors for several types of cancer; however, few of these reports involved MPM. METHODS: As a retrospective study, clinicopathological characteristics and preoperative inflammatory and nutritional parameters were calculated in consecutive patients with MPM who underwent EPP. The prognostic value of the variables was examined using Cox regression, and the candidate preoperative parameters were entered into a multivariate model to determine their independent effects. RESULTS: Of the 61 eligible cases, the CRP/albumin ratio (CAR) was associated with histology, and the CRP index multiplied by the neutrophil ratio (C-NR index) was associated with histology and pathological stage. Patients with CAR >0.125 had a significantly poor survival outcome, and patients with a C-NR index >0.58 also had a significantly poor prognosis. Multivariate analysis showed that age, histology, CRP, albumin, CAR, and C-NR index were independent predictors of 5-year overall survival. CONCLUSION: Our results demonstrated that the CAR and C-NR indices are promising preoperative predictive parameters for the clinical outcomes of EPP in patients with MPM.

Rapid development and rupture of a pneumatocele caused by pulmonary dissection in the early postoperative period of lung resection: a case report.

Air leakage after lung resection is a common complication usually caused by direct injury to the lung parenchyma. Herein we illustrate a case of pneumatocele that developed rapidly in the right middle lobe and ruptured 16 days after right upper lobectomy. A 73-year-old man with chronic obstructive pulmonary disease underwent thoracoscopic right upper lobectomy and partial thymectomy for primary lung cancer and thymic nodules, respectively. Although a small amount of air leakage was observed after the operation, air leakage completely improved on postoperative day (POD) 2, and the chest drain tube was removed on POD 3. The patient's condition was complicated with eosinophilic pneumonia. Steroid therapy was started on POD 13. Dyspnea suddenly developed immediately after defecation on POD 16. Computed tomography (CT) scan showed a large pneumatocele in the right middle lobe, which was not found by CT scan on POD 11. He underwent reoperation on POD 20, and a large thick-walled pneumatocele in the right middle lobe was directly sewn. Histopathologically, the wall of bulla consisted of thickened visceral pleura and thin lung parenchyma, suggesting that this pneumatocele was induced by dissection of subpleural lung parenchyma.

Clinicopathological feature of a resected large mixed squamous cell and glandular papilloma: A case report.

INTRODUCTION AND IMPORTANCE: Solitary endotracheal papilloma is a rare benign lung tumor. It is classified into the following three histological subtypes: squamous cell papilloma (SP), glandular papilloma (GP), and mixed squamous cell and glandular papilloma (MSGP). MSGP is the rarest among them. Herein, we describe a case of a large MSGP. CASE PRESENTATION: A 59-year-old woman underwent computed tomography for the examination of cough, and an 8.2-cm-sized lung mass was noted in the left lingual segment. Bronchoscopy revealed that the left B5 lumen was completely occluded by a tumor. Transbronchial lung biopsy suggested GP; thereafter, a left upper lobectomy was performed. Macroscopic findings showed that the dilated B5 lumen was filled with cauliflower-like tumors. Histopathological findings showed that the majority of the tumors had pseudostratified columnar epithelium, while some had stratified squamous epithelium. The patient was diagnosed with MSGP. Although koilocytosis-like changes, such as perinuclear halo and nuclear deformation, were observed in some portions of the squamous epithelium, immunohistochemical staining was negative for human papillomavirus (HPV). CLINICAL DISCUSSION: HPV infection is reportedly associated with SP but not with GP and MSGP. Therefore, MSGP is considered to be caused by squamous metaplasia of a part of GP; this hypothesis is consistent with the present case. However, only one case of MSGP with HPV infection was recently reported, and the etiology and histological features of MSGP remain unclear. CONCLUSION: There are few reported cases of MSGP, and further case reports are needed to clarify its pathogenesis.

Safety of salvage lung resection after immunotherapy for unresectable non-small cell lung cancer.

BACKGROUND: The safety of salvage lung resection after immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC) is not well understood. METHODS: In this retrospective multicenter study, we reviewed perioperative morbidity and mortality rates in 11 patients (8 men, 3 women; median age 70 years) who underwent salvage lung resection for unresectable NSCLC after ICI therapy in the 4 years since 2017. Operative factors were also compared according to operating time (> 6 h, n = 7; < 6 h, n = 4). RESULTS: The clinical stage at the time of diagnosis was IIIA in 2 patients, IIIB in 4, IVA in 2, and IVB in 3. Eight patients received pembrolizumab and 3 received durvalumab. Two patients received an ICI agent alone, 3 underwent chemoradiotherapy, and 6 received chemotherapy. Lobectomy was performed in 10 cases and bilobectomy in 1 case. All patients underwent complete resection. Median operating time was 429 (range 169-570) min with a median blood loss of 199 (range 10-5, 140) mL. The only intraoperative complication was damage to the pulmonary artery. The perioperative morbidity and mortality rates were 27% and 0%, respectively. The 90-day mortality rate was 9% (1 patient died of acute exacerbation of interstitial pneumonia). Patients in whom the operating time was > 6 h more frequently had lymph node metastasis at the time of initial diagnosis (100% vs 25%, p = 0.02). CONCLUSIONS: Salvage lung resection was tolerated after ICI therapy in these patients. Lymph node metastasis at the time of initial diagnosis might make salvage surgery difficult.

Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer.

BACKGROUND: In survivors of head and neck cancer (HNC), second primary lung cancer (SPLC) often develop as a result of a common risk factor, that is, smoking. A multicenter experience was reviewed to evaluate how the history of a diagnosis of HNC affects the outcomes of patients undergoing pulmonary resection for SPLC. METHODS: A multicenter retrospective analysis of patients hospitalized between January 2012 and December 2018 was performed. From a cohort of 4521 patients undergoing therapeutic pulmonary resection for primary non-small cell lung cancer, 100 patients with a previous history of HNC (HNC group) were identified. These patients were compared with a control group consisting of 200 patients without an HNC history from the same cohort pair-matched with operating facility, age, sex, and pathologic stage of lung cancer. RESULTS: At the time of surgery for SPLC, the HNC group showed malnutrition with a lower prognostic nutritional index compared with the control group (P < .001). The HNC group was determined to have postoperative complications more frequently (P = .02). The 5-year overall survival rates in the HNC and control groups were 59.0% and 83.2%, respectively (P < .001). Statistically, HNC history, lower prognostic nutritional index, squamous cell lung cancer, and TNM stage were identified to be independently associated with poor survival. CONCLUSIONS: Patients with SPLC after primary HNC often present with malnutrition and are predisposed to postoperative complications and poor survival after pulmonary resection.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT).

PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.