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.

Identification of the Best Prognostic Marker Among Immunonutritional Parameters Using Serum C-Reactive Protein and Albumin in Non-Small Cell Lung Cancer.

BACKGROUND: Three immune-nutritional parameters exist for malignant tumors using serum C-reactive protein (CRP) and albumin: the Glasgow prognostic score (GPS), the modified GPS (mGPS), and the CRP-albumin ratio (CAR). However, it remains unclear which of the three parameters is the most predictive of prognosis. Therefore, this study compared the clinical and prognostic significance of these parameters for non-small cell carcinoma (NSCLC). METHODS: The study retrospectively enrolled 596 NSCLC patients who underwent surgical resection at the authors' institution from January 2010 to December 2015 and investigated the clinicopathologic significance of GPS, mGPS, and CAR. The optimal cutoff value for CAR was determined by a receiver operating curve (ROC). RESULTS: The median age of the patients was 69 years. Lymph node metastases were identified in 99 patients, and 455 patients had a diagnosis of stage 1 disease. The positivity for GPS was 7.6%, and that of mGPS (score, 1 or 2) was 12.2%. Of the 596 patients, 480 patients (80.5%) were classified in the high CAR group. In univariate survival analyses, all three parameters were associated significantly with postoperative survival. The multivariate analyses showed CAR to be an independent prognostic factor. Additionally, survival analyses of the stage 1 subgroup were performed because CAR was higher for patients with an advanced stage of disease or lymph node metastases. In these subgroup analyses, CAR also was an independent prognostic factor. CONCLUSION: As the most prognostic index, CAR may be useful among the immunonutritional parameters using CRP and albumin for resected NSCLC.

Pulmonary Resection for a Residual Tumor after Definitive Radiation in Locally Advanced Non-Small Cell Lung Cancer.

OBJECTIVE AND METHODS: To clarify the benefits of surgery for a persistent tumor following definitive radiation in locally advanced non-small cell lung cancer, five patients were retrospectively reviewed. RESULTS: All patients received definitive radiation, and three received concurrent chemotherapy followed by anatomical lung resection for a residual local tumor. The median time from the radiation to surgery was 8.2 weeks. There were no postoperative mortalities. Four patients developed distant metastasis with a mean recurrence-free interval of 7.5 months. CONCLUSIONS: Distant metastasis frequently occurred within a relatively short period after surgery. Further studies with a larger sample size are needed.

A Case of Tension Subcutaneous Emphysema Treated With Minimally Invasive Open-Window Thoracostomy Using a Wound Protector/Retractor and Three-Sided Taping.

Subcutaneous emphysema is a common complication of thoracic surgery. Tension subcutaneous emphysema that causes airway obstruction is rare but life-threatening. This report presents a patient who developed tension subcutaneous emphysema after recurrent secondary pneumothorax surgery which was treated with minimally invasive open-window thoracostomy. A wound protector/retractor and three-sided taping were successfully used to prevent air from entering the subcutaneous space via the wound while draining trapped air without creating an open pneumothorax. This approach is an option for managing subcutaneous and intrathoracic air leakage in emergency situations.

BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression.

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.

Multicenter, Retrospective Study to Evaluate Necitumumab Plus Cisplatin and Gemcitabine After Immune Checkpoint Inhibitors in Advanced Squamous Cell Lung Cancer in Japan: The NINJA Study.

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.

Prediction of true-negative lymph node metastasis in clinical IA non-small cell lung cancer by measuring standardized uptake values on positron emission tomography.

PURPOSE: We developed a method for predicting true-negative lymph node metastases in clinical IA non-small lung cancer (NSCLC) by the combined evaluation of computed tomography (CT), 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) findings and the maximum standardized uptake value (SUVmax) of primary tumors. METHODS: The subjects of this study were 94 patients with clinical stage IA NSCLC who underwent both preoperative CT and FDG-PET. We analyzed the relationship between the SUVmax of primary tumors and various clinicopathological factors to find the best method available for assessing true-negative lymph node metastasis. RESULTS: The pathological stages were IA (n = 80), IB (n = 4), IIA (n = 5), IIIA (n = 4), and IV (n = 1). Pathologic lymph node metastasis was recognized in nine patients and the SUVmax of these tumors ranged from 3.3 to 20.3. A SUVmax of 3.0 was defined as the cut-off point and patients were dichotomized according to this point. Tumors with SUVmax of 3.0 or less were associated with a significantly lower incidence of pleural and vascular invasion and were characterized by the degree of differentiation. CONCLUSION: The SUVmax of primary tumors reflects the grade of malignancy; therefore, the combined evaluation of FDG-PET/CT findings with the SUVmax of primary tumors may help predict lymph node metastasis negativity.

Case report: Success of tepotinib therapy in overcoming resistance to osimertinib in a patient with EGFR-mutant lung adenocarcinoma with a potential acquired MET exon 14 skipping mutation.

Osimertinib is a standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor gene (EGFR) mutations, but most patients with EGFR-mutant NSCLC develop secondary resistance to osimertinib. Mesenchymal-epithelial transition gene (MET) alterations and oncogene fusions have been identified as the most common mechanisms of resistance to osimertinib. However, MET exon 14 skipping mutation (METex14del) as an acquired resistance to osimertinib has rarely been reported. A non-smoking 76-year-old woman was diagnosed with lung adenocarcinoma in the right lower lobe (cT2bN2M1c [pulmonary and bone metastases], cStage IVB). The primary tumor was submitted to cobas® EGFR Mutation Test v2 (Roche Diagnostics Ltd.), next generation sequencing (Oncomine Comprehensive Assay v3; Thermo Fisher Scientific), the AmoyDx® Essential NGS panel (Amoy Diagnostics, Xiamen, China), all of which were positive for EGFR L858R and de novo T790M. We administered daily osimertinib (80 mg/day), and achieved a partial response. However, after 14.0 months, computed tomography showed progression of the primary tumor and lung metastases. Re-biopsy of the primary tumor was conducted, and the specimen was submitted to Archer®MET companion diagnostic for detection of METex14del. Although the primary tumor was negative for METex14del, the re-biopsy specimen was positive for METex14del. We validated that the biopsy specimen of the primary tumor at diagnosis before osimertinib administration was negative for METex14del using local reverse transcription PCR. We administered daily tepotinib (500 mg/day) to the patient as a further-line treatment, and achieved a partial response (tumor shrinkage rate: 34.5%) after 2.0 months, who responded to tepotinib therapy for 8.0 months. We described a patient with lung adenocarcinoma harboring METex14del as a potential acquired resistance to osimertinib, who responded to subsequent tepotinib therapy. Re-biopsy and re-analysis of genetic profiles should be considered in NSCLC patients who develop osimertinib resistance.

Artificial intelligence-derived gut microbiome as a predictive biomarker for therapeutic response to immunotherapy in lung cancer: protocol for a multicentre, prospective, observational study.

INTRODUCTION: Immunotherapy is the fourth leading therapy for lung cancer following surgery, chemotherapy and radiotherapy. Recently, several studies have reported about the potential association between the gut microbiome and therapeutic response to immunotherapy. Nevertheless, the specific composition of the gut microbiome or combination of gut microbes that truly predict the efficacy of immunotherapy is not definitive. METHODS AND ANALYSIS: The present multicentre, prospective, observational study aims to discover the specific composition of the gut microbiome or combination of gut microbes predicting the therapeutic response to immunotherapy in lung cancer using artificial intelligence. The main inclusion criteria are as follows: (1) pathologically or cytologically confirmed metastatic or postoperative recurrent lung cancer including non-small cell lung cancer and small cell lung cancer; (2) age≥20 years at the time of informed consent; (3) planned treatment with immunotherapy including combination therapy and monotherapy, as the first-line immunotherapy; and (4) ability to provide faecal samples. In total, 400 patients will be enrolled prospectively. Enrolment will begin in 2021, and the final analyses will be completed by 2024. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board of each participating centre in 2021 (Kyushu Cancer Center, IRB approved No. 2021-13, 8 June 2021 and Kyushu Medical Center, IRB approved No. 21-076, 31 August 2021). Study results will be disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION NUMBER: UMIN000046428.

Dedifferentiated chondrosarcoma of the lung: report of a case.

This report presents a rare case of pulmonary sarcoma with regional anaplastic changes. A 73-year-old Japanese man with a hamartoma-like nodule of the left lung accompanied by interstitial pneumonia was followed up for 30 months. He underwent a surgical resection due to the rapid growth of the lung nodule. A pathological examination revealed a dedifferentiated sarcoma arising from the chondrosarcoma.

Effectiveness of erlotinib against recurrent pulmonary adenocarcinoma unresponsive to gefitinib: report of a case.

We report a case of recurrent pulmonary adenocarcinoma, found 2 years after resection, which responded extremely well to erlotinib, after gefitinib treatment had failed to evoke any response. This case report provides useful information for thoracic oncologists and shows that we should consider giving erlotinib after gefitinib for recurrent pulmonary adenocarcinoma, even if the gefitinib treatment is ineffective.

Assessing a clinical pathway to improve the quality of care in pulmonary resections.

PURPOSE: To evaluate the efficacy of the current clinical pathway for pulmonary resections. METHODS: This study examined variances from expected clinical pathway outcomes for pulmonary resections performed between 2005 and 2009. Data on a total of 383 patients were retrospectively analyzed. RESULTS: The median length of hospital stay (LOS) using the clinical pathway was 12 days (range: 1-188 days); the mean LOS was 15.5 days. The cost per day with use of the clinical pathway was 102 726 yen. Poor control of pain from intercostal neuralgia was the most frequently observed variance from expected outcomes. It affected 119 of 168 electronic clinical pathway patients (70.8%). The clinical pathway was terminated in 3.9% of patients (15/383) due to serious or life-threatening complications. CONCLUSIONS: This study showed the single institutional experience of the clinical pathway for pulmonary resections. These findings indicate a need to revise certain aspects of the pathway, based on data from our analysis of variances.

The influence of intracellular epidermal growth factor receptor (EGFR) signal activation on the outcome of EGFR tyrosine kinase inhibitor treatment for pulmonary adenocarcinoma.

PURPOSE: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, exhibit up to a 70% response rate against non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the EGFR gene (EGFR). The mechanism of intrinsic resistance of EGFR mutation-positive NSCLC against EGFR-TKIs is not known. The current study assesses the relationship between the molecular expression of EGFR signals and the response to gefitinib treatment in patients with pulmonary adenocarcinoma to elucidate the mechanism of intrinsic resistance to gefitinib. METHODS: The present study included 30 patients with pulmonary adenocarcinoma who were treated with gefitinib for a postoperative recurrence. The correlation between the response to gefitinib treatment and various clinical and molecular features was evaluated. RESULTS: EGFR mutations were detected in 20 (66.7%) of the 30 patients. The response to gefitinib treatment was a complete response in 1 case, partial response in 12 cases, stable disease in 4 cases, and progressive disease in 13 cases. Both univariate and multivariate analyses showed the presence of an EGFR mutation, and the expression of phospho-EGFR (p-EGFR) significantly correlated with a better response to gefitinib treatment. Ten of the 16 p-EGFR positive patients were disease controlled, but all 4 p-EGFR negative patients were intrinsically resistant to EGFR-TKIs (P = 0.025). Other factors including sex, smoking status, serum carcinoembryonic antigen and cytokeratin-19 fragment levels, EGFR, Met proto-oncogene, phospho-Met, and hepatocyte growth factor expression were not associated with the response to gefitinib treatment. CONCLUSION: These results suggest that, even if EGFR mutations were observed, a p-EGFR negative state might be a cause of intrinsic resistance to EGFR-TKIs.

Targeted Therapy for RET Fusion Lung Cancer: Breakthrough and Unresolved Issue.

Molecular drugs targeting mutated or rearranged oncogene drivers have become one of the standard recognized treatments in patients with advanced and recurrent non-small cell lung cancer. RET is located in the long arm of human chromosome 10 and encodes a receptor tyrosine kinase protein, and RET fusion-positive lung adenocarcinoma occurs in 1%-2% of cases. Clinical trials of multikinase inhibitors, including cabozantinib, vandetanib, sorafenib, and lenvatinib, that inhibit RET oncogene activity have shown their antitumor efficacy. Recently, RET inhibitors such as pralsetinib and selpercatinib that are specialized for RET kinase have also been developed, and their efficacy was investigated in previous clinical trials (BLU-667 and LOXO-292). In this review, we summarized the effects and adverse events of multikinase and selective RET inhibitors and the various diagnostic techniques for RET gene fusion. In the perspective part, we focused on the unsolved issues on treatment for RET fusion-positive lung cancer and future developments.

Successful treatment of locally advanced lung cancer using late concurrent chemoradiation therapy administered after immune checkpoint inhibitor plus platinum chemotherapy.

Concurrent chemoradiation therapy (CRT) is the standard of care for patients with unresectable stage II/III lung cancer. However, systemic chemotherapy is required for patients who are ineligible for radical radiation therapy. There is little evidence to date for the safety and efficacy of CRT administered after treatment with immune checkpoint inhibitors (ICIs). The cases reported here had inoperable stage III lung cancer (non-small cell lung cancer and small cell lung cancer) and were ineligible for radical radiation therapy. They were administered ICIs plus chemotherapy and subsequently underwent late concurrent CRT. Because of the remarkable tumor shrinkage achieved by the ICIs plus chemotherapy, adverse events of CRT were tolerable. They were alive without tumor progression as of this report, over 1 year after CRT was terminated. CRT is administered with curative intent, while the intent of immunochemotherapy is palliative. Late concurrent CRT after immunochemotherapy is probably effective and tolerable. After treatment with systemic chemotherapy in patients judged ineligible for radical radiation therapy, radiation therapy should be reconsidered because of its importance once tumor shrinkage has been achieved.

Anti-PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status.

PURPOSE: Anti-programmed death 1 (PD-1) antibodies have emerged as frontline treatments for patients with advanced non-small cell lung cancer (NSCLC) on the basis of global Phase III trials. However, current data regarding responses to anti-PD-1 therapy in older patients with NSCLC or those with poor performance status (PS) are limited. Therefore, we examined the therapeutic effect of anti PD-1 antibody in these patients. PATIENTS: We retrospectively examined consecutive patients treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) from January 2016 to September 2018. RESULTS: We enrolled 125 patients (median age, 60 years), 80.8% of whom were men. Patients aged ≥75 years were considered older patients (n = 15), and those with PS 2-3 were regarded as having poor PS (n = 11). The objective response and disease control rates were 15.4% and 46.2%, respectively, in older patients and 9.1% and 27.3%, respectively, in those with poor PS. Progression-free survival (PFS) and overall survival (OS) did not significantly differ between older and younger patients. However, poor PS was significantly associated with poor survival. High programmed death ligand 1 (PD-L1) expression in tumor specimens (≥50%) was associated with favorable survival in the entire cohort as well as patients with poor PS. Safety analyses demonstrated no significant difference in the occurrence of any adverse event, including grade ≥3 adverse events, between patients with poor PS or older age and the remaining patients. CONCLUSION: Anti-PD-1 therapy had similar efficacy in older and younger patients with NSCLC, whereas survival was significantly worse in patients with poor PS. However, immune checkpoint inhibitors may be considered for patients with poor PS harboring positive PD-L1 expression.

Dramatic intracranial response to tepotinib in a patient with lung adenocarcinoma harboring MET exon 14 skipping mutation.

Mesenchymal-epithelial transition (MET) pathway activation is associated with the mechanisms that influence properties affecting cancer cell survival and invasiveness. The MET exon 14 skipping mutation (METex14del) is found in 2%-3% of patients with non-small cell lung cancer (NSCLC). Previous studies reported that NSCLC patients harboring a METex14del responded well to MET-tyrosine kinase inhibitors (TKIs), including tepotinib. Tepotinib is a highly selective, once-daily oral MET inhibitor that has shown promising clinical activity in patients with NSCLC with METex14del. The Food and Drug Administration accepted a new drug application for tepotinib as a treatment for patients with metastatic NSCLC harboring METex14del in February 2021 [Correction added on 5 March 2021, after first online publication: the FDA approval date for tepotinib has been corrected from 'September 2019' to 'February 2021'.]. However, in the previous clinical trials involving MET-TKIs, only patients with stable central nervous system metastases were eligible, and those with untreated symptomatic brain metastases (BMs) were excluded. Therefore, the efficacy and safety of MET-TKIs in that population remains unknown. We herein report a case of dramatic intracranial response to tepotinib in a patient with symptomatic BMs from lung adenocarcinoma harboring METex14del. In the current report, the symptoms derived from multiple BMs (headache and loss of appetite) rapidly disappeared, and brain magnetic resonance imaging (MRI) examination showed that all the lesions were too small to measure only 23 days after the commencement of tepotinib. For NSCLC patients with multiple BMs, whole-brain irradiation is a standard-of-care therapy, but its adverse effects on neurocognition are concerning. Tepotinib might therefore be a therapeutic option for NSCLC patients with symptomatic multiple BMs harboring METex14del.

Clinical course and prognosis of patients with lung cancer who develop anticancer therapy-related pneumonitis.

BACKGROUND: Pneumonitis can be triggered by anti-cancer therapies: cytotoxic chemotherapy, tyrosine kinase inhibitors, and immune checkpoint inhibitors. There are few treatment options for patients who develop such pneumonitis and their treatment including chemotherapy is generally difficult thus would limit patient's prognosis. In this study, we investigated the clinical course of patients with lung cancer who developed anti-cancer therapy-related pneumonitis. PATIENTS AND METHODS: We retrospectively examined data of patients who had developed pneumonitis triggered by anti-cancer agents and required hospitalization from January 2014 to March 2019 and analyzed their subsequent clinical course and prognosis. RESULTS: The median age of the 58 study patients was 68 years and 82.8% were men. The median interval between first receiving the responsible agent and drug-induced pneumonitis was 7.4 weeks. Approximately 38% of patients were subsequently able to receive some anti-cancer therapy. The median post-pneumonitis overall survival (OS) from commencement of anti-cancer treatment was 13.2 months. No significant differences were found in survival time between treatment agents. However, patients who received some anticancer therapy after pneumonitis had significantly longer survival times than those did not (HR = 4.11, p = 0.0003) and patients who took longer to develop pneumonitis had a longer survival (HR = 2.28, p = 0.0148). Multivariate analysis revealed that short interval to onset and no post-pneumonitis anticancer therapy were independent predictors of short survival. CONCLUSION: Although patients who developed pneumonitis had relatively short survival times, the interval between initial therapy and pneumonitis had survival impact. Survival can be prolonged by administering further cancer treatment after resolution of pneumonitis.

Sarcoid-like reaction of the extrathoracic lymph node in a patient with lung adenocarcinoma treated with pembrolizumab.

Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of non-small cell lung cancer (NSCLC). With the increasing use of ICIs, clinicians should be familiar with their immune-related adverse events, including sarcoid-like reactions, which have been associated with the use of ICIs in patients with cancer. Sarcoid-like reactions are caused by uncontrolled T helper 1-mediated immune responses resulting from ICIs, but their pathophysiology is not fully understood. Sarcoid-like reactions are often clinically important because they mimic metastases from treated cancer. According to previous reports, sarcoid-like reactions are typically observed in intrathoracic locations (lung and/or mediastinal lymph nodes) and the skin. In this study, we report an extremely rare case of extrathoracic sarcoid-like reaction in the right external iliac lymph node following two cycles of pembrolizumab therapy in a patient with lung adenocarcinoma. The laboratory data and computed tomography images suggested that infectious and autoimmune diseases were not considered to be the causative agents. Residual bone metastasis might have caused T helper 1-mediated immune responses by pembrolizumab, and contributed to sarcoid-like reactions in the right external iliac lymph node. Sarcoid-like reactions should be considered in the differential diagnosis of patients with lung cancer treated with ICIs who exhibit worsening extrathoracic lymph node swelling. Clinicians should be cautious not to mistake extrathoracic sarcoid-like reactions of the lymph nodes for progression of the treated disease.

Clinical utility of pretreatment Glasgow prognostic score in non-small-cell lung cancer patients treated with immune checkpoint inhibitors.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) have become one of the standard therapies in non-small-cell lung cancer (NSCLC). Although inflammatory indices, including Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein/albumin ratio (CAR) were reported to be reliable predictors for survival in cancer patients, their clinical utility in NSCLC patients treated with ICIs is unknown. MATERIALS AND METHODS: Advanced or recurrent NSCLC patients (n = 304) treated with ICI monotherapy at the National Hospital Organization Kyushu Cancer Center and Kyushu University Hospital between January 2016 and December 2019 were analyzed. Information on patient demographics, GPS, mGPS, and CAR at diagnosis were collected. The time-dependent area under curves (AUCs) of receiver operating characteristic curves for the prediction of overall survival (OS) for each factor were compared. RESULTS: Of the three indices, GPS was the most significantly correlated with the degree of disease control rate (DCR) (DCR of GPS of 0, 1, and 2: 63.6 %, 49.4 %, and 41.4 %, respectively). The time-dependent AUC values of GPS for the prediction of OS were superior to those of mGPS and CAR (time-dependent AUC values of GPS, mGPS, and CAR for the prediction of 1-year OS: 0.7005, 0.6736, and 0.6565, respectively). GPS was significantly correlated with performance status (PS) (P < 0.0001) and clinical stage (P = 0.0139). GPS in combination with PS effectively predicted survival at 1 year ranging from 83.5 % (GPS = 0, PS = 0) to 25.0 % (GPS = 2, PS = 2, 3). A multivariable analysis revealed that GPS was an independent predictor of PFS and OS (P = 0.0009 and P = 0.0100, respectively). CONCLUSIONS: We report for the first time that GPS represents a simple and useful prognostic factor in NSCLC patients treated with ICIs and should be validated prospectively.