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Abstract Background Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors.

Abstract Background The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non‐small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9‐in‐1 assay, a preapproval assay of the AmoyDx PLC panel. Methods We retrospectively collected data of NSCLC patients enrolled in LC‐SCRUM‐Asia from the Shizuoka Cancer Center between September 2019 and May 2021. Results A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9‐in‐1 and next‐generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9‐in‐1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9‐in‐1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9‐in‐1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS. Conclusion FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay.

Abstract Background To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

ABSTRACT Background Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable gene alterations in non‐small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non‐squamous NSCLC have EGFR mutations. However, no long‐term studies have been conducted including a large number of EGFR‐positive NSCLC patients with postoperative recurrence (PR). Methods We conducted a retrospective observational study of the data of EGFR‐positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post‐recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan–Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis. Results We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82–13.25) and POS was 5.81 years (range, 2.84–16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90–5.61) and POS was 7.07 years (95% CI, 5.88–8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; p

Abstract The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647–1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648–1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.

Abstract Background Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)‐SCLC, to assess whether conventional NE markers are predictive of ICIs. Methods Patients with untreated ED‐SCLC who received first‐line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first‐line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI‐chemo group) and with chemotherapy alone (chemo group). Results A total of 227 patients were included in the ICI‐chemo and chemo groups, respectively. The progression‐free survival (PFS) tended to be better in patients in the ICI‐chemo group than those treated with chemotherapy alone in patients with NE marker‐positive SCLC. In particular, it was statistically significant in patients with chromogranin A‐positive SCLC (p = 0.036). In patients with NE marker‐negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. Conclusion Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker‐negative SCLC.

Abstract Background Amrubicin (AMR) regimens have shown efficacy as second‐line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P‐PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P‐PEG as second‐line chemotherapy for SCLC. Methods We retrospectively reviewed patients with SCLC who received AMR as second‐line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P‐PEG in their regimen, patients (n = 60) were divided into P‐PEG (n = 21) and non‐P‐PEG groups, and their clinical outcomes were evaluated. Results Median of AMR treatment cycles was five (range: 1–39 cycles) in P‐PEG group and four (range: 1–15 cycles) in non‐P‐PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P‐PEG group than in the non‐P‐PEG group. The objective response rates were 52.4% and 30.8%, and median progression‐free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P‐PEG and non‐P‐PEG groups, respectively. Conclusions AMR with P‐PEG as second‐line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P‐PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

Abstract Background Tyrosine kinase inhibitors (TKIs) are effective for the treatment of non‐small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR), but responses are not durable as tumors develop resistance. DS‐1205c is a novel, specific, orally bioavailable, small‐molecule AXL receptor TKI. In preclinical studies, DS‐1205c restored TKI antitumor activity in a TKI acquired‐resistance EGFR‐mutant NSCLC tumor xenograft model. Methods This first‐in‐human, multicenter, open‐label Phase 1 study (registered at ClinicalTrials.gov: NCT03599518) primarily evaluated the safety and tolerability of combination therapy with DS‐1205c and gefitinib in Japanese patients with metastatic or unresectable EGFR‐mutant NSCLC and tumor progression during treatment with EGFR‐TKIs. Patients (n = 20) received DS‐1205c monotherapy (200–1200 mg twice daily [BID]) in a 7‐day safety monitoring period before combination DS‐1205c/gefitinib (250 mg once daily) in 21‐day cycles. Results The observed common treatment‐emergent adverse events (TEAEs) were increased aspartate aminotransferase (35%), increased alanine aminotransferase (30%), rash maculo‐papular (30%), and diarrhea (25%). No serious TEAEs were reported. Plasma concentrations and pharmacokinetic parameters of DS‐1205a (free form of DS‐1205c) were unaffected by concomitant administration of gefitinib. No patient achieved a complete or partial response and 5 patients (25%) had stable disease. Conclusion DS‐1205c was generally safe and well tolerated at all dose levels, but the safety profile of ≤800 mg BID was more favorable than 1200 mg BID. The recommended dose for dose‐expansion cohorts of DS‐1205c in combination therapy with gefitinib was 800 mg BID.

Abstract Carboplatin plus etoposide is a standard treatment for older extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES‐SCLC with PS ≥2, aged ≥71 years, who had received first‐line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3–4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression‐free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0–1 post‐treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression‐free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment‐related death was observed in the PS ≥3 group. The progression‐free survival of patients administered prophylactic granulocyte colony‐stimulating factor (G‐CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression‐free and overall survival in older ES‐SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G‐CSF administration, may be necessary to ensure safety and survival.

Abstract Background Programmed cell death 1 (PD‐1)/programmed cell death ligand (PD‐L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non‐small‐cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown. Methods We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values. Results Sixty‐eight patients (74%) had progressive disease or died. Forty‐four patients (48%) in the low‐BSLD group had a median progression‐free survival (PFS) of 9.5 months, whereas patients in the high‐BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty‐five patients (27%) in the low‐BNML group had a median PFS of 9.6 months, whereas patients in the high‐BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low‐BSLD and low‐BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low‐ (N = 13), medium‐ (N = 42) and high‐burden (N = 37) groups respectively. Conclusions Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.

Abstract Background Despite improvement in the overall survival of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, the effects of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment on bone metastasis remain unclear. This study investigated radiological responses to gefitinib regarding bone metastasis in patients. Methods We treated 260 patients with NSCLC and symptomatic bone metastasis. Thirty-seven patients harboring EGFR mutation were treated with gefitinib for more than 30 days and followed up for more than 3 months (GEF group). We performed a retrospective observational study by selecting 36 cases without EGFR-TKI treatment, at least 3 months of follow-up, and at least two radiological evaluations as the control group. We assessed the best overall radiological response, interval from treatment initiation to appearance of a radiological response, and the local response maintenance rate. Results The best effect in the GEF group was 98% partial response or better, which was significantly higher than the 57% observed in the control group (p

Abstract Background Cancer cachexia and tumor burden predict efficacies of programmed cell death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitors and chemotherapy or pembrolizumab in non‐small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden. Methods In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first‐line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression‐free survival (PFS) and overall survival (OS). Results A total of 157 patients were included in the present study (75 treated with PD‐1/PD‐L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD‐L1 tumor proportion scores

Purpose: This study aimed to clarify the characteristics of and evaluate the risk factors for radiation pneumonitis (RP) induced by chemoradiation therapy (CRT) using accelerated hyperfractionated (AHF) radiation therapy (RT) in patients with limited-stage small cell lung cancer (LS-SCLC). Methods and Materials: Between September 2002 and February 2018, 125 patients with LS-SCLC were treated with early concurrent CRT using AHF-RT. Chemotherapy was comprised of carboplatin/cisplatin with etoposide. RT was administered twice daily (45 Gy/30 fractions). We collected data regarding onset and treatment outcomes for RP, and analyzed the relationship between RP and total lung dose–volume histogram findings. Uni- and multivariate analyses were performed to assess patient- and treatment-related factors for grade ≥2 RP. Results: The median age of patients was 65 years, and 73.6% of participants were men. In addition, 20% and 80.0% of participants presented with disease stage II and III, respectively. The median follow-up time was 73.1 months. Grades 1, 2, and 3 RP were observed in 69, 17, and 12 patients, respectively. Grades 4 to 5 RP were not observed. RP was treated with corticosteroids in patients with grade ≥2 RP, without recurrence. The median time from initiation of RT to onset of RP was 147 days. Three patients developed RP within 59 days, 6 within 60 to 89 days, 16 within 90 to 119 days, 29 within 120 to 149 days, 24 within 150 to 179 days, and 20 within ≥180 days. Among the dose–volume histogram parameters, the percentage of lung volume receiving >30 Gy (V30) was most strongly related to the incidence of grade ≥2 RP, and the optimal threshold to predict RP incidence was V30 ≥20%. On multivariate analysis, V30 ≥20% was an independent risk factor for grade ≥2 RP. Conclusions: The incidence of grade ≥2 RP correlated strongly with a V30 of ≥20%. Contrarily, the onset of RP induced by concurrent CRT using AHF-RT may occur later. RP is manageable in patients with LS-SCLC.

Abstract Background Adipose tissue induces inflammation, which desensitizes the efficacy of immunotherapy. However, several reports show that the therapeutic effect of programed cell death 1 (PD‐1)/programed death‐ligand 1 (PD‐L1) inhibitor(s) monotherapy is significantly better in obese patients. Therefore, the effect of adipose tissue on immunotherapy is unclear. Methods In this study, we retrospectively reviewed patients with advanced non‐small cell lung cancer (NSCLC) who received PD‐1/PD‐L1 inhibitor monotherapy between May 2016 and December 2018. We classified patients into total adipose tissue maintenance or loss groups according to adipose tissue change during the 6 months before treatment and compared the therapeutic effect of PD‐1/PD‐L1 inhibitors between these groups along with the presence or absence of cachexia, a poor prognostic factor. Results Of the 74 patients, 40 (54.1%) were cachexic. Among cachexic patients, we found no clear difference in the overall response rate (ORR) and progression‐free survival (PFS) between the total adipose tissue maintenance and loss group. However, among noncachexic patients, the total adipose tissue loss group had a higher ORR (64.7% vs. 23.5%, p

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are currently the primary treatment option for patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). However, the effect of EGFR‐TKIs are eventually weakened due to resistance, and there is also a differential efficacy based on EGFR mutation subtypes. The combination of angiogenesis inhibitor (AI) with EGFR‐TKI has shown better efficacy than EGFR‐TKI monotherapy, regardless of the mutation subtypes. Nevertheless, the effect of AI eligibility on overall survival (OS) and progression‐free survival (PFS) remains to be elucidated. Thus, we assessed this impact on patients with NSCLC harboring EGFR mutation. Methods In this study, the data for 450 patients with EGFR‐mutant NSCLC, who were treated with EGFR‐TKI monotherapy, were retrospectively analyzed for AI eligibility. The patients were categorized into AI‐eligible (AI fit) and ineligible groups (AI unfit). Results The median PFS of the AI fit group was 12.9 months, compared to 9.6 months in the unfit group (p = 0.007), and OS was also significantly longer in the AI fit group (median OS = 33.0 months) compared to that in the unfit group (18.5 months, p

Abstract Background Local ablative therapy (LAT) may be beneficial for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with oligo-residual disease after treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI). However, this has not been fully established. This study aimed to evaluate the predominant progressive disease (PD) pattern limited to residual sites of disease after treatment with EGFR-TKI. Methods Patients with advanced EGFR-mutated NSCLC treated with EGFR-TKIs as first-line therapy were retrospectively analysed during a 7-year period. Oligo-residual disease was defined as the presence of 1 – 4 lesions (including the primary site) at 3 months from the start of EGFR-TKI treatment. The predictive factors of PD patterns after EGFR-TKI treatment were evaluated. Results A total of 207 patients were included. Three months after the start of EGFR-TKI treatment, 66 patients (32%) had oligo-residual disease. A total of 191 patients had PD, 60 with oligo-residual disease and 131 with non-oligo-residual disease. Regarding the pattern, 44 patients (73%) with oligo-residual disease and 37 patients (28%) with non-oligo-residual disease had PD limited to the residual sites. Multivariate logistic regression analysis at 3 months from the start of EGFR-TKI treatment revealed that oligo-residual disease (P

ABSTRACT Telisotuzumab vedotin (formerly ABBV‐399) is an antibody‐drug conjugate targeting c‐Met–overexpressing tumor cells, irrespective of MET gene amplification status. Safety, pharmacokinetics, and preliminary efficacy of telisotuzumab vedotin were evaluated outside of Japan. This phase 1 open‐label study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of telisotuzumab vedotin in Japanese patients with advanced solid tumors. Telisotuzumab vedotin was administered intravenously at either 2.4 mg/kg (n = 3) or 2.7 mg/kg (n = 6) every 3 weeks, following a 3 + 3 design. Maximum tolerated dose was not reached on the basis of the study design; no dose‐limiting toxicity events were observed. The most common treatment‐emergent adverse events related to telisotuzumab vedotin were peripheral sensory neuropathy (44%), and nausea, decreased appetite, and decreased white blood cell count (33% each). Most frequent grade ≥3 treatment‐emergent adverse events, irrespective of relationship to telisotuzumab vedotin, were decreased neutrophil count and hypoalbuminemia, reported in two patients (22%) each. Systemic exposure of telisotuzumab vedotin at both dose levels was approximately dose proportional. Pharmacokinetic profile in Japanese patients was similar to that previously reported in non‐Japanese patients. Two (22%) patients achieved a partial response, six (67%) had stable disease, one (11%) had progressive disease. Overall disease control rate was 89% (eight of nine patients; 95% confidence interval: 51.8%–99.7%]). Median progression‐free survival was 7.1 months (95% confidence interval: 1.2–10.4). In conclusion, telisotuzumab vedotin demonstrated a manageable safety profile, with antitumor activity in Japanese patients with advanced solid tumors; the recommended phase 2 dose was confirmed as 2.7 mg/kg every 3 weeks. ClinicalTrials.gov registration number: NCT03311477.

Abstract Background Patients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy. Methods We retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016. Results In the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P

Objective: Days spent at home (DASH) near the end of life is considered an important patient-centered goal and outcome because many patients want to stay at home toward the end of life. This study aimed to estimate the individual DASH near the end of life and identify its early predictors, including muscle mass and physical function, among elderly patients with advanced non-small-cell lung cancer (NSCLC). Methods: We conducted a post hoc analysis of the prospective observational study (UMIN000009768) that recruited patients aged ≥ 70 years who were scheduled to undergo first-line chemotherapy because of advanced NSCLC. We measured the muscle mass by bioelectrical impedance analysis at baseline. DASH was calculated as 30 days minus the number of days spent in hospitals, palliative care facilities, or nursing homes during the last 30 days of life. We performed linear regression analyses to evaluate the predictors of DASH. Results: Altogether, 16 women and 28 men with a median overall survival of 15.5 months (range: 2.9–58.9) were included. The median DASH in the last 30 days of life was 8 days (range: 0–30, interquartile range: 0–23). Men had longer DASH than women by 7.3 days. Patients who had good trunk muscle mass index and hand-grip strength had significantly longer DASH than those who did not (4.7 days per kg/m2 increase [P = 0.017] and 0.4 days per kg increase [P = 0.032], respectively). Conclusions: Most elderly patients with advanced NSCLC had a limited DASH near the end of life. The risk factors for reduced DASH were women, reduced muscle mass, and poor physical function at the time of diagnosis of advanced NSCLC. Our findings would encourage early discussions about end-of-life care for patients with advanced cancers with risk factors for short DASH at the time of diagnosis, and thus, improve the quality of end-of-life care.

Abstract There are limited real‐world data on the treatment practices, outcomes, and safety of chemoradiotherapy (CRT) alone in potential candidates for immune checkpoint inhibitors (ICI) for unresectable non‐small cell lung cancer (NSCLC). In this study, we analyzed the safety and efficacy of CRT in patients who underwent CRT and would satisfy the key eligibility criteria for maintenance therapy with durvalumab (eg, no progression after CRT) in real‐world settings (m‐sub) for unresectable Stage III NSCLC between 1 January 2013 and 31 December 2015 at 12 sites in Japan. The m‐sub comprised 214 patients with a median follow‐up of 31.6 months (range 1.9‐65.8 months). Median overall survival (OS) and progression‐free survival (PFS) from completing CRT were 36.4 months (95% confidence interval [CI] 28.1 months to not reached) and 9.5 months (95% CI 7.7‐11.7 months), respectively. Consolidation chemotherapy did not influence OS or PFS. Median PFS was 16.9 vs 9.1 months in patients with vs without epidermal growth factor receptor (EGFR) mutations, with PFS rates of ~20% at 3‐4 years. Pneumonitis was the most common adverse event (according to MedDRA version 21.0J), and about half of events were grade 1. Pneumonitis mostly occurred 10‐24 weeks after starting CRT, peaking at 18‐20 weeks. Esophagitis and dermatitis generally occurred from 0 to 4 weeks, peaking at 2‐4 weeks after starting CRT. Pericarditis was rare and occurred sporadically. In conclusion, the results of the m‐sub provide real‐world insight into the outcomes of CRT, and will be useful for future evaluations of ICI maintenance therapy after CRT.

Abstract Background MET-deregulated non-small cell lung cancer represents an urgent clinical need because of the lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET gene alterations, no conclusive data are currently available. Therefore, we designed the Co-MET study, a single-arm phase II study to assess the efficacy and safety of crizotinib in patients with advanced non-small cell lung cancers harboring MET gene alterations. Methods Co-MET is an open-label, multi-center, single-arm, phase II trial to assess the safety and efficacy of oral crizotinib in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutation (cohort 1) or a high MET gene copy number of ≥ 7 (cohort 2). We will identify MET gene alterations using RT-PCR and/or next-generation sequencing. Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity. A radiology committee will review tumor scans according to the RECIST criteria. The primary endpoint is the objective response rate. Assuming a null hypothesis of 20% objective response rate and an alternative hypothesis of 50% objective response rate for cohort 1, and a one-sided alpha error of 0.05 and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. We set the exploratory sample size for cohort 2 at 10 patients. Discussion The results of this study are expected to provide evidence regarding the usefulness of oral crizotinib for advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive non-small cell lung cancer. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000031623 on 3 March 2018.

Background PD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models.Methods This single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression ≥50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety.Results Of 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63–not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity.Conclusions Atezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression.Trial registration number JapicCTI-184038.

Introduction: Programmed cell death 1 (PD-1) inhibitors have become standard treatment for patients with advanced NSCLC. However, few studies have focused on the impact of cancer cachexia on the efficacy of PD-1 or programmed death-ligand 1 (PD-L1) inhibitors among patients with NSCLC. Methods: We retrospectively reviewed medical records of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy from May 2016 to December 2018. We defined cancer cachexia as unintentional weight loss greater than 5% over 6 months and high PD-L1 as greater than 50% expression on tumor cells. We evaluated the objective response rates (ORRs) and progression-free survival (PFS). Results: Among 108 patients, 52 had cancer cachexia. Patients with cachexia had a lower ORR (15% versus 57%, p < 0.001) and shorter PFS (2.3 mo versus 12.0 mo, p < 0.001) than those without cachexia. Patients with low PD-L1 expression had a lower ORR (14% versus 53%, p < 0.001) and shorter PFS (2.8 mo versus 10.8 mo, p = 0.002) than those with high PD-L1 expression. Multivariate analysis revealed cancer cachexia and low PD-L1 expression as independent negative predictors of PFS. Among patients with cachexia, there was no significant difference in the ORR (p = 0.514) or PFS (p = 0.992) on the basis of PD-L1 expression. Conclusions: Our findings indicate that cancer cachexia might be a negative predictor of the efficacy of PD-1 or PD-L1 inhibitors and reduce the impact of PD-L1 expression on the effect of PD-1 or PD-L1 inhibitors in patients with advanced NSCLC. Further clinical and basic studies are needed.

Abstract Background Acquired immunodeficiency associated with thymoma is a rare disorder. Here we reported a case of acquired immunodeficiency with thymoma, with an unusual pattern of low CD4+ count with normal gammaglobulin levels. Case presentation A 70-year-old man presented to the emergency room of our hospital with a high-grade fever, headache, and nausea. He had a five-year history of unresectable thymoma treatment, including several cytotoxic regimens. He had received thoracic palliative radiotherapy 2 months prior to the emergent visit. During the previous month, he had experienced multiple febrile episodes, dry cough, fatigue, weight loss, and watery diarrhea. Upon admission, he had a high-grade fever, nausea, and immobility. Physical examination revealed indistinct consciousness, neck stiffness, and oropharyngeal candidiasis. Both cerebrospinal fluid and blood cultures yielded multiple short chains of Gram-positive rods later identified as Listeria monocytogenes, so he was diagnosed with Listeria meningitis. Intravenous administration of antibiotics was initiated, and the patient fully recovered and was discharged. Additional examination found normal immunoglobulin levels. Peripheral-blood cell counts revealed low CD4+ cell count (108 CD4+ cells/μl). His CD4+ cell count remained low after discharge. Conclusions Our findings suggest that physicians need to be aware of severe infections due to immunodeficiency with thymoma.

Abstract Background Cancer cachexia in elderly patients may substantially impact physical function and medical dependency. The aim of this study was to estimate the impact of cachexia on activity of daily living (ADL), length of hospital stay, and inpatient medical costs among elderly patients with advanced non-small-cell lung cancer (NSCLC) receiving chemotherapy. Methods Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to receive first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. ADL was assessed using the Barthel index. The disability-free survival time (DFS) was calculated as the time between the date of study entry and the date of onset of a disabling event, which was defined as a 10-point decrease in the Barthel index from that at baseline. The mean cumulative function of the length of hospital stay and inpatient medical costs (¥, Japanese yen) was calculated. Results The study patients comprised 11 women and 19 men, with a median age of 74 (range, 70–82) years. Cachexia was diagnosed in 19 (63%) patients. Cachectic patients had a shorter DFS (7.5 vs. 17.1 months, p

Abstract Background Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non–small cell lung cancer (NSCLC). Methods Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm2/m2), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression. Results Altogether, 11 women and 19 men with a median age of 74 (range, 70–82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm2/m2, 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005). Conclusions Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy. Trial registration Trial registration number: UMIN000009768 Name of registry: UMIN (University hospital Medical Information Network). URL of registry: Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.

PurposeManagement of leptomeningeal metastasis-related hydrocephalus (LM-H) is particularly challenging regarding the control of severe headache, nausea, and vomiting due to intracranial hypertension. To investigate the improvements of performance status and outcome with cerebrospinal fluid (CSF) shunt surgery for LM-H in patients with lung adenocarcinoma.MethodsData on patients with leptomeningeal metastasis-related hydrocephalus from lung adenocarcinoma diagnosed by MR imaging and/or cytological examination were retrospectively analyzed. Between August 2008 and July 2017, the authors reviewed 31 patients requiring CSF shunt, who underwent ventriculo-peritoneal or lumbo-peritoneal shunt.ResultsThe patients consisted of 11 men and 20 women with a median age of 59 years. Twenty-six patients received EGFR-tyrosine kinase inhibitors (TKIs). CSF shunt surgery yielded rapid improvement in the performance status of 90.3% of patients. Median overall survival from the diagnosis of LM in patients with ECOG performance status less than 2 was 7.7 months, and this was significantly longer than those in patients with PS 3 or 4 (4.4 or 1.5 months; pConclusionCSF shunting may be a safe and effective strategy in patients with LM-H from lung adenocarcinoma. A prospective study is needed to establish the effectiveness and safety of palliative CSF shunt for LM-H.

CYFRA 21-1 is a prognostic marker for non–small cell lung cancer. The serum CYFRA 21-1 level is also known as an adjunct for the diagnosis of lung squamous cell carcinoma. This study aimed to examine whether CYFRA 21-1 has predictive implications for nivolumab therapy in patients with advanced lung adenocarcinoma. Of the 79 patients who were treated with nivolumab therapy at the Shizuoka Cancer Center between December 2015 and September 2016, we retrospectively reviewed the data of 50 patients. The patient characteristics were as follows: age

Objectives: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94), PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24), and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13). The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05). Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method.Paired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer's protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems.CTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0-291 cells/7.5 mL) than by the CellSearch system (median 0, range 0-37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system.The MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system.