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Abstract Background Pemetrexed (PEM) is the primary chemotherapy for non‐small cell lung cancer (NSCLC), showing potential for long‐term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. Methods A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. Results Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor‐1 (TTF‐1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p

Abstract Background Several options for second‐line therapy are available for patients with advanced non‐small cell lung cancer (NSCLC); however, the optimal therapy remains unclear. Docetaxel (DTX) monotherapy and DTX plus ramucirumab (RAM) are the recommended second‐line treatment options. However, the efficacy of these treatments remains unsatisfactory. The aim of this study was to identify the clinical characteristics of patients with NSCLC who respond to DTX or DTX + RAM and factors that predict response. Methods Patients with NSCLC treated with DTX or DTX + RAM after second‐line therapy were retrospectively analyzed. Patients were compared with those who responded or did not respond to the post‐treatment efficacy assessment. Results Of 53 patients, 12 (22.6%) had lung cancer that responded to DTX or DTX + RAM therapy (response group). Multivariate analysis identified the absence of immune checkpoint inhibitors (ICIs) in the immediate prior therapy and a reduced dose of DTX after the second cycle as significant independent risk factors predicting nonresponse to DTX and DTX + RAM therapy in patients with NSCLC. The overall survival was significantly longer in the response group compared to the nonresponse group (p = 0.016). Conclusions Our results suggest that DTX and DTX + RAM therapies immediately after treatment with ICI‐containing regimens as well as continuation of DTX without dose reduction after the second cycle may increase the response rate and prolong survival in patients with NSCLC.

Abstract Background Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non‐small cell lung cancer (NSCLC) patients with programmed death ligand‐1 (PD‐L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD‐L1 expression

Abstract Background Amrubicin (AMR) has become the standard of care for post‐relapse small cell lung cancer (SCLC). It has also been reported to achieve long‐term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long‐term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long‐term disease control in patients with recurrent SCLC who would benefit from AMR therapy. Methods The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1–6 cycles (discontinuation group). Results The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p

Abstract Background The clinical characteristics and risk factors for cancer recurrence have not been well evaluated regarding early recurrence in patients with unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC) who receive concurrent chemoradiotherapy (CRT). The aim of this study was to determine the clinical characteristics and risk factors of patients with stage III unresectable LA‐NSCLC treated with CRT who developed early recurrence. Methods We retrospectively reviewed the clinical records of 46 patients diagnosed with stage III unresectable LA‐NSCLC treated with CRT at our center between July 2012 and July 2021. A tumor proportion score (TPS) 50% was defined as “high expression.” Results A total of 17 (37.0%) patients had a confirmed recurrence within 1 year of treatment. More patients had a lower body mass index in the early recurrence group than in the later recurrence group (p = 0.038). A higher number of patients in the late recurrence group underwent surgery after CRT (p = 0.036). Patients with a higher TPS were more likely to experience late recurrence than early recurrence (p = 0.001), whereas more patients with stage N3 disease were in the early recurrence group (p = 0.011). Multivariate analysis identified lower TPS expression as an independent risk factor for early recurrence after CRT. Overall survival was prolonged in the late recurrence group (p

Abstract Background The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non‐small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. Methods We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021. Results Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). Conclusions Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control.

Abstract Background Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non‐small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. Cases The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non‐responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non‐responder group. In the non‐responder group, all patients discontinued treatment due to deterioration of general condition during first‐line treatment. Thus, none of them were able to start the second‐line treatment. Conclusion The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Abstract Background The risk of cancer treatment‐related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. Methods We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. Results Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment‐related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non‐AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment‐related AEs. Conclusions Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment‐related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

Objective: Lung cancer patients presenting with osteoblastic bone metastases at the first visit is rare. We investigated the clinical characteristics and gene mutation rate of non-small cell lung cancer patients with osteoblastic bone metastases at the time of the initial diagnosis. Materials and Methods: We retrospectively screened newly diagnosed non-small cell lung cancer patients with osteoblastic bone metastases who presented from June 2015 to March 2021, and analyzed their clinical characteristics and status of EGFR gene mutations, EML4-ALK translocation and ROS1 rearrangements. For comparison, we collected data from patients with non-small cell lung cancer who had osteolytic bone metastases at their first visit between June 2015 and March 2021. Results: Fifty patients had bone metastases at the initial diagnosis. Among them, eight patients (8/50 = 16%) had osteoblastic bone metastases, and the lung tumors in all of them were histopathologically adenocarcinomas. Among the eight cases, two were EGFR mutation-positive, none were EML4-ALK translocation-positive, two were ROS1 rearrangement-positive, and the remaining four cases were negative for all three gene mutations/rearrangements. Compared with the osteolytic bone metastasis group, the percentage of non-smokers was higher (p = 0.020) and the ROS1 rearrangement positivity rate was higher (p = 0.05) in the osteoblastic bone metastasis group. Conclusion: Our results indicate that osteoblastic bone metastases in NSCLC are suggestive of adenocarcinoma, and that a high proportion of these patients might be positive for ROS1 rearrangements, and hence, indicated for more aggressive diagnostic biopsies.