BACKGROUND/AIM:The efficacy of durvalumab consolidation therapy after chemoradiotherapy (PACIFIC regimen) for patients with epidermal growth factor receptor (EGFR) mutation-positive locally advanced unresectable non-small cell lung cancer (NSCLC) remains unclear. Additionally, data on failure patterns, including in-field recurrence (IFR) and out-of-field recurrence (OFR), are limited. PATIENTS AND METHODS:In this retrospective study, 83 patients with locally advanced unresectable NSCLC treated with the PACIFIC regimen were analyzed. Of them, 10 patients had tumors harboring EGFR mutations. Progression-free survival (PFS), overall survival (OS), and the cumulative incidences of IFR and OFR were evaluated. RESULTS:The median follow-up time was 26.6 months. The 2-year PFS rate was 23% [95% confidence interval (CI)=7-78%] in the EGFR mutation-positive group and 53% (95%CI=42-66%) in the EGFR mutation-negative group (p=0.15). The 2-year cumulative incidence of OFR was significantly higher in the EGFR mutation-positive group (77%, 95% CI=49-100%) than in the EGFR mutation-negative group (26%, 95%CI=16-37%) (hazard ratio=2.90, 95%CI=1.29-6.51, p=0.01). On exploratory multivariate analysis, EGFR mutation positivity, Eastern Cooperative Oncology Group performance status 2-4, and PD-L1 expression <1% were significantly associated with OFR. No significant differences in IFR, OS, and adverse events were observed between the groups. CONCLUSION:Although IFR and safety profiles were comparable between the two groups, EGFR mutation positivity was associated with a higher incidence of OFR. These exploratory findings highlight the limitations of durvalumab consolidation and support the shift toward alternative systemic strategies, such as osimertinib, in patients with EGFR mutation-positive locally advanced unresectable NSCLC.

BACKGROUND:The mean age at diagnosis of sarcoidosis has been increasing worldwide, yet the clinical characteristics and treatment patterns of elderly-onset cases remain insufficiently defined, particularly in Asian populations. METHODS:We retrospectively investigated 187 consecutive Japanese patients newly diagnosed with sarcoidosis at Jichi Medical University Hospital between 2006 and 2018 who fulfilled the 2015 diagnostic criteria. Patients were classified as elderly (≥65 years, n = 49), middle-aged (45-64 years, n = 82), or younger (<45 years, n = 56). Organ involvement was assessed based on the 2023 Japan Society of Sarcoidosis and Other Granulomatous Disorders standards and the 2014 WASOG criteria. The frequency and distribution of systemic therapy (corticosteroids, methotrexate, other immunosuppressants) and treatment indications were compared across age groups. RESULTS:The proportion of women was significantly higher in the elderly than in the younger group (81.6% vs. 41.1%, p < 0.01), as was the frequency of cardiac involvement (12.2% vs. 3.6%, p < 0.05). Systemic therapy was initiated less often in the elderly than in the middle-aged group (10.2% vs. 25.4%, p = 0.026), and all indications involved extrapulmonary lesions (cardiac, n = 3; neurological, n = 1; ocular, n = 1). Most treated patients received systemic corticosteroids, with a median duration of 7.0 months. CONCLUSION:Elderly-onset sarcoidosis in Japan was characterised by a predominance of women and a higher frequency of cardiac involvement. Systemic therapy was infrequently initiated and only for extrapulmonary disease. These findings underscore the need for systematic evaluation of extrapulmonary organs-particularly the heart-and age-adapted multidisciplinary management.

BACKGROUND:Optimal management of advanced thymoma remains uncertain. We compared the efficacy of first-line platinum-anthracycline chemotherapy with other platinum-based regimens in a large Japanese cohort. METHODS:We retrospectively analyzed 157 patients with unresectable or recurrent thymoma treated at 39 institutions (2000-2020). Regimens were categorized as platinum-anthracycline (n = 104) or non-anthracycline platinum (n = 53). Propensity score matching (PSM) balanced baseline characteristics (46 pairs). The primary endpoint was overall response rate (ORR); secondary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS). RESULTS:Median age was 58 years (24-79) and 53% were male; 62% had recurrent disease. Before PSM, ORR was higher with platinum-anthracycline than with non-anthracycline platinum (57% vs 31%; p = 0.0024), while rwPFS (median 15.0 vs 13.4 months; HR 1.07; p = 0.72) and OS (median 84.9 vs 111.9 months; HR 1.36; p = 0.24) did not differ. After PSM, ORR remained higher (58% vs 32%; p = 0.0014) with comparable rwPFS (12.1 vs 11.7 months; HR 0.98; p = 0.98) and OS (93.8 vs 113.5 months; HR 1.41; p = 0.31). Overall, 70% of patients received subsequent local therapy. Among fatal cases, paraneoplastic syndromes occurred in 50%, and infections and cardiovascular events were frequent causes of death in addition to tumour progression. CONCLUSIONS:Although platinum-anthracycline regimens achieved higher response rates, this did not translate into longer rwPFS or OS. Non-anthracycline platinum regimens may be reasonable for selected patients, particularly when treatment tolerability is a priority, within individualized multidisciplinary long-term management. TRIAL REGISTRATION:UMIN000048181.

BACKGROUND:Small bronchoscopic biopsy specimens may be insufficient for molecular testing. Cytology preserves nucleic-acid quality but can be discordant with tissue-based malignant findings. We developed negative-pressure pumping fluid (NPPF), a cytological specimen generated from tissue by negative-pressure cycles, to enrich tissue-derived malignant cells. METHODS:Patients undergoing bronchoscopy for suspected non-small cell lung cancer were prospectively enrolled. Biopsy tissue, bronchial lavage fluid (BLF), and NPPF were collected. Malignant cell detection was compared across specimens, and agreement with tissue was assessed by concordance rates and Cohen's κ. Cytological quality was scored across five domains. In predefined subsets, nucleic-acid yields were compared before and after pumping, and mutation profiling using the MINtS assay was performed on NPPF and BLF when either specimen was cytology-positive. RESULTS:Ninety-nine patients were analysed. Concordance with tissue for malignant cell detection was higher for NPPF than for BLF (90.9% vs 71.7%; κ = 0.75 vs 0.35). The combined BLF/NPPF result, defined as positive when either specimen was positive, closely matched the conventional combined tissue/BLF result (94.9%; κ = 0.81). NPPF scored higher than BLF for minimal cell overlapping, background cleanliness, staining quality, and ease of focusing, whereas BLF showed more uniform cell distribution (all p < 0.001). Negative-pressure pumping increased nucleic-acid yields. In 33 cytology-positive cases, MINtS profiles were concordant between BLF and NPPF samples. CONCLUSIONS:NPPF improved cytological quality and nucleic-acid recovery while preserving biopsy tissue. Its molecular utility requires validation, including direct tissue-NPPF comparison and cytology-negative cases.

8117 Background: Although guidelines list platinum-based combination chemotherapy (Pt-rechallenge) as a second-line strategy for patients with thymoma ineligible for curative-intent therapy, evidence is limited to small case series. We investigated the efficacy of Pt-rechallenge versus non-platinum regimens in the largest retrospective cohort of second-line thymoma treatment reported to date. Methods: This multicenter study analyzed patients treated at 39 Japanese institutions. Of 157 patients ineligible for curative-intent therapy who initiated palliative platinum-based chemotherapy (2000–2020), 91 patients receiving second-line systemic cytotoxic chemotherapy were evaluated. Efficacy outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were compared between second-line Pt-containing (Pt-rechallenge) and non-platinum (non-Pt) regimens. Results: Among the 91 patients (median age 59; 91% ECOG PS 0-1) with a median follow-up of 1056 days, 64 (70%) received Pt-rechallenge and 27 received non-Pt regimens (S-1 [tegafur/gimeracil/oteracil], n=15; pemetrexed, n=6; amrubicin, n=5; paclitaxel, n=1). First-line ORR was 51%, and the median chemotherapy-free interval from first-line chemotherapy was 394 days. Pt-rechallenge achieved a significantly higher ORR than non-Pt chemotherapy (40% vs 5%; p=0.0012). Regarding survival outcomes, median PFS was 8.8 months (95% CI, 5.9–11.9) in the Pt-rechallenge group vs 8.0 months (95% CI, 4.8–30.4) in the non-Pt group (HR, 1.29; 95% CI, 0.77–2.18; p=0.325). Median OS was 70.6 months (95% CI, 53.5–82.4) vs 64.4 months (95% CI, 38.7–not estimable) (HR, 1.12; 95% CI, 0.53–2.37; p=0.759); differences in PFS and OS were not statistically significant. In the Pt-rechallenge cohort, outcomes were stratified by anthracycline (A) use in 1st/2nd-line (A→A, n=17; A→non-A, n=28; non-A→A, n=12; non-A→non-A, n=7): ORRs were 50%, 35%, 27%, and 29%; median PFS were 9.3 (95% CI, 4.5–12.2), 6.4 (95% CI, 4.6–10.6), 21.0 (95% CI, 8.7–41.9), and 4.1 (95% CI, 1.8–9.3) months, respectively. Stratified by platinum-free interval (PFI) (<6 months, n=15; 6–12, n=10; 12–36, n=27; ≥36, n=12), ORR were 14%, 63%, 46%, and 20%; median PFS were 5.8 (95% CI, 1.8–19.8), 7.3 (95% CI, 2.1–14.5), 10.3 (95% CI, 5.5–23.5), and 9.0 (95% CI, 3.1–16.9) months. Conclusions: In this largest comparative study to date, platinum rechallenge demonstrated superior response rates compared to non-platinum regimens, particularly in patients with favorable PFI. Study registration: UMIN000048181.

Background: Anaplastic lymphoma kinase (ALK) fusion genes are present in approximately 3-5% of nonsmall cell lung cancer (NSCLC) cases. Multiple echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion variants have been identified, with variants 1-3 (V1-3) accounting for approximately 90% of cases. However, clinical data on the efficacy of alectinib across these variants remain limited. In this study, we retrospectively evaluated the efficacy of alectinib treatment among ALK-fusion variants. Methods: We performed a retrospective analysis of patients treated with alectinib between January 2019 and December 2024. ALK-fusion variants were identified using Mutation Investigator using Next-era Sequencer (MINtS), a next-generation sequencing-based multigene mutation search system. Progressionfree survival (PFS), response rate, and overall survival (OS) were evaluated. Results: A total of 11 patients (male: n=4, female: n=7) were enrolled (V1: n=4, V2: n=3, V3: n=4); their median age was 75 years. Clinical stages at diagnosis were: stage II (n=1), and stage IV (n=10). Intrapulmonary metastasis was common in patients with V3. The median maximum tumor reduction rates were 90.5% (range, 84.0-92.0%), 63.4% (range, 35.0-84.0%), and 98.0% (range, 67.8-100.0%) for patients with V1, V2, and V3, respectively. The best overall response was partial response (PR) in all patients with V1 and V2. Three patients with V3 had complete response (CR) and one had PR. The median PFS was 16.5 and 15.9 months for patients with V1 and V2, respectively, and not reached for those with V3. Conclusions: In this study, there was no significant difference in the therapeutic effect of alectinib by ALK fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.

The molecular mechanisms underlying metastasis still remain unclear. We previously established a suspension culture using low-attachment culture dishes and demonstrated that cell lines adapted through 2 months suspension culture (termed FL sublines) exhibited higher metastatic potential than their parental counterparts. In this study, we identified the molecules involved in acquiring these phenotypes under low-adhesion conditions. We showed that detached tumor cells in suspension culture formed spheroids that recapitulated tumor cells in the spread-through-air space (STAS), and demonstrated that the anti-adhesion molecule mucin 21 was upregulated in detached lung cancer cells independent of driver mutations. Analyses of both cell lines and primary tumors revealed that mucin 21 is overexpressed in terminal respiratory unit-type lung adenocarcinomas. Mucin 21-knockout cells showed reduced viability and proliferation under adherent and low-attachment conditions, accompanied by enhanced anoikis. Transmission electron microscopy revealed that the intercellular spaces observed in FL sublines during suspension culture were reduced in mucin 21-knockout cells, suggesting impaired acquisition of low adhesive properties. Thus, mucin 21 appears crucial for the survival of terminal respiratory unit-type lung adenocarcinoma cells under both adherent and low-adhesion conditions.

8078 Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy, comprising 1-3% of all lung cancers. It is a high-grade tumor exhibiting heterogeneous characteristics that overlap with both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While chemoimmunotherapy (chemo-IO) has become the standard of care for SCLC and NSCLC, prospective data regarding its efficacy and safety in LCNEC are limited, and the optimal chemotherapy backbone remains unclear. We conducted the NEJ044 study to prospectively evaluate chemo-IO in patients (pts) with advanced LCNEC. Methods: This multi-institutional, prospective, observational study enrolled pts with advanced or recurrent LCNEC. Treatment consisted of atezolizumab and carboplatin combined with either etoposide (IMpower133), paclitaxel and bevacizumab (IMpower150), or nab-paclitaxel (IMpower130). The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints included OS, progression-free survival (PFS), objective response rate, disease control rate, and safety. Results: Between July 2020 and June 2024, 77 pts were enrolled across 31 institutions within the North East Japan Study Group, of whom 76 received treatment. The median follow-up was 29.0 months (mos) (95% CI: 15.2–35.7). Baseline characteristics included: median age 71 years (range 51–83); male, 68 (89%); ECOG PS 0-1, 69 (91%); and postoperative recurrence, 29 (38%). Histology was confirmed as LCNEC in 61 pts (80%) and combined LCNEC in 15 pts (20%). Treatment distribution included the IMpower133 regimen in 56 pts (74%) and IMpower150/130 regimens in 20 pts (26%). The study met its primary endpoint with a 1-year OS rate of 70.1% (95% CI: 58.2–79.2). In the overall population, median OS (mOS) and PFS (mPFS) were 18.5 mos (95% CI: 14.3–22.6), and 6.2 mos (95% CI: 4.8–7.6). Exploratory analysis showed no significant differences in survival by chemotherapy backbone. The IMpower133 cohort demonstrated a 1-year OS of 70.3% (95% CI: 56.1–80.6), mOS of 18.4 mos (95% CI: 13.2-22.3), and mPFS of 5.2 mos (95% CI: 3.9-7.6), compared to a 1-year OS of 69.6% (95% CI: 44.5–85.1), mOS of 19.9 mos (95% CI: 7.3-not evaluable), and mPFS of 7.2 mos (95% CI: 4.3-19.9) in the IMpower150/130 cohort. Grade ≥3 non-hematological adverse events occurred in 23 pts (30%), and febrile neutropenia was observed in 9 pts (11%). Biomarker analysis identified oncogenic drivers in 5 pts (including 3 KRAS mutations). PD-L1 expression was ≥50% in 12%, 1–49% in 34%, and < 1% in 51%; PD-L1 TPS ≥1% was marginally associated with improved OS. Conclusions: The NEJ044 study met its primary endpoint, demonstrating that chemoimmunotherapy provides a favorable 1-year OS of approx. 70% with a manageable safety profile in LCNEC. These prospective results support chemoimmunotherapy as a viable standard treatment strategy for this population. Clinical trial information: UMIN000040876.

8528 Background: EGFR blockade enhances tumor antigen presentation and may potentiate PD-1 inhibition. This phase I/II study evaluated the safety and efficacy of adding necitumumab to pembrolizumab plus platinum-based chemotherapy in patients with previously untreated advanced squamous non–small cell lung cancer (NSCLC), a population with limited biomarker-driven treatment options. Methods: Patients received necitumumab (400–800 mg on days 1 and 8), pembrolizumab (200 mg on day 1), nab-paclitaxel (100 mg/m² on days 1, 8, and 15), and carboplatin (AUC 5 on day 1) every 3 weeks for four cycles, followed by necitumumab plus pembrolizumab maintenance. Phase I used a standard 3+3 dose-escalation design. Per protocol amendment, patients treated at the recommended dose (RD) in phase I (n = 6) and all phase II patients (n = 6) were pooled for efficacy analyses (n = 12). Tumor assessments were performed every 6 weeks per RECIST v1.1. Primary endpoints were safety and objective response rate (ORR). Data cutoff was September 14, 2025. Results: Twenty-one patients were enrolled, including 15 in phase I (400 mg, n = 6; 600 mg, n = 3; 800 mg, n = 6). One dose-limiting toxicity (DLT) occurred in the 800 mg cohort, which was determined as the RD and maximum tolerated dose (MTD). Among the 12 patients treated at the RD, the ORR was 75.0% (9/12; 95% CI, 42.8–94.5), with partial response in 9 patients, stable disease in 1 patient, and progressive disease in 2 patients. The disease control rate was 83.3%. The 24-week survival rate was 95.2%. Median progression-free survival and overall survival were not reached at the time of analysis. The most frequent adverse events (AEs) in 21 patients were hypomagnesemia (66.7%), acneiform dermatitis (66.7%), neutropenia (61.9%), decreased appetite (52.4%), anemia (52.4%), constipation (47.6%), stomatitis (42.9%), and leukopenia (42.9%). Grade 3 and 4 AEs occurred in 66.7% and 28.6% of patients, respectively, with no grade 5 events. Conclusions: The addition of necitumumab to pembrolizumab and platinum-based chemotherapy demonstrated manageable toxicity and resulted in a high ORR in patients with untreated squamous NSCLC. These findings support the potential activity of EGFR blockade–based immunochemotherapy and warrant further clinical investigation. Clinical trial information: 2031210387.

Circulating tumor DNA (ctDNA) monitoring is informative for longitudinal physical tumor burden (PTB) assessment. However, NGS-based ctDNA monitoring is limited by sensitivity, cost, and turnaround time in clinical practice. We developed OTS-Probes, an off-the-shelf digital PCR (dPCR) primer/probe library prepared for more than 1,000 frequently registered somatic mutations. Oligonucleotide sequences with chemically modified bases facilitate to produce approximately 80 bp amplicons for fragmented plasma DNA. Based on the OTS-Select algorithm from an NGS report, 1–4 mutations are readily selected from OTS-Probes for ctDNA monitoring. OTS-Probes provide a sensitive, frequent, and readily PTB assessment for dPCR-based longitudinal ctDNA monitoring.

Abstract Background Amikacin liposome inhalation suspension (ALIS) has been used in several countries including Japan for refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although its efficacy and adverse events have been reported, factors that limit optimal treatment outcomes in real-world practice are not fully understood. Therefore, we aimed to provide practical considerations for optimizing ALIS therapy by identifying factors associated with culture conversion. Methods We retrospectively reviewed the medical records of patients with refractory MAC-PD who were treated with ALIS at a single center between October 2021 and June 2025. Patients treated for ≥ 6 months were included and categorized into culture conversion and non-conversion groups. Clinical characteristics and treatment-related factors were analyzed. Follow-up continued until December 2025. Results During the study period, 30 patients with refractory MAC-PD were treated with ALIS. Three patients who discontinued ALIS within 6 months were excluded from further analysis because of MAC-related death ( n = 1) or severe ALIS-related adverse events ( n = 2). Consequently, 27 patients were included in the analysis. The median age was 69.9 years, and the median duration of ALIS therapy was 14.6 months. The sputum culture conversion rate was 51.8% (14/27; 95% CI, 34.0-69.3%). Pulmonary fungal disease was identified in 7 patients (25.9%), including newly diagnosed cases during ALIS therapy; however, pulmonary fungal disease was not significantly associated with culture conversion. Cavitary lesions and prior aminoglycoside use were significantly associated with non-conversion. In addition, inappropriate ALIS administration, including prolonged intermittent use and inadequate nebulizer handset replacement, was significantly associated with non-conversion. Dysphonia was the most frequent adverse event and occasionally led to prolonged intermittent use of ALIS. ALIS-related lung abnormalities on computed tomography (CT) scans were observed in 21 of 26 patients. Conclusions Cavitary lesions, prior aminoglycoside use, and inappropriate ALIS administration were associated with culture non-conversion. Several factors related to ALIS administration and inhalation management may be modifiable, and appropriate patient education, regular reassessment of inhalation practices, and careful monitoring of ALIS administration may help optimize treatment outcomes.

BACKGROUND:Both atezolizumab and durvalumab combined with platinum-etoposide have become standard first-line treatments for extensive-stage small-cell lung cancer (ES-SCLC), yet head-to-head real-world comparative data remain scarce. METHODS:We conducted a multicenter retrospective cohort study of 234 patients with ES-SCLC treated with atezolizumab plus platinum-etoposide (AEP; n = 126) or durvalumab plus platinum-etoposide (DEP; n = 108) across five Japanese institutions between 2016 and 2023. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier and overlap-weighted Cox models. Safety, a cost-effectiveness (cost-minimization) analysis based on restricted mean survival time-derived quality-adjusted life years (QALYs), and second-line treatment outcomes were also evaluated. RESULTS:Median PFS was 5.0 months for AEP and 5.1 months for DEP (hazard ratio [HR] 0.96; 95% CI, 0.73-1.26), and median OS was 12.0 and 12.1 months for AEP and DEP, respectively (HR 0.94; 95% CI, 0.68-1.31). Safety profiles were broadly equivalent between groups. Economic analysis showed nearly identical QALYs (1.002 vs 1.011) but lower total direct medical cost for AEP (¥4.14 million vs ¥4.88 million). Among 128 patients receiving second-line chemotherapy, those with platinum-sensitive relapse had significantly longer OS than those with platinum-refractory relapse, regardless of regimen. CONCLUSIONS:In real-world practice, AEP and DEP demonstrated equivalent efficacy and safety as first-line treatment for ES-SCLC. Given its lower cost with comparable QALYs, AEP may represent the more cost-minimizing option. The prognostic distinction between sensitive and refractory relapse remains clinically relevant after chemoimmunotherapy.

9044 Background: To date, osimertinib has been commonly used as a first-line treatment for EGFR mutated advanced NSCLC. However, the issue of what constitutes effective treatment after osimertinib failure remains．We evaluated treatment with afatinib plus chemotherapy for EGFR mutated NSCLC resistant to osimertinib. Methods: Patients (pts) with EGFRm (Del19 or L858R) after failure of osimertinib treatment were assigned to a regimen of afatinib 20mg daily combined with carboplatin AUC5 mg/ml/min and pemetrexed 500mg/m2 every 3 weeks followed by maintenance treatment with afatinib plus pemetrexed until disease progression or unacceptable toxicity was noted. The primary endpoint was rate of PFS at 6 months after initiation of treatment (6M-PFSR). The threshold was set at 35% and the expected value at 60% (two-sided P-value of 5% and power of 80%). Thirty-one patients were required, and the target number of patients was set at 35 after accounting for ineligible cases. Secondary endpoints were PFS, OS, ORR, DOR, and Safety. In this study, blood samples were collected before and after study treatment and at the time of PD to examine biomarkers using CAPP-SEQ. This biomarker study is ongoing. Results: Between June 7, 2020 and January 19, 2022, 36 pts were enrolled. One patient was found to meet the exclusion criteria, and the efficacy was analyzed in the other 35 patients. The mean age was 70 years, 60% were women, and 54.3% were nonsmokers. The 6M-PFSR, the primary endpoint, was 57.1%. The confidence interval of 39.3%-71.5% exceeded the threshold of 35%, and the study met its primary endpoint. Notably, 24.1% of pts had a long-term PFS of 1 year or longer. ORR was 48.6%, DCR was 88.6%, median PFS was 8.2M, median DOR was 5.6 M, and median OS was not reached. By mutation type, ORR were similar for Del19 and L858R (46.7% and 50.0%, respectively), but median PFS tended to be longer for Del19 compared to L858R (9.6M and 5.2M, respectively). Pts who responded to previous osimertinib therapy (CR and PR: n = 29) tended to have longer mPFS compared to non-responders (SD, PD, and NE: n = 6) (8.5M and 5.8M, respectively). Adverse events due to TKI and chemotherapy were observed. Diarrhea (52.8%), anorexia (44.4%), fatigue (33.3%), and paronychia (36.1%) were the most frequent adverse events, and these adverse events were predictable and manageable. Interstitial pneumonia developed in three patients (8%), one of whom was the only death in the study. Conclusions: The combination of afatinib and the platinum doublet showed satisfactory efficacy with manageable adverse events in tumors refractory to osimertinib, and met its primary endpoint. OS follow-up and biomarker analyses are still ongoing. This regimen is expected to be a candidate for second-line therapy after osimertinib. Clinical trial information: jRCTs021200005 .

INTRODUCTION:In recent clinical practice, driver gene mutations have been tested using multiplex PCR or next-generation sequencing (NGS), which help determine treatment strategies for non-small cell lung cancer (NSCLC). We developed a new analysis system, the Mutation Investigator using Next-era Sequencer (MINtS), using NGS, which allows for the detection of gene mutations even in cytology specimens with low tumor cell content. Due to its high sensitivity, MINtS has the potential to detect gene mutations even in specimens that are pathologically negative for cancer. In the present study, we examined the utility of MINtS-based mutation detection in cytology-negative specimens. METHODS:We retrospectively analyzed the data of patients who were enrolled in the NEJ021A study, which was a prospective observational study investigating the performance of MINtS. Although NEJ021A was a multicenter study, we included only patients enrolled at Niigata University Medical and Dental Hospital. RESULTS:Cytology specimens from 486 patients with suspected lung cancer were analyzed using MINtS. Among the cytology-positive cases, driver gene mutations were detected in 37.3 % (93/249) of patients, whereas in cytology-negative cases, driver gene mutations were detected in 20.2 % (47/233) of patients using MINtS. Of the 47 patients whose specimens were cytology-negative and MINtS-positive, 42 were histologically or clinically diagnosed with NSCLC and received treatment. CONCLUSIONS:Even in patients without a pathological diagnosis of lung cancer, MINtS can identify driver gene mutations, which can be useful for guiding subsequent treatment decisions.

8557 Background: Although the combination of an anti-PD-L1 antibody and platinum-based chemotherapy has become the standard care for extensive-stage small-cell lung cancer (ES-SCLC) patients (pts), its safety and efficacy for those with a poor PS are unclear. In the NEJ045A study, by adjusting the doses of carboplatin (CBDCA) and etoposide (ETP), durvalumab (DUR) plus CBDCA and ETP demonstrated tolerability and efficacy for ES-SCLC pts with a poor PS, meeting the primary endpoint of tolerability. Here, we report the updated data from NEJ045A, including the long-term effects of ICIs. Methods: Previously untreated ES-SCLC pts with PS 2–3 were enrolled. Eligible pts received 1500 mg DUR plus CBDCA and ETP every 3 to 4 weeks for up to 4 cycles, followed by DUR maintenance therapy. Initial dosages of CBDCA and ETP were AUC 4 and 80 mg/m 2 in PS 2 and AUC 3 and 60 mg/m 2 in PS 3. The dosages for the subsequent cycles were adaptively determined based on the adverse events (AEs) of the previous cycles. Results: From April 2021 to October 2023, 57 pts (43 pts with PS 2 and 14 pts with PS 3) were enrolled. At the data cutoff (Oct 3rd, 2024), the median follow-up period for overall survival among patients with censored data was 23.4 months (12.9-32.7) in the FAS population. The median age was 74 years old (range 55-86). 79% was male. The median number of cycles of induction therapy was 4 (range 1-4), and the median number of cycles of durvalumab maintenance was 3 (range 1-16) in PS 2 and 7 in PS 3 (1-22). A total of 34 patients (64%) completed induction therapy, comprising 28 pts (67%) in PS 2 and 6 pts (50%) in PS 3. Doses of CBDCA and/or ETP were increased during induction therapy in 24% of PS 2, and 18% of PS 3. Updated median PFS in PS 2 and PS 3 were 4.5 months (95% CI, 3.1-5.8) and 4.5 months (95% CI, 1.4-8.2). The 1-year survival rates in PS 2 and PS 3 were 50% (95% CI, 37.0-67.7) and 18% (95% CI, 5.2-63.7). Updated median OS in PS 2 and PS 3 were 11.3 months (95% CI, 6.7- 16.1) and 5.1 months (95% CI, 2.1-8.5). Patients who completed induction therapy demonstrated longer OS compared to those who did not (median OS, 15.0 vs. 3.8 months). Treatment was discontinued in 100% of PS 2 and 93% of PS 3, and the reasons for discontinuation (PD/AE/other) were 79%/12%/9% in PS 2 and 38%/54%/8% in PS 3. Conclusions: DUR + CBDCA + ETP therapy was well tolerated for ES-SCLC with poor PS, and completion of induction therapy was associated with an improvement in OS. Clinical trial information: CRB3180025 .

BACKGROUND:We investigated the association between the development of sarcoidosis and personal or family medical history, with a focus on immune-mediated inflammatory diseases (IMIDs), in a Japanese population. METHODS:In this exploratory case-control study, self-administered questionnaires were completed by 164 patients with newly diagnosed sarcoidosis (64 men, 100 women) who visited public health centres in 7 prefectures between 2018 and 2020 to apply for medical expense subsidies (cases) and by 1779 community-dwelling controls (641 men, 1138 women) undergoing municipal health checkups (controls). The questionnaire collected information on personal and family medical histories, including IMIDs. Logistic regression analyses adjusted for age and sex were used to identify risk factors associated with onset of sarcoidosis. RESULTS:A history of IMIDs was associated with a greater likelihood of sarcoidosis (adjusted odds ratio [aOR] 3.05, 95 % confidence interval [CI] 1.79-5.21). Increased risk was observed for rheumatoid arthritis (aOR 2.63, 95 % CI 1.06-6.53), Sjögren's syndrome (aOR 14.39, 95 % CI 4.30-48.10), and hypothyroidism (aOR 4.91, 95 % CI 2.20-10.97). Some conditions, such as asthma, lymphoma, and insulin use, showed possible associations, with wide CIs including 1.0. Additionally, a family history of sarcoidosis was strongly associated with disease occurrence (aOR 21.30, 95 % CI 3.86-117.68), supporting a potential genetic predisposition consistent with previous epidemiological findings. CONCLUSIONS:This study suggests that sarcoidosis may be associated with IMIDs in the Japanese population. However, its findings should be interpreted with caution, given its exploratory design and limited statistical power.

INTRODUCTION:In locally advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), the efficacy and safety of durvalumab after concurrent chemoradiotherapy (CCRT) remain controversial. METHODS:In this retrospective cohort study, we analyzed treatment outcomes in patients with unresectable stage III sensitizing EGFR-mutant NSCLC who underwent and completed CCRT without progression between July 2015 and June 2022 from 48 institutions in Japan. Patients with confirmed EGFR mutations after recurrence were excluded. Comparisons between groups were conducted using a cohort extracted through propensity score matching (PSM). The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS) and safety of EGFR-tyrosine kinase inhibitor (TKIs) after durvalumab treatment. RESULTS:Out of 162 eligible patients, 106 received consolidation durvalumab following CCRT and 56 did not. After PSM, 56 patients were matched to the durvalumab and CCRT alone groups. The median PFS was significantly longer in patients treated with durvalumab than in those treated with CCRT alone (26.8 months [95 % confidence interval [CI], 13.9-NA] vs. 11.1 months [95 % CI, 9.0-18.2]; hazard ratio [HR], 0.52 [95 % CI, 0.33-0.83]; p = 0.005). While early osimertinib administration following durvalumab tended to increase Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 pneumonitis, there was no significant difference in the frequency of CTCAE grade ≥ 3 adverse events with EGFR-TKIs between the groups (23.5 % vs. 20.8 %). CONCLUSIONS:Durvalumab administration following CCRT prolongs PFS in patients with locally advanced EGFR-mutant NSCLC. Durvalumab can be safely administered if the timing of subsequent osimertinib is carefully managed.

BACKGROUND:The introduction of antifibrotic drugs elicited a significant paradigm shift in the treatment of fibrosing interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF). However, it remains unclear which clinical characteristics of IPF patients predicts therapeutic efficacy, and there has been limited investigation of the relationship between physical findings. The aim of this study was to investigate whether various clinical factors, including physical findings at the initiation of antifibrotic therapy, had an impact on the clinical response to treatment. METHODS:We retrospectively examined baseline clinical characteristics of IPF patients to identify features associated with better responses to antifibrotic drugs. We identified 257 consecutive patients with progressive pulmonary fibrosis who received antifibrotic therapy between March 2009 and May 2021, including 153 patients treated with pirfenidone and 104 patients treated with nintedanib. Of these, 66 patients with IPF had comprehensive baseline data recorded at the time of therapy initiation, including gender, age, smoking history, symptoms, physical findings including digital clubbing, biomarkers, and pulmonary function. Based on pulmonary function at 6 months after initiation of treatment, these patients were classified into a non-deterioration group and a deterioration group. Baseline data at the initiation of antifibrotic therapy were compared between these two groups. RESULTS:Twenty-two patients were classified into the deterioration group and 44 into the non-deterioration group. The annualized change in forced vital capacity (FVC) was -385.8±363.3 mL in the deterioration group and 94.1±207.0 mL in the non-deterioration group. The only significant difference in baseline characteristics between the groups was the presence of digital clubbing, observed in 5 of 22 patients (22.7%) in the deterioration group and in 22 of 44 patients (50.0%) in the non-deterioration group (P=0.04). Our findings indicate that IPF patients with digital clubbing experienced a smaller annual decline in FVC following antifibrotic therapy compared to those without digital clubbing. CONCLUSIONS:These findings suggest that the presence or absence of digital clubbing in IPF patients may predict the annual rate of FVC decline following antifibrotic therapy. Antifibrotic drugs may be more effective in IPF patients who present with digital clubbing.

BACKGROUND:In treatment-naïve advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, approximately 10% to 15% correspond to uncommon mutations. For patients with EGFR uncommon mutations, monotherapy with either a second-generation EGFR tyrosine kinase inhibitor (TKI), afatinib, or a third-generation EGFR-TKI, osimertinib, is recommended as the initial therapy. However, needs remain unmet for patients with central nervous system (CNS) metastases and those who do not respond adequately to single-agent TKI therapy for EGFR uncommon mutations. The recently published FLAURA2 trial showed that osimertinib in combination with platinum-pemetrexed significantly prolonged progression-free survival (PFS) and provided high disease control compared with osimertinib monotherapy for common mutations. Therefore, we planned this phase II study to evaluate the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. PATIENTS AND METHODS:Forty patients will be enrolled in the study. The primary endpoint is the objective response rate, and the secondary endpoints include safety, PFS and overall survival in overall patients, patients with and without CNS lesions at baseline and according to mutation subtype. CONCLUSIONS:In this study, we will explore the efficacy and safety of osimertinib in combination with platinum-pemetrexed in treatment-naïve NSCLC patients with EGFR uncommon mutations. Our findings may provide treatment options for patients with EGFR uncommon mutations, especially those with CNS metastases or those requiring more intensive treatment.