BACKGROUND:Ensitrelvir (ESV) is approved in Japan for the treatment of mild to moderate COVID-19 in standard-risk patients; however, real-world evidence regarding outcomes among hospitalized high-risk patients remains limited. We evaluated whether oral ESV could serve as a feasible alternative to intravenous remdesivir (RDV). METHODS:We conducted a retrospective multicenter cohort study of hospitalized patients with mild to moderate COVID-19 and at least one risk factor for disease progression treated with ESV or RDV between June 2023 and March 2024 at two hospitals in Japan. Patients unable to receive oral therapy were excluded. Propensity score matching adjusted for baseline differences. The primary outcome was a composite of disease progression or all-cause mortality within 28 days. RESULTS:Among 207 patients, 44 received ESV and 163 received RDV. In the overall cohort, the composite outcome occurred in 4 vs. 10 patients (P = 0.49). After matching, 40 patients were included in each group; all patients in the matched cohort had mild disease without oxygen requirement. In the matched cohort, the composite outcome occurred in 4 patients in each group (P > 0.99). Individual components showed no significant differences (mortality: 4 vs. 3; progression: 2 vs. 2). CONCLUSIONS:In this multicenter cohort of hospitalized high-risk patients with mild to moderate COVID-19 able to receive oral therapy, no significant differences were observed between ESV and RDV in the matched cohort of patients with mild disease. ESV may represent a feasible oral alternative in selected high-risk patients able to receive oral therapy.

Interferon-gamma release assays (IGRAs) are widely used for early diagnosis against TB. However, data on their diagnostic utility and clinical significance in elderly patients with active TB remian limited. We retrospectively analyzed patients over 65 years of age who underwent IGRA testing using either T-SPOT.TB (Oxford Immunotec, UK) or QuantiFERON (QFT) (Qiagen, Germany) between 2015–2024. Active pulmonary TB (ATB) was defined as TB confirmed by isolation from respiratory specimens within 90 days of IGRA testing. Latent TB infection (LTBI) was defined as IGRA-positive individuals without microbiological confirmation of TB. For individuals tested multiple times, only the most recent result was included. Values exceeding the detection threshold were recorded as maximum or minimum values. A total of 12,872 T-SPOT.Tb and 7,580 QFT tests were performed during the study period, of which 3,990 and 2,620 tests, respectively, met inclusion criteria. For T-SPOT.TB, 138 (3.5%) were diagnosed with ATB, with a positive rate of 83.3%. The median quantitative scores were 50 (IQR: 16 - 50) for ESAT-6 and 21 (IQR: 9 - 50) for CFP-10. LTBI was identified in 605 patients (15.7%), with median quantitative scores 16 (IQR: 8 - 41) for ESAT-6 and 11 (IQR: 3 - 32) for CFP-10. For QFT, 87 (3.3%) were diagnosed with ATB, with a positive rate of 67.8%. The median quantitative scores were 1.64 (IQR: 0.62 – 4.0) for TB1 and 2.08 (IQR: 0.65 – 4.86) for TB2. The number of LTBI was 198 (7.8 %) with median quantitative scores of 0.85 (IQR: 0.46 – 2.16) for TB1 and 0.94 (IQR: 0.52 – 2.14) for TB2, respectively. The best cut-off values were 3.1 (sensitivity: 23.0%; specificity: 87.4%), 3.6 (sensitivity: 28.7%; specificity: 85.4%) for TB1 and Tb2, 50 (sensitivity: 78.7%; specificity: 42.0%), 33 (sensitivity: 75.5%; specificity: 42.0%) for ESAT-6 and CFP-10, respectively. Quantitative IGRA values were higher in patients with active TB than in those with latent infection. Notably, T.SPOT-TB might be possible to differentiate ATB and LTBI in elderly populations. These findings support the potential clinical utility of TB-SPOT.TB for TB diagnosis in aging populations in Japan. Yoshikazu Mutoh, graduate student, MSD, Co LTD: Honoraria Yusuke Minato, Ph.D., Shionogi & Co., Ltd.: Grant/Research Support Yohei Doi, MD, PhD, GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria

Evidence regarding the diagnostic value of quantitative interferon-gamma release assay (IGRA) results in elderly populations is limited, and large-scale data for QuantiFERON-TB Gold Plus (QFT-Plus) are scarce. We evaluated QFT-Plus and T-SPOT.TB (T-SPOT) for distinguishing active tuberculosis (ATB) from latent infection (LTBI) in elderly individuals in Japan, a super-aged country. We conducted a retrospective, cross-sectional diagnostic accuracy study of patients ≥65 years who underwent IGRA testing between 2015 and 2024 at two hospitals: a tuberculosis referral center (QFT-Plus and T-SPOT) and a tertiary hospital (T-SPOT only). ATB was defined as microbiologically confirmed TB. Quantitative IGRA values were compared between ATB and LTBI in all patients and in IGRA-positive subsets. Receiver operating characteristic (ROC) curves assessed discriminatory performance. Among 10,745 elderly patients (ATB: n = 310; LTBI: n = 1,158), values showed substantial overlap. For T-SPOT, the area under the curves (AUCs) improved at Tosei General Hospital (TGH) (ESAT-6: 0.679, CFP-10: 0.670) in IGRA-positive cases. In contrast, all-patient AUCs at Fujita Health University Hospital (FHUH) were low (ESAT-6: 0.367, CFP-10: 0.362), demonstrating an inverse association, though they improved (ESAT-6: 0.607 and CFP-10: 0.554) in IGRA-positive cases. For QFT-Plus, all-patient AUCs were low (TB1 antigen: 0.462, TB2 antigen: 0.470), but improved in the IGRA-positive cohort (TB1 antigen: 0.630, TB2 antigen: 0.645). The optimal quantitative cutoffs in IGRA-positive cases provided modest diagnostic accuracy. In elderly individuals, quantitative IGRA values alone have limited ability to distinguish ATB from LTBI, but QFT-Plus and T-SPOT show modest improvement in IGRA-positive cases. Although not suitable as a stand-alone diagnostic, quantitative IGRA may assist risk stratification and decision-making in selected scenarios.IMPORTANCETuberculosis remains a major health concern in aging societies, such as Japan, where most patients are elderly adults with impaired immune function. Interferon-gamma release assays (IGRA) are widely used for detecting infection, but the role of their quantitative values in differentiating active tuberculosis from latent tuberculosis infection has been uncertain. Our study is the first to evaluate the quantitative performance of the latest QuantiFERON-TB Gold Plus and T-SPOT.TB specifically in elderly patients, across both a tuberculosis referral hospital and a university hospital. Although absolute separation between active and latent disease was not achieved, we found that, in test-positive individuals, active cases tended to yield higher values, particularly with T-SPOT.TB. This indicates that quantitative information, when interpreted within the clinical context, can assist physicians in assessing risk and guiding further diagnostic steps, offering practical value for improving decision-making in the care of vulnerable elderly patients.

Background and purpose:Functional lung avoidance radiotherapy using four-dimensional computed tomography (4D-CT) ventilation or single-photon emission computed tomography (SPECT) perfusion has been studied, but few have evaluated their combined use. In this study, we examined whether integrating both modalities improves sparing of high functional lungs (HFL) in non-small cell lung cancer (NSCLC).Materials and methods:Forty-seven patients with NSCLC underwent both 4D-CT ventilation and SPECT perfusion imaging; one was excluded, leaving 46 patients for analysis. Functional lung maps were segmented into high-, mid-, and low-functional lungs. Four radiotherapy plans were generated: anatomical (A), ventilation-guided (V), perfusion-guided (Q), and combined ventilation–perfusion-guided (VQ). Dose-volume and dose-function metrics were compared across plans. Correlations between tumor proximity to HFL and dose reduction were also assessed.Results:All function-guided plans significantly reduced the dose to HFL compared to anatomical plans (P < 0.001). The VQ plan achieved the largest reductions in mean lung dose (MLD) to HFL (e.g., ventilation: 11.3 Gy vs. 12.3 Gy; perfusion: 9.98 Gy vs. 11.1 Gy). Function-weighted metrics (e.g., functional MLD) were also lowest in the VQ plan, indicating improved functional sparing. Dose reduction was correlated with tumor proximity to HFL, with the strongest associations observed at 25–35 mm of the planning target volume.Conclusion:Integrating 4D-CT ventilation and SPECT perfusion imaging in radiotherapy planning provides superior sparing of functional lung compared to single-modality or anatomical approaches. The spatial relationship between the tumor and functional lungs plays a key role in determining dosimetric benefits.

BACKGROUND:Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare, progressive interstitial lung disease with a poor prognosis and limited treatment options. No validated instruments exist for assessing health status in patients with iPPFE. We aimed to evaluate the performance of the St. George's Respiratory Questionnaire (SGRQ) in this population. METHODS:We retrospectively analyzed data from 56 consecutive patients with iPPFE who were evaluated at Tosei General Hospital between January 2008 and May 2017. We examined internal consistency, test-retest reliability, construct validity, known-groups validity, responsiveness, and the minimal important difference (MID) for the SGRQ. RESULTS:The SGRQ showed acceptable internal consistency (Cronbach's α: 0.75-0.92) and test-retest reliability (intraclass correlation coefficient: 0.79-0.93). Construct validity was supported by significant correlations between the SGRQ scores and clinically meaningful variables, including body mass index, flat chest index, and residual volume to total lung capacity ratio, which reflect distinctive features of iPPFE. Known-groups validity was supported by significant differences in the SGRQ total scores among groups categorized by the Gender-Age-Physiology index stage or history of pneumothorax/pneumomediastinum. Responsiveness was supported by significant correlations between changes in the SGRQ scores and changes in clinically meaningful variables over 12 months. Additionally, changes in the SGRQ total scores significantly differed between the stable and deteriorated groups classified by changes in forced vital capacity or the modified Medical Research Council dyspnea scale. The estimated MID for the SGRQ total score was 8.0 points. CONCLUSIONS:These findings suggest that the SGRQ may be useful for assessing health status in patients with iPPFE.

Background Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) often manifests with a usual interstitial pneumonia (UIP) pattern and has a poor prognosis similar to idiopathic pulmonary fibrosis (IPF). Despite radiological similarity to IPF, RA-UIP typically shows greater inflammation. This study aimed to investigate the formation of cysts mimicking honeycombing radiologically in RA-UIP. We hypothesized that the pathogenesis of these cystic structures may differ from that of IPF. Methods We retrospectively analyzed patients with rheumatoid arthritis who had a UIP/probable UIP pattern on high-resolution computed tomography and underwent surgical lung biopsy. IPF/UIP hallmark features, inflammatory cell infiltration, and inducible bronchus-associated lymphoid tissue (iBALT) in bronchioles and alveoli were assessed, and their contribution to cyst formation was examined. Changes after immunosuppressive therapy were evaluated using the Wilcoxon signed-rank test. Results Six patients with RA-UIP were included. No patient showed moderate-to-severe IPF/UIP hallmark features. All patients exhibited moderate-to-severe inflammatory cell infiltration; 83% showed plasma cell infiltration and 67% had iBALT. Moderate-to-severe intralobular bronchiolar destruction and adjacent alveolar structural damage were observed in 67% and 83% of patients, respectively, leading to cyst formation. In treated patients (n = 5), median %FVC increased from 85.7 to 113.6 (P = 0.04) and median %DLCO increased from 64.9 to 89.7 (P = 0.04). Conclusions In this small, selected cohort, cyst formation in RA-UIP may result from inflammation-related destruction of small airways and adjacent alveolar structures rather than solely from the fibrotic remodeling typical of IPF/UIP. Immunosuppressive therapy may provide clinical benefit in selected patients.

BACKGROUND:Healthcare professionals are increasingly providing medical information to patients. However, few objective evaluations of the information's usefulness exist. This study aimed to evaluate patient satisfaction with medical information sources, including the JLCS Guidebook and patient advocacy groups, using the European Organization for Research and Treatment of Cancer's (EORTC) Quality of Life 25-item information module (QLQ-INFO25). METHODS:Patients with thoracic malignancies were enrolled in the trial in response to calls from patient support groups and the Japanese Lung Cancer Society. Patient satisfaction was based on information obtained from the 2019 Japanese Lung Cancer Society's patient guidebook and a web-based survey of patients with lung cancer. Satisfaction with the information was analyzed using EORTC QLQ-INFO25 scores and stratified by guidebook use (users vs. non-users). RESULTS:Of 332 participants (110 male, 222 female), 283 (85.2%) completed the questionnaire, among which 82 (29.0%) read the guidebook. Participants found the research through online sources or by responding to an invitation from their primary physician or patient support group. Seventy-one users (91%) were satisfied with the guidebook content, as indicated by their individual QLQ-INFO25 scale scores. No statistically significant differences were observed between guidebook users and non-users; however, a trend toward higher satisfaction was noted among participants who used both the guidebook and advocacy groups. CONCLUSIONS:Our findings suggest that guidebooks and advocacy groups may contribute to improved patient satisfaction; however, further controlled studies are warranted. Our results provide an objective basis for discussing information provision for patients with lung cancer. Strategies should be developed to communicate information reflecting patients' diverse backgrounds.

BACKGROUND:Interstitial lung abnormalities (ILA) are CT-detected interstitial abnormalities that may represent early-stage interstitial lung disease (ILD). However, histopathologic correlations remain limited, with previous studies reporting conflicting results. In 2025, the American Thoracic Society (ATS) established criteria defining the boundary between ILA and ILD. This study aimed to investigate the histopathological spectrum of Fleischner-defined ILA, correlate findings with CT features and outcomes, and reclassify cases according to 2025 ATS criteria. METHODS:This retrospective study analyzed 30 consecutive patients who underwent surgical lung biopsy between January 2010 and December 2021. All cases had ILA per Fleischner Society criteria and were reclassified using 2025 ATS criteria. Three pulmonary pathologists evaluated dominant and co-existing histopathological patterns. Two chest radiologists independently assessed CT findings. Overall survival was compared between usual interstitial pneumonia (UIP)-related and non-UIP-related groups using Kaplan-Meier analysis. RESULTS:Twenty patients (66.7 %) were men; mean age was 63.6 ± 6.5 years; 27 (90 %) had fibrotic ILA. The most common dominant pattern was UIP (43.3 %), followed by nonspecific interstitial pneumonia (NSIP) and bronchiolocentric interstitial pneumonia (BIP) (20 % each). Overall, 96.7 % of cases met 2025 ATS criteria for ILD (subclinical ILD). On CT, all UIP and NSIP cases showed reticular opacity and traction bronchiectasis, while BIP typically exhibited branching linear opacities. During median follow-up of 92.1 months, overall survival did not differ significantly between UIP-related and non-UIP-related groups (p = 0.595). CONCLUSIONS:This study of Fleischner-defined ILA, predominantly reclassified as subclinical ILD by 2025 ATS criteria, demonstrates diverse histopathological patterns beyond UIP, including BIP, highlighting pathological heterogeneity.

BACKGROUND:Pulmonary hypertension (PH) commonly complicates interstitial lung disease (ILD) and is associated with poor prognosis. Although pulmonary vasodilators may improve clinical parameters, they can also cause severe hypoxemia; thus, reliable noninvasive tools are needed to assess treatment response. We investigated whether changes in four-stratum risk stratification category before and after vasodilator therapy are associated with prognosis in patients with ILD-PH. METHODS:Clinical data before and after vasodilator therapy were retrospectively collected from consecutive patients with ILD-PH at a single ILD-specialty center in Japan between May 2007 to September 2023. Four-stratum risk stratification was performed using World Health Organization functional class, brain natriuretic peptide or N-terminal pro-brain natriuretic peptide, and 6-min walk distance. Cox proportional hazard analyses adjusted for ILD-gender-age-physiology index, mean pulmonary arterial pressure, and time from PH diagnosis to pulmonary vasodilator therapy were used to evaluate associations between risk stratification and transplant-free survival. RESULTS:Among 64 patients, 6 were categorized as low risk, 30 as intermediate-low risk, 21 as intermediate-high risk, and 7 as high risk. Vasodilator therapy improved pulmonary hemodynamics and led to improvement in risk category in 9 patients and deterioration in 14. Post-treatment risk stratification provided good prognostic discrimination. Multivariate Cox analysis showed that post-treatment risk scores were independently associated with transplant-free survival (adjusted HR 3.286, 95% CI 1.897-6.258). CONCLUSIONS:Post-treatment four-stratum risk stratification was associated with transplant-free survival in patients with ILD-PH.

Objective Electronic patient-reported outcome (ePRO) measures are increasingly used in respiratory care, yet evidence regarding their feasibility and measurement performance in real-world clinical settings remains limited. The S 3 -NIV questionnaire is a brief patient-reported outcome tool assessing respiratory symptoms, sleep quality, and side effects in patients receiving non-invasive ventilation (NIV). This study aimed to develop a Japanese electronic version of the S 3 -NIV questionnaire and to evaluate its feasibility and internal consistency. Methods The S 3 -NIV questionnaire was translated into Japanese according to ISPOR Translation and Cultural Adaptation guidelines. After linguistic validation, a web-based electronic version was developed. A cross-sectional observational feasibility study was conducted in patients with chronic respiratory failure receiving home NIV. The Japanese electronic version of the Severe Respiratory Insufficiency (SRI) questionnaire was used as a comparator. Internal consistency was assessed using Cronbach’s alpha coefficients. Results Seven patients successfully completed the electronic questionnaires, confirming technical feasibility. Internal consistency was acceptable to high for the S 3 -NIV total score and respiratory symptoms subscore (Cronbach’s alpha = 0.79 and 0.92, respectively), whereas the sleep and side-effects subscore showed low internal consistency (alpha = 0.31). Several subscales of the electronic SRI questionnaire also demonstrated low alpha coefficients. Conclusion Although the Japanese translation of the S 3 -NIV questionnaire was linguistically validated and electronically feasible, reduced internal consistency was observed in specific subscales. Similar findings in the electronic SRI questionnaire suggest that factors related to mode of administration may influence measurement properties; however, this hypothesis requires confirmation in adequately powered equivalence studies.

OBJECTIVES:To enhance prognostic modeling in patients with non-small cell lung cancer (NSCLC), we developed and externally validated a novel radiomics framework integrating region-specific feature selection and stacked modeling of radiomic signatures derived from anatomical and dosimetric subregions. METHODS:This retrospective, multi-institutional study included 137 patients with advanced-stage NSCLC treated with either three-dimensional conformal radiotherapy (3D-CRT) or volumetric modulated arc therapy (VMAT). From pre-treatment computed tomography (CT) images, 837 radiomic features were extracted per region from segmented volumes including the gross tumor volume (GTV), peritumoral tissue, lung parenchyma, and dose-defined regions. Region-wise feature selection was performed using least absolute shrinkage and selection operator (LASSO)-Cox regression to generate four regional radiomic scores (Radscores). A final Stacked Radiomics model was constructed by combining these scores using survival-guided Cox regression coefficients. Prognostic performance was evaluated using the concordance index (C-index), Kaplan-Meier analysis, and log-rank testing. RESULTS:In the training cohort, the Stacked model demonstrated superior prognostic accuracy (C-index = 0.86), compared to the Layer-wise (0.83) and Conventional models (0.79). External validation confirmed the robustness of the Stacked model (C-index = 0.87), outperforming the Layer-wise (0.74) and Conventional models (0.73). Region-specific analysis revealed that GTV and peripheral regions contributed most to survival prediction, while lung parenchyma features had limited generalizability. CONCLUSIONS:Our survival-driven, region-aware radiomics framework significantly improves outcome prediction in advanced-stage NSCLC, offering a promising approach for personalized risk stratification and treatment planning.

BACKGROUND:Non-small cell lung cancer (NSCLC) is diagnosed using small biopsy samples obtained by bronchoscopy or transthoracic lung core biopsy, and treated with immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and programmed cell death protein ligand-1 (PD-L1) inhibitors, as the first-line therapy. However, the clinical benefits of first-line PD-1/PD-L1 inhibitors in non-small cell carcinoma-not otherwise specified (NSCC-NOS) remain unclear. This study aimed to clarify the clinical efficacy of first-line PD-1/PD-L1 inhibitors in patients with NSCC-NOS. METHODS:We retrospectively enrolled patients with recurrent or unresectable advanced NSCLC treated with first-line PD-1/PD-L1 inhibitors, with or without chemotherapy, at three medical institutions. We adjusted for patient characteristics using propensity score matching (PSM) and analyzed the impact of the histological subtype, NSCC-NOS, on survival outcomes in patients with NSCLC treated with immunotherapy. RESULTS:Of the 312 eligible patients, 42 (13.5%) had a histological subtype of NSCC-NOS. Significantly more patients had PD-L1 ≥ 50% in the NSCC-NOS group than in the Non NSCC-NOS group (P = 0.01). After PSM, 41 patients with NSCC-NOS and 123 with other histological subtypes (Non NSCC-NOS) were analyzed. The median progression-free survival (PFS) and the median overall survival (OS) of patients with NSCC-NOS were significantly longer than those of patients with Non NSCC-NOS, respectively (median PFS: 14.8 vs. 6.1 months, P < 0.01; median OS: 33.4 vs. 15.1 months, P = 0.04, log-rank test). CONCLUSIONS:NSCC-NOS is a histological subtype that is highly responsive to first-line PD-1/PD-L1 inhibitors with or without chemotherapy.

BACKGROUND:Small-field dosimetry plays a pivotal role in stereotactic body radiation therapy (SBRT), where high-precision dose delivery is essential. In multi-institutional clinical trials, quality assurance (QA) becomes increasingly critical due to the variability in linear accelerator (linac) output calibration and treatment planning system (RTPS) configurations. Conventional relative dose factor, which assess relative dose outputs, lack absolute dose information and thus cannot verify the consistency of linac calibration or monitor unit (MU)-to-dose conversion across institutions. These limitations may compromise treatment quality and undermine the integrity of clinical trials. Therefore, an enhanced QA method that incorporates absolute dosimetry is required. PURPOSE:This study introduces and implements a novel credentialing procedure for small-field dosimetry in SBRT clinical trials using the absorbed dose per MU, expressed in cGy/MU. By integrating absolute dose information into the verification process, this method aims to evaluate both linac output calibration and small-field modeling accuracy across institutions. METHODS:A nationwide dosimetric survey was conducted involving 545 beams from 120 institutions participating in Japan Clinical Oncology Group (JCOG) trials. Treatment plans were created in each institution's RTPS by prescribing 10 Gy to the isocenter for square field sizes of 2 × 2 to 10 × 10 cm2. Doses were calculated at depths of 5 and 10 cm in a virtual water phantom under a fixed source-to-surface distance of 90 cm. The absorbed dose per MU values were calculated and compared against multicenter averages stratified by linac type and beam energy. A ±3% tolerance criterion was applied for credentialing. Institutions with deviations were contacted and corrective actions were taken as needed. RESULTS:Of the 545 beams analyzed, 97.8% met the ±3% tolerance criteria. Discrepancies in the ten beams were attributed to small-field beam modeling errors or incorrect RTPS MU-to-dose settings, which were subsequently corrected through feedback. Although variations were observed between the dose calculation algorithms and RTPSs, the differences were within 0.6%, 0.4%, and 1.6%, respectively. The credentialing process proved robust in standardizing dose calculations for clinical trial participation. CONCLUSION:The proposed absorbed dose per MU-based method enables comprehensive small-field dosimetry evaluation by incorporating absolute dose verification into the credentialing process. This approach effectively identifies calibration inconsistencies that are not detectable using traditional relative dose factor methods. Its application across a large cohort of institutions demonstrated high accuracy and inter-institutional consistency, reinforcing its utility as a practical QA tool in SBRT clinical trials. By enhancing standardization in RTPS performance and linac output verification, this method strengthens the foundation of safe and reliable SBRT implementation in multi-center clinical research.

BACKGROUND/AIM:Pembrolizumab combined with pemetrexed is efficacious in older patients with metastatic non-squamous non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of <50%. However, treatment-related pneumonitis is concerning, and its impact on clinical outcomes is not fully understood. In this study, we examined the effect of pneumonitis on treatment efficacy and survival in the CJLSG1901 study, with a focus on differences in baseline patient characteristics. PATIENTS AND METHODS:Subgroup analyses were performed to explore the efficacy and safety of pembrolizumab plus pemetrexed in older patients with metastatic non-squamous NSCLC, focusing on whether pneumonitis developed after treatment initiation. RESULTS:Of the 48 patients included, five and four patients developed grade 1-2 and grade 3 pneumonitis, respectively. The pneumonitis group was predominantly male; postoperative recurrence was nearly twice as common in the group. Patients with pneumonitis received fewer treatment cycles. The objective response rates were 44.4% and 35.9% in the pneumonitis and non-pneumonitis groups, respectively. The median progression-free survival was shorter in the former. In contrast, the median overall survival was comparable between the groups. CONCLUSION:Although patients with pneumonitis had numerically higher response rates, their survival outcomes were comparable to those of patients without pneumonitis.

This survey examined the real-world practice of radiotherapy for small-cell lung cancer (SCLC) in Japan, focusing on treatment strategies for limited-disease SCLC (LD-SCLC) and extensive-disease SCLC (ED-SCLC). This study aimed to identify inter-institutional differences, optimize treatment strategies and explore opportunities for standardization. A questionnaire was distributed to members of the Japanese Radiation Oncology Study Group, and responses were collected from 15 December 2023 to 14 March 2024. Responses to 11 questions specifically related to SCLC treatment strategies were analyzed. Among the 112 institutions, 38.3% did not set an upper age limit for concurrent chemoradiotherapy in LD-SCLC, whereas 31.3% set the limit at 80 years. The most commonly used chemotherapy regimen was cisplatin plus etoposide (79.5%), and the predominant radiotherapy fractionation schedule was twice-daily 45 Gy in 30 fractions (97.3%). Elective nodal irradiation (ENI) was ommited in 30.4% of institutions, while 17.9% reported performing ENI in all cases. Intensity-modulated radiation therapy (IMRT) was introduced in 71.4% of institutions, with D50% as the most frequently used dose-prescription method (47.5%). After achieving complete response, 16.1% of institutions routinely perform prophylactic cranial irradiation (PCI) in all patients. Hippocampus-sparing PCI was not widely used at the time of the survey (13.3%). In conclusion, this Japanese nationwide survey highlighted the SCLC treatment patterns and differences compared with non-small lung cancer (NSCLC). ENI omissions and IMRT have become increasingly adopted for SCLC, whereas clinical target volume margin definitions show some variation compared with NSCLC. Regular surveys are essential to monitor the evolution of treatment strategies.

Lung cancer is one of the malignancies for which new clinical evidence has accumulated most rapidly in recent years. In parallel with advances in systemic therapy, radiotherapy has also evolved substantially with the development of high-precision techniques such as stereotactic body radiotherapy (SBRT), intensity-modulated radiotherapy, and particle therapy. These technological innovations, together with the introduction of immunotherapy and targeted therapies, have reshaped the role of radiotherapy within multidisciplinary treatment strategies for non-small cell lung cancer (NSCLC). This review summarizes current clinical practice and emerging perspectives in radiotherapy for NSCLC across disease stages. In early-stage disease, the established role of SBRT and the potential advantages of particle therapy as curative strategies for medically inoperable patients and for operable patients who refuse surgery are outlined. For locally advanced NSCLC, evolving treatment paradigms in the era of immunotherapy are reviewed, including concurrent chemoradiotherapy followed by consolidation immunotherapy, as well as ongoing efforts to reduce treatment-related toxicity through advances in radiotherapy techniques. In addition, the emerging role of radiotherapy as local consolidative therapy for oligometastatic stage IV NSCLC is highlighted, with attention to recent randomized trials and the challenges of patient selection. As treatment strategies for NSCLC continue to evolve rapidly, radiotherapy is expected to play an increasingly important role in multidisciplinary management. Further research is required to optimize treatment sequencing, identify patients most likely to benefit from radiotherapy, and refine its integration with modern systemic therapies. Radiotherapy remains a key component of multidisciplinary management for non-small cell lung cancer (NSCLC). This review summarizes current clinical evidence and the evolving roles of radiotherapy across disease stages, including early-stage, locally advanced, and oligometastatic NSCLC.

BACKGROUND:Experience with helmet noninvasive ventilation (NIV) for COVID-19-related acute hypoxemic respiratory failure in Asian populations is limited. In this single-center retrospective study, we describe our experience with helmet NIV in selected CPAP responders with COVID-19-related acute hypoxemic respiratory failure in Japan. METHODS:We included adults with COVID-19-related acute hypoxemic respiratory failure treated with NIV between January 2020 and December 2023. Patients who continued facemask NIV were assigned to the facemask group and those switched to helmet NIV after continuous positive airway pressure (CPAP) titration to the helmet group. The primary endpoints in the helmet group were tracheal intubation and 28-day mortality; exploratory comparisons of physiological parameters and outcomes were performed between groups. RESULTS:Fifty patients were included, 19 in the helmet group. In the helmet group, the tracheal intubation rate was 31.6% and 28-day mortality was 5.2%. Switching from facemask to helmet NIV significantly reduced respiratory rate and increased the ROX index, indicating improved oxygenation, without major adverse events. Compared with the facemask group, the helmet group tolerated higher CPAP levels and had longer NIV duration, whereas intubation rates, ventilator-free days, and mortality did not differ significantly between groups. CONCLUSIONS:Helmet NIV was feasible in a highly selected subset of patients who showed favorable responses to CPAP and was associated with improvements in oxygenation and respiratory rate. Owing to the substantial selection bias and small sample size, all between-group comparisons are exploratory and hypothesis-generating.

Rationale: While Interstitial Pneumonia with Autoimmune Features (IPAF) was proposed in 2015, and several studies have shown that IPAF-UIP has a similar prognosis to IPF, the prognostic impact of individual IPAF histopathological features with histological UIP(h-UIP) pattern in interstitial lung disease (ILD) remains inadequately studied. Objective: To investigate the prognostic significance of individual IPAF histopathological features in patients with idiopathic interstitial pneumonias (IIPs) showing h-UIP pattern. Methods: Among 524 patients with ILD from 39 institutes who underwent surgical lung biopsy, 444 were diagnosed with IIPs through multidisciplinary discussion meetings using a cloud-based integrated database. Of these, 323 patients with pathologically confirmed UIP pattern were retrospectively analyzed. UIP pattern was defined as cases in which pathological features of UIP were confirmed by expert pathologists. The relationship between individual IPAF histopathological features and prognosis was evaluated using Cox proportional hazards model. A subsequent analysis was performed in a subgroup of patients with UIP or probable UIP pattern on HRCT. Results: The median age was 66 years (60-70), with 223 males (69%). The cohort included 209 patients with IPF and 114 with unclassifiable ILD. Of the pathological UIP patterns, 122 cases showed UIP pattern alone, while the remaining cases demonstrated concurrent features including NSIP (n=134), bronchiolocentric IP (n=52), PPFE (n=13), OP (n=17), and other unclassifiable features (n=52). HRCT patterns were distributed as follows: UIP (n=36), probable UIP (n=177), and others (n=109).Histopathological IPAF features included interstitial lymphoid aggregates in 42 (13%), cellular infiltration in 59 (18%), bronchiolitis in 18 (6%), pleuritis in 13 (4%), NSIP in 134 (41%), and OP in 16 (5%). In the Cox proportional hazards model adjusted for ILD-GAP, the following hazard ratios were observed: lymphoid aggregates (HR 0.31, 95% CI 0.14-0.73, p=0.007), interstitial cellular infiltration (HR 0.80, 0.47-1.4, p=0.41), bronchiolitis (HR 0.33, 0.082-1.4, p=0.13), pleuritis (HR 1.1, 0.35-3.5, p=0.85), OP (HR 0.67, 0.29-1.6, p=0.37), NSIP (HR 0.89, 0.59-1.4, p=0.60), and UIP or probable UIP pattern on HRCT (HR 1.3, 0.86-2.1, p=0.19).In cases with UIP pattern on HRCT, lymphoid aggregates maintained significance with HR 0.18 (95%CI 0.056-0.59, p=0.005). Conclusions: In ILD with h-UIP pattern, lymphoid aggregates served as a significant prognostic indicator, while the coexistence of NSIP or OP patterns did not impact prognosis. The presence of lymphoid aggregates in histological findings may account for the heterogeneous clinical courses observed in UIP patients.

BACKGROUND AND OBJECTIVE:Patients with interstitial lung disease (ILD) often experience exertional desaturation even without resting hypoxemia, resulting in limited exercise capacity. While oxygen administration can extend exercise time in a majority of patients with ILD, the factors determining the oxygen effects are unclear. We aimed to investigate the clinical significance of respiratory and pulmonary haemodynamic parameters for the oxygen effects on exercise time in patients with ILD. METHODS:We retrospectively analysed patients with ILD who underwent comprehensive evaluation including right heart catheterisation from 2017 to 2021. Patients were divided into oxygen responders, defined as an improvement of at least 100 s or 33% in exercise time with oxygen supplementation compared with medical air inhalation, and non-responders. Univariate and multivariate logistic regression analyses were conducted to evaluate significant factors for oxygen responders. RESULTS:Among 86 patients, 50 (58.1%) were oxygen responders. Pulmonary functional tests and ventilation parameters at cardiopulmonary exercise testing were similar between the groups. Mean pulmonary arterial pressure (mPAP) (21 mmHg vs. 19 mmHg, p = 0.049) was higher in oxygen responders. Univariate logistic analysis demonstrated that the ILD-Gender-Age-Physiology index, mPAP, 6-min walking distance, peak work rate, and lowest ventilatory equivalent for carbon dioxide were significant variables for oxygen effects on exercise time. Multivariate analysis demonstrated that elevated mPAP was independently associated with the oxygen effects on exercise time. CONCLUSION:Approximately 60% of the patients with ILD who experienced exertional desaturation without resting hypoxemia were oxygen responders. mPAP was associated with the oxygen effects on exercise time.