Anti-programmed death 1 (PD-1) antibodies, a type of immune checkpoint inhibitor (ICI), have enhanced survival rates in non-small cell lung cancer (NSCLC). While some patients with NSCLC have pre-existing interstitial lung disease (ILD), data on the long-term safety and effectiveness of anti-PD-1 antibodies for this group are still unclear. We examined patients with advanced NSCLC who experienced recurrence after surgery or radiotherapy and received anti-PD-1 antibody monotherapy at Aichi Cancer Center Hospital from December 2015 to December 2018. The study assessed the connection between progression-free survival (PFS) and overall survival (OS) with respect to pre-existing ILD, and also investigated how ICI-induced pneumonitis impacted OS. Among the 200 patients, 35 (17.5

In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (EFS) and pathologic complete response in patients with resectable non-small cell lung cancer (R-NSCLC), with a safety profile consistent with the individual agents. We report EFS from a second planned interim analysis, interim disease-free survival (DFS) and overall survival (OS), and safety, after all patients completed/discontinued treatment. In this phase III, double-blind, placebo-controlled study, patients with treatment-naïve R-NSCLC (stage II-IIIB [N2]) were randomly assigned (1:1) to neoadjuvant platinum-based chemotherapy plus durvalumab/placebo (once every 3 weeks, four cycles) presurgery and then adjuvant durvalumab/placebo (once every 4 weeks, 12 cycles). Efficacy was analyzed in the modified intention-to-treat population (n = 740; for DFS, its resected subpopulation), which excluded patients with documented EGFR/ALK aberrations. As of May 10, 2024 (median follow-up, 25.9 months [censored patients]), EFS benefit favoring the durvalumab arm remained consistent (hazard ratio [HR], 0.69 [95% CI, 0.55 to 0.88]). Numerical improvement in DFS (HR, 0.66 [95% CI, 0.47 to 0.92]) and OS (HR, 0.89 [95% CI, 0.70 to 1.14]) favored the durvalumab arm. Maximum grade 3/4 adverse events occurred in 15.4% and 10.6% of the durvalumab and placebo arms, respectively, during adjuvant treatment. These results further support perioperative durvalumab plus neoadjuvant chemotherapy as a new treatment option.

Background The global KEYNOTE-671 (clinicaltrials.gov, NCT03425643) study demonstrated significantly improved survival with perioperative pembrolizumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in early-stage non–small-cell lung cancer (NSCLC). We present findings from Japanese participants from KEYNOTE-671. Methods Eligible participants (≥18 years) with previously untreated stage II, IIIA, or IIIB (N2) NSCLC were randomized 1:1 to neoadjuvant pembrolizumab 200 mg or placebo plus cisplatin-based chemotherapy every 3 weeks for ≤4 cycles followed by surgery and adjuvant pembrolizumab or placebo for ≤13 cycles (⁓9 months). Primary endpoints were event-free survival (EFS) and overall survival (OS). Results Among 82 participants enrolled in Japan, 39 were randomized to pembrolizumab and 43 to placebo. Median time from randomization to database cutoff (August 19, 2024) was 52.7 (range, 32.7‒74.9) months. The 48-month EFS rates (95% CIs) were 60.3% (42.8%‒74.0%) and 39.2% (24.8%‒53.4%), respectively, and the EFS HR was 0.54 (95% CI, 0.29‒1.02). For OS, 48-month rates (95% CIs) were 79.5% (63.1%‒89.2%) and 68.9% (52.4%‒80.7%), and the OS HR was 0.76 (95% CI, 0.33‒1.78). Grade ≥3 treatment-related AEs occurred in 23 participants (59%) treated with pembrolizumab and 20 participants (47%) with placebo; there were no deaths due to treatment-related AEs. Conclusions Perioperative pembrolizumab plus neoadjuvant chemotherapy improved efficacy versus neoadjuvant chemotherapy alone and had manageable safety in Japanese participants enrolled in KEYNOTE-671, supporting the use of perioperative pembrolizumab in Japanese patients with early-stage NSCLC. (ClinicalTrials.gov, NCT03425643)

BACKGROUND:Lung cancer patients with interstitial pneumonia (IP) have limited treatment options due to the risks associated with therapeutic intervention. The underlying causes of IP in these patients are diverse, and there is currently no detailed molecular pathological classification or an established understanding of the effectiveness of anti-fibrotic medications such as nintedanib. This study aimed to elucidate the mechanism of action of nintedanib by analyzing differential RNA expression between normal and fibrotic lung tissues from lung cancer patients with IP. METHODS:RNA was analyzed from the non-tumor lung tissue of 7 patients with IP who received nintedanib before surgery. Non-tumor lung tissue was obtained from 12 lung cancer patients without IP complications who underwent radical surgery between 2017 and 2022 from the tissue bank of our institution. Fibrotic lung tissue from six IP patients who received nintedanib before surgery and 7 who did not (where RNA analysis was possible). Gene expression and microenvironmental analyses were performed using RNA sequencing data. RESULTS:Nintedanib modulated inflammation in non-tumor lung tissue, suppressing PLA2G2D and upregulating CST2 and MMP11, suggesting minimal impact on normal tissue and a favorable safety profile. In fibrotic lung lesions, nintedanib suppressed MUC6, ITLN1, and AREG expression. xCell2 analysis indicated reduced plasma cells and increased smooth muscle, muscle, adipocyte, and endothelial cells, suggesting normalization of tissue remodeling. INTERPRITATION:Nintedanib appears to exert anti-inflammatory effects and promote tissue repair in non-tumor lung, while facilitating tissue remodeling in fibrotic areas, indicating potential benefits in patients with interstitial pneumonia and lung cancer.

Epstein-Barr virus-associated gastric cancer (EBVaGC) is a distinct histological and molecular subtype of gastric cancer. Histologically, it is characterized by marked lymphocytic infiltration; molecularly, it exhibits a hypermethylated phenotype. The diagnosis of surgical pathology relies on the detection of BEV-encoded RNA in situ hybridization (EBER-ISH) in tumor cells. To diagnose the histological type related to EBV is crucial, as EBVaGC is a potential target for treatment with programed cell death-1/programed cell death ligand-1 inhibitors. This study comprehensively analyzed viral and tumor gene expression in EBVaGC using RNA sequencing (RNA-seq). Six cases of EBVaGC, including one with heterogeneous EBER-ISH expression, were investigated. RNA was extracted from formalin-fixed, paraffin-embedded tissue sections and analyzed using RNA-seq. EBER-ISH-positive and negative areas from tumors with heterogeneous EBER-ISH expression were separately collected using modified manual microdissection techniques. EBV gene expression in EBVaGCs varied among the tumors. Viral gene expression was observed even in EBER-ISH-negative lesions in tumors showing heterogeneous EBER-ISH expression. Gene expression and set enrichment analyses revealed that EBVaGC was highly immunogenic, whereas EBER-ISH-negative lesions were not. However, EBVaGC tumor gene expression patterns, including EBER-ISH-negative lesions, were classified into the same cluster. Viral RNA expression in EBVaGC was heterogenous and even EBER expression fluctuates, suggesting that EBV infection in EBVaGC may not be detected by EBER-ISH alone.

In this article, we describe a previously underrecognized pattern of aerogenous dissemination to the lungs, based on 2 cases of sinonasal DEK::AFF2 carcinoma. Over follow-up periods of 10 and 18 years, respectively, both patients exhibited recurrent multiple endotracheal and endobronchial metastases. These lesions were successfully managed with endoscopic tumor resection. No lymph node involvement or distant metastases beyond the trachea and bronchi were observed; they were entirely absent in one case and largely absent in the other. Based on these clinical courses, the tracheobronchial dissemination was most plausibly interpreted as aerogenous rather than lymphatic or hematogenous spread. DEK::AFF2 carcinoma appears to exhibit three key biological features favoring aerogenous dissemination: anatomic location of the primary tumor, loss of intercellular adhesion, and strong affinity for ciliated respiratory epithelium. These cases may help enhance our understanding of aerogenous tumor cell spread, including phenomena such as spread through air spaces (STAS).

Pulmonary spindle cell tumors are aggressive neoplasms with limited systemic treatment options, although a subset may harbor actionable genomic alterations. Because conventional fusion assays may miss rearrangements involving atypical or previously uncharacterized partners, we systematically investigated oncogenic fusions in pulmonary spindle cell tumors using anchored multiplex PCR-based targeted RNA sequencing. Formalin-fixed, paraffin-embedded tumor samples from 11 surgically resected pulmonary spindle cell tumors, excluding metastatic sarcomas, were analyzed using the FusionPlex Sarcoma panel supplemented with custom primers for RET, NTRK1, NTRK2, and NRG1. Two tumors (18.2%) harbored ALK fusions, identified as PPFIBP1::ALK and SYCL3::ALK. Both tumors showed positive ALK immunohistochemical staining. Histologically, the PPFIBP1::ALK-positive tumor was composed of spindle-shaped cells with a layered architecture, whereas the SYCL3::ALK-positive tumor showed relatively round cells arranged in clusters with collagenous stroma, highlighting the morphologic heterogeneity of ALK-rearranged pulmonary spindle cell tumors. These findings expand the molecular spectrum of pulmonary spindle cell tumors and identify rare ALK fusion partners in this setting. Our results support the incorporation of ALK immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of ALK-directed therapy in these rare tumors.

At the first interim analysis of the global, randomized, phase 3, double-blind ADRIATIC trial in patients with limited-stage small-cell lung cancer (LS-SCLC) not progressing after concurrent chemoradiotherapy (cCRT), consolidation durvalumab significantly improved overall survival (OS; hazard ratio [HR] 0.73) and progression-free survival (PFS) by blinded independent central review (BICR; HR 0.76) versus placebo (dual primary endpoints). We report an exploratory analysis in patients enrolled in Japan. Patients received durvalumab 1500 mg (N = 264), durvalumab+tremelimumab 75 mg (4 doses, N = 200; arm remained blinded), or placebo (N = 266) every 4 weeks for ≤ 24 months. Prior cCRT ± prophylactic cranial irradiation (PCI) was per local standards of care. In the Japan subgroup, 19 and 31 patients received durvalumab and placebo, respectively; prior cCRT comprised cisplatin-etoposide/carboplatin-etoposide in 94.7/5.3% and 87.1/12.9% and once-daily/twice-daily radiotherapy in 10.5/89.5% and 0/100%; 52.6% and 58.1% received PCI. Median OS was not reached versus 44.9 months (3-year OS 67.4% versus 58.1%; HR 0.67, 95% CI 0.24-1.62). Median PFS by BICR was 44.2 versus 29.4 months (24-month PFS 59.6% vs. 58.6%; HR 1.05, 95% CI 0.44-2.36); median PFS by investigator assessment (sensitivity analysis) was 44.2 versus 19.7 months (24-month PFS 65.6% vs. 47.0%; HR 0.68, 95% CI 0.28-1.51). With durvalumab and placebo, 21.1% and 19.4% had maximum grade 3-4 adverse events (AEs), 21.1% and 9.7% had AEs leading to treatment discontinuation, and 52.6% and 45.2% had pneumonitis/radiation pneumonitis (grade 3-4: 0% and 6.5%). In conclusion, consolidation durvalumab demonstrated a favorable risk/benefit profile in Japanese patients with LS-SCLC post cCRT. Trial Registration: ClinicalTrials.gov identifier: NCT03703297.

BACKGROUND:High-grade serous ovarian carcinoma (HGSOC) accounts for 70% of all ovarian cancer cases and 80% of related deaths. TP53 mutations are common; however, other driving genetic factors are not well understood. In this study, we used RNA sequencing to explore the genetic background of HGSOC in patients with unclear profiles. METHODS:This study included 80 patients with a pathological diagnosis of HGSOC. RNA sequencing was performed to analyze gene expression and detect fusion. RESULTS:We identified 18 novel potential driver fusion gene candidates, including in-frame and frameshift fusions, in 80 patients with high-grade serous ovarian cancer (HGSOC). Of these, ST7-OT4::MET, STK24::DOCK9, GAB::PAK1, HDAC1::LCK, ESR1::LATS1, ZNF157::CDK16, NEK7::RP11-85M11.2, CAMKK1::R2RX1, HNRNPUL1::AXL, DYRK1A::GART, MAPKAPK2::DYRK3, and FER::GS1421I3.2 involved fusion partners harboring protein kinase domains. Notably, TAOK1::PIPOX and PSMD11::NLK were identified in the same case, similar to SH3PXD2A::BMPR1A and EIF3H::CAMK2D in another case. In addition, SLMAP::NTRK3 involves NTRK3, a known fusion partner. The remaining fusions, SWAP70::ZNF143, WDR25::YY1, and NR2F6::MYO9B, included partners with DNA-binding domains. CONCLUSIONS:This study identified candidate driver fusion genes and suggested new therapeutic targets for HGSOCs.

BACKGROUND:Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma, accounting for 3%-10% of cases. It is often associated with KRAS mutations or, in nonsmokers, NRG1 fusions. Approximately 20% of IMAs have unclear genomic backgrounds. This study aimed to clarify the genomic etiology of these cases through a retrospective molecular analysis and RNA sequencing. PATIENTS AND METHODS:This study analyzed 107 cases of NSCLC that were treated by surgical resection at Aichi Cancer Center from 2009 to 2023, with a focus on IMAs. For cases with unclear genomic backgrounds, RNA sequencing was conducted to identify potential driver gene alterations, and the results were compared to those of known KRAS-positive cases. Statistical analyses, including Cox regression and Kaplan-Meier analyses, were used to evaluate risk factors, recurrence-free survival, and the prognosis. RESULTS:In this study, 107 cases of resected IMA were analyzed. KRAS mutations were found in 70.1% of cases, followed by NRG1 fusions (9.2%), and other mutations. A novel fusion gene, ATP6V1H::LYN, was discovered in 1 case. RNA sequencing and a gene set enrichment analysis revealed distinct molecular pathways in KRAS-positive tumors, including the activation of oxidative phosphorylation and TNFα-NF-κB signaling. Tumors with no driver gene alterations exhibited a higher frequency of copy number variations and tumor mutational burden than KRAS and NRG fusion-positive cases. CONCLUSION:IMAs are characterized by relatively higher incidences of harboring KRAS mutations and NRG fusion genes, revealing potential therapeutic targets including druggable mutations and immune-related markers, while highlighting the heterogeneous genomic background and utility of RNA sequencing.

8009 Background: In AEGEAN, perioperative durvalumab (D) + neoadj CT significantly improved the primary endpoints of event-free survival (EFS) and pathological complete response (pCR) vs neoadj CT alone in pts with R-NSCLC. Prior analyses of AEGEAN suggest that pts without ctDNA clearance during neoadj Tx or with molecular residual disease (MRD; i.e. ctDNA detected) at a landmark timepoint after Sx (adj C1D1) had worse outcomes. Using data from all biomarker-evaluable pts, we report exploratory analyses for associations of post-Sx MRD status with pt characteristics, neoadj ctDNA dynamics, pathological response, genomic mutations and outcomes. Methods: AEGEAN is a double-blind PBO-controlled study (NCT03800134). Adults with Tx-naïve R-NSCLC (stage II–IIIB[N2]) and ECOG PS 0/1 were randomized 1:1 to receive neoadj platinum-based CT + D or PBO IV (Q3W, 4 cycles) before Sx followed by D or PBO IV (Q4W, 12 cycles) after Sx. Efficacy was assessed in the mITT population, which excluded pts with known EGFR / ALK aberrations. ctDNA analysis was performed on plasma collected before each neoadj Tx cycle, Sx, and adj C1, C3/4 and C10/11 using pt-specific tumor-informed assays. Whole exome sequencing analysis of diagnostic tumor biopsies was performed to identify mutations associated with MRD status at the post-Sx landmark. Results: Among MRD-evaluable pts, 10% (17/168) were MRD-positive (D, n=10; PBO, n=7) and 90% (151/168) were MRD-negative (D, n=78; PBO, n=73) at the landmark timepoint (median 6.9 wk post-Sx). 88% [15/17] of MRD-positive pts were initially diagnosed with stage III disease. In the D arm, the majority of MRD-positive pts (9/10) also had ctDNA detected at the pre-Sx visit. No MRD-positive pts in the D arm had pCR or major pathological response. As expected, overall disease-free survival (DFS) rates at 12 mo were worse in MRD-positive (14.3%; 95% CI, 2.4–36.3) vs MRD-negative pts (89.3%; 95% CI, 82.6–93.5). In both arms, MRD-positive pts had worse DFS outcomes vs MRD-negative pts (D: HR, 21.28; 95% CI, 7.70–58.83; PBO: HR, 14.29; 95% CI, 4.94–41.36) with DFS trends favoring the D vs PBO arm, particularly in pts with no ctDNA detected (MRD-negative: HR, 0.56; 95% CI, 0.26–1.20; MRD-positive: HR, 0.78; 95% CI, 0.26–2.36). Mutated genes associated with MRD-positive status in the D arm included KEAP1 and KMT2C ; despite small pt numbers, EFS benefit in the D vs PBO arm was not evident in pts with the mutations (m) (KEAP1 m: HR, 1.39; 95% CI, 0.29–6.77; KMT2C m : HR, 2.03; 95% CI, 0.70–5.91). In contrast, EFS benefit was evident in pts with wild type (wt) ( KEAP1 wt: HR, 0.54; 95% CI, 0.36–0.79; KMT2C wt: HR, 0.52; 95% CI, 0.35–0.78). Conclusions: Exploratory analyses based on post-Sx MRD status and genomic analysis identified a small high-risk subgroup of pts with markedly worse prognosis with potentially reduced benefit from the AEGEAN regimen. Clinical trial information: NCT03800134 .

In the randomized phase III CheckMate 77T study, perioperative nivolumab showed statistically significant and clinically meaningful improvement in event-free survival (EFS) vs. placebo in patients with resectable, non-metastatic non-small cell lung cancer (NSCLC). Here, we report efficacy and safety outcomes in the Japanese subpopulation. Adults with resectable stage IIA-IIIB NSCLC were randomized 1:1 to neoadjuvant nivolumab plus chemotherapy or chemotherapy plus placebo every 3 weeks for ≤ 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for ≤ 13 cycles. Assessments included EFS (primary endpoint), pathological complete response (pCR), major pathological response (MPR), and safety. A total of 68 Japanese patients were randomized to perioperative nivolumab (n = 40) or placebo (n = 28). At 24.9 months' median follow-up, median EFS was not reached (NR; 95% CI: 21.4-NR) with perioperative nivolumab vs. 12.1 (95% CI: 8.1-NR) months with placebo (hazard ratio, 0.46 [95% CI: 0.22-0.95]); 18-month EFS rates were 76.6% vs. 42.9%, respectively. The pCR rate (95% CI) was 42.5% (27.0%-59.1%) with perioperative nivolumab vs. 0% (0%-12.3%) with placebo (odds ratio [OR], not available); MPR rate (95% CI) was 52.5% (36.1%-68.5%) vs. 7.1% (0.9%-23.5%), respectively (OR, 14.37; 95% CI: 3.00-68.82). Grade 3-4 treatment-related and surgery-related adverse events with perioperative nivolumab vs. placebo occurred in 55.0% vs. 39.3% and 16.7% vs. 19.2% of patients. Consistent with the global population, perioperative nivolumab improved EFS, pCR, and MPR vs. placebo in the Japanese subpopulation, with no new safety signals reported, supporting its use in Japanese patients with resectable NSCLC. Trial Registration: ClinicalTrials.gov identifier, NCT04025879.

In this article, we describe a previously underrecognized pattern of aerogenous dissemination to the lungs, based on 2 cases of sinonasal DEK::AFF2 carcinoma. Over follow-up periods of 10 and 18 years, respectively, both patients exhibited recurrent multiple endotracheal and endobronchial metastases. These lesions were successfully managed with endoscopic tumor resection. No lymph node involvement or distant metastases beyond the trachea and bronchi were observed; they were entirely absent in one case and largely absent in the other. Based on these clinical courses, the tracheobronchial dissemination was most plausibly interpreted as aerogenous rather than lymphatic or hematogenous spread. DEK::AFF2 carcinoma appears to exhibit three key biological features favoring aerogenous dissemination: anatomic location of the primary tumor, loss of intercellular adhesion, and strong affinity for ciliated respiratory epithelium. These cases may help enhance our understanding of aerogenous tumor cell spread, including phenomena such as spread through air spaces (STAS).

INTRODUCTION:In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN. METHODS:Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics. RESULTS:A total of 737 out of 740 mITT patients received treatment, 366 and 371 in the durvalumab and placebo arms, respectively; 80.6% and 80.7% underwent surgery, 77.6% and 76.7% completed surgery, and of the 295 and 302 patients who underwent surgery, 17.3% and 22.2% had delayed surgery. The median time from last neoadjuvant dose to surgery was 34.0 days in both arms. Of the patients who underwent surgery, similar proportions had open (49.2% versus 50.7%) and minimally invasive (49.2% versus 47.0%) procedures; lobectomy was the most common procedure (88.1% versus 85.4%). R0 resection rates were numerically higher in the durvalumab versus placebo arm (94.7% versus 91.3%). The median time from surgery to first adjuvant dose was 50.0 versus 52.0 days. In exploratory analyses, a numerically higher proportion of patients in the durvalumab versus placebo arm with baseline N2 nodal status had downstaging from N2 to N0 (47.3% versus 40.2%) or, with baseline N1 nodal status, from N1 to N0 (53.6% versus 46.2%) after surgery. Similar proportions had surgical complication(s) (59.1% versus 60.1%), primarily grade 1 or 2 (53.0% versus 51.8%, modified safety analysis set). CONCLUSION:The addition of durvalumab to neoadjuvant chemotherapy had no detrimental effect on the feasibility, approach, type, or timing of surgery and was associated with a tolerable surgical safety profile, versus neoadjuvant chemotherapy alone. CLINICAL TRIAL INFORMATION:ClinicalTrials.Gov Identifier: NCT03800134.

ABSTRACT Background This study evaluated the safety, long‐term survival, and prognostic factors associated with salvage pulmonary surgery following systemic therapy for initially unresectable non‐small cell lung cancer (NSCLC). Methods Between 2014 and 2024, this single‐center retrospective review identified 32 patients (median age: 61.0 years) with NSCLC initially considered unresectable who subsequently underwent curative‐intent pulmonary resection after chemotherapy, targeted therapy, and/or immunotherapy. The primary endpoint was overall survival (OS); secondary endpoints included recurrence‐free survival (RFS), major morbidity (Clavien–Dindo grade ≥ IIIa), and R0 resection rate. The Kaplan–Meier method and log‐rank test were employed. Results Reasons for unresectability at initial diagnosis were distant metastasis (n = 20; 62.5%), N3 nodal disease (n = 6; 18.8%), bulky N2 nodal disease (n = 3; 9.4%), and tumor or nodal extension requiring pneumonectomy (n = 3; 9.4%). Overall, 65.6% patients underwent lobectomy, with R0 resection achieved in 81.3% and pathological complete or major response observed in 15.6%. Overall complication and major morbidity rates were 12.5% and 3.1%, respectively; no 90‐day mortality was observed. After a median follow‐up of 40.1 months, median OS was not reached, whereas median RFS was 49.9 months; 5‐year OS and RFS were 75.0% (95% CI 51.6–88.3) and 46.3% (95% CI 26.3–64.2), respectively. Notably, adenocarcinoma histology was significantly more prevalent in the good‐prognosis group (88.9% vs. 35.7%, p = 0.003). Conclusions Salvage pulmonary surgery following systemic therapy is safe, yielding a 5‐year OS rate of 75% in carefully selected patients with advanced NSCLC. Prevalent adenocarcinoma histology in the good‐prognosis cohort is associated with superior outcomes.

Human papillomavirus (HPV), particularly strains 16 and 18, contributes to oropharyngeal squamous cell carcinoma (OPSCC), even in non-smokers and non-drinkers. This study investigated gene expression variations in HPV-positive OPSCCs according to the virus genotype. An RNA sequencing analysis of 36 p16-positive OPSCC patients revealed distinct expression patterns between tumors with only E6/E7 transcripts (E6E7) and those with additional E5 transcripts (E5-added). The E6E7 group displayed activation of FOS-related pathways and the NF-κB signaling pathway. Notably, the genes associated with tumor growth and cancer antigens differed between the groups. These findings suggest that the presence of HPV E5 might influence the transformation stages and gene expression, potentially affecting patient outcomes. The E5-added group expressed multiple cancer-associated antigens, presenting potential targets for personalized immunotherapy approaches for HPV-positive OPSCC.

Targeted therapy is now the standard of care in driver–oncogene-positive non-small cell lung cancer (NSCLC). Its initial clinical effects are remarkable. However, almost all patients experience treatment resistance to targeted therapy. Hence, chemotherapy is considered a subsequent treatment option. In patients with driver–oncogene-negative NSCLC, combined immune checkpoint inhibitors (ICIs) and chemotherapy as the first-line therapy has been found to be beneficial. However, the efficacy of ICI plus chemotherapy against driver–oncogene-positive NSCLC other than epidermal growth factor receptor mutation and anaplastic lymphoma kinase fusion is unclear. Using the hospital medical records, we retrospectively reviewed advanced or recurrent NSCLC patients who were treated with chemotherapy with or without ICIs at Aichi Cancer Center Hospital between January 2014 and January 2023. Patients with druggable rare mutations such as KRAS-G12C, MET exon 14 skipping, HER2 20 insertion, BRAF-V600E mutations, and ROS1 and RET rearrangements were analyzed. In total, 61 patients were included in this analysis. ICI plus chemotherapy was administered in 36 patients (the ICI-chemo group) and chemotherapy in 25 patients (the chemo group). The median progression-free survival (PFS) rates were 14.0 months in the ICI-chemo group and 4.8 months in the chemo group (hazard ratio [HR] = 0.54, 95