Pub Date : 2026-01-12DOI: 10.1007/s10147-025-02954-4
Situo Zheng, Yosuke Morodomi, Yoshikazu Yonemitsu
Despite multimodal treatment options, most gastrointestinal (GI) cancers remain associated with high mortality rates and poor responsiveness to immunotherapy. The remarkable success of immune cell-based therapies in hematologic malignancies has raised interest in translating adoptive cell therapies to GI cancers. Among these approaches, natural killer (NK) cell-based therapies offer potent cytotoxicity, and a favorable safety profile. Multiple NK cell platforms are now under preclinical and clinical development, demonstrating encouraging therapeutic efficacy in GI malignancies. Nevertheless, challenges such as limited in vivo persistence, immunosuppressive tumor microenvironment (TME), and heterogeneous expression of NK cell therapy targeted antigens continue to limit therapeutic benefit. Recent advances are being explored to overcome these barriers and enhance NK cell persistence and specificity. This review summarizes recent progress in NK cell-based immunotherapy for GI cancers, highlights representative clinical trials, and discusses strategies to improve efficacy and durability. With continued innovation, NK cell-based therapy holds promise to become an essential component of the future immunotherapy landscape for GI malignancies.
{"title":"Current development and challenges of NK cell-based immunotherapy for gastrointestinal cancers.","authors":"Situo Zheng, Yosuke Morodomi, Yoshikazu Yonemitsu","doi":"10.1007/s10147-025-02954-4","DOIUrl":"https://doi.org/10.1007/s10147-025-02954-4","url":null,"abstract":"<p><p>Despite multimodal treatment options, most gastrointestinal (GI) cancers remain associated with high mortality rates and poor responsiveness to immunotherapy. The remarkable success of immune cell-based therapies in hematologic malignancies has raised interest in translating adoptive cell therapies to GI cancers. Among these approaches, natural killer (NK) cell-based therapies offer potent cytotoxicity, and a favorable safety profile. Multiple NK cell platforms are now under preclinical and clinical development, demonstrating encouraging therapeutic efficacy in GI malignancies. Nevertheless, challenges such as limited in vivo persistence, immunosuppressive tumor microenvironment (TME), and heterogeneous expression of NK cell therapy targeted antigens continue to limit therapeutic benefit. Recent advances are being explored to overcome these barriers and enhance NK cell persistence and specificity. This review summarizes recent progress in NK cell-based immunotherapy for GI cancers, highlights representative clinical trials, and discusses strategies to improve efficacy and durability. With continued innovation, NK cell-based therapy holds promise to become an essential component of the future immunotherapy landscape for GI malignancies.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts.
Methods: Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5 mg; C1D8, D15 and C2 onwards, 45 mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1-21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate.
Results: At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing.
Conclusion: Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.
{"title":"Efficacy and safety of subcutaneous mosunetuzumab in combination with lenalidomide and as a monotherapy in Japanese patients with relapsed/refractory follicular lymphoma.","authors":"Shinichi Makita, Koji Izutsu, Yuko Mishima, Takahiro Kumode, Junya Kuroda, Nobuhiro Kanemura, Noriko Fukuhara, Kazuyuki Shimada, Chiemi Mori, Atsuko Kawasaki, Takeshi Miyake, Dai Maruyama","doi":"10.1007/s10147-025-02957-1","DOIUrl":"https://doi.org/10.1007/s10147-025-02957-1","url":null,"abstract":"<p><strong>Background: </strong>JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts.</p><p><strong>Methods: </strong>Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5 mg; C1D8, D15 and C2 onwards, 45 mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1-21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate.</p><p><strong>Results: </strong>At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing.</p><p><strong>Conclusion: </strong>Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR T cell therapy, has demonstrated efficacy in relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, real-world data from commercial settings outside the United States remain limited.
Methods: To evaluate the safety and effectiveness of commercial-use liso-cel in Japan, we conducted a single-center retrospective study of patients with R/R LBCL who received commercial-use liso-cel at our institution between November 2021 and November 2024.
Results: 56 patients received liso-cel infusion. The median age was 66.5 years, and 55.4% had primary refractory disease. Liso-cel was administered as second-line therapy in 14 patients (25.0%) and as third-line or later therapy in 42 patients (75.0%). The best overall response rate was 80.4%, with a complete response rate of 78.6%. At a median follow-up of 12.3 months, 1 year progression-free survival (PFS) and overall survival rates were 69.5% and 86.4%, respectively. The 1 year PFS rates were 68.5% for diffuse large B cell lymphoma not otherwise specified, 100% for primary mediastinal large B cell lymphoma (PMBCL), and 30% for high-grade B cell lymphoma (HGBCL). Grade ≥ 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were observed in one patient each. Multivariate analysis identified HGBCL subtype and higher pre-infusion metabolic tumor volume as independent adverse factors for PFS.
Conclusion: Commercial-use liso-cel demonstrated high response rates and favorable safety in Japanese patients with R/R LBCL. Patients with PMBCL had excellent outcomes, whereas those with HGBCL showed poorer prognosis, indicating a need for further therapeutic strategies.
背景:Lisocabtagene maraleucel (liso-cel)是一种抗cd19 CAR - T细胞疗法,已经证明对复发/难治性(R/R)大B细胞淋巴瘤(LBCL)有效。然而,来自美国以外商业环境的真实数据仍然有限。方法:为了评估商业使用的liso-cel在日本的安全性和有效性,我们对2021年11月至2024年11月在我们机构接受商业使用的liso-cel的R/R LBCL患者进行了单中心回顾性研究。结果:56例患者接受利索细胞输注。中位年龄为66.5岁,55.4%为原发性难治性疾病。14例(25.0%)患者使用Liso-cel作为二线治疗,42例(75.0%)患者使用Liso-cel作为三线或后续治疗。最佳总有效率为80.4%,完全有效率为78.6%。中位随访时间为12.3个月,1年无进展生存期(PFS)和总生存率分别为69.5%和86.4%。1年无特异性弥漫性大B细胞淋巴瘤的PFS为68.5%,原发性纵隔大B细胞淋巴瘤(PMBCL)为100%,高级别B细胞淋巴瘤(HGBCL)为30%。≥3级细胞因子释放综合征和免疫效应细胞相关神经毒性综合征各1例。多因素分析发现HGBCL亚型和较高的输注前代谢肿瘤体积是PFS的独立不利因素。结论:商业使用的liso-cel在日本的R/R LBCL患者中显示出高的缓解率和良好的安全性。PMBCL患者预后良好,而HGBCL患者预后较差,表明需要进一步的治疗策略。
{"title":"Real-world effectiveness and safety of lisocabtagene maraleucel for relapsed/refractory large B cell lymphoma in Japan.","authors":"Tetsuro Ochi, Shinichi Makita, Anna Hiratsuka, Risa Nishiyama, Kimiteru Ito, Akiko Miyagi Maeshima, Wataru Takeda, Noriko Iwaki, Suguru Fukuhara, Wataru Munakata, Koji Izutsu","doi":"10.1007/s10147-025-02946-4","DOIUrl":"https://doi.org/10.1007/s10147-025-02946-4","url":null,"abstract":"<p><strong>Background: </strong>Lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR T cell therapy, has demonstrated efficacy in relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, real-world data from commercial settings outside the United States remain limited.</p><p><strong>Methods: </strong>To evaluate the safety and effectiveness of commercial-use liso-cel in Japan, we conducted a single-center retrospective study of patients with R/R LBCL who received commercial-use liso-cel at our institution between November 2021 and November 2024.</p><p><strong>Results: </strong>56 patients received liso-cel infusion. The median age was 66.5 years, and 55.4% had primary refractory disease. Liso-cel was administered as second-line therapy in 14 patients (25.0%) and as third-line or later therapy in 42 patients (75.0%). The best overall response rate was 80.4%, with a complete response rate of 78.6%. At a median follow-up of 12.3 months, 1 year progression-free survival (PFS) and overall survival rates were 69.5% and 86.4%, respectively. The 1 year PFS rates were 68.5% for diffuse large B cell lymphoma not otherwise specified, 100% for primary mediastinal large B cell lymphoma (PMBCL), and 30% for high-grade B cell lymphoma (HGBCL). Grade ≥ 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were observed in one patient each. Multivariate analysis identified HGBCL subtype and higher pre-infusion metabolic tumor volume as independent adverse factors for PFS.</p><p><strong>Conclusion: </strong>Commercial-use liso-cel demonstrated high response rates and favorable safety in Japanese patients with R/R LBCL. Patients with PMBCL had excellent outcomes, whereas those with HGBCL showed poorer prognosis, indicating a need for further therapeutic strategies.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1007/s10147-025-02955-3
Noriomi Matsumura
{"title":"PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs in Japan; imlunestrant for breast cancer, tafasitamab for follicular lymphoma, atezolizumab for thymic carcinoma, retifanlimab for anal canal squamous cell carcinoma, and tagraxofusp for blastic plasmacytoid dendritic cell neoplasm.","authors":"Noriomi Matsumura","doi":"10.1007/s10147-025-02955-3","DOIUrl":"https://doi.org/10.1007/s10147-025-02955-3","url":null,"abstract":"","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Although human papillomavirus (HPV) vaccines effectively prevent cervical cancer, the HPV vaccination rates in Japan remain low because of concerns about alleged neurological adverse events. Darja Kanduc proposed a flawed hypothesis that molecular mimicry between HPV and human proteins could induce cross-reactive antibodies, causing autoimmune organ damage, even when only the portions of amino acid (AA)-sequences of the epitopes were identical between HPV and human proteins.
Methods: In this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9-23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database.
Results: We found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and respiratory syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having "partial molecular mimicry" than HBV and RSV.
Conclusions: Our current in silico analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events.
{"title":"Lack of molecular mimicry between HPV vaccine L1 antigen and human proteins by a computational analysis.","authors":"Kazuhiro Nishioka, Kentaro Sekiyama, Reona Shiro, Ikuo Tsunoda, Noriomi Matsumura","doi":"10.1007/s10147-026-02961-z","DOIUrl":"https://doi.org/10.1007/s10147-026-02961-z","url":null,"abstract":"<p><strong>Background: </strong>Although human papillomavirus (HPV) vaccines effectively prevent cervical cancer, the HPV vaccination rates in Japan remain low because of concerns about alleged neurological adverse events. Darja Kanduc proposed a flawed hypothesis that molecular mimicry between HPV and human proteins could induce cross-reactive antibodies, causing autoimmune organ damage, even when only the portions of amino acid (AA)-sequences of the epitopes were identical between HPV and human proteins.</p><p><strong>Methods: </strong>In this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9-23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database.</p><p><strong>Results: </strong>We found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and respiratory syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having \"partial molecular mimicry\" than HBV and RSV.</p><p><strong>Conclusions: </strong>Our current in silico analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To evaluate the real-world safety and efficacy of immune checkpoint inhibitors (ICIs) in Japanese patients with persistent, recurrent, or metastatic cervical cancer.
Methods: In this multicenter observational study at four Japanese institutions, 100 patients with recurrent, persistent, or advanced cervical cancer received pembrolizumab or cemiplimab. Primary endpoints were objective response rate (ORR) and the incidence of immune-mediated adverse events (imAEs) and grade 3-5 AEs. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Logistic and Cox regression were used to explore prognostic factors.
Results: Eighteen patients (18%) achieved complete response and 44 (44%) partial response, yielding an ORR of 62.0% and a disease control rate of 77.0%. Median PFS and OS were 10.4 and 22.0 months, respectively. ORR was 74.0% in the first-line setting and 29.6% in the second-line setting. Among patients who met KEYNOTE-826 eligibility criteria, ORR was 82.9% and median PFS 16.1 months. Cemiplimab, which was mainly used as off-label retreatment in frail or previously ICI-exposed patients, showed limited activity (ORR 5.6%). ImAEs occurred in 45.0% of patients, with grade 3-5 events in 19.0% and six treatment-related deaths. Poor performance status and recurrent disease were associated with lower response and shorter PFS, whereas PD-L1 tumor proportion score ≥ 50% and grade 3-5 imAEs were associated with longer PFS.
Conclusion: In this real-world cohort, ICIs, particularly pembrolizumab, demonstrated substantial antitumor activity with acceptable toxicity in Japanese patients with advanced cervical cancer, especially when used as first-line therapy and in patients fulfilling KEYNOTE-826 eligibility criteria.
{"title":"Real-world safety and efficacy of immune checkpoint inhibitors in Japanese patients with persistent, recurrent, or metastatic cervical cancer: a multicenter prospective and retrospective study.","authors":"Kazuhisa Kitami, Shiho Kuji, Natsuko Kamiya, Hiroko Machida, Junki Koike, Reiko Watanabe, Takeshi Hirasawa, Nao Suzuki, Etsuko Miyagi, Kazuyoshi Kato","doi":"10.1007/s10147-025-02951-7","DOIUrl":"https://doi.org/10.1007/s10147-025-02951-7","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the real-world safety and efficacy of immune checkpoint inhibitors (ICIs) in Japanese patients with persistent, recurrent, or metastatic cervical cancer.</p><p><strong>Methods: </strong>In this multicenter observational study at four Japanese institutions, 100 patients with recurrent, persistent, or advanced cervical cancer received pembrolizumab or cemiplimab. Primary endpoints were objective response rate (ORR) and the incidence of immune-mediated adverse events (imAEs) and grade 3-5 AEs. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Logistic and Cox regression were used to explore prognostic factors.</p><p><strong>Results: </strong>Eighteen patients (18%) achieved complete response and 44 (44%) partial response, yielding an ORR of 62.0% and a disease control rate of 77.0%. Median PFS and OS were 10.4 and 22.0 months, respectively. ORR was 74.0% in the first-line setting and 29.6% in the second-line setting. Among patients who met KEYNOTE-826 eligibility criteria, ORR was 82.9% and median PFS 16.1 months. Cemiplimab, which was mainly used as off-label retreatment in frail or previously ICI-exposed patients, showed limited activity (ORR 5.6%). ImAEs occurred in 45.0% of patients, with grade 3-5 events in 19.0% and six treatment-related deaths. Poor performance status and recurrent disease were associated with lower response and shorter PFS, whereas PD-L1 tumor proportion score ≥ 50% and grade 3-5 imAEs were associated with longer PFS.</p><p><strong>Conclusion: </strong>In this real-world cohort, ICIs, particularly pembrolizumab, demonstrated substantial antitumor activity with acceptable toxicity in Japanese patients with advanced cervical cancer, especially when used as first-line therapy and in patients fulfilling KEYNOTE-826 eligibility criteria.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Policy recommendations for promoting nuclear medicine therapy in Japan 2025, from the Working Group for promoting nuclear medicine therapy of the Japan Society of Clinical Oncology.","authors":"Kotaro Suzuki, Hideaki Miyake, Anri Inaki, Shoko Takano, Yasutoshi Kuboki, Takashi Mizowaki, Katsumasa Nakamura, Makoto Ueno, Shigemi Matsumoto, Daisuke Obinata, Tohru Nakagawa, Masato Murakami, Yoshiyuki Majima, Megumu Yokono, Masao Namba, Takayuki Yoshino","doi":"10.1007/s10147-025-02925-9","DOIUrl":"https://doi.org/10.1007/s10147-025-02925-9","url":null,"abstract":"","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The evolving prognosis of colorectal cancer (CRC) over extended periods following surgery has not been comprehensively characterized. This study aimed to delineate long-term patterns in conditional survival (CS), evaluate the changing relevance of CRC recurrence surveillance versus management of fatal non-cancer conditions, and suggest follow-up indicators tailored to postoperative duration.
Methods: We examined trends in conditional overall survival (cOS), disease-specific survival (cDSS), and non-disease-specific survival (cNDSS) by tumor stage in 2,996 patients (stage 0-IV) who underwent surgical resection for CRC. Furthermore, we conducted a multivariate analysis in a cohort of 1,529 patients surviving more than 5 years to identify predictors of long-term survival.
Results: Over a median observation period of 60.4 months, 745 deaths were recorded (478 CRC-related, 243 unrelated to CRC, and 24 unknown). Stage-wise CS analyses revealed crossover points of cDSS and cNDSS at 3 years post-surgery in stage II and at 6 years in stages III/IV. Multivariate analysis identified age ≥ 80, CEA ≥ 5.0 ng/mL, CA19-9 ≥ 37.0 U/mL, albumin ≤ 4.1 g/dL, anemia, RDW ≥ 14.9%, and platelet count ≤ 150 × 109/L as independent risk factors in 5-year survivors.
Conclusions: The importance of CRC recurrence surveillance was most prominent within the first 3 years after surgery in stage II and within 6 years in stages III/IV. Our findings underscore the need to customize surveillance strategies based on duration since surgery and indicate that the aforementioned clinical parameters may serve as useful markers in 5-year survivors.
{"title":"Sequential changes in conditional survival of patients following surgical resection of colorectal cancer and indicators for follow-up beyond 5 years.","authors":"Ryotaro Goto, Hideo Miyake, Hidemasa Nagai, Yuichiro Yoshioka, Junichi Takamizawa, Norihiro Yuasa","doi":"10.1007/s10147-025-02956-2","DOIUrl":"https://doi.org/10.1007/s10147-025-02956-2","url":null,"abstract":"<p><strong>Background: </strong>The evolving prognosis of colorectal cancer (CRC) over extended periods following surgery has not been comprehensively characterized. This study aimed to delineate long-term patterns in conditional survival (CS), evaluate the changing relevance of CRC recurrence surveillance versus management of fatal non-cancer conditions, and suggest follow-up indicators tailored to postoperative duration.</p><p><strong>Methods: </strong>We examined trends in conditional overall survival (cOS), disease-specific survival (cDSS), and non-disease-specific survival (cNDSS) by tumor stage in 2,996 patients (stage 0-IV) who underwent surgical resection for CRC. Furthermore, we conducted a multivariate analysis in a cohort of 1,529 patients surviving more than 5 years to identify predictors of long-term survival.</p><p><strong>Results: </strong>Over a median observation period of 60.4 months, 745 deaths were recorded (478 CRC-related, 243 unrelated to CRC, and 24 unknown). Stage-wise CS analyses revealed crossover points of cDSS and cNDSS at 3 years post-surgery in stage II and at 6 years in stages III/IV. Multivariate analysis identified age ≥ 80, CEA ≥ 5.0 ng/mL, CA19-9 ≥ 37.0 U/mL, albumin ≤ 4.1 g/dL, anemia, RDW ≥ 14.9%, and platelet count ≤ 150 × 10<sup>9</sup>/L as independent risk factors in 5-year survivors.</p><p><strong>Conclusions: </strong>The importance of CRC recurrence surveillance was most prominent within the first 3 years after surgery in stage II and within 6 years in stages III/IV. Our findings underscore the need to customize surveillance strategies based on duration since surgery and indicate that the aforementioned clinical parameters may serve as useful markers in 5-year survivors.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Comprehensive genomic profiling (CGP) has been publicly reimbursed in Japan for 5 years, yet its impact on survival in real-world provincial settings remains unclear.
Methods: We retrospectively analyzed 914 patients with solid tumors who underwent tissue- or blood-based CGP at our institute between December 2019 and July 2023.
Results: The median age of patients was 66 years. Colorectal (18.9%) and pancreatic (16%) cancers were most common. Actionable alterations were detected in 87.5%, and druggable alterations in 58.3% of patients. Genomically matched therapy was administered to 10.9% of patients, who had better survival than those with druggable alterations who did not receive therapy [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.42-0.74] or those without actionable alterations (HR 0.63, 95% CI 0.47-0.83). A progression-free survival ratio > 1.3 was observed in 39.4% of patients. Multivariate analysis confirmed matched therapy was an independent favorable prognostic factor. Despite lower detection and treatment rates with blood-based CGP because of false negatives, survival benefit was preserved. Patients referred from external institutions had delayed CGP testing, but treatment benefit was slightly greater. Survival improvement was not observed in patients undergoing four or more prior regimens.
Conclusion: CGP-guided matched therapy may improve survival even in provincial settings. To optimize clinical utility, the appropriate CGP panel must be offered to the appropriate patient at the optimal time.
背景:综合基因组分析(CGP)在日本已经公开报销了5年,但其对现实世界省级环境中生存的影响尚不清楚。方法:我们回顾性分析了2019年12月至2023年7月在我们研究所接受组织或血液基础CGP的914例实体肿瘤患者。结果:患者中位年龄66岁。结直肠癌(18.9%)和胰腺癌(16%)最为常见。87.5%的患者检测到可操作的改变,58.3%的患者检测到可用药的改变。10.9%的患者接受了基因组匹配治疗,其生存率高于未接受治疗的可药物改变患者[风险比(HR) 0.56, 95%可信区间(CI) 0.42-0.74]或无可操作改变患者(HR 0.63, 95% CI 0.47-0.83)。39.4%的患者无进展生存率为bb0 1.3。多因素分析证实匹配治疗是一个独立的有利预后因素。尽管由于假阴性,基于血液的CGP的检出率和治愈率较低,但生存获益得以保留。从外部机构转介的患者延迟了CGP检测,但治疗效果略好。在接受四种或更多先前治疗方案的患者中未观察到生存改善。结论:cgp引导下的匹配治疗可提高局部患者的生存率。为了优化临床效用,必须在最佳时间向适当的患者提供适当的CGP面板。
{"title":"Prognostic impact of genomically matched therapy for solid cancers using real-world data from a provincial hospital in Japan.","authors":"Yoshinaga Okugawa, Takumi Fujiwara, Takahito Kitajima, Junya Tsuboi, Takeshi Sasaki, Yoshiki Okita, Masaki Ohi, Ryotaro Hashizume, Hiroshi Imai, Ikuyo Mochiki, Yasutaka Tono, Kanako Saito, Satoshi Tamaru, Takahiro Inoue, Toshiro Mizuno, Kaname Nakatani, Yuji Toiyama","doi":"10.1007/s10147-025-02931-x","DOIUrl":"10.1007/s10147-025-02931-x","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive genomic profiling (CGP) has been publicly reimbursed in Japan for 5 years, yet its impact on survival in real-world provincial settings remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed 914 patients with solid tumors who underwent tissue- or blood-based CGP at our institute between December 2019 and July 2023.</p><p><strong>Results: </strong>The median age of patients was 66 years. Colorectal (18.9%) and pancreatic (16%) cancers were most common. Actionable alterations were detected in 87.5%, and druggable alterations in 58.3% of patients. Genomically matched therapy was administered to 10.9% of patients, who had better survival than those with druggable alterations who did not receive therapy [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.42-0.74] or those without actionable alterations (HR 0.63, 95% CI 0.47-0.83). A progression-free survival ratio > 1.3 was observed in 39.4% of patients. Multivariate analysis confirmed matched therapy was an independent favorable prognostic factor. Despite lower detection and treatment rates with blood-based CGP because of false negatives, survival benefit was preserved. Patients referred from external institutions had delayed CGP testing, but treatment benefit was slightly greater. Survival improvement was not observed in patients undergoing four or more prior regimens.</p><p><strong>Conclusion: </strong>CGP-guided matched therapy may improve survival even in provincial settings. To optimize clinical utility, the appropriate CGP panel must be offered to the appropriate patient at the optimal time.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"73-83"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The clinical utility of immediate complete lymph node dissection (CLND) following positive sentinel node (SN) remains controversial in acral melanoma (AM), in Asian populations where AM is more prevalent. This study aimed to compare the survival outcomes of immediate CLND versus observation (OBS) in Japanese patients with stage III sole AM and positive SN.
Methods: This retrospective, multicenter study included 154 patients (CLND: 90, OBS: 64) with stage III sole AM with positive SN, across 44 Japanese institutions. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), regional metastasis-free survival (RMFS), and overall survival (OS) were compared between the two groups. Cox multivariable analysis and propensity score matching (PSM) were performed to adjust for potential confounders.
Results: With a median follow-up of 3.9 years, non-significant differences were observed in RFS, DMFS, RMFS, or OS between the CLND and OBS groups (P = 0.33, 0.32, 0.08, and 0.21, respectively). Cox multivariable analysis identified N3a nodal stage as an independent negative factor for OS (HR: 2.6, P = 0.02), whereas CLND and other variables were not associated. After PSM, 92 (46 each) were matched. RFS and DMFS remained comparable (P = 0.16 and 0.19), with a non-significant trend toward improved RMFS in the CLND group (P = 0.08), and no difference in OS (P = 0.14).
Conclusions: Immediate CLND did not provide a survival advantage over OBS in patients with stage III sole AM and positive SN. These findings do not support the routine use of CLND in this population. Trial registration Not applicable.
{"title":"Prognostic outcomes of immediate complete lymph node dissection versus observation in patients with acral melanoma of the sole with sentinel node metastasis: a retrospective, multicenter study.","authors":"Sadao Inoue, Shigeru Koizumi, Naoya Yamazaki, Yuki Ichigozaki, Hiroshi Kitagawa, Yukiko Kiniwa, Sayuri Sato, Toshihiro Takai, Reiichi Doi, Takamichi Ito, Masahito Yasuda, Yutaka Kuwatsuka, Takeo Maekawa, Jun Asai, Takuya Miyagawa, Shigeto Matsushita, Takeru Funakoshi, Yosuke Yamamoto, Takashi Inozume, Akiko Kishi, Tatsuya Takenouchi, Hiraku Kokubu, Shusaku Ito, Yoshiyasu Umeda, Yuki Yamamoto, Shoichiro Ishizuki, Shiro Iino, Hiroshi Uchi, Tomoe Nakagawa, Kazuhiro Inafuku, Takahiro Haga, Takahide Kaneko, Masahiro Nakagawa, Hideki Kamiya, Masaru Arima, Toshihiko Hoashi, Azusa Hiura, Nobuo Kanazawa, Keiko Manabe, Masashi Ishikawa, Kenji Asagoe, Utsugi Iwasawa, Takafumi Kadono, Naohito Hatta, Shoichiro Minami, Eiji Nakano, Dai Ogata, Satoshi Fukushima, Hisashi Uhara, Kenta Nakama, Takaya Komori, Ken Igawa, Yasuhiro Nakamura","doi":"10.1007/s10147-025-02936-6","DOIUrl":"10.1007/s10147-025-02936-6","url":null,"abstract":"<p><strong>Background: </strong>The clinical utility of immediate complete lymph node dissection (CLND) following positive sentinel node (SN) remains controversial in acral melanoma (AM), in Asian populations where AM is more prevalent. This study aimed to compare the survival outcomes of immediate CLND versus observation (OBS) in Japanese patients with stage III sole AM and positive SN.</p><p><strong>Methods: </strong>This retrospective, multicenter study included 154 patients (CLND: 90, OBS: 64) with stage III sole AM with positive SN, across 44 Japanese institutions. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), regional metastasis-free survival (RMFS), and overall survival (OS) were compared between the two groups. Cox multivariable analysis and propensity score matching (PSM) were performed to adjust for potential confounders.</p><p><strong>Results: </strong>With a median follow-up of 3.9 years, non-significant differences were observed in RFS, DMFS, RMFS, or OS between the CLND and OBS groups (P = 0.33, 0.32, 0.08, and 0.21, respectively). Cox multivariable analysis identified N3a nodal stage as an independent negative factor for OS (HR: 2.6, P = 0.02), whereas CLND and other variables were not associated. After PSM, 92 (46 each) were matched. RFS and DMFS remained comparable (P = 0.16 and 0.19), with a non-significant trend toward improved RMFS in the CLND group (P = 0.08), and no difference in OS (P = 0.14).</p><p><strong>Conclusions: </strong>Immediate CLND did not provide a survival advantage over OBS in patients with stage III sole AM and positive SN. These findings do not support the routine use of CLND in this population. Trial registration Not applicable.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"214-222"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}