Japanese journal of clinical oncology最新文献

{"title":"Long-term clinical outcomes after salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy.","authors":"Kenta Onishi, Yasushi Nakai, Fumisato Maesaka, Mitsuru Tomizawa, Takuto Shimizu, Shunta Hori, Daisuke Gotoh, Makito Miyake, Kazumasa Torimoto, Kaori Yamaki, Isao Asakawa, Fumiaki Isohashi, Kiyohide Fujimoto, Nobumichi Tanaka","doi":"10.1093/jjco/hyaf037","DOIUrl":"10.1093/jjco/hyaf037","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the clinical outcomes of patients who developed prostate-specific antigen failure after radical prostatectomy and were treated with salvage radiotherapy (SRT).</p><p><strong>Methods: </strong>This retrospective study included 167 patients who received SRT between January 2008 and August 2017 at a single center. Cumulative and periodic genitourinary and gastrointestinal adverse events and the chronologic changes in quality of life were evaluated before and 1, 3, 6, 12, 24, 36, 48, and 60 months after SRT.</p><p><strong>Results: </strong>The median follow-up duration after SRT was 83 months. The 5- and 7-year biochemical recurrence-free rates were 52.6% and 47.9%, respectively. Multivariate analysis revealed the following independent risk factors for recurrence after SRT: higher total Gleason score (≥8), higher pathological T stage, negative resection margin, and shorter period between radical prostatectomy and biochemical recurrence-free. The cumulative incidence rates of grade 2 or higher genitourinary and gastrointestinal adverse events after SRT were 27.4% and 9.4%, respectively. Bowel function worsened after SRT and showed significant deterioration 5 years after SRT, compared with pre-treatment. Five years post SRT, the rates of patients whose physical and mental component scores were < 50 were 44.1% and 34.3%, respectively.</p><p><strong>Conclusions: </strong>Prostate-specific antigen recurrence occurred in approximately half of the patients after SRT, with a higher Gleason score, higher pathological T stage, negative resection margin, and shorter period between radical prostatectomy and first biochemical recurrence identified as risk factors. Besides the adverse events, careful attention to long-term quality-of-life deterioration must be considered when considering indications for SRT.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"626-635"},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of 4 L lymphadenectomy in solid dominant clinical stage I non-small cell lung cancer in the left upper lobe.","authors":"Yukio Watanabe, Aritoshi Hattori, Mariko Fukui, Takeshi Matsunaga, Kazuya Takamochi, Kenji Suzuki","doi":"10.1093/jjco/hyaf032","DOIUrl":"10.1093/jjco/hyaf032","url":null,"abstract":"<p><strong>Objectives: </strong>The significance of station 4 L lymph node dissection (LND) for early-stage non-small cell lung cancer (NSCLC) is unknown.</p><p><strong>Methods: </strong>We evaluated 342 patients who underwent complete anatomical resection and mediastinal LND for radiologically solid dominant clinical (c)-Stage I left upper lobe NSCLC between 2008 and 2022. Solid dominant was defined as a consolidation tumor ratio >0.5, on thin-section computed tomography. After matching, postoperative complications and outcomes between the 4 L LND and non-4 L LND groups were compared. Predictors of 4 L metastasis was also identified using logistic regression analysis.</p><p><strong>Results: </strong>4LND was performed in 215 patients (63%), and 4 L metastasis was detected in 11 patients. Matching yielded 108 pairs. Recurrent nerve paralysis was more frequent in the 4LND group (P = 0.02) with no significant differences in the overall survival (OS) (5y OS: 85.2% vs. 86.3%, P = 0.66) and recurrence-free survival (RFS) (5y RFS: 78.4% vs. 78.5%, P = 0.51) between the 4 L LND and non-4 L LND groups. Logistic regression analysis determined solid component size >20 mm (P = 0.02) and pleural indentation (P = 0.02) on computed tomography findings as clinical risk factors for 4 L metastasis. The predictive criteria for 4 L metastasis were defined as solid component size ≤20 mm without pleural indentation (specificity: 100%, positive predictive value: 100%).</p><p><strong>Conclusions: </strong>4 L LND had a higher frequency of recurrent nerve palsy, although no survival improvement was observed in solid dominant c-Stage I left upper NSCLC. 4 L LND may be omitted for solid component size ≤20 mm without pleural indentation.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"636-642"},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-center retrospective study of malignant ectomesenchymoma in children.","authors":"Yiran Meng, Yan Su, Ge Zhang, Wei Yang, Zhe Li, Yuanhu Liu, Yanzhen Li, Zhang Xuexi, Qiaoyin Liu, Nian Sun, Zhiyong Liu, Shengcai Wang, Xin Ni","doi":"10.1093/jjco/hyaf040","DOIUrl":"10.1093/jjco/hyaf040","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to summarize the clinical and pathological characteristics of Malignant Ectomesenchymoma (MEM) and provide an overview of the available treatment options.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on data from 11 children diagnosed with MEM at Beijing Children's Hospital between 2012 and 2023.</p><p><strong>Results: </strong>The study included nine male and two female patients, with a median age of 3 years (range, 1.5-11.0 years). The most commonly affected sites were the head and neck (45.6%), followed by the limbs (27.2%) and the pelvis/abdomen (27.2%). Nine children presented with localized MEM, while two had metastatic disease at the time of diagnosis. Among the nine children who underwent surgery, four received a combination of radiotherapy and chemotherapy, while five were treated with chemotherapy alone. Two children received only conservative treatment. The median follow-up period was 5.8 years (range, 0.7-12.3 years). Children who received both radiotherapy and chemotherapy had a significantly lower relapse rate compared to those treated with chemotherapy alone (2/6 vs. 5/5, P = 0.046). Additionally, children with FOXO1(+) tumors had lower survival rates than those with FOXO1(-) tumors (0/2 vs. 7/8). The 5-year overall survival rate was 79%, while the event-free survival rate was 14%.</p><p><strong>Conclusions: </strong>Combining chemotherapy with local treatments such as surgery and radiotherapy can improve the prognosis for children with MEM. Radiotherapy may be beneficial in reducing the incidence of adverse effects in patients with MEM.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"621-625"},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304.","authors":"Satoshi Tsukushi, Kazuhiro Tanaka, Toshiyuki Kunisada, Ryunosuke Machida, Satoshi Takenaka, Akira Kawai, Hirohisa Katagiri, Masanobu Takeyama, Makoto Endo, Katsuhiro Hayashi, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Shinichirou Yoshida, Toshio Kojima, Akio Sakamoto, Jungo Imanishi, Ryosuke Kita, Toshifumi Ozaki, Yukihide Iwamoto","doi":"10.1093/jjco/hyaf027","DOIUrl":"10.1093/jjco/hyaf027","url":null,"abstract":"<p><strong>Background: </strong>The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial.</p><p><strong>Methods: </strong>A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT.</p><p><strong>Results: </strong>Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%-14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33-66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases.</p><p><strong>Conclusion: </strong>Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"603-609"},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local therapy for oligometastatic prostate cancer.","authors":"Taketo Kawai, Satoru Taguchi, Tohru Nakagawa, Haruki Kume","doi":"10.1093/jjco/hyaf048","DOIUrl":"10.1093/jjco/hyaf048","url":null,"abstract":"<p><p>Traditionally, systemic therapy based on androgen deprivation therapy (ADT) has been the primary approach for treating metastatic prostate cancer. Local therapies targeting metastatic lesions have rarely been employed for cancer control. However, the advent of next-generation imaging modalities, such as choline positron emission tomography (PET), whole-body magnetic resonance imaging, and prostate-specific membrane antigen (PSMA)-PET, has enabled the detection of oligometastases that were previously undetectable using conventional imaging techniques, such as computed tomography and bone scintigraphy. This has led to increased attention to local therapy for oligometastatic prostate cancer with cancer control. Oligometastatic prostate cancer can be classified into three categories: de novo oligometastases (oligometastases identified at initial diagnosis), oligorecurrence (oligometastases arising after radical treatment of primary tumor), and oligoprogression (activation of oligometastases following ADT failure). Evidence from randomized controlled trials (RCTs) supports the efficacy of local therapy in these contexts. The phase III STAMPEDE trial demonstrated that the addition of prostate radiotherapy to ADT improved the overall survival in patients with de novo low-volume metastatic prostate cancer. Furthermore, in the STOMP and ORIOLE trials, phase II RCTs have shown that metastasis-directed therapy significantly prolongs progression-free survival (PFS) in patients with oligorecurrent prostate cancer after radical treatment. For oligoprogressive castration-resistant prostate cancer, the phase II ARTO trial demonstrated that the addition of radiotherapy targeting oligometastases to first-line abiraterone acetate and prednisone treatments improved PFS. With the global adoption of PSMA-PET, local therapy for primary tumor and metastases in oligometastatic prostate cancer is expected to play an increasingly prominent role in the future.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"571-577"},"PeriodicalIF":1.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicenter, open-label, randomized, controlled study to test the utility of electronic patient-reported outcome monitoring in patients with unresectable advanced cancers or metastatic/recurrent solid tumors.","authors":"Naruto Taira, Naomi Kiyota, Yuichiro Kikawa, Eiki Ichihara, Kyoko Kato, Kaoru Kubota, Ryosuke Tateishi, Akinobu Nakata, Keiichiro Nakamura, Yukiya Narita, Katsuyuki Hotta, Hiroji Iwata, Akihiko Gemma, Kojiro Shimozuma, Kei Muro, Tetsuya Iwamoto, Yuki Takumoto, Takeru Shiroiwa, Takashi Fukuda, Takuhiro Yamaguchi, Yasuhiro Hagiwara, Hironobu Minami","doi":"10.1093/jjco/hyaf033","DOIUrl":"10.1093/jjco/hyaf033","url":null,"abstract":"<p><p>Electronic patient-reported outcome (ePRO) monitoring for patients undergoing cancer chemotherapy may provide qualified and early detection of adverse events or disease-related symptoms, leading to improved patient care. The aim of this study is to examine whether addition of ePRO monitoring to routine medical care contributes to improved overall survival and quality of life of cancer patients undergoing chemotherapy. Patients with unresectable advanced cancers or metastatic/recurrent solid tumors receiving systemic chemotherapy will be randomized to an ePRO monitoring group and a usual care group. The ePRO group will conduct weekly symptom monitoring using an electronic device after study enrollment until the end of the study. Monitoring results will be returned to medical personnel and used as information for patient care. The primary endpoints are overall survival and health related quality of life. The initial target sample size for the study was 1500 patients. However, due to delays in enrollment, the target was readjusted to 500 patients. Enrollment has been completed, and the study is now in the follow-up phase.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"547-555"},"PeriodicalIF":1.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine release syndrome induced by dabrafenib and trametinib therapy in BRAF V600E-mutant non-small cell lung cancer.","authors":"Toshiyuki Sumi, Taiki Ishigooka, Keigo Matsuura, Takumi Ikeda, Yuichi Yamada, Hirofumi Chiba","doi":"10.1093/jjco/hyaf004","DOIUrl":"10.1093/jjco/hyaf004","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) with BRAF V600E mutations is responsive to targeted therapies, such as dabrafenib and trametinib. However, these treatments can lead to serious adverse events, including cytokine release syndrome (CRS). Herein, we report the case of a 75-year-old man with stage IVB NSCLC and a BRAF V600E mutation who developed severe CRS, manifesting hepatic and renal dysfunction, following treatment with dabrafenib and trametinib. Despite initial fever management, the patient's renal function deteriorated rapidly, necessitating hemodialysis. Elevated cytokine levels, including interleukin-6, interferon-γ, and tumor necrosis factor α, were detected. The patient was treated with steroid pulse therapy, which resulted in fever resolution, and his renal function gradually improved. Hemodialysis was discontinued as renal function recovered. This case underscores the importance for early recognition and management of CRS in patients receiving targeted therapies. Prompt intervention with steroids may prevent CRS progression and mitigate associated organ dysfunction. Further investigation is required to clarify the mechanisms of CRS in patients receiving targeted therapy, particularly in the absence of prior immune checkpoint inhibitor use.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"539-542"},"PeriodicalIF":1.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of osteosarcopenia on short- and long-term outcomes in patients with gastric cancer.","authors":"Wataru Kai, Yasuhiro Takano, Yasunobu Kobayashi, Hironori Kanno, Nobuyoshi Hanyu, Ken Eto","doi":"10.1093/jjco/hyaf003","DOIUrl":"10.1093/jjco/hyaf003","url":null,"abstract":"<p><strong>Backgrounds: </strong>Osteopenia and sarcopenia are associated with adverse clinical outcomes. This study investigated the impact of osteosarcopenia on short- and long-term outcomes after gastrectomy for gastric cancer.</p><p><strong>Methods: </strong>The present study included patients who underwent gastrectomy for gastric cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images. Sarcopenia was evaluated by measuring the skeletal muscle cross-sectional area at the third lumbar vertebra level. Osteosarcopenia was defined as the coexistence of osteopenia and sarcopenia. We investigated the relationship of preoperative osteosarcopenia with short- and long-term outcomes after gastrectomy for gastric cancer.</p><p><strong>Results: </strong>Of all 122 patients, 38 (31%) patients were diagnosed with osteosarcopenia. Multivariate logistic regression analysis revealed that osteosarcopenia (P = .008) was an independent risk factor for postoperative complications. Furthermore, multivariate Cox regression analysis revealed that male sex (P = .007), and osteosarcopenia (P = .038) were independent predictors of disease-free survival, while osteosarcopenia (P = .045) and pathological T stage ≥3 (P = .033) were independent predictors of overall survival.</p><p><strong>Conclusions: </strong>Osteosarcopenia was a strong predictor of short- and long-term outcomes after gastrectomy for gastric cancer. Preoperative screening of osteosarcopenia may be helpful for better management of patients with gastric cancer.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"477-483"},"PeriodicalIF":1.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast cancer surveillance for epithelial ovarian cancer patients with BRCA1 and BRCA2 pathogenic variants: a single-center retrospective study.","authors":"Junko Hasegawa-Minato, Mikako Tochigi, Shuko Miyahara, Kei Kudo, Yusuke Shibuya, Chiaki Hashimoto, Masumi Ishibashi, Shogo Shigeta, Hideki Tokunaga, Muneaki Shimada","doi":"10.1093/jjco/hyaf010","DOIUrl":"10.1093/jjco/hyaf010","url":null,"abstract":"<p><strong>Objectives: </strong>To identify a method for breast cancer (BC) surveillance in patients with epithelial ovarian cancer (EOC) with germline BRCA1/2 pathogenic variants (gBRCA1/2m) and the incidence of BC after EOC in the era of broad PARP inhibitors use.</p><p><strong>Methods: </strong>We retrospectively analyzed the data on EOC patients who had gBRCA1/2m by genetic testing between January 2017 and August 2023 in our single center.</p><p><strong>Results: </strong>Of 125 patients with EOC, 33 had gBRCA1/2m. Of these, 27 (81.8%) underwent BC surveillance, 20 ultrasound and/or mammography, and seven magnetic resonance imaging (MRI). The median time from EOC diagnosis to the initiation of BC surveillance was 8 months. EOC recurrence was significantly lower in the group with MRI than in the group without MRI (no case vs. 10 cases, P = .0261). The duration from EOC diagnosis to the start of BC surveillance was longer in the group with MRI than in the group without MRI (21 vs. 7 months, P = .1033). Two (6.1%) patients developed BC after EOC. Both cases were early stage, triple-negative BCs that occurred more than 3 years after the diagnosis of stage III EOC.</p><p><strong>Conclusions: </strong>With the advent of PARP inhibitors, long-term survival is expected to increase, and a certain number of patients with EOC after initial treatment may benefit from BC surveillance using MRI. In particular, BC surveillance with MRI may be considered for patients who have not experienced EOC recurrence for more than 2 years.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"484-489"},"PeriodicalIF":1.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status of cancer genome medicine for pancreatic ductal adenocarcinoma.","authors":"Toshifumi Doi, Takeshi Ishikawa, Michihisa Moriguchi, Yoshito Itoh","doi":"10.1093/jjco/hyaf012","DOIUrl":"10.1093/jjco/hyaf012","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis; however, advancements in cancer genome profiling using next-generation sequencing have provided new perspectives. KRAS mutations are the most frequently observed genomic alterations in patients with PDAC. However, until recently, it was not considered a viable therapeutic target. Although KRAS G12C mutations for which targeted therapies are already available are infrequent in PDAC, treatments targeting KRAS G12D and pan-KRAS are still under development. Similarly, new treatment methods for KRAS, such as chimeric antigen receptor T-cell therapy, have been developed. Several other potential therapeutic targets have been identified for KRAS wild-type PDAC. For instance, immune checkpoint inhibitors have demonstrated efficacy in PDAC treatment with microsatellite instability-high/deficient mismatch repair and tumor mutation burden-high profiles. However, for other PDAC cases with low immunogenicity, combination therapies that enhance the effectiveness of immune checkpoint inhibitors are being considered. Additionally, homologous recombination repair deficiencies, including BRCA1/2 mutations, are prevalent in PDAC and serve as important biomarkers for therapies involving poly (adenosine diphosphate-ribose) polymerase inhibitors and platinum-based therapies. Currently, olaparib is available for maintenance therapy of BRCA1/2 mutation-positive PDAC. Further therapeutic developments are ongoing for genetic abnormalities involving BRAF V600E and the fusion genes RET, NTRK, NRG, ALK, FGFR2, and ROS1. Overcoming advanced PDAC remains a formidable challenge; however, this review outlines the latest therapeutic strategies that are expected to lead to significant advancements.</p>","PeriodicalId":14656,"journal":{"name":"Japanese journal of clinical oncology","volume":" ","pages":"443-452"},"PeriodicalIF":1.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}