Japanese Journal of Clinical Oncology

Okano, Naohiro; Pirozzi, Angelo; Abidoye, Oluseyi; Hoyek, Celine; Eslinger, Cody; Zheng-Lin, Binbin; Jamal, Fares; Sahwan, Oudai; Sonbol, Mohamad Bassam; Uson Junior, Pedro Luiz Serrano; Hayashi, Masato; Sato, Taro; Nishioka, Mariko; Nagashima, Fumio; Bekaii-Saab, Tanios; Borad, Mitesh J; Hironaka, Shuichi

doi: 10.1093/jjco/hyaf052pmid: 40173029

Biliary tract cancer (BTC) remains among the most challenging malignancies with a poor prognosis and limited treatment options, particularly in pretreated patients. As most patients experience disease progression after first-line treatment, effective second-line and subsequent treatments are required. Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest. Moreover, most clinical trials demonstrated modest efficacy of molecular-targeted agents for molecularly unselected pretreated advanced BTC. Patients with advanced BTC carry a relatively high druggable genetic alteration rate and have shown promising responses to molecular-matched therapies targeting gene alterations such as FGFR2 fusions/rearrangements, IDH1 mutation, and HER2 overexpression/amplification. Additionally, tumor-agnostic approaches, including BRAF V600E, NTRK fusion, and RET fusion, have expanded the treatment options for some patients. Immune checkpoint inhibitors have shown limited efficacy as mono- or combination therapy in patients with pretreated advanced BTC. Therefore, developmental efforts have shifted to immune checkpoint inhibitor and other combinations such as vascular endothelial growth factor receptor inhibitors or radiation. In addition to refining combination strategies to enhance the therapeutic potential of immune checkpoint inhibitor, future research should focus on elucidating the tumor microenvironment. This review delineates the evolution of systemic therapies in patients with pretreated advanced BTC. By examining past developments and recent advances through prospective trials, it highlights novel approaches that may improve outcomes in this challenging disease.

Izubuchi, Yuya; Tanaka, Takaaki

doi: 10.1093/jjco/hyaf056pmid: 40336169

Perivascular epithelioid cell tumors (PEComas) are a rare family of mesenchymal tumors that includes angiomyolipoma, lymphangioleiomyomatosis, pulmonary clear cell “sugar” tumors, and PEComa-not otherwise specified. This study aimed to provide a comprehensive review of the clinical features, molecular biology, and current status of PEComa treatment. It reportedly occurs at several sites, including the uterus, kidney, liver, lung, abdominopelvic soft tissue, gastrointestinal organs, retroperitoneum, soft tissue, bone, and skin. More common in women, it occurs in young to middle-aged people. Although the disease generally follows a benign course, cases of malignant PEComa have been reported. Malignant PEComa is characterized by a large tumor size, a high mitotic rate, and the presence of necrosis and nuclear atypia. Immunohistochemically, PEComas typically express melanocytic markers such as human melanoma black 45 (HMB45) and melanoma antigen (melan-A) and muscle markers such as smooth muscle actin (α-SMA), desmin, and caldesmon. More recently, a subtype of PEComa harboring TFE3 gene rearrangement that is mutually exclusive with tuberous sclerosis complex (TSC) mutations has been identified. The identification of TFE3 gene rearrangement can help confirm the diagnosis. The distinctive features of these TFE3-rearranged PEComas include a young-age tendency, the absence of an association with tuberous sclerosis, predominant alveolar architecture and epithelioid cytology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Surgery is the curative treatment of choice; however, there are reports of cases and randomized controlled trials showing the efficacy of mTOR inhibitors. To the best of our knowledge, there are no reports of radiation therapy’s efficacy.

Shinomiya, Hirotaka; Fujita, Takeshi; Nibu, Ken-ichi

doi: 10.1093/jjco/hyaf058pmid: 40215384

Auditory canal cancer is a rare form of carcinoma, making it extremely challenging to establish standard treatments through prospective studies. To date, no prospective comparative trials have been conducted, and standard treatment protocols have largely been derived from meta-analyses of case series. Several controversies remain unresolved, including the necessity of prophylactic neck dissection, the criteria for postoperative radiotherapy, and the choice between surgical treatment and chemoradiotherapy for advanced cases. These questions remain difficult to address owing to the rarity of the disease. This article aims to review the existing literature on external auditory canal squamous cell carcinoma, summarize current knowledge, and highlight areas for future research. Early-stage cancers have a favorable prognosis, with surgical treatment and postoperative radiotherapy serving as standard approaches for high-risk groups. The treatment of advanced-stage cancer remains challenging, although oncological outcomes have improved over time. Surgery combined with postoperative radiotherapy is commonly used; however, studies have shown no significant difference in prognosis compared with definitive chemoradiotherapy. Treatment strategies should be tailored to each individual case, with careful consideration of quality of life. Outcomes for inoperable cases remain extremely poor, highlighting the urgent need for new therapeutic strategies.

Yamakawa, Kohei; Ogata, Dai; Namikawa, Kenjiro; Nakano, Eiji; Yamaguchi, Yukie; Yamazaki, Naoya

doi: 10.1093/jjco/hyaf071pmid: 40381218

Cutaneous angiosarcoma (cAS) is a rare and aggressive malignant vascular tumor that arises from endothelial cells lining the blood vessels. It can occur in any part of the body, but most commonly, it affects the skin and soft tissues. cAS has a poor prognosis with a 5-year survival rate of only 9%. This review summarizes the current understanding of angiosarcoma pathogenesis, clinical presentation, diagnosis, and treatment approaches. Recent advances in molecular characterization have identified recurrent genetic alterations that may lead to the development of novel targeted therapies. Multidisciplinary management combining surgery, radiation, and systemic therapy remains the mainstay of treatment; however, outcomes remain poor for metastatic disease. Ongoing research into the molecular drivers of cAS and immunotherapeutic approaches offers hope for improving the outcomes of this challenging malignancy.

Fukuda, Akito; Mizuno, Takaaki; Yoshida, Tatsuya; Sunami, Kuniko; Kubo, Takashi; Koyama, Takafumi; Yonemori, Kan; Okusaka, Takuji; Kato, Ken; Ohe, Yuichiro; Yatabe, Yasushi; Yamamoto, Noboru

doi:

Qian, Rong; Zhang, Huai; Liu, Xu; Huang, Shuangying; Qi, Shengwei; Zhao, Nana; Wang, HuiJuan; Liao, Dan; Jin, Man

doi: 10.1093/jjco/hyaf053pmid: 40205947

ObjectiveIn this prospective observational cohort study, we aim to investigate the risk factors for early postoperative anastomotic leakage (AL) in patients undergoing rectal cancer resection.MethodsThis study included 459 patients with rectal cancer who underwent treatment at our hospital from January 2021 to October 2022. All patients were hospitalized for 1 week postoperatively and observed for the occurrence of AL. Fasting venous blood samples (5 mL) were collected from all cases 1 day before surgery and 1, 2, and 3 days after surgery, and serum levels of interleukins (IL)-17, IL-6, IL-1β, tumor necrosis factor-α, and C-reactive protein (CRP) were determined using enzyme-linked immunosorbent assay. Demographic, clinical data, intraoperative hypothermia, and nutritional indicators were collected for all patients. Statistical analysis was performed using SPSS 25.0 software.ResultsAL patients had significantly lower hemoglobin, albumin (ALB) levels, and a higher proportion of intraoperative hypothermia compared to patients in the non-AL group (P < .05). On the first, second, and third days after surgery, patients in the AL group had significantly higher levels of serum CRP, IL-1β, and IL-17 compared to the non-AL group. Pearson’s correlation analysis showed a positive correlation between serum IL-17 levels and CRP levels. Serum IL-17 had the highest predictive value for early AL, with an area under the curve (AUC) of 0.755 cutoff value of 94.77 pg/mL, a sensitivity of 70.1%, and a specificity of 66.0%. Moreover, logistic regression analysis indicated that intraoperative hypothermia, decreased ALB levels, and increased CRP, IL-1β, and IL-17 levels on the first day after surgery were identified as risk factors for early AL in rectal cancer patients.ConclusionsThis study found a significant elevation of IL-17 levels in the serum of patients who experienced early postoperative AL. Furthermore, intraoperative hypothermia and elevated IL-17 levels on the first day after surgery were identified as risk factors for early postoperative AL in rectal cancer patients.

Zhou, Xuelian; Fan, Tingting

doi: 10.1093/jjco/hyaf042pmid: 40062451

BackgroundTo establish a nomogram model for predicting chemotherapy-induced nausea and vomiting (CINV) in patients with gynecological malignancies based on relevant risk factors.MethodsThis retrospective study included patients with gynecological malignancies hospitalized in the oncology department of Affiliated People’s Hospital of Jiangsu University between February 2020 and October 2021. Patients were divided into a training set (between February 2020 and December 2020) and a validation set (between January 2021 and October 2021). Basic and clinical characteristics were collected and analyzed by univariate and multivariate logistic regression. A nomogram was constructed and assessed with the receiver operating characteristic curve (ROC). We have also conducted an external validation using data from 297 patients with gynecological malignancies admitted to two oncology wards at our hospital (140 patients from Ward 1 and 157 patients from Ward 2).ResultsThis study comprised 148 patients in the training set and 148 in the validation set. Multivariate analysis revealed age <60 years (OR (Odds Ratio) = 4.001, 95% CI (Confidence interval) 1.349–11.872, P = 0.012), presence of motion sickness (OR = 3.841, 95% CI 1.200–12.296, P = 0.023), history of pregnancy-related vomiting (OR = 4.067, 95% CI 1.203–13.751, P = 0.024), and the use of moderate/high emetogenic chemotherapy drugs (OR = 10.299, 95% CI 2.858–37.115, P < 0.001) as independent risk factors for CINV. These factors were incorporated into a nomogram, which exhibited an area under the ROC (AUC) of 0.844, with a sensitivity of 81.4% and specificity of 80.0% at the optimal cut-off point of 159.48. The AUC for validation was 0.945, with sensitivity and specificity of 91.5% and 87.1% at the optimal cut-off point of 159.48, respectively. The external validation results showed an AUC of 0.704 (95% CI: 0.648–0.755), with a sensitivity of 93.33% and specificity of 48.15% (P = 0.001).ConclusionThe developed nomogram, incorporating age, moderate/high emetogenic chemotherapy drugs, motion sickness, and pregnancy vomiting history, showed good discrimination for CINV.

Sasakura, Yukie; Hatanaka, Makiko; Ishizawa, Kenichi

doi: 10.1093/jjco/hyaf044pmid: 40156871

BackgroundAlemtuzumab is a monoclonal antibody directed against CD52 on T and B lymphocytes and is used to treat lymphoproliferative disorders including chronic lymphocytic leukaemia (CLL). This postmarketing surveillance, as mandated by the Japanese health authorities, investigated the safety and effectiveness of alemtuzumab in Japanese patients receiving alemtuzumab for relapsed/refractory CLL.MethodsThis was an observational, prospective study conducted in patients with lymphoproliferative disorders who received alemtuzumab in routine clinical practice in Japan between March 2015 and June 2023. Follow-up was for 24 weeks after alemtuzumab administration. Endpoints were adverse drug reactions (ADRs), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), and factors associated with safety and effectiveness.ResultsSafety was evaluated in 179 patients with lymphoproliferative disorders (112 males and 67 females; median age 68 years) and effectiveness in 95 with relapsed/refractory CLL. Overall, 138 patients (77.1%) developed an ADR (most commonly cytomegalovirus [CMV]-related events [37.4%]), 100 (55.9%) developed serious ADRs (most commonly CMV-related events [31.3%]), and 93 (52.0%) developed grade ≥ 3 ADRs (most commonly decreased platelet count [13.4%]). Of 95 patients with relapsed/refractory CLL, 39 (41.1%) had an ORR (15 complete and 24 partial responses). At 24 weeks, PFS and OS rates were 55.5% and 70.0%, respectively. The ORR was significantly associated with Rai classification, performance status, and treatment days or duration.ConclusionsThis prospective postmarketing surveillance study confirms the effectiveness and manageable safety profile of alemtuzumab for Japanese patients with relapsed/refractory CLL.