Explore the vast range of titles available.

Patients with advanced cancer undergo comprehensive genomic profiling in Japan only after treatment options have been exhausted. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation‐based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by the conditional Kendall τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival‐prolonging chemotherapy with adjustment for length bias was 937 (886–991), 1225 (1152–1368), and 585 (553–617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor‐specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine with nab‐paclitaxel‐treated groups as first‐line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real‐world clinicogenomic data. Length bias due to delayed enrollment in comprehensive genomic profiling tests makes accurate survival analysis impossible. This study enrolling 8813 Japanese patients with advanced cancer who underwent a profiling test showed a worse prognosis for patients who underwent profiling tests in early timing. Our adjusting method for length bias made it possible to analyze overall survival and the prognostic impact of oncogenic mutations and treatments.

To examine clinico-pathological factors associated with surgical complications and postoperative therapy for clinical stage IB-IIB cervical cancer. This nationwide multicenter retrospective study examined women with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy plus pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group (n = 693). Multivariate models were used to identify independent predictors of perioperative grade 3-4 complications and bladder dysfunction. The overall intraoperative and postoperative complication rates were 3.3% and 9.8%, respectively. Clinical stage was not associated with perioperative complications (P = 0.15). Radiotherapy-based adjuvant therapy was significantly associated with an increased risk of postoperative complications (radiotherapy alone: adjusted-odds ratio [OR] 3.19, 95% confidence interval [CI] 1.46-6.99, P = 0.004; radiotherapy plus chemotherapy: adjusted-OR 3.26, 95%CI 1.66-6.41, P = 0.001), whereas chemotherapy was not (P = 0.45). Nerve-sparing surgery significantly reduced the risk of postoperative bladder dysfunction (adjusted-OR 0.57, 95%CI 0.37-0.90, P = 0.02) whereas adjuvant chemotherapy increased the risk of bladder dysfunction (adjusted-OR 2.06, 95%CI 1.16-3.67, P = 0.01). Among women receiving adjuvant chemotherapy, nerve-sparing radical hysterectomy significantly reduced the risk of bladder dysfunction (15.0% versus 32.9%, OR 0.31, 95%CI 0.14-0.68, P = 0.004). After propensity score matching, survival outcomes were similar with both types of adjuvant therapy (radiotherapy-based versus chemotherapy, P>0.05). Our study highlighted two distinct complication profiles of adjuvant therapy after radical hysterectomy for clinical stage IB-IIB cervical cancer, with radiotherapy increasing grade 3-4 adverse events and chemotherapy increasing bladder dysfunction. In this setting, nerve-sparing surgery may be useful if chemotherapy is being considered for adjuvant therapy.

BackgroundRadiotherapy (RT) is effective in cervical cancer; radiation-induced lymphopenia correlates with poor survival outcome in several cancer types. We investigated the association of total lymphocyte count (TLC) with survival outcomes in patients with cervical cancer.MethodsWe retrospectively reviewed 168 patients with cervical cancer initially treated with definitive RT. We obtained clinicopathological data and TLCs before RT and at the end and at 6 months after RT. Patient-, treatment-, and tumor-specific factors were evaluated to determine their predictive values for overall survival. The association of overall and progression-free survivals with lymphopenia at each point was evaluated.ResultsMedian follow-up duration was 44 (interquartile range: 25–67) months. Median TLCs before RT and at the end and at 6 months after RT were 1625/mm3, 400/mm3, and 800/mm3 (interquartile range: 1270–1930/mm3, 290–550/mm3, and 600–1067/mm3), respectively. For overall survival, in addition to FIGO stage, body mass index, histology, treatment, and presence of para-aortic lymph node metastasis, lymphopenia at 6 months after RT was a poor prognostic factor in multivariate analysis (P = 0.0026; hazard ratio [HR], 3.06; 95% confidence interval [CI]: 1.48–6.33). For progression-free survival, TLCs before and at 6 months after RT were poor prognostic factors in univariate analysis (P = 0.0318 and 0.0081, respectively); however, the latter was the only independent prognostic factor in multivariate analysis (P = 0.0021; HR, 2.67; 95% CI: 1.43–4.99).ConclusionPost-RT persistent lymphopenia could be a poor prognostic factor for patients with cervical cancer who receive RT.

Uterine sarcomas have very poor prognoses and are sometimes difficult to distinguish from uterine leiomyomas on preoperative examinations. Herein, we investigated whether deep neural network (DNN) models can improve the accuracy of preoperative MRI-based diagnosis in patients with uterine sarcomas. Fifteen sequences of MRI for patients (uterine sarcoma group: n = 63; uterine leiomyoma: n = 200) were used to train the models. Six radiologists (three specialists, three practitioners) interpreted the same images for validation. The most important individual sequences for diagnosis were axial T2-weighted imaging (T2WI), sagittal T2WI, and diffusion-weighted imaging. These sequences also represented the most accurate combination (accuracy: 91.3%), achieving diagnostic ability comparable to that of specialists (accuracy: 88.3%) and superior to that of practitioners (accuracy: 80.1%). Moreover, radiologists’ diagnostic accuracy improved when provided with DNN results (specialists: 89.6%; practitioners: 92.3%). Our DNN models are valuable to improve diagnostic accuracy, especially in filling the gap of clinical skills between interpreters. This method can be a universal model for the use of deep learning in the diagnostic imaging of rare tumors.

BackgroundThe standard treatment for stage IB–IIB cervical cancer is radiotherapy or radical hysterectomy; after radical hysterectomy, adjuvant concurrent chemoradiotherapy is recommended for patients with high risk factors. However, adjuvant concurrent chemoradiotherapy can cause severe gastrointestinal and urinary toxicity.Primary ObjectiveTo assess whether postoperative adjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival in patients with high risk cervical cancer.Study HypothesisAdjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival and will reduce severe toxicities.Trial DesignPatients with high risk factors after radical hysterectomy will be randomized 1:1 to receive adjuvant concurrent chemoradiotherapy or adjuvant chemotherapy. Treatment will be started within 6 weeks of surgery. The concurrent chemoradiotherapy group will receive whole pelvis irradiation (50.4 Gy) and cisplatin (40 mg/m2/week). The chemotherapy group will receive paclitaxel (175 mg/m2) plus cisplatin (50 mg/m2) or carboplatin (AUC=6) every 3 weeks for six cycles.Major Inclusion/Exclusion CriteriaPatients with high risk stage IB–IIB cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma) who underwent radical hysterectomy are eligible for the study. High risk is defined as the presence of pelvic lymph node metastasis and/or parametrial invasion.Primary EndpointThe primary endpoint is overall survival.Sample Size250 patients in total are required.Estimated Dates for Completing AccrualThis study began in November 2019, and 250 patients will be accrued within 5 years.Trial Registration NumberThe study has been registered with the Japan Registry of Clinical Trials (jRCTs041190042).

PurposeStereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost.Materials and methodsICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival.ResultsTwenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III–IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10–84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases.ConclusionThese findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer.Study registrationThis study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).

A Chinese cabbage yellows-suppressing fungal strain (S69) isolated from a suppressive field soil to the disease was identified to be Pseudothielavia terricola, based on phylogenetic analyses and morphological observations. Phylogenetic studies were completed using individual and combined data sequences of ITS-LSU, rpb2, and tub2, and indicated that the identified fungal strain belonged to a monophyletic clade that also included P. arxii and P. terricola. Morphological observations revealed that the fungal ascospores had apical germ pores, a distinctive characteristic of P. terricola but not of P. arxii. Additional observed morphological characteristics of S69 were also similar to P. terricola.

Introduction: Endometrial cancer (EC) with deficient mismatch repair (dMMR) is a promising target for immune checkpoint inhibitor therapy. However, dMMR tumors are heterogeneous, and those with MLH1 promoter methylation respond less favorably to pembrolizumab monotherapy than Lynch syndrome-associated cases. Evidence for optimal treatment strategies in pembrolizumab-refractory dMMR tumors remains limited. Case Presentation: We report a woman in her 50s with recurrent endometrial carcinoma who was initially treated with surgery for stage IA, grade 1 endometrioid carcinoma. After recurrence with peritoneal dissemination and liver metastases, she received paclitaxel plus carboplatin with temporary response, followed by pembrolizumab monotherapy after detection of MSI-high status. However, disease progression occurred after two cycles. Immunohistochemistry (IHC) revealed loss of MLH1 and PMS2 expression, and EPM2AIP1 IHC suggested MLH1 promoter methylation. Given her preserved performance status, lenvatinib plus pembrolizumab (LP) therapy was initiated. Tumor markers, including CA125, decreased rapidly. Radiological assessments demonstrated marked shrinkage of peritoneal and liver metastases, with a durable response lasting at least 6 months. Adverse events, including stomatitis, hand-foot syndrome, arthritis, hypothyroidism, anorexia, fatigue, and fever, were manageable with supportive care and dose modification. Conclusion: This case illustrates that LP therapy can achieve a favorable response in dMMR EC with MLH1 promoter methylation after pembrolizumab failure. Further studies are warranted to clarify the biology of methylated dMMR tumors, establish individualized treatment strategies, and develop practical diagnostic systems to identify MLH1 promoter methylation.

Background The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC‐IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC‐IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics. Methods We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB–IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score‐matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non‐adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs. Results Among the 1613 patients with CC‐IR, 619 and 994 were in the non‐treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3‐year progression‐free survival (PFS) rates were 88.1% and 90.3% in the non‐treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3‐year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors. Conclusion Adjuvant therapy is optional for some patients with CC‐IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors.

Introduction Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Methods Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. Results This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Conclusion Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136).