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Risk of relapse or progression remains high in the treatment of most patients with epithelial ovarian cancer, and development of a molecular predictor could be a valuable tool for stratification of patients by risk. We aimed to develop a microRNA (miRNA)-based molecular classifier that can predict risk of progression or relapse in patients with epithelial ovarian cancer. We analysed miRNA expression profiles in three cohorts of samples collected at diagnosis. We used 179 samples from a Multicenter Italian Trial in Ovarian cancer trial (cohort OC179) to develop the model and 263 samples from two cancer centres (cohort OC263) and 452 samples from The Cancer Genome Atlas epithelial ovarian cancer series (cohort OC452) to validate the model. The primary clinical endpoint was progression-free survival, and we adapted a semi-supervised prediction method to the miRNA expression profile of OC179 to identify miRNAs that predict risk of progression. We assessed the independent prognostic role of the model using multivariable analysis with a Cox regression model. We identified 35 miRNAs that predicted risk of progression or relapse and used them to create a prognostic model, the 35-miRNA-based predictor of Risk of Ovarian Cancer Relapse or progression (MiROvaR). MiROvaR was able to classify patients in OC179 into a high-risk group (89 patients; median progression-free survival 18 months [95% CI 15–22]) and a low-risk group (90 patients; median progression-free survival 38 months [24–not estimable]; hazard ratio [HR] 1·85 [1·29–2·64], p=0·00082). MiROvaR was a significant predictor of progression in the two validation sets (OC263 HR 3·16, 95% CI 2·33–4·29, p<0·0001; OC452 HR 1·39, 95% CI 1·11–1·74, p=0·0047) and maintained its independent prognostic effect when adjusted for relevant clinical covariates using multivariable analyses (OC179: adjusted HR 1·48, 95% CI 1·03–2·13, p=0·036; OC263: adjusted HR 3·09 [2·24–4·28], p<0·0001; and OC452: HR 1·41 [1·11–1·79], p=0·0047). MiROvaR is a potential predictor of epithelial ovarian cancer progression and has prognostic value independent of relevant clinical covariates. MiROvaR warrants further investigation for the development of a clinical-grade prognostic assay. AIRC and CARIPLO Foundation.

The objective of this study was to develop a nomogram model based on the natural progression of tumor and other radiological features to discriminate between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. A retrospective analysis was conducted on 15,655 cases of lung adenocarcinoma diagnosed at our institution between January 2010 and June 2023. Primary nodular invasive mucinous adenocarcinomas and non-mucinous adenocarcinomas with at least two preoperative CT scans were included. These patients were randomly assigned to training and validation sets. Univariate and multivariate analyses were employed to compare tumor growth rates and clinical radiological characteristics between the two groups in the training set. A nomogram model was constructed based on the results of multivariate analysis. The diagnostic value of the model was evaluated in both the training and validation sets using calibration curves and receiver operating characteristic curves (ROC). The study included 174 patients, with 58 cases of mucinous adenocarcinoma and 116 cases of non-mucinous adenocarcinoma. The nomogram model incorporated the maximum tumor diameter, the consolidation/tumor ratio (CTR), and the specific growth rate (SGR) to generate individual scores for each patient, which were then accumulated to obtain a total score indicative of the likelihood of developing mucinous or non-mucinous adenocarcinoma. The model demonstrated excellent discriminative ability with an area under the receiver operating characteristic curve of 0.784 for the training set and 0.833 for the testing set. The nomogram model developed in this study, integrating SGR with other radiological and clinical parameters, provides a valuable and accurate tool for differentiating between solitary nodular pulmonary mucinous adenocarcinoma and non-mucinous adenocarcinomas. This prognostic model offers a robust and objective basis for personalized management of patients with pulmonary adenocarcinomas.

Background Studies suggest radioguided seed localization (RSL) yields fewer positive margins than wire-guided localization (WL). The goal of this study is to determine whether RSL is superior to WL. Methods Women with confirmed invasive or ductal carcinoma in situ (DCIS) undergoing localization and breast conserving surgery were enrolled. Outcomes measured include positive margin and reoperation rates, specimen weight, operative and localization times, and surgeon and radiologist ranking of procedural difficulty. Results Randomization was centralized, concealed, and stratified by surgeon with 153 patients in the WL group and 152 in RSL group. Localizations were performed using either ultrasound (70%) or mammographic guidance (30%). Pathology was either DCIS (18%) or invasive carcinoma (82%). Procedures were performed at 3 sites, by 7 surgeons. Only difference found for patient and tumor characteristics was more multifocal disease in RSL group. Using intention-to-treat analysis, there were no differences in positive margins rates for RSL (10.5%) and WL (11.8%), ( P = .99) or for positive or close margins (<1 mm) (RSL 19% and WL 22%; P = .61). Mean operative time (minutes) was shorter for RSL (RSL 19.4 vs WL 22.2; P < .001). Specimen volume, weight, reoperation and localization times were similar. Surgeons ranked the seed technique as easier ( P = .008), while radiologists ranked them similarly. Patient’s pain rankings during wire localization were higher ( P = .038). Conclusions In contrast to other trials positive margin and reoperation rates were similar for RSL and WL. However, for RSL operative times were shorter, and the technique was preferred by surgeons, making it an acceptable method for localization.

Background Appendiceal cancer is a rare disease that has proven difficult to study in prospectively. Our initial report of this trial showed minor hematologic toxicity with both mitomycin C and oxaliplatin and similar 3-year survival. We now report an update of the first prospective randomized trial for appendiceal cancer with 10-year follow up. Patients and Methods Patients with mucinous appendiceal neoplasms and evidence of peritoneal dissemination were enrolled in the Multicenter Randomized Trial to evaluating HIPEC for 120 min with oxaliplatin (200 mg/M 2 ) or mitomycin C (40 mg). Overall survival and disease-free survival were calculated at 10 years and compared between the groups. Results A total of 121 patients were included in the study. The patients were 57% female, with a mean age of 55.3 years (range 22–82 years). The disease was low grade in 71% and high grade in 29%. The average peritoneal cancer index (PCI) score was 18 (SD 10) in the mitomycin C group and 17.9 (SD 9.4) in the oxaliplatin group ( p  = 0.94). The 10-year survival rate was 56.2% (SE 7.2) with mitomycin C and 47.5% (SE 8.4) with oxaliplatin, p  = 0.83. The 10-year progression-free survival rate in the mitomycin C group was 45.2% (SE 8.4) compared with 50.4% (SE 6.7) in the oxaliplatin group, p  = 0.95. Median survival was 9.1 years after HIPEC with oxaliplatin, and median not reached for the mitomycin C group (> 5.6 years). Conclusions Oxaliplatin and mitomycin C have similar long-term efficacy for hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal neoplasms and peritoneal dissemination. Long-term survival is experienced by most patients after cytoreduction surgery (CRS) and HIPEC for appendiceal neoplasms.

Background and aimsAccurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN.MethodsPatients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment.ResultsOf the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98–24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60–39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56–14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40–32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900.ConclusionsUsing random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.

Appendiceal mucinous neoplasms are a rare and heterogeneous group of diseases with challenging clinical management decisions. They account for less than 1% of all cancers but their incidence is on the rise. Treatment is based on their stage and histology. Appendiceal neoplasms frequently metastasize inside the abdomen; this leads to tumor cell growth in the abdominal cavity, known as peritoneal carcinomatosis, and buildup of mucinous material, known as pseudomyxoma peritonei. While low-grade, early-stage tumors can be effectively treated with limited surgical resection, patients with low-grade, advanced-stage disease require peritoneal debulking and hyperthermic intraperitoneal chemotherapy. Therapeutic options for high-grade, advanced-stage mucinous tumors of the appendix have not been well established. Debulking surgery with hyperthermic intraperitoneal chemotherapy preceded and/or followed by systemic chemotherapy has been utilized based on some prospective but not randomized data. We present a case of mucinous adenocarcinoma of the appendix treated with neoadjuvant chemotherapy followed by cytoreductive surgery/hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Preoperative chemotherapy provided a favorable histologic response by converting initial mucinous appendiceal adenocarcinoma histology to a high-grade mucinous appendiceal neoplasm.

We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C‐ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty‐three patients were enrolled between April 2010 and March 2014. Treatment consisted of C‐ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C‐ion RT. In the phase 2 component, the efficacy and safety of C‐ion RT with concurrent chemotherapy were evaluated using the dose determined in the phase 1 component. The median follow‐up duration was 30 months. Two patients did not receive chemotherapy because of anemia or leukocytopenia immediately prior to commencing treatment; 31 patients were analyzed. None of the patients developed dose‐limiting toxicities. The recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2 component, two patients developed Grade 3–4 toxicities in the gastrointestinal tract, due to repeated laser coagulation or peritonitis caused by appendicitis. In the patients treated with the RD, the 2‐year local control, progression‐free survival, and overall survival rates were 71%, 56%, and 88%, respectively. C‐ion RT with concurrent weekly cisplatin was well tolerated in patients with locally advanced uterine cervical adenocarcinoma. Our findings support further investigations into the efficacy of this strategy. The efficacy and safety of carbon ion radiotherapy with concurrent chemotherapy was evaluated in patients with locally advanced uterine cervical adenocarcinoma. This strategy was well tolerated in the majority of patients.

Background The purpose of this study was to describe hospital and geographic variation in 30-day risk of surgical complications and death among colorectal cancer (CRC) patients and the extent to which patient-, hospital-, and census-tract-level characteristics increased risk of these outcomes. Methods We included patients at least 66 years old with first primary stage I–III CRC from the 2000–2005 National Cancer Institute’s Surveillance, Epidemiology, and End Results data linked with 1999–2005 Medicare claims. A multilevel, cross-classified logistic model was used to account for nesting of patients within hospitals and within residential census tracts. Outcomes were risk of complications and death after a complication within 30 days of surgery. Results Data were analyzed for 35,946 patients undergoing surgery at 1,222 hospitals and residing in 12,187 census tracts; 27.2 % of patients developed complications, and of these 13.4 % died. Risk-adjusted variability in complications across hospitals and census tracts was similar. Variability in mortality was larger than variability in complications, across hospitals and across census tracts. Specific characteristics increased risk of complications (e.g., census-tract-poverty rate, emergency surgery, and being African-American). No hospital characteristics increased complication risk. Specific characteristics increased risk of death (e.g. census-tract-poverty rate, being diagnosed with colon (versus rectal) cancer, and emergency surgery), while hospitals with at least 500 beds showed reduced death risk. Conclusions Large, unexplained variations exist in mortality after surgical complications in CRC across hospitals and geographic areas. The potential exists for quality improvement efforts targeted at the hospital and/or census-tract levels to prevent complications and augment hospitals’ ability to reduce mortality risk.

ObjectiveWe conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB–IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.MethodsThirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m2) or docetaxel (DTX, 60 mg/m2) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events.ResultsTwenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%–75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild.ConclusionsTaxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB–IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

Background Five percent to 20% of stage I endometrial cancer patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy develop vaginal and pelvic recurrences. Adjuvant radiotherapy can improve locoregional control but not survival. This randomized trial aimed to determine whether a modified radical (Piver–Rutledge class II) hysterectomy can improve survival and locoregional control compared to the standard extrafascial (Piver–Rutledge class I) hysterectomy. Methods Eligible patients ( n  = 520) with stage I endometrial cancer were randomized to class I or class II hysterectomy. Primary endpoint was overall survival. Results The median length of parametria and vagina removed were 15 and 5 vs. 20 mm and 15 mm for class I and class II hysterectomy, respectively ( P  > 0.001). Operating time and blood loss were statistically significantly higher for class II hysterectomy. At a median follow-up of 70 months, 51 patients had died. Five-year disease-free and overall survival were similar between arms (87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm, respectively). The unadjusted hazard ratios for recurrence was 0.91 (95% confidence interval, 0.55–1.51, P  = 0.72), and the hazard ratio for death was 0.77 (95% confidence interval, 0.44–1.33, P  = 0.35). Conclusions Class II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy, but when an adequate vaginal cuff transection is not feasible with class I hysterectomy, a modified radical hysterectomy allows to obtain an optimal vaginal and pelvic control of disease with a minimal increase in surgical morbidity.