Abstract only
542
Background: Cisplatin-based chemotherapy remains the perioperative treatment in muscle-invasive bladder carcinoma (MIBC). Recent evidence suggests that immune checkpoint inhibitors ...could be incorporated in this setting. Olaparib is a PARP inhibitor with well-established activity in HRD tumor. Results from trials assessing the combination of durvalumab and olaparib suggest a synergistic effect. However, a molecular characterization is crucial to warrant a rational development. Methods: A phase II clinical trial was designed to assess the impact of neoadjuvant treatment with the combination of durvalumab plus olaparib in the molecular profile of MIBC (NCT03534492; SOGUG-2017-A-IEC(VEJ)-2). Efficacy and safety were secondary objectives. Subjects with cT2-T4a MIBC aimed for cystectomy were treated during 6 to 8 weeks pre-cystectomy. Diagnostic and surgical samples, pre and postreatment blood samples have been collected for the molecular analysis. We present results regarding efficacy and safety. Results: From November 2018 to October 2019 28 patients have been enrolled. 52%/48% of patients had PS 0/1. Median age was 70. TNM stage was: pT2 in 73,6% patients, pT3 in 10.6%, pT4 in 15.8% and 10.6% presented nodal spread. 13 patients have completed neoadjuvant treatment so far and 12 have undergone cystectomy. A wound dehiscence and one death related to surgical procedures were postoperative complications. Pathological complete response rate is 44,5%. Radiological evaluation is ongoing. 10 serious adverse events non-treatment related have been communicated. Any grade of toxicity has been reported in 91% of patients but adverse events grade 3-4 was detected in only 8.3% of cases. Grade 1 pruritus was the unique IR adverse event described in one patient. PARP inhibitors-related adverse events were grade 1 nausea and vomiting (25%), and grade 1 anemia (25%). Conclusions: Preliminary clinical data suggest that Durvalumab in combination with Olaparib could be active and well-tolerated neoadjuvant treatment of MIBC. Molecular characterization and biomarker discovery will be presented separately. Clinical trial information: NCT03534492.
Abstract only
815
Background: The addition of oxaliplatin to fluorouracil and leucovorin as adjuvant therapy for patients with stage II and III colon cancer (CC) has been analyzed in two large, ...randomized trials, MOSAIC and C-07 trials. The updated results of these studies showed that the addition of oxaliplatin enhances overall survival by approximately 5% in patients with stage III disease but has no effect in patients with stage II disease. Methods: We retrospectively included patients with stage II and III CC that were operated between 2009 and 2014 in the Ramón y Cajal University Hospital from Madrid. We perform a multivariable Cox model analysis to estimate the benefit of the chemotherapy stratifying by oxaliplatin in each stage. The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes, perforation, obstruction, grade and age. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (281 stage II and 283 stage III). 305 did not receive any chemotherapy, 61 received monotherapy with fluoropyrimidines (FP) and 198, FP and oxaliplatin. The median follow-up in the entire cohort was 49 months. Globally, adjuvant chemotherapy (either with FP alone or with the combination with oxaliplatin) showed no benefit in DFS (HR of 1.18 and 0.98, respectively). The benefit in OS was significant either for FP alone (HR: 0.46, p: 0.029) and for the combination treatment (HR: 0.41, p: 0.001). Patients with stage II treated with FP in monotherapy showed no benefit, neither in DFS nor OS (HR for DFS: 2.2, p: 0.1; HR for OS: 0.5, p: 0.22). The benefit was neither seen with the addition of oxaliplatin (HR for DFS: 2, p: 0.11; HR for OS: 0.85, p: 0.7). Stage III patients treated with FP presented a HR for DFS of 0.76 (p: 0.5) and a HR for OS of 0.42 (p: 0.087). The HR for DFS with oxaliplatin was 0.53 (p: 0.07). A significant improvement in OS was observed, with a HR of 0.22 (p < 0.001). Conclusions: The addition of oxaliplatin in the adjuvant treatment of stage III patients showed a trend towards improvement in DFS and a significant benefit in OS compared to not receiving chemotherapy. On the contrary, patients with stage II did not benefit from this treatment, neither in DFS nor OS.
Abstract only
842
Background: The standard adjuvant treatment for patients with stage III colon cancer is 6 months with fluoropyrimidines and oxaliplatin. The Intergroup Trial INT-0035 was the first ...large-scale study to demonstrate a significant reduction in the risk of death with adjuvant FU plus levamisole in patients with stage III colon cancer. In the MOSAIC study, the addition of oxaliplatin to fluoropyrimidines in patients with resected stage II to III colon cancer showed OS and DFS benefit of oxaliplatin. However, no significant benefit was observed in either DFS or OS in patients with stage II disease, therefore the benefit of adjuvant chemotherapy is still controversial in those patients. Methods: We retrospectively included patients with stages II and III colon cancer that were operated between 2009 and 2014 in the University Ramón y Cajal Hospital from Madrid. We calculate DFS and OS at 48 months and we perform a multivariable Cox model analysis to estimate the benefit of the chemotherapy in each stage. The model was further adjusted by including the following confounders: ECOG-PS, number or removed nodes ( < 12 or ≥ 12), grade and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied > 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (281 stage II and 283 stage III). 259 received chemotherapy and 305 did not. The median follow-up in the entire cohort was 49 months. The median DFS and OS were not reached at the moment of the analysis. DFS and OS at 48 months were both 78.5%. Globally, chemotherapy did not improve DFS (HR 1.05, p: 0.83) but OS was significantly better (HR 0.47, p: 0.001). By stage, chemotherapy did not improve DFS in stage II (HR: 1.6, p: 0.2) nor OS (HR 0.76, p: 0.43). In stage III, chemotherapy showed a trend to improve DSF (HR: 0.61, p: 0.075) and did improve OS (HR: 0.31, p < 0.0001). Conclusions: The multivariable analysis showed a chemotherapy benefit in patients with stage III colon cancer, with a 39% reduction in the risk of recurrence and a 69% in the risk of death; however, in stage II patients these benefits were not found either in DFS or OS.
Abstract only
655
Background: Adyuvant chemotherapy is a unified therapeutic principle in colon cancer (CC). However, many prognostic factors are arising to determine who really benefits from ...adyuvant chemotherapy in order to avoid overtreatment. Primary tumor location of CC is emerging as an important prognostic factor owing to distinct biological features. However, there is hardly any evidence showing the benefit of treatment according to primary tumor location. Methods: We retrospectively included patients with stage II and III CC that underwent surgical resection between 2009 and 2014 HURyC. We performed a multivariable Cox model analysis to estimate the benefit of chemotherapy according to tumor location in terms of DFS and OS. The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes ( < 12 or ≥ 12), use of adyuvant chemotherapy and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied > 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (267 left sided and 297 right sided). The median follow-up of the entire cohort was 49 months. Globally, chemotherapy did not improve DFS neither in right sided or left sided CC (HR: 0.81, p: 0.58; HR 1.31, p: 0.4, respectively). As for OS, it was improved when adding chemotherapy in both sides (right sided CC HR 0.51, p: 0.061 and left sided CC HR 0.42, p: 0.009). By stages, chemotherapy did not improve DFS or OS according to tumor localization in stage II. In right sided stage III, there was a trend to improve both DFS and OS (HR: 0.54, p: 0.14; HR: 0.39, p: 0.1, respectively). In left sided stage III, there was a trend to improve DFS (HR: 0.66, p: 0.36) and there was an improvement in OS (HR: 0.23, p < 0.001). Conclusions: The multivariable analysis showed benefit of chemotherapy in both right and left sided CC in terms of OS, exhibiting more benefit those patients with left sided CC.
Abstract only
703
Background: Primary tumor location of colon cancer (CC) is emerging as an important prognostic factor owing to distinct biological features. However, this factor still does not ...represent a prognostic parameter when deciding for adyuvant or palliative chemotherapy. In a meta-analysis of 66 studies including patients with all stages of disease, left-sided primary tumor location was associated with a significantly reduced risk of death and this was independent of other prognostic factors. Methods: We retrospectively included patients with stage II and III CC that underwent surgical resection between 2009 and 2014 HURyC. We performed a multivariate Cox model analysis to estimate if tumor location is an independent prognostic factor for overall survival (OS). The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes ( < 12 or ≥ 12), perforation, grade, use of adyuvant chemotherapy and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied > 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (267 left sided and 297 right sided). The median follow-up of the entire cohort was 49 months. Globally, right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.74, p: 0.128; HR: 0.94, p: 0.75, respectively). By stages, stage II right sided CC seemed to show better DFS (HR: 0.45, p: 0.02), although no significant differences were found in OS (HR: 1.004, p: 0.98). Stage III right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.87, p: 0.585; HR: 0.66, p: 0.19, respectively). Conclusions: The multivariate analysis did not show significant differences in terms of prognostic relevance of primary tumor location in the adyuvant setting.
Ovarian cancer (OC) is a deadly disease that affects a large number of women worldwide. Machine Learning (ML) models can help in the early detection of this disease, however, the use of these models ...may be limited by their lack of interpretability and the difficulty to evaluate their performance. In this work, five types of datasets were used, employing clinical features, different types of coding genomic features, and combining both. The use of interpretable ML (IML) models (one linear and one nonlinear model) provided us with better interpretability of the five feature sets. Following this study, nine binary classification models were compared, and the Accuracy, Recall, and Area Under the Curve were analyzed. The results showed that ML models employed the combination of clinical features and genomes with the coding of the position of genes in patients significantly improves the prediction. We demonstrated that the inclusion of different preprocessed patient data and especially through the information provided by IML models, can help clinicians to understand the disease better and make informed treatment decisions.
PDF