A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)

Use of Machine-Learning Algorithms in Intensified Preoperative Therapy of Pancreatic Cancer to Predict Individual Risk of Relapse

Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations

Simultaneous resection of colorectal cancer and synchronous liver metastases: what determines the risk of unfavorable outcomes? An international multicenter retrospective cohort study

BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes. METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression. RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013). CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections

Prescription in patients with chronic heart failure and multimorbidity attended in primary care

Item does not contain fulltextBACKGROUND: Multimorbidity and polypharmacy pose challenges to improving the quality of care. OBJECTIVES: To determine the association between prescription of recommended treatment in ambulatory patients with chronic heart failure and multiple comorbidities and hospitalisation events. DESIGN: A population-based retrospective cohort study in Catalonia (north-east Spain). PARTICIPANTS: We included 7173 newly registered patients with chronic heart failure (59% women; mean [SD] age 76.3 [10.7] years). Patients were selected from the electronic patient records of primary care practices and followed for three years. OUTCOME MEASURES: Prescription of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and beta-blockers (BBs). RESULTS: Prescription of ACEI/ARBs in patients managed in primary care without a hospitalisation event during the follow-up rose from 50.8 to 83.5% for 0 and >/=4 comorbidities, respectively, and for ACEI/ARBs and BB from 13.1 to 30.6% for 0 and >/=4 comorbidities respectively. Patients with a hospitalisation event were treated more often (ACEI/ARBs or 1.47 [1.17 to 1.85]; ACEI/ARBs and BB or 1.41 [1.17 to 1.69]). Comorbid conditions receiving more treatment were hypertension (ACEI/ARBs or 3.75 [3.33 to 4.22]; ACEI/ARBs and BB or 1.40 [1.23 to 1.59]), diabetes mellitus (ACEI/ARBs or 1.79 [1.57 to 2.04]; ACEI/ARBs and BB or 1.33 [1.18 to 1.49]) and ischaemic heart disease (ACEI/ARBs or 1.25 [1.10 to 1.42]; ACEI/ARBs and BB or 3.01 [2.68 to 3.38]). CONCLUSION: Prescription of recommended treatment in patients with chronic heart failure increased as the number of comorbidities increased. Family physicians can provide equivalent care to more complex patients and those less complex, according to the number of comorbidities