Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

INTRODUCTION: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. METHODS: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test. RESULTS: Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001). CONCLUSION: A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS.

Integrating Downstaging in the Risk Assessment of Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: Validation of Valentini's Nomograms and the Neoadjuvant Rectal Score.

BACKGROUND: Adjuvant chemotherapy is controversial in patients with locally advanced rectal cancer after preoperative chemoradiation. Valentini et al developed 3 nomograms (VN) to predict outcomes in these patients. The neoadjuvant rectal score (NAR) was developed after VN to predict survival. We aimed to validate these tools in a retrospective cohort at an academic institution. PATIENTS AND METHODS: VN and the NAR were applied to 158 consecutive patients with locally advanced rectal cancer treated with chemoradiation followed by surgery. According to the score, they were divided into low, intermediate, or high risk of relapse or death. For statistical analysis, we performed Kaplan-Meier curves, log-rank tests, and Cox regression analysis. RESULTS: Five-year overall survival was 83%, 77%, and 67% for low-, intermediate-, and high-risk groups, respectively (P = .023), according to VN, and 84%, 71%, and 59% for low-, intermediate-, and high-risk groups, respectively (P = .004), according to NAR. When the score was considered as a continuous variable, a significant association with the risk of death was observed (NAR: hazard ratio, 1.04; P < .001; VN: hazard ratio, 1.10; P < .001). CONCLUSION: We confirmed the value of these scores to stratify patients according to their individual risk when designing new trials.

An integrative cross-design synthesis approach to estimate the cost of illness: an applied case to the cost of depression in Catalonia.

BACKGROUND: Cost of illness (COI) studies are carried out under conditions of uncertainty and with incomplete information. There are concerns regarding their generalisability, accuracy and usability in evidence-informed care. AIMS: A hybrid methodology is used to estimate the regional costs of depression in Catalonia (Spain) following an integrative approach. METHODS: The cross-design synthesis included nominal groups and quantitative analysis of both top-down and bottom-up studies, and incorporated primary and secondary data from different sources of information in Catalonia. Sensitivity analysis used probabilistic Monte Carlo simulation modelling. A dissemination strategy was planned, including a standard form adapted from cost-effectiveness studies to summarise methods and results. RESULTS: The method used allows for a comprehensive estimate of the cost of depression in Catalonia. Health officers and decision-makers concluded that this methodology provided useful information and knowledge for evidence-informed planning in mental health. CONCLUSIONS: The mix of methods, combined with a simulation model, contributed to a reduction in data gaps and, in conditions of uncertainty, supplied more complete information on the costs of depression in Catalonia. This approach to COI should be differentiated from other COI designs to allow like-with-like comparisons. A consensus on COI typology, procedures and dissemination is needed.

Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens.

Adjuvant chemotherapy prolongs survival in patients with breast cancer, but it also causes side effects such as ovarian-function suppression. The incidence of chemotherapy-induced amenorrhea (CIA) varies depending on the patients' age, dose and the type of chemotherapy that they receive. CIA produced by anthracycline-based regimens has been widely studied, but less is known about the incidence of CIA caused by the combined use of taxanes and anthracyclines. It has been suggested that tamoxifen might influence the maintenance of amenorrhea. However, most studies of CIA have explored series of patients with hormone-sensitive and hormone-resistant tumors, so data about CIA could be strongly influenced by endocrine adjuvant therapy. The aims of our study were to assess the incidence of CIA with the addition of taxanes to anthracyclines regimens in pre- or perimenopausal patients diagnosed with hormone-sensitive breast cancer and to determine predictive factors for CIA. A retrospective non-randomized study was conducted in the Hospital Clinico Universitario of Valencia, Spain. Three hundred and five premenopausal and perimenopausal patients were recruited between January 1998 and May 2005, 212 of whom had been treated with anthracycline-based regimens and 93 with a combination of anthracyclines and taxanes. Amenorrhea was permanent in 222 patients (93.7%) and menses returned in 6.3%. CIA was present in 75.5% of patients treated with anthracyclines and in 82.7% of patients treated with anthracyclines and taxanes. This difference did not reach statistical significance (p = 0.16). CIA appeared in 95% of patients older than 45 years, while the proportion of CIA decreased to 52% in patients younger than 40 years. This suggests age as an important predictive factor for CIA (p < 0.001). Although a slightly superior incidence of CIA in patients with hormone-sensitive tumors treated with combination regimens was observed, no statistically significant difference in incidence was found. Age was found to be the main predictive factor for CIA in both groups.