Role of Chemoradiation in the Adjuvant Treatment of Radically Resected Pancreatic Cancer Patients: A Mono-Institutional Retrospective Analysis.

INTRODUCTION: Pancreatic cancer (PC) represents an unfavorable prognosis condition, even in patients with resectable disease. The aim of this series was to investigate the role of treatment intensification with adjuvant chemoradiation (CRT) in radically resected PC patients. METHODS: Data from PC patients who underwent radical surgery, adjuvant chemotherapy (CT), and CRT throughout a 20-year period were retrospectively collected. Actuarial local control (LC) and the overall survival (OS) were the primary endpoints, with disease-free survival and metastasis-free survival (MFS) representing secondary endpoints. RESULTS: The analysis included 108 PC patients treated with adjuvant CRT and CT from January 2000 to August 2019. Median age was 66 years (range: 40-83), and all patients underwent radical surgical resection with adjuvant CT (88, 81.5%) plus concomitant CRT (101, 93.5%) or radiotherapy alone (7, 6.5%). The median dose delivered to the tumor bed was 50.4 Gy (range: 45-50.6 Gy), while median dose to regional lymphatic drainage stations was 39.6 Gy (range 39.6-45 Gy). Concomitant CT was a gemcitabine-based regimen in the vast majority of patients (87, 80.6%). Median follow-up time was 21 months; the 2- and 5-year LC rates were 75.8% and 59.1%, respectively. Perineural invasion at pathological assessment was found significantly associated with LC (p = 0.028). Median OS was 40 months with 2- and 5-year OS rates of 73.9% and 41.6%, respectively. CONCLUSIONS: The outcomes of this series suggest to investigate the possible impact of adding adjuvant CRT to CT in PC patients. Timing and combination of modern CRT with new systemic therapies need to be further investigated to personalize therapy and optimize clinical advantages.

Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.

BACKGROUND: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. RESULTS: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008). CONCLUSION: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.

Clinical, Pathological and Prognostic Features of Rare BRAF Mutations in Metastatic Colorectal Cancer (mCRC): A Bi-Institutional Retrospective Analysis (REBUS Study).

Recently, retrospective analysis began to shed light on metastatic colorectal cancers (mCRCs) harboring rare BRAF non-V600 mutations, documenting a distinct phenotype and a favorable prognosis. This study aimed to confirm features and prognosis of rare BRAF non-V600 mCRCs compared to BRAF V600E and BRAF wild-type mCRCs treated at two Italian Institutions. Overall, 537 cases were retrospectively evaluated: 221 RAS/BRAF wild-type, 261 RAS mutated, 46 BRAF V600E and 9 BRAF non-V600. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided, had a lower tumor burden and displayed a lower grade and an MMR proficient/MSS status. In addition, non-V600 mCRC patients underwent more frequently to resection of metastases with radical intent. Median overall survival (mOS) was significantly longer in the non-V600 compared to the V600E group. At multivariate analysis, only age < 65 years and ECOG PS 0 were identified as independent predictors of better OS. BRAF V600E mCRCs showed a statistically significant worse mOS when compared to BRAF wild-type mCRCs, whereas no significant difference was observed between BRAF non-V600 and BRAF wild-type mCRCs. Our study corroborates available evidence concerning incidence, clinicopathologic characteristics and prognosis of BRAF-mutated mCRCs.

Challenges in Crohn's Disease Management after Gastrointestinal Cancer Diagnosis.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.

PTEN in Colorectal Cancer: Shedding Light on Its Role as Predictor and Target.

Molecular assessment of colorectal cancer (CRC) is receiving growing attention, beyond RAS and BRAF, because of its influence on prognosis and prediction in cancer treatment. PTEN (phosphatase and tensin homologue), a tumor suppressor, regulating cell division and apoptosis, has been explored, and significant evidence suggests a role in cetuximab and panitumumab resistance linked to the epidermal growth factor receptor (EGFR) signal transduction pathway. Factors influencing PTEN activity should be analyzed to develop strategies to maximize the tumor suppressor role and to improve tumor response to cancer treatment. Therefore, an in-depth knowledge of the PI3K-Akt pathway-one of the major cancer survival pathways-and the role of PTEN-a major brake of this pathway-is essential in the era of precision medicine. The purpose of this literature review is to summarize the role of PTEN as a predictive factor and possible therapeutic target in CRC, focusing on ongoing studies and the possible implications in clinical practice.