An Unexpected Tumor Reduction: Treatment with Olaparib Monotherapy in Heavily Pretreated BRCA2 Mutated Metastatic Pancreatic Cancer

PARP inhibitors are largely recognized as active drugs in BRCA-mutated breast and ovarian malignancies. In pancreatic ductal adenocarcinoma, the PARP inhibitor olaparib has recently been approved as maintenance treatment in patients with germline BRCA mutations reaching disease control after a platinum-based first line chemotherapy, proving significant benefit on progression free survival. On the other hand, little evidence is available regarding olaparib as single agent after progression with standard treatment in BRCA-mutated pancreatic ductal adenocarcinoma. A 61-year-old female patient harboring germline BRCA2 mutation was treated at our institution for a pancreatic ductal adenocarcinoma with lung and liver metastases. The patient received three previous lines of treatment with standard therapies, as follows: after the third line treatment failure, we started a further line of treatment with olaparib in off-label prescription. After the first two cycles, a CT scan documented partial response, with complete regression of lung metastases. The response was maintained after four cycles, with further response and clinical benefit. The radiologic and clinical response was maintained for 6 months. This case highlights the potential of olaparib as single agent after progression with standard treatment in BRCA-mutated pancreatic cancer

An overview on clinical, pathological and molecular features of lung metastases from colorectal cancer

Introduction: Lung metastases occur in 10-20% of patients with colorectal cancer (CRC). Most of them are treated with palliative intent and have a poor prognosis. Pulmonary metastasectomy may be a curative option for carefully selected patients with 5-year survival rates ranging from 25% to 60%. However, up to 70% of patients develop recurrence after pulmonary metastasectomy. Therefore, the identification of prognostic factors is essential in CRC patients with resectable lung metastases. Areas covered: This review aims at summarizing the actual body of knowledge available on lung metastases from CRC focusing on their clinical, pathological and molecular profile. Moreover, we provide an update on experts' attitudes towards lung metastasectomy, adjuvant or perioperative chemotherapy. Expert opinion: Traditional clinical prognosticators such as the total number of pulmonary metastases, carcinoembryonic antigen (CEA) serum levels before surgery, and presence of lymph node metastases cannot provide reliable criteria to predict survival after lung metastasectomy. Indeed, research efforts have been directed in recent years toward studying the biological characteristics of lung lesions to better define prognosis and response to treatment, and ultimately shed new light on their proper local and systemic management

Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches

The introduction of immunotherapy has revolutionized the oncological targeted therapy paradigm. Microsatellite instability (MSI) identifies a subgroup of colorectal cancers (CRCs) which respond to treatment with immune checkpoint inhibitors. Tissue biopsy is currently the gold standard for the assessment of MSI/Mismatch Repair deficiency (MMRd) by means immunohistochemistry or molecular assays. However, the application of liquid biopsy in the clinic may help to overcome several limitations of tissue analysis and may provide great benefit to the diagnostic scenario and therapeutic decision-making process. In the context of MSI/MMRd CRC, the use of liquid biopsy may allow to establish MSI/MMR status if tissue sampling cannot be performed or in case of discordant tissue biopsies. Liquid biopsy may also become a powerful tool to monitor treatment response and the onset resistance to immunotherapy over time and to stratify of MSI/MMRd patients according to their risk of relapse and metastases. The aim of this review is to summarize the main technical aspects and clinical applications, the benefits, and limitations of the use of liquid biopsy in MSI/MMRd colorectal cancer patients

Organ donor screening for carbapenem-resistant gram-negative bacteria in Italian intensive care units: the DRIn study

The 759 cases of brain death declaration (BDD [Italian law, 6 hours of observation time]) that occurred in 190 Italian intensive care units (ICUs) between May and September 2012 were studied to quantify carbapenem-resistant gram-negative bacteria (CR-GN) isolated in organ donors, to evaluate adherence to national screening guidelines, and to identify risk factors for CR-GN isolation. Mandatory blood, bronchoalveolar lavage, and urine cultures were performed on the BDD day in 99% of used donors. Because results were rarely made available before transplant, >20% of transplants were performed before obtaining any microbiological information, and organs from 15 of 22 CR-GN cases were used. Two (lung-liver) of the 37 recipients died, likely because of donor-derived early CR-GN sepsis. ICU stay >3 days (odds ratio [OR] = 7.49, P = .004), fever (OR = 3.11, P = .04), age <60 years (OR = 2.80, P = .06), and positive ICU epidemiology (OR = 8.77, P = .07) were associated with CR-GN isolation. An association between single ICU and risk of CR-GN was observed, as a result of differences across ICUs (ICC = 29%; 95% confidence interval [CI] 6.5%-72%) probably related to inadequate practices of infection control. Continuous education aimed at implementing priority actions, including stewardship programs for a rational use of antimicrobials, is a priority in healthcare systems and transplant networks. Improved awareness among ICU personnel regarding the importance of early CR-GN detection and timely alert systems might facilitate decisions regarding organ suitability and eventually save recipient lives

Immunotherapy in Gastrointestinal Cancers

Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients’ selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life

Outcome of patients with colorectal cancer undergoing lung metastases resection: a single-institution retrospective analysis

This study was undertaken to review a single-institution cohort of patients with metastatic colorectal cancer undergoing lung resection after a multidisciplinary evaluation and to investigate the main prognostic factors for survival

The oncological multidimensional prognostic index is a promising decision-making tool: A real-world analysis in older patients with metastatic colorectal cancer

Background: Approximately 50% of colorectal cancers occur in older patients. In-ternational societies recommend geriatric tools to optimise treatment of older patients. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment used to classify patients as fit, vulnerable, or frail. The CGA-based oncological multidimensional prognostic index (onco-MPI) also classifies patients as high-, intermediate-, or low-risk based on tumour characteristics. We investigated the role of CGA and onco-MPI in older patients with meta-static colorectal cancer (mCRC) in a real-world setting. Methods: Data for consecutive mCRC patients aged >70 years were retrieved from a prospec-tively maintained database from 2010 to 2020. We analyzed patients' and tumours' character-istics, and the CGA domains. Onco-MPI was calculated by a validated algorithm derived from CGA domains. Pearson's test was used to verify whether onco-MPI scores and chemotherapy administration were correlated. Results: The study included 488 mCRC patients with a mean age of 76.1 years. According to CGA, 52% of patients were fit, 28% vulnerable, and 20% frail. According to onco-MPI, 9% were low, 54% intermediate, and 37% high-risk. The median OS was 22.7 months. The following factors improved OS: 0-1 ECOG PS, low onco-MPI, fit based on CGA, chemo-therapy administration, and doublet regimen. Chemotherapy administration significantly correlated with onco-MPI scores, leading to a survival gain regardless of the risk subgroups. First-line regimen had no impact on survival across the CGA and onco-MPI categories. Conclusion: CGA and onco-MPI scores confirmed their prognostic impact in older mCRC pa-tients and may aid in decision-making and subgroup stratification in dedicated trials. 2022 Published by Elsevier Ltd

Simultaneous Care in Oncology: A 7-Year Experience at ESMO Designated Centre at Veneto Institute of Oncology, Italy

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients’ characteristics and SCOC outcomes through internal procedure indicators. Data were retrieved from the SCOC prospectively maintained database. There were 753 eligible patients. The median age was 68 years; primary tumor sites were gastrointestinal (75.2%), genitourinary (15.0%) and other sites (9.8%). Predominant symptoms were psychological issues (69.4%), appetite loss (67.5%) and pain (65.9%). Dyspnea was reported in 53 patients (7%) in the referral form, while it was detected in 226 patients (34.2%) during SCOC visits (p < 0.0001). Median survival of patients after the SCOC visit was 7.3 months. Survival estimates by the referring oncologist were significantly different from the actual survival. Psychological intervention was deemed necessary and undertaken in 34.6% of patients, and nutritional support was undertaken in 37.9% of patients. Activation of palliative care services was prompted for 77.7% of patients. Out of 357 patients whose place of death is known, 69.2% died at home, in hospice or residential care. With regard to indicators’ assessment, the threshold was reached for 9 out of 11 parameters (81.8%) requested by the procedure. This study confirmed the importance of close collaboration between oncologists and palliative care teams in responding properly to cancer patients’ needs. The introduction of a procedure with indicators allowed punctual assessment of a team’s performance