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Introduction/BackgroundPatients (pts) with ovarian cancer experiencing a platinum-sensitive (PS) recurrence are generally re-exposed to platinum agents (PCT). The addition of bevacizumab (BEV) or PARP inhibitors (PARPi) as concomitant and/or maintenance therapy has shown to improve progression free survival (PFS). In the absence of direct comparisons coming from randomized trials (RCTs), we have performed a network meta-analysis to evaluate differences in terms of efficacy between BEV and PARPi in pts with PS recurrent ovarian cancer (rOC), according to BRCA status.MethodologyWe searched PubMed, Embase and Medline for RCTs involving pts with PS rOC treated with BEV (n=3, 1563 pts) or PARPi (n=5, 1839 pts). Only trials with PFS as primary endpoint were included. Analyses have been done pooling pts who had received PARPi in three groups, according to the available data on BRCA genes status: all comers (AC), BRCA mutated pts (BRCAm) and BRCA wild-type pts (BRCAwt). A frequentist approach has been used with R statistical software. To rank the effect size of treatments, surface under the cumulative ranking value (SUCRA) has been applied.ResultsIn AC pts, PARPi improved PFS compared to BEV (hazard ratio [HR]=0.70, 95% CI 0.54–0.91). In BRCAm pts the gain in PFS for PARPi was even higher compared to BEV (HR=0.46, 95% CI 0.36–0.59). In BRCAwt pts the benefit of PARPi over BEV was not statistically significant (HR=0.87, 95% CI 0.63–1.20) but PARPi had the highest likelihood of being ranked as the best treatment in terms of efficacy according to SUCRA (90% and 60%, respectively for PARPi and BEV).ConclusionAccording to indirect comparisons, PARPi performed the best for the treatment of PS rOC, especially in BRCAm pts who had not previously received PARPi. BEV could be still an option in BRCAwt pts.DisclosureFabio Puglisi: Roche, AstraZeneca (honoraria and research founding). No conflict of interest is to be declared for the remaining authors. The authors receive no financial support for this study.

Background Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. Methods This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross‐sectional areas (cm2) using CT scan data through the Picture archiving and communication system (PACS) image system. Results In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2/m2. Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2. Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow‐up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression‐free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23–3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30–4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil–lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06–1.61, P = 0.010). Conclusions Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data.

Background HER2 is the only validated predictive biomarker in gastro-oesophageal carcinoma (GOC). However, several factors, such as heterogeneity in protein expression, shortage of evaluable tumour tissue and need for quick target assessment, underline the usefulness of a pre-screening tool in order to anticipate HER2 status. Methods Data from 723 consecutive GOC analysed for HER2 at four Italian Institutions were collected. HER2 positivity was defined as 3+ by immunohistochemistry (IHC) or 2+ with gene amplification by in situ hybridisation (ISH). A multivariate logistic regression model was built using data from 413 cases, whereas 310 patients served as validation cohort. C-index, visual inspection of the calibration plot, Brier score and Spiegelhalter z -test were used to assess the performance of the nomogram. Results HER2 positive rate was 17.4%. Four variables were retained after adjustment in the final model: grading, Lauren’s histotype, pathologic material analysed (surgical specimen/biopsy) and site of tissue collection (primary tumour/metastases). Visual inspection of the calibration plot revealed a very good overlap between predicted and observed probabilities, with a Brier score of 0.101 and a non-significant Spiegelhalter z -test ( P  = 0.319). C-index resulted in 0.827 (95%CI 0.741–0.913). Conclusion A simple nomogram based on always-available pathologic information accurately predicts the probability of HER2 positivity in GOC.

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data.

Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed and third most deadly cancer worldwide. Surgery is the main treatment option for early disease; however, a relevant proportion of CRC patients relapse. Here, variations among preoperative and postoperative serum metabolomic fingerprint of CRC patients were studied, and possible associations between metabolic variations and cancer relapse were explored. Methods: A total of 41 patients with stage I-III CRC, planned for radical resection, were enrolled. Serum samples, collected preoperatively (t0) and 4–6 weeks after surgery before the start of any treatment (t1), were analyzed via NMR spectroscopy. NMR data were analyzed using multivariate and univariate statistical approaches. Results: Serum metabolomic fingerprints show differential clustering between t0 and t1 (82–85% accuracy). Pyruvate, HDL-related parameters, acetone, and 3-hydroxybutyrate appear to be the major players in this discrimination. Eight out of the 41 CRC patients enrolled developed cancer relapse. Postoperative, relapsed patients show an increase of pyruvate and HDL-related parameters, and a decrease of Apo-A1 Apo-B100 ratio and VLDL-related parameters. Conclusions: Surgery significantly alters the metabolomic fingerprint of CRC patients. Some metabolic changes seem to be associated with the development of cancer relapse. These data, if validated in a larger cohort, open new possibilities for risk stratification in patients with early-stage CRC.

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

‘Drug holidays’ (DH) for metastatic colorectal cancer (mCRC) were introduced to preserve quality of life. We studied factors associated to a DH offer in first line. We retrospectively analyzed 754 consecutive patients treated with chemotherapy for mCRC in two Italian institutions between 2005 and 2017. Associations between baseline clinical-pathological factors and DH (56 or more days of treatment interruption) were investigated.  In 754 patients, previous metastasectomy, previous thermoablation and previous surgery of primary tumor were independently associated with DH. Excluding procedures or clinical trials: primary rectal cancer and resection of primary tumor were significantly associated to DH. DH was offered to patients with lower burden of disease, but further investigations are needed to safely guide a holiday strategy. In general, survival of patients affected by metastatic colorectal cancer (mCRC) has increased over the last few years. In order to avoid heavy treatment-related toxicities, treatment breaks called ‘Drug Holidays’ (DH) have been introduced for mCRC. In medical literature, it is still not clear if completely stopping therapy could be more beneficial, and safe, for patients responding to chemotherapy, compared to continued or de-potentiated therapies. We conducted a retrospective study on 754 patients treated in first-line for mCRC to find the factors that are associated to the choice of DH offer. We found that medical oncologists tend to adopt DH for patients who undergo metastasectomies and thermoablations during first-line therapy, or have their primary tumor removed. Excluding procedures on metastases, primary tumor located in the rectum and resection of primary tumor were factors associated to DH offer. Further investigations are needed to identify which are the most relevant factors that could help choosing a safe DH strategy.