BackgroundAdvances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients.Materials and methodsA real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery.ResultsOverall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome.ConclusionsClinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.

Despite a reduction of both incidence and mortality of CRC in the elderly population, several studies published in the last decade have shown an increase in the incidence of early-onset CRC (EO-CRC). Clinical and prognostic data on this setting are limited and conflicting. The aim of our study was to evaluate the clinical, prognostic, and molecular differences in a large group of patients (pts) with early onset mCRC. We collected data from 589 metastatic EO-CRC from 4 different Italian Institutions. A historical control group of 316 pts > 50-year-old was also included in the analysis. All pts had one or more metastatic sites, molecular profiling available (including RAS, BRAF, and MSI status), and underwent at least one line of treatment. The main objective of the study was to evaluate clinical outcome in terms of median overall survival for the global population of EO-CRC pts and in different molecular subgroups according to RAS and BRAF status. In the EO-CRC group median age was 44 (±6) and 67 (±11) in the historical control group. M/F ratios were 2:1 and 1:1, respectively. In the overall population mOS was 34,1 in EO-CRC pts vs 42,0 months (mo) (p = 0,0006) in the control group. In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 28,6 vs 36,0 mo in the control group (p = 0,0065). In RAS/BRAF wild type subgroup mOS in EO-CRC pts was 44,1 vs 49 mo (p = 0,13). Finally, in the BRAF V600E mutated subgroup EO-CRC pts showed a 16 mo mOS vs 26 mo (p = 0,04). In the overall population mPFS was 12,0 in EO-CRC pts vs 10,0 mo (p = 0,02) in the control group. Furthermore, the overall response rate (ORR) was 53% in EO-CRC and 69% in LO-CRC. Our work including a large population of EO-CRC pts indicates a general worse prognosis for pts with early onset colorectal cancer compared to late onsets. Interestingly this seems to occur regardless of the molecular status. On the other hand, findings in the RAS/BRAF wild type population might also suggest a less unfavourable impact of EO-CRC on prognosis possibly related to anti-EGFR therapy. Subsequent investigations will be needed to further understand the specific clinical and molecular characteristics of this growing group of pts to better define the more appropriate treatment strategy.

About 50% of colorectal cancers occur in elderly patients (pts). The oncological societies suggest using geriatric tools to customize treatment. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment, classifying pts as fit, vulnerable or frail. Oncological multidimensional prognostic index (oncoMPI) is a CGA-based score which includes also tumour characteristics, classifying pts in high-, intermediate- and low-risk group. We investigated the role of CGA and oncoMPI in metastatic colorectal cancer (mCRC) elderly pts in a real-world setting. Consecutive mCRC pts aged ≥70 years were prospectively evaluated at Istituto Oncologico Veneto from 2010 to 2020. Pts' demographics, CGA (ECOG PS, comorbidities, medications, pain, caregiver presence, BMI, ADL and IADL, Mini Mental Status Examination, Geriatric Depression Scale), tumor characteristics (primary tumor location, RAS/BRAF status, metastases' number), lines and regimens of chemotherapy (CT) were analysed. OncoMPI was calculated by a validated algorithm from the CGA domains. Correlation between onco-MPI and first-line decision-making was investigated by Pearson's chi-squared test. A total of 488 mCRC pts were included, 287 males. Mean age was 76.1 years, ECOG PS was < 2 in 84%. According to CGA, 52% of pts were classified as fit, 28% vulnerable and 20% frail. According to oncoMPI score, 9%, 54% and 37% of pts were low, medium and high risk, respectively. Median overall survival (OS) was 22.7 months. The following factors were significantly associated with OS: ECOG PS (0-1 vs > 1, HR 2.4), CGA (fit vs frail, HR 2.4), oncoMPI score (low vs high risk, HR 1.7), metastases' number (1 vs > 1, HR 2.1), CT administration (none vs at least one line, HR 0.63), first-line regimen (monotherapy vs doublet, HR 0.7). CT administration correlated with oncoMPI scores (Pearson's test p-value < 0.0001) providing a survival gain in all the risk subgroups. CGA and oncoMPI confirmed their prognostic role in mCRC elderly pts. CGA-derived oncoMPI may help to drive decision-making in clinical practice and to standardize subgroups of the heterogenous population of elderly in clinical trials.

A complete tumor response to neoadjuvant chemo-radiation (CRT) for locally advanced rectal cancer (LARC) is associated with better outcomes, but it is achieved in only 20-30% of patients (pts). The potential role of concomitant medications in addition to CRT has been evaluated in many studies to enhance response rate, but data are not definitive. In this multicentric, retrospective study, we investigated the influence of various concomitant medications on outcomes in this setting of pts. 246 pts treated at Azienda Ospedaliero-Universitaria of Modena, University of Parma, and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori from 2003 to 2018 were retrospectively identified. Demographical and clinicopathological data of potential interest were collected. Odds Ratio (OR) was used to assess the association between the use of concomitant drugs and outcomes (Dworak tumor regression grade [TRG] and disease-free survival [DFS]). All pts received neoadjuvant CRT. Of them, 15.8% were taking antihypertensive drugs, 3.7% statins, 1.2% antiplatelet drugs, and 1.6% antidiabetic drugs. Moreover, 30.5% of pts were taking ≥2 of these drugs simultaneously. Roughly 40% of pts have experienced CRT-related toxicity, leading to a dose reduction or treatment discontinuation in 27% of cases. Of the 221 surgical specimens available, a Dworak TRG score 3-4 was achieved in 30.7% of cases. At both univariate and multivariate analysis, we found an association between statins and a Dworak 3-4 (OR 8.78, p=0.01). Furthermore, statins were also significantly associated with more frequently CRT-related toxicity (OR 2.39, p=0.0098) and a more frequent chemotherapy dose reduction or discontinuation (OR 2.26, p=0.03). No correlations were found between the use of the evaluated drugs and the DFS. Despite a higher frequency of chemotherapy interruption or dose reduction and radiotherapy interruption, in this series of pts with LARC treated with neoadjuvant CRT, the concomitant use of statins proved to be associated with better tumor regression, according to the Dworak system. Larger prospective trials are awaited to confirm this hypothesis.

Background ABC portend a dismal prognosis despite standard chemotherapy treatment. A proper risk-stratification is key to optimize the benefit-to-risk ratio of palliative treatment. The PNI is an immune-inflammatory and nutritional indicator showing to be prognostic across a number of malignancies. We aimed at investigating the impact on survival of the PNI in ABC patients (pts) treated with 1L. Methods Electronic medical records of pts diagnosed with ABC and treated with 1L between 2002 and 2018 at the Modena Cancer Centre were retrospectively reviewed. Clinical, pathological and biochemical variables of potential interest were collected. The PNI was calculated as follows: 10 × serum albumin concentration (g/dL) + 0.005 × peripheral lymphocyte count (number/mm2) and dichotomized using the ROC analysis with 36.7 as the cut-off value. Univariate and multivariate analysis were performed to assess the impact of covariates on overall survival (OS). Kaplan-Meier survival curves were generated and log-rank testing was used to make comparisons. Results Overall, 114 pts fulfilled the inclusion criteria and were included in the analysis. 51% (n = 58) were female and 49% (n = 56) had an ECOG PS of 0. 35% (n = 40) of pts received a platinum/gemcitabine doublet, while 65% (n = 74) were treated with other regimens. The median OS in the cohort was 8.1 months. At the univariate analysis the following covariates were associated with OS: PNI (P 36.7 and Conclusions We demonstrated an independent prognostic role for the PNI in a cohort of ABC treated with 1L. Since it is based on easy-to-collect and inexpensive parameters it should be implemented in the clinical practice to improve the accuracy of current available tools. Legal entity responsible for the study Francesco Caputo. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.