Baseline and Longitudinal Neutrophil-to-Lymphocyte Ratio as Prognostic Factor for Metastatic Colorectal Cancer: A Secondary Analysis of the ITACa Randomized Trial.

PURPOSE: We aimed to investigate the prognostic role of baseline and longitudinal levels of neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy + bevacizumab (CT + B) or chemotherapy only. Additionally, we investigated whether treatment outcomes were mediated by the longitudinal biomarker. METHODS: Data from an Italian randomized phase III trial were used. The main end point was progression-free survival (PFS). To address research questions, a series of joint models of longitudinal and survival data were specified, and the direct and indirect treatment effects were quantified. RESULTS: Data for 239 patients, 113 (47.3%) treated with CT + B and 126 (52.7%) with CT only, were included in the analyses. The effect of NLR seemed to be mediated by the longitudinal trajectory of the biomarker. Only in the patient subgroup treated with CT + B, the baseline NLR retained a direct effect on PFS. Regarding the effect of treatment on PFS, two scenarios were observed. In the subgroup of patients with low baseline, NLR bevacizumab showed a direct protective effect only (hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.98]), whereas in the subgroup with high baseline NLR, there was evidence for an adverse direct effect (HR, 1.63 [95% CI, 1.03 to 2.57]) and a protective indirect-which is mediated by the longitudinal biomarker-effect (HR, 0.71 [95% CI, 0.55 to 0.90]). CONCLUSION: In our study, inflammatory indexes collected longitudinally showed a significant adverse prognostic role, thus suggesting the collection and use of such data for better clinical decision making. In the specific setting, we considered this is particularly important as the treatment effect seemed to be modified by both the baseline and longitudinal inflammation statuses. However, further research is needed to understand the possible factors underlying these results.

Inflammatory indices as prognostic markers in metastatic colorectal cancer patients treated with chemotherapy plus Bevacizumab.

Background: Validated predictors of sensitivity or resistance to Bevacizumab (Bev) are not available, and Inflammatory Indexes (IIs) has been reported to be useful prognostic factors in various malignant solid tumours, including metastatic colorectal cancer (mCRC). Objectives: To explore the prognostic value of IIs in mCRC patients treated with first-line chemotherapy plus Bev. Design: One hundred and eighty-two patients diagnosed with mCRC and treated with first line chemotherapy plus Bev were considered for this prospective non-pharmacological study. Neutrophil, lymphocyte, platelet, aspartate transaminase (AST) and lactate dehydrogenase (LDH) tests were carried out at baseline and before each treatment cycle, according to clinical practice. Methods: Pre-treatment Systemic Immune-inflammation Index (SII), Colon Inflammatory Index (CII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) were evaluated to assess a correlation with progression-free survival (PFS) and overall survival (OS). Results: In the overall population, PFS and OS were lower in patients with high SII (HR 1.64, p = 0.006 and HR 1.75, p = 0.004, respectively) and high ALRI (HR 2.13, p = 0.001 and HR 1.76, p = 0.02, respectively), but no difference was detected according to CII value. The multivariate analysis confirmed both SII and ALRI as independent prognostic factors for PFS (HR 1.64 and 2.82, respectively) and OS (HR 1.65 and 2.12, respectively). Conclusion: Our results demonstrate and confirm that IIs, and in particular SII and ALRI, are easy to measure prognostic markers for patient candidates to first line chemotherapy plus Bev for mCRC.

Inflammatory Indexes can predict the efficacy of bevacizumab in metastatic colorectal cancer Bevacizumab (Bev) is a humanized monoclonal antibody with antiangiogenic activity, used in combination with chemotherapy as a standard first line treatment for many metastatic colorectal cancer patients. Validated predictors of sensitivity or resistance to Bevacizumab are not available, although several studies have investigated this issue in recent years. In this study, we investigated whether some selected baseline inflammatory indexes levels, namely Systemic Immune-inflammation Index (SII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) could predict the survival in patients with metastatic colorectal cancer treated with Bevacizumab plus chemotherapy. We enrolled 182 patients diagnosed with mCRC and treated with first line chemotherapy plus Bev. For each patient we tested blood neutrophils, lymphocytes, platelets, aspartate transaminase (AST) and lactate dehydrogenase (LDH) before each treatment cycle, according to clinical practice. We calculated the SII value as platelet count × neutrophil count/lymphocyte count, and ALRI as AST/lymphocyte count. We found that patients with high SII and high ALRI values had lower survival as compared to those with low values. These parameters represent reproducible, inexpensive and easy to measure biomarkers to be used in both clinical practice and clinical trials, for patient selection.

Analysis of EVs from patients with advanced pancreatic cancer identifies antigens and miRNAs with predictive value.

The identification of predictive factors for treatment of pancreatic cancer (PC) is an unmet clinical need. In the present work, we analyzed blood-derived extracellular vesicles (EVs) from patients with advanced PC in order to find a molecular signature predictive of response to therapy. We analyzed samples from 21 patients with advanced PC, all receiving first-line treatment with gemcitabine + nab-paclitaxel. Isolated EVs have been analyzed, and the results of laboratory have been matched with clinical data in order to investigate possible predictive factors. EV concentration and size were similar between responder and non-responder patients. Analysis of 37 EV surface epitopes showed a decreased expression of SSEA4 and CD81 in responder patients. We detected more than 450 expressed miRNAs in EVs. A comparative survey between responder and non-responder patients showed that at least 44 miRNAs were differently expressed. Some of these miRNAs have already been observed in relation to the survival and gemcitabine sensitivity of tumor cells. In conclusion, we showed the ability of our approach to identify EV-derived biomarkers with predictive value for therapy response in PC. Our findings are worthy of further investigation, including the analysis of samples from patients treated with different schedules and in different settings.

Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment.

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (pinteraction = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; pinteraction = 0.032). Median PTS was 4.0 months (95% CI 2.8−5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT.

Recurrent pneumothorax in a patient with liposarcoma as either a complication of lung micrometastasis or a potential adverse event from antibiotic therapy: A case report.

Spontaneous pneumothorax (PNX) is an infrequent manifestation of primary lung cancer, soft tissue sarcoma and metastasis. There are no easily accessible data in the literature regarding the correlation between PNX and antibiotics, whereas cases of PNX following chemotherapy have been observed. Only 1-10% of treatment-related adverse events are estimated to be reported to the Food and Drug Administration. The present study described a case of PNX of the left lung in a 70-year-old treatment-naive patient with retroperitoneal liposarcoma. The PNX developed after 8 days of treatment with levofloxacin and after 6 days of piperacillin/tazobactam treatment for a suspicious inflammatory area in the right lung detected by an FDG-PET scan before the patient started chemotherapy. A chest CT scan confirmed the presence of metastasis in the right lung, but neither FDG-PET/CT nor CT showed metastatic disease in the left lung. A total of 14 days after the end of the third cycle of doxorubicin (2 months after the initial diagnosis of PNX), the patient manifested a massive PNX of the right lung. In conclusion, these findings indicated that spontaneous PNX could be linked to the use of some antibiotics.

Gene mutational profile of BRCAness and clinical implication in predicting response to platinum-based chemotherapy in patients with intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Biliary tract cancers are rare malignancies with a poor prognosis and scarce therapeutic strategies. The significance of BRCAness in this setting is already unknown. METHOD: Tissue specimens of BTC patients treated with platinum-based chemotherapy have been analyzed through the FOUNDATIONPne assay. RESULTS: 72/150 (48%) BRCAness mutated and 78/150 (52.0%) wild type (WT) patients were included. The most commonly mutated genes in the BRCAness mutated group were: ARID1A (N = 32, 44%), CDKN2A (N = 23, 32%), KRAS/NRAS (N = 16, 22%), CDKN2B (N = 13, 18%), BRCA2 (N = 13, 18%), PBRM1 (N = 12, 17%), ATM (N = 11, 15%), FGFR2 (N = 10, 14%), TP53 (N = 8, 11%), IRS2 (N = 7, 10%), CREBBP (N = 7, 10%) (table 3, figure 1). At the univariate analysis BRCAness mutation was associated with longer median Progression Free Survival (mPFS) (HR 0.68; 95% CI 0.49-0.95; p = 0.0254); it was not associated with longer mOS but a trend toward a benefit in survival was found (HR 0.77; 95% CI 0.50-1.19; p = 0.2388). Patients with BRCAness mutation showed a higher percentage of disease control rate (77.8 vs 67.9; p = 0.04) compared to patients WT. Multivariate analysis confirmed BRCAness mutation (HR 0.66; 95% CI: 0.45-0.98; p = 0.0422) as independent favorable prognostic factors for PFS and a positive trend was found for OS (HR 0.84; 95% CI: 0.53-1.33; p = 0.3652). CONCLUSION: BRCAness BTC patients showed a better PFS compared BRCAnessWT patients after exposure to platinum-based chemotherapy. Moreover, the OS curves' trend showed in our analysis suggests that BRCAness mutated patients could benefit from a maintenance therapy with PARPi.

Conversion Surgery in Gastric Cancer Carcinomatosis.

Background: After the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer. Methods: All patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received. Results: A total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8-64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2-26.8) and after upfront surgery 14.7 (10.9-21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2-29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2-60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8-64.0) in those partially regressed (p = 0.742). Conclusions: Conversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.

CNA Profiling of Single CTCs in Locally Advanced Esophageal Cancer Patients during Therapy Highlights Unexplored Molecular Pathways.

BACKGROUND: Here, we monitored the evolution of CTCs spread in 11 patients affected by locally advanced EC who were undergoing therapy. METHODS: In this perspective study, we designed multiple blood biopsies from individual patients: before and after neoadjuvant chemo-radio therapy and after surgery. We developed a multi-target array, named Grab-all assay, to estimate CTCs for their epithelial (EpCAM/E-Cadherin/Cytokeratins) and mesenchymal/stem (N-Cadherin/CD44v6/ABCG2) phenotypes. Identified CTCs were isolated as single cells by DEPArray, subjected to whole genome amplification, and copy number aberration (CNA) profiles were determined. Through bioinformatic analysis, we assessed the genomic imbalance of single CTCs, investigated specific focal copy number changes previously reported in EC and aberrant pathways using enrichment analysis. RESULTS: Longitudinal monitoring allowed the identification of CTCs in at least one time-point per patient. Through single cell CNA analysis, we revealed that CTCs showed significantly dynamic genomic imbalance during treatment. Individual CTCs from relapsed patients displayed a higher degree of genomic imbalance relative to disease-free patients' groups. Genomic aberrations previously reported in EC occurred mostly in post-neoadjuvant therapy CTCs. In-depth analysis showed that networks enrichment in all time-point CTCs were inherent to innate immune system. Transcription/gene regulation, post-transcriptional and epigenetic modifications were uniquely affected in CTCs of relapsed patients. CONCLUSIONS: Our data add clues to the comprehension of the role of CTCs in EC aggressiveness: chromosomal aberrations on genes related to innate immune system behave as relevant to the onset of CTC-status, whilst pathways of transcription/gene regulation, post-transcriptional and epigenetic modifications seem linked to patients' outcome.

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies.

In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1-65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8-13.2) and 14.3 (95% CI 12.0-18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6-33.0), and the R0 resection rate was 13.7% (95% CI 5.8-21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19-9 were associated with improved OS and PFS. Concerning OS, log(CA19-9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02-1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46-4.96); for PS 2, HR was 4.18 (95% CI 0.90-19.46); p = 0.003. Low CA19-9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52-0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.

Comprehensive analysis of DNA damage repair genes reveals pathogenic variants beyond BRCA and suggests the need for extensive genetic testing in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a major cause of cancer death. In an effort to improve treatment strategies and outcomes, DNA damage repair (DDR) pathways have been introduced as a new target in PC and in other cancers, through the exploitation of synthetic lethality. Furthermore, genes involved in DDR are among the major determinants of cancer susceptibility. In addition to the well-known BRCA1 and BRCA2 genes, a plethora of other targets in the same pathways are now emerging. METHODS: We analyzed samples from 60 patients, affected by PC and already tested for BRCA, using a panel with 24 other cancer susceptibility genes. RESULTS: We detected 8 pathogenic or likely pathogenic mutations (13.3% of samples analyzed), 4 of which were found in non-BRCA genes (2 in ATM, 1 each in PALB2 and RAD50). Furthermore, 4 pathogenic or likely pathogenic mutations were found in patients without a personal or familial history of cancer. CONCLUSIONS: Our results suggest that genetic testing with a comprehensive gene panel should be perfomed in all patients with PC, in order to allow screening for PC and other gene-related cancers in all at risk family members and to assess patients' eligibility for emerging therapeutic options.

Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen.

LESSONS LEARNED: The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen. A comparison with calcium levofolinate (Ca-Lev) showed a similar toxicity profile. The advantages of Na-Lev over Ca-Lev might be the faster drug preparation and the shorter time of drug administration. BACKGROUND: The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration. METHODS: The study opened in November 2015 and closed in August 2019. Patients with gastrointestinal cancers who were candidates for treatment with the FOLFIRI regimen were included in this nonrandomized study. Age ≥18 years, life expectancy >3 months, adequate bone marrow reserve, adequate hepatic and renal function, and an ECOG performance status of 0-2 were required. Patients in the Ca-Lev arm received a 2-hour infusion of Ca-Lev followed by 5-FU, whereas those in the Na-Lev arm received Na-Lev and 5-FU administered in a single 48-hour pump. RESULTS: Sixty patients were enrolled, 30 in each arm. Patient characteristics were balanced. Grade (G)1-2 adverse events occurred in 18 (60.0%) and 19 (63.4%) patients of Na-Lev and Ca-Lev cohorts, respectively, whereas G3-4 adverse events occurred in 12 (40.0%) and 11 (36.6%) patients, respectively. The use of Na-Lev enabled us to save approximately 13 minutes for drug preparation and 2 hours for treatment administration, per patient per cycle. CONCLUSION: Na-Lev showed a reassuring toxicity profile and a favorable impact on drug preparation and administration.

Sequential Treatment of Sorafenib-Regorafenib Versus Sorafenib-Physician's Choice: A Propensity Score-Matched Analysis.

BACKGROUND: Regorafenib has been shown to improve clinical outcomes compared to placebo, becoming a standard second-line therapy for sorafenib-progressed and -tolerated hepatocellular carcinoma (HCC) patients. OBJECTIVE: We performed a multicentre, retrospective study in Italy and Korea to evaluate the effectiveness of the treatment sequence sorafenib-regorafenib compared with sorafenib and physician's choice in a real-life setting. PATIENTS AND METHODS: A propensity score model was developed to control the results for baseline variable imbalances between the arm treated with sorafenib and regorafenib (S-R) and the arm treated with sorafenib and physician's choice (S-P). Survival analysis was conducted on the matched population. RESULTS: After the application of propensity score matching, we analysed 99 patients in the arm treated with S-R and 99 patients in the arm treated with S-P. For the S-R group, the median overall survival was 22.2 months (95% CI 17.1-27.4), compared to 17.9 months (95% CI 15.1-50.0) for the S-P group. The results of the univariate analysis showed a 31% reduction of death risk for patients treated with S-R (p = 0.0382) compared to patients treated with S-P. Interaction tests highlighted the predictive role of alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and extrahepatic spread. CONCLUSION: This study provides additional proof of the superiority of the S-R treatment over the S-P treatment approach in advanced HCC patients from a real-life setting.

Effects of Metformin and Vitamin D on Clinical Outcome in Cholangiocarcinoma Patients.

BACKGROUND AND AIMS: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. METHODS: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. RESULTS: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32-0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52-0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26-0.73, p = 0.0016). CONCLUSIONS: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.

The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation.

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox's proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04-5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

Heterogeneity of Response and Immune System Activity during Treatment with Nivolumab in Hepatocellular Carcinoma: Results from a Single-Institution Retrospective Analysis.

Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options; in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.

Neoadjuvant treatment (FOLFOX4 plus hypofractionated tomotherapy) for patients with locally advanced rectal cancer: a multicenter phase II trial.

AIMS: This study aims to evaluate the safety and efficacy of a new neoadjuvant regimen (FOLFOX4 plus hypofractionated tomotherapy) in patients with locally advanced rectal cancer. METHODS: Patients with stage II-III rectal cancer were treated with the pre-operative chemoradiotherapy regimen comprising FOLFOX4 (two cycles), TomoTherapy (25 Gy in five consecutive fractions, one fraction per day in 5 days on the clinical target volume at the isodose of 95% of the total dose), FOLFOX4 (two cycles), followed by surgery with total mesorectal excision and adjuvant chemotherapy with FOLFOX4 (eight cycles). The primary endpoint was pathological complete response (pCR). RESULTS: Fifty-two patients were enrolled and 50 patients were evaluable. A total of 46 (92%) patients completed chemoradiotherapy according to the study protocol and 49 patients underwent surgery. Overall, 12 patients achieved a pCR (24.5%, 95% CI 12.5-36.5). The most common grade 3 or more adverse events were neutropenia and alteration of the alvus. Adverse reactions due to radiotherapy, mainly grade 1-2 dermatitis, tenesmus, urinary dysfunction and pain, were tolerable and fully reversible. The most important surgical complications included infection, anastomotic leakage and fistula, all resolved with conservative treatment. CONCLUSION: FOLFOX and hypofractionated TomoTherapy is effective and safe in patients with locally advanced rectal cancer. Long-term efficacy needs to be further evaluated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02000050 (registration date: 26 November 2013) https://clinicaltrials.gov/ct2/show/NCT02000050.

Prognostic role of a new index (multi inflammatory index) in patients with metastatic colorectal cancer: results from the randomized ITACa trial.

AIMS: We created a new index (Multi Inflammatory Index, MII) composed of an inflammatory index [neutrophil-to lymphocyte-ratio (NLR): MII-1; platelet-to-lymphocyte ratio (PLR): MII-2; or systemic immune-inflammation index (SII): MII-3] and C-reactive protein (CRP). Our aim was to evaluate the prognostic and/or predictive capacity of the MII in the randomized ITACa (Italian Trial in Advanced Colorectal Cancer) study on patients with metastatic colorectal cancer undergoing first-line chemotherapy. METHODS: Between November 2007 and March 2012, baseline NLR, PLR; SII and CRP were available for 131 patients, 66 receiving chemotherapy plus bevacizumab and 65 receiving chemotherapy alone. RESULTS: Patients with low (<25) MII-1 levels had a better outcome than those with high (⩾25) levels: median progression-free survival (PFS) was 12.4 versus 8.9 months [hazard ratio (HR) = 1.74, 95% confidence interval (CI) 1.21-2.51, p = 0.003] and median overall survival (OS) was 30.9 months versus 15.0 months (HR = 2.05, 95% CI 1.40-3.02, p = 0.0002), respectively. Similar results were obtained for patients with low (<1424) MII-2 levels compared with those with high (⩾1424) levels: median PFS was 12.6 versus 8.9 months (HR = 1.95, 95% CI 1.35-2.82, p = 0.0004) and median OS was 32.4 versus 14.6 months, respectively (HR = 2.42, 95% CI 1.64-3.57, p < 0.0001). Patients with low (<6068) MII-3 levels had a longer median PFS and OS than those with high (⩾6068) levels: 12.6 versus 8.9 months (HR = 1.91, 95% CI 1.33-2.76, p = 0.005) and 30.9 versus15.0 months (HR = 2.10, 95% CI 1.43-3.09, p = 0.0002), respectively. Following adjustment for clinical covariates, multivariate analysis confirmed all MII indexes as independent prognostic factors for predicting PFS and OS. CONCLUSION: All MII indexes appear to be useful as prognostic markers. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01878422 (registration date: 07/06/2013) https://clinicaltrials.gov/ct2/show/NCT01878422.

Erratum: Passardi, A. et al. Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study. Cancers 2019, 11, 663.

The authors wish to make the following corrections to this paper [...].