Background: immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC). Aim: to identify specific patient subgroups that would derive survival benefit from ICIs. Methods: a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out. Results: four phase-III-RCTs were identified with data on the following variables: primary location(Gastric vs GOJ); age(<= 65 vs 65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology (intestinal vs diffuse), PD-L1 expression(>= 1% vs < 1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR: 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR: 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males. Conclusion: The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, how ever other predictors are eagerly needed to further refine patient selection.

BACKGROUND:Health-related quality of life (HRQoL) is not universally assessed in metastatic colorectal cancer (mCRC) patients. We tried to identify patient subgroups for whom HRQoL assessment should be strongly encouraged. METHODS:Consecutive mCRC patients who had been deemed candidates for first-line chemotherapy were enrolled in a prospective study (NCT03873064) and asked to complete the HRQoL questionnaire EORTC QLQ-C30. Primary endpoint was the Global Health Status (GHS) of EORTC QLQ-C30. A nomogram was built for prediction of low GHS (i.e., <67%). RESULTS:Among recruited patients (n=173), a univariable logistic regression analysis (LRA) found that body mass index (BMI <23), age (>65 years) and sex (female) were significantly associated with low GHS. The multivariable LRA confirmed they were independently associated with the outcome (P values of 0.04-0.004). BMI, age and sex were included in a final predictive model (C-statistics, 67%; P=0.001) and used to build a nomogram. A total nomogram score ≥72 was associated with a risk of 28% or higher of having a low GHS. The 28% risk cut-off had a sensitivity of 90% and a specificity of 34% for identifying low GHS. A decision curve analysis revealed that a risk threshold of 28% of the model was associated to an added net benefit of ≥4% when using the nomogram. Low GHS was recorded in 58% vs. 23% of patients with >28% vs. <28% risk according to the nomogram, respectively (odds ratio 3.54, P=0.0004). CONCLUSIONS:High BMI together with young age and male sex were protective against HRQoL deterioration. In centers where HRQoL is not routinely assessed, such an assessment should be at least made for mCRC patients at risk according to the proposed nomogram (i.e., over 65-year-old females with BMI <23).

BACKGROUND:Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity.METHODS:mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance.RESULTS:Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases.CONCLUSIONS:PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management.

BACKGROUND AND AIM:Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. METHODS:In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. RESULTS:A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. CONCLUSIONS:The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed.

Detection sensitivity of real-time PCR for liquid biopsy has been reported to be about 0.1-0.5%. We evaluated the clinical utility of this technique in the management of metastatic colorectal cancer patients (mCRC) patients. Plasma DNA-binding magnetic beads (MagCore® Plasma DNA Extraction Kit) and selective detections of exons 2, 3 and 4 of KRAS and NRAS and exon 15 of BRAF mutations, by qualitative Real-Time PCR, (EasyPGX®) were used to assess circulating tumor (ct)DNA at baseline in consecutive mCRC patients (from September 2018 to February 2020). ctDNA mutations were compared to tissue RAS/BRAF status and correlated with progression-free survival (PFS) of standard first-line chemotherapy (either FOLFIRI or FOLFOX or FOLFOXIRI plus bevacizumab for tissue mutated patients or panitumumab/cetuximab in wild type patients). Enrolled patients (n = 49, 16 female, 33 male) had a median age of 64 years (range 39-84 years). According to liquid biopsy, the prevalence of KRAS/NRAS (RAS) and BRAF mutation was 26.5% and 10.2%, respectively. As compared to tissue mutation status, 11 cases were RAS discordant: 4 patients wt in tissue and mutated in plasma (WTT/MUTP) and 7 patients mutated in tissue and wt in plasma (MUTT/WTP). ctDNA BRAF V600E mutation was found in 5 patients with a 100% concordance with tissue status. After a median follow up of 10 months (range 2 to 20 months), median (m) PFS in tissue + plasma RAS wild type patients (T+PWT), was 15.9 months (reference group). Among RAS mutated patients both in tissue and liquid biopsy (T+PMUT) mPFS was 8.2 months, with an HR for PFS of 5.45 (95% CI 1.75-16.92) compared to T+PWT population (p-value 0.0061). A long mPFS was observed among MUTT/WTP patients (24.4 months, difference not statistically significant as compared to T+PWT patients, p-value 0,07), probably because of an inferior tumor burden making the RAS mutation undetectable in ctDNA. mPFS in WTT/MUTP patients was as short as 10.3 months, similar to that of T+PMUT patients (p-value 0.2520), indicating the remarkable informative value of liquid biopsy (more aggressive tumor behavior due to the acquisition of ras mutation during disease progression). Patients with V6005 BRAF mutation had the worst prognosis: median PFS, 2.5 months, HR 13.67 (95% CI 3.61-51.7) as compared to T+PWT, p-value < 0.0001. Liquid biopsy for RAS and BRAF mutations using available kits of real-time PCR is feasible in clinical practice and was associated with a more informative prognostic value than tissue mutational status. A larger sample size is needed to confirm the results. The value of longitudinal ctDNA assessment during standard first-line chemotherapy using this technique is underway.

417 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: 11 systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, alkaline phosphatase (ALP), c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value.Selected variables were then analysed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and ALP categorized as < vs > 150 IU/L were found as the most meaningful independent predictors of OS [(HR 1.30 (95%CI 1.02-1.65), 2.00 (95%CI 1.09-3.66), 2.82 (95%CI 1.29-6.20) and p values 0.04, 0.01, 0.02, respectively)] and used to build the GIPI nomogram. Nomogram-based lowest(l), mid and highest(h) risk tertiles were associated with median(m)OS of 14.5,10.6 and 2.4 months(mos), respectively [HR of l vs h 0.26 (95%CI 0.12-0.53), p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR > 6, CRP > 15 mg/L, ALP < 150 IU/L (n: 31) had a mOS of 3.9mos vs 14.5mos of pts with no risk factor (n: 26) (HR 2.72, p 0.0005). Conclusions: GIPI, combining NLR, CRP and ALP, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second line ICIs. Its implementation with analysis of PD-L1 expression in the present cohort is ongoing. GIPI merits validation in external cohorts and prospective clinical trials.

Background Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC. Objective Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC. Methods Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram. Results Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL ( n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor ( n = 28) (HR 2.48; p = 0.0015). Conclusions GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials.

4530 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: Ten systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value. Selected variables were then analyzed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and albumin categorized as < vs > 30 g/dL were found as the most meaningful independent predictors of OS and used to build the GIPI nomogram. Nomogram-based lowest (l), mid-low, mid-high and highest (h) risk quartiles were associated with median(m)OS of 14.9, 7.1, 5.6 and 2.1 months (mos), respectively [HR of l vs h 4.94, p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR >6, CRP >15 mg/L, albumin <30 g/dL (n: 29) had a mOS of 3.9 mos vs 14.2 mos of pts with no risk factor (n: 28) (HR 2.48, p 0.001). Conclusions: GIPI, combining NLR, CRP and Albumin, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second-line ICIs. Its implementation in correlation with PD-L1 expression in the present cohort is ongoing. GIPI merits validation in independent cohorts and prospective clinical trials.

Introduction: Metastatic pancreatic cancer (mPC) is still associated with poor prognosis and limited therapeutic options. Gemcitabine plus nab-paclitaxel (GnP) is a standard first-line chemotherapy associated with a 38% rate of grade 3-4 neutropenia. Moreover, grade 2 neutropenia is also frequent and demands dose-delaying. Grade 2 to 4 (g2-4) neutropenia may thus significantly affect GnP efficacy. Here we propose a nomogram to select patients (pts) at risk of g2-4 neutropenia who can benefit from the prophylactic use of granulocyte growth factors thus optimizing GnP efficacy. Methods: A total of 74 full-dose GnP cycles (12 patients) were analysed. The following baseline data were collected: site of the primary tumor within the pancreas (head vs body/tail); the presence or absence of a biliary stent; presence of nodal, hepatic or pulmonary metastasis; body mass index (BMI); Charlson Comorbidity Index (CCI); count of neutrophils, lymphocytes and platelets; hemoglobin, creatinine, sGOT, sGPT, and total bilirubin levels. All these variables were assessed for grade ≥ 2 neutropenia prediction. Neutropenia was graded according to the Common Toxicity Criteria (CTC) v.4.02. Results: Median (range) pre-cycle neutrophils, platelets and hemoglobin were 4000/μL (1500-19000), 259000/μL (100000-717000) and 12 gr/dL (9.5-16.1), respectively. Grade 2-4 neutropenia was recorded after 22% of cycles. In univariate logistic regression analysis (LRA) of 25 candidate predictors, platelets, neutrophils, and presence of lung metastasis were found to be significantly associated with the risk of g2-4 neutropenia (p-values from 0.07 to 0.02) and were assessed in a multivariable model. A multivariable LRA confirmed the three variables to be significantly associated with g2-4 neutropenia and were all included in a final predictive model (R2 index 23%, C-statistics 75%; P = .007). The model was internally validated with 100 boot-strap resamples (corrected R2 21%). The three variables were used to build up the nomogram with the following scoring system: absence of lung metastasis = 23 points; any 50000 decrease in platelets = 2.5 points starting from 0 points for ≥ 750000 platelets; any 2000 decrease in neutrophils = 2 points starting from 0 points for ≥ 20000 neutrophils. A score ≥ 126 was associated with a g2-4 neutropenia risk ≥ 25%. The 25% risk cut-off had the best discriminatory power according to a Receiver Operating Characteristic (ROC) analysis (sensitivity 81%, specificity 68%). A Decision Curve Analysis revealed that for a threshold of risk of 25% or higher, there was an added net benefit of ≥ 37% patients adequately identified as at risk of grade 2-4 neutropenia by using the nomogram as compared to a 'treat-all' policy. In our cohort, patients with a predicted risk ≥ 25% had an incidence of grade 2-4 neutropenia of 41% as compared to 7% of patients with a predicted risk ≤ 25% (Relative Risk 5.69; P < .003) Conclusion: mPC without lung metastasis and low pre-cycle neutrophil and platelet counts are at increased risk of GnP-induced grade 2-4 neutropenia. Patients with a predicted risk ≥ 25% according to the proposed nomogram should be considered for prophylactic use of growth factors.

Introduction: Health-related quality of life (HRQoL) is of utmost importance for metastatic colorectal cancer (mCRC) patients (pts). The response rate of administered HRQoL questionnaires is suboptimal mainly because they are perceived as time-expensive. Presented here is a nomogram that identified mCRC pts at higher risk of poor HRQoL and hence more in need of an adequate HRQoL assessment. Methods: Consecutive mCRC pts who were candidates for first-line chemotherapy were asked to complete the EORTC QLQ-C30 questionnaire at baseline. The primary endpoint was the Global Health Score (GHS) of EORTC QLQ-C30. Anthropometric, demographic, lifestyle, and clinical characteristics were used to build up the nomogram for predicting the risk of having a low GHS (<67%). Results: 173 pts (69 females, 104 males) were enrolled: median (range) age and Body Mass Index (BMI) were 65 years (44-88) and 25 kg/m2 (14-36), respectively. Univariable logistic regression analysis (LRA) for low GHS prediction was performed using the following variables: gender, age, height, BMI, civil status, education level, main caregiver, coffee consumption, alcohol use, and smoking status. It was found that age, BMI, and gender were significantly associated with the outcome (p-values from 0.04 to 0.01). Multivariable LRA confirmed age, BMI, and gender to be independently associated with low GHS (p-values from 0.04 to 0.004) and were all included in a final predictive model (R2 index 12%, C-statistics 67%; P = .001). The model was internally validated with 100 bootstrap resamples (corrected R2 10%). The three variables were used to build up the nomogram with the following scoring system: BMI ≤ 23 = 77 points, female = 72 points, age > 65 years = 100 points. A total score of 172 or more was associated with a ≥ 66% risk of having a low GHS. The 66% risk cut-off had the best discriminatory power according to a receiver operating characteristic (ROC) analysis (specificity 85%, sensitivity 60%). Decision curve analysis revealed that for a threshold of risk of 66% or higher, there was an added net benefit of ≥ 25% patients adequately identified as low GHS patients by using the nomogram as compared to a ‘survey-all’ policy. In our cohort, patients with a predicted risk of 66% or higher had a 73% prevalence of low GHS as compared with 23% of patients with a predicted risk ≤ 28% (Odds Ratio 8.92; P < .0001). Conclusion: Female patients over 65 years old and male patients over 65 with a BMI ≤ 23 had a ≥ 66% risk of reporting poor quality of life and need to be adequately assessed with complete HRQoL questionnaire administration.

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3–4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0–1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0–1, Odds Ratio 25.8, p 0.049. AJCC grade 0–1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Introduction: Baseline NLR has been found to have a significant prognostic value in metastatic pancreatic adenocarcinoma (mPA) patients. However, NLR assessment during the entire course of mPA disease has never been reported. Methods: We analyzed 1025 cell blood counts (CBCs) saved to PTV-BIO.CA.RE. (Biospecimen Cancer Repository) in 44 mPA patients (23.3 CBCs/patient) who had reached the overall survival endpoint (death ascertained) and NLR was calculated as per standard. Trend of NLR over the remaining weeks to death was analyzed, and where a clear correlation was observed a standard regression analysis was performed. Potential association between NLR trends and short survival was analyzed. Results: NLR values over the time had a clear biphasic trend, remaining roughly constant (median NLR 2.5, 95% CI 2.2-2.7) up to 24 weeks prior to death (correlation coefficient R 0.03, p 0.603) and then displaying a marked rectilinear increase from week -24 to death (time 0) (R 0.48, p < 0.001). The equation that expressed the rectilinear increase of NLR during the last 24 weeks of life was NLR=9.663 – 0.325* (weeks-to-death), indicating an increase of about +0.3 in NLR for every week passing from -24 to 0 (death). A NLR above 3.0 with a confirmed increase of > +0.3 points/week in two subsequent CBCs was able to predict an imminent death (within 24 weeks) in 97.8% of cases (Relative Risk as compared with NLR < 3 and/or increase rate < 0.3points/week: 2.75, p < 0.0001). Conclusion: Longitudinal assessment of NLR in mPA patients is able to predict with great precision death occurring within 24 weeks. Treatments able to lessen the unfavourable NLR increase rate of + 0.3 points/week are likely to change the natural history of this disease.

Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.

249 Background: Relationship between BMI and HR-QoL has been extensively studied in CRC survivors. Increasing BMI has been recently associated with improved survival in mCRC pts, however data on the relationship between BMI and common HR-QoL measures in mCRC are scarce Methods: The EORTC QLC C30 and the NCCN distress thermometer (DT) and problem list (PL) questionnaires were administered to consecutive mCRC pts candidate for firstline chemotherapy. The effect of BMI on HR-QoL were analyzed using the Kruskal-Wallis and Mann-Whitney tests. The interaction between BMI and other variables of interest (such as inflammatory indexes) for the effect on HR-QoL was also analysed using a logistic regression analysis Results: Of 135 screened pts, 119 completed the questionnaires. A direct association was observed between BMI and GH score, with the score gradually improving from BMI 14 to 21, then plateauing between 21 and 41. A significantly lower GH was observed for BMI < 21 vs > 21 (GH 50 vs 67, p 0.014). DT and BMI were not correlated. BMI was inversely associated with practical problems (mean number of reported problems 0.7 vs 0.4 for BMI < 24 vs > 24, p0.012). The other components inversely associated with BMI were appetite loss, pain and fatigue (which were higher for BMI < 21 , p values 0.033, 0.015 and 0.007, respectively). A direct association with BMI was also observed for social and physical functioning (p values 0.002 and 0.05, respectively). Median BMI in pts with GH score < 25 vs > 25 was 19 vs 25, p 0.05. Percentage of pts with very low BMI (BMI < 21) was 38% vs 2% for pts with GH < 25 vs > 25, respectively, Odds Ratio 32.4, p 0.0007. Among 15 common clinical and biochemical analysed variables, the inflammatory index neutrophil/lymphocyte ratio (NLR) demonstrated a significant interaction with BMI for the effect on GH, with the direct association between BMI and GH only retained in pts with low NLR and a deteriorated GH in pts with high NLR regardless of BMI, test for interaction p 0.013 Conclusions: Low BMI is associated with deteriorated HR-QoL in mCRC pts with low NLR approaching a first-line treatment. Adequate nutritional support and anti-inflammatory approaches would improve HR-QoL in these pts.

Background: The increased number of quality of life (QoL) studies in the oncology setting highlighted the negative effects of chemotherapy administration, including toxicity, on health-related (HR) QoL during or after treatment. However, the predictive value of pre-treatment HRQoL assessment on the subsequent occurrence of chemotherapy-related side effects, has never been tested. The present study aimed to investigate whether baseline patients' perception of well-being, as HRQoL index, could influence both subject perception of chemotherapy-induced side effects and objectively measured parameters of toxicity. Methods: A total of 110 cancer patients (41% male, mean age 62 ± 10.49 years) treated at the Medical Oncology Unit of the Tor Vergata Clinical Center, were enrolled. Primary tumors were gastrointestinal (53%), breast (32%), head/neck/lung (10%), uro-gynecological (5%). The following self-reported questionnaires were administered before chemotherapy start: 1) the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT) and 2) the EORTC QLQ-C30. Chemotherapy-related toxicity was recorded in medical records according to NCI-CTC v4.0 criteria. Data were analyzed using MedCalc statistical software. The predictors of side effects toxicity were assessed using logistic regression analysis. Primary endpoint was overall toxicity incidence grade 0-2 vs. grade 3-4. The following variables were analyzed: age, sex, primary tumors, Karnofsky Performance Status, Global Health Status (GHS) and Distress. The effect size of predictors was estimated using adjusted odds ratio (OR) with 95% CI. A p-value lower than 0.05 was considered as statistically significant for all tests. Results: GHS values were stratified in three categories, low (0-25), medium (26-49) and high (50-100) levels of QoL. Patient distribution according to GHS levels were 7.3% in the low, 13.6% in the medium and 79.1% in the high QoL category. In the whole population, age, sex and GHS were found significantly associated to chemotherapy-induced toxicity at the univariate analysis (p = 0.01, p = 0.02, p = 0.03, respectively). However, at multivariate analysis GHS was the only independentpredictor of the occurrence of chemotherapy-related side effects (AOR: 2.78, 95% CI: 1.01-7.62; p = 0.04), particularly of grade 3-4 toxicity. Conclusions: Pre-chemotherapy evaluation of health-related QoL parameters, might represent a useful tool to predict common chemotherapy-related side effects occurrence.

BACKGROUND: High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA). OBJECTIVE: In the present study, we aimed at investigating the prognostic value of NL R in two homogeneous groups of chemotherapy-naïve metastatic PDA patients. Patients were treated with either gemcitabine (GEM) or gemcitabine/oxaliplatin (GEMOXA). We also assessed whether NLR could identify patients benefiting from the use of oxaliplatin. METHODS: Consecutive PDA patients treated at the Medical Oncology Unit of Tor Vergata University Hospital of Rome with either GEM or GEMOXA were included (n= 103). NLR was assessed before and during chemotherapy and correlated with outcome together with common clinical and biochemical variables. RESULTS: Among 17 analyzed variables NLR, Karhofsky Perfomance Status (KPS), d-dimer and erythrocyte sedimentation rate were found to be significantly associated with median Overall Survival (mOS) at the univariate analysis. Only NLR and KPS were independent prognosticator at multivariate analysis, with NLR displaying the highest statistical significance. NLR was also predictive of oxaliplatin activity, as only patients with NLR > 2.5 (cutoff determined upon ROC analysis) derived benefit from GEMOXA over GEM. CONCLUSIONS: NLR is both an independent prognostic and predictive factor in metastatic PDA, since only patients with high NLR seem to benefit from the addition of oxaliplatin. NLR may help select patients for whom a particularly poor prognosis might justify more intensive, yet less tolerable, combination regimens.

Introduction: We previously reported results on 17 rectal cancer patients (pts) treated with neoadjuvant CisCape-RT (ESMO World GI 2011). We here present the final report of 52 patients treated with the CisCape-RT regimen. Methods: Fifty-two non-metastatic pts (male:female, 35:17 pts, median age 63 years, range 41-77), clinically staged with endoscopic ultrasound and chest/abdomen/pelvis CT scan as cT2cN1 (5 pts), cT3cN0 (18), cT3cN1 (21), cT3cN2 (4) or cT4cN1 (4), with histologically confirmed moderately (43 pts) or poorly (9) differentiated rectal adenocarcinoma (median distance from the anal verge 5 cm, range 2-13) were treated with standard pelvic radiotherapy (45 Gy/25 fractions) and concurrent capecitabine (825 mg/m2 twice daily days 1 through 14 and 22 through 35) plus cisplatin (40 mg/m2 once every three weeks). Results: radical surgery was performed in 92% of pts, median time elapsed from CRT commencement to surgery was 108 days (76-178), 3 pts underwent palliative surgery because of progression. Complete pathologic response (pCR) was documented in 9 pts (17%). Based on pre-treatment assessment, T and N down-staging were observed in 41% and 38% of pts, respectively. Primary tumour was down-sized in 14 pts (82%) with the median longest diameter reducing from 5.0 cm (range 1.6-16.0) before CRT to 2.0 cm (0-10.0) after CRT, two-tailed p = 0.001 (according to Wilcoxon test for paired samples). Grade 3-4 toxicities occurred in 35% of pts. Median progression-free and overall survival were not yet reached after a median follow-up of 30 months. Conclusion: Despite a good pCR rate, the high occurrence of grade 3-4 toxicities with CisCape-RT makes this regimen not suitable for larger phase III trials.

Among the possible genetic contributors to cancer-related venous thromboembolism (VTE), vascular endothelial growth factor (VEGFA) could play an important role, as an imbalance of the VEGFA system (either disease-related or drug-induced) may result in a disturbance of vascular homeostasis. Thus, this study was designed to investigate the predictive role of eight different VEGFA gene promoter single nucleotide polymorphisms (SNPs) for a first VTE episode in cancer out-patients undergoing chemotherapy. To this purpose, VEGFA gene promoter polymorphisms were analysed in 297 cancer patients using polymerase chain reaction amplification and direct DNA sequencing analysis. One hundred forty unrelated healthy subjects from the same geographical area were also analysed in order to evaluate and compare genotype/haplotype frequencies in our ethnicity. VTE occurred in 26 (9%) of cancer patients with a median time-to-event of 3.4 months. Association analyses showed that -1154G/A polymorphism was significantly associated with the risk of chemotherapy-triggered VTE, with the A allele exerting a protective role both in the overall population (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.07-0.58) or in bevacizumab-treated metastatic patients (HR: 0.09, 95%CI: 0.01-0.86) in whom VEGFA -1154AA genotype also conferred a reduced risk of early progression (HR: 0.58, 95%CI: 0.34-0.98). These results suggest that VEGFA may represent a candidate gene contributing to VTE development in chemotherapy treated cancer patients and that -1154G/A SNP might provide useful clinical information on the efficacy and toxicity of bevacizumab in metastatic patients. Validation studies are needed for translation into clinical practice.