Antonella Nardecchia

Immune reaction and colorectal cancer: friends or foes?

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

Neutrophil/lymphocyte ratio helps select metastatic pancreatic cancer patients benefitting from oxaliplatin

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 NLR 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.

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt

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.

BMI and health-related quality of life (HR-QoL) in patients with metastatic colorectal cancer (mCRC).

249Background: 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 (GH 50 vs 67, p 0.014). DT and BMI...