ORIGINAL RESEARCH ARTICLE
Journal of
Clinical Predictive Circulating Peptides in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy
Cellular Physiology
SARA CROTTI,1,2 MARIA VITTORIA ENZO,3 CHIARA BEDIN,2,3 SALVATORE PUCCIARELLI,3 ISACCO MARETTO,3 PAOLA DEL BIANCO,4 PIETRO TRALDI,5 ENNIO TASCIOTTI,6 MAURO FERRARI,6 FLAVIO RIZZOLIO,1 GIUSEPPE TOFFOLI,1 ANTONIO GIORDANO,7 DONATO NITTI,3 AND MARCO AGOSTINI2,3,6* 1
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano (PN), Italy
2
Istituto di Ricerca Pediatrica- Città della Speranza, Corso Stati Uniti 4, Padova, Italy
3
First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padova, Italy
4
Clinical Trials and Biostatistics Unit, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy
5
CNR-IENI, Corso Stati Uniti 4, Padova, Italy
6
Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas
7
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45–50.4 Gy in 25–28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight 6 MV) using a conventional fractionation (>50 Gy in 28 fractions, 1.8 Gy per day, 5 sessions per week) and 5-fluorouracil was administered as neoadjuvant chemotherapy drug by bolus or continuous venous infusion. A standard total mesorectal excision was performed after 7 weeks (median value) to completion of preoperative chemoradiotherapy (interquartile range 6–8 weeks). Patients’ response to pCRT has been evaluated after histological evaluation of surgical resection as the tumor regression grade (TRG) according to Mandard et al. (Mandard et al., 1994) by a pathologist. Briefly, the classification parameters were: TRG1, absence of viable cancer cells in the resected specimen; TRG2, presence of residual cancer cells; TRG3, fibrosis outgrowing residual cancer cells; TRG4, residual cancer cells outgrowing fibrosis; and TRG5, absence of response. Clinical characteristics and TRG classification of patients included in this study are reported in Table 1.
JOURNAL OF CELLULAR PHYSIOLOGY
TABLE 1. Patients’ and treatment characteristics. Tumour Regression Grade (TRG) is calculated according to Mandard et al., (13). Gy ¼ Gray; ypTNM ¼ pathologic classification performed after multimodality therapy (yp) based on the assessment of the primary tumor (T), regional lymph nodes (N) and distant metastasis (M) Characteristic Age Median (range yrs) Sex Male Female Tumor distance from anal verge 7 cm >7 cm Total radiotherapy dose delivered 50 Gy 2-fold between controls and cancer patients. Whiskers: 10–90 percentile, P-value from t-Student’ test: **P-value
Journal of
Clinical Predictive Circulating Peptides in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy
Cellular Physiology
SARA CROTTI,1,2 MARIA VITTORIA ENZO,3 CHIARA BEDIN,2,3 SALVATORE PUCCIARELLI,3 ISACCO MARETTO,3 PAOLA DEL BIANCO,4 PIETRO TRALDI,5 ENNIO TASCIOTTI,6 MAURO FERRARI,6 FLAVIO RIZZOLIO,1 GIUSEPPE TOFFOLI,1 ANTONIO GIORDANO,7 DONATO NITTI,3 AND MARCO AGOSTINI2,3,6* 1
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano (PN), Italy
2
Istituto di Ricerca Pediatrica- Città della Speranza, Corso Stati Uniti 4, Padova, Italy
3
First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padova, Italy
4
Clinical Trials and Biostatistics Unit, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy
5
CNR-IENI, Corso Stati Uniti 4, Padova, Italy
6
Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas
7
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45–50.4 Gy in 25–28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight 6 MV) using a conventional fractionation (>50 Gy in 28 fractions, 1.8 Gy per day, 5 sessions per week) and 5-fluorouracil was administered as neoadjuvant chemotherapy drug by bolus or continuous venous infusion. A standard total mesorectal excision was performed after 7 weeks (median value) to completion of preoperative chemoradiotherapy (interquartile range 6–8 weeks). Patients’ response to pCRT has been evaluated after histological evaluation of surgical resection as the tumor regression grade (TRG) according to Mandard et al. (Mandard et al., 1994) by a pathologist. Briefly, the classification parameters were: TRG1, absence of viable cancer cells in the resected specimen; TRG2, presence of residual cancer cells; TRG3, fibrosis outgrowing residual cancer cells; TRG4, residual cancer cells outgrowing fibrosis; and TRG5, absence of response. Clinical characteristics and TRG classification of patients included in this study are reported in Table 1.
JOURNAL OF CELLULAR PHYSIOLOGY
TABLE 1. Patients’ and treatment characteristics. Tumour Regression Grade (TRG) is calculated according to Mandard et al., (13). Gy ¼ Gray; ypTNM ¼ pathologic classification performed after multimodality therapy (yp) based on the assessment of the primary tumor (T), regional lymph nodes (N) and distant metastasis (M) Characteristic Age Median (range yrs) Sex Male Female Tumor distance from anal verge 7 cm >7 cm Total radiotherapy dose delivered 50 Gy 2-fold between controls and cancer patients. Whiskers: 10–90 percentile, P-value from t-Student’ test: **P-value
