Tumor Response Prediction In Locally Recurrent Or Advanced Rectal Cancer And Phase I Study

Partâ… Phase â…  clinical study of concurrent chemoradiation with hydroxycamptothecin for unresectable or locally relapsed rectal cancerPurpose:To determine the maximal tolerated dose and the dose-limiting toxicity of hydroxycamptothecin (HCPT) concurrently combined with three-dimensional conformal radiotherapy (3DCRT) for unresectable or locally relapsed rectal cancer.Methods:Twenty-two patients with rectal cancer were enrolled into phase I study on2004-2007years. HCPT was intravenously administered concurrently with3DCRT weekly or twice a week, dose given from6,8,10mg/m2and4,6,8,10mg/m2, respectively. Total radiation dose of DT50Gy was delivered to the whole pelvis in a fraction of2Gy per day for5weeks, with10-16Gy subsequent boost to tumor area. Dose-limiting toxicities (DLT) were defined as grade3or higher non-hematologic toxicity or grade4hematologic toxicity.Results:In the twice a week group, DLTs of grade3diarrhea were observed in2patient treated at dose of6mg/m2. In the weekly group, DLTs of grade3diarrhea and radiation-induced dermatitis were observed in1patient at dose of8mg/m2, and were not observed in the next3patients at the same dose level. However, at dose of10mg/m2,2patients had grade3diarrhea or nausea. The5-year overall survival was23%, with median survival time of18months.Conclusion:HCPT given concurrently with3DCRT is safe and tolerable for patients with unresectable or locally relapsed rectal cancer. Either8mg/m2weekly or4mg/m2twice a week can be recommended for further study. The dose-limiting toxicities are grade3diarrhea, nausea and radiation-induced dermatitis. Part IIRepeated Endorectal ultrasonographies predict the tumor response of preoperative chemo-radiotherapy in rectal cancerPurpose:To assess the value of repeated endorectal ultrasonographies (EUS) in predicting the efficacy of preoperative chemo-radiotherapy(CRT) for locally advanced rectal cancer.Methods:Patients with histopathologically proven, clinical stage â…¡/â…¢ rectal adenocarcinoma were enrolled prospectively. A dose of50Gy in25fractions for5weeks was delivered to the whole pelvic with concurrent chemotherapy of Capecitabine at dose of1650mg/m2/day and Oxaliplatin at dose of50mg/m2/week. Total Mesorectal Excision (TME) was performed6to8weeks after CRT. Endoscopic ultrasound measurements of primary tumor maximum diameter were performed before (EUS1), during (EUS2) and after (EUS3) CRT in all patients. The ratios for EUS2/EUS1and EUS3/EUS1were calculated and correlations between relative values in primary tumor maximum diameter, tumor regression grade, the T down-staging rate and the pathological complete response (pCR) rate were assessed.Results:Between October2010and October2012, EUS1, EUS2and EUS3measurements were completed in37patients with median age of54years old. There were20males and17females patients enrolled. pCR and T down-staging rate was21.6%and47.2%, respectively. The median primary tumor maximum thickness of EUS1, EUS2and EUS3were13.1mm (5.7-41.2mm),10.6mm (5.5-25.4mm) and8.8mm (4.3-12.6mm), respectively. There was no significant correlation between value of EUS2/EUS1and tumor regression grade (p=0.074). However, the value of EUS3/EUS1correlated with the pCR rate and tumor regression grade (p=0.021, p=0.046) but not with the T down-staging rate (p=0.353). In addition, the value of EUS3correlated with the pCR rate (p=0.010).Conclusion:Repeated endorectal ultrasonographies may predict therapeutic efficacy of preoperative chemo-radiotherapy for locally advanced rectal cancer.