Locally Advanced Rectal Cancer Adjuvant Therapy Model To Optimize The Study

Partâ… :The dosimetric study of intensive modified radiation therapy in local advanced rectal cancer.Purpose:traditional pelvic irradiation caused a high dose and volume of small bowel and induced a high incidence of toxicity of small bowel,such as diarrhea,nausea and vomiting.IMRT technique could decrease the irradiation volume and dose of adjacent normal tissue.So,we designed this study to confirm the protection of small bowel by IMRT.Material and methods:Ten patients diagnosed with local advanced rectal cancer were chosen for this study.All patients were staged in T3-4 and/or N+ by pelvic MRI and ERUS.The targets,bowel,bladder and femur head were contoured.We used two kinds of irradiation techniques,3DCRT and 5-field IMRT,to design the treatment plan and compared the difference of dose distribution of targets and normal tissues in these two techniques.Results:The patients in this study included 5 T3 and 5 T4 patients.By comparing the dose distribution,the targets had the same dose distribution in two plans.However,IMRT had a significant advantage of protection of normal tissues.The volume of small bowel irradiated to 45Gy was 114.1+/-9.4cc and 48.7+/-17.5cc respectively in 3DCRT and IMRT.The same advantage was also shown in bladder and femur head.Conclusion:IMRT could significant decrease the normal tissues irradiated high dose volume to protect the normal tissue.In the further study,the advantage of IMRT could be confirmed in clinical patients. Partâ…¡:The clinical application and high risk factors analysis in neoadjuvant chemoradiation therapy in local advanced rectal cancer using intensive modified radiation therapyPurpose:currently,preoperative chemoradiotherapy had become the standard treatment of local advanced rectal cancer.However,about 20-30% patients were resistant to preoperative CRT.In this study,we enhanced the treatment dose dense,based on evidence,and explored potential predictive factors to make treatment strategy better.Material and methods:A total of 32 patients diagnosed with T3-4 and/or N+ by pelvic MRI and ERUS were accrued in this study.IMRT was used and total dose was set 44Gy/20Fx.Oxaliplatin of 50mg/m2 qw and Xeloda 625mg/m2 bid d1-5 qw were used concurrent with radiotherapy.Radical surgery was operated in the 6 weeks after CRT and a cycle of Xeloda, 1000mg/m2 bid d1-14,was used in the 3^rd week after CRT.Tumor response of preoperative CRT was evaluated by tumor regression grade(TRG) system and RECIST system respectively.Toxicity was evaluated by CTC 3.0 criteria.Results:Four out of 32 patients refused to receive a radical surgery because of a significant regression of primary tumor.In the 28 patients receiving radical surgery,pathological complete response(pCR) was found in five cases;three patients were evaluated with almost CR(only little tumor cells left).Lower rectal location,non-signet-ring cell carcinoma showed a higher incidence of pCR.Two kind of grading system,TRG and RECIST showed a difference in evaluating the tumor response.Grade 3/4 toxicity of hematologic,gastrointestinal and mucocutaneous was 3.1%, 12.5%and 28.1%respectively.Conclusion:With the use of IMRT technique,it provided more opportunity to increase the irradiation dose for more pCR rate.The distance from anal verge,as a potential predictive factor of preoperative CRT,needed a further study to confirm. Partâ…¢:Adjuvant therapy for T3NO rectal cancer in the TME era-how do we select high risk patients?Purpose:Adjuvant therapy for T3NO rectal cancer as the routinely necessary is controversial either in aspect of radiation or the use of intensity regimen of chemotherapy.The key point is to select the high risk population to avoid overtreatment.Some clinical characteristics were analyzed,such as vascular/lymphatic invasion,positive CRM, inadequate dissected lymph nodes,poor differentiation of tumor cell etc. However,there are no consistent high risk factors regarding to if we should give adjuvant therapy or not for patients of T3NO rectal cancer. In this retrospective study,we evaluated both clinical features and biomarkers and attempted to find risk factors for this group of patients.Material and methods:From January 2000 to December 2005,a total of 1300 patients of rectal adenocarcinoma were treated with TME in Cancer Hospital, Fudan University,Shanghai.Of them 131 patients with T3NO were analyzed in our study.The median follow-up interval was 45.4 months.A series of potential risk factors,including clinico-pathological features and biomarkers were used to predict local recurrence(LR),disease-free survival(DFS) and overall survival(OS) rate.About 85.5%patients received adjuvant chemotherapy and 6.9%patients were treated with postoperative radiotherapy.Results:The 5-year OS,DFS and LR for all T3NO patients were 88.9%,68.4% and 89.8%respectively.There are three factors,tumor location less than 5cm from anus verge,low P21 and high CD44v6 expression were showed significantly correlated to poor outcomes.Patients with two or more risk factors out of three had a high 5-year local recurrent rate of 19.3% compared with that of 6.8%in low risk patients.Low P21 and high CD44v6 expression also showed more correlation with poorer DFS.The 5-year DFS were decreased from 79.3%,65.9%to 16.9%in patients expression these two marks with none,either and both.Conclusion:Our study showed adjuvant radiation should be recommended for T3NO rectal patient with at least two out of three risk factors.Adjuvant chemotherapy was necessary for all T3NOMO patients and patients with CD44V6 and low P21 expression should be treated with more aggressive chemotherapy like locally advanced rectal cancer. Partâ…£:A two-phase clinical study of exploring the best radiotherapy time during the whole period of adjuvant therapy.Purpose:In the previous study completed in Korea,early radiotherapy concurrent with chemotherapy after radical surgery demonstrated a better prognosis compared with late radiotherapy.However,with the report of MOSAIC trial,the adjuvant chemotherapy regimen had transferred from 5-Fu alone to combined 5-Fu and Oxaliplatin.We need more evidence to clarify the best radiotherapy time during the whole period of adjuvant therapy.Material and methods:patients with lower anterior resection were accrued in this study,radiotherapy was carried in the fourth week after surgery. Oxaliplatin of 50mg/m2 qw and Xeloda 625mg/m2 bid d1-5 qw were used concurrent with radiotherapy.Toxicity was evaluated by CTC 3.0 criteria. The study was designed as Simon two-phase design,in the first phase,a total of 15 patients were accrued,and if more than or equal to 9 patients had grade 3 toxicity,we had 85%power to confirm the toxicity caused by early radiotherapy more than 50%.Otherwise,another 15 patients of the second phase were accrued,we would have 85%power to confirm the high toxicity of more than 50%if 18 out of 30 patients had grade 3 toxicity.Results:From 2008.7 to 2008.11,15 patients were treated with early radiotherapy concurrent with combined chemotherapy.Grade 3 gastrointestinal toxicity occurred in 12 patients and hematologic toxicity occurred in 2 patients.According to Simon design,we had 85% power to confirm the toxicity caused by early radiotherapy more than 50%.Conclusion:Currently,early radiotherapy would cause a high incidence of severe gastrointestinal toxicity while concurrent with combined chemotherapy.