Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase Ⅱ study

AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy(HART)and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil(325 mg/m^2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade Ⅲ-Ⅳ gastrointestinal toxicity, 2 patients had grade Ⅲ-Ⅳ hematologic toxicity, and 1 patient had grade Ⅴ toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade Ⅳ tenesmus. Complete pathological response was achieved in 6 patients(21%), while near-complete pathological response was obtained in 9(31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Evaluation of whole-course three-dimensional conformal radiotherapy combined with late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma patients

Objective： The aim of the study was to evaluate the therapeutic effect and safety of whole-course three-dimensional conformal radiotherapy （3DCRT） combined with late-course accelerated hyperfractionated radiotherapy （LCAFR） on patients with esophageal carcinoma. Methods： one hundred and one patients with esophageal carcinoma were divided into two groups. Observing group （49 cases） were treated by whole-course 3DCRT. Patients in control group （52 cases） were treated by conventional radiotherapy. Clinical efficiencies and radiation toxicities were compared between two groups. Results： The side effects including radiation esophagitis （63.2%） and tracheitis （49.0%） decreased in observing group, but there was no significant difference between two groups （69.2% and 55.7% in controls）. The 1-, 2-and 3-year tumor local control rates and overall survival rates in the observing group were significantly improved compared with the control group, being respectively 87.8%, 75.5%, 63.3% vs 71.2%, 55.8%, 42.3% and 85.7%, 71.4%, 46.7% vs 69.2%, 51.9%, 26.9% （all P 0.05）. Conclusion： The therapeutic effect of whole-course 3DCRT combined with LCAFR for esophageal carcinomas is superior to conventional radiotherapy.

Clinical role of ^(18)F-FDG PET/CT-based simultaneous modulated accelerated radiotherapy treatment planning for locally advanced nasopharyngeal carcinoma

Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography （PET/CT）-guided dose escalation radio- therapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally ad- vanced nasopharyngeal carcinoma （NPC）. Methods Atotal of 48 patients with stage IIl-IVa NPC were recruited and randomly administered PET/CT- guided dose escalation chemoradiotherapy （group A） or conventional chemoradiotherapy （group B）. The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray （Gy） in 32 fractions （f） to the gross target volume （GTV）： planning target volume （PTV） 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous （IV） on days 1-4] and docetaxel （75 mg/m2 IV on days 1 and 8） administered during treatment weeks 1 and 4. All patients received 2-4 cycles of adjuvant chemotherapy of the same dose and drug regimen. Results The use of fluorine-18-fluorodeoxyglucose （18F-FDG） PET/CT significantly reduced the treat- ment volume delineation of the GTV in 83.3% （20/24） of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively （P = 0.019）. The 5-year disease free survival （DFS） rates were 95.8% and 75.0%, respectively （P = 0.018）. The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival （OS） rates were 95.8% and 79.2%, re- spectively. Differences in OS improvement were insignificant （P = 0.079）. Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1-2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity. Conclusion The use of 18F-FDG PET/CT-guided dose escalation radiotherapy is well tolerated and can reduce local recurrence rates for patients with locally advanced NPC compared to conventional chemora- diotherapy.

Clinical Study on Simultaneous Modulated Accelerated Radiotherapy and Concurrent Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma

OBJECTIVE To evaluate the clinical efficacy and toxicities of simultaneous modulated accelerated radiotherapy （SMART） and concurrent chemotherapy for locally advanced nasopharyngeal carcinoma. METHODS Eightyseven patients with nasopharyngeal carcinoma received SMART from April 2002 to September 2006. According to the UICC staging system, 30 patients were diagnosed as stage IIb, 42 patients stage III, 13 patients stage IVa and 2 patients stage IVb. The intensitymodulated radiotherapy was delivered with the ＂step and shoot＂ SMART technique with the prescribed dose of 66-76 Gy （2.2-2.4 Gy/day） to the gross tumor volume （GTV） and positive neck lymph nodes （GTVLN）, with 60 Gy （2.0 Gy/day） to the highrisk clinical target volume （CTV1）, encompassing the area around the nasopharynx and the upper neck, and with 54 Gy （1.8 Gy/day） to the lowrisk clinical target volume （CTV2）, including the lower neck and supraclavicular area. Among all the patients, 31 received 2 cycles of SMART concurrently with 5 fluorouracil （5-Fu） and cisplatin （the FP group） and 56 received 2 cycles of concurrent cisplatin. All the patients received 3 to 4 cycles of adjuvant combination chemotherapy of cisplatin and 5fluorouracil starting from the 1st month after completion of SMART. RESULTS With a median follow up of 59 months （ranging from 19 to 85 months）, the 1, 2 and 3year overall survival rates were 100%, 94.6% and 91.3% respectively. Acute mucositis and pharyngitis were more frequently observed in the FP group than in the cisplatin group. CONCLUSION SMART technique provides an excellent opportunity to spare normal tissue and is probably more biologically effective. Combination of single cisplatin was more tolerable.