| IntroductionPancreatic cancer is disgnosied at an advanced stage in most patients. There hasbeen a significant increasing trend in the incidence of pancreatic cancer in China.Besides surgical resection, modern medicine has provided barely any effective way oftreating the disease. Currently, three-dimensional conformal radiotherapy (3DCRT)has been accepted as the standard therapy for patients with advanced pancreaticcancer. Former researches indicated that traditional Chinese medicine (TCM) hadsome advantages in treating pancreatic cancer patients, especially those in advancedstages. However, most of those researches were small retrospective studies or casereports. Experimental researches on TCM for pancreatic cancer were even fewer. So itis urgent to carry out systemic and comprehensive clinical trails as well asexperimental researches to better expose the exact effects of TCM in multidisciplinarymanagement of pancreatic cancer.Objective:We aimed to understand the way, effects and mechanism of Qiyihuaji herbalDecoction and 3DCRT in treating advanced pancreatic cancer through retrospectiveclinical researches and experimental studies, which may help to define the value ofthe integrative modality for the management of advanced pancreatic cancer.Material and methods:1．A clinical Research on Qiyihuaji herbal Decoction and Three-dimensionalconformal radiotherapy for the Treatment of Advanced Pancreatic Cancer:From May 2002 to October 2006, seventy-nine advanced pancreatic cancerpatients confirmed by cytology or histology were selected from patient database.Pancreatic cancer patients were treated by chemoradiotherapy and traditional Chinese medicine. A median of 2-course transcatheter arterial chemoembolization (TACE) wasgiven. Three-dimensional conformal radiotherapy (3DCRT) was delivered by 3-4coplanar or non-coplanar fields. The mean tumor dose was 38．96Gy±40Gy byconventional fractionation (1．8-2Gy/fraction, 5 fractions a week), Acutegastrointestinal complication was graded according to common toxicity criteria (CTC),National Cancer Institute. Patients were assessed CT scan performed approximately 1month after completion of therapy. Responses were categorized by WHO criteria.Survival was estimated from the date of initiation of treatment by Kaplan-Meiermethod.2 Effect of traditional Chinese medicine in intestine with radiation induced damage inmiceICR mice were used for jejunal crypt survival assay. The animals were irradiatedwith 8 and 12 Gy for jejunal crypt survival assay. The groups of QYXJ herbs at a doseof 50g/kg weight, 25g/kg weight and 50g/kg weight were given orally 3 days beforeirradiation. ZYSGT were given orally 3 days before irradiation. The mice of controlgroups were given the same volume of saline The group of Gemcitabine at a dose of120mg/kg weight was given i.p. 6 hours before irradiation. For the determination ofjejunal crypt stem cell survival, the microcolony technique described by Withers wasused. At 3．5 days after irradiation, the animals were killed. Sections of the jejunumwere prepared for histological examination in each animal and 4 mm sections werecut,and stained with hematoxylin-eosin. The regenerating crypts in the jejunalcross-section were counted. Only crypts with ten or more cells were counted.3 Radiosensitization research of Qiyihuaji herbal Decoction in BALB/C naked miceimplanted with SW1990BALB/C naked mice with SW1990 in the back legs were irradiated underair-breathing conditions. Unanestherized mice were immobilized in a special designedjig. When the transplanted tumor diameter reached 0．8 to 1 cm, the mice randomizedinto two groups: the control group (i.e. radiation alone at different single dose) and theQiyihuaji herbal Decoction group (i.e. radiation with prior given QYXJ herbs). Every8 mice in each group were irradiated by different single dose, 0Gy, 6Gy, 9Gy, 12Gy,15Gy and 18Gy respectively. The groups of QYXJ herbs at a dose of 25g/kg weightwere given orally 3 days before irradiation. The mice of control groups were given the same volume of saline. The maximal and minimal diameters of the tumor wererecorded with vernier caliper and measured at 2-3 days intervals untile the tumorsgrew to at least 15mm in diameter. The volume of tumors was calculated by theSteel's formula. The tumor growth tendency and the tumor growth delay wereobserved. The dose-response curves were made using the tumor growth delayprogram and sensitization enhancement ratio (SER) was calculated.Results:1．A clinical Research on Qiyihuaji herbal Decoction and Three-dimensionalconformal radiotherapy for the Treatment of Advanced Pancreatic Cancer:Treatment-related gastrointestinal complication was assessable in all 79 patients.Eighteen patients had acute gastrointestinal bleeding with CTC Grade 1 and2 in 15cases and Grade 3 and 4 in 3 patients. Immediate tumor response was evaluated 1month after 3DCRT for all patients. One patient was complete response, five patientsachieved partial response and fifth-four patients were in stable disease. Seventypatients were observed progressive disease. The overall survival rates at half, 1-and2-years were 47．4%, 23．8% and 12．5%, respectively, with a median survival period of6 months. The half, 1-and 2-years progression-free rates were 37．2%, 19．4% and11．1%, respectively, with a median time to progress of 4 months. Karnofskyperformance scale (KPS), distant metastasis and serum CA19-9 were identified asindependent predictors for overall survival by Cox proportional regression analysis.2 Effect of traditional Chinese medicine in intestine with radiation induced damage inmiceUnirradiated controls show the density of crypts at the bases of the villi. There isan average of about 136．7 crypts per complete circumference. Qiyihuaji herbalDecoction and ZYSGT, when given alone without iradiation, produced little apparentcrypt change. Pre-treatment with Qiyihuaji herbal Decoction with radiation did notresulted in a significant increase or decrease in the number of surviving cryptscompared with those in the irradiation control irradiated by 8Gy and 12Gyγ-rays.Irradiated with 8 Gy, pre-treatment with ZYSGT did not change the number ofsurviving crypts compared with those in the irradiation control. Irradiated with 12 Gy,pre-treatment with ZYSGT resulted in a significant increase in the number ofsurviving crypts. Pre-treatment with Gemcitabine resulted in a significant decreased in the number of surviving crypts compared with those in the irradiation control.3 Radiosensitization research of Qiyihuaji herbal Decoction in BALB/C naked miceimplanted with SW1990Without radiation, growth delay time of the saline group and the Qiyihuajiherbal Decoction group were 8．55±1．37 days and 9．29±2．09days, resperctively. Asingle radiation dose of 6Gy, 9Gy, 12Gy, 15Gy and 18Gy induced a significantregrowth delay in all tumors. After combined the Qiyihuaji herbal Decoction withradiation treatment, the tumor growth delay was prolonged compared to the controlgroup. The curve of the Qiyihuaji herbal Decoction combined with radiation groupcompared with that of the radiation group, obviously shifted to the left, the averagesensitization enhancement ratio (SER) was 1．37．The synergistic interactionbetwween Qiyihuaji herbal Decoction and radiation was enhanced after single doseirradiation.Conclusion:1．The combined modality of 3DCRT and Qiyihuaji herbal Decoction was benefit toadvanced pancreatic cancer, and warrant for further prospective trial.2．KPS, distant metastasis and serum CA19-9 were identified as independentpredictors for overall survival.3．The results of this study suggest that Qiyihuaji herbal Decoction is not aradioprotective agent. Our results indicated that ZYSGT might be a usefulradioprotector. Further studies are needed to better characterize the protectivenature of ZYSGT. Gemcitabine enhanced radiation response on normal tissue.4．Qiyihuaji herbal Decoction combined with radiation have the radiosensitizingeffect in mice with SW1990．The Qiyihuaji herbal Decoction shows greatpotential as a new type of radiosensitizer and worthy for further studies.
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