Dosimetric comparison of doses to organs at risk using 3-D conformal radiotherapy versus intensity modulated radiotherapy in postoperative radiotherapy of periampullary cancers: implications for radiation dose escalation.

CONTEXT: Postoperative periampullary cancers with high risk features are managed with adjuvant chemo radiotherapy. Doses of 40-50 Gy have generally been used in conventional radiotherapy. Dose escalation with conventional radiotherapy has been restricted due to surrounding critical organs. OBJECTIVE: The objective of this dosimetric analysis was to evaluate the dose of radiation received by organs at risk using 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT). METHODS: Ten postoperative patients of periampullary cancers were selected for this dosimetric analysis. Planning CT scans films were taken with slice thickness of 2.5 mm and transferred to Eclipse treatment planning system. The clinical target volume (CTV) included the postoperative tumor bed and draining lymph nodal areas. A 1 cm margin was taken around the CTV to generate the planning target volume (PTV). Critical structures contoured for evaluation included bowel bag, bilateral kidneys, liver, stomach and spinal cord. IMRT plans were generated using seven field coplanar beams and 3DCRT planning was done using one anterior and two lateral fields. A dose of 45 Gy in 25 fractions was prescribed to the PTV. RESULTS: V45 for bowel bag was 212.3 ± 159.0 cc (mean volume ± standard deviation) versus 80.9 ± 57.4 cc in 3DCRT versus IMRT (P=0.033). The V28 dose analysis for bilateral kidneys showed a value of 32.7±23.5 cc (mean volume ± standard deviation) versus 7.9 ± 7.4 cc for 3DCRT versus IMRT, respectively (P=0.013). The D60 for liver using 3DCRT and IMRT was 28.4 ± 8.6 Gy (mean dose ± standard deviation) and 19.9 ± 3.2 Gy, respectively (P=0.020). CONCLUSIONS: Doses to bowel bag, liver and kidneys was significantly reduced using IMRT leaving ample scope for dose escalation.

Intraluminal implantation of radioactive stents for treatment of primary carcinomas of the peripancreatic-head region: a pilot study.

BACKGROUND: Patients diagnosed with bile-duct, pancreatic-head, and ampullary carcinomas have a poor prognosis. OBJECTIVE: This study evaluated the potential curative efficacy and safety of intraluminal brachytherapy by using radioactive stents for palliative treatment of these patients. DESIGN AND SETTING: Patients with inoperable extrahepatic bile-duct (n = 2), pancreatic-head (n = 6), or ampullary (n = 3) carcinomas were treated by intraluminal implantation of radioactive stents designed according to a computerized treatment-planning system. INTERVENTIONS: Both radioactive stents and commonly used self-expanding metallic or plastic stents were placed in the common bile duct (CBD) of the patients. For pancreatic carcinoma, the combination of radioactive CBD and pancreatic duct (PD) stents or only a radioactive PD stent was chosen according to the tumor position. MAIN OUTCOME MEASUREMENTS: Survival, tumor status, and complications were assessed during the follow-up period. RESULTS: A total of 16 radioactive stents were successively placed in all 11 patients. There were no life-threatening complications. The median survival was 150 days. After 2 months of the placement of radioactive stents, 8 patients (72.7%) had stable disease, whereas 3 patients (27.3%) showed progressive disease. CONCLUSIONS: The combination of radioactive stents and metallic and/or plastic stents was technically feasible and tolerable in patients with advanced tumors around the pancreatic-head area.

Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.

BACKGROUND: Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases. OBJECTIVE: The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated. METHODS: In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors). RESULTS: After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P = 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P = 0.12) neither on the development of liver metastases (log-rank P = 0.76) and consequently, no effect on overall survival. CONCLUSION: This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted.

Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

Pancreaticoduodenectomy for periampullary tumours: a review article based on Surveillance, End Results and Epidemiology (SEER) database.

INTRODUCTION: This study set to examine relative survival of patients with periampullary cancers undergoing pancreaticoduodenectomy (PD). METHODS: Using the Surveillance, End Results and Epidemiology (SEER) database, this study identified 9877 patients with non-metastatic pancreatic adenocarcinoma who underwent PD between 2004 and 2013. RESULTS: Ampullary carcinomas have the best survival among periampullary malignancies. Lymph node ratio is a significant prognostic factor, even when stratified by tumour types. Patients receiving adjuvant radiotherapy following PD have superior survival than patients without radiotherapy (median 25 vs 20 months, p < 0.001), particularly ductal adenocarcinoma (HR: 0.74, CI95% 0.69-0.78; p < 0.001), cholangiocarcinoma (HR: 0.75, CI95% 0.59-0.97; p = 0.027), and ampullary carcinoma (HR: 0.79, CI95% 0.64-0.98; p = 0.029) with greatest survival benefit at 1-year postresection. CONCLUSION: Future studies aiming to further define genetic signatures of individual periampullary cancers would allow a personalised therapeutic approach in improving survival.

Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct.

PURPOSE: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. METHODS AND MATERIALS: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. RESULTS: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5-year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). CONCLUSIONS: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy.

Extrahepatic portal vein occlusion without recurrence after pancreaticoduodenectomy and intraoperative radiation therapy.

PURPOSE: Although there are no definitive studies that characterize the survival benefit of intraoperative radiation therapy (IORT), the therapy does not seem to produce significant complication. In our institution, pancreaticoduodenectomy (PD) and IORT are often complicated by the development of extrahepatic portal vein occlusion (EHPO). The aim of this study was to characterize the phenomenon of EHPO after PD and IORT. METHODS AND MATERIALS: Between September 1992 and December 2001, 107 patients received macroscopic curative PD for periampullary disease in our institution. IORT (radiation dose: 20 Gy) was performed in 53 of these patients. Criteria for diagnosis of EHPO were as follows: (1) computerized tomography findings of occlusive extrahepatic portal vein, (2) symptoms of portal hypertension, and (3) confirmation to exclude tumor recurrence from origin of EHPO, because this study examined whether EHPO was a complication of PD and IORT. RESULTS: EHPO was diagnosed in 12 patients. Among patient and operative variables, IORT was the only statistically significant factor associated with a diagnosis of EHPO (p = 0.0052). The median developed time to EHPO and overall survival after surgery in EHPO patients were 358 days and 2,562 days, respectively. Eight patients (67%) with EHPO died during the follow-up period. At 5 years after therapy, EHPO was diagnosed in 67% of survivors who had received IORT. CONCLUSIONS: Patients undergoing IORT and PD have a relatively high incidence of EHPO, and patients who develop postoperative EHPO have poor prognoses.

Adjuvant therapy for ampullary carcinomas: the Mayo Clinic experience.

PURPOSE: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. METHODS AND MATERIALS: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. RESULTS: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p=0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p=0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. CONCLUSIONS: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

Geometric shifting of the porta hepatis during posthepatectomy radiotherapy for biliary tract cancer.

PURPOSE: To evaluate geometric shifting of the porta hepatis induced by liver regeneration during radiotherapy (RT) after partial hepatectomy for biliary tract cancer. METHODS AND MATERIALS: Between August 2004 and August 2005, the study enrolled 10 biliary tract cancer patients who underwent hemihepatectomy or more extensive surgery and were scheduled to receive postoperative RT. All patients received 4500 cGy RT in 25 fractions with concurrent 5-fluorouracil. Before RT and in the third and fifth weeks during RT, the liver volume was determined using CT, and geometric location of the porta hepatis was determined using a conventional simulator. RESULTS: The liver volume increase during RT was 246.6 +/- 118.2 cm(3). The overall actual shifting length of the porta hepatis was 9.8 +/- 2.5 mm, with right and left hepatectomy causing a 10.1 +/- 1.7 mm shift to the right or 9.2 +/- 4.3 mm shift to the left, respectively. The actual shifting length of the porta hepatis was proportional to the increase in liver volume during RT (r = 0.742, p = 0.014). CONCLUSION: The results of this study have demonstrated that the porta hepatis can be shifted by liver regeneration after partial hepatectomy. We recommend an additional RT margin or adaptive RT (repeat planning at several intervals during the treatment course) to avoid exclusion of the porta hepatis from the RT target volume after partial hepatectomy for biliary tract cancer.

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer.

PURPOSE: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer. METHODS: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography. RESULTS: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively. CONCLUSIONS: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

Preoperative chemoradiation for patients with pancreatic cancer: toxicity of endobiliary stents.

PURPOSE: A recent multicenter study of preoperative chemoradiation and pancreaticoduodenectomy for localized pancreatic adenocarcinoma suggested that biliary stent-related complications are frequent and severe and may prevent the delivery of all components of multimodality therapy in many patients. The present study was designed to evaluate the rates of hepatic toxicity and biliary stent-related complications and to evaluate the impact of this morbidity on the delivery of preoperative chemoradiation for pancreatic cancer at a tertiary care cancer center. PATIENTS AND METHODS: Preoperative chemoradiation was used in 154 patients with resectable pancreatic adenocarcinoma (142 patients, 92%) or other periampullary tumors (12 patients, 8%). Patients were treated with preoperative fluorouracil (115 patients), paclitaxel (37 patients), or gemcitabine (two patients) plus concurrent rapid-fractionation (30 Gy; 123 patients) or standard-fractionation (50.4 Gy; 31 patients) radiation therapy. The incidences of hepatic toxicity and biliary stent-related complications were evaluated during chemoradiation and the immediate 3- to 4-week postchemoradiation preoperative period. RESULTS: Nonoperative biliary decompression was performed in 101 (66%) of 154 patients (endobiliary stent placement in 77 patients and percutaneous transhepatic catheter placement in 24 patients). Stent-related complications (occlusion or migration) occurred in 15 patients. Inpatient hospitalization for antibiotics and stent exchange was necessary in seven of 15 patients (median hospital stay, 3 days). No patient experienced uncontrolled biliary sepsis, hepatic abscess, or stent-related death. CONCLUSION: Preoperative chemoradiation for pancreatic cancer is associated with low rates of hepatic toxicity and biliary stent-related complications. The need for biliary decompression is not a clinically significant concern in the delivery of preoperative therapy to patients with localized pancreatic cancer.

Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma.

PURPOSE: To evaluate a single institution's experience with intraoperative radiation therapy (IORT) in combination with attempted surgical resection for pancreatic and periampullary adenocarcinoma. METHODS AND MATERIALS: From May 1986 until June 2001, 77 patients at LDS Hospital underwent attempted surgical resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially curative resection was defined as surgery with negative or microscopic positive margins. No patients had metastatic disease at the time of surgery and IORT. Forty-four patients with tumors located in the pancreas and 9 patients with periampullary tumors underwent potentially curative surgical resection and IORT. Twenty-four patients had pancreatic tumors deemed unresectable and underwent surgical bypass and IORT. Actuarial survival was calculated from the date of IORT until last follow-up or death by use of the Kaplan-Meier method. RESULTS: Patients undergoing a potentially curative resection and IORT for periampullary adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial survival, compared with a median survival of 16 months and a 19% 5-year actuarial survival for patients undergoing the same treatment for pancreatic adenocarcinoma (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had a median survival of 11 months and a 0% 3-year survival, significantly worse than patients able to undergo surgical resection and IORT (p = 0.0002). The operative mortality for all patients undergoing potentially curative resection and IORT was 3.7%. CONCLUSIONS: Intraoperative radiation therapy is well tolerated and does not increase the morbidity or mortality of potentially curative surgical resection for pancreatic or periampullary adenocarcinoma. Patients with periampullary adenocarcinoma have a better prognosis than those with pancreatic adenocarcinoma, and patients with unresectable pancreatic disease fared worse.

Adjuvant chemoradiotherapy in periampullary cancers--Where does it stand with conformal radiotherapy: A single institution experience.

BACKGROUND: Treatment of periampullary cancer involves Whipple surgery, followed by adjuvant radiotherapy and chemotherapy. Postoperative radiotherapy is particularly useful in managing high-risk patients (tumors involving the pancreas, poorly differentiated histology, involved lymph nodes and positive margins). Here, we review our results of treatment of 84 patients treated by surgery and adjuvant radiotherapy and chemotherapy. MATERIAL AND METHODS: A retrospective analysis of 84 patients of periampullary cancers treated in our department between January 2007 and December 2012 was carried out. All patients underwent Whipples surgery followed by postoperative radiotherapy 45-50 Gy/25-28 number in those presenting with high-risk features. Radiotherapy was delivered using three-dimensional conformal technique with 6 MV photons using three field treatment plans. Chemotherapy was given for 6 cycles using gemcitabine and oxaliplatin regimen repeated 2 weekly. RESULTS: Eighty four postoperative patients with high-risk features were available for the final analysis. There were 69 males and 15 female patients. There were 34.5% stage I, 57.1% stage II and 8.3% stage III patients. At end of adjuvant treatment with radiotherapy and chemotherapy 70% patients had a complete response, 7.5% had residual disease, 15% showed progressive disease, 5% were dead and 2.5% defaulted the treatment. The mean number of chemotherapy cycles received was 2.6. At 1 year follow-up the probability of disease free survival was 80% for node-negative patients versus 73% for node-positive disease (P = 0.27). Patients with stage up to IIA had a 1 year disease free survival of 83% versus 40% for patients with stage beyond IIA (P = 0.024). CONCLUSIONS: Our results showed a trend favoring lymph node negative status with disease free survival. With computed tomography based planning, adequate delineation of draining nodes is possible, and radiation toxicity has significantly decreased. Adequate coverage of nodal basins during radiotherapy planning is important, and stage of the disease seems to be an important prognostic factor.

Curative surgery for adenocarcinoma of the pancreas/ampulla of Vater: the role of adjuvant pre or postoperative radiation therapy.

From 1972 to 1981, 7 patients received adjuvant external beam radiation therapy before (5 patients) or after (2 patients) a curative Whipple operation for adenocarcinoma of the pancreas (5 patients) or ampulla of Vater (2 patients). Via supervoltage, 4000-4520 rad/20-25 fractions/4-5 1/2 weeks were delivered to the tumor bed and draining lymphatics. Two patients (of 4 at risk) are 5-year survivors; 3 are alive-without-disease at 1-2 years follow-up. Distant metastases have developed to date in 3 patients. A marginal miss occurred at the edge of radiation portal in 1 patient, and no true in-field failures have occurred. Complications occurred in 2 patients. Because of the high incidence of local-regional failures after curative surgery alone for adenocarcinoma of the pancreas or ampulla of Vater, the above results suggest that adjuvant radiation therapy should be considered as a modality to potentially improve treatment results.

Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy.

Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium192 (Ir192). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 "equivalent" cGy to his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir192 wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died--5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Mean survival time from initial laparotomy and bypass was 16.1 months, and from radiotherapy completion was 8.3 months. Evolution of radiation treatment techniques for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir192 intracavitary boost is well tolerated and provides significant palliation. Survival of these aggressively managed patients approaches that of patients with primarily resectable tumors.

Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels.

PURPOSE: Primary endpoints were 1. To determine if, in the context of postoperative adjuvant therapy of pancreatic and nonpancreatic periampullary adenocarcinoma, continuous infusion (C.I.) 5-fluorouracil (5-FU) and leucovorin (Lv), combined with continuous-course external-beam radiotherapy (EBRT) to liver (23.4-27.0 Gy), regional lymph nodes (50.4-54.0 Gy) and tumor bed (50.4-57.6 Gy), followed by 4 months of C.I. 5-FU/Lv without EBRT could be given with acceptable toxicity. 2. To determine an estimate of disease-free and overall survival (DFS, OS) with this treatment in this context. Secondary endpoints were 1. To observe the effects of therapy at two different dose levels of irradiation, and 2. To observe for correlations among DFS, OS and CA 19-9 levels during therapy. METHODS: Patients received C.I. 5-FU 200 mg/m2 and Lv 5 mg/m2 Monday through Friday during EBRT, and 4 cycles of the same chemotherapy without EBRT were planned for each 2 weeks of 4, beginning 1 month following the completion of EBRT. Therapy was to begin within 10 weeks of surgery and patients were monitored for disease recurrence, toxicity, and CA 19-9 levels before the start of EBRT/5-FU/Lv, before each cycle of C.I. 5-FU/Lv, and periodically after the completion of therapy. There were two EBRT dosage groups: Low EBRT, 23.4 Gy to the whole liver, 50.4 Gy to regional nodes and 50.4 Gy to the tumor bed; High EBRT, 27.0 Gy to the whole liver, 54.0 Gy to regional nodes, and 57.6 Gy to the tumor bed. RESULTS: 29 patients were enrolled and treated (23 with pancreatic cancer, and 6 with nonpancreatic periampullary cancer). Of these, 18 had tumor sizes > or = 3 cm and 23 had at least one histologically involved lymph node; 6 had histologically positive resection margins. Mean time to start of EBRT/5-FU/Lv was 53 +/- 2 days following surgery. The first 18 patients were in the Low EBRT Group and the last 11 in the High EBRT Group. Toxicity was moderate and manageable, including a possible case of late radiation hepatitis. Median DFS was 8.3 months (pancreatic cancer patients 8.5 months) and OS was 14.1 months (pancreatic cancer patients 15.9 months). Among patients with pancreatic cancer, results were similar for the Low and High EBRT Groups (DFS: 8.3 vs. 8.6 months; OS: 14.4 vs. 16.9 months, respectively). With a mean follow up of 2.6 +/- 0.3 years for the surviving patients and a minimal follow-up of 2.5 years, 27 of 29 pts have relapsed and 25 pts have died. A rise in CA 19-9 levels preceded clinical relapse by 9.1 +/- 1.5 months. Time to first relapse by site showed inverse correlation with dose of radiotherapy to that site: peritoneal (5 +/- 1 month), hepatic (7 +/- 0.9 months), regional nodes/tumor bed (9.6 +/- 1.8 months). Mean postresection CA 19-9 level was 63.3 +/- 16.2 U/ml. Postresection CA 19-9 values did not correlate with survival, margin status, or with the identification of metastatic carcinoma in resected lymph nodes. However, among patients with histologically involved nodes in the resected specimen, postresection CA 19-9 values did correlate with the number of positive nodes identified (p = 0.05). CONCLUSIONS: Although toxicity was acceptable, survival results were not improved over those seen with standard adjuvant treatment. Most patients relapsed before the planned chemotherapy cycles were completed, or within 100 days thereof, suggesting disease resistance to C.I. 5-FU/Lv as used in this study. Although this regimen is not recommended for further study, the doses of EBRT utilized may be suitable for evaluation with other chemotherapy combinations. Postoperative CA 19-9 levels did not correlate with survival, but did correlate with the number of histologically involved lymph nodes found in the resected specimen among node-positive patients. Moreover, rising CA 19-9 levels anticipated ultimate clinical failure by 9 months.

Adjuvant chemoradiotherapy for "unfavorable" carcinoma of the ampulla of Vater: preliminary report.

HYPOTHESES: Adjuvant chemoradiotherapy decreases the risk of local recurrence in patients with adenocarcinoma of the ampulla of Vater and high-risk features. Adjuvant chemoradiotherapy for this population can be administered safely and without much morbidity. DESIGN: Controlled, prospective, single-arm study. SETTING: Tertiary care referral hospital. PATIENTS: From June 1995 to March 1999, 12 patients (7 men and 5 women; median age, 66 years; age range, 38-78 years) with "unfavorable" ampullary carcinoma were treated with adjuvant chemoradiotherapy. All patients underwent pancreaticoduodenectomy, and all pathologic findings were confirmed at Stanford University Medical Center, Stanford, Calif. Unfavorable features were defined as involved lymph nodes (n = 10), involved surgical margins (n = 1), poorly differentiated histological features (n = 3), tumor size greater than 2 cm (n = 6), or the presence of neurovascular invasion (n = 4). INTERVENTIONS: Four to 6 weeks after undergoing pylorus-preserving pancreaticoduodenectomy with regional lymphadenectomy, patients began adjuvant chemoradiotherapy consisting of concurrent radiotherapy (45 Gy) and fluorouracil by protracted venous infusion (225-250 mg/m(2) per day, 7 days per week) for 5 weeks. MAIN OUTCOME MEASURES: Local recurrence, distant recurrence, overall survival rate, and treatment-related toxic effects. RESULTS: All patients completed the prescribed treatment course. Toxic effects were assessed twice a week during treatment and graded according to the National Cancer Institute Common Toxicity Criteria Scale. One patient required a treatment interruption of 1 week for grade III nausea/vomiting. No grade IV or V toxic effects were observed. At median follow-up of 24 months (range, 13-50 months), 8 of 12 patients were alive and disease free. One patient was alive but had disease recurrence. Three patients died of this disease (liver metastases). Actuarial overall survival at 2 years was 89%, and median survival was 34 months. One surviving patient developed a local recurrence and a lung lesion. Actuarial overall survival and median survival were better than in a parallel cohort with resected high-risk pancreatic cancer (n = 26) treated with the same adjuvant chemoradiotherapy regimen (median survival, 34 vs 14 months; P<.004). CONCLUSIONS: Adjuvant chemoradiotherapy for carcinoma of the ampulla of Vater is well tolerated and might improve control of this disease in patients with unfavorable features.

A case of mucosa-associated lymphoid tissue lymphoma of the ampulla of Vater: successful treatment with radiation therapy.

Mucosa-associated lymphoid tissue (MALT) lymphoma of the papilla of Vater is rare, and little is known of either its association with Helicobacter pylori infection or the optimal treatment modalities. We describe the first case of MALT lymphoma involving the major papilla that remained unchanged despite eradication of H. pylori, but which regressed following radiotherapy. A 46-year-old asymptomatic man was admitted to hospital for treatment of MALT lymphoma involving the papilla of Vater. Duodenal endoscopy showed multiple granules around the major ampulla, and biopsies revealed mucosal proliferation of centrocyte-like cells, lymphoepithelial lesions, hyperplastic lymphoid follicles and plasmacytic differentiation. The lymphoma cells were positive for B-cell but negative for T-cell markers, and expressed Bcl-2 but showed no immunoreactivity for CD5, CD10 and cyclin D, consistent with MALT lymphoma. The patient was successfully treated with triple therapy of lansoprazole, amoxicillin and clarithromycin for 1 week for coexisting H. pylori infection in the stomach, but the lymphoma lesions remained unchanged. Then, involved-field irradiation was applied at a total dose of 30 Gy delivered in 1.5 Gy fractions without any adverse events. Six months later, repeat endoscopy revealed disappearance of the granular lesions and lack of lymphoma cells in biopsy specimens. Four years after the commencement of radiotherapy, the patient is still in complete remission. Radiotherapy seems a safe and effective treatment modality for low-grade MALT lymphoma of the ampulla of Vater.

Imaging positron emitting radionuclides generated during radiation therapy.

In vivo generated positron emitting radioisotopes, primarily C-11 and N-13, have been documented following therapy with accelerators larger than 10 MeV. Six patients had positron emission tomography 15 to 25 minutes after radiation therapy with a 42 MeV accelerator. Five patients had recurrent colorectal malignancy, and one required therapy for a carcinoma of the common bile duct. We sought to determine whether state-of-the-art PET technology could be used to monitor the three-dimensional activity distribution of radiation-induced radioactivity. At the time of the examination all six patients had sufficient concentrations of C-11 and N-13 activity in the irradiated volume to permit the evaluation of the activity distribution. We found significant activity at the body surface, which permitted field delineation. We conclude that the in vivo generated radioactivity can be monitored with PET.

Intraductal hepatocellular carcinoma treated by intralumenal brachytherapy.

Hepatocellular carcinoma (HCC) rarely presents as biliary tract occlusion [1,2]. Intralumenal iridium-192 brachytherapy has been used to treat extrahepatic bile duct carcinoma and may be curative if the macroscopic tumour has been resected surgically [3]. We describe a rare event, a case of HCC presenting with biliary tract occlusion treated with intralumenal iridium-192 brachytherapy.