Radiation therapy of pancreatic cancer]

We have been using external beam radiotherapy (EBRT) and intraoperative radiotherapy (IORT) for both resectable and unresectable pancreatic cancer patients. EBRT (50-60 Gy) was combined with IORT (25-33 Gy) whenever possible, but otherwise EBRT or IORT was given alone. In patients with unresectable tumor but no distant metastasis, the median survival time (MST) was 7.5 months (M) for the EBRT group and 9 M for the EBRT+IORT group. These MST's were significantly longer than the MST of 3 M of patients who had been treated without radiation (historical control). In non-Stage IV patients undergoing non-curative resection, the MST was 12.5 M for the EBRT group, 15.5 M for the EBRT+IORT group, and 7 M for the historical control. In patients undergoing macroscopic curative resection, the MST was 14 M for the EBRT group, 10 M for the EBRT+IORT group, and 10.5 M for the historical control. In Stage IV patients (with distant metastasis), the MST was 4.5 M for the EBRT group, 4 M for the EBRT+IORT group, 2 M for the IORT group, and 2.5 M for the historical control. Thus, radiotherapy appeared useful especially in non-Stage IV patients undergoing non-curative or no resection. A decrease or relief of pain was obtained in 90% of patients with unresectable lesions. Radiotherapy seems to play an important role in the treatment of pancreatic cancer but more aggressive combined treatment seems to be necessary to further improve the dismal prognosis of pancreatic cancer patients.     

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.     

术中和体外照射治疗晚期胰腺癌

目的 :分析不能手术切除的晚期胰腺癌术中放射 (IORT)和体外放射 (EBRT)治疗的疗效。方法 :回顾我院 1987- 1999年 75例不能手术切除的晚期胰腺癌患者进行单纯IORT、单纯EBRT和IORT加EBRT治疗的临床资料。结果 :单纯IORT、单纯EBRT和IORT加EBRT治疗的 1年生存率分别为15 2 %、14 3%和 31 8% ,IORT加EBRT治疗的结果优于前两者 ,P <0 0 5。结论 :IORT加EBRT治疗可以延长晚期胰腺癌患者的生存期     

胰腺癌术中放射治疗的价值

目的：回顾总结诸多放射治疗方式对胰腺癌治疗的价值。方法：1986－1999年间收治的无法手术切除的晚期胰腺癌患者68例，伴有严理和中度腹背痛的65例作为研究对象，其中无腹背痛的3例除外，单纯接受术中放射治疗25例，术中放射治疗加体外放射治疗20例，单纯体外放射治疗20例，另外单纯手术治疗胰腺癌30例作对照。结果：（1）单纯术中放射治疗组患者背痛和腹痛的完全缓解率为47％，部分缓解率为34％，总疼痛缓解率为81％，术后2周内见效，中位生存期为5．9个月（从治疗开始计算）。（2）术中放射治疗加体外放射治疗组患者背痛和腹痛的缓解率同单纯疗后4周左右见效，中位生存期是4．5个月。（4）单纯手术治疗组中位生期7个月。结论：术中放射治疗加体外放射治疗能明显延长晚期胰腺癌患者的生存期，而且能明显缓解患者的疼痛，见效快，提高了患者的生活质量。     

Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.     

Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma

BACKGROUND: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU). METHODS: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method. RESULTS: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months. CONCLUSIONS: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma.     

IORT在不可切除局部晚期胰腺癌治疗中作用

目的 探讨电子线IORT在不可切除局部晚期胰腺癌中的价值。方法 回顾分析2009—2014年本院行电子线IORT的不可切除局部晚期胰腺癌共167例患者的OS期、LR率、不良反应。IORT剂量10~20 Gy。术后12例体外照射、56例同步CRT、17例化疗。Kaplan-Meier法计算生存率,Logrank法检验差异和单因素预后分析,Cox模型多因素预后分析。结果 随访率100%。中位OS期10.3个月,2年OS率为22.0%。中位PFS 6.3个月,2年PFS率为9.9%。CSS期11.2个月,2年CSS率为23.6%。仅行IORT时,<15 Gy、15 Gy和>15 Gy的中位OS及1年OS率分别为6.2个月和10.0%、9.1个月和39.6%、22.2个月和74.4%(P=0.000)。术后辅助治疗模式中IORT+CRT的中位OS期11.6个月,生存最佳(P=0.033)。单因素分析显示IORT剂量、肿瘤大小和限光筒直径为影响预后因素(P=0.000、0.006、0.007),多因素分析显示IORT联合术后放疗、IORT剂量为影响预后因素(P=0.006、0.000)。结论 对于不可切除局部晚期胰腺癌,电子线IORT是安全有效治疗手段,避开胃肠组织前提下适当增加剂量可提高疗效,术后CRT可更好延长生存且不增加不良反应。     

Moderate dose intraoperative and external beam radiotherapy for locally recurrent rectal carcinoma.

BACKGROUND AND PURPOSE: Late adverse effects (i.e. neuropathy, chronic bowel obstruction) limit the effective dose given in intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). Initial results of a multi-modality treatment approach using moderate dose IORT and moderate dose EBRT are presented. PATIENTS AND METHODS: Thirty-one consecutive patients with recurrent rectal carcinomas had IORT and EBRT after complete (R0, n = 14) or incomplete resection (R1, n = 9; R2, n = 8). The mean [ORT dose was 13.7 Gy (range 12-20 Gy) supplemented with an EBRT dose of 41.4 Gy. Twenty-two patients had preoperative EBRT and 22 patients had concomitant chemotherapy (5-FU, Leucovorine). RESULTS: After a median follow-up of 28 months, 16 patients had re-recurrent disease and 11 patients had died. Nine patients failed locally (four in-field, four marginal and one anastomotic re-recurrence), three combined with distant metastasis, resulting in overall and IORT infield local control rates of 71% and 87%, respectively. Distant metastases alone were found in seven patients. The 4-year overall and relapse-free survival rates were 58% and 48%, respectively. After incomplete resection the local failure rate increased (R0 21%, R1/2 35%) and the 4-year relapse-free survival rate decreased significantly (29% versus 71%) due to a markedly increased distant metastasis rate (53% versus 7%). Acute and late toxicities were not increased. CONCLUSION: The combination of moderate dose IORT and EBRT is a safe and efficacious component in a multi-modality treatment approach.     

Surgical management of retroperitoneal sarcomas associated with external and intraoperative electron beam radiotherapy.

AIMS: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). METHODS: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9meV. EBRT dose varies between 45-50 Gy. RESULTS: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases.Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. CONCLUSIONS: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.     

软组织肉瘤手术加术中放疗的临床研究

目的:探讨软组织肉瘤术中放疗的意义。方法:对39例软组织肉瘤患者行根治或姑息性手术,术中放疗在术中放疗手术室进行,术中根据肿瘤大小,选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy,姑息手术者剂量加大至36Gy。术后辅以外照射治疗,常规设野,5/周,2Gy/次,总量40～50Gy。初发病灶10例,术后复发29例。结果:39例患者随访12～64个月,3、5年局控率分别为71.8%和64.1%。3年生存率为82.0%。结论:术中放疗具有较高的局控率,比之其他治疗具有许多优点,将获得较高的生存率。     

Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma

PURPOSE: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. RESULTS: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. CONCLUSION: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.     

Management of carcinoma of the esophagus: the role of radiotherapy.

This is an analysis of treatment results over a 23-year period in 241 patients with carcinoma of the esophagus. The treatment for unresectable patients was external beam radiotherapy (EBRT) alone (mean dose 55 Gy) in 137 (57%) combined with brachytherapy (mean dose 50 + 40 Gy) in 46 (19%), and chemotherapy alone in 3 (1%) patients. In the 55 resectable patients, treatment was resection alone in 9 (4%), and combined with radiotherapy (mean dose 43 Gy) in 46 (19%) patients. The 1-, 2-, and 5-year survival for the 241 patients was 36, 15, and 5%, respectively (median 38 weeks). The 5-year survival was 18% for radiotherapy (RT)-surgery (S) patients, 11% for EBRT with brachytherapy, 2% for EBRT alone, and 0% for patients who had S alone, p less than 0.001. Survival correlated well with initial performance status, treatment, stage of disease, tumor size, radiation dose, and degree of response, p less than 0.001, but not with tumor location in the esophagus and patients' race and sex, p = 0.44. Serious complications occurred in 5 (2%) patients treated with RT alone and in 4 (7%) patients treated with S alone or combined with RT. The leading cause of death was persistent or recurrent tumor in the chest found in 39% patients.     

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis

PURPOSE: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. METHODS AND MATERIALS: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. RESULTS: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). CONCLUSION: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.     

42例晚期胰腺癌的术中放射治疗

目的　探讨姑息性手术结合术中放射治疗对晚期胰腺癌的疗效。方法　对 4 2例未能切除的晚期胰腺癌患者进行姑息性手术合并术中放疗。用 9～ 16MeV电子线在直视下照射病灶区域 ,照射量 2 0～ 30Gy。同时与未行术中放疗的 5 9例患者进行对比。结果　术中放疗组患者腹痛和腰背痛完全缓解率为 6 6 .7% ,部分缓解率为 2 6 .2 % ,总有效率为 92 .9%。未行术中放疗的 5 9例患者腹痛和腰背痛完全缓解率为 15 .3% ,部分缓解率为 2 5 .4 % ,总有效率为 4 0 .7% (P <0 .0 0 1)。术中放疗组平均生存期为 16 .7个月 ,对照组为 11.9个月 (P >0 .0 5 )。结论　姑息性手术结合术中放疗能够有效地控制晚期胰腺癌患者的腹痛和腰背痛 ,改善生活质量 ,并可适当延长生存期。     

Intraoperative radiation therapy (IORT) for locally unresectable pancreatic cancer

To evaluate the therapeutic effect of IORT for unresectable locally advanced pancreatic cancer, 11 patients treated with IORT and 15 patients treated with palliative therapy only were retrospectively examined. The mean age of the IORT group was 61.9 years, 5 cases were classified into surgical stage IVa, and 6 into stage IVb. The mean age of the palliative therapy group was 69.1 years; 5 cases were classified into surgical stage IVa and 10 into stage IVb. The tumor size was measured in 6 cases in the IORT group, before and after IORT. The tumor was enlarged in 1 case, not changed in 4 cases, and reduced in 1 case. The serum CA19-9 level was measured in 8 cases of the IORT group. Serum CA19-9 was increased in 3 cases, not changed in 4 cases, and decreased in 1 case after IORT. ECOG pain scores were obtained in 9 patients who had complained of pain before IORT, and the score decreased in 7 cases. The median survival was 7.6 months in the IORT group and 3.0 months in the palliative therapy group. IORT may improve patients' QOL by decreasing their pain. However, further studies are necessary to confirm the efficacy of IORT for survival of locally unresectable pancreatic cancer patients, because the patient profile in this study was different in the two groups.     

Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields.

A retrospective study evaluated 15 patients with pelvic recurrence of colorectal cancer in a previously irradiated region who received intraoperative radiation therapy (IORT) as part of salvage therapy. Total prior external beam radiation therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy. Three patients received additional EBRT as a post-operative course of 25.2 Gy in 14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local control rate of 19% at 12 months and median overall survival of 9 months. Patients with less extensive clinical presentations of anastomotic non-fixed transmural recurrence, isolated pelvic node metastasis and rectal recurrence following local excision had a local control rate of 42% at 36 months and median survival of 43 months. We conclude that clinical presentation of recurrent disease is an important prognostic factor. The value of IORT may be limited to patients with less extensive clinical presentations.     

Japan gastric trials in intraoperative radiation therapy

Based upon our clinical results indications of intraoperative radiotherapy (IORT) for gastric cancer were summarized as follows: (a) The primary tumor must be surgically removed. (b) There must be no metastases to the liver or peritoneum. (c) Serosal invasion must be limited to the posterior wall of the stomach. IORT is not adaptable to patients in whom there is direct invasion of the peritoneum beyond the anterior wall because of the ease of peritoneal dissemination. (d) All unresectable lesions must be encompassed by a single radiation field. (e) No significant difference between cumulative survival of patients with Stage I gastric cancer who were treated by IORT or surgery alone was found. Therefore IORT may be of no benefit to the prognosis of patients with Stage I gastric cancer. As for the IORT dose, it is recommended that for clinically undetectable lesions a single dose of 28 Gy be delivered. For macroscopic remnants 30-35 Gy should be delivered depending upon the residual tumor size. The electron energy is selected so that the entire lesion is included by the 90% isodose line. When IORT is applied to a curative operation, the radiation field is positioned toward the lymph node groups around the celiac axis, which are hard to eliminate by a surgical procedure.     

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 ≥ 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.     

A case of gemcitabine-based chemo-radiation therapy for locally advanced unresectable pancreatic cancer

A 49-year-old man was admitted to our hospital with vomiting. Abdominal CT revealed an avascular tumor at the uncinate process of the pancreas measuring 36x30 mm. Preoperative serum CA 19-9 was 361 U/ml. During laparotomy,the tumor was deemed unresectable (T4NXM0, Stage IVa),and duodenojejunostomy was performed. External-beam radiotherapy (EBRT) (50.4 Gy/28Fr) with concurrent twice-weekly gemcitabine (GEM) (40 mg/m(2)/day) was delivered. In the outpatient setting, and 1,000 mg/m(2) of GEM was administered intravenously on days 1, 8, and 15. Cycles were repeated every 28 days. The patient received 13 cycles of GEM chemotherapy until the appearance of a grade 2 facial rash. A decrease in tumor size was observed, and the serum CA 19-9 level dropped to 16 U/ml. He remained well without any symptoms and pursued normal activity for 33 months. He died of peritoneal dissemination 43 months after diagnosis. Gemcitabine-based chemo-radiation seems to be a safe and effective regimen for unresectable pancreatic cancer.     

Peripheral neuropathies following experimental intraoperative radiation therapy (IORT)

Injury to peripheral nerves in the lumbar para-aortic region was evaluated in beagle dogs 2 years following fractionated irradiation (EBRT), intraoperative irradiation (IORT), or a combination of IORT and EBRT. Time to onset of peripheral neuropathy was determined by means of serially completed neurological and electrophysiological examinations. Peripheral neuropathies were seen beginning as early as 6 months following 35 Gy (or greater) IORT only and 35 Gy plus 50 Gy EBRT. The incidence of peripheral neuropathies increased with increasing IORT doses beginning at 15 Gy. Onsets of peripheral neuropathies following IORT alone were clustered between 6 and 18 months, with onset in some dogs occurring as late as 24 months. The combination of IORT and EBRT resulted in an incidence and latency to onset of neuropathies similar to that seen with IORT alone. Neuropathies were not seen with EBRT alone at doses from 50 Gy to 80 Gy. Recovery of nerve function did not occur in affected dogs. Histological studies of nerves 2 years following irradiation demonstrated loss of axons and myelin, with a corresponding increase in endoneurial, perineurial, and epineurial connective tissue. Percentage of axon and myelin decreased to about 60% of normal at 15 Gy IORT, and additionally at higher doses. An insignificant decrease in percentage of axon and myelin was seen following EBRT alone. A significant lesion occurring in and around nerves at most IORT doses was necrosis and hyalinization of the media of small arteries and arterioles. The dose for a 50% probability for causing severe vessel lesions in the 2-year study was 19.5 Gy IORT only and 18.7 Gy when IORT was combined with EBRT. These lesions were not seen with any EBRT only dose. These studies suggest that peripheral nerve is a dose limiting normal tissue in IORT. Neuropathies appear to result from direct effects of irradiation on nerve and secondary effects to nerve resulting from damage to regional vasculature.