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.     

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 intraoperative radiotherapy for unresectable pancreatic cancer

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.     

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.     

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。     

Postoperative radiotherapy in carcinoma of the cervix with microscopically positive resection margin

Background Patients with cervical cancer who have positive surgical resection margins after radical hysterectomy are at increased risk for local recurrence. The results of postoperative pelvic radiotherapy for cervix cancer with microscopically positive surgical resection margins were analyzed to evaluate the role of radiotherapy. Methods Between 1979 and 1992, 60 patients with cervix carcinoma were treated with postoperative radiotherapy after radical hysterectomy and pelvic lymphadenectomy because of microscopic positive vaginal (48 patients), or parametrial (12 patients) resection margins. Patients were treated with external beam radiation therapy (EBRT) alone (12 patients), or EBRT plus vaginal ovoid irradiation (VOI) (48 patients). The median follow-up period was 55 months. Results The 5-year actuarial disease-free and overall survival rates for all patients were 75% and 84%, respectively. The overall recurrence rate was 23% (14/60). Among the 48 patients with positive vaginal resection margins, 4 had pelvic recurrence (8%), and 7 had distant metastasis (15%); the recurrence rate was 21% (9/43) in those treated with EBRT and VOI, and 40% (2/5) in the EBRT-only treated group. In the 12 patients with positive parametrial margins, 3 patients (25%) had distant metastases. The most significant prognostic factor was lymph node metastasis. Complications resulting from radiotherapy occurred at a rate of 32% (19/60), and grade III complications occurred in 3 patients (5%). Conclusion Postoperative radiotherapy can produce excellent control rates in patients with microscopically positive resection margins. In patients with positive vaginal margins, whole pelvic EBRT and VOI is recommended.     

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。     

Intraoperative radiation therapy for recurrent head-and-neck cancer: the UCSF experience

PURPOSE: To review a single-institutional experience with the use of intraoperative radiation therapy (IORT) for recurrent head-and-neck cancer. METHODS AND MATERIALS: Between 1991 and 2004, 137 patients were treated with gross total resection and IORT for recurrence or persistence of locoregional cancer of the head and neck. One hundred and thirteen patients (83%) had previously received external beam radiation as a component of definitive therapy. Ninety-four patients (69%) had squamous cell histology. Final surgical margins were microscopically positive in 56 patients (41%). IORT was delivered using either a modified linear accelerator or a mobile electron unit and was administered as a single fraction to a median dose of 15 Gy (range, 10-18 Gy). Median follow-up among surviving patients was 41 months (range, 3-122 months). RESULTS: The 1-year, 2-year, and 3-year estimates of in-field control after salvage surgery and IORT were 70%, 64%, and 61%, respectively. Positive margins at the time of IORT predicted for in-field failure (p = 0.001). The 3-year rates of locoregional control, distant metastasis-free survival, and overall survival were 51%, 46%, and 36%, respectively. There were no perioperative fatalities. Complications included wound infection (4 patients), orocutaneous fistula (2 patients), flap necrosis (1 patient), trismus (1 patient), and neuropathy (1 patient). CONCLUSIONS: Intraoperative RT results in effective disease control with acceptable toxicity and should be considered for selected patients with recurrent or persistent cancers of the head and neck.     

A study of radiotherapy modalities combined with continuous 5-FU infusion for locally advanced gastrointestinal malignancies.

AIM: We describe the feasibility of combining infusional 5-fluorouracil (5-FU) with intraoperative radiation therapy (IORT). METHODS: Patients with surgically resectable locally advanced gastrointestinal cancers were treated concurrently during surgery with IORT and a 72 h infusion of 5-FU. Patients without previous external beam radiation therapy (EBRT) were subsequently treated with EBRT (40-50Gy) concurrent with a 21-day continuous infusion of 5-FU. Pancreatic, gastric, duodenal, ampullary, recurrent colorectal, and recurrent anal cancer were included. RESULTS: During IORT/5-FU, no chemotherapy-related grade III or IV hematologic or gastrointestinal toxicity was noted. Post-surgical recovery or wound healing was not affected. One of nine patients who received post-operative radiation required a treatment break. During follow-up, there were more complications in patients with pelvic tumours, especially those with previous radiation. Nine patients have had local and/or local regional recurrences, two of these in the IORT field. CONCLUSIONS: Treatment with a combination of IORT and 5-FU followed by EBRT and 5-FU is feasible. However, long-term complications may be increased in previously irradiated recurrent pelvic tumours.     

Influence of radiation dose on positive surgical margins in women undergoing breast conservation therapy

PURPOSE: Positive surgical margins adversely influence local tumor control in breast conservation therapy (BCT). However, reports have conflicted regarding whether an increased radiation dose can overcome this poor prognostic factor. In this study, we evaluated the influence of an increased radiation dose on tumor control in women with positive surgical margins undergoing BCT.METHODS AND MATERIALS: Between 1978 and 1994, 733 women with pathologic Stage I-II breast cancer and known surgical margin status were treated at Thomas Jefferson University Hospital with BCT. Of these 733 patients, 641 women had a minimal tumor bed dose of 60 Gy and had documentation of their margin status; 509 had negative surgical margins, and 132 had positive surgical margins before definitive radiotherapy. Complete gross excision of the tumor and axillary lymph node sampling was obtained in all patients. The median radiation dose to the primary site was 65.0 Gy (range 60-76). Of the women with positive margins (n = 132), the influence of higher doses of radiotherapy was evaluated. The median follow-up time was 52 months.RESULTS: The local tumor control rate for patients with negative margins at 5 and 10 years was 94% and 88%, respectively, compared with 85% and 67%, respectively, for those women with positive margins (p = 0.001). The disease-free survival rate for the negative margin group at 5 and 10 years was 91% and 82%, respectively, compared with 76% and 71%, respectively, for the positive margin group (p = 0.001). The overall survival rate of women with negative margins at 5 and 10 years was 95% and 90%, respectively. By comparison, for women with positive surgical margins, the overall survival rate at 5 and 10 years was 86% and 79%, respectively (p = 0.008). A comparison of the positive and negative margin groups revealed that an increased radiation dose (whether entered as a dichotomous or a continuous variable) >65.0 Gy did not improve local tumor control (p = 0.776). On Cox multivariate analysis, margin status and menopausal status had prognostic significance for local tumor control and DFS.CONCLUSION: Patients with positive surgical margins have a higher risk of local tumor recurrence and worse survival when undergoing BCT. Higher doses of radiation are unable to provide an adequate level of local control in patients with positive margins.     

Control of aftereffects due to intraoperative radiotherapy

In cases of treating a pancreatic cancer, an aneurysm and thrombus of the abdominal aorta, necrosis of the vertebral body, and damage to the peripheral nerves can be caused by intraoperative radiotherapy (IORT). These aftereffects have been observed in tests conducted in experimental animal reported by Colorado State University. Similarly, our clinical experiences have led us to set safety guidelines to prevent damage due to IORT. The safety level of a radiation dose for IORT alone is limited to 30 Gy, and for IORT combined with external beam radiotherapy, from 20 Gy (IORT) plus 50 Gy (EBRT). Using these parameters, among 58 cases of a pancreatic tumor treated by IORT, only one case subsequently developed a pseudoaneurysm at the stump of splenic artery.     

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment

PURPOSE: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation. METHODS AND MATERIALS: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection. RESULTS: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively. CONCLUSIONS: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.     

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.     

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.     

Novel chemoradiotherapy for locally advanced pancreatic cancer using arterial infusion chemotherapy following the alteration of peripancreatic blood flow

Radiotherapy employing intraoperative radiation therapy (IORT) in combination with postoperative external beam radiation therapy (EBRT) is an effective treatment for unresectable pancreatic cancer. To achieve an even greater therapeutic outcome, 13 patients with unresectable pancreatic cancer were treated by IORT in combination with EBRT plus locally intensive arterial infusion chemotherapy. In order to increase drug delivery to the primary tumor, the splenic and major pancreatic arteries, except for the gastroduodenal artery (GDA), were embolized by radiological intervention prior to the arterial infusion chemotherapy, and the administration of gemcitabine, CDDP, and 5-FU to the primary tumors via GDA was followed during EBRT. The values of serum tumor markers were decreased in all patients, and tumor regression was detected on CT scans in 6 patients. The evaluation of survival benefit of this treatment modality is ongoing, but it did not prolong the survival time of patients with second stage lymph node metastases. One of the advantages of this method was able to perform also in charge of hepatic arterial infusion chemotherapy concurrently, but we experienced liver abscess in 2 patients.     

Future directions in intraoperative radiation therapy

It is difficult to establish the degree of effectiveness of IORT as a component of treatment in some of the malignancies currently being treated by IORT. Locally advanced pancreatic cancer is a typical example of a neoplasm for which it has been challenging to find effective advances in treatment. The survival time of patients who have this disease is limited to 9 to 12 months (median), with a 2-year survival rate of 10% to 20% following even the most effective chemoradiation. It is perhaps overly optimistic to expect that IORT will significantly enhance survival, because currently available systemic treatment options have not meaningfully affected either overall patient survival times or the rate of distant metastasis in either the adjuvant setting or for metastatic disease. It is encouraging, however, that Willett has reported five patients with 5-year survival times in the Massachusetts General Hospital IOERT series for unresectable pancreatic cancer (C.G. Willett, personal communication, 2002). Also encouraging is the report from the Medical College of Ohio of a 5-year rate of 33% in a small group of patients with resectable pancreatic cancers treated with single IORT doses (without EBRT or chemotherapy) as the sole adjuvant to surgical resection. At the same institution, during the same time period, the same group of surgeons observed that no patient with resectable pancreatic cancer survived longer than 13 months following surgical resection alone [7]. Exciting possibilities involve the use of IORT when treating early-stage malignant disease, as is detailed in the chapter on breast cancer. The use of [table: see text] IORT as adjuvant therapy seems to be associated with an extremely low incidence of in-breast local recurrence. Whether this is because of early stage of the disease or the adjuvant EBRT is not entirely clear at the time of this writing. (The results of ongoing randomized studies may not be powered sufficiently to resolve the question.) Because the local recurrence rate currently is extremely low (only one reported recurrence), however, this finding is promising. Also exciting is the use of IORT as the sole radiation [table: see text] treatment following limited excision of breast cancer. The results of the Lanciano and Milano trials (see chapter 12) are awaited with great interest. Equally exciting is the finding of meaningful survival of 20% to 40% of patients who have local or regionally recurrent cancers when IORT is used as a component of treatment together with EBRT, maximal resection, and chemotherapy, as indicated. Many of these patients still have excessive rates of both local and distant relapse, however, necessitating the rationale for well-controlled multi-institutional studies that involve alternate systemic therapies, radiation sensitizers, among other criteria.     

Feasibility and first results of multimodality treatment, combining EBRT, extensive surgery, and IOERT in locally advanced primary rectal cancer

PURPOSE: To assess the outcome of aggressive multimodality treatment with preoperative external beam radiation therapy (EBRT), extended circumferential margin excision (ECME) and intraoperative electron beam radiation therapy (IOERT) in patients with locally advanced primary rectal cancer. METHODS AND MATERIALS: Thirty-eight patients with primary locally advanced rectal cancer, but without distant metastases, received multimodality treatment. CT-scan showed extension to other structures in 15 patients (39%) and definite infiltration into the surrounding structures in 23 patients (61%). All patients received preoperative EBRT (dose range 25-61 Gy) and 82% received 50.4 Gy. The resection types were: 12 low anterior resections (31%), 14 abdomino-perineal resections (37%), 6 abdomino-transsacral resections (16%), and 6 pelvic exenterations (16%). The IOERT dose ranged from 10 to 17.5 Gy depending on the completeness of the resection. RESULTS: There was no perioperative mortality. The resection margins were microscopically negative in 31 patients (82%), microscopically positive in 4 (10%), and positive with gross residual disease in 3 patients (8%). Pelvic recurrences were observed in 5 patients (13%) including 3 IOERT infield failures. The overall 3-year local control, disease-free survival (DFS), and survival rates were 82%, 65%, and 72%, respectively. Negative resection margins were the most significant prognostic factor with regard to DFS (p = 0.0003) and distant control (p = 0.002) compared with cancer involved surgical margins. CONCLUSION: A high percentage of curative resections can be achieved in this group of patients with locally advanced rectal cancers. Adding IOERT to preoperative EBRT and ECME achieves high local control rates and possibly improves survival.     

Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma.

PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease.     

Intra-operative irradiation (IORT) for primary advanced and recurrent rectal cancer. a need for randomised studies

The aim of this study was to determine the impact of intra-operative irradiation (IORT) combined with pre-operative external beam irradiation (EBRT) and surgical resection in patients with locally advanced primary or recurrent rectal cancer. 64 patients with locally advanced primary cancer and 104 with recurrence had EBRT (46-50 Gy) before surgery. 80 patients received IORT (median dose 15 Gy energy 12 MeV). 80 patients had R0 resections, 47 R1 and 41 R2 resections. More R1 resections were performed in the IORT group, more R0 and R2 resections in the non-IORT group. Median follow-up was around 22 months. 146 patients were resected, 22 had exploratory laparotomy. The cumulative overall survival was similar for both the IORT and non-IORT groups. 5-year survival for primary cancers was 48% versus 28% for recurrences. No R2 resections survived 3.5 years. 5-year-survival for R0 resections was nearly 60% and around 30% for R1 resections. The survival curves of the patients given and not given IORT treatment was not statistically different when R0, R1 and R2 resections were analysed separately. IORT did not seem to influence the local recurrence rate when R0 and R1 resections were analysed separately or in a multivariate analysis. The IORT and non-IORT groups were not identical with regard to type of cancer and R-stage. Still the lack of an identifiable impact of IORT suggests that there is a need for randomised studies of the IORT effect.