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.     

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.     

A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.     

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.     

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.     

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.     

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。     

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.     

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.     

Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis

PURPOSE: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT+IORT). METHODS AND MATERIALS: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. RESULTS: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p=0.019). CONCLUSIONS: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (approximately 50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT+external RT).     

Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy.

AIMS: High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. MATERIAL AND METHODS: Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. RESULTS: One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. CONCLUSION: This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement.     

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。     

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.     

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.     

Efficacy and safety of intraoperative radiotherapy in breast cancer: a systematic review

The objective of this study is to assess the efficacy and safety of intraoperative radiotherapy (IORT) for early breast cancer through a systematic review. Fifteen studies met the inclusion criteria. Most studies assessed the combined treatment with IORT (10-24 Gy) and external beam radiotherapy (EBRT) (45-50 Gy) on early stage breast cancer (T_0-2). Local control was over 95% for 1 and 4 years of follow-up and the 5-year overall survival was 99%. The TARGIT-A study found a similar survival comparing IORT with standard treatment. The incidence of acute and chronic complications was scarce. IORT is well tolerated by patients and acute and late toxicities are low. There are no differences in survival for IORT treated patients versus standard treatment.     

Chemoradiation therapy for stage IV pancreatic cancer

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.     

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system

INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50 KV) is an innovative technique that can be used both for accelerated partial breast irradiation (APBI) and intraoperative boosting in patients affected by breast cancer. Immediately after tumor resection the tumor bed can be treated with low-distance X-rays by a single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBRT), the purpose of IORT is to cover the tumor bed safely. This report will focus on the feasibility and technical aspects of the Intrabeam device and will summarize our experience with side effects and local control. MATERIALS AND METHODS: Between February 2002 and June 2003 57 breast cancer patients, all eligible for breast conserving surgery (BCS), were treated at the Mannheim Medical Center with IORT using the mobile X-ray system Intrabeam. The patient population in this feasibility study was not homogeneous consisting of 49 patients with primary stage I or II breast cancer, seven with local recurrence after previous EBRT and one with a second primary in a previously irradiated breast. The selection criteria for referral for IORT included tumor size, tumor cavity size, margin status and absence of an extensive intraductal component. The previously irradiated patients with local recurrences and 16 others received IORT as single modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was 20 Gy prescribed to the applicator surface. EBRT was delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18-MV photons. Patients were assessed every three months by their radiation oncologist or surgeon during the first year after treatment and every six months thereafter. Breast ultrasound for follow-up was done every six months and mammographies once yearly. Acute side effects were scored according to the CTC/EORTC score and late side effects according to the Lent-Soma classification. RESULTS: Twenty-four patients received IORT only; eight patients because they had received previous radiotherapy, 16 because of a very favorable risk profile or their own preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the prescribed dose is delivered in an isotropic dose distribution around spherical applicators. Treatment time ranged between 20 and 48 minutes. No severe acute side effects or complications were observed during the first postoperative days or after 12 months. One local recurrence occurred 10 months after surgery plus IORT followed by EBRT. In two patients distant metastases were diagnosed shortly after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients. As a preliminary boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. The treatment is well tolerated and does not cause greater damage than the expected late reaction in normal tissue.