Experience of three years with intra-operative radiation therapy using the Lyon intra-operative device.

Since November 1985, we have performed 54 Intra-Operative Radiation Therapy (IORT) interventions, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality, morbidity, and average of survival rates were compared with a non-randomized control group: mortality and morbidity rates were similar in the two groups, with or without IORT. The follow-up period was too short for any valid conclusions about IORT in gastric cancer to be reached. However, in the case of unresectable pancreatic cancer, a significant difference was observed in survival rates when patients were treated by surgery alone or surgery and IORT (4.7 months), and when they were treated by surgery, IORT and external postoperative radiotherapy (8.9 months) (p less than 0.05). The study also examined the relief of abdominal and back pain in patients with unresectable pancreatic cancer: in our experience, survival was longer and more comfortable for patients treated with surgery and IORT. In conclusion, it appears that today IORT is without doubt a good palliative treatment for unresectable pancreatic cancer, but more experience is needed before a conclusion can be reached regarding resectable pancreatic cancer and gastric cancer.     

术中放射治疗晚期胰腺癌45例

目的　探讨术中放射治疗 (简称放疗 )对晚期胰腺癌的疗效。方法　使用直线加速器 ,对 1986～ 1997年期间收住我院 ,伴有严重背痛和腹痛的无法切除的晚期胰腺癌患者 45例进行术中放疗。结果　本组患者背痛和腹痛的完全缓解率为 5 6 % ,部分缓解率为 40 %。平均生存期为7 5个月。同期进行的 30例胰腺癌切除患者 ,其平均生存期为 7个月 ,两者差异无显著意义。结论　术中放疗尽管不能明显延长晚期胰腺癌患者的平均生存期 ,但能明显缓解患者的疼痛 ,提高患者的生活质量 ,仍然不失为一种有效的晚期胰腺癌姑息治疗方法。     

Are complications in intraoperative radiation therapy more frequent than in conventional treatment?

To evaluate whether intraoperative radiation therapy (IORT) results in higher complication rates than conventional radiotherapy, 119 patients were studied who entered four prospectively randomized clinical trials that compared IORT with conventional therapy. Malignant neoplasms included 33 gastric carcinomas, 35 retroperitoneal sarcomas, 22 resectable pancreatic cancers, and 29 unresectable pancreatic cancers. One hundred thirty-six complications developed among 66 patients who received conventional therapy, and 108 complications developed among 53 patients who received IORT. There was no statistical significance between treatment groups with respect to the overall incidence of complications. Analysis of types of complications by tumor type using Fisher's exact test revealed only one significant complication: an increased rate of sepsis among the patients with retroperitoneal sarcoma who received conventional therapy compared with their IORT cohorts. The overall complication rate associated with IORT was equivalent to conventional radiotherapy in the treatment of these malignant neoplasms and supported the use of IORT where clinically indicated.     

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??Effect assessment of intraoperative radiotherapy for advanced pancreatic cancer WANG Cheng-feng. Department of Pancreatic and Gastric Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Chinese National Cancer Center, Beijing 100021??China
Abstract The treatment effect of advanced pancreatic cancer is poor, and the treatment methods are more controversial. Intraoperative radiotherapy??IORT?? has accurate target positioning??around certain viscera protection??good local control and less complications??which can prolong survival and improve quality of life. Intraoperative tissue cytology determination is convenient and safe. IORT can relieve biliary obstruction, remove or prevent the digestive tract obstruction at the same time??which is an effective treatment of advanced pancreatic cancer. IORT based comprehensive treatment, multidisciplinary, multiple therapy for advanced pancreatic cancer is a kind of good curative effect??convenient operation and safe treatment. But the equipment is expensive and high environmental requirements are the short board.     

Treatment perspectives in locally advanced unresectable pancreatic cancer.

Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-fluorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at 1 year, two patients at 2, 3 and 4 years. A second-look operation was performed in four patients 6, 11, 12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer.     

Value of Extended Resection and Intraoperative Radiotherapy for Resectable Pancreatic Cancer

Since 1984 intraoperative radiotherapy (IORT) combined with extended resection for pancreatic cancer has been performed in our clinic to prevent local recurrence. Following extended resection, a dose of 30 Gy of 9- to 12-MeV electrons is administered to the operative field, including the paraaortic area from the diaphragm above to the inferior mesenteric artery below. The 5-year survival rate was 15.3% in all 37 cases, 20.2% in patients who had macroscopic tumor clearance, and 16.9% in patients with stage IVa tumor according to the Japanese classification. In autopsies of 10 patients who underwent combined therapy, four had local recurrence enclosed by thick, firm connective tissue. There was no local control recurrence in two patients who underwent noncurative resection. Enhanced local control induced by the combined therapy, however, has only a limited impact on overall survival because of the systemic spread of disease, especially hepatic metastases. At present, as we have no effective treatment for hepatic metastases, it is important to perform an extended resection with IORT on carefully selected patients. The combined therapy may offer the best approach to control local recurrence when dealing with advanced, but not highly advanced, cancer as defined by the stage of tumor. Therefore a combination of IORT and extended resection can have an impact on the results of surgical treatment for pancreatic cancer when anticancer treatment of hepatic metastases is established.     

不可切除胰腺癌治疗策略的更新与意义

目前,不可切除胰腺癌治疗策略是以全身系统化疗为主,放疗、介入、姑息性手术等局部治疗为辅,达到减轻病人局部症状,提高生活质量,延长生存期的目的。体能较好病人推荐FOLFIRINOX或吉西他滨（GEM）联合白蛋白结合型紫杉醇方案化疗,中位生存期可延长至接近1年,约15%局部晚期初始不可切除病人有可能转化为可切除。GEM联合厄洛替尼依然是各指南靶向药物的惟一一线推荐,抗肿瘤基质药物人重组透明质酸酶α（PEGPH20）有望取得突破性进展。美国国家综合癌症网络（NCCN）指南推荐程序性细胞死亡蛋白-1（PD-1）及其配体（PD-L1）抑制剂用于高度微卫星不稳定（MSI-H）或错配修复缺陷（dMMR）不可切除胰腺癌病人,免疫治疗进入二线标准推荐。强调多学科综合治疗协作组（MDT）模式及个体化精准治疗理念。     

Early experience with intraoperative radiotherapy in patients with resected pancreatic adenocarcinoma

BACKGROUND: The use of intraoperative radiotherapy (IORT) in patients with resected pancreatic adenocarcinoma has not been clearly defined. METHODS: The medical records of our first 22 patients receiving IORT for resected pancreatic adenocarcinoma (2001 to 2006) were reviewed and compared with the records of 27 consecutive patients not receiving IORT for resected pancreatic adenocarcinoma (2004 to 2006). RESULTS: There were no 30-day mortalities in either group, and complication rates were similar. Local recurrence occurred in 18% in the IORT group (median 14 months) and 12% in the no-IORT group (median 7 months). Distant recurrence occurred in 47% in the IORT group (median 11 months) and 32% in the no-IORT group (median 6.5 months). Median overall, stage-specific, and location-specific survival did not differ between the groups. CONCLUSIONS: Although limited in size and follow-up, our experience showed that complications, recurrence, and survival were not affected by IORT, but time to recurrence may be longer with IORT.     

Clinical results of intraoperative radiation therapy for patients with locally recurrent and advanced tumors having colorectal involvement

BACKGROUND: Intraoperative radiation therapy (IORT) may be useful in the treatment of patients who have a locally advanced primary and recurrent abdominopelvic neoplasm with colorectal involvement. METHODS: A retrospective review of colorectal cancer patients treated since 1999 with IORT using the Mobetron device. RESULTS: Forty patients underwent colectomy or proctectomy with IORT. All patients had evidence of local extension to contiguous structures and based on preoperative staging were deemed by the operating surgeon as being likely to have incomplete resection. IORT was selected as an alternative to sacrectomy or exenteration for an expected close margin in 10 patients. Mean survival was 35 +/- 26 months, and 1 patient had local recurrence. CONCLUSIONS: The introduction of IORT has allowed a selective treatment approach to locally advanced primary and recurrent neoplasms, which traditionally would have been deemed unresectable. Using IORT, extended resections may be avoided in selected high-risk patients with low risk of local recurrence and minimal morbidity.     

术中放疗在直肠癌治疗中的应用

放疗与手术、化疗是治疗肿瘤的主要手段,术中放疗在直肠癌中的应用仍处于起步阶段。直肠癌患者接受术中放疗有术前或者术后放疗无法超越的优势,术中放疗可提高局部进展期直肠癌的局部控制率,可提高局部复发性直肠癌的总体生存率。总体而言,术中放疗是安全可行的,在直肠癌中的应用前景光明。     

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??Interpretation of an updated treatment strategy for unresectable pancreatic adenocarcinoma TENG Zan??LIU Yun-peng. Department of Medical Oncology??the First Hospital of China Medical University??Shenyang 110001??China
Corresponding author: LIU Yun-peng??E-mail??ypliu@cmu.edu.cn
Abstract At present??the treatment strategy for unresectable pancreatic adenocarcinoma is mainly based on systemic chemotherapy and adopts local treatment such as radiotherapy??intervention??and palliative surgery as support??so as to relieve local symptoms??improve quality of life??and prolong survival of patients. It is suggested that patients with good performance status accept combination chemotherapy including FOLFIRINOX or gemcitabine (GEM) with nab-paclitaxel. With these treatments??the median survival of patients is extended to nearly 1 year and approximately 15% of locally advanced unresectable diseases have the opportunity to become resectable. Erlotinib plus gemcitabine combination therapy is still the only choice of target therapy in first-linetreatment according to recommendation. There will be a promising breakthrough in Pegvorhyaluronidase alfa (PEGPH20) by improving the tumor microenvironment. PD-1/PD-L1 inhibitors are recommended for patients with previously treated MSI-H/dMMR unresectable pancreatic cancer by guidelines. Individualized precise treatment for cancer and multidisciplinary team (MDT) meetings are widely accepted and emphasized by guidelines.     

Impact of radiotherapy on palliative gastroenterostomy in pancreatic cancer.

The previously unaddressed impact of radiotherapy and vagotomy on palliative gastroenterostomy (GE) in patients with unresectable pancreatic cancer was studied. Sixty-eight patients were retrospectively evaluated. A higher overall incidence of complications was found in the group (N = 44) undergoing irradiation as well as gastroenterostomy compared to a group undergoing gastroenterostomy alone. The increased complications were due to 16 episodes of bleeding among the irradiated patients. Rates of obstructive complications were similar for both groups (20%). Rates of bleeding were highest among patients undergoing prophylactic GE and irradiation compared to those receiving GE alone. Vagotomy in 12 patients who were irradiated did not appear to protect against bleeding. We found the irradiated prophylactic GE to provide poor palliation in patients with unresectable pancreatic cancer and recommend it not be performed if radiotherapy is to be used for attempt in local control of unresectable pancreatic cancer.     

Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma.

Since 1978 we have used electron beam intraoperative radiation therapy (IORT) to deliver higher radiation doses to pancreatic tumors than are possible with external beam techniques while minimizing the dose to the surrounding normal tissues. Twenty-nine patients with localized, unresectable, pancreatic carcinoma were treated by electron beam IORT in combination with conventional external radiation therapy (XRT). The primary tumor was located in the head of the pancreas in 20 patients, in the head and body in six patients, and in the body and tail in three. Adjuvant chemotherapy was given in 23 of the 29 patients. The last 13 patients have received misonidazole (3.5 mg/M2) just prior to IORT (20 Gy). At present 14 patients are alive and 11 are without evidence of disease from 3 to 41 months after IORT. The median survival is 16.5 months. Eight patients have failed locally in the IORT field and two others failed regionally. Twelve patients have developed distant metastases, including five who failed locally or regionally. We have seen no local recurrences in the 12 patients who have been treated with misonidazole and have completed IORT and XRT while 10 of 15 patients treated without misonidazole have recurred locally. Because of the shorter follow-up in the misonidazole group, this apparent improvement is not statistically significant. Fifteen patients (52%) have not had pain following treatment and 22 (76%) have had no upper gastrointestinal or biliary obstruction subsequent to their initial surgical bypasses and radiation treatments. Based on the good palliation generally obtained, the 16.5-month median survival, and the possible added benefit from misonidazole, we are encouraged to continue this approach.     

Influence of Intraoperative Radiotherapy (IORT) on Perioperative Outcome after Surgical Resection of Rectal Cancer

Background

Intraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only.

Methods

A total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared.

Results

Of the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 ± 84 vs 177 ± 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate.

Conclusions

Intraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long-term follow-up.     

Does Intraoperative Radiation Therapy Improve Local Tumor Control in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Adenocarcinoma? A Propensity Score Analysis

Background  Locoregional recurrence (LRR) is an important factor after pancreaticoduodenectomy (PD) for pancreatic cancer. Intraoperative radiation therapy (IORT) administered to the resection bed may improve local tumor control. Methods  We performed a retrospective analysis of patients who underwent PD at Thomas Jefferson University Hospital (TJUH) between 1995 and 2005 to identify patients who underwent resection with and without IORT. Data collected included age, gender, complications, margin status, stage, survival, and recurrence. Unadjusted analyses of the IORT and non-IORT groups were performed using Fisher’s chi-square method for discrete variables and Wilcoxon rank sum test for continuous variables. To account for biases in patient selection for IORT, a propensity score was calculated for each patient and adjusted statistical analyses were performed for survival and recurrence outcomes. Results  Between January 1995 and November 2005, 122 patients underwent PD for periampullary tumors, including 99 pancreatic cancers. Of this group, 37 patients were treated with IORT, and there was adequate follow-up information for a group of 46 patients who underwent PD without IORT. The IORT group contained a higher percentage of Stage IIB or higher tumors (65%) than in the non-IORT group (39.1%), though differences in stage did not reach significance (P = .16). There was a nonsignificant decrease in the rate of LRR in patients who had IORT (39% non-IORT vs. 23% IORT, P = .19). The median survival time of patients who received IORT was 19.2 months, which was not significantly different than patients managed without IORT, 21.0 months (P = .78). In the propensity analyses, IORT did not significantly influence survival or recurrence after PD. Conclusions  IORT can be safely added to management approaches for resectable pancreatic cancer, with acceptable morbidity and mortality. IORT did not improve locoregional control and did not alter survival for patients with resected pancreatic cancer. IORT is an optional component of adjuvant chemoradiation for pancreatic cancer. In the future, IORT may be combined with novel therapeutic agents in the setting of a clinical trial in order to attempt to improve outcomes for patients with pancreatic cancer. Presented as Poster Presentation at the American Hepatico-Pancreato-Biliary Association, April 2008, Ft. Lauderdale, FL.     

Results of surgery and adjuvant radiotherapy for pancreatic cancer

We retrospectively reviewed the cases of 34 patients with pancreatic cancer who underwent resection between January 1988 and December 1996. Adjuvant radiotherapy was performed in 24 patients, with 13 receiving both intra- and postoperative radiotherapy, 2 receiving postoperative radiotherapy (PORT) alone, and 9 receiving intraoperative radiotherapy (IORT) alone. The 1- and 3-year survival rates for all 34 patients were 59% and 19%, respectively, with a median survival of 13 months. At the time of the analysis, three patients were still alive. Recurrence patterns were assessed in 25 patients who had had no distant metastases at the time of surgery, had survived more than 3 months after surgery, and had undergone close surveillance for recurrence. Based on computed tomography (CT) and autopsy findings, a total of 15 (60%) of these 25 patients had local recurrence, 13 (52%) had liver metastases, and 8 (32%) had both. Eight (62%) of the 13 patients who received IORT and/or PORT developed local recurrence, and we failed to detect any survival advantage of IORT and/or PORT over surgery alone. However, autopsies revealed a suppressive effect of radiation on cancer growth, and local recurrence was not considered to be the direct cause of death in any of the patients, nor did any of the patients develop gastrointestinal obstruction due to local recurrence. The incidence of liver metastasis in the patients with and without tumor invasion of the portal system was 80% (8/10) and 33% (5/15), respectively. The patients who did not develop liver metastasis had significantly longer survivals than who did. Further improvements of survival await effective prophylactic treatment for liver metastases. Received for publication on July 4, 1997; accepted on Aug. 27, 1997     

Intraoperative radiotherapy for resectable and unresectable pancreatic carcinoma

Eighty patients with pancreatic carcinoma were treated by intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of 111 patients treated by surgery alone. For resectable patients, the radiation dose was 30 Gy and the average field sizes were 8 or 10 cm; for unresectable patients, these values were 20–30 Gy and 6 or 8 cm, respectively. No side effects of IORT were observed. In 49 resectable stage III patients, the IORT group (n=16) had a higher survival rate than the non-IORT group (n=33); i.e., 1-year survival rates of 44.6% vs 23% and 2-year survival rates of 37.2% vs 7.7% after surgery (P<0.05). However, there was no significant difference in survival rate between the IORT group (n=28) and the non-IORT group (n=29) in 57 resectable patients in stage IV. In unresectable patients, the IORT group (n=31) (P<0.05) had a higher survival rate than the non-IORT group (n=38) (P<0.05). The palliative effect of IORT on abdominal or back pain was evaluated in 15 patients who had such symptoms and did not undergo tumor resection. Overall, pain decreased or disappeared in 13 of these patients (87%). Offprint requests to: A. Nakao     

Efficacy of computerized tomography in the preoperative staging of pancreatic carcinoma

The increasing use of nonoperative methods for the diagnosis and palliative treatment of pancreatic cancer has placed greater emphasis on computerized tomography (CT) in staging of this malignancy. The present study was done to review our experience with CT in staging pancreatic cancer, specifically its efficacy in predicting lesions amenable to curative versus noncurative surgical treatment. Sixty six consecutive patients with pancreatic cancer who were considered potential candidates for surgical resection and who had preoperative CT scans over the 4-year period from 1982 through 1986 were studied. Preoperative CT scans were reviewed by a radiologist without knowledge of patients' surgical management. CT criteria for unresectable disease include hepatic and distant metastasis as well as evidence of locally advanced disease, including peripancreatic fascial extension, extension of tumor to locally contiguous structures, vascular encasement/invasion, and local lymphadenopathy. CT predicted resectability with a sensitivity of 75 per cent and a positive predictive value of 38 per cent. Unresectability was predicted with a sensitivity of 72 per cent and positive predictive value of 93 per cent. CT incorrectly predicted unresectable disease in three patients who had a curative resection. CT was most reliable when it predicted unresectability due to the presence of hepatic and/or distant metastasis. CT predicted unresectability with least sensitivity using criteria for locally advanced disease. Therapeutic decisions for nonoperative management of patients with pancreatic cancer based upon CT predictions of unresectable disease, especially predictions of unresectability solely on the basis of locally advanced disease, can not be recommended at this time.     

Surgical approaches and techniques in intraoperative radiotherapy for intra-abdominal, retroperitoneal, and pelvic neoplasms

Eighty-five patients with locally advanced intra-abdominal, retroperitoneal, and pelvic malignant diseases have been treated at the National Cancer Institute (NCI) with electron beam intraoperative radiotherapy (IORT). In general, IORT was performed after resection to the tumor bed and to areas of locoregional spread. IORT was delivered directly to some unresectable tumors. The median survival for the entire NCI patient group was 13.9 months, with 34% of the patients projected to achieve local control of disease at 5 years. Multiple abutting IORT fields were used in 76% of the patients; they encompassed treatment areas as large as 569 cm2 and involved as many as five separate IORT applications. Multiple fields were matched along straight edges on the treatment applicators or provided by means of lead shielding strips. Areas of field overlap were prevented by the use of lead shields. Surgical approaches and radiotherapeutic techniques of multiple field matching have been developed and are detailed for carcinoma of the pancreas, carcinoma of the stomach, sarcomas of the retroperitoneum, carcinoma of the rectum, and tumors of the pelvic girdle.     

Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer

BACKGROUND: The prognosis of patients with resected pancreatic cancer remains poor. This study evaluated the effect of adoptive immunotherapy (AIT) using intraportal infusion of lymphokine-activated killer (LAK) cells after curative resection and intraoperative radiation therapy (IORT) on advanced pancreatic cancer. METHODS: Twenty-nine consecutive patients with advanced pancreatic cancer (Japan Pancreas Society stage III or IV) were divided into two groups. The control group (n = 17) underwent tumour resection and IORT. The treatment group (n = 12) underwent resection, IORT and intraportal infusion of LAK cells combined with recombinant interleukin 2 (rIL-2). The incidence of liver metastasis and the survival rate of these two groups were compared. RESULTS: Although the overall survival between groups was not statistically different (P = 0.082), there were more patients (four) alive 3 years after operation in the test group (36 per cent versus zero), and the incidence of liver metastases in the treatment group was significantly lower (three of 12 versus ten of 15; P < 0.05). LAK therapy influenced survival positively in multivariate analysis. CONCLUSION: These preliminary observations suggest that AIT warrants further study as a possible adjuvant for patients undergoing curative resection and IORT for pancreatic cancer.