Surgical management of single and multiple brain metastases: results of a retrospective study.

BACKGROUND: Advancement in diagnosis and treatment of various cancer entities led to an increasing incidence of brain metastases in the last decades. Surgical excision of single and multiple brain metastases is one of the central treatment options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the benefit of surgery with/without whole-brain radiation therapy (WBRT) in single brain metastases and the influence of image guidance for brain metastases resection, 104 patients were retrospectively evaluated for post-operative outcome. PATIENTS AND METHODS: Between January 1994 and December 1999 150 patients were surgically treated for brain metastases at the Department of Neurosurgery at the Technical University of Dresden. Outcome could be evaluated in 104 patients with respect to special treatment strategies and survival time (69 patients with single and 35 patients with multiple lesions). RESULTS: Most metastases originated from primary lung and breast tumours. Karnofsky performance score improved on average by 10 after surgery. The extent of the extracerebral tumour burden was the main influence on survival time. Patients' age below 70 years was combined with prolonged survival time (median survival time, MST: 4.5 months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16 months, whereas patients with singular lesions had a MST of 7 and 4 months, depending on the extent of the extracerebral tumour growth. Additional post-operative WBRT with 30 Gy was combined with an increase in MST in patients with single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8 months). In addition, the rate of recurrent cerebral tumour growth was distinctly higher in the non-WBRT group. Neuronavigation did not significantly improve post-operative survival time. In 80% of patients extracerebral tumour growth limited patients' survival. CONCLUSION: Surgery is an initial treatment option in patients with single and multiple brain metastases especially with large tumours (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with single brain metastasis by decreasing local and distant tumour recurrence. Neuronavigational devices permit a targeted approach. Multiple processes can be extirpated in one session without prolonging the hospitalisation time for the patient. However, neuronavigational devices cannot assure complete tumour resection.     

Outcome after radiosurgery for brain metastases in patients with low Karnofsky performance scale (KPS) scores

PURPOSE: The objective of this retrospective study was evaluation of the outcome after stereotactic radiosurgery (SRS) in patients with intracranial metastases and poor performance status. METHODS AND MATERIALS: Forty consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores < or =50 (mean, 43 +/- 8; median, 40) treated with SRS were analyzed. Poor performance status was caused by presence of intracranial metastases in 28 cases (70%) and resulted from uncontrolled extracerebral disease in 12 (30%). RESULTS: Survival after SRS varied from 3 days to 11.5 months (mean, 3.8 +/- 2.9 months; median, 3.3 months). Survival probability constituted 0.50 +/- 0.07 at 3 months and 0.20 +/- 0.05 at 6 months posttreatment. Cause of low KPS score (p = 0.0173) and presence of distant metastases beside the brain (p = 0.0308) showed statistically significant associations with overall survival in multivariate Cox proportional hazards regression analysis. Median survival was 6.0 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were absent, 3.3 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were present, and 1.0 month if poor performance status resulted from extracerebral disease. CONCLUSIONS: Identification of the cause of low KPS score (cerebral vs. extracerebral) in patients with metastatic brain tumor(s) may be important for prediction of the outcome after radiosurgical treatment. If poor patient performance status without surgical indications is caused by intracranial tumor(s), SRS may be a reasonable treatment option.     

Integration of gamma knife surgery in the management of cerebral metastases from melanoma

The aim of this study was to investigate the effect of gamma knife surgery on the local control of cerebral metastases from melanoma and to assess survival. In 29 patients, 105 of 178 cerebral metastases were treated with gamma knife surgery. Only five patients had metastases confined to the brain. Of the 96 metastases with magnetic resonance imaging follow-up, 61.5% regressed by more than 50% of the pretreatment volume, 25% regressing by more than 90% and 13.5% completely. The median survival from gamma knife surgery was 5.7 months (longest survival, 38 months). In multivariate analyses, a larger number of lesions requiring treatment (P < 0.001), recursive partitioning analysis class (P = 0.009) and a long time interval from initial melanoma diagnosis to detection of cerebral metastases (P = 0.001) influenced survival. It can be concluded that gamma knife surgery is a useful adjunct in the management of cerebral metastases from melanoma and has a significant impact on local control. Its greatest potential may be achieved in conjunction with systemic chemotherapy, especially in the presence of extracerebral metastases.     

Intracranial metastases of malignant melanoma treated by surgery

Metastases in 25 patients with intracranial metastases from malignant melanoma were extirpated. Two patients had a second operation after six and ten months because of tumor recurrence. Single brain metastaσes were found in 20 and multiple in five patients. The interval between the primary tumor and the intracranial metastases varied from 17 years to six months. Three patients died due to complications from surgery. The median survival time was five months (mean survival ten months). Complete relief of symptoms was observed in 17 and partial relief in two patients. The quality of life was improved in 17 patients and 14 of these 17 went back to their ordinary occupation. The indications for neurosurgery are restricted in patients with extracranial or with multiple intracranial metastases.     

Treatment outcome of patients with brain metastases from malignant germ cell tumors

BACKGROUND: Multiinstitutional experience with the management of cerebral metastases from malignant germ cell tumors (MGCT) is presented. METHODS: Clinical data regarding brain metastases from MGCT at diagnosis (Group 1 [56 patients]) or after cisplatin-based chemotherapy (Group 2 [83 patients]) were collected retrospectively. All patients in Group 1 received "conventional" cisplatin-based chemotherapy supplemented by cerebral radiotherapy (36 patients) and/or neurosurgery (10 patients). In the patients in Group 2 cerebral metastases were detected a median of 9 months after the initiation of chemotherapy. Thirty-five patients received chemotherapy, 59 patients received radiotherapy, and 25 patients underwent neurosurgery. RESULTS: The 5-year cause specific survival rate in Group 1 was 45% (95% confidence interval [CI], 31-59%). Neurosurgery and the absence of extracerebral, nonpulmonary visceral disease, but not cerebral radiotherapy, were independent predictors of good prognosis. The 5-year cause specific survival rate in Group 2 was 12% (95% CI, 4-20%), but was 39% among patients with an isolated brain recurrence (24 patients). Radiotherapy, but not chemotherapy, represented an independent predictor of good prognosis together with brain metastases at first recurrence and the absence of extracerebral recurrence. CONCLUSIONS: Among patients with brain metastases at the time of diagnosis of an MGCT, cisplatin-based chemotherapy resulted in a 5-year cause specific survival rate of 45%, with cerebral radiotherapy having limited impact. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but increased to 39% in patients with an isolated brain recurrence. Cerebral radiotherapy (and neurosurgery) represent essential treatment modalities for patients in whom brain metastases are diagnosed after induction chemotherapy.     

Resection of brain metastases from colorectal carcinoma in 73 patients

BACKGROUND: At the time of diagnosis of colorectal carcinoma, 2-3% of patients are likely to be harboring brain metastases, and another 10% of patients will develop brain lesions during the course of their disease. The purpose of this study was to examine the clinical course of a group of patients with metastatic brain disease who underwent surgical resection in a single institution. The authors believe this information will be useful for establishing prognostic factors and for clinical decision making. METHODS: Between 1974 and 1993, 709 consecutive patients underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cancer Center. Seventy-three patients had histologically confirmed colorectal carcinoma. The medical records of these patients were reviewed retrospectively, and the data were analyzed by univariate and multivariate analysis. RESULTS: The median age of the 43 women and 30 men was 61.5 years. The median interval from the time of diagnosis of the primary tumor and the development of brain metastases was 27.6 months. The primary colorectal tumor was resected in all patients, and the median survival from the day of surgery was 38 months. The median survival from the time of craniotomy was 8.3 months. The 1-year and 2-year survival rates were 31.5% and 6.8%, respectively. Postoperative mortality was 4%. Gender, presence of multiple metastases, presence of lung lesions, and adjuvant brain radiation after craniotomy appeared to have no impact on survival as determined by multivariate Cox analysis. Only the presence of cerebellar brain metastases was associated with decreased survival. CONCLUSIONS: The results of this series, which the authors believe is the largest series of resected brain metastases from colorectal carcinoma published to date, indicate that surgical resection may increase the survival of these patients. Analysis of prognostic factors shows that infratentorial tumor location is associated with a poorer survival compared with supratentorial tumor location (5.1 months vs. 9.1 months; P < 0.002). In patients with recurrent brain disease, repeated resection is a worthwhile consideration because it may prolong survival compared with patients who do not undergo re-resection.     

Surgical treatment of brain metastases. Clinical and computerized tomography evaluation of the results of treatment

The results of treatment of brain metastases in a series of 125 patients who underwent surgery with or without postoperative radiation from 1978 through 1982 were analyzed. The major sites of primary tumor included the lung (40%), melanoma-skin (11%), kidney (11%), colon (8%), soft tissue sarcoma (8%), breast (6%), and a variety of others (15%). At the time of craniotomy, disease was considered limited to the central nervous system in 63 patients (50%). After surgery, 83 patients (66%) were neurologically improved, and 26 (21%) had their deficits stabilized. The overall median survival was 12 months, and 25% lived 2 years. Eight patients (12%) are alive 5 years or more following surgery. Survival varied with site of primary tumor, location of brain metastasis, extent of systemic disease, and neurologic deficit at time of craniotomy. Over a follow-up period ranging from 18 months to 6 years, 42 patients (34%) developed either local recurrences or other sites of brain metastases. These data suggest that although craniotomy followed by radiation is highly effective in the initial treatment of selected patients with brain metastases, alternate therapies require investigation in view of the high central nervous system relapse rate in long-term survivors.     

Clinical picture, diagnosis and treatment of the brain lesions in lymphosarcomas

The study group included 11 patients with brain metastases of disseminated lymphosarcoma. The most common clinical course was progression of the disease which manifested itself in the advancement of general cerebral symptoms as well as focal ones indicative of hemisphere, subcortex or cerebral trunk involvement. High single intravenous doses of cyclophosphamide and rubomycin and radiotherapy or their combination appeared highly effective in cases of brain specific involvement: complete or partial regression of neurologic symptoms was observed in 7 and 3 patients, respectively. Radiation treatment was followed by COP, COAP or CAMP polychemotherapy to curb extracerebral disease progression. Low median survival of patients with brain metastases (5.1 months) was due to extracerebral tumor progression. However, brain metastases were not immediate death-causing factors.     

Clinical outcome of hypofractionated conventional conformation radiotherapy for patients with single and no more than three metastatic brain tumors, with noninvasive fixation of the skull without whole brain irradiation

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated conventional conformation radiotherapy (HCCRT) with noninvasive fixation of the skull on patients with single or several brain metastases. METHODS AND MATERIALS: The subjects were 44 patients who had three or fewer brain metastases (26 solitary, 18 multiple). Treatment was conducted on 65 metastases by rotational conformal beam or multiple fixed coplanar beams with a standard linear accelerator. The planning target volume consisted of the tumor and a 1-cm safety margin. The median isocentric dose was 24 Gy (range, 18-30 Gy) in 3-5 fractions. Whole-brain irradiation was not applied as an initial treatment. RESULTS: Actuarial local tumor control rates at 6 months and 1 year were 78.4% and 71.9%, respectively. In-field recurrence was noted in 10 of 65 tumors, and repeat HCCRT was applied in 5 tumors. Actuarial overall survival rates at 1 year, 2 years, and the median survival time were 50.8%, 24.1%, and 5.8 months, respectively. The patients with an active primary cancer and poor performance status had a poorer prognosis than those without those factors. Actuarial freedom from second brain metastases rates at 6 months, 1 year, and 2 years were 86.6%, 69.0%, and 40.9%, respectively. Second brain metastases were observed in 9 of 44 patients. Lung adenocarcinomas had a higher risk of second brain metastasis than others. Treatment-related severe early or late complications were not observed in this series. CONCLUSIONS: Hypofractionated conventional conformation radiotherapy achieved sufficient tumor control and survival. The results suggest that HCCRT would be one of the alternatives for patients with either solitary or several brain metastases.     

Carcinoid metastasis to the brain

BACKGROUND: Carcinoid tumors rarely metastasize to the brain. The objectives of the current study were to assess the frequency of brain metastasis from carcinoid tumors, determine correlates of survival, and describe treatment modalities and their outcomes. METHODS: Between January 1977 and December 2003, 1633 patients with a carcinoid tumor were registered at The University of Texas M. D. Anderson Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis. RESULTS: The median age at the time patients were diagnosed with brain metastasis was 60 years. The metastases were treated with whole-brain radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent surgical resection, 7 of whom (29%) also received WBRT. The median survival time for the entire cohort after diagnosis of the primary tumor was 2.3 years (95% confidence interval [CI], 0.5-4.1 years), and the median survival time after the diagnosis of brain metastasis was 10.0 months (95% CI, 4.0-16.0 months). The longest median survival observed after the diagnosis of brain metastasis (3.2 years) occurred in patients who underwent resection and received WBRT. In the multivariate analysis, the adjusted rate ratio for comparison of all treatments versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3-26.1; P = 0.024). A positive effect of surgery followed by WBRT on the duration of survival was detected in patients with a single metastasis (P = 0.084) as well as in those with multiple metastases (P = 0.018). CONCLUSIONS: Prolonged survival was observed in patients < 65 years old as well as in those who underwent surgery and received WBRT in comparison with other treatments. Whenever feasible, neurosurgical resection followed by WBRT seems to be the indicated treatment in patients with brain metastases from carcinoid tumors.     

Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review

The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.     

Brain metastases from gynecological cancers: factors that affect overall survival

We retrospectively reviewed factors that affected overall survival for patients with gynecological cancers that had metastasized to the brain. Between January 1985 to November 1999, we treated 25 patients with brain metastases from gynecological malignancies (cervix n=6, endometrium n=10, and ovary n=9). Various patient and tumor characteristics were identified and analyzed for their significance. Median age was 46 years old (range, 37-78 years) with the majority of tumors being adenocarcinoma (20/25 patients). The treatment consisted of whole brain radiation therapy (WBRT) in 11 patients, focal therapy (surgery and/or stereotactic radiosurgery [SRS]) in 6 patients, and combination therapy (WBRT and surgery and/or SRS) in 8 patients and resulted in median survivals of 6 months, 7 months and 11 months, respectively. Overall median survival was 7.3 months (range, 1 to 88 months). Cause of death was systemic in 9, neurologic in 8 and progression of primary in 2. Those with single lesions had better median survivals compared to those with multiple lesions (17 months vs. 3 months, p=0.017). Our results suggest that patients with a single lesion had improved outcomes. We encourage enrollment of patients with brain metastases onto prospective clinical trials.     

Stereotactic radiosurgery for multiple brain metastases from breast carcinoma

BACKGROUND: The current study analyzed the feasibility and outcome of stereotactic radiosurgery (SRS) for treatment of brain metastases from breast carcinoma. METHODS: During an 8-year period, 151 patients with a combined total of 620 brain metastases from breast carcinoma underwent 197 outpatient SRS procedures. Sixty-three percent of all patients had multiple brain metastases. The median tumor volume was 2.2 cm(3) (range, 0.1-20.9 cm(3)). The mean prescribed tumor dose was 19 +/- 4 grays. Local/distant tumor recurrences were treated with additional radiosurgical therapy for patients with stable systemic disease. All patients were categorized according to the Radiation Therapy Oncology Group classification. Survival time and freedom from local tumor recurrence were analyzed using the Kaplan-Meier method. Prognostic factors were identified using the Cox proportional hazards model. RESULTS: The overall median survival duration was 10 months after SRS. Ninety-four percent of patients did not experience local brain tumor recurrence after radiosurgery. In addition, 70.2% of patients did not have disease recurrence in the brain. Most patients died of systemically progressing malignancy. A Karnofsky performance score > 70 and recursive partitioning analysis Class I were related to prolonged survival in the univariate and multivariate analyses. Age, whole-brain radiotherapy, surgery, number of metastases, chemotherapy, and latency period from diagnosis of the primary tumor to the development of brain metastases did not reach prognostic relevance in the multivariate model. Patients with RPA I, II, and III survived 34.9, 9.1, and 7.9 months, respectively. There was no treatment related permanent morbidity and mortality. The transient morbidity rate was 17%. Sixteen patients exhibited symptomatic transient complications related to treatment. CONCLUSIONS: The results of the current study indicate that SRS is a feasible treatment concept for selected patients with multiple brain metastases from breast carcinoma.     

Radiosurgery in the treatment of malignant brain tumors

Brain metastases are an attractive target for radiosurgery. Over a period of 6 years, 400 patients with brain metastases have been treated with radiosurgery. Of these patients, 61% had solitary brain metastases and 39% had multiple brain metastases. Local control was achieved in 90% and improvement of severe neurological symptoms in 76%. The median survival time was 8 months. The significant prognostic factors for survival in patients with solitary brain metastases were age, Karnofsky performance status, severity of symptoms, extent of progressive malignant disease outside the brain, histology, interval between diagnosis of primary tumor and brain metastasis, and minimum applied dosage. The significant prognostic factors in patients with multiple brain metastases were sex, Karnofsky performance status and presence of progressive disease outside the brain.     

Radiosurgery in the treatment of malignant brain tumors

Brain metastases are an attractive target for radiosurgery. Over a period of 6 years, 400 patients with brain metastases have been treated with radiosurgery. Of these patients, 61% had solitary brain metastases and 39% had multiple brain metastases. Local control was achieved in 90% and improvement of severe neurological symptoms in 76%. The median survival time was 8 months. The significant prognostic factors for survival in patients with solitary brain metastases were age, Karnofsky performance status, severity of symptoms, extent of progressive malignant disease outside the brain, histology, interval between diagnosis of primary tumor and brain metastasis, and minimum applied dosage. The significant prognostic factors in patients with multiple brain metastases were sex, Karnofsky performance status and presence of progressive disease outside the brain.     

立体定向放疗与全脑放疗在多发脑转移瘤治疗中的作用分析

目的 总结立体定向放疗(SRT)加或不加全脑放疗(WBRT)治疗多发脑转移瘤的结果,探讨WBRT和SRT在多发脑转移瘤治疗中的作用。方法 1995—2010年收治的98例新诊断的多发(2~13个病灶)脑转移瘤患者。单纯SRT44例,WBRT加SRT54例。剂量分割模式依据转移瘤部位、体积及是否WBRT。用Kaplan-Meier法计算生存率,Cox回归模型进行各因素预后分析。中位生存期(MST)为从脑转移瘤放疗开始至各种原因所致死亡的时间的中位数。结果 全组患者中位随访时间12个月,随访率为100%。全组MST为13.5个月,其中SRT组、WBRT加SRT组的分别为13.0、13.5个月(χ²=0.31,P=0.578)。多因素分析显示仅卡氏评分(χ²=6.25,P=0.012)、原发灶诊断及脑转移瘤诊断间隔时间(χ²=7.34,P=0.025)和颅外病变情况(χ²=4.20,P=0.040)是预后因素。结论 SRT是多发脑转移瘤患者有效治疗手段,单纯SRT可取得与WBRT加SRT相似的生存期。首程SRT可能是多发脑转移瘤患者的另一治疗选择。     

An evaluation of the surgical management of melanoma of the brain

Thirty-two patients with histologically proved metastatic malignant melanoma of the brain were evaluated. Intracranial surgery was performed in 19 and was considered not indicated in 13 patients. Following intracranial surgery, satisfactory improvement in neurologic deficits was observed in 14 (74%) patients. The median survival after occurrence of brain metastases was 5–6 months (1 – 15 months) for the surgical group; and for the nonsurgical group, patients with multiple brain metastases and multiple visceral involvement did not survive beyond a median of 1 month (range 0.5–6 months). Intratumor hemorrhage with substantial intracerebral hematoma was present in 7 (41%) out of 17 craniotomies. The overall incidence of intratumor hemorrhage found at autopsy was 59% for the entire series. Among ail the cases with intratumor hemorrhage, only 2 patients who received chemotherapy after craniotomy developed thrombocytopenia with fatal intracranial hemorrhage. The latter cause-and-effect correlation could not be assessed in the other patients. As a result of this retrospective study, we have observed that patients with malignant melanoma and evidence of single brain metastasis without multiple visceral involvement seemed to benefit more from palliative surgery. Moreover, intratumor hemorrhage was a frequent occurrence and should be considered in the differential diagnosis of a patient with malignant melanoma and rapid deterioration of neurologic deficits.     

立体定向放射治疗肺癌脑转移疗效分析

目的探讨不同放射治疗方法对肺癌脑转移的疗效.方法176例由病理学证实的肺癌脑转移患者分为4组:单纯全脑放疗(WBRT)组、全脑放疗加立体定向放射外科(WBRT SRS)组、单纯立体定向放射治疗(SRT)组、全脑放疗加立体定向放射治疗(WBRT SRT)组.SRS治疗单次靶区平均周边剂量8～20Gy,总剂量20～32Gy;SRT治疗单次靶区平均周边剂量2～5Gy,总剂量25～60Gy;WBRT1.8～2Gy/次,总剂量30～40Gy.结果四组的局部控制率分别为47.0%、87.7%、86.5%和78.0%;中位生存期分别为5.0,11.0,11.5和10.0个月;局部无进展生存期分别为3.33,8.33,9.33和7.67个月;颅脑无新病灶生存期分别为4.11,8.57,9.03和6.12个月.在死因分析中,WBRT组死于脑转移的比率为57.6%,较其他三组高.而WBRT SRS组的晚期放射反应的发生率为12.2%,较其他组高.结论肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗,治疗失败后再行挽救性全脑照射或立体定向放疗.对于多发脑转移,全脑放疗加立体定向放射治疗(WBRT SRT)在提高生存率以及减少并发症方面优于其他治疗方法.     

多发脑转移瘤放疗方式与预后

 目的 探讨多发脑转移瘤放疗方式与预后的关系。方法 112例多发脑转移瘤患者分别采用全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗，分析不同放疗方法的生存期及脑转移致死率。结果 全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗组的中位生存期分别为3．8、7．8及8．0个月。脑转移致死率全脑照射组67．7％，立体定向放射治疗组15．7％，全脑照射结合立体定向放射治疗组11．6％。结论 立体定向放射治疗可使脑转移灶较少的患者局控率提高，生存期延长。     

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.