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。     

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.     

A case report of intraabdominal bleeding in unresectable pancreatic cancer after intraoperative radiotherapy

We report a death case of 56-year-old male with unresectable pancreatic cancer. Its diagnosis was locally-advanced cancer of pancreatic head (Stage IVa) in February 2006. However, he desired no medical treatment until obstructive jaundice (T-Bil 25 mg/dL) appeared. In September 2006, endoscopic biliary metallic stenting was performed and the obstructive jaundice had improved. In November 2006, systemic chemotherapy (S-1 +gemcitabine) was performed. After the chemotherapy, vomiting had appeared because of duodenal stenosis. In December 2006, gastrojejunostomy and intraoperative radiotherapy (IORT) were performed, and the dose of oxicodon was decreased. However, in January 2007, he was suddenly in a state of bleeding-shock and died because of intraabdominal bleeding. The autopsy demonstrated the rupture of splenic pseuoaneurysm due to necrotizing pancreatitis of pancreatic tail, and cancer of pancreatic head was almost viable and IORT was not effective.     

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.     

External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer

One hundred fifty-nine patients with unresectable but localized pancreatic cancer, as defined at exploratory laparotomy, were treated at the Mayo Clinic between February 1974 to April 1985. Postoperative therapy consisted of 4000 to 6000 cGy external beam irradiation (XRT) alone in 122 patients or 4500 to 5500 cGy XRT in combination with an intraoperative electron boost in 37. In addition, 132 (both groups) received 5-fluorouracil (5-FU) chemotherapy. Local control (LC) at 1 year was 82% with XRT + intraoperative radiation therapy (IORT) versus 48% with XRT and 66% versus 20% at 2 years respectively (P less than 0.0005). Due to the high incidence of hematogenous and/or peritoneal spread in both groups (abdominal failure in 54 and 56% of patients at risk), the decreased frequency of local progression did not translate into an improved survival. Neither median nor long-term survival of the two treatment groups (XRT versus XRT + IORT) was statistically different (median 12.6 months versus 13.4 months, P = 0.25). With tumor arising in the head of the pancreas, survival at 2 years was 18% as opposed to 0% for other locations (P less than 0.01). On the basis of a Cox multivariate analysis, no other treatment or prognostic factor significantly altered survival. Until the problem with systemic failure (usually abdominal) can be resolved, the median and long-term survival of patients with pancreatic carcinoma is likely to remain unchanged. Since IORT appears to improve local control, we will continue to utilize IORT in phase 1, 2 studies which also attempt to decrease the incidence of abdominal failures. Even with IORT + XRT combinations, the incidence of local progression is excessive and radiation dose modifiers need to be evaluated.     

Residual, unresectable, or recurrent colorectal cancer: external beam irradiation and intraoperative electron beam boost +/- resection

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.     

Intraoperative and external beam radiotherapy in advanced resectable gastric cancer: technical description and preliminary results

Twenty-two patients with resectable gastric cancer treated with intraoperative radiotherapy and external beam irradiation, in a Phase I-II oriented study, were analyzed. Tumor Stages were III & IV in 18 cases (82%). Tumor histology was described as diffuse undifferentiated type in 14 cases (63%). Following surgical resection of the primary tumor, IORT 15 Gy was delivered in the celiac axis area, using high energy electron beams ranging from 9 to 20 MeV. External beam irradiation fields covered the draining nodal areas of the upper abdomen and the gastric bed. There were no postoperative deaths. Reversible postoperative complications were recorded in 14 patients (63%). Long term complications observed were vertebral collapse and liver hemangiomas. First sites of recurrence have been: hepatic hilum (three cases), peritoneum combined with central axis nodes (two cases), liver metastasis (one case), and lung metastasis (one case). Survival data shows a follow-up period ranging from 1+ to 33+ months, with a median survival time for the entire group of 13+ months. At the time of this report, 16 patients (72%) are still alive and six have died (four from progressive malignant disease and two from intercurrent disease). From this preliminary data, it can be concluded that a combined approach with surgical resection, intraoperative radiotherapy, and external beam irradiation is feasible in advanced gastric carcinoma, and is not limited by toxicity or any complications observed. Despite this intense loco-regional therapeutic approach, the upper abdominal failure rate has been demonstrated in 22% of the cases.     

The role of intraoperative radiotherapy in pancreatic cancer

In single-institution studies, IORT at appropriate doses seems to safely improve local control in patients who have locally advanced pancreatic cancer, compared with historical controls. IORT also has been a component of adjuvant treatment programs that have led to excellent local control in resected patients. When considering the use of IORT, it is essential to have an understanding of the physical characteristics of the electron beam and how it can differ with the use of flat and beveled applicators. Although apparent improvement in local control with the use of IORT seems to have produced some improvement in median survival rates, high rates of distant failure continues to prevent a significant improvement in long-term survival. Because effective local control in patients with unresectable pancreatic cancer is a prerequisite to the development of curative therapies, the development of improved systemic therapies in patients with locally advanced pancreatic cancer will likely make local therapies such as the use of IORT even more important in the future.     

Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer

PURPOSE: Full-dose gemcitabine and concurrent radiotherapy is a promising treatment approach in unresectable pancreatic cancer. This study was conducted to assess the pattern of failure and toxicity associated with the use of conformal treatment volumes, omitting prophylactic lymph node irradiation. METHODS AND MATERIALS: Seventy-four patients with locally advanced pancreatic cancer were treated between 1997 and 2005 with full-dose (1000 mg/m(2), Days 1, 8, and 15) gemcitabine and concurrent radiotherapy (36 Gy [median] in 15 daily fractions). The planning target volume (PTV) was limited to the gross tumor volume (GTV) plus 1-cm margin. Patient computed tomography (CT) scans were systematically reviewed to determine the pattern of failure. Kaplan-Meier and Cox-regression models were used to analyze freedom from local progression (FFLP), distant failure, overall survival (OS), and toxicity. RESULTS: With a median follow-up of 10.6 months (20.6 months in living patients), the 1-year and 2-year FFLP rates were 64% and 38%, respectively. Four patients (5%) failed in the peripancreatic lymph nodes (3 in-field and 1 marginal failure). Median OS was 11.2 months. Analyzed as a time-dependent covariate, local failure was a significant predictor of OS (p = 0.0074). Sixteen patients (22%) had significant gastrointestinal (GI) toxicity (> or = Grade 3). PTV correlated with significant GI toxicity (p = 0.007). CONCLUSIONS: Freedom from local progression in unresectable pancreatic cancer is suboptimal. In conjunction with full-dose gemcitabine, the use of conformal fields encompassing only the GTV helps reduce toxicity and does not result in marginal failures. Our findings provide rationale for intensification of local therapy in conjunction with more effective systemic therapy.     

术中放疗在胰腺癌中的应用进展

虽然胰腺癌手术方式和放、化疗方案有了长足发展,但胰腺癌仍然是致死率最高的恶性肿瘤,5年总生存率仅约为4%。研究表明,胰腺癌局部复发进展是致死率高的重要原因,局部切除后失败率仍高达50%~80%。所以,如何提高胰腺癌局部控制率一直是关注的热点。由于胰腺临近的器官、组织(如骨髓、脊髓、肾脏、肝脏、肠等)较多从而限制外照射(EBRT)剂量。提高局部控制率和减少治疗毒副反应是未来治疗的趋势。术中放疗有剂量学和直视下治疗的优势,已越来越多的应用于胰腺癌的治疗,成为综合治疗中的重要部分。本文整理、总结了近年来有关胰腺癌术中放疗临床研究结果,以期为广大临床医生提供参考。     

Comparison of mammographic findings after intraoperative radiotherapy or external beam whole breast radiotherapy

Background

The TARGIT (TARGeted Intraoperative Radiotherapy) trial was designed to compare local recurrence and complication rates in breast cancer patients, prospectively randomised to either EBRT (external beam whole breast radiotherapy) or a single dose of IORT (intraoperative radiotherapy). The aim of our study was to compare follow-up mammographic findings, ultrasound and biopsy rates in each group.

Methods

Follow-up imaging and breast biopsies of women from one centre participating in the TARGIT-A trial were independently reviewed by two radiologists blinded to the radiotherapy treatment received.

Results

The cohort consisted of 141 patients (EBRT n = 80/IORT n = 61). There was no significant difference in the patient or disease characteristics of the two groups. The number of follow-up mammograms and length of follow-up was similar (EBRT/IORT n = 2.0/2.4; 4.3yr/5.1yr; p = 0.386 χ² test). There were no significant differences in mammographic scar or calcification appearances of the post-operative site. Generalised increase in breast density and skin thickening were more common in the EBRT compared to the IORT group (p = 0.002; p = 0.030, χ² test respectively). A trend towards additional ultrasound at follow-up was observed in the IORT group (15 of 61 [24.6%] versus 11 of 80 [13.8%]), however this was not statistically significant (p = 0.100 χ² test). No disease recurrence was demonstrated on any of the breast biopsies taken. Only one biopsy was reported as fat necrosis in the IORT group.

Conclusions

Mammographic changes were more common following EBRT, although more additional follow-up ultrasounds were performed in the IORT group. IORT is not detrimental to subsequent radiological follow up.     

The role of external beam radiotherapy in the treatment of small-cell lung cancer

External beam radiotherapy plays a significant role in the treatment of small cell lung cancer. In patients with limited stage disease (LD), thoracic irradiation improves locoregional tumor control, increases the percentage of patients achieving a complete response (CR), and produces significant increases in survival. As a result, combined modality therapy (chemotherapy/radiotherapy) is considered the treatment of choice in patients with LD. Radiotherapy plays a less significant role in extensive diseased patients, but nonetheless increases CR in the chest and has palliative benefit. Elective cranial irradiation decreases the development of central nervous system failure, thereby improving the quality of life of many patients. Its use, however, should be restricted to patients achieving CR to therapy and doses should be modest. Both whole-body and hemi-body irradiation have significant activity against the disease but should be considered strictly investigational.     

A pilot study of preoperative continuous infusion 5-fluorouracil, external microwave hyperthermia, and external beam radiotherapy for treatment of locally advanced, unresectable, or recurrent rectal cancer

PURPOSE: To determine the feasibility of combining external beam radiotherapy, continuous infusion 5-fluorouracil (5-FU), and external microwave hyperthermia in patients with locally advanced, unresectable, or recurrent adenocarcinoma of the rectum. METHODS AND MATERIALS: From 7/95 through 2/99, 15 patients were enrolled in the study. The treatment regimen consisted of continuous infusion 5-FU 250 mg/m(2)/d 7 days/week beginning on day 1, external beam radiotherapy to the pelvis, 4500 cGy, 180 cGy/d 5 days/week using a 3 or 4-field technique, and external microwave hyperthermia on days 3, 8, 15, 22, and 29. Chemotherapy was stopped on the last day of radiotherapy. Surgical resection, if feasible, was scheduled 3-6 weeks after completing thermochemoradiotherapy. For this regimen to be considered feasible, no more than 2 of the 15 patients should fail to complete therapy due to life-threatening toxicity. Toxicity was scored using National Cancer Institute Criteria. RESULTS: All patients completed the chemoradiotherapy portion of the protocol. Eleven of the 15 patients completed all 5 hyperthermia treatments. Of the 4 patients who did not receive the full course of hyperthermia, only 1 patient had treatment stopped due to life-threatening toxicity. The other 3 patients did not complete hyperthermia due to scheduling errors (n = 2) or patient request (n = 1). Five of 15 patients required a treatment interruption due to toxicity > or = Grade 3. Seven patients experienced lesser degrees of toxicity which did not require treatment interruption. Three patients experienced no side effects. The most common toxicities were dermatitis and diarrhea. Of the 14 patients in whom surgery was planned, 11 (79%) were resectable. There was one pathologic complete response. CONCLUSIONS: It is feasible to deliver thermochemoradiotherapy, as prescribed in this study, to patients with locally advanced, unresectable, or recurrent rectal cancer. The therapy is moderately toxic, with one-third of patients requiring temporary treatment interruptions. The regimen appears active against rectal cancer, and appears to warrant further consideration as a treatment option for this patient population.     

Radiation dose to laterally transposed ovaries during external beam radiotherapy for cervical cancer

The purpose of this study was to estimate the radiation dose to laterally transposed ovaries from external beam radiotherapy for cervical cancer. Dose measurements were performed in a modified humanoid phantom using a 6 MV photon beam. The dependence of the ovarian dose upon the field size, the distance from the primary irradiation field and the presence of wedges or gonadal shielding was determined. For a tumor dose of 45 Gy, ovarian dose was 0.88-8.51 Gy depending on the field size employed and the location of the transposed ovary in respect to the treatment field. Positioning of 7 cm thick shielding reduced the dose to ovary by less than 19%. The use of wedges increased the ovarian dose by a factor up to 1.5. Accurate radiographic localization of the ovaries allows the use of the presented dosimetric results to obtain a reasonable prediction of the ovarian dose.     

适形放射治疗联合热疗治疗晚期胰腺癌的疗效及临床受益反应观察

为了评价适形放疗联合热疗治疗晚期胰腺癌的疗效及临床受益反应,对34例胰腺癌患者给予适形放疗,2Gy/次,5次/周,总剂量50-70 Gy;热疗2次/周,每次60-90 min,共计6次。结果82.4%患者胸背部疼痛明显缓解,临床受益反应有效率91.2%;放疗后2个月复查CT,肿瘤缩小〉25%者76.5%;1、2年生存率分别为38.2%和20.6%。初步研究结果提示,适形放射治疗联合热疗治疗晚期胰腺癌,疗效较好,并发症少,可显著提高患者生活质量,是不能手术患者较好的治疗方式。     

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION: A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS: Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS: Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS: It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.     

Cis-platin and radiotherapy in the treatment of unresectable lung cancer

The goal of this pilot study was to verify the efficacy of the association of cisplatin plus radiotherapy in the treatment of lung cancer. Thirty-seven consecutive patients entered the study. They were treated with radiotherapy (four weekly doses of 2.5 Gy for a total of 50 Gy) and cis-platin once weekly (12 mg/m2). Partial remission was obtained in 15 patients, and 1 patient had a complete remission. Three patients previously inoperable underwent surgical treatment. The actuarial survival curve of the 29 evaluable patients showed a mean survival of 8.5 months. The mean survival of the latter is not evaluable because half of the patients are still alive after 12 to 30 months. No hematologic or renal toxicity was observed with the above schedule.