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.     

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.     

Outcome of R1 resection in patients undergoing pancreatico-duodenectomy for pancreatic cancer

Background

Pancreatico-duodenectomy (PD) is the only potentially curative treatment for pancreatic cancer, but most surgeons are reluctant to perform a palliative resection. The aim was to define the outcome for microscopically incomplete PD (R1).

Methods

Ninety-nine consecutive patients underwent laparotomy to perform PD. Sixty-seven patients were resected and 32 underwent palliative bypass (PSB) because of locally advanced disease.

Results

Of the 67 PD, 27 were classified as R0 and 40 as R1. Median survival for R0, R1 and PSB were 24, 18 and 9 months, respectively. Survival in the PSB group was 34% at 1 year and 0% at 2 years. 1-, 2- and 5-year survival in the R0 and R1 groups was 79% and 70%, 48.3% and 39.1%, 21.5% and 9.9%, respectively. Compared to PSB, both other groups were less likely to die over follow-up (p = 0.002). Survival was not significantly different between the R0 and R1 groups (p = 0.21). Perioperative morbidity and mortality were similar in the PD and PSB groups (29.9% and 3.0% vs 31.3 and 3.1%, respectively, p = 1.00).

Conclusions

Better survival in the resection group and similar perioperative risk would support the decision to perform PD even when there is the possibility of incomplete microscopic clearance.     

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。     

术中放疗联合区域动脉灌注治疗晚期胰腺癌

目的 评价术中放疗联合区域动脉灌注治疗晚期胰腺癌的效果。方法 17例晚期胰腺癌减黄手术时行IORT，胃网膜右动脉插管采用5—氟尿嘧啶(5—FU) 表阿霉素(E—ADM) 丝裂霉素(MMC)方案行区域灌注化疗，其中6例术后行外照射放疗。结果 疼痛缓解率70．59％(12／17)，临床受益指数35．29％(6／17)，局部病灶部分缓解23．53％(4／17)。中位生存11个月，1年生存率35．29％(6／17)。结论 IORT结合区域动脉灌注化疗毒副作用轻微，可明显提高临床受益率，延长生存期。     

Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection

BACKGROUND AND OBJECTIVES: Streak type, defined by the presence of white streaks at the advancing margin of tumor invasion; focal dedifferentiation, seen as undifferentiated cancer cells with an infiltrative pattern at the invasive front; and perineural invasion have been demonstrated to be prognostic factors in patients with colorectal cancer. We performed a prospective study to examine the usefulness of these features as prognostic factors. METHODS: We reviewed a total of 391 patients who underwent curative surgery for colorectal cancer between May 1997 and June 1999. Of these, 50 patients with multiple cancers were excluded, and a total of 341 patients were finally entered into the study. RESULTS: Of the prognostic factors investigated, depth of invasion, lymph node status, lymphatic invasion, venous invasion, growth type, streak type, focal dedifferentiation, and perineural invasion were significant prognostic factors in univariate analysis. In multivariate analysis, lymph node status, depth of invasion, and perineural invasion were significant prognostic factors. The survival of patients with perineural invasion was significantly poorer than that of patients without perineural invasion in both stage II and III cancer. CONCLUSIONS: Perineural invasion status can be used to facilitate the selection of colorectal cancer patients for adjuvant chemotherapy and should be described in routine pathology reports.     

Survival benefit of adjuvant chemoradiotherapy for positive or close resection margin after curative resection of pancreatic adenocarcinoma

BackgroundThis study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma.MethodsFrom 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group).ResultsLocoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS.ConclusionsAdjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.     

Preoperative systemic inflammation predicts postoperative infectious complications in patients undergoing curative resection for colorectal cancer

The presence of systemic inflammation before surgery, as evidenced by the glasgow prognostic score (mGPS), predicts poor long-term survival in colorectal cancer. The aim was to examine the relationship between the preoperative mGPS and the development of postoperative complications in patients undergoing potentially curative resection for colorectal cancer. Patients (n=455) who underwent potentially curative resections between 2003 and 2007 were assessed consecutively, and details were recorded in a database. The majority of patients presented for elective surgery (85%) were over the age of 65 years (70%), were male (58%), were deprived (53%), and had TNM stage I/II disease (61%), had preoperative haemoglobin (56%), white cell count (87%) and mGPS 0 (58%) in the normal range. After surgery, 86 (19%) patients developed a postoperative complication; 70 (81%) of which were infectious complications. On multivariate analysis, peritoneal soiling (P<0.01), elevated preoperative white cell count (P<0.05) and mGPS (P<0.01) were independently associated with increased risk of developing a postoperative infection. In elective patients, only the mGPS (OR=1.75, 95% CI=1.17–2.63, P=0.007) was significantly associated with increased risk of developing a postoperative infection. Preoperative elevated mGPS predicts increased postoperative infectious complications in patients undergoing potentially curative resection for colorectal cancer.     

胃癌术后复发转移类型及其对放疗靶区设计的临床意义

目的总结胃癌术后复发转移类型和部位,探讨术后预防性放疗的照射范围。方法回顾性分析139例胃癌根治术后出现复发转移的患者,所有患者出现复发转移均经CT影像学检查作出临床诊断,其中残胃和吻合口复发36例均由病理组织学证实。结果139例中65例为多部位复发转移,其中残胃复发为9.4%（13/139）,吻合口复发为16.5%（23/139）,肝脏转移为38.8%（54/139）,腹腔淋巴结转移为62.6%（87/139）,腹壁转移为11.5%（16/139）,盆腔种植为7.9%（11/139）,肺转移为2.9%（4/139）。腹腔淋巴结转移患者中胃周淋巴结转移为13.8%（12/87）,胰周淋巴结转移为31.0%（27/87）,腹主动脉旁淋巴结转移为55.2%（48/87）,其中原发于胃底贲门癌患者腹腔淋巴结转移仅为4.6%（4/87）,原发于胃体部的胃癌患者腹腔淋巴结转移为32.2%（28/87）,原发于胃窦部的胃癌患者腹腔淋巴结转移为63.2%（55/87）。结论胃癌患者根治术后局部复发转移的部位主要发生在区域淋巴结,并以胰周和腹主动脉旁淋巴结转移多见,胃体和胃窦部肿瘤患者根治术后较易出现淋巴结转移,因此术后预防性放疗应主要针对胃体和胃窦部的胃癌患者,放射野应包括胰周和腹主动脉旁淋巴结范围。     

术中放疗应用于胰腺癌的疗效与安全性meta分析

目的比较术中放疗(IORT)联合常规治疗(手术联合放化疗)与单纯常规治疗对胰腺癌疗效与安全性等预后的影响。方法全面检索PubMed、Cochrane Library、Web of Science、Embase、维普、知网、万方、中国生物医学文献服务系统(SinoMed)等数据库收录的文献, 对符合纳入标准的文献进行筛选并提取数据, 采用RevMan 5.4软件进行meta分析。结果共纳入11项研究, 共813例患者, 根据合并结果显示, 与单纯常规治疗相比, IORT联合常规治疗可提高胰腺癌的总体生存率(HR=0.66, 95%CI为0.54～0.81, Z=4.03, P<0.001), 且不会增加治疗相关不良反应(OR=1.00, 95%CI为0.69～1.46, Z=0.01, P=0.99), 但不能使局部控制率获益(HR=0.56, 95%CI为0.31～1.01, Z=1.93, P=0.05)。结论 IORT联合常规治疗组胰腺癌患者总体生存率明显优于单纯常规治疗组, 两组的不良反应无差异, 值得临床推广应用。     

胰腺癌根治术与术后辅助外放疗的疗效比较

目的 探讨术后放疗对胰腺癌患者生存率的影响.方法 44例胰腺癌患者分为手术组(根治性外科切除)和手术+放疗组(根治性外科切除后接受外放疗),比较两组患者的治疗效果.结果 手术组平均生存期为453 d,中位生存期为379 d.手术+放疗组平均生存期789 d,中位生存期为665 d.手术组和手术+放疗组的1、3、5年生存率分别为46.3%、8.3%、4.2%和65.2%、20.2%、14.1%,手术+放疗组优于手术组(P=0.017).手术+放疗组局部复发率及区域淋巴结转移率低于手术组(P<0.05),且并发症发生率并不高于手术组(P>0.05).结论 胰腺癌根治术后结合放疗有助于改善患者生存期.     

Resection-line involvement in gastric cancer patients undergoing curative resections: implications for clinical management.

BACKGROUND: Resection-line involvement has been suggested as an important prognostic factor for gastric cancer. METHODS: The relationship between resection-line involvement and outcome was examined in patients undergoing potentially curative resection for gastric cancer. RESULTS: Tumor positive resection-lines were seen in 22 of the 259 evaluable patients (8.4%). Resection-line involvement was associated with tumor location (P = 0.01) and tumor differentiation (P = 0.02). Positive margins were associated with worse survival. However, if both groups of patients are stratified according to lymph node metastases, resection-line involvement determined a shorter survival only in patients with N0 stage disease. CONCLUSIONS: Our data suggest, in the case of positive margins, that re-laparatomy should be considered only for patients with N0 stage disease, while patients with metastatic lymph nodes should be watched closely without the need for a more aggressive surgical approach.     

Prognostic factors in patients undergoing curative irradiation for breast cancer

We have evaluated 147 patients who received primary curative irradiation for breast cancer to determine if there were any common factors that predisposed to failure. There were 10 local recurrences, for an overall local control rate of 93.2%, with a 2 to 16 year follow-up. Disease-free survivals were 85% in Stage I, 69% in Stage II, and 50% in Stage III. Age seemed to be a determinant, with a 31.6% local recurrence rate in women under 50 vs. a 3.1% rate of local recurrence in women age 50 or older when treated. We have also noted a correlation between the radiation dose and local recurrence, with a recurrence rate of 9.1% following a dose of 6000 rad or less, vs. a rate of 4.7% with a dose of 6400 rad or more. The size of the primary carcinoma and the status of the axillary lymph nodes, each considered individually, were not significant prognostic factors. There was no relationship between recurrence and the performance of an axillary dissection. There was evidence suggesting that the recurrence rate was lower when a wide local excision was performed, compared to a lesser procedure. Multiple foci of carcinoma and a high nuclear grade appear to have a poor prognosis. Five of the recurrences occurred early (under 2 years) and three of these were accompanied by fatal distant metastases. None of the five patients with late recurrences (37 to 116 months) developed metastatic disease, suggesting that late recurrences may have a better prognosis.     

乳腺癌保乳手术加术中放疗40例临床分析

目的:研究乳癌保乳手术中采用术中放疗对疾病治疗的远期疗效。方法:对我院1998年1月~1999年12月40例Ⅰ-Ⅱb期的乳腺癌患者行肿瘤广泛切除 腋窝淋巴结清扫术 术中放疗术。结果:经5年随访观察,40例患者仅1例局部复发,其余患者均健在,无远处转移,无明显放疗反应,双乳对称,外形美观。结论:乳腺癌保乳治疗 术中放疗对于患者的局部复发率及远期生存率均有较明显的影响,降低了局部复发率。     

The effects of bevacizumab on postoperative complications in patients undergoing colorectal and pancreatic cancer resection

Bevacizumab (Avastin?; rhuMab VEGF), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has seen increased use in the perioperative treatment of colorectal and pancreatic cancer. Little is known, however, regarding its impact on surgical outcomes in patients undergoing resection. The objective of this review was to examine if the addition of bevacizumab to existing neoadjuvant regimens increases morbidity after cancer resection. J. Surg. Oncol. 2010;102:539–542. © 2010 Wiley‐Liss, Inc.     

Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases

BackgroundThe benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer.MethodsAmong 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery.ResultsThe overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival.ConclusionsSurgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.     

Imaging-guided curative surgical resection of pancreatic cancer in a xenograft mouse model

Pancreatic cancer is the fourth leading cause of cancer related deaths in North America. The poor survival statistics are due to the fact that there are no reliable tests for early diagnosis and no effective therapies once metastasis has occurred. Surgical resection is the only curative treatment for pancreatic cancer; however, only less than 15% of the patients are eligible for surgery at diagnosis. New therapies are urgently needed for this malignant disease. And combinational therapy including surgery, chemotherapy and molecular targeted therapy may further improve the efficacy of individual therapies. However, a reliable mouse model which mimics the human disease and can be used for testing the surgical treatment and surgery-based combinational therapy is not available. In this study, we have established a mouse model for curative surgical resection of pancreatic cancer. Human pancreatic cancer cells were used to create orthotopic xenografts in nude mice, distal pancreatectomy was performed using imaging-guided technology to remove the pancreatic tumors, and sham surgery was performed in the control group. All mice survived the operation and no complication was observed. Surgical resection at early stage improved the survival rate and quality of life of the mice compared with the sham surgery and surgical resection at the late stage. If combined with other therapies such as chemotherapy and molecular targeted therapy, it could further improve the outcome of pancreatic cancer. This mouse model is a useful tool to study the surgical therapy and the tumor recurrence of pancreatic cancer, and could potentially impact the therapeutic choices for this deadly disease.