重视交界性可切除胰腺癌的处理

胰腺癌是预后最差的常见恶性肿瘤之一,2008年全美胰腺癌新发病例数为37680例,死亡病例数为34290例,死亡发病比为0.91,居恶性肿瘤死亡率的第4位,5年生存率＜5%[1].手术切除仍是治疗胰腺癌的主要手段,胰腺癌根治术后5年生存率在15%～25%[2-5].     

潜在可切除性胃癌的新辅助化疗

目的 总结潜在可切除胃癌的新辅助化疗(neoadjuvant chemotherapy,NAC)的现状.方法 通过PubMed,以胃肿瘤、胃癌/癌、新辅助治疗/化疗及术前治疗/化疗为关键词,检索近5年的相关文献.并检索2007及2008年ASCO年会的相关进展.总结NAC在胃癌中的研究现状,评价其必要性和可行性,分析病例选择依据、缓解预测因子及存在的问题和发展方向. 结果共检索随机对照试验7个,其中3个为Ⅲ期试验.已进行的多数研究显示,NAC在胃癌的治疗中是安全、有效和可行的.但生存取得显著改善的NAC随机研究尚少,缺乏严格NAC与单独手术或围手术期化疗与辅助化疗对比的NAC随机研究.如何选择适当的病例、有效的NAC方案和治疗缓解的预测,尚需要解决.结论 NAC在胃癌的治疗中是安全、有效和可行的,但仍需进一步严格的前瞻性随机Ⅲ期试验证实.新的细胞毒性药物和分子靶向治疗可能是将来进展的实质基础.     

Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Background

The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy.

Methods

A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes.

Results

We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable.

Conclusions

In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

     

FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma

Background

Both FOLFIRINOX and gemcitabine/nab-paclitaxel (G-nP) are used increasingly in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA). This study aimed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable (R) and borderline resectable (BR) head PDA.

Methods

A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed. Comparative analysis was performed using inverse-probability-weighted (IPW) estimators. The end points of the study were overall survival (OS) and an 80% reduction in CA19-9 with NAT.

Results

In this study, 193 patients were analyzed, with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP (p?=?0.214). The patients who received FOLFIRINOX were younger and had fewer comorbidities, more BR disease, and larger tumors than those treated with G-nP (all p?<?0.05). The two regimens were equally effective in achieving an 80% decline in CA19-9 (p?=?0.8). The R0 resection rates were similar (80%), but FOLFIRINOX was associated with a reduction in pN1 disease (56% vs. 72%; p?=?0.028). The receipt of adjuvant therapy was similar (74 vs. 75%; p?=?0.79). In the Cox regression analysis with adjustment for baseline and treatment-related variables (FOLFIRINOX vs. G-nP, age, gender, computed tomography (CT) tumor size, BR vs. R, pre-NAT CA19-9), regimen type was not associated with a survival benefit. In the IPW analysis of 166 patients, however, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP (p?=?0.012).

Conclusions

Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA. In this study, neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates.

     

Preoperative Capecitabine and Concurrent Radiation for Borderline Resectable Pancreatic Cancer

Background

Patients with borderline resectable pancreatic ductal adenocarcinoma (PDA) represent a high-risk group of patients due to tumor or patient-related characteristics. The optimal management of these patients has not been fully defined.

Materials and Methods

All patients undergoing evaluation for PDA between 2005 and 2008 were identified. Clinical, radiographic, and pathological data were retrospectively reviewed. Patients were staged as borderline resectable using the M.D. Anderson Cancer Center (MDACC) classification.

Results

A total of 170 patients with PDA were identified, 40 with borderline resectable disease. Of these, 34 borderline resectable patients (85%) completed neoadjuvant therapy and were restaged; pancreatic resection was completed in 16 patients (46%). Also, 8 patients completed 50 Gy of radiation in 28 fractions in 6 weeks, whereas 8 patients received 50 Gy in 20 fractions in 4 weeks plus chronomodulated capecitabine. An R0 resection was achieved in 12 of the 16 patients (75%). Also, 5 patients (63%) treated in 20 fractions had >90% pathologic response versus 1 (13%) treated in 28 fractions (P < .05). Borderline resectable patients completing surgery had similar survival to patients with resectable disease who underwent surgery. Patients receiving accelerated fractionation radiation had improved survival compared with patients treated with standard fractionation protocol.

Conclusions

A neoadjuvant approach to borderline resectable PDA identifies patients who are most likely to benefit from pancreatic resection. Preoperative capecitabine-based chemoradiation is an effective, well-tolerated treatment for these patients. Neoadjuvant therapy for borderline resectable PDA warrants further investigation using treatment schedules that can safely intensify irradiation dose.     

Defining Venous Involvement in Borderline Resectable Pancreatic Cancer

Background

Pancreatic adenocarcinoma impinging the portal and/or superior mesenteric vein (PV-SMV) is classified as borderline resectable, and preoperative chemoradiation is recommended to increase the margin-negative resection rate. There is no consensus about what degree of venous impingement constitutes borderline resectability.

Methods

All patients undergoing potentially curative pancreatectomy for pancreatic adenocarcinoma were reviewed. Venous involvement was classified by preoperative computed tomography according to Ishikawa types: (I) normal, (II) smooth shift without narrowing, (III) unilateral narrowing, (IV) bilateral narrowing, (V) bilateral narrowing with collateral veins.

Results

From 1990–2009, 109 patients underwent resection of pancreatic adenocarcinoma involving the PV-SMV. Seventy-four patients received preoperative chemoradiation, whereas 35 did not. Patients who received preoperative therapy had a significantly longer median overall survival rate of 23 months compared with 15 months for patients without preoperative therapy (P = 0.001). Preoperative chemoradiation was associated with higher R0 resection rate and negative lymph nodes (both P < 0.0001) but did not affect the need for vein resection. When stratified by Ishikawa types, preoperative therapy was associated with improved overall survival among patients with types II and III but not types IV and V. Similarly, the correlation between preoperative therapy and R0 resection rate was observed only among patients with Ishikawa types II and III.

Conclusions

Preoperative therapy for borderline resectable pancreatic adenocarcinoma is associated with higher margin-negative resection and survival rates in patients with Ishikawa type II and III tumors, defined as a smooth shift or unilateral narrowing of the PV-SMV. Patients with bilateral venous narrowing were less likely to benefit from preoperative treatment.     

Potential Contribution of Preoperative Neoadjuvant Concurrent Chemoradiation Therapy on Margin-Negative Resection in Borderline Resectable Pancreatic Cancer

Background  

Margin-negative pancreatectomy provides only chance to cure pancreatic cancer. However, borderline resectable pancreatic cancer (BRPCa) has the risk of incomplete palliative resection.     

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.     

Adjuvant Chemotherapy After Neoadjuvant Chemotherapy for Pancreatic Cancer is Associated with Improved Survival for Patients with Low-Risk Pathology

Annals of Surgical Oncology - With limited evidence, the benefit of adjuvant chemotherapy (AT) after completion of neoadjuvant chemotherapy (NT) and surgical resection for patients with pancreatic...     

Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-institutional Phase 2 Trial

Background

Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma (PDAC), but recurrence rates are high even after purported curative resection. First-line treatment with gemcitabine and S-1 (GS) is associated with promising antitumor activity with a high response rate. The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting.

Methods

In a multi-institutional single-arm phase 2 study, neoadjuvant chemotherapy (NAC) with gemcitabine and S-1, repeated every 21 days, was administered for two cycles (NAC-GS) to patients with resectable and borderline PDAC. The primary end point was the 2-year survival rate. Secondary end points were feasibility, resection rate, pathological effect, recurrence-free survival, and tumor marker status.

Results

Of 36 patients enrolled, 35 were eligible for this clinical trial conducted between 2008 and 2010. The most common toxicity was neutropenia in response to 90 % of the relative dose intensity. Responses to NAC included radiological tumor shrinkage (69 %) and decreases in CA19-9 levels (89 %). R0 resection was performed for 87 % in resection, and the morbidity rate (40 %) was acceptable. The 2-year survival rate of the total cohort was 45.7 %. Patients who underwent resection without metastases after NAC-GS (n = 27) had an increased median overall survival (34.7 months) compared with those who did not undergo resection (P = 0.0017).

Conclusions

NAC-GS was well tolerated and safe when used in a multi-institutional setting. The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC.     

A Systematic Review and Meta-analysis of Survival and Surgical Outcomes Following Neoadjuvant Chemoradiotherapy for Pancreatic Cancer

Introduction  

This systematic review and meta-analysis aims to characterize the surgically important benefits and complications associated with the use of neoadjuvant chemoradiotherapy for the treatment of both resectable and initially unresectable pancreatic cancer. Studies were identified through a systematic literature search and analyzed by two independent reviewers. Survival, peri-operative complications, death rate, pancreatic fistula rate, and the incidence of involved surgical margins were analyzed and subject to meta-analysis.