临界可切除胰腺癌新辅助治疗研究进展

临界可切除胰腺导管腺癌（BR-PDAC）约占初诊胰腺癌患者的20%,介于可切除与不可切除之间,具有高度的解剖学、生物学、身体条件等方面的异质性。侵袭性的生物学行为决定这部分患者应优先考虑新辅助治疗而不是直接手术,从而达到R0切除避免术后的早期复发。然而,这一治疗模式仍然存在争议。根据这一主题的最新研究,本文从BR-PDAC的定义、新辅助治疗选择与评估、新辅助治疗后手术结果、新辅助治疗后辅助治疗的疗效等方面进行综述。     

Clinical challenges associated with utility of neoadjuvant treatment in patients with pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an increasingly common cancer with a persistently poor prognosis, and only approximately 20% of patients are clearly anatomically resectable at diagnosis. Historically, a paucity of effective therapy made it inappropriate to forego the traditional gold standard of upfront surgery in favour of neoadjuvant treatment; however, modern combination chemotherapy regimens have made neoadjuvant therapy increasingly viable. As its use has expanded, the rationale for neoadjuvant therapy has evolved from one of ‘downstaging' to one of early treatment of micro-metastases and selection of patients with favourable tumour biology for resection. Defining resectability in PDAC is problematic; multiple differing definitions exist. Multidisciplinary input, both in initial assessment of resectability and in supervision of multimodality therapy, is therefore advised. European and North American guidelines recommend the use of neoadjuvant chemotherapy in borderline resectable (BR)-PDAC. Similar regimens may be applied in locally advanced (LA)-PDAC with the aim of improving potential access to curative-intent resection, but appropriate patient selection is key due to significant rates of recurrence after excision of LA disease. Upfront surgery and adjuvant chemotherapy remain standard-of-care in clearly resectable PDAC, but multiple trials evaluating the use of neoadjuvant therapy in this and other localised settings are ongoing.     

Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives

Pancreatic adenocarcinoma (PDAC) is one of the most common and lethal human cancers worldwide. Surgery followed by adjuvant chemotherapy offers the best chance of a long-term survival for patients with PDAC, although only approximately 20% of the patients have resectable tumors when diagnosed. Neoadjuvant chemotherapy (NACT) is recommended for borderline resectable pancreatic cancer. Several studies have investigated the role of NACT in treating resectable tumors based on the recent advances in PDAC biology, as NACT provides the potential benefit of selecting patients with favorable tumor biology and controls potential micro-metastases in high-risk patients with resectable PDAC. In such challenging cases, new potential tools, such as ct-DNA and molecular targeted therapy, are emerging as novel therapeutic options that may improve old paradigms. This review aims to summarize the current evidence regarding the role of NACT in treating non-metastatic pancreatic cancer while focusing on future perspectives in light of recent evidence.     

边缘可切除胰腺癌新辅助治疗优化策略的研究进展

胰腺癌具有高度侵袭性,预后差,仅少数患者在确诊时存在手术根治机会。随着医学技术的发展,介于明确可切除与不可切除胰腺癌之间,划分出了一种特殊类型,即边缘可切除胰腺癌（BRPC）。此类胰腺癌根治性手术难度大,R0切除率低、复发风险高,新辅助治疗在提高BRPC的R0切除率和延长生存期上发挥了重要的作用。如何优化新辅助治疗策略、改善BRPC患者的预后值得临床重视。     

Neoadjuvant chemoradiation with IMRT in resectable and borderline resectable pancreatic cancer

PurposeNeoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR).Materials and methodsAll patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels.ResultsNeoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2 years was 2% (95% CI 0–6%) and 9% (95% CI 0.6–17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11 months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47 months (36–60).ConclusionNeoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa.     

局部进展期直肠癌新辅助治疗策略研究进展

局部进展期直肠癌(LARC)的治疗极具挑战性,仅凭手术切除难以达到满意疗效,近年来LARC诊治倾向于多学科协作(MDT)模式,依托其出现的新辅助治疗策略是LARC诊治的里程碑式进展.目前,LARC首选疗法为新辅助放化疗联合全直肠系膜切除术.本文围绕LARC新辅助治疗主要方案作一综述,以期为临床诊疗提供参考.     

Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma

Background

The most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT.

Methods

From January 1996 to December 2006, 64 patients with LAPA (borderline, n = 49; unresectable, n = 15) received 5-fluorouracil-cisplatin-based CRT. Of the 64 patients, 47 had progressive disease at restaging. Laparotomy was performed for 17 patients, and PD was performed in 9 patients (resected group). Fifty-five patients had CRT followed by gemcitabine-based chemotherapy (unresected group).

Results

The median survival and overall 5 years survival duration of all 64 patients were 14 months and 12%, respectively. The mean delay between diagnosis and surgical resection was 5.5 months. Mortality and morbidity from PD were 0% and 33%, respectively. The median survival of the resected group vs. the unresected group was 24 months vs. 13 months. Three specimens presented a major pathological response at histological examination. No involved margins were found and positive lymph nodes were found in one patient. Resected patients developed distant metastases.

Conclusions

PD after CRT was safe and resected patients had interesting survival rates. However, resected patients developed metastatic disease and new neoadjuvant regimens are needed to improve the survival of these patients.     

Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy

BackgroundPancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection.Materials and methodsProspectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed.ResultsBetween 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010).ConclusionPatients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.     

伊立替康在局部晚期宫颈癌患者新辅助化疗中的应用效果

目的：探讨伊立替康在局部晚期宫颈癌患者新辅助化疗中的应用效果。方法按照随机数字表法将114例局部晚期宫颈癌患者均分为实验组和对照组,实验组患者给予伊立替康联合顺铂治疗,对照组患者给予多西他赛联合顺铂治疗,比较2组近期疗效。结果实验组患者RR率明显高于对照组,差异具有统计学意义（P＜0．05）。实验组患者白细胞减少、血小板减少、中性粒细胞减少、恶心呕吐发生率明显低于对照组,差异具有统计学意义（P＜0．05）;实验组患者Ⅲ～Ⅳ级白细胞减少、中性粒细胞减少、恶心呕吐发生率明显低于对照组,差异具有统计学意义（ P＜0．05）。2组患者化疗后躯体功能、角色功能、认知功能、情绪功能和社会功能评分均明显升高,与同组化疗前比较,差异具有统计学意义（P＜0．05）;实验组患者化疗后躯体功能和情绪功能均明显高于对照组,差异具有统计学意义（P＜0．05）。结论伊立替康能够有效提高顺铂新辅助化疗的临床效果,减少化疗期间不良反应,提高患者生活质量。     

局部晚期乳腺癌新辅助放疗研究进展

乳腺癌发病率居世界女性癌症发病率首位,随着医学技术的进步,乳腺癌患者总生存率得到了提高,但是局部晚期乳腺癌的治疗仍然是棘手的临床问题。对于局部晚期乳腺癌,术后辅助放疗是常规治疗手段,而新辅助放疗在局部晚期乳腺癌治疗中地位尚不明确,本文综述局部晚期乳腺癌新辅助放疗的相关研究进展,希望为局部晚期乳腺癌的治疗提供参考。     

Neoadjuvant therapy in resectable pancreatic cancer: A promising curative method to improve prognosis

Currently, 15 randomized controlled trials (RCTs) have been designed to investigate whether neoadjuvant therapy (NAT) benefits patients with resectable pancreatic adenocarcinoma (R-PA) compared to surgery alone. Five of them have acquired results so far; however, corresponding conclusions have not been obtained. We speculated that the reason for this phenomenon could be that some prognostic factors had proven to be adverse through upfront surgery curative patterns, but some of them were not regarded as independent baseline characteristics, which is important to obtaining comparability between the NAT and upfront surgery groups. This fact could cause bias and lead to the difference in the outcomes of RCTs. In this review, we collate data about risk factors (such as tumor size, resection margin, and lymph node status) influencing the prognoses of patients with R-PA from five RCTs and discuss the possible reasons for the varying outcomes.     

Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?

Pancreatic cancer remains one of the deadliest cancers due to difficulty in early diagnosis and its high resistance to chemotherapy and radiation. It is now clear that even patients with potentially resectable disease require multimodality treatment including chemotherapy and/or radiation to improve resectability and reduce recurrence. Tremendous efforts are currently being invested in refining preoperative staging to identify optimal surgical candidates, and also in developing various neoadjuvant or adjuvant regimens to improve surgical outcome. Although at present no studies have been done to directly compare the benefit of neoadjuvant versus adjuvant approaches, accumulating evidence suggests that the neoadjuvant approach is probably beneficial for a subset of the patient population, particularly those with borderline resectable disease in which complete surgical resection is almost certainly unachievable. In this article, we review the literature and rationales of neoadjuvant chemotherapy and chemoradiation, as well as their potential limitations and caveats. We also review the pathological findings following neoadjuvant therapies, and potential surgical complications that may be associated with neoadjuvant therapies.     

Neoadjuvant FOLFIRINOX for Borderline Resectable Pancreas Cancer: A New Treatment Paradigm?

Background.

Borderline resectable pancreatic cancer is best treated by multimodality therapy. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) tripled the response rate and significantly increased median survival for patients with advanced pancreatic cancer and shows promise for neoadjuvant use. Toxicity concerns prompted a careful analysis of our initial FOLFIRINOX experience.

Methods.

All patients diagnosed with borderline resectable, biopsy-proven pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX between July 2010 and December 2012 were reviewed. Primary outcome was surgical resectability. Secondary outcomes were treatment-related toxicities and survival.

Results.

FOLFIRINOX followed by gemcitabine- or capecitabine-based chemoradiation was initiated in 18 patients. The most common grade 3 or 4 toxicities during chemotherapy were gastrointestinal, including nausea/emesis (n = 5), weight loss (n = 3) and diarrhea (n = 2), and hematologic (n = 2; neutropenia); five patients (36%) required a total of six admissions. Neoadjuvant therapy was completed in 15 of 18 patients (83%), and 12 (67%) underwent pancreatectomy (10 Whipple, 2 total pancreatectomy) including portal vein resection/reconstruction in 10 (83%). Disease progression precluded surgery in 6 of the 18 patients (33%). All 12 resected patients had negative (R0) margins. Only 2 of 12 (17%) were node positive (median node count: 26.5 [range: 15–39]). There were no in-hospital or 30-day mortalities and no clinical pancreatic leaks or reoperations. Of the 12 patients who completed all intended therapy, 7 (58.3%) are alive, including 5 who have no evidence of disease (median months from diagnosis: 22 months [range: 18–35 months). The six patients who did not complete all planned therapy are deceased (months from diagnosis: 6.9–17.5 months).

Conclusion.

FOLFIRINOX followed by chemoradiation as neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma is safe, and our initial experience suggests favorable resection rates compared with previous reports in this high-risk patient population.     

紫杉醇联合顺铂新辅助化疗治疗局部晚期子宫颈癌的疗效分析

目的 探讨紫杉醇联合顺铂新辅助化疗治疗局部晚期子宫颈癌的疗效.方法 回顾分析130例接受子宫广泛切除术以及盆腔淋巴结清扫术的局部晚期子宫颈癌患者的临床资料,根据治疗方案将这些患者分为新辅助化疗组(74例)与直接手术组(56例),前者在术前行1～3个疗程的紫杉醇联合顺铂新辅助化疗.结果 新辅助化疗组血清糖类抗原125 (CA125)、鳞状细胞癌抗原(SCCA)、肿瘤直径在化疗前后差异有统计学意义(P＜0.01).新辅助化疗组完全缓解(CR) 12例、部分缓解(PR)43例、疾病稳定(SD) 11例、疾病进展(PD)8例,总缓解率74.3％,疾病控制率89.2％.新辅助化疗组手术时间、术中出血量、术后病理检查淋巴结转移率显著低于直接手术组,差异有统计学意义(P＜0.05),但2组患者术后病理检查深肌层受累率、淋巴脉管间隙浸润率、切缘阳性率等情况差异无统计学意义(P＞0.05).结论 紫杉醇联合顺铂新辅助化疗治疗局部晚期子宫颈癌的近期疗效良好,具有缩小肿瘤体积、降低手术难度、减少手术损伤、降低淋巴结转移率等优点.