Pathologic Nodal Status Predicts Disease-Free Survival After Neoadjuvant Chemoradiation for Gastroesophageal Junction Carcinoma

Background The incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival. Methods A retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001. Results The median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett’s esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)—not the degree of primary tumor response—predicted DFS. Conclusions The nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short. Presented at the 43rd Annual Meeting of the Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002.     

Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods.

Methods

Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0–0.4 (strong partial response, SPR), TRR > 0.4–1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan–Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders.

Results

There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016).

Conclusions

TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.     

胃癌的新辅助化疗

胃癌是人类最常见的恶性肿瘤之一，手术切除仍是最主要的治疗手段，绝大多数早期胃癌通过手术可以获得治愈，但手术不能改变残留癌细胞局部复发及远处转移的生物学特性，尤其是进展期胃癌术后局部复发和转移的发生率仍可高达60％以上，复发和转移是治疗失败的主要原因。胃癌术后的保驾化疗在临床开展已有半个多世纪，但术后化疗的临床效果不尽人意。随着人们对肿瘤生物学行为认识的提高，胃癌的治疗模式正向围绕手术开展的化疗、介入治疗、免疫治疗等综合治疗方面发展。近年来，在『临床开展的术前辅助化疗，也即新辅助化疗（neoadjuvantchemotherapy），治疗效果肯定，并受到愈来愈多患者的接受。     

进展期胃癌新辅助化疗的研究进展

目的总结进展期胃癌新辅助化疗的研究进展。方法采用文献复习的方法,对有关进展期胃癌新辅助化疗研究进展的文献进行综述。结果进展期胃癌的新辅助化疗可显著提高R0切除率,提高远期生存率,降低死亡风险。对于无远处转移的局部进展期胃癌的新辅助化疗时间一般为6~9周,然后根据疗效评价结果决定是否进行手术治疗;进一步深入的临床研究及化疗敏感程度检测方法的改进有助于新辅助化疗标准的统一。结论进展期胃癌新辅助化疗的疗效已比较明确,但其在适应证、化疗方案、用药时限、疗效评价指标等方面尚无明确的统一标准,仍需要多中心、大型的临床试验进行深入的研究。     

进展期胃癌新辅助化疗的临床实践与面临的问题

“胃癌的生长是无限的,而外科手术范围却是有限的;把无限生长的胃癌控制在有限的手术范围之内——胃癌的新辅助化疗”。     

FLEEOX新辅助化疗对进展期胃癌患者营养状况的影响

目的 研究FLEEOX新辅助化疗方案对进展期胃癌患者营养状况的影响.方法 根据纳入和排除标准,共选择2010年12月至2011年10月期间我科收治的难以手术切除并进行了新辅助化疗的48例胃癌患者,利用机体组成分析仪测定化疗前、后机体组成成分的变化,同时检测血液相关营养学指标.结果 患者化疗后,体重、细胞内液、体重指数、蛋白质、体脂肪、体细胞群及上臂周长均较化疗前表现为略下降,而细胞外液、身体水分含量、无机盐、骨骼矿物质含量、非脂群、骨骼肌及上臂无脂肪周长较化疗前均表现为略轻度上升,但各项指标差异均无统计学意义(P＞0.05);血液中白蛋白、前白蛋白、总蛋白、转铁蛋白及淋巴细胞均较化疗前出现不同程度下降,但差异均无统计学意义(P＞0.05).结论 进展期胃癌患者接受化疗期间营养状况无明显变化,FLEEOX新辅助化疗未加重患者营养不良的状况.     

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.     

Response to Preoperative Chemotherapy Predicts Survival in Patients Undergoing Hepatectomy for Liver Metastases from Gastric and Esophageal Cancer

Background

The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM.

Methods

Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated.

Results

Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24 %, respectively. Postoperative morbidity and mortality rates were 32 and 4 %, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9 %, P?=?.005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0 %, P?P?=?.045).

Conclusion

For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.     

Complete Response to Neoadjuvant Chemoradiation for Rectal Cancer Does Not Influence Survival

Background: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation.Methods: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses.Results: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases.Conclusions: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Reduced Incidence of Nodal Micrometastasis after Major Response to Neoadjuvant Chemoradiation in Locally Advanced Esophageal Cancer

Background

Neoadjuvant treatment modalities for esophageal cancer were developed to improve local tumor control as well as to reduce lymph node metastases and distant metastases in patients with locally advanced esophageal cancer. The influence on nodal micrometastasis has not yet been evaluated.

Methods

This study includes 52 patients with localized (cT2-4, Nx, M0) esophageal cancers (21 adenocarcinomas, 31 squamous cell cancers) who received neoadjuvant chemoradiation (36Gy, 5-FU, cisplatin) followed by transthoracic en bloc esophagectomy with two field lymphadenectomy. The extent of histomorphologic regression was categorized into major (< 10%) and minor response (>10% vital residual tumor cells) as recently reported. A total of 1186 lymph nodes were diagnosed as negative for metastases by routine histopathological analysis and were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3.

Results

Twenty-two tumors (42.3%) showed a major histopathologic response whereas in 30 tumors (57.7%) only a minor response was present. Of 32 patients with a pN0 category, major response was present in 19 (59.4%) tumors, whereas 13 (40.6%) tumors showed minor response. Nine (69%) out of 13 patients with minor response had AE1/AE3-positive cells in their lymph nodes, whereas only four (21%) out of 19 pN0-patients with major response showed nodal micrometastasis (P = 0.013, χ²-test).

Conclusions

If tumors show a major histomorphologic response following neoadjuvant chemoradiation, the presence of nodal micrometastasis is significantly reduced compared to those with minor response.     

Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer

n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n= 13); or UFT 600 mg/day (P2 group, n= 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n= 17), H1 (n= 12), and H2 (n= 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.     

进展期胃癌术中区域化疗研究现状

目的探讨进展期胃癌术中区域化疗的可行性、安全性、有效性及其机理。方法复习国内、外相关文献并进行分析与综述。结果与全身化疗相比,进展期胃癌术中区域化疗可以增加肿瘤组织的药物浓度,降低全身性毒副反应,提高生存率,改善生存质量。结论术中区域化疗作为进展期胃癌的辅助手段已逐渐应用于临床,其疗效肯定,具有推广应用价值,但对其深入认识尚需更多的病例积累与系统研究。     

Response to Neoadjuvant Chemotherapy Does Not Predict Overall Survival for Patients With Synchronous Colorectal Hepatic Metastases

Objective  We investigated the relation between response to neoadjuvant chemotherapy and overall survival (OS) in patients with colorectal liver metastases (CLM). Background  It has previously been reported that patients with synchronous CLM whose disease progresses while receiving neoadjuvant chemotherapy or who do not receive neoadjuvant chemotherapy experience worse survival than patients whose disease responds to neoadjuvant chemotherapy. Methods  By means of a prospectively maintained surgical database, between 1995 and 2003, we identified 111 patients with a synchronous CLM who received neoadjuvant chemotherapy before hepatic resection. The disease of all 111 patients was deemed resectable, and patients underwent hepatic resection with curative intent. Results  The median OS after liver resection was 62 months, with a median follow-up of 63 months. Median OS was similar between the three study groups classified by response to neoadjuvant chemotherapy (complete or partial response, 58 months; stable disease, 65 months; and disease progression, 61 months; P = .98). By univariate analysis, carcinoembryonic antigen level after liver resection of <5 ng/dL, size of metastatic lesion of ≤5 cm, lymph node–negative primary tumor, and disease-negative margins were associated with improved survival. Patients in the disease progression group had more positive margins and metastases >5 cm in size than patients in the complete or partial response group and the stable disease group. Patients whose tumor progressed but who received postoperative hepatic arterial infusion had a trend toward improved survival compared with those who did not receive hepatic arterial infusion (70% vs. 50% at 3 years, permutation log rank test P = .12). Conclusions  Response to neoadjuvant chemotherapy did not correlate with OS even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.     

MRI and FDG-PET for Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Background

The purpose of this study was to assess the value of magnetic resonance imaging (MRI) and additional ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC).

Methods

Data on 40 patients with LARC, who were treated with NAC and underwent MRI and FDG-PET/CT before and after NAC, were analyzed retrospectively. Surgery was performed at a median of 6 weeks after NAC and the images were compared with the histological findings. The tumor regression grade 3/4 was classified as a responder.

Results

Sixteen patients were pathological responders. Receiver operating characteristic (ROC) analysis revealed that MRI total volume after NAC (MRI-TV2) and ΔMRI-TV had the highest performance to assess responders (area under the ROC curve [AUC] 0.849 and AUC 0.853, respectively). The reduction rate of the maximum standardized uptake value (ΔSUVmax) was also an informative factor (AUC 0.719). There seems no added value of adding FDG-PET/CT to MRI-TV2 and ΔMRI-TV in assessment of NAC responders judging from changes in AUC (AUC of ΔSUVmax and MRI-TV2 was 0.844, and AUC of ΔSUVmax and ΔMRI-TV was 0.846).

Conclusions

MRI-TV2 and ΔMRI-TV were the most accurate factors to assess pathological response to NAC. Although ΔSUVmax by itself was also informative, the addition of FDG-PET/CT to MRI did not improve performance. Patients with LARC who were treated by induction chemotherapy should receive an MRI examination before and after NAC to assess treatment response. A more than 70 % volume reduction shown by MRI volumetry may justify the omission of subsequent radiotherapy.     

八珍汤加减方在老年进展期胃癌新辅助化疗中的疗效及其意义

目的:评价八珍汤加减方在老年性进展期胃癌新辅助化疗中的疗效及其临床意义。方法:收集丽水市中心医院胃肠外科2016年8月—2018年8月收治的60例局部进展期胃癌,随机分为常规组和治疗组,每组30例,常规组采用SOX方案(替吉奥联合奥沙利铂)新辅助治疗3次后行手术治疗,治疗组在常规组的基础上加用八珍汤加减方治疗后行手术治疗。比较两组患者行新辅助化疗3次后的有效率及手术根治切除率。比较第1次及第3次新辅助化疗期间的不良反应,以及行新辅助化疗前、后的免疫功能(包括CD3+、CD4+、CD8+、CD4+/CD8+),Karnofsky(KPS)评分评价两组的生活质量并进行比较。结果:治疗组的总有效率及手术根治切除率均高于常规组。行新辅助化疗后,治疗组的CD3+、CD4+、CD4+/CD8+水平均高于常规组,生活质量改善情况优于常规组,差异均有统计学意义(P0.05)。在行第3次新辅助化疗期间,治疗组Ⅲ-Ⅳ级消化道及骨髓不良反应发生率低于常规组,两组比较差异有统计学意义(P0.05)。结论:老年性进展期胃癌新辅助化疗患者加用八珍汤加减方可增强患者免疫功能,改善患者化疗期间的生活质量,减少化疗的不良反应,提高患者的近期疗效。     

Neoadjuvant Chemotherapy of Breast Cancer: Tumor Markers as Predictors of Pathologic Response,Recurrence, and Survival

Abstract: This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR?) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR? patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR? patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR? and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.     

Neoadjuvant Chemotherapy Is Associated with Improved Survival Compared with Adjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer Only after Complete Pathologic Response

Introduction  

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy.