Neoadjuvant chemoradiation may be associated with improved pathologic response in pancreatic cancer

BackgroundNeoadjuvant therapy is increasingly utilized in the management of pancreatic adenocarcinoma. The type of neoadjuvant therapy and its effect on pathologic response remains understudied.MethodsA retrospective review was performed on patients who underwent neoadjuvant therapy followed by pancreatectomy. Multivariable regressions were used to determine associations between neoadjuvant therapy regimens and pathologic response.ResultsSeventy-five patients with pathologic responses available for review received FOLFIRINOX (61%) or gemcitabine with nab-paclitaxel (39%). Demographics, histologic differentiation, and utilization of chemoradiation were similar between the groups. Multivariable logistic regression demonstrated that chemoradiation was associated with an increased likelihood of a complete or near-complete pathologic response and a decreased rate of lymphovascular invasion and lymph node positivity. Neither chemotherapy regimen nor number of cycles administered were associated with pathologic response.ConclusionsNeoadjuvant chemoradiation may be associated with complete or near-complete pathologic response regardless of chemotherapy regimen in pancreatic cancer patients.     

局部进展期乳腺癌新辅助化疗后保乳手术31例报告

目的探讨局部进展期乳腺癌新辅助化疗降期后保乳手术治疗的可行性。方法2002年1月-2005年6月我院接受新辅助化疗后行保乳治疗的31例局部进展期乳腺癌。化疗方案：①TE：表阿霉素60mg／m^2，紫杉醇150mg／m^2，21d为1个周期；②CEF：表阿霉素60mg／m^2，环磷酰胺600mg／m^2，5-FU600mg／m^2，21d为1个周期，共3～4周期。在新辅助化疗完成后，临床体检、B超和钼靶乳房x线检查评估新辅助化疗疗效，符合保乳条件且病人有保留乳房的愿望可接受保乳治疗。手术方式为象限切除或肿块局部广泛切除联合腋窝淋巴结清扫。术后常规行辅助放疔、化疗和内分泌治疗。结果新辅助化疗总有效率（overaul response rate，ORR）90．3％（28／31）；临床完全缓解（complete response，CR）25．8％（8／31），其中病理完全缓解（pathologic complete response，pCR）4例（12．9％，4／31），临床部分缓解（partial response，PR）20例（64．5％，20／31），无进展病例。经过34个月中位随访期（4～46个月），局部复发率6．5％（2／31）；3例术后发生远处转移，转移部位分别为肺、肝脏、脑膜和骨，远处转移率9．7％（3／31），其中1例死亡。对保乳综合治疗结束后满1年的25例进行乳腺外形的评估，外形优16．0％（4／25），良40．0％（10／25），差44．0％（11／25）。结论经新辅助化疗降期后的局部进展期乳腺癌进行保乳手术治疗效果满意，规范化的切除和术后放疗、全身综合治疗是保乳治疗成功的关键。     

乳腺癌新辅助化疗后前哨淋巴结活检术的研究

目的 探讨乳腺癌病人新辅助化疗后前哨淋巴结活检的可行性。方法对2003年11月至2004年10月住院治疗中的57例Ⅱ、Ⅲ期乳腺癌病人行新辅助化疗后，临床检查腋窝淋巴结阴性行前哨淋巴结活检术（SLNB）。结果57例中检出前哨淋巴结（SLN）53例，检出率93．0％。SLN对腋窝淋巴结状况预测的敏感性为89．7％，特异性为100．0％，准确性为94．3％，阳性预测值为100．0％，阴性预测值为88．9％，假阴性率为5．7％。肿瘤对化疗反应为CR（完全缓解）、PR（部分缓解）和SD（稳定）的SLN检出率分别为100．0％、96．7％和70．0％（P〈0．01）。SLN假阴性3例均为腋窝淋巴结转移数〉4个者。结论Ⅱ、Ⅲ期乳腺癌实施新辅助化疗后。行SLNB可获得与早期乳腺癌SLNB相似的效果。     

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit

ObjectivesNeoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care.Materials and methodsAll patients aged 18–70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors.ResultsA total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0–100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%).ConclusionNAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.     

ET与CEF新辅助化疗方案的临床疗效比较

目的比较ET与CEF两种不同新辅助化疗方案治疗乳腺癌的疗效及不良反应。方法收集130例Ⅱa-Ⅲc期乳腺癌患者,分为两组,分别接受ET组（多西紫杉醇加表阿霉素）和CEF组（环磷酰胺加表阿霉素加5-Fu）化疗方案治疗。其中ET组64例,CEF组66例,化疗21天为1个周期。所有的患者均完成2—4个周期新辅助化疗后评价疗效。结果乳腺癌新辅助化疗总有效率（ORR）ET组为85．9％（57／64）,CEF组为71．2％（47／66）。主要不良反应是脱发、乏力、恶心、呕吐、腹泻,两组间不良反应无显著性差异。ET组3度以上粒细胞缺乏、粒细胞缺乏性发热、外周性水肿、关节痛、肌痛、神经感觉异常发生率较CEF组高（P〈0．05）,但不良反应均可耐受。结论两组新辅助化疗方案对乳腺癌的原发肿瘤均有效。ET组的疗效及不良反应均高于CEF组。     

每周紫杉醇联合卡铂新辅助化疗对乳腺癌的疗效

目的评价紫杉醇联合卡铂对乳腺癌的新辅助化疗效果。方法对我科在2005年1月-2007年1月25例经病理证实的女性乳腺癌患者人组接受紫杉醇和卡铂化疗进行回顾性分析。结果总有效率88．0％（22／25）,其中CR24．0％（6／25）,PR64．0％（16／25）,SD12．0％（3／25）,无PD病例。25例中,雌激素受体阳性者有效率86．7％（13／15）。雌激素受体阴性者有效率70．0％（7／10）。Her-2阳性有效率100％（6／6）。Her-2阴性者有效率89．5％（17／19）。全组患者治疗后腋窝淋巴结降期率为36．0％（9／16）。结论紫杉醇联合卡铂每周方案新辅助治疗局部中晚期乳腺癌有较高的疗效,毒性反应可耐受。     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in a patient with operable breast cancer

PURPOSE: This study was undertaken to assess the feasibility of performing a sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after undergoing neoadjuvant chemotherapy (NAC). METHOD: Between January 2002 and December 2003, women with primary breast cancer who had a breast tumor measuring larger than 3 cm in unilateral diameter were eligible for NAC. All patients who had completed NAC underwent lymphatic mapping with labeled (99m)Tc phytate on the day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes (SLN) were sent for a frozen-section examination. RESULTS: The rate of SLN identification was 71%. Both the sensitivity and negative predictive value of SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were restricted to patients with a breast tumor measuring less than 3 cm and clinically negative nodes after NAC, the rate of SLN identification increased to 93% from 71% while still maintaining the 0% false negative rate. CONCLUSION: Sentinel lymph node biopsy after NAC is therefore considered to be a feasible and accurate method to predict the AXLN status in patients who have a breast tumor measuring less than 3 cm in unilateral diameter and a clinically negative AXLN status at the time of surgery after NAC.     

Surgical timing following neoadjuvant chemotherapy for breast cancer affects postoperative complication rates

BackgroundNeoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer. The time interval from last dose of cytotoxic chemotherapy to surgery (TTS) can vary widely. We aimed to evaluate the effect of TTS on postoperative complications.MethodsA retrospective review for women treated with NAC at our institution between January 2011 through December 2016 was performed. Charts were reviewed for postoperative wound complications, and multivariate analysis was performed.Results455 patients were identified. Median TTS was 30 days (range 11–228). On multivariate analysis, TTS of less than 28 days was associated with 70% higher odds of any wound complication (p < 0.05). Increasing age had the strongest association with the presence of any wound complication (p < 0.0001). The majority of complications were treated in the outpatient setting (n = 80, 83%).ConclusionFollowing NAC for breast cancer, TTS less than 28 days is a risk factor for postoperative wound complications; however, the majority of complications are minor and treated in the outpatient setting. Additional data are needed to determine optimal TTS for oncologic outcomes.     

乳腺癌新辅助化疗后腋窝淋巴结的变化

目的评价新辅助化疗对乳腺癌腋窝淋巴结的影响。方法45例Ⅱ、Ⅲ期乳腺癌接受新辅助化疗后手术(新辅助化疗联合手术组),根据体检、B超及钼靶像计数腋窝淋巴结总数和阳性、阴性淋巴结数,与未行新辅助化疗直接手术治疗的79例乳腺癌(直接手术组)比较,观察腋窝淋巴结的变化。结果新辅助化疗联合手术组检出腋窝总淋巴结和阳性淋巴结为(16.9±5.9)枚和(2.5±2.2)枚,显著低于直接手术组的(20.8±8.0)枚和(3.9±3.0)枚(t=-2.856,P=0.005;t=2.790,P=0.006),2组阴性淋巴结分别为(14.4±5.4)枚和(16.7±7.0)枚,无统计学差异(t=-1.904,P=0.055)。新辅助化疗联合手术组40例随访6~19个月,平均10个月;直接手术组67例随访7~21个月,平均12个月,2组各有4例复发。结论乳腺癌经新辅助化疗后行腋窝淋巴结清扫所检出的淋巴结总数和阳性淋巴结数减少。     

Ki67预测乳腺癌新辅助化疗效果的临床研究

目的检测接受新辅助化疗的乳腺癌组织化疗前Ki67(细胞增殖核抗原)的表达,探讨其与新辅助化疗效果的关系。方法接受含蒽环类药物新辅助化疗的乳腺癌患者46例,化疗前空心针穿刺获取标本,免疫组化SP法检测乳腺癌组织中Ki67的表达,利用百分数定量Ki67的表达水平,统计学分析Ki67的表达水平与临床病理特征以及新辅助化疗临床效果的关系。结果在Ki67高表达(25%的癌细胞阳性)和低表达(≤25%的癌细胞阳性)的乳腺癌患者中,两组的临床病理特征相似,Ki67高表达组和低表达组的术前化疗临床缓解率分别为85.0%和46.15%,ki67的表达水平与化疗效果有显著相关性(χ2=9.787,P=0.027)。结论新辅助化疗前乳腺癌组织Ki67的表达水平可作为预测乳腺癌新辅助化疗效果的分子指标。     

新辅助化疗对局部晚期乳腺癌的疗效分析

目的探讨新辅助化疗对局部晚期乳腺癌的疗效。方法对56例行新辅助化疗的局部晚期乳腺癌患者的临床资料进行总结分析。56例患者中ⅢA期30例，ⅢB期15例，ⅢC期11例。采用AC方案（环磷酰胺600mg/m^2静脉滴注，阿霉素60mg/m^2或表阿霉素90mg/m^2静脉滴注，第1日，21d为1个周期）或ET方案（表阿霉素90mg/m^2静脉滴注，第1日；多西他塞75mg/m^2静脉滴注，第2日；地塞米松16mg/d，第1-3日口服，21d为1个周期）。化疗3-4个周期后观察疗效，结果全部患者临床有效率（完全缓解＋部分缓解）为71.5%（40/56例），临床获益率（完全缓解＋部分缓解＋病情稳定）为95.4%，病理完全缓解率8.9%（5/56例）。38例（67.9%）重获根治手术机会，中位随访时间40个月，总生存率为62.5%（35/56例），无瘤生存率为39.3%（22/56例）。结论新辅助化疗能降低局部晚期乳腺癌术前TNM分期，使部分患者重获根治性手术机会。     

fMRI(磁共振功能成像)对乳腺癌新辅助化疗评估的研究进展

【摘要】〓能够早期评估乳腺癌新辅助化疗疗效的方法很大程度上有助于病人治疗方案的制定,所以对于找寻精准且无创的方法的需求则日益上升。目前,MRI技术能够根据肿瘤大小、形态及强化程度等形态学变化对疗效进行评估,而且已有越来越多新兴技术能够从微观分子层面早期反映新辅助化疗后肿瘤变化,这些技术包括动态对比增强(DCE-MRI)、磁共振波谱(MRS)、磁共振弥散加权成像(DWI)、体素内不相干运动(IVIM)。作者综述MRI新技术在评估乳腺癌新辅助化疗疗效中的应用。     

The role of Oncoplastic Breast Surgery in the management of breast cancer treated with primary chemotherapy

ObjectiveThe purpose of this study was to evaluate the benefit of Oncoplastic Breast Conserving Surgery (BCS) compared to standard BCS after primary CT, in terms of oncologic safety and cosmetic outcomes.BackgroundThe development of new drugs has led to greater use of primary chemotherapy (CT) for bulky breast cancer (BC) and has allowed wider indications for conservative surgery.Patients and methodsWe identified 259 patients consecutively treated with BCS for primary BC from January 2002 to November 2010. All patients had undergone Oncoplastic Breast Surgery (OBS) or standard BCS after primary CT. Mastectomy rates, and oncological and cosmetic outcomes were compared.ResultsA total of 45 OBS and 214 standard BCS were analyzed. The median tumor size was 40 mm in the two groups (p = 0.66). The median operative specimen volumes were larger in the OBS group than in the standard group (respectively, 180 cm³ and 98 cm³, p < 0.0001). Re-excision (9% vs 2%) and mastectomy (24% vs 18%) rates were similar (p = 0.22 and p = 0.30) in the standard BCS group and in the OBS group respectively. At a median follow-up of 46 months, local relapse (p = 0.23) and distant relapse (p = 0.35) rates were similar.ConclusionOBS allows excision of larger volumes of residual tumor after primary CT. OBS outcomes results were similar to those of standard BCS.Oncoplastic Breast Conserving Surgery (BCS) after primary chemotherapy allows wider breast resection than standard BCS. Survival and relapse probabilities are similar in both groups.     

Cost-effectiveness of neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer

ObjectivesTo determine the costs of treatment and the duration of survival, adjusted for quality of life, for patients with muscle-invasive bladder cancer treated with immediate radical cystectomy (RC) or with neoadjuvant chemotherapy (NAC) with intent for subsequent RC.Methods and materialsA retrospective review of our institutional review board–approved database identified patients with muscle-invasive bladder cancer treated at our institution from 2004 to 2011. Patients were divided into those receiving RC alone and those receiving NAC before planned RC. Patients who refused RC following NAC were included in an intention-to-treat analysis. Survival duration was converted to quality-adjusted life years (QALYs), and costs of treatment per QALY were determined.ResultsA total of 119 patients (65.4%) received RC alone and 63 (34.6%) received NAC, 38 of whom proceeded to cystectomy as planned. Mean total costs were $42,890 and $52,429 for RC and NAC, respectively (P = 0.005). The 5-year overall survival was 31.7% and 42.5% for the RC-only group and the NAC group, respectively (P = 0.034). The 5-year overall survival measured in QALYs was 21.9% and 42.9% for the RC-only and the NAC groups, respectively (P = 0.021). The increased cost for NAC was $5,840 per additional life year gained (95% CI: $1,772–$9,909) and $6,187 per additional QALY gained (95% CI: $1,877–$10,498).ConclusionsThe use of NAC is associated with a significant increase in quality-adjusted survival. The additional cost per QALY gained is approximately $6,000. The cost-utility analysis of NAC compares favorably with other cancer-specific therapies.     

表阿霉素联合多西紫杉醇新辅助化疗治疗三阴乳腺癌的疗效及预后评价

目的探讨三阴乳腺癌(TNBC)与非三阴乳腺癌(non-TNBC)接受表阿霉素联合多西紫杉醇方案(ET方案)的化疗敏感性及预后方面的差别。方法对接受ET新辅助化疗方案治疗的249例乳腺癌患者进行回顾性分析。依据免疫组化雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体2(HER2)表达水平将乳腺癌分为三阴乳腺癌及非三阴乳腺癌两类,分析三阴与非三阴乳腺患者接受ET新辅助化疗方案后,二者病理疗效及远期生存的差别。结果 249例患者中,54(21.7%)例为三阴乳腺癌,195(78.3%)例为非三阴乳腺癌。三阴乳腺癌的病理完全缓解(pCR)率为25.9%,明显高于非三阴乳腺癌的12.3%(P=0.019)。三阴乳腺癌患者,特别是新辅助化疗后仍有癌残留的患者,其5年无病生存率(DFS)及5年的总生存率(OS)均明显低于非三阴乳腺癌(P值均<0.05)。获得pCR的乳腺癌患者5年的DFS和OS均明显高于化疗后仍有癌残留的患者(P值均<0.05)。获得pCR的三阴乳腺癌与非三阴乳腺癌患者的DFS(P=0.837)及OS(P=0.398)均无统计学差异。结论本研究结果表明,相比于非三阴乳腺癌患者,三阴乳腺癌患者具有更高的病理完全缓解率,但预后却较差。     

Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer

Background After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. Methods Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. Results SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. Conclusions SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.     

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

BackgroundAccuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT.MethodsThis retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR). Post-operatively, the pathologic response was defined as absence of tumor cells (ypT0), presence of non-invasive tumor cells (ypTis) or invasive tumor cells (ypTinv). Sensitivity and specificity of US as well as false negative rate (FNR), negative predictive value (NPV) and positive predictive value (PPV) were analysed for receptor subtypes. A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR.Results50 patients (40.3%) achieved pCR, 39 (78.0%) had a corresponding cCR. Overall sensitivity was 60.8% and specificity 78.0% for US-predicted remission. NPV and FNR differed substantially between subtypes. NPV was highest (75.0%) in triple negative (TN) subtype, while FNR was low (37.5%). Therefore, pathological response was most accurately predicted for TN cancers. NPV for human-epidermal-growth-factor-receptor-2-positive/hormone-receptor-positive (HER2+/HR+) was 55.6%, for HER2+/HR- 64.3% and for HER2-/HR+ 16.7%, FNRs were 40.0%, 71.4% and 32.3%, respectively. Receptor subtypes impacted pCR significantly (p-value: 0.0033), cCR correlated positively with pCR (p-value: 0.0026).ConclusionUS imaging is insufficient to predict pCR with adequate accuracy. Receptor subtypes, however, affect diagnostic precision of US and pathologic outcome.     

Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change in practice

ObjectivesChemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND).Materials and methodsA prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied.Results165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months.ConclusionThere is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.     

Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer

Background

Neoadjuvant chemotherapy reduces tumor size before surgery in women with breast cancer. The aim of this study was to assess the ability of mammography and ultrasound to predict residual tumor size following neoadjuvant chemotherapy.

Methods

In a retrospective review of consecutive breast cancer patients treated with neoadjuvant chemotherapy, residual tumor size estimated by diagnostic imaging was compared with residual tumor size determined by surgical pathology.

Results

One hundred ninety-two patients with 196 primary breast cancers were studied. Of 104 tumors evaluated by both imaging modalities, ultrasound was able to size 91.3%, and mammography was able to size only 51.9% (χ²P < .001). Ultrasound also was more accurate than mammography in estimating residual tumor size (62 of 104 [59.6%] vs 33 of 104 [31.7%], P < .001). There was little difference in the ability of mammography and ultrasound to predict pathologic complete response (receiver operating characteristic, 0.741 vs 0.784).

Conclusions

Breast ultrasound was more accurate than mammography in predicting residual tumor size following neoadjuvant chemotherapy. The likelihood of a complete pathologic response was 80% when both imaging modalities demonstrated no residual disease.