Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer

Purpose

Recently, Ki67 index (cell proliferation marker) has been attracting a considerable attention as a prognostic factor in breast cancer but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has rarely been examined.

Experimental design

Primary breast cancer patients (n = 102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited in the study. Ki67, estrogen receptor (ER) and progesterone receptor (PR) and breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry and HER2 was determined by FISH in tumor tissues obtained before and after NAC, and their association with patient prognosis (relapse-free survival) was examined.

Results

Of the 102 patients, pCR was achieved in 30 (29.4%). In the 72 non-pCR patients, Ki67 index significantly (P < 0.001) decreased after NAC. Ki67 index after NAC, but not Ki67 index before NAC, was significantly associated with a patient prognosis (P = 0.022). Multivariate analysis has shown that Ki67 index after NAC is a marginally significant (P = 0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein before and after NAC are not significant.

Conclusions

Ki67 after NAC, but not before NAC, is prognostic in breast cancer patients, and might be clinically useful in the prognosis prediction of patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein before and after NAC are unlikely to be useful as prognostic factors in these patients.     

Prognostic relevance of tertiary lymphoid organs following neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma

The efficacy of preoperative neoadjuvant chemoradiotherapy (NAC) in cases of pancreatic cancer with extremely poor prognoses has been reported. In this study, we aimed to identify novel biomarkers that reflect prognoses following chemoradiotherapy using tertiary lymphoid organs (TLO) expressed in the tumor microenvironment. Resected tumor specimens were obtained from 140 pancreatic cancer patients. We retrospectively investigated the clinical relevance of TLO by categorizing patients into those who underwent upfront surgery (surgery first [SF]) and those who received NAC. The immunological elements within TLO were analyzed by immunohistochemistry (IHC). In the IHC analysis, the proportions of CD8+ T lymphocytes, PNAd+ high endothelial venules, CD163+ macrophages and Ki‐67+ cells within the TLO were higher in the NAC group than in the SF group. In contrast, the proportion of programmed cell death‐1+ immunosuppressive lymphocytes within TLO was lower in the NAC group than in the SF group. The NAC group demonstrated favorable prognoses compared with the SF group. In the multivariate analysis, the TLO/tumor ratio was determined as an independent predictive prognostic factor. In conclusion, the administration of preoperative chemoradiotherapy may influence the immunological elements in the tumor microenvironment and result in favorable prognoses in pancreatic ductal adenocarcinoma patients.     

Unfavorable Cancer-specific Survival After Neoadjuvant Chemotherapy and Radical Cystectomy in Patients With Bladder Cancer and Squamous Cell Variant: A Multi-institutional Study

BackgroundNonurothelial carcinoma (UC) malignancies have traditionally been considered to have a more aggressive clinical course, and little is known about their response to neoadjuvant therapy. We examined the effect of neoadjuvant chemotherapy (NAC) on a large population of patients with bladder cancer (BCa) with different histologic variants (HVs).Patients and MethodsWe relied on a retrospective, multicenter database of 2858 patients with BCa who had undergone radical cystectomy with or without NAC from 1990 to 2017. Pure and mixed HVs were grouped into 6 categories: squamous cell carcinoma (SCC; n = 283; 45%), other subtypes (n = 95; 15%), micropapillary (n = 85; 14%), adenocarcinoma (n = 65; 10%), small cell (n = 54; 8.6%), and sarcomatous (n = 47; 7.6%). Kaplan-Meier and Cox regression analyses were used to examine cancer-specific survival (CSS) according to the HV, using pure UC as the reference. Logistic regression models were used to examine the odds of clinical-to-pathologic downstaging after NAC according to the HV.ResultsOverall, we identified 2229 cases of pure UC and 629 cases of BCa with HVs at radical cystectomy. Of the 450 NAC-treated patients, only those patients with SCC (n = 44; 9.8%) had had worse CSS (median CSS, 33 vs. 116 months; P < .001) and higher mortality rates (hazard ratio, 2.1; P = .03) compared with those with pure UC (n = 328; 72.9%). The results of the analyses were also confirmed when the pure and mixed cases were considered separately. After adjusting for NAC, only SCC showed a lower rate of clinical-to-pathologic downstaging (odds ratio, 0.4; P = .03) compared with UC.ConclusionsSCC was the HV exhibiting the lowest effect of NAC in terms of activity and CSS. Compared with pure UC, SCC seemed to be insensitive to traditional NAC regimens.     

乳腺癌新辅助化疗前后Ki67变化对疗效及预后的意义

目的：探讨乳腺癌新辅助化疗（NACT）前后Ki67表达变化对疗效和预后预测的临床意义。方法：回顾性分析汕头大学医学院附属肿瘤医院2009年12月—2013年9月期间收治的104例乳腺癌NACT后手术的患者。采用免疫组织化学评估配对的化疗前穿刺活检标本和手术切除标本中Ki67的表达情况。根据NACT前后Ki67的变化分为Ki67下降组和Ki67未下降（不变或升高）组,并对两组的临床病理学资料进行比较和生存分析。结果：NACT后Ki67下降组占62.5%（65/104）,未下降组占37.5%（39/104）。NACT前高表达Ki67的患者经NACT后Ki67显著下降（63/91,P < 0.01）。Ki67下降组更容易获得有效的临床效果即达到临床完全/部分缓解（59/65,P=0.005）,且NACT后Ki67下降值与临床疗效相关（r=0.302,P=0.002）。NACT后Ki67下降组的无病生存率明显高于Ki67未下降组,差异有统计学意义（P=0.027）;Ki67下降组的总生存率高于Ki67未下降组,但差异无统计学意义（P=0.171）。结论：乳腺癌NACT后Ki67表达下降可能是疗效和预后的预测因子。     

Organic cation transporter 2 for predicting cisplatin-based neoadjuvant chemotherapy response in gastric cancer

Some studies have shown the usability of neoadjuvant chemotherapy (NAC) in gastric cancer (GC). Nevertheless there are a few predictive markers of the effectiveness of NAC in GC. The aim of this study is to assess the predictive impact of organic cation transporter 2 (OCT2) expression on response to neoadjuvant chemotherapy (NAC) in gastric cancer. We retrospectively assessed 66 patients with advanced gastric cancer received NAC with S-1/cisplatin or paclitaxel/cisplatin. Expression levels of OCT2 were assessed by immunohistochemistry in pre-chemotherapy biopsies and correlated with clinicopathologic parameters including pathologic response. High expression level of OCT2 (OCT2^high) was significantly associated with intestinal type according to Laurén classification (P = 0.03) and low histologic grade (P = 0.03). In univariate analysis of the entire cohort, no variables showed any significant association with a response, although intestinal type (P = 0.09), low histologic grade (P = 0.09), and OCT2^high (P = 0.07) tended to be more frequent in responders compared with non-responders. When the two treatment groups were separately assessed in the univariate analysis, a significantly higher rate of OCT2^high was observed in responders compared with non-responders in the S-1/cisplatin group (P = 0.001). In addition, multivariate analysis identified OCT2^high as the sole independent predictor of response (P = 0.04). However, in the paclitaxel/cisplatin group, no variables were associated with response. Taken together, our results suggest that OCT2^high may represent a potential predictor of response to NAC with S-1/cisplatin in gastric cancer.     

Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3-4aN0M0 compared to cT2N0M0 bladder cancer

In this study, we compared complete pathological downstaging (pCD, ≤(y)pT1N0) and overall survival (OS) in patients with cT2 versus cT3–4aN0M0 UC of the bladder undergoing radical cystectomy (RC) with or without neoadjuvant chemo- (NAC) or radiotherapy (NAR). A population-based sample of 5,517 patients, who underwent upfront RC versus NAC + RC or NAR + RC for cT2-4aN0M0 UC between 1995–2013, was identified from the Netherlands Cancer Registry. Data were retrieved from individual patient files and pathology reports. pCD-rates were compared using Chi-square tests and OS was estimated by Kaplan–Meier analyses. Multivariable analyses were conducted to determine odds (OR) and hazard ratios (HR) for pCD-status and OS, respectively. We included 4,504 (82%) patients with cT2 and 1,013 (18%) with cT3–4a UC. Median follow-up was 9.2 years. In cT2 UC, pCD-rate was 25% after upfront RC versus 43% (p < 0.001) and 33% (p = 0.130) after NAC + RC and NAR + RC, respectively. In cT3–4a UC, pCD-rate was 8% after upfront RC versus 37% (p < 0.001) and 16% (p = 0.281) after NAC + RC and NAR + RC, respectively. In cT2 UC, 5-year OS was 57% and 51% for NAC + RC and upfront RC, respectively (p = 0.135), whereas in cT3–4a UC, 5-year OS was 55% for NAC + RC versus 36% for upfront RC (p < 0.001). In multivariable analysis for OS, NAC was beneficial in cT3–4a UC (HR: 0.67, 95%CI 0.51–0.89) but not in cT2 UC (HR: 0.91, 95%CI 0.72–1.15). NAR did not influence OS. In conclusion, NAC + RC was associated with superior pCD compared to RC alone and NAR + RC. Superior OS for NAC + RC compared to RC alone was especially evident in cT3–4a disease.     

ALDH1 is an independent prognostic factor for patients with stages II–III rectal cancer after receiving radiochemotherapy

Background:

About one in five patients with locally advanced rectal cancer (RC) suffers recurrence or distant metastasis after neoadjuvant therapy. We investigated how cancer stem cell markers change after neoadjuvant therapy and how these markers relate to recurrence.

Methods:

Pretreatment biopsies and postoperative specimens were taken from 64 patients with locally advanced rectal adenocarcinoma who received preoperative radiochemotherapy (RCT) between sampling. Samples were tested immunohistochemically for CD44, LGR5, ALDH1 and CD166; scores were dichotomised as high or low. The median follow-up period was 36 months.

Results:

High expression of CD44, LGR5, ALDH and CD166 was found in 38%, 5%, 48% and 10%, respectively, before RCT and 86%, 33%, 71% and 52%, respectively, after RCT. CD44 (P=0.001), LGR5 (P=0.049) and CD166 (P=0.003) were significantly upregulated after RCT. Whereas no recurrence was seen during the follow-up in the low ALDH group, 40% of the high ALDH group suffered recurrence. In multivariate COX analysis, postoperative ALDH1 independently predicted poor prognosis in patients with RC who received RCT (P=0.0095).

Conclusion:

Preoperative RCT upregulates expression of stem cell markers in patients with RC. High post-treatment ALDH1 expression predicts poor prognosis for these patients after neoadjuvant therapy.     

青年乳腺癌患者新辅助化疗后免疫组化标记的改变及其对预后的影响分析

目的:分析青年乳腺癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)后免疫组化标记的改变及其对预后的影响。方法:选取年龄≤40岁行新辅助化疗的133例乳腺癌患者,依据NAC前后免疫组化标记值的变化分为<10%组、10%~30%组、>30%组,对比变化幅度和生存率与病理分级的相关性。结果:青年乳腺癌患者NAC后的pCR率与HR、Ki67水平、分子分型及淋巴结状态密切相关;PR在NAC前后的变化幅度能够显著影响DDFS、OS及MPG分级,而ER、Ki67的变化幅度与生存和MPG分级无关。结论:青年乳腺癌患者NAC后PR的变化幅度与MPG分级密切相关,并能够显著影响患者的DDFS和OS。     

Pathological features of triple‐negative breast cancers that showed progressive disease during neoadjuvant chemotherapy

Clinical progressive disease (cPD) occurs during neoadjuvant chemotherapy (NAC) in 3%–5% of triple‐negative breast cancer (TNBC) patients. We aimed to identify the histopathological and immunohistochemical parameters that are correlated with the TNBC that showed cPD. We identified 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group). Using surgically resected tumor specimens, we performed histopathologic examinations and immunohistochemical analysis of 11 molecules that appeared relevant to epithelial‐mesenchymal transition (EMT), and basal‐like, molecular apocrine and other features. Metaplastic carcinomas (MPCs) and high proliferation (≥50 mitoses per 10 high‐power fields or ≥50% Ki‐67 score) were more frequent in the cPD than in the control (41% vs 3%, P < 0.001, and 86% vs 50%, P = 0.0049, respectively). Positive cytokeratin 5/6, ZEB1, TWISTNB, vimentin, and HMGB1 expressions and negative androgen receptor were more frequent in the cPD than in the control. By an unsupervised hierarchical cluster analysis incorporating these 11 molecules, the 102 TNBCs were divided into two major clusters and seven subclusters that appeared to correspond to intrinsic subtype, cPD status, histological type, and clinical outcome. In 27% of cPD cases, the MPC component appeared only in the post‐NAC specimens. The combinations of high proliferation, metaplastic features, and immunohistochemical statuses of some EMT and basal‐like markers and androgen receptor appeared to be able to characterize the TNBCs that showed cPD after NAC.     

Still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival

IntroductionDistant recurrence, especially liver metastases, occurs in one-third of rectal cancer patients initially treated with curative therapy and is still an unsolved problem. The identification of patients at risk is crucial for enabling individualized treatment.Material and methodsAll patients undergoing curative resection for histologically confirmed rectal cancer after neoadjuvant radiochemotherapy between January 2001 and December 2015 were included. Sections were stained for Ki67, CD44, apoptosis and CD133. Patients were categorized based on whether they were found to have (CD44⁺/Ki67⁺) or not have (CD44⁺/Ki67⁺) still proliferating tumor cells.Results218 patients who underwent R0 resection for stage I-III rectal cancer were selected. In 37 (17%) of these patients, CD44⁺/Ki67⁺ tumor cells were found. In multivariable Cox regression analysis, patients with CD44⁺/Ki67⁺ cells had significantly impaired overall (hazard ratio (HR): 3.84, 95% CI: 1.77–8.31, p = 0.001) and relative survival (HR 3.44, 95% CI: 1.46–8.09). The previous results were confirmed after propensity-score matching. In mediation-analysis, the presence of CD44⁺/Ki67⁺ cells was associated with a substantial direct effect on overall (HR 1.92, 95% CI: 1.09–9.28) and relative survival (HR 1.63, 95% CI: 1.31–6.38).ConclusionsThe presence of still proliferating CD44⁺/Ki67⁺ tumor cells after neoadjuvant radiochemotherapy was associated with impaired oncological long-term outcomes. Characterization of these cells should be performed.     

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

IntroductionThe addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.MethodsAll LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.ResultsOf 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).ConclusionTreatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.     

Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers

The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline‐taxane‐based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer‐related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation (P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification (P < 0.001 for both ypT0/isypN0 and ypT0/is) were related to higher pCR rates. PIK3CA mutation (P = 0.040 for ypT0/isypN0) and CCND2 amplification (P = 0.042 for ypT0/is) showed reduced sensitivity to NAC. Patients with MAPK pathway alteration had low pCR rates (P = 0.043 for ypT0/is). Patients with TP53 mutation (?) PIK3CA mutation (?) ERBB2 amplification (+) CCND1 amplification (?), TP53 mutation (+) PIK3CA mutation (?) ERBB2 amplification (+) CCND1 amplification (?) or TP53 mutation (+) PIK3CA mutation (+) ERBB2 amplification (+) CCND1 amplification (?)had significantly higher pCR rates (P < 0.05 for ypT0/isypN0 and ypT0/is) than wild type genotype tumors. Some cancer genetic alterations as well as pathway alterations were associated with chemosensitivity to NAC treatment. Our study may shed light on the molecular characteristics of breast cancer for prediction of NAC expectations when breast cancer is first diagnosed by biopsy.     

Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer

Oestrogen receptor (ER) negative breast cancers are more likely to achieve a pathological complete response (pCR) to neoadjuvant chemotherapy compared to those with ER positive tumours. ER positive tumours exhibit low proliferation and ER negative cancers high proliferation. The aim of this study was to determine to what extent the better response of ER negative cancers correlates with proliferation rate. A retrospective analysis of a prospectively maintained database identified 175 neoadjuvant chemotherapy patients with tissue available for Ki67 analysis. On univariate analysis, pre-therapy Ki67 (P = 0.04), ER status (P = 0.002), HER2 status (P = 0.004) and grade (P = 0.0009) were associated with a pCR. In a multivariate model, HER2 was the only significant predictor of pCR. No significant relationship between pre-therapy Ki67 and relapse-free and overall survival was demonstrated. Ki67 is not an independent predictor of clinical CR or pCR. Aspects of ER status beyond its inverse relationship with proliferation may contribute to its predictive value for pCR.     

Assessing the Impact of Neoadjuvant Chemotherapy on the Management of the Breast and Axilla in Breast Cancer

BackgroundNodal status is a sensitive prognostic indicator in breast cancer. Axillary metastases may be an indication for neoadjuvant systemic therapy. The aims of this study were to compare pathologic response rates to neoadjuvant chemotherapy (NAC) in the breast and axilla across different molecular subtypes of breast cancer and to compare the predictive value of axillary assessment before and after chemotherapy in determining final nodal status in this cohort of patients.Patients and MethodsThe cohort comprised patients undergoing NAC from 2003 to November 2012. Data regarding patient and tumor characteristics, management, and outcomes were obtained from a prospectively maintained database and analyzed using PASW Statistics, version 18 (SPSS Inc, Chicago, IL).ResultsTwo hundred two cancers were identified in 196 patients. One hundred thirty-one (65%) diagnostic axillary procedures were performed, 105 (80%) before NAC, of which 93 (89%) were positive. In 28 (30%), downstaging was noted before NAC. Human epidermal growth factor receptor 2 (HER2) subtypes had the highest rate of complete pathologic response (n = 11 [61%]) and negative axillary clearance (AXCn) (n = 11 [69%]). Of 177 AXCns, 68 (38%) were negative before NAC.ConclusionAXCn in patients undergoing NAC remains controversial. HER2 subtypes are less likely to have axillary involvement after NAC and may demand different management.     

Imunoexpression of Ki-67 and p53 in Rectal Cancer Tissue After Treatment with Neoadjuvant Chemoradiation

Introduction

Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice.

Aim

The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment.

Patients and Methods

Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG).

Results

Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p?=?0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p?=?0.052. We have not found any difference among metastasis development in the groups (p?=?0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p?=?0.041). Patients with positive or negative p53 tumors had similar survival (p?=?0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p?=?0.069).

Conclusion

The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.     

Tumor-Infiltrating PD-1+ Immune Cell Density is Associated with Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer

BackgroundElevated tumor-infiltrating T-cell density is associated with favorable outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Here, we evaluated the significance of programmed cell death 1 (PD-1)-positive cells, regulatory T cells, and macrophages in response to CRT and prognosis.Patients and MethodsWe assessed CD8+, PD-1+, FOXP3+, CD68+, and CD163+ intratumoral and stromal cell densities by immunohistochemistry using pre-treatment biopsies from 275 patients with rectal cancer treated with neoadjuvant CRT. We determined the impact of these measurements on response to CRT and survival. Response to CRT was determined by tumor regression grade (TRG) of surgical specimens, with good responders defined as TRG3-4.ResultsIntratumoral CD8+ and PD-1+ cell densities were significantly higher in good responders than in poor responders, whereas stromal CD68+ cell density was significantly lower in good responders as compared with poor responders. The multivariable analysis revealed high intratumoral CD8+ and PD-1+ cell densities to be independently associated with good responders (CD8: odds ratio [OR], 2.27; 95% confidence interval [CI], 1.21 – 4.34, P = .010; PD-1: OR, 1.97; 95%CI, 1.03 – 3.84, P = .039), and improved recurrence-free survival (CD8: hazard ratio [HR], 0.56; 95%CI, 0.32 – 0.98, P = .044; PD-1: HR, 0.37; 95%CI, 0.19 – 0.71, P = .002). Only high intratumoral CD8+ cell density was associated with improved overall survival (P = .022).ConclusionPre-treatment high intratumoral PD-1+ and CD8+ cell densities were independently associated with good response to CRT and improved recurrence-free survival, with high intratumoral CD8+ cell density additionally associated with improved overall survival. These values may serve as predictive and prognostic biomarkers in rectal cancer.     

Impact of neoadjuvant therapy on postoperative complications in non-small-cell lung cancer patients subjected to anatomic lung resection

ObjectiveTo study the impact of neoadjuvant therapies on postoperative complications and mortality among non-small-cell lung cancer (NSCLC) patients subjected to anatomic lung resection and included in the Spanish cohort of the video-assisted thoracic surgery (GE-VATS) multicenter database.MethodsThe study included a total of 3085 patients from 33 centers between December 2016 and March 2018. We performed a comparative analysis of the complications and mortality in patients who received neoadjuvant therapies (n = 263) versus those who did not (n = 2822). A propensity score-matched analysis was used to adjust for potential confounders. Association between exposure in two groups and outcomes were estimated by logistic regression weighted by inverse of probability of receiving the treatment that actually received.ResultsIn the unadjusted analysis, the chemotherapy (CT) and chemoradiotherapy (CRT) group presented a higher frequency of ICU readmissions, reinterventions, empyema, cardiovascular complications, a greater frequency of atrial fibrillation, and an increased need for blood product transfusions. In the adjusted group, CT and CRT patients had a higher rate of cardiovascular complications (CT p = 0.002; OR 2.29; 95% CI 1.34–3.94 and CRT p = 0.001; OR 2.90; 95% CI 1.52-5-52), arrhythmias (CT p = 0.013; OR 2.23; 95% CI 1.18–4.20 and CRT p = 0.046; OR 2.22; 95% CI 1.01–4.90) and transfussions (CT p = 0.042; OR 2.95; 95% CI 1.04–8.35 and CRT p < 0.001; OR 7.74; 95% CI 3.01-19-92).ConclusionsBased on our series, neoadjuvant CT and CRT were associated with a higher rate of cardiovascular complications, arrhythmias and transfussions in patients with NSCLC subjected to anatomic lung resection.     

Outcomes and survival following neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus: Inverse propensity score weighted analysis

BackgroundEsophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach.MethodsDemographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate.ResultsData for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p = 0.807), including major complications (24.0% vs. 23.6%, p = 0.943) and anastomotic leak (7.8% vs. 5.6%, p = 0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p = 0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p = 0.006. There was no difference between groups for overall or disease-free survival.ConclusionThis study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are still lacking.     

Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter,randomized, phase-II study

BackgroundLuminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting.Patients and MethodsPatients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² × 4 cycles followed by docetaxel 100 mg/m² × 4 cycles [EC-T]) or HT (exemestane 25 mg daily × 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging.ResultsNinety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT.ConclusionsLuminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.