Neoadjuvant Chemotherapy With mFOLFOXIRI Without Routine Use of Radiotherapy for Locally Advanced Rectal Cancer

IntroductionAlthough neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC.Patients and MethodsPatients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT_0-2N₀M₀. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety.ResultsOverall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated.ConclusionNeoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.     

局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析

目的:探索局部进展期直肠癌(LARC)经新辅助化疗后病理完全缓解（pCR）和肿瘤降期（ypT0-1）的预测因素。方法:回顾性分析71例经新辅助化疗后进行全直肠系膜切除术的局部进展期直肠癌患者的临床资料,分析其临床特征,筛选经新辅助化疗后达到pCR及肿瘤降期（ypT0-1）的预测因子。结果:单因素分析结果显示肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.001）、基线临床N分期为N0期（P=0.019）以及新辅助治疗2周期后影像评估为缓解（P=0.002）与直肠癌新辅助化疗后的高pCR率有关;肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.029）以及新辅助治疗2周期后影像评估为缓解（P=0.007）与直肠癌新辅助化疗后的高肿瘤降期率（ypT0-1）有关。多因素Logistic回归分析结果显示,肿瘤占肠腔环周大小（P=0.013）、基线CEA水平（P=0.042）以及基线临床N分期（P=0.038）是影响直肠癌新辅助化疗后pCR的独立预测因子;肿瘤占肠腔环周大小（P=0.001）是影响直肠癌新辅助化疗后肿瘤降期（ypT0-1）的独立预测因子。结论:初始诊断时肿瘤占肠腔环周大小、基线CEA水平及淋巴结是否阳性对局部进展期直肠癌新辅助化疗后pCR有预测作用,肿瘤占肠腔环周大小对局部进展期直肠癌新辅助化疗后肿瘤降期（ypT0-1）有预测作用。     

Mucinous Adenocarcinoma Predicts Poor Response and Prognosis in Patients With Locally Advanced Rectal Cancer: A Pooled Analysis of Individual Participant Data From 3 Prospective Studies

PurposeTo evaluate the predictive implications and prognosis of mucinous adenocarcinoma (MAC) in locally advanced rectal cancer (LARC) with intensified neoadjuvant treatment.MethodsIndividual patient data of LARC patients from 3 prospective clinical trials was analyzed. Neoadjuvant treatment regimens comprised chemoradiotherapy (CRT) with fluorouracil (5-FU) or mFOLFOX6, neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI. The postoperative pathological result, local recurrence and disease-free survival (DFS) were retrospectively analyzed in patients with MAC and adenocarcinoma (AC) with neoadjuvant treatment.ResultsTotally, 743 patients were recruited, with 620 patients eligible for analysis. Fifty-three (8.5%) patients were MAC. The pathological complete response (pCR) rate and tumor downstaging rate (ypStage 0-I) between MAC and AC patients was 7.5% vs. 22.0% (P = .01) and 20.8% vs. 48.7% (P < .001), respectively. Among patients receiving preoperative CRT with 5FU or mFOLFOX6, the pCR rate and tumor downstaging rate between MAC and AC patients was 11.1% vs. 27.3% (P = .03) and 23.7% vs. 52.6% (P = .001), respectively. Regarding neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI, the pCR rate and tumor downstaging rate was 0 vs.13.2% (P = .11) and 11.8% vs. 42.5% (P = .03) between MAC and AC group, respectively. With the median follow-up time of 38.9 months, the 3-year DFS and 3-year locoregional recurrence rate was 58.4% vs. 77.6% (P = .02) and 26.0% vs. 5.7% (P = .001) in the MAC and AC group, respectively. MAC (hazard ratio [HR] 1.85, 95% confidence interval [CI], 1.15-2.98), PNI (HR 3.23, 95% CI, 1.85-5.72) and LVI (HR 2.04, 95% CI, 1.02-4.08) were independent prognosis factors and were associated with worse DFS.ConclusionsPatients with MAC of the rectum are associated with a lower pCR rate and tumor downstaging rate, higher incidence of local recurrence, and poorer DFS with neoadjuvant treatment.     

Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

BACKGROUNDPatients with clinical T4 colorectal cancer (CRC) have a poor prognosis because of compromised surgical margins. Neoadjuvant therapy may be effective in downstaging tumors, thereby rendering possible radical resection with clear margins. AIMTo evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.METHODSThis study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection. Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents, either FOLFOX or capecitabine. A circumferential resection margin (CRM) of < 1 mm was considered to be a positive margin. We defined pathological complete response (pCR) as the absence of any malignant cells in a specimen, including the primary tumor and lymph nodes. A multivariate logistic regression model was used to identify independent predictive factors for pCR.RESULTSFor 86 patients who underwent neoadjuvant chemoradiotherapy and surgery, the rate of pCR was 14%, and the R0 resection rate was 91.9%. Of the 61 patients with rectal cancer, 7 (11.5%) achieved pCR and 5 (8.2%) had positive CRMs. Of the 25 patients with colon cancer, 5 (20%) achieved pCR and 2 (8%) had positive CRMs. We observed that the FOLFOX regimen was an independent predictor of pCR (P = 0.046). After a median follow-up of 47 mo, the estimated 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.8% and 61.4%, respectively. Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS (P = 0.014) and OS (P = 0.001). Patients who achieved pCR exhibited longer DFS (P = 0.042) and OS (P = 0.003) than those who did not.CONCLUSIONNeoadjuvant concurrent chemoradiotherapy engenders favorable pCR and R0 resection rates among patients with T4 CRC. The R0 resection rate and pCR are independent prognostic factors for patients with T4 CRC.     

HER2 and response to anthracycline-based neoadjuvant chemotherapy in breast cancer

BackgroundThe predictive role of human epidermal growth factor receptor 2 (HER2) to adjuvant anthracycline-based chemotherapy remains controversial. Here, we investigated the association between HER2 status and pathological response in breast cancer patients who received neoadjuvant anthracycline-based regimens.Patients and methodsWomen (n = 538) with operable primary breast cancer received neoadjuvant anthracycline-based chemotherapy. Pathological complete response (pCR) was defined as no invasive breast tumor cells in breast after completion of neoadjuvant chemotherapy. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core biopsy breast cancer tissue obtained before initiation of neoadjuvant chemotherapy.ResultsIn this cohort of 538 patients, 23.9% of patients achieved a pCR in their breast. HER2-positive tumors had a lower rate of pCR than did HER2-negative tumors (14.7% versus 25.7%, P = 0.013); negative HER2 status remained as an independent favorable predictor of pCR after adjusted for age, estrogen receptor, progesterone receptor, tumor size, chemotherapy cycles, and tumor grade in a multivariate analysis (odds ratio = 3.14; 95% confidence interval = 1.60–6.16, P = 0.001). Furthermore, patients with a pCR had a higher 3-year disease-free survival (DFS) rate than did patients without a pCR (P = 0.007).ConclusionWomen with HER2-negative breast cancers rather than HER2-positive tumors benefit from anthracycline-based neoadjuvant chemotherapy.     

Downstaging of Muscle-Invasive Bladder Cancer Using Neoadjuvant Gemcitabine and Cisplatin or Dose-Dense Methotrexate,Vinblastine, Doxorubicin,and Cisplatin as Single Regimens or as Switch Therapy Modalities

BackgroundConsensus guidelines recommend gemcitabine and cisplatin (GC) or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) as equally preferable neoadjuvant chemotherapy before cystectomy for muscle-invasive bladder cancer. This study sought to compare the ability of GC and ddMVAC to achieve pathologic response; and to evaluate the benefit of switching regimens after 1 or 2 cycles of the other.Patients and MethodsPatients aged ≥ 18 with muscle-invasive bladder cancer (≥ cT2) and who had received either GC or ddMVAC as neoadjuvant chemotherapy followed by cystectomy were retrospectively evaluated using the electronic medical record. Patients who received 1 or 2 cycles of one regimen followed by several cycles of the other regimen before cystectomy were classified as switch therapy patients. This study assessed the rates of pathologic complete response (pCR) and any degree of downstaging.ResultsAmong 109 patients who received GC or ddMVAC, 7 (21%) of 33 ddMVAC patients demonstrated pCR, and 19 (25%) of 76 GC patients demonstrated pCR (odds ratio, 1.24; 95% confidence interval, 0.46-3.31; P = .67). Downstaging rates were 39% for ddMVAC and 50% for GC (P = .31). Thirty-three of 36 patients aged ≥ 70 years received GC (P < .001). Four of 7 patients treated with switch therapy showed downstaging, and 2 of 7 experienced pCR.ConclusionThere was no difference in pCR rates between GC and ddMVAC, and patients were most often able to receive 3 or 4 cycles of treatment. Switch therapy may be of benefit in patients whose disease has a poor initial response.     

Neoadjuvant intraperitoneal and systemic paclitaxel combined with apatinib and S-1 chemotherapy for conversion therapy in gastric cancer patients with positive exfoliative cytology: a prospective study

BackgroundTo explore the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel chemotherapy combined with apatinib and S-1 in the treatment of gastric cancer patients with positive exfoliative cytology.MethodsPatients with gastric cancer (P₀CY₁) who were confirmed to have free cancer cells (FCCs) in the abdominal cavity after laparoscopic exploration from April 2018 to August 2019 were enrolled. All patients underwent NIPS chemotherapy using paclitaxel combined with apatinib and S-1 treatment. Laparoscopic exploration was performed after 3 cycles of conversion therapy. The primary study endpoint was the FCC negative rate, and the secondary study endpoints were overall survival time (OS), progression-free survival time (PFS), objective response rate (ORR), disease control rate (DCR), and safety indicators.ResultsOut of 312 advanced gastric cancer patients who underwent laparoscopic exploration, 36 patients with P₀CY₁ gastric cancer were identified and enrolled in this study. After 3 cycles of conversion therapy, the ORR was 80.56% and the DCR was 94.44%. All patients underwent secondary laparoscopic exploration, and the FCC conversion rate was 77.78%. All patients with negative FCC underwent R0 surgical resection, with a median follow-up time of 11.4 months. The median survival time was 15.5 months, and the 1-year OS was 80.55%. The median PFS was 14.4 months, and the 1-year PFS was 75.00%. Treatment-related grade 3 adverse reactions were mainly leukopenia and neutropenia. No grade 4 adverse reactions were observed. There were no reported deaths related to chemotherapy or surgery in the study cohort.ConclusionsNIPS with paclitaxel combined with apatinib and S-1 treatment may increase the FCC negative rate of P₀CY₁ gastric cancer patients.     

Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21 755 patients from the Japanese breast cancer registry

BackgroundWe investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.Patients and methodsRecords of more than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.ResultspCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.ConclusionWe confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.     

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial

BackgroundThe neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort.Patients and methodsPatients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0.ResultsHigher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%,P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3–4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline.ConclusionIn HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane–epirubicin–cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.     

Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer

Introduction

Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands.

A simple system for grading the response of breast cancer to neoadjuvant chemotherapy

BackgroundThe response of primary breast cancer to chemotherapy is usually expressed either as a pathological complete remission (pCR) or as ‘no pCR’. A more quantitative measure is called for.Patients and methodsThe ‘neoadjuvant response index’ (NRI) was calculated by adding a breast response score (a number from a five-point scale) to an axillary response score (a number from a three-point scale) and dividing this by the score that would have been obtained in case of a pCR in both breast and axilla. Consequently, the NRI is a number between 0 (representing no response) and 1 (a pCR of both breast and axilla).ResultsThe NRI was calculated in 267 patients who had received neoadjuvant chemotherapy. The average NRI was 0.48 (median 0.40). Forty-one patients (15%) had an NRI of 0; 55 patients (21%) had an NRI of 1 (pCR). ‘Highly endocrine responsive’ tumors responded substantially less than ‘incompletely endocrine responsive’ ones. In triple negatives, an NRI of >0.70 was associated with a better recurrence-free survival than a lower NRI.ConclusionsThe NRI proposed here may be useful to better reflect the efficacy of neoadjuvant systemic regimens than the binary pCR–‘no pCR’ system.     

Feasibility Study of Nanoparticle Albumin-Bound-Paclitaxel and S-1 Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With Operable Breast Cancer: A Prospective Study

BackgroundThe efficacy and safety of nanoparticle albumin-bound (nab)-paclitaxel combined with S-1 in patients with operable breast cancer is uncertain. We evaluated the feasibility of this combination followed by epirubicin/cyclophosphamide (EC) as neoadjuvant chemotherapy in such patients.Patients and MethodsThis was an open-label, single-arm, phase II, single-institution prospective study of 4 cycles of nab-paclitaxel (260 mg/m²) administered intravenously on day 1 in combination with S-1 (65 mg/m² orally twice daily) on days 1 to 14 every 21 days followed by EC as neoadjuvant chemotherapy.ResultsOf 30 patients, 1 required a dose interruption for nab-paclitaxel combined with S-1; 4 required a dose reduction for nab-paclitaxel, 1 for S-1, and 4 for EC. Mean relative dose intensities of nab-paclitaxel, S-1, and EC were 98.0%, 99.3%, and 98.2%, respectively. Overall clinical response rate was 96.7%. In histological response, grade 3, pathological complete response (pCR; ypT0/is and ypN0) rate was 63.3% and grade 2b (near pCR) was 3.3%. pCR was observed in 57.1% of luminal B human epidermal growth factor receptor type 2 (HER2)-negative patients, 55.6% of luminal B HER2-positive patients, 100% of HER2-positive patients, and 57.1% of triple-negative breast cancer patients. Grade 3/4 neutropenia was observed in 1 patient during nab-paclitaxel combined with S-1 and in 7 during EC treatments. The most frequent nonhematological severe adverse events were grade 3 peripheral neuropathy in 2 patients and grade 3 arthralgia in 2 patients during nab-paclitaxel combined with S-1.ConclusionTri-weekly nab-paclitaxel with S-1 followed by EC is effective and well tolerated as neoadjuvant chemotherapy in patients with operable breast cancer.     

Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer

BackgroundWe sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab.Patients and methodsTwo hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (<pCR, n = 115); as well as by pathologic stage. Locoregional recurrence-free (LRFS), distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) rates were compared.ResultsThe median follow-up was 63 (range 53–77) months. There was no difference in clinical stage between patients with pCR or <pCR. Compared with patients achieving <pCR, those with the pCR had higher 5-year rates of LRFS (100% versus 95%, P = 0.011), DMFS (96% versus 80%, P < 0.001), RFS (96% versus 79%, P < 0.001), and OS (95% versus 84%, P = 0.006). Improvements in RFS and OS were seen with decreasing post-treatment stage. Failure to achieve a pCR was the strongest independent predictor of recurrence (hazard ratio [HR] = 4.09, 95% confidence interval [CI]: 1.67–10.04, P = 0.002) and death (HR = 4.15, 95% CI: 1.39–12.38, P = 0.011).ConclusionspCR and lower pathologic stage after neoadjuvant chemotherapy with trastuzumab are the strongest predictors of recurrence and survival and are surrogates of the long-term outcome in patients with HER2-overexpressing disease.     

Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients

Purpose

We aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.

Methods

Medical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.

Results

Of a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.

Conclusion

The pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.     

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.Material and methodsA systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).ResultsNine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.ConclusionIn TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.PROSPERO registration numberCRD42018080042.     

mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A Propensity Score Matching Analysis

BackgroundPreoperative chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, CRT failed to impact metastatic recurrence and the risk of side effects on bowel and genitourinary remained a concern. Neoadjuvant chemotherapy alone with mFOLFOX6 or FOLFOXIRI had been investigated in LARC. Here, we tried to compare the efficacy of mFOLFOXIRI with mFOLFOX6 as neoadjuvant chemotherapy in LARC.Patients and MethodsBetween January 2014 and December 2019, patients with LARC receiving neoadjuvant chemotherapy with mFOLFOXIRI or mFOLFOX6 were retrospective analyzed, including data from a prospective trial (NCT02217020). All patients underwent total mesorectal excision (TME). The propensity-score matching was preformed to adjust baseline potential confounders and to estimate differences in outcomes between patients receiving mFOLFOXIRI and mFOLFOX6. Survival analysis was done using Kaplan–Meier analysis and Cox proportional regression analysis.ResultsThe median follow-up time was 31.1 months. After propensity score matching, 156 patients were available for comparison in each group. The pathological complete response (pCR) rate was 17.9% vs. 5.1% (P< .001), the incidence rate of anastomotic fistula was 3.2% vs. 9% (P = .03), the 3 year disease-free survival (DFS) rate was 75% vs. 66.7% (P = .047) and the distant metastasis rate was 16.4% versus 26.6% (P = .013) for mFOLFOXIRI and mFOLFOX6 group, respectively. Patients receiving mFOLFOXIRI had higher incidence of grade III and/or IV nausea and/or vomiting (7.6% vs. 2.5%, P = .04).ConclusionsNeoadjuvant mFOLFOXIRI regimens improved pCR rate and survival outcome, reduced the rate of distant metastasis and anastomotic fistula when comparing with propensity-score matched controls of mFOLFOX6 neoadjuvant chemotherapy.MicroAbstractThis trial assessed the short-term and long-term effects of neoadjuvant chemotherapy with mFOLFOXIRI and mFOLFOX6 in patients with locally advanced rectal cancer. Comparing with propensity-score matched historical control of chemoradiotherapy, neoadjuvant mFOLFOXIRI chemotherapy was well tolerated and led to higher rates of 3 year disease-free survival in patients with locally advanced rectal cancer.     

Utility of 18F-FDG PET for Predicting Histopathologic Response in Esophageal Carcinoma following Chemoradiation

IntroductionFor patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) followed by surgical resection, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) response to neoadjuvant CRT and pCR.MethodsMaximum standardized uptake values and standardized uptake ratios (SURs) were measured before and after CRT. SUR was normalized to liver uptake and mediastinal blood pool uptake. FDG PET complete response was defined as metabolic activity normalization to hepatic and blood pool activity. The correlation between FDG PET parameters and pCR was examined through logistic regression analyses.ResultsIn total, 193 patients were monitored for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and stage T3 (75%). Complete FDG PET response and pCR occurred in 27% and 34% of patients, respectively. Histologic findings, chemotherapy type, tumor stage, and radiation dose were not significantly associated with complete radiographic response. The rates of pCR in patients with and without radiographic complete response were 42% and 31% (p = 0.17), respectively. No predictive correlation was found between pCR and change in maximum standardized uptake value (p = 0.25), in SUR normalized to blood pool uptake (p = 0.20), or in SUR normalized to liver uptake (p = 0.15). The 5-year OS rate was 46% for patients with a complete FDG PET response versus 44% without a complete response (p = 0.78). The 5-year OS rate of patients who achieved pCR was 49% versus 43% for patients with residual tumor (p = 0.04).ConclusionFor patients with esophageal cancer who received neoadjuvant chemoradiation, pretreatment and posttreatment FDG PET parameters did not correlate with pCR or OS.     

Characterization of Weakly Hormone Receptor (HR)-Positive,HER2-Negative Breast Cancer and Current Treatment Strategies

BackgroundHormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status is critical for determining management of breast cancer. Previous reports of small cohorts with weak HR-positive (HR+)/HER2-negative (HER2-) disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative breast cancer (TNBC). This study aims to further characterize this group, focusing on pCR rates following NAC.Patients and MethodsPatients with stage I-III, HR+/HER2- breast cancer were identified using the University of Wisconsin Hospital Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of estrogen and progesterone receptor (≤33%), treatment, and follow-up data.ResultsData was reviewed from 2,900 patients and a total of 64 patients met inclusion criteria. Eighty percent received chemotherapy, about half with NAC (n = 30, 48%). Of 28 patients who received NAC followed by breast and axillary surgery, 12 (43%; 95% CI 25%-63%) had pCR (ypT0/Tis/ypN0). Of the 11 patients who had biopsyproven nodal disease at diagnosis and NAC followed by axillary surgery, 7 (64%, 95% CI 31%-89%) patients had pCR at the axilla. Only one patient with pCR developed recurrent disease. For those that recurred, median time to recurrence was 13.6 (5.6-48.7) months.ConclusionsBreast cancers that are HER2- and weakly HR+ treated with NAC demonstrated pCR rate more similar to TNBC than breast cancers that are strong HR+. Neoadjuvant approaches may improve pCR rates, which provides important prognostic information. Clinical trials should be developed to focus on this unique patient cohort.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy

BACKGROUND: We surveyed single-center and multi-center studies pertaining to sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy to compare the results with those of our current study to evaluate the feasibility and accuracy of SLNB after neoadjuvant chemotherapy. METHODS: From October 2001 to July 2003, 80 patients who had neoadjuvant chemotherapy underwent curative surgery and axillary lymph node dissection (ALND) after SLNB at the Center for Breast Cancer, National Cancer Center. A MEDLINE search was performed using the keywords breast cancer, sentinel lymph node biopsy, and neoadjuvant chemotherapy. RESULTS: Our results showed that 42 (52.6%) of 80 patients had downstaging of the primary tumor; 9 patients (11.3%) had pathologic complete response (pCR) and 33 (41.3%) had pathologic partial response (pPR). 26 patients (32.5%) showed complete axillary clearance after neoadjuvant chemotherapy. Among them, 5 patients (6.3%) revealed pCR of both the primary tumor and axillary metastasis. SLNB was successful in 61 of 80 patients (76.3%) and there were 3 false negatives, yielding a false negative rate (FNR) of 7.3% (3/41), a negation prediction value (NPV) of 87.0%(20/23), and an accuracy of 95.1% (58/61). Thirteen out of 16 studies retrieved by to MEDLINE pertaining SLNB after neoadjuvant chemotherapy concluded its feasibility and accuracy with a identification rate of 82%-100% and a FNR of 17-100%. CONCLUSION: Most studies, including ours, concluded that SLNB after neoadjuvant chemotherapy is accurate and could be an alternative to ALND.     

A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade

BackgroundThe presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown.Patients and methodsThe PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (N = 148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks.ResultsIn PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%).ConclusionsOn-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy.Clinical trial numberNCT01973660.