Survival Benefit Of Neoadjuvant Chemotherapy Research Articles

Patients With Muscle-Invasive Bladder Cancer With Lymphovascular Invasion in Transurethral Resection Specimen Benefits Most From Platinum-Based Neoadjuvant Chemotherapy

PurposeThe survival benefit of neoadjuvant chemotherapy (NAC) before definitive radical cystectomy (RC) varied among patients, suggesting proper selection of patients for NAC to maximize the survival benefit. This study aimed to investigate the role of lymphovascular invasion (LVI) in transurethral resection (TUR) specimens in selecting patients with MIBC for NAC. MethodsTwo retrospective cohorts of patients with cT2-4aN0 MIBC who underwent RC from 2004 to 2015 provided by Lund University were included. Inverse probability weighting was applied to make the NAC-treated (NAC) and untreated (non-NAC) cohorts comparable. Survival benefits were estimated with Kaplan-Meier curves and Cox proportional hazards models. The primary endpoint was cancer-specific survival (CSS). LVI in TUR specimens and molecular taxonomies (BASE47, UNC, and LundTax) were examined, and bulk RNA-seq datasets were explored for LVI-relevant signatures. ResultsA total of 341 patients with cT2-4aN0 MIBC were included. The NAC cohort included 125 patients, whereas the non-NAC cohort included 216 patients. The 3-year CSS benefit of NAC was 7.1%. For patients with positive LVI in TUR specimens, the 3-year CSS benefit of NAC was 26.2% (48.1% vs. 74.3%), with a risk reduction of 56% (HR = 0.44, P = .03). A sensitivity analysis confirmed a significant interaction between LVI and NAC. This study failed to identify the molecular subtypes that maximized the survival benefit of NAC. Exploration of LVI-relevant signatures remains inconclusive. ConclusionsLVI in TUR specimens could help identify patients with MIBC who would derive maximal survival benefit from NAC. Further prospective validation is necessary.

Effectiveness of neoadjuvant chemotherapy followed by radical surgery in young patients with locally advanced cervical cancer

To investigate the efficacy and survival benefit of neoadjuvant chemotherapy (NACT) followed by type C radical surgery in patients with locally advanced cervical cancer (LACC) and moderate risk factors for recurrence. The clinical and pathological data of 338 cases with stage IB3 and IIA2 cervical carcinoma who received NACT followed by radical surgery from January 2008 to December 2018 were collected. In line with the clinical response, the patients were divided into a chemotherapy-effective group (n = 309) and a chemotherapy-ineffective group (n = 29), and the clinical and pathological characteristics of the two groups were compared. Survival was analyzed using the Kaplan-eier method. After NACT and surgical resection, 309 (91.4%, 309/338) patients experienced a clinical response. Fewer patients had a maximum tumor diameter ≥5 cm in the chemotherapy-effective group compared with the chemotherapy-ineffective (p = 0.021). The 5-year progression-free survival (PFS) and overall survival (OS) rates were higher in the chemotherapy-effective group (86.29% and 85.75%, respectively) than in the chemotherapy-ineffective group (77.64% and 75.56%, respectively; p < 0.001). Among patients with high-risk and moderate-risk factors, the 5-year PFS and OS rates were higher in the patients who received chemotherapy (95.90% and 94.81%) than in those who received CCRT (78.06% and 77.25%, respectively; p < 0.001). NACT followed by surgical resection may be an appropriate treatment strategy for young patients with LACC, allowing them to avoid radiochemotherapy and the resultant damage to ovarian and vaginal function. A future prospective study of this treatment strategy is warranted.

National Cancer Database Analysis of Gallbladder Cancer: Evaluating Survival Benefit of Neoadjuvant Chemotherapy in Early-Stage Gallbladder Cancer

National Cancer Database Analysis of Gallbladder Cancer: Evaluating Survival Benefit of Neoadjuvant Chemotherapy in Early-Stage Gallbladder Cancer

National Trends and Factors Affecting the Utilization of Neoadjuvant Chemotherapy

Background: A survival benefit of neoadjuvant chemotherapy (NAC) in resectable pancreatic cancer (PDAC) necessitating pancreaticoduodenectomy has been reported even for early stage. Despite this, NAC continues to being sparingly utilized nationally. This study investigates trends in NAC utilization and aims at identifying factors affecting NAC utilization.

Survival Benefit of Neoadjuvant Chemotherapy for Locally Advanced Adenocarcinoma of Esophagogastric Junction.

Adenocarcinoma of the esophagogastric junction (AEG) is refractory even when curative resection is followed by adjuvant chemotherapy. This study evaluated the efficacy of neoadjuvant chemotherapy (NAC) using an oral fluoropyrimidine-platinum regimen for AEG. Out of 35 patients with locally advanced AEG who underwent curative resection, 21 who underwent surgery first and 14 who received NAC were retrospectively compared in terms of survival. The NAC regimens comprised of S-1 or capecitabine plus oxaliplatin or cisplatin; trastuzumab was added to six borderline resectable cases. The downstaging rate was 50% and the pathological response rate including complete response (29%) was 50%. The three-year relapse-free survival in the NAC group was significantly superior than the surgery-first group (78% vs. 22%, p=0.011). The NAC group had a significantly longer median survival time than the surgery-first group (NR vs. 29 months, p=0.032). NAC using an oral fluoropyrimidine-platinum regimen may provide survival benefit in AEG.

Clinical Outcomes of Neoadjuvant Chemotherapy in Colorectal Cancer Patients With Synchronous Resectable Liver Metastasis: A Propensity Score Matching Analysis.

PurposeThe survival benefit of neoadjuvant chemotherapy (NAC) prior to surgical resection in colorectal cancer with liver metastases (CRCLM) patients remains controversial. The aim of this study was to compare overall outcome of CRCLM patients who underwent NAC followed by surgical resection versus surgical treatment first.MethodsWe retrospectively analyzed 429 patients with stage IV colorectal cancer with synchronous liver metastases who underwent simultaneous liver resection between January 2008 and December 2016. Using propensity score matching, overall outcome between 60 patients who underwent NAC before surgical treatment and 60 patients who underwent surgical treatment first was compared.ResultsBefore propensity score matching, metastatic cancer tended to involve a larger number of liver segments and the primary tumor size was bigger in the NAC group than in the primary resection group, so that a larger percentage of patients in the NAC group underwent major hepatectomy (P < 0.001). After propensity score matching, demographic features and pathologic outcomes showed no significant differences between the 2 groups. In addition, there was no significant difference in short-term recovery outcomes such as postoperative morbidity (P = 0.603) and oncologic outcome, including 3-year overall survival rate (P = 0.285) and disease-free survival rate (P = 0.730), between the 2 groups.ConclusionNAC prior to surgical treatment in CRCLM is considered a safe treatment that does not increase postoperative morbidity, and its impact on oncologic outcome was not inferior.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUNDThe potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored.AIMTo compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone.METHODSA total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics.RESULTSThe NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG.CONCLUSIONDespite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

Survival benefit of neoadjuvant chemotherapy and surgery versus surgery first for resectable colorectal liver metastases: a cohort study.

There is continued debate about the survival benefit of neoadjuvant chemotherapy (neoCT) in patients with resectable colorectal liver metastases (CRLM). In this retrospective cohort study, we included 201 patients with metastatic colorectal cancer who underwent their first CRLM resection and achieved resection of all sites of disease. We compared the overall survival (OS) and progression-free survival (PFS) between patients who received neoCT prior to CRLM resection with those who underwent CRLM upfront. A multivariable Cox proportional hazard regression analysis was performed to adjust for potential confounders. A total of 101 of 201 (51.2%) patients received chemotherapy prior to CRLM resection and 100 of 201 had surgery upfront. Multivariable Cox proportional hazard regression showed no statistically significant difference in the hazard of death for those given neoCT prior to resection of CRLM compared with surgery first for both OS and PFS (OS: hazard ratio 1.74, 95% confidence interval 0.85-3.55, P=0.127, PFS: hazard ratio 1.42, 95% confidence interval 0.93-2.19, P=0.107). In our series of patients with metastatic colorectal cancer who achieved surgical resection of all sites of disease, neoCT prior to CRLM resection was not associated with any survival benefit.

Survival outcomes of neoadjuvant chemotherapy-related strategies compared with concurrent chemoradiotherapy for locally advanced cervical cancer: a meta-analysis of randomized controlled trials.

The survival benefits of neoadjuvant chemotherapy (NAC) compared with those of concurrent chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC) patients remain uncertain. Meta-analysis was used to compare NAC and CRT. A systematic search was performed up to 9 September 2020. Survival outcomes were analyzed based on event frequency or hazard ratios (HRs). Multilevel mixed-effects logistic regression was applied to analyze the effect of regimen variables on survival outcomes. Analysis based on Cox regression showed that CRT was better than NAC + radical hysterectomy (RT) (HR 1.25; 95% confidence interval (CI)) 1.02-1.54; p = 0.034) in terms of overall survival (OS). According to multilevel mixed-effects model analysis comparing NAC + RT and CRT, LACC patients who used cisplatin instead of carboplatin had a better Progression-free survival (PFS) (odds ratio (OR) 1.54; 95% CI 1.08-2.20; p = 0.016). When NAC + CRT and CRT were compared, gemcitabine administration was associated with a decrease in PFS (OR 0.47; 95% CI 0.22-0.99; p = 0.047). Increased doses of cisplatin and paclitaxel were associated with survival improvement. Based on traditional meta-analysis, CRT was better than NAC + RT in terms of OS. Carboplatin instead of cisplatin as part of the NAC + RT strategy or gemcitabine use in NAC + CRT may not be a good choice. An increased total dosage of paclitaxel and/or cisplatin as part of NAC + CRT and CRT strategies may improve the survival outcome of LACC patients.

The survival benefit of neoadjuvant chemotherapy for resectable colorectal liver metastases with high tumor burden score.

The indications for neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLMs) remain unclear. Tumor burden score (TBS) is a prognostic tool based on tumor size and number of tumors. However, its utility in the NAC setting for initially resectable CRLM has never been investigated. TBS is a distance from the origin on a Cartesian plane to the coordinates (x, y) = (tumor size in centimeter, number of tumors). TBS < 3 was defined as "TBS-low", whereas TBS ≥ 3 as "TBS-high". Between 2008 and 2018, 102 patients who underwent hepatectomy for resectable CRLM were retrospectively analyzed using the Kaplan-Meier method and Cox proportional hazards regression models. Among the TBS-low (n = 46) and TBS-high (n = 56) groups, baseline patient characteristics were mostly similar except for TBS-related parameters. NAC was more frequently administered in the TBS-high group (p = 0.038). The overall survival (OS) rates were similar between the two groups. Subgroup analysis showed that NAC was associated with non-significantly improved 5-year OS in the TBS-high group [76.1% with NAC and 54.9% without NAC (p = 0.093)]. In multivariate analysis, NAC was an independent prognostic factor for favorable OS only in the TBS-high group, while adjuvant chemotherapy (AC) was associated with improved OS only in the TBS-low group. In patients with resectable CRLM, the TBS-high population had a survival benefit from NAC, while the TBS-low population benefited from AC. TBS may serve as an indicator for patients who will benefit from NAC.

Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review.

The role of perioperative or neoadjuvant chemotherapy for locally advanced colon cancer is unclear. Emerging evidence such as the FOXTROT trial is challenging the conventional norm of upfront operation for these patients. However, these trials have yet to reach statistical significance. MEDLINE, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI) and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) and observational studies of patients with locally advanced colon cancer were included. The intervention arm was neoadjuvant chemotherapies while the comparator arm was adjuvant chemotherapies. Studies which reported outcomes of interests included overall survival, disease-free survival, R0 resection rate, perioperative complications and adverse effects of chemotherapy were chosen. We identified five eligible randomized trials and two observational studies, including 29,504 patients. Neoadjuvant therapies exhibited statistically significant improvement in overall survival [hazard ratio (HR) =0.76, 95% confidence interval (CI): 0.65-0.89, P=0.0005], and disease-free survival (HR =0.74, 95% CI: 0.58-0.95, P=0.02). R0 resection rate fell slightly short of significance [odds ratio (OR) =1.86, 95% CI: 0.95-3.62, P=0.07]. Risk of peri-operative complications did not differ between groups when examining abdominal infection [risk ratio (RR) =1.14, 95% CI: 0.59-2.18, P=0.70] and anastomotic leakage (RR =0.83, 95% CI: 0.53-1.31, P=0.42). No statistical differences in complications from chemotherapy were reported. This meta-analysis highlights the potential survival benefit of neoadjuvant chemotherapy compared to adjuvant chemotherapy for locally advanced colon cancer, without an increase in surgical morbidity. Neoadjuvant or perioperative approaches may be considered an alternative to upfront surgery followed by chemotherapy for locally advanced colon cancer.

Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12-26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04).Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.

Survival benefit of neoadjuvant chemotherapy in pathologic T2N0 or lower urothelial carcinoma patients: evidence to support the use of neoadjuvant chemotherapy.

BackgroundTo evaluate the survival benefit of neoadjuvant chemotherapy (NAC) in pathologic T2N0 or less patients.MethodsA total of 526 patients with less than pT2N0 underwent radical cystectomy. Patients were divided into three groups: non-NAC, those who did not receive NAC; partial NAC, those who received less 3 cycles of NAC; and complete NAC, those who received 3 cycles of NAC.ResultsMedian follow up was 74.6 (range, 24–311) months. Recurrent-free survival (RFS) was significantly (P=0.041) higher in the non-NAC group than that in the complete NAC group. Overall survival (OS) was significantly (P=0.039) higher in the non-NAC group than that in the complete NAC group. There was no significant difference between the partial NAC group and the complete NAC group. In patients with pT0, the NAC group had higher pT0 ratio than the non-NAC group (33.3% vs. 21.1%). A total of 66.6% of NAC patients were down-staged to less than T2. In univariate and multivariate analyses, recurrence was significantly related to pathologic T stage (P<0.001), concurrent carcinoma in situ (CIS) (P=0.002), and the number of removed lymph nodes (LNs) (P=0.001). Survival was significantly related to pathologic T stage (P<0.001), lymphovascular invasion (LVI) (P=0.002), the number of removed LNs (P<0.001), and the presence of NAC (P=0.047).ConclusionsPatients with pT2 or lower underwent NAC showed similar prognosis as patients with pT2 or lower who did not undergo NAC.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUNDSurvival benefit of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC) is a debatable issue. Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs. For those who achieve pathological complete response (pCR), NAC significantly prolonged prolapsed-free survival and overall survival. For those with poor response, NAC yielded no survival benefit, only toxicity and increased risk for tumor progression during chemotherapy, which may hinder surgical resection. Thus, predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIMTo establish a nomogram for predicting pCR to NAC for AGC patients.METHODSTwo-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study. Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR. Based on these predictors, a nomogram model was developed and internally validated using the bootstrap method.RESULTSpCR was confirmed in 27 patients (27/208, 13.0%). Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level, lymphocyte ratio, lower monocyte count and tumor differentiation grade were associated with higher pCR. Concordance statistic of the established nomogram was 0.767.CONCLUSIONA nomogram predicting pCR to NAC was established. Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters, it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Survival outcomes of neoadjuvant versus adjuvant chemotherapy in early-stage pancreatic adenocarcinoma: A subgroup analysis of the National Cancer Database.

e16777 Background: Early-stage disease is diagnosed in 10-20% of patients with pancreatic adenocarcinoma (PAC). The current standard of care is upfront surgery followed by adjuvant chemotherapy (AC). The administration of the latter may be limited due to postoperative complications. The aim of this study is to determine the subgroups of patients with early-stage PAC who derive maximum benefit of neoadjuvant chemotherapy (NAC). Methods: Using the National Cancer Database 2004-15, we identified 20,003 patients with clinical stage I or II PAC who had surgery and received chemotherapy in any sequence. The baseline characteristics were compared using Pearson's chi‐square test between patients who received NAC versus AC. A separate multivariate Cox-proportional Hazard regression analysis was done for each subgroup to identify patients with the maximum survival benefit from NAC. Hazard ratio (HR) &lt; 1 connotes survival benefit in favor of NAC. Results: Of the study population, 24% of the patients received NAC. The patients in the NAC group had more PAC of head (80% vs 73%), stage II disease (72% vs 53%), CA19-9 levels 50 U/ml (66% vs 59%), multiagent chemotherapy (68% vs 27%) and were treated at an academic facility (66% vs 52%) compared to the AC group. The p-value was &lt; 0.001 for all comparisons. The age and sex distribution were similar in both groups. On multivariate survival analysis in the overall population, NAC had improved survival compared to AC (HR 0.88 95%CI 0.82-0.93, p &lt; 0.001). Subgroup multivariate survival analysis is shown in the table. Conclusions: In early stage PAC, there is a trend towards survival benefit of NAC compared to AC in most subgroups. The maximum benefit is seen in younger patients with Stage II disease, high CA19-9 levels and fewer comorbidities who receive multiagent chemotherapy. This finding may partly be explained by better tolerability of preoperative compared to postoperative chemotherapy. A randomized clinical trial is needed to establish the optimal chemotherapy timing in patients with early-stage PAC who are treated with curative intent. [Table: see text]

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

Although upfront surgery has been the gold standard for pancreatic adenocarcinoma that is planned for resection, it should be compared with the alternative strategy of neoadjuvant therapy. Despite the many reports of the efficacy of neoadjuvant therapy, most of them were not comparative. Recently Prep‐02/JSAP05 study clearly demonstrated the significant survival benefit of neoadjuvant chemotherapy over upfront surgery for pancreatic adenocarcinoma that is planned for resection. These findings opened a new chapter of neoadjuvant therapy. Ongoing trials are expected to confirm the evidence. This review summarizes the past, present, and future perspectives of neoadjuvant therapy and its optimization.

Abstract P2-16-36: Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis

Abstract INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly being used for locally advanced breast cancers (BCs) or aggressive BC tumors. However, no survival benefit of the neoadjuvant approach over receiving chemotherapy in the adjuvant setting has been proven so far in HER2-positive early breast cancer (BC) patients. The objective of this study was to compare the prognosis of patients with an HER2-positive BC treated with NAC to patients treated with adjuvant chemotherapy (AC). MATERIALS AND METHODS: We retrospectively identified in our institutional database 203 patients with HER2-positive BCs treated with NAC plus trastuzumab and 701 patients treated with adjuvant chemotherapy. As the treatment was not randomly allocated, we used a propensity score with an Inverse probability of received treatment weighting (IPTW) to generate a pseudo-population in which each covariate combination was balanced between treatment groups. The disease free (DFS), distant metastasis free (DMFS) and overall survival (OS) were evaluated using a weighted Cox model. The interactions with poor prognosis factors (initial tumour size, tumour grade, hormone receptor status and initial clinical nodal status) were tested to evaluate the effect of the NAC in high-risk tumours. RESULTS: By construction, patients, tumor characteristics and trastuzumab use were similar between the population treated with NAC and the population treated with adjuvant CT. No difference was found regarding DFS (p=0.3) neither DMFS (p=0.4) in the global population. However, there was a significant interaction effect between the strategy and the initial clinical nodal status, with a DFS benefit of NAC over AC in the node-positive group (HR 0.53 CI95% [0.31- 0.89]), as well as for DMFS (HR 0.39 95%CI [0.20-0.77]). We found a significant benefit in OS with the neoadjuvant strategy when compared with the adjuvant strategy (HR = 0.12 95%CI [0.03-0.47], p=0.002) and this difference was significant irrespective of tumour size, initial clinical nodal status and hormone receptor status. CONCLUSION: In patients with HER2-positive BCs, receiving NAC is associated with an improved OS when compared with chemotherapy received in the adjuvant setting. Our results support the fact that NAC should become a standard of care in HER2-positive tumours. Citation Format: Enora Laas, Arnaud Bresset, Jean Guillaume Feron, Jean-Yves Pierga, Florence Coussy, Audrey Bellesoeur, Beatriz Grandal, Eléonore De Guillebon, Sonia Rozette, Clemence Evrevin, Thomas Gaillard, Marick Lae, Anne Sophie Hamy, Fabien Reyal. Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-36.

Survival Benefit of Neoadjuvant Chemotherapy with S-1 Plus Docetaxel for Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis

BackgroundPostoperative docetaxel plus S-1 (DS) chemotherapy is expected to be the standard therapeutic strategy for pStage III gastric cancer based on the results of the JACCRO GC-07 study. Neoadjuvant chemotherapy (NAC) is thought to have several advantages over adjuvant settings.ObjectiveThis study aimed to compare the efficacies of NAC DS and the surgery-first strategy for advanced gastric cancer patients with D2 gastrectomy.MethodsThis was a retrospective, single-institution observational study. Of 171 patients with locally advanced (cStage IIB or III) gastric cancer who underwent curative D2 gastrectomy and received NAC DS and/or S-1 adjuvant chemotherapy between 2011 and 2017, 76 (after propensity score matching for 132 patients who met the eligibility criteria) were enrolled in this study. The 3-year progression-free survival (PFS) rate was used to directly compare efficacies between NAC DS patients and surgery-first patients.ResultsThe 3-year PFS rates for the NAC DS group were significantly higher than those for the surgery-first group (80.0 vs. 58.7; p = 0.037), and the progression hazard ratio of the NAC DS group compared with the surgery-first group was 0.394 (95% confidence interval 0.159–0.978; p = 0.045).ConclusionsThe NAC DS group showed a high 3-year PFS compared with the surgery-first group, with standard S-1 postoperative chemotherapy or observation. NAC DS can be expected to be beneficial as the standard therapy for advanced gastric cancer and should be adopted for the test arm of a randomized controlled phase III trial.

Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1)

BackgroundFew patients with pancreatic cancer may be candidates for immediate surgical resection at the initial diagnosis. Even if patients with borderline resectable pancreatic cancer (BRPC), micrometastases may occur before surgery. Therefore, neoadjuvant therapy is vital for improved survival, which has been confirmed in previous studies that neoadjuvant chemotherapy with or without radiotherapy provides superior overall compared with upfront surgery. However, question of whether the addition of radiotherapy to neoadjuvant chemotherapy can improve prognosis compared with chemotherapy alone is a challenging matter. Moreover, most of previous studies only adopted conventional radiotherapy as the neoadjuvant modality though stereotactic body radiation therapy (SBRT) has been proven effective and commonly employed in pancreatic cancer. Also, no studies have evaluated the efficacy of S-1 as the neoadjuvant chemotherapy regimen for BRPC albeit similar prognosis has been found between S-1 and gemcitabine in advanced pancreatic cancer. Hence, the aim of this study is to investigate whether neoadjuvant chemotherapy plus SBRT results in better outcomes compared with neoadjuvant chemotherapy alone and also compare the efficacy of gemcitabine plus nab-paclitaxel with SBRT and S-1 plus nab-paclitaxel with SBRT.MethodsPatients with biopsy and radiographically confirmed BRPC, no prior treatment and severe morbidities are enrolled. They will be randomly allocated into three groups: neoadjuvant gemcitabine plus nab-paclitaxel, neoadjuvant gemcitabine plus nab-paclitaxel with SBRT and neoadjuvant S-1 plus nab-paclitaxel with SBRT. Standard doses of gemcitabine and nab-paclitaxel are used. The radiation dose of SBRT is 7.5-8Gy/f for 5 fractions. Surgical resection will be performed 3 weeks after SBRT. Artery first approach pancreaticoduodenectomy or radical antegrade modular pancreatosplenectomy will be used for the tumor in the head or body and tail of the pancreas, respectively. The primary endpoint is overall survival. The secondary outcomes are disease free survival, pathological complete response rate, R0 resection rate and incidence of adverse effects.DiscussionIf results show the survival benefits of neoadjuvant chemotherapy plus SBRT and similar outcomes between S-1 and gemcitabine, it may provide evidence of clinical practice of this modality for BRPC.Trial registrationThe study has been registered in ClinicalTrial.gov (NCT03777462).

Squamous cell carcinoma of the bladder: poor response to neoadjuvant chemotherapy.

Squamous cell carcinoma (SCC) of the bladder is a rare, aggressive malignancy. Unlike urothelial cell carcinoma, SCC is resistant to chemotherapy and guidelines recommend radical cystectomy (RC) without neoadjuvant chemotherapy (NAC). We aimed to evaluate the current management and survival of patients with invasive SCC treated with or without NAC. 671 patients with invasive SCC bladder cancer from 2004 to 2015 in the National Cancer Data Base were identified. Patients were stratified by treatment with RC alone or NAC prior to RC (NAC + RC). Survival analysis was performed with Kaplan-Meier and Cox regression. Secondary outcomes included length of stay and readmission. Of 671 patients, 92.8% were treated with RC alone and 7.2% with NAC + RC. Cox regression for mortality was performed including age, Charlson score, clinical stage, and NAC. Increased risk of mortality was noted with increasing age (OR 1.01, p = 0.023) and Charlson score of 1-3 (HR 1.58-1.68, p < 0.05). NAC did not confer survival advantage (HR 1.17, p = 0.46). On Kaplan-Meier analysis, the overall survival was equivalent (log-rank p = 0.804). Hospital stay and readmission were similar between RC and NAC + RC groups. Analysis of a national tumor registry suggests a lack of overall survival benefit for NAC with localized, muscle invasive SCC of the bladder. Further research directed at chemotherapy regimens for SCC is needed to optimize treatment and improve survival outcomes.