Neoadjuvant Therapy Group Research Articles

Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive breast cancer: A Surveillance, Epidemiology, and End Results population‐based study

AbstractBackgroundPersistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking.MethodsData on patients with T1cN0M0‐stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well‐balanced cohorts for the NAT and AT groups. Kaplan–Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer–specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT.ResultsAfter PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35–0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37–0.98; p = .041). A logistic regression model revealed that White race and hormone receptor–negative status independently predicted pCR.ConclusionsFor patients with T1cN0M0‐stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Abstract A015: Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) has consistently poor outcomes, even for early-stage tumors that undergo resection (>70%), despite completion of prescribed perioperative systemic therapy. Mucin 5AC (MUC5AC), a heavy glycoprotein, exists in two major glycoforms: heavily glycosylated mature (MM) and less glycosylated immature (IM) forms. MM is located in the apical region and extracellular space, whereas IM is in the perinuclear region. Our previous work demonstrated the association between MM and treatment response and outcomes in resected PDA after neoadjuvant therapy (NAT). In this study, we investigate the impact of MUC5AC tissue expression in resected PDA samples on recurrence site characteristics (local (LR) vs. distant metastasis (mets) vs. both LR and mets). Resected PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores (0-300) were calculated. Logistic regression was used to study this association of interest. We had 100 R-PDA (43 received NAT, and 57 had upfront surgery (UpS)) available for testing. The median age of diagnosis was 65 years, and 50% were males. Most of the patients in the NAT group received FOLFIRINOX (n=36) and received gemcitabine/nab-paclitaxel (n=5) or FOLFOX (n=2). The median number of doses received is 6 (range 2-9). The results in these groups can be summarized as follows: a) 35/43 had recurrence (LR=7, mets=21, and LR+mets=7), with the liver being the most common site of metastasis (13/28) followed by lung (5/28) and peritoneum (5/28), b) Higher IM expression (mean H-score) was significantly (p=0.0275) higher in LR+mets (H-score 196) than in LR (H-score 69) or mets (H-score 115) groups, c) Higher MM expression (mean H-score) was also significantly different among these groups (LR vs. mets vs. LR+mets = 81 vs. 120 vs. 206, p= 0.0358), e) similar trend of mean H-scores was noted in FOLFIRINOX sub-group (LR vs. mets vs. LR+mets = 205 vs. 109 vs. 60, p=0.0185 for IM and 65 vs. 116 vs. 205, p=0.0329 for MM). No significant association between recurrence patterns and tissue MUC5AC expression in the UpS group. These findings concur with our prior observations, underscoring the clinical significance of MUC5AC in resected PDA post-NAT and suggesting its potential role in facilitating pancreatic tumor cell metastasis. Although larger prospective studies are needed to confirm these results, our study highlights MUC5AC as a potential therapeutic target to prevent metastasis in early-stage PDA, potentially improving overall outcomes. Citation Format: Ashish Manne, Lianbo Yu, Ashwini Esnakula. Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A015.

Surgical outcomes of neoadjuvant endocrine treatment in early breast cancer: meta-analysis.

Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed. A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy. PubMed and EMBASE were searched to identify RCT and cohort studies between 1946 and 27 March 2024. Two independent reviewers manually screened the identified records and extracted the data. Risk of bias was assessed using the Cochrane Collaboration tools and random-effects meta-analysis was done with ReviewManager. The search identified 2390 articles eligible for screening. The review included 20 studies (12 cohort and 8 RCTs); 19 were included in the meta-analysis with a total of 6382 patients. Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. 0.44 to 0.64). Subgroup analysis showed similar improvement in the mastectomy rate in the neoadjuvant endocrine therapy group versus control group irrespective of study type (RCT: RR 0.58, 95% c.i. 0.50 to 0.66; cohorts: RR 0.48, 95% c.i. 0.33 to 0.70). There was no difference in the mastectomy rate by duration of neoadjuvant endocrine therapy (more than 4 months: RR 0.57, 95% c.i. 0.42 to 0.78; 4 months or less than 4 months: RR 0.52, 95% c.i. 0.43 to 0.64). Most of the studies were characterized by moderate-quality evidence with significant heterogeneity. Neoadjuvant endocrine therapy is associated with a reduction in mastectomy rate. Given the moderate methodological quality of previous studies, further RCTs are required. CRD42020209257.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study.

Regarding when to treat gastric cancer and ovarian metastasis (GCOM) and whether to have metastatic resection surgery, there is presently debate on a global scale. The purpose of this research is to examine, in real-world patients with GCOM, the survival rates and efficacy of metastatic vs non-metastasized resection. To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM. This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People's Hospital from June 2009 to July 2023. The diagnosis of all patients was confirmed by pathology. The primary study endpoints included overall survival (OS), ovarian survival, OS after surgery (OSAS), disease-free survival (DFS), differences in efficacy. This study had 41 patients in total. The surgical group (n = 27) exhibited significantly longer median OS (mOS) and median overall months (mOM) compared to the nonoperative group (n = 14) (mOS: 23.0 vs 6.9 months, P = 0.015; mOM: 18.3 vs 3.8 months, P = 0.001). However, there were no significant differences observed in mOS, mOM, median OSAS (mOSAS), and median DFS (mDFS) between patients in the surgical resection plus neoadjuvant therapy group (n = 11) and those who surgical resection without neoadjuvant therapy group (n = 16) (mOS: 26.1 months vs 21.8 months, P = 0.189; mOM: 19.8 vs 15.2 months, P = 0.424; mOSAS: 13.9 vs 8.7 months, P = 0.661, mDFS: 5.1 vs 8.2 months, P = 0.589). Compared to the non-surgical group, the surgical group's survival duration and efficacy are noticeably longer. The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

“Find Your Y”: histological differences in early stage (pT) and post-treatment (ypT) oesophageal adenocarcinoma with implications for salvage endoscopic resection

AimsCurrent guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited....

Analysis of neoadjuvant therapy effect on 30-day postoperative outcomes in gallbladder cancer

BackgroundThe role of neoadjuvant therapy (NAT) in gallbladder cancer (GBC) is not well established. We sought to evaluate the effect of NAT on postoperative outcomes following surgical resection of GBC. We hypothesized that patients receiving NAT would have similar rates of 30-day mortality, readmission, and postoperative complications (e.g. bile leakage and liver failure) compared to those who did not receive NAT. MethodsThe 2014–2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Hepatectomy database was queried for patients that underwent surgery for GBC. Propensity scores were calculated to match patients in a 1:2 ratio based on age, comorbidities, functional status, and tumor staging. ResultsA total of 37 patients undergoing NAT were matched to 74 patients without NAT. There was no difference in any matched characteristics. Compared to the NAT group, the no NAT cohort had similar rates of postoperative bile leakage (NAT 13.5 % vs. no NAT 10.8 %, p = 0.31), postoperative liver failure (5.4 %, vs. 8.1 %, p = 0.60), 30-day readmission (10.8 % vs. 10.8 %, p = 1.00), and 30-day mortality (10.8 % vs. 2.7 %, p = 0.075). All 30-day complications were similar except for a higher rate of postoperative blood transfusion (NAT 32.4 % vs. no NAT 10.8 %, p = 0.005). ConclusionIn patients undergoing surgical resection for GBC, those with and without NAT had similar rates of readmission and 30-day mortality, however NAT was associated with an increased risk for transfusion. Despite use of a large national database, this study may be underpowered to adequately assess the effect of NAT on perioperative GBC outcomes and thus warrants further investigation.

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial

BackgroundThe high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC.MethodsThis multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint.DiscussionSynergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC.Trial registrationwww.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.

A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo) adjuvant therapy in patients with early triple-negative breast cancer: Korean Cancer Study Group BR 15-1 PEARLY trial.

LBA502 Background: Triple-negative breast cancer (TNBC) is known for its high risk of early relapse and poor prognosis. Platinum agents have shown to increase pathological complete response (pCR) rates when added to neoadjuvant chemotherapy for TNBC. However, evidence regarding the survival benefit of platinum in this setting remains inconclusive. The PEARLY trial is a multicenter, randomized, open-label, phase 3 study designed to assess the efficacy and safety of carboplatin in combination with anthracycline/taxane therapy compared to standard anthracycline/taxane alone as either neoadjuvant or adjuvant treatment in early-stage TNBC. Methods: Patients with stage II or III TNBC were randomly assigned to either the carboplatin arm or the standard therapy arm, stratified by nodal status, institution, treatment setting (neoadjuvant vs adjuvant), and germline BRCA status. The standard therapy involved doxorubicin and cyclophosphamide (AC) followed by taxane treatment. The experimental arm included carboplatin in addition to taxane following AC. The primary endpoint was event-free survival (EFS), defined as disease progression or inoperable status for neoadjuvant therapy group, local or distant recurrence, occurrence of a second primary cancer, or death from any cause, while secondary endpoints encompassed overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety. With a planned enrollment of 878 patients, the trial aimed for 80% power to detect a hazard ratio of 0.70 for EFS at a two-sided alpha level of 0.05, anticipating 248 EFS events over a 5-year follow-up period. Results: Between Jan 2016 and Jun 2020, 868 patients across 22 institutions in South Korea were enrolled. At a median follow-up of 51.1 months, carboplatin significantly improved EFS compared to the control arm (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.50 to 0.93; p=0.017). The 5-year EFS rates were increased from 74.4% to 81.9%, demonstrating a 7.5% difference. Subgroup analysis showed consistent benefits across various patient categories. Secondary endpoints like IDFS and DRFS also favored carboplatin arm. OS data were immature, a total of 43 patients (10.2%) in the carboplatin arm and 57 patients (13.1%) in the control arm died (HR 0.66; 95% CI: 0.42 to 1.01). Grade ≥3 treatment-related adverse event rates were 74.6% (1 death due to infection) in the carboplatin arm and 56.7% (2 deaths due to infection and suicide) in the control arm. Conclusions: The addition of carboplatin to standard anthracycline followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. The safety profile was consistent with the known expectations for each regimen. Clinical trial information: NCT02441933 .

Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study

PurposeWe investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. MethodsA total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. ResultsIn resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. ConclusionsNAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

A real-world evaluation of tislelizumab in patients with head and neck cancer.

Various studies support the use of programmed cell death protein 1 (PD-1) blockades, also known as immune checkpoint inhibitors (ICIs), to treat head and neck cancer (HNC). Tislelizumab is a humanised immunoglobulin G4 (IgG4) monoclonal antibody with a high affinity and specificity for PD-1. However, the "real-world" clinical evidence of tislelizumab for HNC is limited. In this study, the medical records of 39 patients with head and neck squamous cell carcinoma (HNSCC) or nasopharyngeal carcinoma (NPC) who received tislelizumab between January 2021 and March 2022 were reviewed retrospectively. Tislelizumab was administered to 15 patients during neoadjuvant therapy (Group 1), five patients during adjuvant therapy (Group 2), 14 patients during consolidation therapy (Group 3), and five patients during salvage therapy (Group 4). The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). The median age of enrolled patients was 55 (range, 28-83) years. The median follow-up time was 27.1, 26.1, 28.6, and 20.9 months for Groups 1, 2, 3, and 4, respectively. The mean PFS and OS of Groups 1, 2, 3, and 4 were 21.5 and 22.8; 24.1 and 24.2; 26.9 and 28.1; and 13.9 and 17.1 months, respectively. In Groups 1 and 4, the objective response rate (ORR) was 86.7% and 60%, respectively. Meanwhile, except for one (2.6%) patient with grade 4 enteritis, the other observed non-haematological adverse events (AEs) were ≤ grade 2. Tislelizumab demonstrated promising efficacy and tolerability in patients with HNSCC or NPC in a real-world setting, consistent with previous reports.

Prognostic value of neoadjuvant therapy for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomized controlled trials.

To investigate the prognostic value of preoperative neoadjuvant therapy (NT) compared to upfront surgery (US) in patients with resectable and borderline resectable pancreatic cancer. PubMed, Embase, Web of Science were searched to collect randomized controlled trials on preoperative neoadjuvant therapy versus upfront surgery for resectable and borderline resectable pancreatic cancer before April 7, 2023, and data were extracted after screening according to inclusion and exclusion criteria, and HRs were obtained indirectly using enguage software; Stata 12.0 software was used for data analysis. A total of 8 randomized controlled trials (RCTs) were included in this study, comprising a total of 1058 cases, including 503 cases in the NT group and 555 cases in the US group. Using an intention-to-treat population (ITT) analysis, the results showed that neoadjuvant treatment improved the R0 resection rate (RR 2.71, 95% CI 1.59-4.62; P = 0.000; I2 = 46.20%) and overall survival (HR 0.66, 95% CI 0.54-0.82; P = 0.000; I2 = 0.00%). In the subgroup of patients with resectable pancreatic cancer, the R0 resection rate in the NT group versus the US group (RR 1.14, 95% CI 0.93-1.39; P = 0.196; I2 = 0.00%) and overall survival (HR 0.89, 95% CI 0.64-1.24; P = 0.489; I2 = 0.00%) were not statistically significant. Preoperative neoadjuvant treatment is of prognostic value in patients with borderline resectable pancreatic cancer, as it increases the R0 resection rate and improves overall survival compared to upfront surgery.

Utilization of Neoadjuvant Therapy in Gastrointestinal Stromal Tumors of the Stomach: Analysis of the 2006–2018 National Cancer Database

BackgroundNeoadjuvant tyrosine kinase inhibitor (TKI) therapy has reduced tumor burden and improved survival in both primary and recurrent gastrointestinal stromal tumors (GISTs). However, no clear guidelines exist on optimal patient selection for neoadjuvant therapy (NAT). Our aim was to analyze factors and outcomes associated with the therapeutic sequence of TKI therapy before and/or after surgery for gastric GISTs. MethodsWe performed a retrospective study of patients surgically treated for a gastric GIST utilizing the 2006–2018 National Cancer Database. We examined demographic, clinical, and pathological characteristics associated with NAT versus adjuvant therapy (AT) using logistic regression. ResultsOf the 3732 patients, 20.4% received NAT and 79.6% had AT. Among patients receiving therapy, NAT significantly increased over our study period (12% to 30.7%). A majority of the AT group received a partial gastrectomy (77.9%) compared with the NAT group who received more near-total/total gastrectomy or gastrectomy with en bloc resection (p < 0.001). In a multivariable model, patients were more likely to receive NAT when insured (private, aOR: 2.37, 95% CI: 1.31–4.29), treated at an academic/research program (aOR: 1.83, 95% CI: 1.49–2.56), had tumors located in the proximal stomach (aOR: 1.40, 95% CI: 1.06–1.86), tumor size > 10 cm (aOR: 1.88, 95% CI: 1.41–2.51), and received near-total/total gastrectomy (aOR: 1.81, 95% CI: 1.42–2.29). There were no differences in outcomes. ConclusionNAT for gastric GIST has increased in utilization. NAT was used in patients with larger tumors and who underwent more extensive resection. Despite these factors, outcomes were similar to patients receiving only AT. More studies are required to determine the therapeutic sequence for gastric GISTs.

A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: A Reanalysis of Data From the NEOCRTEC5010 Trial

This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma. We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N=451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant chemoradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P=.5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R2=0.605). Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor.

Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits.

Patients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy. The whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to identify predictive biomarkers for guiding treatment selection. Comparing the transcriptome profiling of pre- and post-treatment LAPCa specimens, NHT and NCHT shared 1917 up- and 670 down-regulated DEGs at least 2-fold. Pathway enrichment analysis showed up-regulated pathways in response to NHT and NCHT were both enriched in cytokine receptor interaction pathways, and down-regulated pathways in response to NCHT were enriched in cell cycle pathways. By comprehensive transcriptome profiling of 64 baseline specimens, ten predictive markers were identified. We integrated them into the signature to evaluate the relative benefits of neoadjuvant therapy, which categorizes patients into two subgroups with relative bPFS benefits from either NHCT or NHT. In the high-score (≥ -95.798) group (n = 37), NCHT treatment led to significantly longer bPFS (P< 0.0001), with a clear and early separation of the Kaplan-Meier curves. In the low-score (< -95.798) group (n = 27), NHT also led to significantly longer bPFS (P=0.0025). In this study, we proposed the first predictive transcriptomic signature might potentially guide the effective selection of neoadjuvant therapy in LAPCa and might provide precise guidance toward future personalized adjuvant therapy. The study was approved by the Ethics Committee of Renji Hospital affiliated to Shanghai Jiao Tong University (Ky2019-087).

Propensity-score matched analysis of the pathologic outcomes and survival benefits of neoadjuvant therapy in stage II-III anal adenocarcinoma.

Anal adenocarcinomas are a rare condition which account for less than 10% of anal cancers. The present study aimed to assess the impact of neoadjuvant therapy on the clinical and pathologic outcomes and overall survival (OS) of patients with stage II-III anal adenocarcinomas after abdominoperineal resection (APR). A retrospective cohort study of patients with anal adenocarcinoma in the US National Cancer Database (NCDB) (2010-2020) was conducted. Propensity-score matching was used to compare patients who received neoadjuvant therapy (neoadjuvant therapy group) to the no-neoadjuvant group. The primary outcome was 5-year OS whereas secondary outcomes included conversion to open surgery, hospital stay, surgical margins, 30-day mortality, 90-day mortality, and 30-day readmission. A total of 742 patients (56% male) with a mean age of 63.6 ± 12.4 years were included. A total of 214 patients in the neoadjuvant group were matched with 107 in the no-neoadjuvant group. The mean OS was similar between the two groups (47.5 vs. 44.8 months, p = 0.253). Patients who received neoadjuvant therapy had a longer median time between diagnosis and surgery (151 vs. 54 days, p < 0.001), lower 90-day mortality (1.9% vs. 6.7%, p = 0.046), more pT0 tumors (15.7% vs. 0%), less pT3-4 tumors (28.4% vs. 36.4%, p = 0.001), less pN1-2 tumors (22.9% vs. 34.7%, p < 0.001), and less lymphovascular invasion (16.2% vs. 40%, p < 0.001) than the no-neoadjuvant group. Both groups had similar conversion rates, hospital stay, 30-day mortality, 30-day readmission, and positive surgical margins. Neoadjuvant therapy before APR was associated with significant downstaging of anal adenocarcinomas and lower 90-day mortality, yet similar OS to patients who were surgically treated without neoadjuvant treatment.

Neoadjuvant Chemotherapy Efficacy and Safety in Borderline Resectable Pancreatic Cancer

The current study was designed to investigate the safety and effectiveness of neoadjuvant therapy in patients with borderline resectable pancreatic cancer. The study was a retrospective case control with propensity score similarity. From January 2017 to June 2022, data regarding 70 patients who had received radical resection of pancreatic cancer at the department of hepatobiliary and pancreatic surgery of first affiliated hospital of Huzhou university was acquired. The neoadjuvant therapy group consisted of 35 patients who underwent neoadjuvant therapy before surgery. Patients who received extensive surgical resection were included in the control group directly. The effect of the neoadjuvant therapy group was evaluated before the operation and serum tumor markers carcinoembryonic antigen, cancer antigen 125 and cancer antigen 19-9 levels were compared before and after neoadjuvant therapy. Comparative analyses of perioperative surgical variables, postoperative pathological symptoms and postoperative complications were performed between both groups. Among the patients without complete remission or progressive disease after neoadjuvant therapy, 13 cases (37.14 %) were evaluated as partial response and 22 cases (62.86 %) were assessed as stable disease. After neoadjuvant therapy, serum levels of cancer antigen 19-9, cancer antigen 125 and carcinoembryonic antigen indexes revealed a significant (all p<0.05) downward trend. There were no statistically significant differences (all p>0.05) between the two groups regarding surgery type, operation duration, intraoperative blood loss, number of cases requiring blood transfusion, or postoperative hospital stay. Neoadjuvant treatment patient’s tumor diameters and the number of removed lymph nodes were significantly less (p<0.05) than those of the control group and their R0 resection rates were significantly greater (p<0.05) than those of the control group. There was no substantial variation in the frequency of complications between both groups (p>0.05). Preoperative neoadjuvant therapy for patients with minimally resectable pancreatic cancer can lower tumor marker levels. Moreover, it can produce a specific curative impact without raising surgical risk levels and boosting the R0 resection rate, which is safe and appropriate.

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases

IntroductionMany patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. MethodsWe performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the “sandwich” chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. ResultsA total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. ConclusionsIn this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial

Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery. ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete. Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia. Recruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. Cancer Research UK.

A total neoadjuvant chemotherapy approach is associated with improved recurrence-free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC.

The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases(CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival(RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, theTNT approach was independently associated with improved RFS. In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.