Neoadjuvant Chemotherapy For Stage Research Articles

Circulating tumor DNA as a predictor of treatment response to neoadjuvant chemotherapy in stage 2/3 rectal cancer without high risks: Subset analysis from the COPEC trial.

e15623 Background: Circulating tumor DNA (ctDNA) serves as a valuable tool for minimal residual disease (MRD) assessment. It has been reported as a promising noninvasive biomarker for the dynamic monitoring of treatment response of metastatic colorectal cancers to chemotherapy and locally advanced rectal cancers (LARC) to neoadjuvant chemoradiotherapy. However, the potential role of ctDNA in neoadjuvant chemotherapy (NCT) in LARC remains unexplored. The present study aims to investigate the value of ctDNA in NCT based on a prospective, multicentered, non-inferior, randomized, controlled trial (ClinicalTrials.gov ID, NCT04922853). The COPEC trial enrolls stage 2/3 LARC with low or intermediate and is designed to determine the optimal time (after 2 or 4 cycles of CAPOX) to evaluate treatment response based on pathological regression grades. Methods: Colonoscopy biopsy was taken before neoadjuvant therapy. Peripheral blood samples were collected before neoadjuvant (baseline, BL), one cycle (C1) and two cycles (4-cycle group, C2) after NCT, before surgery (BS), and within one month after surgery (postoperative, OP). All tissue biopsy and plasma specimens were analyzed by NGS assays using the MinerVA platform (Genecast Biotechnology Co., Ltd). MRI tumor regression grade (mrTRG) was assessed after 2 and 4 cycles (4-cycle group) of NCT. The primary outcome was the accuracy of ctDNA in the prediction of pathological tumor regression grade (pTRG). Results: A total of 151 LARC patients were enrolled, including 82 in the 2-cycle group and 69 in the 4-cycle group. The ctDNA was detectable in 87.4% (132/151), 39.6% (55/139), 29.0% (18/62), 38.4% (58/151), and 4.4% (6/138) at BL, C1, C2, BS and OP, respectively. The ctDNApositivity rates were significantly lower in good responders determined by mrTRG (mrTRG 1-3) compared to mrTRG 4-5 group at C1 (29% vs. 63.89%, p < 0.001), C2 (20% vs.56.25%, p = 0.011), and BS time points (23.85% vs. 74.36%, p < 0.001). Furthermore, the ctDNA-positivity rates at C1 in the good response group determined by TRG (pTRG 0-1) were 6.25%, significantly lower than that in the pTRG 2-3 group (49.53%). At neither C2 nor BS time point, patients in the pTRG 0-1 subgroup were detected as ctDNA positive while the ctDNA positivity rates for patients in pTRG 2-3 subgroup were 39.13% and 50%, respectively. Additionally, the mean of hGE/ml was 0.045 in pTRG 0-1 group at C1, significantly lower comparing to 1.337 in pTRG 2-3 group (p < 0.001). Conclusions: We find that dynamic monitoring of ctDNA status was a useful tool in early predicting the effect of (treatment response to) NCT in LARC patients with low/intermediate risks. The monitoring of ctDNA status can supplement MRI in determining the NCT response and could potentially help identify poor responders to discontinue the treatment with inadequate efficacy. Clinical trial information: NCT04922853 .

Bevacizumab with Paclitaxel and Carboplatin as Neo Adjuvant Chemotherapy for Stage 4 Ovarian Cancer- Case Report

Ovarian cancer, the fifth most common neoplasia in women, presents challenges in diagnosis and treatment, often resulting in poor prognosis due to advanced stage at diagnosis and limited treatment options. Platinum-based chemotherapy and surgery have been the mainstay treatments, but efforts to improve outcomes with additional cytotoxic drugs have yielded mixed results. Angiogenesis plays a crucial role in tumor growth and metastasis, leading to the investigation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Clinical trials have demonstrated its efficacy in delaying disease progression in ovarian cancer. This case report illustrates the successful use of neoadjuvant chemotherapy followed by surgery and maintenance therapy with bevacizumab and olaparib in a patient with advanced ovarian cancer, highlighting the potential benefits of this treatment approach in improving survival outcomes.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes.

Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC's survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524-0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713-1.205). Notably, patients treated with NAC for stage <ypT2ypN+ tumours experienced reduced OS compared to their counterparts who did not receive NAC. The HR was 3.111 (95%CI 1.249-7.746). Given that persistent nodal disease after NAC correlates with a worse prognosis, additional post-operative treatments should be considered.

P59-2 Improved survival with neoadjuvant chemotherapy in stage III pancreatic cancer: a single institutional experience

There is increasing evidence that neoadjuvant chemotherapy in stage III pancreatic cancer resulted in higher rate of conversion surgery and improved survival. This study aims to investigate the practice pattern and how initial treatment strategy impact the outcome of stage III pancreatic ductal adenocarcinoma (PDAC).

Copy number aberration burden on circulating tumor DNA predicts recurrence risk after neoadjuvant chemotherapy in patients with triple-negative breast cancer: Post-hoc analysis of phase III PEARLY trial.

603 Background: Our previous study reported prognostic significance of copy number aberration (CNA) burden on low-pass whole genome sequencing (LP-WGS) based circulating tumor DNA (ctDNA) analysis in metastatic breast cancer patients. Here, we report the prognostic value of ctDNA CNA burden measured before neoadjuvant chemotherapy in stage II-III triple-negative breast cancer (TNBC) patients enrolled in phase III PEARLY trial (NCT02441933, BIG Supporter Study BIG 19-01, KCSG BR15-01). Methods: The PEARLY trial was performed as a randomized, open-label, multicenter, phase III study to test the efficacy and safety of adding carboplatin to (neo)adjuvant chemotherapy in patients with stage II-III TNBC. Patients were randomized in a 1:1 ratio to receive 4 cycles of AC followed by the taxane or taxane plus carboplatin (AUC 5, tri-weekly 4 cycles) as neoadjuvant or adjuvant therapy. This post-hoc baseline ctDNA analysis (before neoadjuvant chemotherapy) included only the neoadjuvant patient cohort with available baseline ctDNA results (n = 465, median follow-up 16.8 months), while it was blinded for randomization information (carboplatin or not). We used "I-score" method to estimate CNA burden of ctDNA by LP-WGS to be matched with disease-free survival (DFS) after primary surgery. Results: The baseline ctDNA I-score level was positively associated with clinical T and N stage, while baseline I-score was not different between patients with pathologic complete response (pCR) and non-pCR. We listed 465 patients in the order in which they underwent primary surgery, and then alternated patients to be assigned to exploratory cohort (n =232) and validation cohort (n = 233). The DFS was significantly shorter in high I-score (I-score ≥ 7.81) patients compared with low I-score (I-score &lt; 7.81) patients in exploratory cohort. The high I-score independently predicted poor DFS adjusted for clinical T stage, clinical N stage, and pCR status (hazard ratio [HR] 3.88, p = 0.003). In the validation cohort, high I-score was validated to be associated poorer DFS, and multivariate Cox analysis validated the independent prognostic impact of I-score on DFS (HR 2.04 , p = 0.050). The high baseline I-score patients showed shorter DFS both in pCR-positive and pCR-negative patients. The 12-month DFS rate for pCR (+)/Low I-score patients was 98%, whereas that of pCR(-)/High I-score patients was 61.3 % in the validation cohort. Conclusions: The baseline ctDNA CNA burden on LP-WGS before neoadjuvant chemotherapy robustly predicts recurrence risk in stage II-III TNBC patients. The ctDNA I-score showed prognostic value independently from pCR status, suggesting ctDNA I-score can serve as a useful clinical determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients. Clinical trial information: NCT02441933.

A case-control study of healthcare disparities in sex and gender minority patients with breast cancer.

6517 Background: Disparities in the quality of diagnosis and treatment of breast cancer in sex and gender minority (SGM) populations are largely undefined. Only 24% of studies funded by the National Cancer Institute capture data on sexual orientation, while only 10% capture data on gender identity. To address this gap, the National Academies 2020 Report calls for adding sexual orientation and gender identity (SOGI) to ongoing data collection efforts. This case-control study matching SGM patients with breast cancer to cisgender heterosexual controls is the result of linking SOGI data to the Stanford University Healthcare (SHC) Oncoshare breast cancer database, which integrates data from the electronic medical record (EMR) and California Cancer Registry. Methods: An initial database query across the SHC EMR was performed for charts containing SOGI terms in patients with breast cancer seen in SHC Oncology. 686 charts were identified for manual review and after eliminating false positives, the sample was reduced to 92 SGM patients, who were then matched by year of diagnosis, age, stage, ER-status, and HER-2 status to cisgender heterosexual controls within Oncoshare. Additional data on demographics, diagnosis, treatment, and relapse were then manually abstracted from the EMR. Results: The SGM cohort was comprised of 80% lesbians, 13% bisexuals and 6% transgender men. The median age at diagnosis across both groups was 49. SGM patients were 72% white, 4% Asian, 12% Black or Latinx 6% other compared to 63% white, 24% Asian, 6% Black or Latinx, 6% other in the controls (p = 0.0006). Thirteen percent and 32% of SGM patients engaged in risky alcohol and illicit drug use respectively, compared to 3% and 6% of controls (p = 0.028; p &lt; 0.0001). Estrogen exposure risk factors including median age of menarche, first delivery, menopause, and use of exogenous estrogens were balanced between the two groups, but SGM patients had fewer children (median 0 vs 2, p &lt; 0.0001). There was a delay in time to diagnosis from symptom onset in SGM patients versus controls (median 64 days vs 37 days, p = 0.043). There was no difference in surgical approach, use of post-lumpectomy radiation, or use of neoadjuvant chemotherapy for stage III disease. However, SGM patients were less likely to undergo chest reconstruction (55% vs 82%, p = 0.0098) and if ER+, to complete ≥5 years of ER-directed therapy (53% vs 72%, p = 0.048). SGM patients used more alternative medicine (46% vs 29%, p = 0.033) and had a higher rate of documented refusal of recommended oncologic treatments (38% vs 21%, p = 0.0088). Correspondingly, SGM patients experienced a higher recurrence rate (31% vs 14%, p = 0.0124). Conclusions: To our knowledge, this is the first study to examine quality of diagnosis and treatment of breast cancer in SGM patients. Several novel potential healthcare disparities are identified, which should be further evaluated in population-based studies to inform interventions.

Stage IV colon cancer patients without DENND2D expression benefit more from neoadjuvant chemotherapy.

According to the EPOC study, chemotherapy could improve 5-year disease-free survival of stage IV colon cancer patients by 8.1%. However, more molecular biomarkers are required to identify patients who need neoadjuvant chemotherapy. DENND2D expression was evaluated by immunohistochemistry in 181 stage IV colon cancer patients. The prognosis was better for patients with DENND2D expression than patients without DENND2D expression (5-year overall survival [OS]: 42% vs. 12%, p = 0.038; 5-year disease-free survival: 20% vs. 10%, p = 0.001). Subgroup analysis of the DENND2D-negative group showed that patients treated with neoadjuvant chemotherapy achieved longer OS than patients without neoadjuvant chemotherapy (RR = 0.179; 95% CI = 0.054–0.598; p = 0.003). DENND2D suppressed CRC proliferation in vitro and in vivo. Downregulation of DENND2D also promoted metastasis to distant organs in vivo. Mechanistically, DENND2D suppressed the MAPK pathway in CRC. Colon cancer patients who were DENND2D negative always showed a worse prognosis and were more likely to benefit from neoadjuvant chemotherapy. DENND2D may be a new prognostic factor and a predictor of the need for neoadjuvant chemotherapy in stage IV colon cancer.

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer

BackgroundNeoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients’ genomic characteristics.MethodsWe prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery. Patients received epirubicin and cyclophosphamide for 4 cycles, followed by another 4-cycle docetaxel, and human epidermal growth factor receptor (HER2) positive patients were additionally treated with herceptin when using docetaxel (EC-T(H)). NAC responses were evaluated as pathologic complete response (pCR) or non-pathologic complete response (non-pCR). Genomic features related to NAC responses were identified by profiling baseline tumor tissues sampled one day before NAC, using whole-exome sequencing. Differentially expressed genes and up-/down-regulated pathways were investigated by performing RNA-sequencing.ResultsA total of 25 stage II/III BC patients were enrolled, including 5 patients ultimately evaluated as pCR and 20 patients evaluated as non-pCR. PIK3CA (48%) and TP53 (40%) mutations were enriched in patients not achieving pCR. Mutated phosphatidylinositol-3-kinase-AKT (PI3K-AKT) pathway and homologous recombinational repair pathway were also more frequently observed in patients evaluated as non-pCR. Significant arm-level amplifications (8q24.23 and 17q12) and deletions (1p32.2, 4p14, 7q11.23, 10q21.3, 11q23.3, etc.) were identified among patients not achieving pCR, while patients achieving pCR displayed no significant copy number alterations. Significantly up-regulated expression of PI3K-AKT pathway genes was also detected among patients failed to achieve pCR, compared to patients achieving pCR.ConclusionCompared to BC patients achieving pCR to NAC, aberrant activation of PI3K-AKT pathway genes were more frequently observed in patients not achieving pCR, consistent with the significant up-regulation of PI3K-AKT pathway gene expression in the non-pCR subgroup. Together, these findings indicate that upregulated PI3K-AKT pathway serves as a potential indicator of lack of response to NAC in stage II/III BC patients, and other effective therapeutic options are urgently needed for those resistant patients.

Neoadjuvant chemotherapy for HER2-positive breast cancer using dose-consolidated regimens and dual anti-HER2 blockade with pertuzumab and trastuzumab (preliminary results)

The main goal of neoadjuvant chemotherapy (NACT) in aggressive breast cancer (BC) subtypes (triple-negative, HER2-positive) is to achieve complete pathological response (pCR), since it is associated with a significant decrease in the likelihood of recurrence and death. Currently, the standard approach for HER2+ BC stage II–III is NACT with the inclusion of a double anti-HER2 blockade, since this significantly increases the frequency of pCR. To date, it remains unclear whether the intensification of modern anthracycline-taxane-containing regimens of NACT affects the incidence of pCR in different BC subtypes, including HER2-positive, provided that a double anti-HER2 blockade is used.The aim of our prospective observational study from daily clinical practice was to assess the efficacy (according to the RCB system and the frequency of pCR) and tolerability of dose-dense NACT in stage II–III HER2-positive BC.Materials and methods. The study included 86 patients, mean age 45 years (26–74 years), in 96.5% of cases, the tumor was represented morphologically by invasive cancer of a nonspecific type, in 53.5% of the tumors had a positive luminal B HER2 phenotype, in 46.5% – non-luminal HER2+. The majority of patients (67.4%) had locally advanced inoperable breast cancer; in 80.2% of cases, metastatic lesions of regional lymph nodes were determined. NACT included anthracyclines and taxanes: four cycles of AC in a dose-dense regimen (once every 2 weeks), then four cycles of docetaxel 75 mg/m2 once every 3 weeks + trastuzumab + pertuzumab.Results. The frequency of pCR = RCB0 in the entire group was 54.7% (47/86), in locally advanced breast cancer – 55.9%, in operable breast cancer – 51.9%. In the luminal HER2+ subtype, the frequency of pCR was lower than in the non-luminal HER2+ subtype – 43.5% vs 67.5%, however, the differences were statistically insignificant (p = 0.09). The frequency of RCB0–I in ER+ HER2+ subtype was 60.9%, as in ER-HER2+ – 80%. Conclusions. In our study, for the first time, the efficacy of dose-dense NACT in HER2+ breast cancer was assessed; it was shown that the frequency of pCR and RCB0–I correspond to those in standard anthracycline-taxane-containing regimens. In the context of the use of double anti-HER2 blockade, the anthracycline stage, most likely, does not need to be escalated, since this does not lead to an increase in the frequency of complete pathomorphological regressions.

Les traitements péri-opératoires des cancers bronchiques non à petites cellules (CNPC) : standards actuels et perspectives: Perioperative treatments for non-small cell lung cancer (NSCLC): Current standards and perspectives

Surgery is the main treatment in stage I-IIIA NSCLC. Several phase 3 randomized adjuvant and neoadjuvant trials with platinum-based chemotherapy were performed in stage I, II and III A NSCLC. These trials demonstrated a significant 5% benefit in 5y-survival estimated with adjuvant or neo-adjuvant chemotherapy in stage II and IIIA. This benefit was confirmed in two meta-analyses of individual participant data. Conversely for the stage I the benefit of chemotherapy was suggested only for tumors > 4 cm. Lung-ART/IFCT-0503 trial did show the lack of benefit for adjuvant radiotherapy for N2 patients. The perioperative impact of targeted treatments in NSCLC with molecular alterations is actually suggested by one study in patients with EGFR mutations. Finally, the role of immune checkpoints inhibitors is currently evaluated in neoadjuvant and adjuvant phase 3 trials. Preliminary results are encouraging.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Dose-dense Paclitaxel and Carboplatin as Neoadjuvant Chemotherapy for Stage IIB/IIIA Non-small Cell Lung Cancer – A Phase II trial

AimsThe approach to potentially resectable non-small cell lung cancer (NSCLC) remains controversial. There is a benefit of neoadjuvant chemotherapy (NACT), but the ideal regimen is unknown. We evaluated the efficacy and safety of dose-dense NACT in potentially resectable NSCLC in this phase II trial. Materials and methodsPaclitaxel at 80 mg/m2 on days 1, 8 and 15 with AUC-6 carboplatin on day 1, 3 weekly for four cycles was evaluated as NACT. Patients with Eastern Cooperative Oncology Group performance status 0–2, stage IIB and IIIA (with only non-bulky N2 nodes) were included. The primary end point was the objective response rate. Secondary end points included toxicity, progression-free survival, recurrence-free survival, complete resection rate and overall survival. The relative dose intensity (RDI) was calculated to define tolerability (CTRI/2016/05/006916). ResultsIn total, 37 patients were enrolled (median age 55 years). Most (78.8%) were smokers. Most patients had adenocarcinoma (57.6%) and stage IIIA disease (81.0%) according to the seventh American Joint Committee on Cancer staging system. Seventy-eight per cent of patients completed four cycles. The objective response rate was 75.6% with a complete response in 10.8%. The mean RDI of paclitaxel was 88.61%, with 68.0% of patients able to maintain an RDI ≥85.0%. In total, 187 toxicity events were recorded (120 grade 1, 64 grade 2 and three grade 3 events). Common toxicities were peripheral neuropathy (20.3%), myalgia (19.8%), nausea (15.7%) and neutropenia (10.2%). There were no treatment-related deaths. Seventeen patients underwent surgery (lobectomy 82.4%). After a median follow-up of 47 months (95% confidence interval 27–50.7 months), the median progression-free survival was 9.6 months (7.4–17.4) and overall survival was 29.2 months (16.0–37.2). ConclusionDose-dense paclitaxel–carboplatin is feasible, safe and efficacious and should be evaluated further in potentially resectable NSCLC.

Factors influencing the response to neoadjuvant chemotherapy in stage III triple-negative breast cancer patients

Introduction: Breast cancer is a significant burden to women’s health worldwide, mainly due to the diagnostic tendency at the advanced stages, metastasis, and chemoresistance. Therefore, this study aimed to determine the relationship between age, histological grading, menopausal status, Ki-67, and the percentage of tumor-infiltrating lymphocyte (TIL) to the neoadjuvant chemotherapy response in stage III TNBC patients.Methods: This study was a case-control analytic observational study. Samples were obtained using a consecutive sampling method. All patients’ and clinicopathological characteristics were extracted from medical records, including the chemotherapeutic response.Results: This study found no association between age and menopausal status to chemoresistance. Meanwhile, tumor grade, Ki-67, and TIL were significantly associated with chemotherapeutic resistance. Finally, multivariate analysis showed that only Ki-67 was independently associated with chemoresistance with R 14.4 (CI: 1.80-115.73) and a p-value = 0.012.Conclusion: High Ki-67 was independently associated with increased chemoresistance to neoadjuvant chemotherapy in stage III triple-negative breast cancer patients.

Abstract PS6-07: Comparison of breast cancer staging models in patients after neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is commonly utilized for breast cancer, however no consensus exists on the best way to stage these patients following treatment. Importantly, the American Joint Commission on Cancer (AJCC) 8th edition staging system did not specifically address staging after NAC. However, previous work by our group has shown that the pathologic prognostic stage does stratify patients with respect to outcomes. Our objective was to compare performance of the AJCC pathologic prognostic staging system to a second staging model, the Residual Cancer Burden (RCB) Index which takes into account residual tumor size, cellularity, lymph node status and size of any lymph node metastases. Methods: A retrospective review identified patients with stage I-III invasive breast cancer treated with NAC from 2004-2014 at Dana-Farber Cancer Institute. Patients were excluded if they did not have RCB reported on final pathology. Disease-free survival (DFS) was defined as any recurrence or death from any cause, and overall survival (OS) as death from any cause. DFS and OS were calculated using the Kaplan-Meier method for each staging model. Receiver operator characteristic (ROC) curves were used to assess model fit using the c-statistic and the Hanley method to compare c-statistics. Results: A total of 802 patients underwent NAC for stage I-III breast cancer. The median age was 48 years (range 22-86). Most patients presented with cT2 (n=470, 58.6%) or cT3 (n=188, 23.4%) and cN1 (n=422, 52.6%) disease. The majority (n=563, 70.2%) presented with grade 3 disease. In terms of subtype, 296 (36.9%) patients had hormone receptor-positive, HER2 negative, 261 (32.5%) HER2+, and 245 (30.5%) triple negative disease. Median follow up was 79.5 months (range 4-169). There were 176 recurrences including 32 local, 25 regional, and 145 distant recurrences. 676 (76.8%) patients were alive at last follow-up. The Table depicts the 7-year DFS and OS estimates for each of the staging models. The ROC c-statistics for DFS model fit were statistically similar, 0.72 for AJCC pathologic prognostic stage and 0.71 for RCB (p=NS). The c-statistics for OS were 0.74 and 0.71 respectively (p=NS). Conclusions: Our results provide additional external validation of the AJCC pathologic prognostic stage and RCB’s ability to stratify patients after NAC with respect to survival outcomes. These data can be used to inform subsequent revisions of the AJCC breast cancer staging system. Estimated 7-year DFS and OS in Potential Staging Models for Breast Cancer Patients after NAC (n=802)7yr-DFS7yr-OSPathologic Prognostic StageStage 0 (n=228)92.9%94.8%Stage IA (n=193)81.7%90.2%Stage IB (n=173)74.5%86.6%Stage IIA (n=105)62.2%71.5%Stage IIB (n=11)70.2%57.3%Stage IIIA (n=40)62.2%75.4%Stage IIIB (n=27)56.7%83.0%Stage IIIC (n=25)27.8%28.2%C-statistic (95% CI)0.72 (0.68-0.76)0.74 (0.69-0.79)RCB0 (n=226)93.5%94.8%I (n=118)83.0%90.0%II (n=278)75.9%85.0%III (n=180)55.1%69.9%C-statistic (95% CI)0.71 (0.67-0.75)0.71 (0.66-0.75) Citation Format: Olga Kantor, Alison Laws, Ricardo G Pastorello, Stephanie Wong, Tanujit Dey, Stuart Schnitt, Tari A King, Elizabeth A Mittendorf. Comparison of breast cancer staging models in patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-07.

Neoadjuvant chemotherapy improves outcomes in resectable pancreatic adenocarcinoma: an updated national cancer database analysis

Presenter: Wade Christopher MD | Providence Saint John's Cancer Institute Background: Systemic chemotherapy has been shown to have a survival benefit for all stages of pancreatic adenocarcinoma. Historically adjuvant chemotherapy (AC) was given for all patients. However, recently there has been a shift towards neoadjuvant chemotherapy (NAC) for both resectable and borderline resectable pancreatic adenocarcinoma. This shift has been driven by the observation that many post-operative patients are unable to undergo treatment with AC secondary to surgical complications. The objective of this study was to compare survival and oncologic outcomes of NAC versus AC for early stage resectable pancreatic cancer. Methods: Patients age 18 years and older with stage I or II pancreatic adenocarcinoma in the 2010-2017 National Cancer Database were identified. Patients were grouped as receiving NAC + surgery compared to those patients who underwent upfront surgery +/- AC. Logistic regression evaluated the oncologic outcomes of positive resection margins and positive lymph nodes after NAC. Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability weighting (IPTW) using propensity score matching was used to compare overall survival (OS). Results: In 19,415 patients with early stage pancreatic adenocarcinoma who underwent surgery, upfront NAC led to a 13% risk reduction of a positive resection margin when compared to surgery +/- AC (odds ratio [OR]:0.87; 95%CI 0.78-0.97), and a 59% decreased risk of positive lymph nodes at the time of surgery (OR:0.41; 95%CI 0.38-0.45), after controlling for patient clinical and pathological risk factors. The median overall survival for all patients treated with NAC was 2.56 years versus 1.95 years for surgery +/- AC (3 and 5 year OS for NAC patients was 43.14% and 26.44%; 3 and 5 year OS for surgery +/- AC patients was 34.94% and 22.42%) (Log-rank p-value < 0.001). The subgroup of stage I patents had a median OS of 2.69 years with NAC versus 2.20 years for surgery +/- AC (Log-rank p-value < 0.001). The subgroup of stage II patients had a median OS of 2.49 years with NAC versus 1.75 years for surgery +/- AC (Log-rank p-value < 0.001). In the Cox proportional-hazards regression analyses with IPTW using propensity score matching, NAC also had a significant OS benefit for all patients (hazards ratio [HR]:0.80; 95%CI 0.78–0.83), as well as for Stage I (HR:0.89; 95%CI 0.84–0.94) and Stage II patients (HR:0.71; 95%CI 0.68–0.75) individually. The survival benefit of NAC remained when only patients that had both surgery and chemotherapy (HR:0.90; 95%CI 0.86–0.93) were evaluated. However, in this cohort, when stratified by clinical stage, NAC was only associated with an improved OS for stage II patients (HR:0.80; 95%CI 0.76–0.84) with no significant OS benefit from NAC for Stage I patients. Conclusion: NAC appears to confer a survival benefit for patients with early stage pancreatic adenocarcinoma. NAC also decreased the risk of a positive resection margin as well as positive lymph nodes at the time of surgical resection. In stage I patients that were able to receive both surgery and chemotherapy, the timing of chemotherapy did not impact survival.

Lymph Node Ratio after Neoadjuvant Chemotherapy for Stage II/III Breast Cancer: Prognostic Value Measured with Gini's Mean Difference of Restricted Mean Survival Times.

Restricted mean survival time (RMST), recommended for reporting survival, lacks a tool to evaluate multilevel factors. The potential of the Gini’s mean difference of RMSTs (Δ) is explored in a comparison of a lymph node ratio-based classification (LNRc) versus a number-based classification (ypN) applied to stage II/III breast cancer patients who received neoadjuvant chemotherapy and underwent axillary dissection. Number of positive nodes (npos) classified patients into ypN0, npos = 0, ypN1, npos = [1,3], ypN2, npos = [4,9], and ypN3, npos ⩾ 10. Ratio npos/(number of nodes examined) of 0, (0,0.20], (0.20,0.65], and >0.65, classified patients into Lnr0 to Lnr3, respectively. Unadjusted and Cox-adjusted RMSTs were computed for the ypN and LNRc’s. At a follow-up time horizon of 72 months for 114 node-negative and 254 node-positive patients, unadjusted ypN0-ypN3 RMSTs were 62.4-41.4 months, Δ = 11.9 months (95%CI: 7.4-16.9), and Lnr0-Lnr3 62.4 to 36.3 months, Δ = 14.0 months (95%CI: 10.1-18.1). Cox models’ ypN1-ypN3 hazard ratios were 1.81-3.30, and Lnr1-Lnr3 1.52-4.39. Δ from Cox-fitted survival were ypN 8.1 months (95%CI: 5.9-10.5), LNRc 10.5 months (95%CI: 8.4-12.8). In conclusion, Gini’s mean difference is applicable to well established data in keeping with the literature on LNRc. It provides an alternative view on the improvement gained with a lymph node ratio-classification over using a number-classification.

Cancers bronchiques non à petites cellules (CBNPC) résécables et immunothérapie : état des lieux et perspectives: Resectable non-small cell lung cancers (NSCLC) and immunotherapy: status and outlook

Surgery is the main treatment in stage IA-III NSCLC. Several phase 3 randomized adjuvant and neoadjuvant trials with platinum-based chemotherapy were performed in stage I, II and IIIA NSCLC. These trials demonstrated a significant 5% benefit in 5y-survival estimated with adjuvant or neoadjuvant chemotherapy in stage II and IIIA. This benefitwas confirmed in two meta-analyses of individual participant data. Conversely for the stage I the benefit of chemotherapy was suggested only for tumors > 4cm. Adjuvant radiotherapy for N2 patients is not recommended based on the recent results of the large international phase 3 trial Lung-ART/IFCT-0503. The perioperative impact of targeted treatments in NSCLC with molecular alterations is actually suggested by the ADAURA study in patients with EGFR mutations. Finally, in the review, we will present the first results of immune checkpoints inhibitors, currently evaluated in neoadjuvant and adjuvant trials.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study

ObjectiveDecrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. MethodsCT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests. ResultsPaired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3–4 adverse events. ConclusionDecreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.

Les traitements péri-opératoires des cancers bronchiques non à petites cellules (CNPC) : standards actuels et perspectives: Perioperative treatments for non-small cell lung cancer (NSCLC): Current standards and perspectives

AbstractSurgery is the main treatment in stage I-IIIA NSCLC. Several phase 3 randomized adjuvant and neoadjuvant trials with platinum-based chemotherapy were performed in stage I, II and III A NSCLC. These trials demonstrated a significant 5% benefit in 5y-survival estimated with adjuvant or neo-adjuvant chemotherapy in stage II and IIIA. This benefit was confirmed in two meta-analyses of individual participant data. Conversely for the stage I the benefit of chemotherapy was suggested only for tumors > 4 cm. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The perioperative impact of targeted treatments in NSCLC with molecular alterations is actually suggested by one study in patients with EGFR mutations. Finally, the role of immune checkpoints inhibitors is currently evaluated in neoadjuvant and adjuvant phase 3 trials. Preliminary results from neoadjuvant phase 2 trials are encouraging.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

204P Metformin with neoadjuvant chemotherapy in stage II-III breast cancer: A phase II clinical trial

204P Metformin with neoadjuvant chemotherapy in stage II-III breast cancer: A phase II clinical trial