Neoadjuvant Systemic Chemotherapy Research Articles

Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer

Triple negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

Abstract PO5-26-02: Changes in Breast Cancer Optoacoustic Imaging Features During Neoadjuvant Therapy and Correlation with Pathologic Response: A feasibility study

Abstract Purpose: To evaluate the association of optoacoustic imaging (OA/US) feature changes with neoadjuvant therapy response and compare with volumetric changes. Methods and Materials: In an IRB approved, HIPAA compliant single arm, single-institution study, 20 breast cancer patients scheduled to undergo neoadjuvant systemic chemotherapy (NAC) were prospectively enrolled to undergo optoacoustic imaging (OA/US) at baseline, prior to cycle 2(Postcycle 1), mid-therapy (mid-chemo)and pre-operative(pre-op) timepoints using a standardized scan protocol. % change in volume was recorded for each timepoint. OA/US features: internal vessels (OAint), total internal hemoglobin (OAHb), internal deoxyHb, external peripheral zone (OApz), boundary zone (OAbz) scored using a previously validated schema. Pathology was collected from standardized reports using residual cancer burden (RCB) and pathologic complete response (pCR) as end points. RCB0-II were classified as responders, RCB-III as non-responders. Descriptive statistics displayed as mean and standard deviation and compared using Wilcoxon Rank-Sum test. Association of volume change was performed using odds ratio (OR) generated from univariate logistic regressions (P-Value < 0.05 for significance). Results: Mean patient age was 50.4 years (SD± 9.5), index cancer size: 26.3mm (SD±9.7). Surgical pathology showed pCR in 6(30%), partial response in 11(55%), no response in 3(15%) cancers, with mean overall residual cellularity of 32.7%(SD±33.5). Mean % residual volume was not significantly different between responders vs nonresponders. [PostCycle 1 (43.7 ± 25.3 vs 38.5 ± 24.8, p=0.7), mid-chemo (64.2 ± 30.9 vs. 65.8 ± 24.6, p=0.8), pre-op (82.9 ± 23.5 vs 89.3 ± 8.4, p=0.9) timepoints. Regression analysis did not show significant correlation of %vol change with pCR at any timepoint (p >0.05). Postcycle 1, OAHb change was significantly higher in patients who had pCR (76.4% vs 108.8%; p=0.02). At pre-op scan, greater decreases were seen in all OA/US scores in cancers that achieved pCR compared to non-pCR [OAbz (25.0% vs. 84.7% P = 0.03; OAint (40.0% vs. 90.3% P = 0.03);OAHb (18.3% vs. 91.8%; P = 0.03); deoxyHb (26.7% vs. 104.8%; P = 0.02), total OAext (25.8% vs. 88.1%; P = 0.03); total internal (16.2% vs. 91.6%; P = 0.03)]. Conclusions: OA/US feature changes demonstrate higher correlation with pCR than volumetric shrinkage in this feasibility study and show promise as a potential tool to non-invasively identify pCR. Table. Percentage Change in Optoacoustic Ultrasound (OA/US) Feature Scores from Baseline, Stratified by (pathologic complete response (pCR). Citation Format: Baṣak Dogan, Berat Bersu Ozcan, Heather McArthur, Yan Peng. Changes in Breast Cancer Optoacoustic Imaging Features During Neoadjuvant Therapy and Correlation with Pathologic Response: A feasibility study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-02.

Abstract PO4-27-07: A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2)

Abstract Background: Camizestrant is a next-generation oral selective estrogen receptor (ER) degrader and pure ER antagonist being investigated in early and advanced breast cancer (BC). In postmenopausal women with advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative BC and disease recurrence or progression on or after ≤1 endocrine therapy (ET) in the advanced setting, camizestrant significantly prolonged progression-free survival compared with fulvestrant in the Phase 2 SERENA-2 trial. Camizestrant may also provide benefit in the early BC setting. Following locoregional therapy (surgery ± radiotherapy), standard adjuvant treatment of ET with or without chemotherapy and/or a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has shown significant benefit in decreasing the risk of recurrence of stage I–III ER-positive/HER2-negative BC. However, BC recurrence as incurable metastatic disease is still common. Thus, adjuvant therapeutic options with improved clinical outcomes are needed. The CAMBRIA-2 study (NCT05952557) aims to assess whether upfront camizestrant can improve outcomes compared with standard ET as adjuvant treatment in patients with ER-positive/HER2-negative early BC with an intermediate-high or high risk of recurrence after definitive locoregional therapy. Trial design: This ongoing Phase 3, randomized, open-label study is enrolling women (pre-, peri-, or postmenopausal) and men with ER-positive/HER2-negative (HER2-negative status defined as immunohistochemistry 0, or 1+, or in situ hybridization-negative) early BC who are at intermediate-high or high risk of recurrence (as defined in the protocol) after having completed definitive locoregional therapy (surgery ± radiotherapy) ± (neo)adjuvant systemic chemotherapy, and who have no evidence of disease. Patients may have received up to 12 weeks of (neo)adjuvant ET prior to randomization. Patients are randomized (1:1) to receive camizestrant 75 mg ± abemaciclib ± luteinizing hormone-releasing hormone (LHRH) agonist or standard ET of the investigator’s choice (any aromatase inhibitor or tamoxifen) ± abemaciclib ± LHRH agonist for up to 7 years. The primary endpoint is invasive BC-free survival (IBCFS) (Standardized Definitions for Efficacy End Points [STEEP] 2.0 criteria). Secondary endpoints include invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Primary endpoint analysis will use a stratified log-rank test adjusting for stratification factors, assuming a two-sided significance level of 5%. Approximately 5500 patients will be randomized. Clinical trial identification: NCT05952557 Editorial acknowledgment: Writing assistance was provided by Clare Davis of BOLDSCIENCE Inc., funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca Funding: This study was supported by AstraZeneca. Citation Format: Sibylle Loibl, Yeon Park, Sara Tolaney, Ioanna Gioni, Simon Johnston, Teresa Klinowska, Ingrid A. Mayer, Raquel Nunes, Barbara Pistilli, Mary Stuart, Angela Quintana, Andrew Walding, Michael Gnant. A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-07.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy plus Neoadjuvant Intraperitoneal and Systemic Chemotherapy for Gastric Cancer with Malignant Ascites

Abstract Background: Patients with gastric cancer (GC) and malignant ascites (MA) usually have poor outcomes and a high risk of recurrence and mortality, even after curative gastrectomy or chemotherapy. Systemic chemotherapy has been prescribed for patients with GC and MA; however, most of these patients expire within 1 year. Aim: To evaluate the outcomes of laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in the outcomes of GC patients with MA. Methods: We enrolled 62 patients with GC and MA between January 1, 2016, and March 1, 2021. Four patients were excluded because of extraperitoneal metastasis, and two patients were ineligible. A total of 56 patients underwent biweekly staging laparoscopy and LHIPEC with NIPS. We also performed staging laparoscopy to evaluate the effectiveness of LHIPEC + NIPS. Results: The mean survival time of the 56 patients was 20.8 months. The overall complication rate was 33.93%. After the LHIPEC + NIPS intervention, the peritoneal cancer index score (P < 0.001), ascites volume (P = 0.003), and cytology (P < 0.001) significantly improved compared to before the intervention; quality of life (Eastern Cooperative Oncology Group) was also better than before the intervention (P = 0.002), and no discomfort was noted postintervention. Conclusion: LHIPEC + NIPS is feasible for the treatment of GC with MA and may improve patients’ quality of life.

Neoadjuvant chemo-immunotherapy is improved with a novel pulsed electric field technology in an immune-cold murine model.

Chemo-immunotherapy uses combined systemic therapies for resectable and unresectable tumors. This approach is gaining clinical momentum, but survival increases leave considerable room for improvement. A novel form of Pulsed Electric Field (PEF) ablation combines focal tissue destruction with immune activation in preclinical settings. The PEFs induce lethal cell damage without requiring thermal processes, leaving cellular proteins intact. This affords PEF a favorable safety profile, improved antigenicity, and significant immunostimulatory damage-associated molecular pattern release compared to other focal therapies. Preclinical investigations demonstrate a combinatorial benefit of PEF with immunostimulation. This study evaluates whether this proprietary PEF therapy induces an immunostimulatory effect sufficient to augment systemic neoadjuvant chemotherapy and immunotherapy to reverse metastatic disease in an immune-cold murine tumor model. To determine whether PEF improves a neoadjuvant chemo-immunotherapy standard-of-care, partial PEF ablation was delivered to orthotopically inoculated 4T1 metastatic tumors in addition to combinations of cisplatin chemotherapy and/or αPD-1 immunotherapy, followed by resection. In addition, to determine whether PEF combined with chemo-immunotherapy improves local and metastatic response in unresectable populations, partial PEF ablation was added to chemo-immunotherapy in mice that did not receive resection. Blood cytokines and flow cytometry evaluated immune response. Partial PEF ablation generates an immunostimulatory tumor microenvironment, increases systemic immune cell populations, slows tumor growth, and prolongs survival relative to neoadjuvant systemic therapies-alone. These data suggest the addition of this proprietary PEF locoregional therapy may synergize with systemic standard-of-care paradigms to improve outcomes with potential or demonstrated metastatic disease in both resectable and unresectable patient cohorts.

A commentary on 'Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study'.

A commentary on 'Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study'.

Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be noninferior to nCRT with respect to short-term oncological outcomes few data exist on perioperative outcomes. Perioperative morbidity including anastomotic leaks is associated with a negative effect on oncological outcomes, probably due to a delay in proceeding to adjuvant therapy. Thus, we aimed to compare conversion rates, rates of sphincter-preserving surgery and anastomosis formation rates in patients undergoing rectal resection after either TNT or standard nCRT. An institutional colorectal oncology database was searched from January 2018 to July 2023. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a noncolorectal primary, those operated on emergently or who had local excision only. Outcomes evaluated included rates of conversion to open, sphincter-preserving surgery, anastomosis formation and anastomotic leak. A total of 119 patients were eligible for inclusion (60 with standard nCRT, 59 with TNT). There were no differences in rates of sphincter preservation or primary anastomosis formation between the groups. However, a significant increase in conversion to open (p = 0.03) and anastomotic leak (p = 0.03) was observed in the TNT cohort. In this series TNT appears to be associated with higher rates of conversion to open surgery and higher anastomotic leak rates. While larger studies will be required to confirm these findings, these factors should be considered alongside oncological benefits when selecting treatment strategies.

Systemic Cisplatin Does Not Affect the Bone Regeneration Process in a Critical Size Defect Murine Model.

Osteosarcoma (OS) is the most common primary malignant bone tumor, and the current standard of care for OS includes neoadjuvant chemotherapy, followed by an R0 surgical resection of the primary tumor, and then postsurgical adjuvant chemotherapy. Bone reconstruction following OS resection is particularly challenging due to the size of the bone voids and because patients are treated with adjuvant and neoadjuvant systemic chemotherapy, which theoretically could impact bone formation. We hypothesized that an osteogenic material could be used in order to induce bone regeneration when adjuvant or neoadjuvant chemotherapy is given. We utilized a biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of systemic chemotherapy in a murine critical size defect model. We found that in the presence of neoadjuvant or adjuvant chemotherapy, MHA/Coll is able to enhance and increase bone formation in a murine critical size defect model (11.16 ± 2.55 or 13.80 ± 3.18 versus 8.70 ± 0.81 mm3) for pre-op cisplatin + MHA/Coll (p-value = 0.1639) and MHA/Coll + post-op cisplatin (p-value = 0.1538), respectively, at 12 weeks. These findings indicate that neoadjuvant and adjuvant chemotherapy will not affect the ability of a biomimetic scaffold to regenerate bone to repair bone voids in OS patients. This preliminary data demonstrates that bone regeneration can occur in the presence of chemotherapy, suggesting that there may not be a necessity to modify the current standard of care concerning neoadjuvant and adjuvant chemotherapy for the treatment of metastatic sites or micrometastases.

Neo-adjuvant PIPAC and Systemic Chemotherapy in Management of Synchronous Peritoneal Metastasis From Gastric Cancer

Introduction: Polycystic Ovarian Disorder (PCOD) is a prevalent endocrine illness in women of reproductive age. It has hormonal abnormalities, irregular menstrual cycles and tiny ovarian cysts. Lifestyle and food affect PCOD development and maintenance, coupled with Peritoneal metastasis from gastric cancer remains a major problem. The aim of our study is a retrospective analysis in two different groups with used PIPAC as neo-adjuvant management of synchronous peritoneal metastasis. Group A: 42 patients received as neo-adjuvant treatment 2 cycles of PIPAC (Doxorubicin 3 mgr/m2, cisplatin 10 mgr/m2) and 6 cycles of neo-adjuvant systemic chemotherapy with FLOT and we performed CRS+HIPEC (with cisplatin 80 mgr/m2, mitomycin 35 mgr/m2) for 90 min and 6 cycles of adjuvant systemic chemotherapy with FLOT. Group B: 26 patients received 4 cycles of neo-adjuvant systemic chemotherapy with FLOT, we performed CRS+HIPEC as Group A and 4 cycles of systemic chemotherapy with FLOT. For patients of Group A, the Median survival time is 46months.Group B patients had a median OS of 36 months. For patients of Group A, the Median Disease Time (DFS) was 37 months. Group B patients had a median DFS of 30 months. For each degree increase in the PCI pre score and for the same treatment group, the PCI posr score increases by 0.573 degrees. Group 2, for the same PCIpre score, have a 163% higher PCI posr score. On patients with singet ring cell adenocarcinoma there is a statistical significance difference in OS for PIPAC group. Patients of group A had a median OS of 26 months. For patients of group B, the median OS was 14 months. Morbidity and mortality in both groups are 53,4% and 4,7% for Group A and 44,5% and 5,5% for Group B respectively. The neo-adjuvant PIPAC with systemic chemotherapy might be a promising approach for patients with peritoneal metastasis from gastric cancer. PIPAC is a safe and well tolerated procedure.

Neoadjuvant chemotherapy for stage II–III breast cancer: a single-center experience

IntroductionWe conducted this study to reflect a single-center experience with the use of neoadjuvant systemic chemotherapy (NAC) for the management of women with operable breast cancer.MethodsWe conducted a retrospective chart review on all women presenting with operable, stage II–III, breast cancer and were scheduled for NAC at Suez Canal University Hospital. The primary outcome of this study was to estimate the proportion of patients with breast cancer who become eligible for breast-conserving surgery (BCS) after (NAC).ResultsA total of 147 patients were included. Before the initiation of chemotherapy, only 66 (44.9%) patients were indicated for (BCS). A total of 40 (49.4%) new patients, out of the 81 patients who were ineligible before chemotherapy, became eligible for BCS after NAC (95% CI 39.3–61.9%). On the other hand, 8 (12.1%) patients became ineligible for BCS after NAC, out of 66 patients who were initially eligible. Out of the 98 eligible patients for BCS after chemotherapy, 72 (73.5%) patients underwent the surgery, and the remaining 26 (26.5%) patients chose modified radical mastectomy (MRM). A total of 55 out of 72 (76.4%) patients achieved pathological complete response (pCR). One woman (0.1%) experienced relapse in the 3rd year of follow-up and three women (2%) experienced relapse in the 5th year of follow-up. We found a statistically significant relationship between patients who became eligible for breast-conserving surgery and both age and estrogen receptor negativity (p = 0.001 and 0.007, respectively).ConclusionNAC can play a crucial role in increasing the rate of eligibility for BCS among women with operable, stage II–III, breast cancer.

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study.

Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P =0.002) and CSS (33.0 vs. 27.0 months, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95% CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95% CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

FTP3.7 Influence of neoadjuvant treatment strategy on operability in locally advanced rectal cancer

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). Neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) further improves pCR rates. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be non-inferior to nCRT with respect to short-term oncological outcomes, little data exists on perioperative outcomes. Factors such as conversion, sphincter preservation and anastomosis rates do not impact oncological outcomes but affect quality of life (QOL). Methods An institutional colorectal oncology database was interrogated from inception (2009) to November 2022. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a non-colorectal primary, those operated on emergently or who had local excision only. Primary outcomes were rates of conversion to open, sphincter preserving surgery and anastomosis formation. Results In total 156 patients were eligible for inclusion (standard nCRT, n= 111, TNT, n=45). Sphincter preservation and anastomosis formation were more frequent in the nCRT cohort, while conversion rates were higher in the TNT cohort. Although these differences were not statistically different, the conversion value approached significance (sphincter preservation, 70% vs 62%, p=0.3484; anastomosis, 72% vs 64%, p=0.4632, conversion, 34% vs 17%, p=0.0501). Conclusions In this series TNT appears to be associated with higher conversion rates and lower rates of anastomosis formation. While larger studies will be required to confirm these findings, QOL factors should be considered alongside oncological benefits when selecting treatment strategies.

Postoperative recurrence in locally advanced rectal cancer: how does neoadjuvant treatment affect recurrence pattern?

BackgroundThe treatment strategy for locally advanced rectal cancer (LARC) has recently expanded from total mesorectal excision to additional neoadjuvant chemoradiotherapy (nCRT) and/or systemic chemotherapy (NAC). Data on disease recurrence after each treatment strategy are limited.MethodsClinical stage II to III rectal cancer patients who underwent curative surgery between July 2005 and February 2021 were analyzed. The cumulative incidence and site of first recurrence were assessed. The median follow-up duration was 4.6 years.ResultsAmong the 332 patients, we performed nCRT and NAC in 15.4% (N=51) and 14.8% (N=49), respectively. The overall recurrence rate was 23.5% (N=78). Although several differences in tumor stage or location were observed, there was no significant difference in the rate among the surgery alone (N=54, 23.3%), nCRT (N=11, 21.6%), and NAC (N=13, 26.5%) groups. In this cohort, the local recurrence rate (18.4%) was higher than the rate of distant metastasis in the NAC group (14.3%). All patients with recurrence in the nCRT group had distant metastases (N=11: one patient had distant and local recurrences simultaneously). For pathological stage 0-I, the recurrence rate was higher in the nCRT and NAC groups than in the surgery-alone group (nCRT, 10.0%; NAC, 15.4%; and surgery-alone, 2.0%). Curative-intent resection of distant-only recurrences significantly improved patients’ overall survival (hazard ratio [95% confidence interval], 0.34 [0.14–0.84]), which was consistent even when stratified according to neoadjuvant treatment. Regardless of neoadjuvant treatment, >80% of recurrences occurred in the first 2.2 years, and 98.7% within 5 years after surgery.ConclusionRegardless of neoadjuvant treatment, detecting distant metastases with intensive surveillance, particularly in the first 2 years after surgery, is important. Also, even if neoadjuvant treatment can downstage LARC to pathological stage 0-I, careful follow-up is needed.

A Systematic Review of Short-Term Outcomes of Minimally Invasive Thoracoscopic Surgery for Lung Cancer after Neoadjuvant Systemic Therapy.

Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk.

Frequency of axillary nodal complete pathological response of breast cancer patients in neoadjuvant chemotherapy setting: A cross-sectional study.

Pathological complete response (pCR) occurs in about 20-30% of patients undergoing systemic neoadjuvant therapy. This leads to the idea of sparing the patient the morbidity associated with axillary surgery. "Wait and watch" policy for cancers which achieve complete pathological response on neoadjuvant systemic therapy is a well-established practice in various cancers like the esophagus, rectum and larynx. This has led to organ preservation protocols being practiced worldwide for these cancers without affecting the overall survival of the patient. We believe patients undergoing a complete pathological response in the breast may be spared axillary surgery. Axillary surgery leads to morbidity and extra financial burden with no added advantage in survival. A total of 326 patients with breast cancer who had received neoadjuvant systemic chemotherapy from 2015 to 2020 were included in our retrospective study. Final histopathology of the breast and axillary surgery was noted to report the frequency of complete pathological response. The frequency of positive nodal disease with respect to stage, grade and type of cancer was measured. Among 326 patients, our study showed that 53% of patients with complete pathological response in breast also had complete response in the axilla compared to 43% with incomplete pathological response. No significant difference was found for age, menopausal status, initial tumor size when patients with complete pathological response were compared to non or partial responders. The rate of complete pathological response was higher in patients with clinically node negative patients after NACT, hormone negative, HER2 positive and triple negative population. Our results indicated that 53% of the patients who developed complete pathological response in the breast underwent needless axillary procedure. Axillary surgery can be staged after the breast surgery if residual tumor is present on the histopathological specimen. In case of pCR, omission of axillary surgery can be considered. However, a larger population, multi-centric studies are needed for treatment guidelines.

Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

AB152. SOH23ABS_225. Operability after total neoadjuvant therapy for rectal cancer

Background: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). Neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) further improves pCR rates. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be non-inferior to nCRT with respect to short-term oncological outcomes, little data exists on perioperative outcomes. Factors such as conversion, sphincter preservation and anastomosis rates do not impact oncological outcomes but affect quality of life (QOL).

P119 Recurrence Score® result by the 21-gene assay before and after systemic neoadjuvant chemotherapy in patients with HR+ HER2-breast cancer.

P119 Recurrence Score® result by the 21-gene assay before and after systemic neoadjuvant chemotherapy in patients with HR+ HER2-breast cancer.

Preoperative downstaging of pancreatic cancer is associated with improved survival after multi-agent chemotherapy, but not after radiation

BackgroundDownstaging has been associated with improved survival for many cancers. However, the implications of downstaging are unclear for pancreatic cancer in an era of effective neoadjuvant systemic chemotherapy. MethodsNCDB retrospective cohort study of resected pancreatic carcinoma treated with neoadjuvant therapy. ResultsThe study included 73,985 patients: 66,589 with no neoadjuvant therapy, 2,102 neoadjuvant radiation therapy (N-RT), 3,195 neoadjuvant multiagent chemotherapy (N-MAC) and 2.099 with both neoadjuvant radiation and multiagent chemotherapy. There was increased use of N-MAC over the period of this study. Patients selected for treatment with N-MAC had longer survival from surgery on univariate (23.1 vs. 18.7 months, p = < 0.01) and multivariate analyses HR 0.81 (0.76–0.87, p < 0.001) compared to those selected with N-RT. Downstaging was similar in N-RT and N-MAC groups (25.1 vs. 24.1%, p = 0.43). Downstaging following N-MAC was associated with a survival benefit, HR 0.85 (0.74–0.98). However, downstaging following N-RT was not associated with a survival advantage, HR 1.12 (0.99–0.99). ConclusionClinicians have rapidly adopted N-MAC for treatment of pancreatic cancer. Although the rates of downstaging are similar between treatment groups, response translates into increased survival only with N-MAC and not with N-RT.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS±HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p=0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p=0.039) and peritoneal carcinomatosis index >10 (p=0.009), were factors independently associated with worse OS. Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.