Administration Of Neoadjuvant Chemotherapy Research Articles

Abstract PS04-03: Survival benefit of regional nodal irradiation in clinically node-positive breast cancer following neoadjuvant chemotherapy and breast-conserving surgery

Abstract Introduction: In recent years, there has been increasing use of neoadjuvant chemotherapy (NAC) and pathologic complete response (pCR) rates for certain breast cancer phenotypes (40-70%). Although encouraging, this has resulted in uncertainties in traditional axillary management. Meanwhile, clinically node-positive (cN+) patients who have a low burden of disease downstaged to node-negative (ypN0) after NAC and get breast-conserving surgery (BCS) may avoid an axillary lymph node dissection (cALND) but still have regional nodal irradiation (RNI) recommended regardless of axillary surgery. Those who remain node-positive (ypN+) undergo cALND and RNI with an increased risk of lymphedema. In this study, we evaluated the survival benefit of RNI in cN+ patients after NAC and BCS. Methods: We reviewed (cN+) stage I-III non-inflammatory female breast cancer patients who underwent NAC followed by BCS between 2010 and 2020 in the National Cancer Database (NCDB). Patients having a history of another malignancy who received hormone therapy or radiotherapy before surgery or whose pathologic nodal status (ypN) was unknown were excluded. Overall survival (OS) from surgery was compared between those who did and did not receive RNI. Patient and tumor characteristics were compared across subgroups using chi-square and Wilcoxon rank sum tests. Weighted Kaplan-Meier curves and log-rank tests were used to assess the effect of RNI on OS. As a sensitivity analysis, analyses were stratified based on yPN status. Finally, multivariable logistic regression was used to determine predictors of receiving RNI. Results: The 8,250 cN+ patients had a mean age of 54.6±11.1 years. In total, 69.1% of patients were White, 23.9% were Black, and 10.2% were Hispanic. The mean number of removed and positive nodes were 10.0 ±7.8 and 2.3±3.8. The most common histology and phenotype were invasive ductal carcinoma (IDC) in 94.3% and hormone-positive (HR+) in 41.0%. Breast and nodal pCR rates were 25.9% and 34.7%, with nodal pCR achieved in 20.7%, 46.0%, and 44.4% of HR+, HER2+, and triple-negative tumors. RNI was performed in 52.1% of the patients (45.3% of the yPN0 and 55.9% of the yPN+). The mean number of nodes removed was 10.4±7.8 in the RNI+ and 9.6±7.7 in the RNI- groups (P < 0.01). The mean number of positive nodes was 2.6±4.0 in the RNI+ and 1.9±3.6 in the RNI- groups (P < 0.01). On multivariable analysis, the predictors of RNI administration included the number of positive nodes (p < 0.01), cN stage (p < 0.01), cT3 (p < 0.01), and tumor phenotype (p < 0.01). Grade I tumors (p=0.04) and Medicare beneficiaries (p=0.01) were less likely to get RNI. The survival rates were 79.9% and 81.9% in the RNI+ and RNI– groups, with a median follow-up of 62.1±31.4 and 62.8±32.2 in the RNI+ and RNI- groups. In the entire cohort, ypN0 patients had improved OS when compared with ypN+ patients (p < 0.001), but in adjusted analyses, there was no difference in OS between those who did and did not receive RNI (p=0.6). There was also no difference in OS comparing those who did and did not receive RNI in the ypN0 (p=0.96) or ypN+ (p=0.76) groups. Conclusion: For breast cancer patients having a modest nodal burden of disease and BCS after NAC, traditional prognostic factors such as stage and nodal status, as well as phenotype, grade, and the presence or absence of pCR, impact overall survival. Although some such factors appear to bias practitioners into giving RNI for patients undergoing NAC and BCS, RNI after NAC and BCS does not improve OS, regardless of pCR status, even at a mean follow-up time of 5.5 years. Further studies evaluating the impact on local control and longer-term outcomes should be pursued to enable the creation of specific guidelines surrounding indications for RNI based on the initial burden of disease and the final response from NAC administration. Citation Format: Mahtab Vasigh, Richard Bleicher, Austin Williams, Allison Aggon, Mary Pronovost, Andrea Porpiglia, Matthew Pierotti, Christian Cruz Pico. Survival benefit of regional nodal irradiation in clinically node-positive breast cancer following neoadjuvant chemotherapy and breast-conserving surgery [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 PS04-03.

Durvalumab and tremelimumab before surgery in patients with hormone receptor positive, HER2-negative stage II-III breast cancer.

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR). The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.

Prognostic Value of Inflammatory Burden Index in Advanced Gastric Cancer Patients Undergoing Multimodal Treatment.

Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker's system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13-7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28-5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32-4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18-0.90) and TO achievement (HR = 0.42, 95% CI 0.22-0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment.

An empirical survey on the adaption of neoadjuvant chemotherapy in bladder cancer.

To determine the adaption of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) in Germany, Austria and Switzerland and especially underlying reasons for potential low adherence to guidelines. We conducted a non-validated survey amongst 336 urologic departments in Germany, Austria and Switzerland. RedCap questionnaires were electronically distributed and included 23 items concerning the general NAC administration standards and guideline compliance in patient counselling regarding actual treatment. Return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as standard-of-care, only 49% of eligible patients actually receive NAC. An advanced disease stage (≥cT3) and a high tumor-volume were mentioned to support application of NAC, whereas 35% of responders worry a deterioration of patients' preoperative status due to NAC. Furthermore, 26.7% of respondents are concerned about the low extent of survival benefit. Application of NAC in eligible MIBC-patients in Germany, Austria and Switzerland remains low. Although the majority of urologic departments discusses NAC and acknowledges the need for intensified treatment in advanced disease stages, not all eligible patients will actually receive NAC before radical cystectomy.

Blood regulator of G protein signalling 1 as a potential prognostic biomarker in surgical nonsmall cell lung cancer patients: Correlation with clinical features and survival.

Regulator of G protein signalling 1 (RGS1) closely regulates malignant phenotypes and tumour immunity in several cancers, while its clinical value in nonsmall cell lung cancer (NSCLC) is by far rarely reported. Consequently, this study aimed to explore the linkage of blood RGS1 with clinical features and prognosis in surgical NSCLC patients. Two-hundred and ten surgical NSCLC patients were consecutively enrolled in this study, whose RGS1 in peripheral blood mononuclear cells was determined before treatment via reverse transcriptional-quantitative polymerase chain reaction. Additionally, the blood RGS1 was also collected from 30 healthy controls (HCs). Blood RGS1 was increased in NSCLC patients compared with HCs (P < 0.001). Elevated blood RGS1 was related to lymph node (LYN) metastasis (P = 0.001), higher tumour-nodes-metastasis (TNM) stage (P = 0.004), neoadjuvant chemotherapy administration (P = 0.044), shortened accumulative disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.013) in NSCLC patients. A multivariate Cox's regression analysis showed that blood RGS1 high expression could independently reflect shortened DFS (hazard ratio = 1.499, P = 0.023), whereas it could not independently predict OS (P > 0.050). Furthermore, blood RGS1 high expression was associated with shortened OS (P = 0.020) in patients with neoadjuvant therapy and with worse DFS (P = 0.028) and OS (P = 0.026) in patients with adjuvant therapy, while blood RGS1 was not linked with DFS or OS in patients without neoadjuvant or adjuvant therapy (all P > 0.050). Elevated blood RGS1 correlates with LYN metastasis, neoadjuvant chemotherapy administration, worse DFS and OS, which might serve as a useful prognostic biomarker for surgical NSCLC patients.

Nationwide Outcomes After Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer-A Propensity Score-Matched Analysis.

The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort. Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.

Does neo-adjuvant chemotherapy improve the negative effect of lymphovascular invasion in survival after radical cystectomy?

PurposeThere is a lack of studies in the literature to evaluate the impact of the specific benefit of the use of neo-adjuvant chemotherapy (NAC) on the negative effect of lymphovascular invasion (LVI) on prognosis. We aimed to evaluate the survival differences of patients according to the presence of LVI with and without administration of NAC before radical cystectomy (RC). Materials and methodsWe retrospectively evaluated data of the patients who underwent RC with pelvic lymphadenectomy and urinary diversion for bladder cancer recorded in the bladder cancer database of the Turkish Uro-oncology Association between 2007 and 2021. Patient demographics, follow-up time and overall survival (OS) were noted. ResultsA total of 633 subjects included in the analyses. Median follow-up time was 24 months (IQR 12–54). Five years OS of the whole cohort was 55.1%. This was 54.7% and 59.9% in NAC- and NAC+ groups (P = 0.683), respectively. It was also 35.7% and 65.7% in LVI+ and LVI- patients (P < 0.0001), respectively. There was a significant difference between LVI+ and LVI- patients (33.2% vs. 68.2%, P < 0.0001) in NAC- group, but similar 5-year OS was found (53.2% vs. 64.5%, P = 0.552) in NAC+ group. In multivariable analyses, female gender, pN stages, presence of variant histology and LVI were significant independent predictive factors for OS in the whole cohort and in the NAC- group. However, gender association, pN stages and LVI lost significance in NAC+ group. ConclusionPresence of LVI significantly reduced OS, and the NAC treatment improved the negative effects of LVI on OS. Our findings encourage the use of NAC before RC.

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

BackgroundThe treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC.MethodsClinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection.ResultsNinety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98).ConclusionsSurgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Axillary Conversion after Neoadjuvant Chemotherapy-A Single-Tertiary Centre Experience and Review of the Literature.

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before 99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8-96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies.

Neoadjuvant Chemotherapy Prior to Radical Cystectomy for Muscle-Invasive Bladder Cancer With Variant Histology: A Systematic Review and Meta-Analysis of Survival Outcomes and Pathological Features

PurposeTo conduct systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy (NAC) on survival and histopathological outcomes of variant histology (VH) of urothelial carcinoma (UC) of bladder. MethodsThis systematic review was registered in PROSPERO (CRD42023389115). Literature search was conducted in PubMed/Medline, Embase, and Cochrane Library for studies published up to January 2023. Population, intervention, comparator, outcome, and study design were as follows: bladder cancer patients with VH (population), neoadjuvant chemotherapy (intervention), radical cystectomy only (comparators), oncological survival and pathologic response (outcomes), and retrospective or prospective (study design). ResultsFinally, a total of 17 studies were included in the present study (quantitative analysis, n = 17; qualitative analysis, n = 12). Pooled HR was 0.49 (95% CI: 0.31-0.76; P = .002) for OS. Pooled HR was 0.61 (95% CI: 0.38-0.98; P = .04) for CSS. Pooled HR was 0.44 (95% CI: 0.21-0.93; P = .03) in PFS. Pooled OR was 6.61 (95% CI: 4.50-9.73; P < .00001) in complete pathologic response. Pooled OR was 9.59 (95% CI: 3.56-25.85; P < .00001) in any pathologic response. Evidence quality assessments for each 5 comparisons using the GRADE approach were that Certainty was moderate in 1, low in 1, and very low in 3. ConclusionsAdministration of NAC before surgery in bladder cancer patients with VH might confer better survival outcomes and higher pathologic down staging rate than no administration of NAC before surgery.

PD46-11 ASSESSING THE ROLE OF NEOADJUVANT CHEMOTHERAPY IN UPPER TRACT UROTHELIAL CARCINOMA EVOLUTION

You have accessJournal of UrologyCME1 Apr 2023PD46-11 ASSESSING THE ROLE OF NEOADJUVANT CHEMOTHERAPY IN UPPER TRACT UROTHELIAL CARCINOMA EVOLUTION Neeta D'Souza, Andrew B. Katims, Ali Mouzannar, Eugene J. Pietzak, David Solit, Kwanghee Kim, and Jonathan A. Coleman Neeta D'SouzaNeeta D'Souza More articles by this author , Andrew B. KatimsAndrew B. Katims More articles by this author , Ali MouzannarAli Mouzannar More articles by this author , Eugene J. PietzakEugene J. Pietzak More articles by this author , David SolitDavid Solit More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , and Jonathan A. ColemanJonathan A. Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Systemic neoadjuvant chemotherapy (NAC) may apply selective pressure on tumors and shape cancer evolution. In bladder cancer, intratumor genetic heterogeneity can help predict response to NAC, with RB1, ERCC2, ATM, and FANCC mutations significantly associated with a positive response to NAC. Molecular studies have shown upper tract urothelial carcinoma (UTUC) to be genetically distinct from bladder cancer with a significantly worse response to NAC, yet still harboring significant intratumor heterogeneity. This study aims to assess the effect of NAC in selecting chemotherapy-resistant mutations among the intratumor heterogeneity in UTUC. METHODS: We identified patients with UTUC who underwent platinum-based NAC followed by nephroureterectomy treated at Memorial Sloan Kettering Cancer Center. Patients with complete response to NAC were excluded. Pre-NAC biopsy and post-NAC nephroureterectomy samples underwent next generation targeted gene sequencing through MSK-IMPACT. Mutational frequency among the 505 tested genes was compared in the pre-and post- treatment cohorts to assess for significant changes (p<0.05). RESULTS: We identified 15 patients with UTUC that had an incomplete response/progression of disease after NAC with gemcitabine/cisplatin as determined by final pathology at radical nephroureterectomy. The median age at the time of NAC was 60 (IQR 55-70). The most common mutations are seen in Figure 1. The most common mutated genes in pre-NAC UTUC biopsy were TERT (53.3%), KMT2D (40.0%), and ARID1A (33.3%). Post-chemotherapy, the most common mutations were TERT (56.3%), FGFR3 (31.3%), and KMT2D (31.3%). There were no significant differences between the frequency of mutations pre- and post-NAC. There was no decrease in the frequency of RB1, ERCC2, ATM, and FANCC post-NAC. CONCLUSIONS: Administration of NAC did not select for specific resistant mutations in the global tumor landscape. It is possible that changes to the tumor microenvironment, sub-clonal expansion, or differences in expression may be identified through RNA based studies. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1174 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neeta D'Souza More articles by this author Andrew B. Katims More articles by this author Ali Mouzannar More articles by this author Eugene J. Pietzak More articles by this author David Solit More articles by this author Kwanghee Kim More articles by this author Jonathan A. Coleman More articles by this author Expand All Advertisement PDF downloadLoading ...

MP65-01 RISK FACTORS FOR PARASTOMAL HERNIATION: A SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS-MEDICARE DATA ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP65-01 RISK FACTORS FOR PARASTOMAL HERNIATION: A SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS-MEDICARE DATA ANALYSIS Diboro Kanabolo, Sarah Holt, Jonathan Wright, and George Schade Diboro KanaboloDiboro Kanabolo More articles by this author , Sarah HoltSarah Holt More articles by this author , Jonathan WrightJonathan Wright More articles by this author , and George SchadeGeorge Schade More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003323.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A frequent complication of stoma creation is parastomal herniation (PSH), defined as any palpable bulge or radiologic defect containing bowel in the parastomal region. Reported incidence rates are up to 50% for patients in the 24 months following ileal conduit (IC) surgery. To better understand risk factors for PSH in those undergoing cystectomy and ileal conduit (RC/IC) procedure, we examined a contemporary cohort of patients through combined Surveillance, Epidemiology and End Results-Medicare data (SEER-MD). METHODS: Using SEER-MD, patients with PSH after cystectomy and IC were identified. This was performed using CPT codes to identify surgery patients and subsequent diagnostic the new ICD-10 PSH specific code (K43.5) post-surgery, for those with surgery between 2015 and 2019. Risk factors of interest included: race, sex, socioeconomic status, marital status, COPD, smoking, obesity status, neoadjuvant chemotherapy administration, and tumor stage. An adjusted Cox Proportional-Hazards model was utilized for statistical analysis, enabling assessment of time to PSH from receipt of surgery and to account for censored patients. RESULTS: Of 1,838 patients identified as having undergone RC/IC, 132 patients (7 %) developed PSH in the followup period. The median time to PSH was 11.5 months (IQR: 6.5-18.7 months). The greatest risk factor in our cohort of patients for development of PSH was obesity (HR 2.05, 95% CI 1.48-2.98). The lowest socioeconomic quartile was also associated with greater risk of PSH (HR 1.49, 95% CI 1.01-2.22). Sex, COPD diagnosis, gender, race, smoking status, neoadjuvant chemotherapy, and tumor stage were not significantly associated with risk of PSH, although the female sex, Black/Hispanic race, and pT4 lesions showed elevated HR estimates. Marital status of “Divorced/Separated/Widowed” was significantly associated with PSH (HR 1.66, 95% CI 1.04-2.66) vs. “Married”, however due to a large portion of “unknown” marital status in our cohort, this finding may not be clinically meaningful. CONCLUSIONS: While the SEER-MD incidence rate is far below 50%, this reflects a mutable coding process subject to variation in capture by provider. With the available cohort, our model demonstrated an increased risk of PSH for obese and low SES patients undergoing RC/IC surgery. Both weight loss prevention strategies and careful symptom monitoring must be pursued in this population. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e890 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diboro Kanabolo More articles by this author Sarah Holt More articles by this author Jonathan Wright More articles by this author George Schade More articles by this author Expand All Advertisement PDF downloadLoading ...

The Potential of Expression of Cyclin-D1 on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma.

Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) need indicators to track their progress during treatment. The goal of this research is to learn how cyclin D1 works in conjunction with taxane and non-taxane therapy for people with IBC. There were 31 examples divided into two groups, based on: those using a different type of NC (taxane- or non-taxane-based), and NC administration time (before or after). Tumor grade, age, PR, ER, Ki-67, HER2, and Cyclin D1 expression were among the factors considered. Using immunohistochemical labeling, we were able to categorize cyclin D1 levels according to a threshold value, and we supplemented this with data we found in our databases. To analyze the data, we used a modified linear model. The expression of Cyclin D1 decreased after NC delivery (p=0.086). Cyclin D1 expression was reduced in the taxane group (p=0.792). The non-taxane group also saw no differences in outcomes (p = 0.065). There was a larger decrease in Cyclin D1 expression in the non-taxane group compared to the taxane group, but the difference was not statistically significant (p=0.200). Cyclin D1 expression, even if the differences are not statistically significant, may be a prognostic indicator of NC reaction in IBC. The involvement of Cyclin D1 in NC warrants more research with bigger IBC sample sizes.

Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3.

Neoadjuvant chemotherapy (NAC) may alter the immune landscape of patients with early breast cancer (BC), potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy. This issue has been investigated in the current study in which alterations in the plasma concentrations of 16 soluble co-stimulatory and co-inhibitory, immune checkpoints were measured sequentially in a cohort of newly diagnosed, early BC patients (n=72), pre-treatment, post-NAC and post-surgery using a Multiplex® bead array platform. Relative to a group of healthy control subjects (n=45), the median pre-treatment levels of five co-stimulatory (CD27, CD40, GITRL, ICOS, GITR) and three co-inhibitory (TIM-3, CTLA-4, PD-L1) soluble checkpoints were significantly lower in the BC patients vs. controls (p<0.021-p<0.0001; and p<0.008-p<0.00001, respectively). Following NAC, the plasma levels of six soluble co-stimulatory checkpoints (CD28, CD40, ICOS, CD27, CD80, GITR), all involved in activation of CD8+ cytotoxic T cells, were significantly increased (p<0.04-p<0.00001), comparable with control values and remained at these levels post-surgery. Of the soluble co-inhibitory checkpoints, three (LAG-3, PD-L1, TIM-3) increased significantly post-NAC, reaching levels significantly greater than those of the control group. PD-1 remained unchanged, while BTLA and CTLA-4 decreased significantly (p<0.03 and p<0.00001, respectively). Normalization of soluble co-stimulatory immune checkpoints is seemingly indicative of reversal of systemic immune dysregulation following administration of NAC in early BC, while recovery of immune homeostasis may explain the increased levels of several negative checkpoint proteins, albeit with the exceptions of CTLA-4 and PD-1. Although a pathological complete response (pCR) was documented in 61% of patients (mostly triple-negative BC), surprisingly, none of the soluble immune checkpoints correlated with the pCR, either pre-treatment or post-NAC. Nevertheless, in the case of the co-stimulatory ICMs, these novel findings are indicative of the immune-restorative potential of NAC in early BC, while in the case of the co-inhibitory ICMs, elevated levels of soluble PD-L1, LAG-3 and TIM-3 post-NAC underscore the augmentative immunotherapeutic promise of targeting these molecules, either individually or in combination, as a strategy, which may contribute to the improved management of early BC.

Abstract P4-06-10: Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting

Abstract Background: Breast cancer is the second most commonly diagnosed cancer in North American women. The administration of neoadjuvant chemotherapy (NAC) is the mainstay of treatment for individuals with high risk disease in an effort to reduce the extent of surgery, evaluate the role of additional adjuvant therapies (based on pathologic response to NAC), and improve disease-free and overall survival (OS). Anthracyclines have been shown to increase response rates leading to a greater likelihood of pathologic complete response compared to non-anthracycline regimens. However, for some individuals anthracyclines are omitted from the NAC regimen due to toxicities including greater immunosuppression, cardiac toxicity and risk of acute leukemia. We established a population-based cohort of individuals treated with NAC for breast cancer. We report the outcomes of women selected for treatment with non-anthracycline NAC compared to those treated with anthracyclines. Methods: This is a retrospective population-based cohort study using linked health administrative data held at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. We identified adult women diagnosed with stage I-III breast cancer (ICD-10 C50^) between 2012 and 2020 who received NAC. Administration of at least 50% of the planned chemotherapy regimen was required. We excluded patients with bilateral breast cancer, previous malignancy and male sex. NAC regimens were classified as anthracycline and non-anthracycline-containing regimens. To address confounding between those receiving anthracycline and other regimens, we built a propensity score model including patient and disease characteristics. The association with OS was calculated using Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using cause-specific Cox proportional hazards models. Models were adjusted for the propensity score, radiation treatment as a time-varying covariate, age, socioeconomic status, breast cancer stage and receptor sub-type, as well as Charlson comorbidity index. Results: A total of 4,180 women were identified with a median follow up of 62 months (IQR 44 – 85). Of these, 279 (6.7%) were treated with non-anthracycline regimens compared to 3,901 treated with anthracycline. Patients who received non-anthracyclines were older (median 62 years vs. 50 years; p &amp;lt; 0.001), and less likely to have stage III disease (33.0% vs. 48.7%; p &amp;lt; 0.001), and harbor triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p &amp;lt; 0.001). They were more likely to have no recorded comorbidities (89.2% vs. 96.5%; p &amp;lt; 0.001), undergo mastectomy (82.1% vs. 71.9%; p &amp;lt; 0.001), and sentinel lymph node biopsy (44.4% vs. 32.3%; p &amp;lt; 0.001). After propensity score and multivariable adjustment, women selected for treatment with non-anthracycline regimens had similar OS (HR 0.85, 95% CI 0.60-1.21) and BCSS (cause-specific HR 0.76, 95% CI 0.46-1.25) compared to those treated with anthracyclines. When stratified by stage, women treated with non-anthracycline regimens did not have significantly higher incidences of breast cancer death or death from any cause (stages I, II, and III Gray’s Test p-value all &amp;gt; 0.1). The mean OS was 7.2 years for women who received non-anthracycline regimens (95% CI 7.0 – 7.4) compared to 7.9 years for those who received anthracycline (95% CI 7.9 – 8.0) (log-rank p = 0.100). Conclusions: Women with stage I-III breast cancer treated with non-anthracycline NAC regimens are a highly selected population. These patients were older and healthier, with earlier stage disease and more favorable subtype (i.e. non-TNBC) when compared to those treated with anthracycline NAC. Our results demonstrate that women were well selected to omit anthracyclines and did not have worse survival outcomes. Further research is needed to better understand in whom anthracycline can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Matthew Castelo, Rinku Sutradhar, Lena Nguyen, Neil Faught, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-10.

Impact of neoadjuvant chemotherapy on pathological stage and survival in sarcomatoid bladder cancer.

530 Background: Sarcomatoid bladder cancer is an extremely rare and aggressive histological variant with poor prognosis and limited consensus regarding its management given rarity and lack of high-quality data. Radical cystectomy (RC) is the mainstay of treatment in muscle-invasive disease and adjuvant therapy is often offered to eligible patients with high-risk features. Data regarding the role of neoadjuvant chemotherapy (NAC) for this variant is limited. Methods: The National Cancer Database was queried to identify patients diagnosed with sarcomatoid bladder cancer from 2004 to 2018. Patients older than 18 years with cT2-4aN0-1M0 sarcomatoid bladder cancer who received curative-intent surgery were included in the analyses. Clinical T4b/N2-3/M1 disease and receipt of adjuvant chemotherapy were employed as exclusion criteria. The population was divided into two cohorts based on the receipt of NAC. Chi-Square and Mann Whitney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed to adjust for confounding factors associated with overall survival. Models were adjusted for age, race, sex, income, stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 573 patients were identified - 70% were males and 93% were White; 139 (25%) received NAC (NAC+) while 434 (75%) did not (NAC-). NAC+ patients were younger (65 vs 71 years, p &lt; 0.001). Downstaging to pT0-1N0 at the time of RC was significantly more frequent in the NAC+ group compared to the NAC- group (32 (24.5%) vs. 28 (6.8%), p = 0.001). Overall survival (OS) was also significantly longer in the NAC+ group (median of 40.8 vs. 19.4 months, log-rank p = 0.003). On multivariable analysis, NAC+ (Hazard Ratio (HR) = 0.73, 95% CI 0.56-0.91, p = 0.02), pathological downstaging to pT0-1N0 (HR = 0.5, 95% CI 0.31- 0.8, p &lt; 0.001), and any pathological upstaging (HR 4.1, 95% CI 1.5-6.6, p &lt; 0.001) were independently associated with all-cause mortality, while other factors were not (Table). Conclusions: In this large retrospective analysis, administration of NAC in muscle-invasive sarcomatoid bladder cancer was associated with higher rates of downstaging to non-muscle-invasive disease at the time of RC and reduced all-cause mortality. [Table: see text]

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

IntroductionPrimary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. MethodsClinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. ResultsThe median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan–Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). ConclusionsWith multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

A Comparison of Standard Neoadjuvant Long-Course Chemoradiotherapy and Near-Total Neoadjuvant Therapy in Rectal Cancer: A Matched Pair Analysis at Equal Time Interval

<h3>Purpose/Objective(s)</h3> To investigate the efficacy of neoadjuvant chemotherapy administration following standard long-course chemoradiotherapy (LCCRT) before surgery (near-TNT), and to compare the outcomes with standard LCCRT in locally-advanced rectal cancer. <h3>Materials/Methods</h3> A total of 156 patients with cT3-4, cN0-2 rectal adenocarcinoma were included in this retrospective analysis, comprised of 79 patients treated with near-TNT, and 77 patients treated with LCCRT. Near-TNT defined as the incorporation of fluoropyrimidine plus oxaliplatin-based chemotherapy into the 12 weeks period between LCCRT and surgery. The patients treated with near-TNT and LCCRT were matched for cTNM stage at the same institution. The primary aim was to compare the pathologic complete response (pCR), and the secondary end-points were to compare the sphincter preservation and toxicity and safety of the treatments. <h3>Results</h3> A pCR was achieved in 40 of 156 patients (25.6 %) in the total population. The pCR were 24,1 % and 27,3 % with near-TNT and LCCRT, respectively (p=0,781). There was also no significant difference between near-TNT and LCCRT in term of sphincter preservation rate (65.8 % with near-TNT and 71.4 with LCCRT, p=0.561). The median tumor size was 2.5 cm (range: 0.2-10) after LCCRT, and 1.5 cm (range: 0.1-8) after near-TNT (p<0,001). Although near-TNT resulted in increased chemotherapy-related toxicity (p<0001), the treatment did not lead increased postoperative complications. When the groups compared with the Clavien-Dindo score, near-TNT group showed better postoperative complication rates (p=0,008). Additionally, near-TNT group exhibited better postoperative duration of hospitalization (p=0.002). <h3>Conclusion</h3> Though the addition of chemotherapy between the time interval of LCCRT and definitive surgery did not lead pCR rates, it might induce better tumor downsizing together with a cost of treatment-related toxicities. Besides downsizing effects, a positive postoperative complication rates make near-TNT as a potential treatment-approach in locally-advanced rectal cancer.

Management of positive peritoneal cytology gastric cancer patients

Prognosis of patients with stage IV gastric cancer remains up to date dramatically poor. A subgroup of these patients has only positive peritoneal cytology in the peritoneal lavage and represents a target issue of the recent ongoing research. The administration of neoadjuvant chemotherapy, either systemic or intraperitoneal or hyperthermic intraoperative peritoneal chemotherapy, with a variety of combinations of drugs has assisted some of these patients to become peritoneal cytology negative, with a significant implication in their prognosis. Staging laparoscopy is widely used to detect occult peritoneal disease and has, therefore, reduced the number of unnecessary laparotomies. However, recent reports point out a low sensitivity of staging laparoscopy and cytological exam in detecting viable cancer cells and focus on the need of more accurate methods of examining the peritoneal fluid by immunohistochemistry or molecular assays. This review focuses on the latest scientific evidence regarding the optimal management of positive peritoneal cytology gastric cancer patients.

Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer (462)

Objectives: The utilization of neoadjuvant chemotherapy (NACT) for advanced-stage uterine cancer is increasing. However, the relationship between NACT administration and the type of surgical approach used for interval debulking surgery (IDS) remains unknown. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. Methods: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy versus a minimally invasive approach. To account for imbalances in confound- ers, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. Cox proportional hazards models to compare all-cause mortality between the groups were examined. Results: A total of 1,618 women with stage IV uterine cancer who received NACT were identified. Overall, minimally invasive IDS was performed in 31.1% of the cohort. MIS use increased from 16.2% in 2010 to 40.4% in 2017 (p<0.001). More recent years of diagnosis and performance of surgery at a comprehensive cancer center or integrated network cancer center were associated with increased use of MIS (p<0.05). Women with serous and clear cell tumors and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance), were less likely to undergo a minimally invasive surgical approach (p<0.05). The median OS was 28 months (95% CI: 23.7-30.7) and 24.3 months (95% CI: 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and overall survival (HR: 0.90, 95% CI: 0.71-1.14). Conclusions: Among women with stage IV uterine cancer treated with neoadjuvant chemotherapy, the performance of minimally invasive debulking surgery is common and increasing. Compared to laparotomy, MIS does not appear to negatively impact survival. Objectives: The utilization of neoadjuvant chemotherapy (NACT) for advanced-stage uterine cancer is increasing. However, the relationship between NACT administration and the type of surgical approach used for interval debulking surgery (IDS) remains unknown. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. Methods: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy versus a minimally invasive approach. To account for imbalances in confound- ers, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. Cox proportional hazards models to compare all-cause mortality between the groups were examined. Results: A total of 1,618 women with stage IV uterine cancer who received NACT were identified. Overall, minimally invasive IDS was performed in 31.1% of the cohort. MIS use increased from 16.2% in 2010 to 40.4% in 2017 (p<0.001). More recent years of diagnosis and performance of surgery at a comprehensive cancer center or integrated network cancer center were associated with increased use of MIS (p<0.05). Women with serous and clear cell tumors and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance), were less likely to undergo a minimally invasive surgical approach (p<0.05). The median OS was 28 months (95% CI: 23.7-30.7) and 24.3 months (95% CI: 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and overall survival (HR: 0.90, 95% CI: 0.71-1.14). Conclusions: Among women with stage IV uterine cancer treated with neoadjuvant chemotherapy, the performance of minimally invasive debulking surgery is common and increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.