Administration Of Neoadjuvant Chemotherapy Research Articles

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.

Is less more in the surgical treatment of early-stage cervical cancer?

This article discusses recent developments towards less radical surgical treatment for early-stage cervical cancer. Surgery is the standard treatment for early-stage cervical cancer. In the last decades, new treatment strategies have been developed aiming to reduce morbidity, without hampering oncological safety. We provide an update of the latest knowledge on safety and morbidity following less radical surgical procedures in early-stage cervical cancer. In cervical cancer with a tumour size of 2 cm or less, radical surgery (simple hysterectomy or fertility-sparing conisation) may be a well tolerated option. For patients with larger lesions (>2 cm) and wishing to preserve fertility, administration of neoadjuvant chemotherapy followed by less extensive surgery appears to be a feasible and well tolerated alternative to abdominal trachelectomy. With regard to lymph node assessment, increasing evidence shows the feasibility of the sentinel lymph node procedure instead of full pelvic lymphadenectomy. Prospective trials reporting on oncological safety are awaited.It is important to exercise caution when new surgical strategies are introduced. Despite promising retrospective data, prospective randomized studies may present unexpected results, for instance, minimally invasive radical hysterectomy showed inferior results compared to laparotomy. There is a shift towards less radical treatment for early-stage cervical cancer. This review explores whether and when less is really more.

Exploring the Expression of Survivin on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma

Background: Biomarkers are required to monitor the response to neoadjuvant chemotherapy (NC) in patients with invasive breast cancer (IBC). The purpose of this study is to determine the function of Survivin in the administration of NC, both taxane- and non-taxane-based, to patients with IBC.&#x0D; Methods: Thirty-one samples were categorized according to the NC's administrative status (before or after) and the type of NC used (taxane- or non-taxane-based). Age, tumor grade, receptor status (ER, PR, HER2, Ki-67), and survivin expression were evaluated. Survivin expressions were evaluated by IHC staining and categorized according median H-score cut-offs, while other data were collected from archives. Data was gathered and analyzed using generalized linear model. &#x0D; Results: Survivin expression decreased following NC administration, although not significantly (p=0.285). The taxane group had lower survivin expression. Statistically, this was not significant (p=0.329). The non-taxane group had the same outcome (p=0.792). The decline in survivin expression was greater in the taxane group than in the non-taxane group, although it was not statistically significant (p=0.369).&#x0D; Conclusion: Although the changes in survivin expression were not statistically significant, when clinical and laboratory data are analyzed, survivin expression has the potential to be a predictive biomarker of NC response as well as clinical outcome in IBC.

Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3+, CD8+, and Immunoscore Are Associated with a Pathological Complete Response.

Simple SummaryIn 2021, the World Health Organization announced that breast cancer had overtaken lung cancer to become the most common cancer globally, accounting for 12% of all new cancer cases, with younger women resident in low-income countries having the lowest 5-year survival rates. The main aim of the current study was to evaluate the prognostic utility of an innovative, objective, computer-assisted, digital imaging procedure known as the Immunoscore for clinical research (ISCR) as a strategy to reveal the efficiency of the anti-tumor cellular immune landscape of the tumor microenvironment (TME) in biopsies taken from women diagnosed with early breast cancer prior to administration of neoadjuvant chemotherapy followed by surgical resection. Our results demonstrated the ability of the ISCR to enumerate tumor-infiltrating lymphocytes in the TME and, in particular, to illustrate the spatial arrangement of these cells, which, importantly, correlated with clinical outcome, measured as the pathological complete response.Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the “Immunoscore Clinical Research” (ISCR). The original Immunoscore® is a prognostic tool that categorizes the densities of CD3+ and CD8+ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0–4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3+ and CD8+ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm2) of CD3 CT, CD8+ CT, CD3+ IM, and CD8+ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3+, and CD8+ lymphocytes, as well as the ISCR in relation to pCR following NACT.

Laparoscopic liver resection for colorectal liver metastases: retrospective analysis of prognostic factors and oncological outcomes in a single-center cohort.

Laparoscopic liver resection (LLR) has gained acceptance as an effective treatment for colorectal liver metastases (CRLM) in selected patients, providing similar oncologic outcomes compared to open liver resection (OLR). The aim of this study was to determine prognostic factors for survival outcomes associated with LLR for CRLM. A single-center retrospective analysis of a prospectively maintained database was performed. The inclusion period ranged from September 2011 until mid-March 2020. Two hundred consecutive LLRs were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates equalled 54.8% and 49%, respectively. A pushing (HR = 5.42, 95% CI 1.56-18.88, p = 0.008), as well as a replacement (3.87, 1.05-14.2, p = 0.04) growth pattern of the CRLM, poor differentiation of the primary colorectal cancer (CRC) (3.72, 1.72-8.07, p < 0.001) and administration of neoadjuvant chemotherapy (NAC) (2.95, 1.28-6.8, p = 0.01) were identified as independent predictors of a worse OS. Requirement of more than 6 cycles of NAC (6.17, 2.37-16.03, p < 0.001), a replacement (4.96, 1.91-12.87, p < 0.001), as well as a pushing (4.3, 1.68-11, p = 0.002) growth pattern of the CRLM and poor differentiation of the primary CRC (2.61, 1.31-5.2, p = 0.006) were identified as independent predictors of a worse DFS. LLR for CRLM offers adequate long-term oncologic outcomes. OS and DFS rates are negatively affected by the administration of NAC and by pathological features, including the differentiation grade of the primary CRC and the histological growth pattern of the CRLM.

PD51-11 CONCOMITANT VS STAGED LYMPHADENECTOMY IN CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: RECURRENCE PATTERNS AND SURVIVAL OUTCOMES

PD51-11 CONCOMITANT VS STAGED LYMPHADENECTOMY IN CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: RECURRENCE PATTERNS AND SURVIVAL OUTCOMES

Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer.

Although local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anticancer immunity. We evaluated serial blood samples from patients with advanced epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition across the course of therapy. Serial blood samples from 10 patients with advanced high-grade serous ovarian cancer treated with neoadjuvant chemotherapy (NACT) were collected before the initiation of chemotherapy, after the third and sixth cycles, and approximately 2 months after completion of chemotherapy. T-cell function was evaluated using ex vivo IFNγ ELISpot assays, and the dynamics of T-cell repertoire and immune cell composition were assessed using bulk and single-cell RNA sequencing (RNAseq). T cells exhibited an improved response to viral antigens after NACT, which paralleled the decrease in CA125 levels. Single-cell analysis revealed increased numbers of memory T-cell receptor (TCR) clonotypes and increased central memory CD8+ and regulatory T cells throughout chemotherapy. Finally, administration of NACT was associated with increased monocyte frequency and expression of HLA class II and antigen presentation genes; single-cell RNAseq analyses showed that although driven largely by classical monocytes, increased class II gene expression was a feature observed across monocyte subpopulations after chemotherapy. NACT may alleviate tumor-associated immunosuppression by reducing tumor burden and may enhance antigen processing and presentation. These findings have implications for the successful combinatorial applications of immune checkpoint blockade and therapeutic vaccine approaches in EOC.

Treatment disparities in muscle-invasive bladder cancer: Evidence from a large statewide cancer registry.

To identify patient-level factors that can lead to treatment disparities for muscle invasive bladder cancer, we examine factors associated with receipt of definitive therapy, type of definitive therapy, and neoadjuvant chemotherapy administration in a statewide cohort of muscle-invasive bladder cancer patients. We identified 2,434 patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2015 using the Pennsylvania Cancer Registry. We divided the cohort into three subsamples to examine receipt of treatment: definitive therapy among all muscle-invasive bladder cancer patients (n = 1548), cystectomy (n = 1254) vs. trimodal therapy (n = 294), and neoadjuvant chemotherapy among radical cystectomy patients (n = 1156). Multivariable logistic regression models controlling for patient-level covariates, including insurance status, and socioeconomic disadvantage (based on Area Deprivation Index from census tract data) were estimated to examine factors associated with each treatment outcome. Only 64% of muscle-invasive bladder cancer patients underwent definitive therapy. Those receiving trimodal therapy were more likely to be covered by Medicare than those undergoing cystectomy. Uninsured patients were less likely to undergo definitive treatment and Medicare-insured patients were less likely to undergo cystectomy as their definitive therapy. Patients with greater socioeconomic disadvantage were less likely to receive definitive treatment, undergo cystectomy, or receive neoadjuvant chemotherapy. Over the course of the study period, there was increased neoadjuvant chemotherapy use, but a persistent gap by neighborhood socioeconomic status. Socioeconomic disadvantage and insurance status are patient-level factors associated with suboptimal treatment for muscle-invasive bladder cancer.

Contemporary Trends of Systemic Neoadjuvant and Adjuvant Intravesical Chemotherapy in Patients With Upper Tract Urothelial Carcinomas Undergoing Minimally Invasive or Open Radical Nephroureterectomy: Analysis of US Claims on Perioperative Outcomes and Health Care Costs.

New evidence indicates that minimally invasive surgery (MIS) (laparoscopic or robotic-assisted [LNU, RANU]) reaches oncologic equivalence compared with Open Radical Nephroureterectomy (ORNU) for high-risk upper-tract urothelial carcinoma (UTUC). Recently, European Association of Urology (EAU) Guidelines suggested implementing neoadjuvant chemotherapy (NAC) to standard treatment to improve oncologic outcomes of high-risk UTUC. We aimed (1) To explore contemporary trends of MIS for RNU in the United States and to compare perioperative outcomes and costs with that of ORNU. (2) To determine the trends of NAC and postoperative intravesical chemotherapy (PIC) administration for high-risk UTUC and to assess their contribution to perioperative outcomes and costs. The Optum Clinformatics Data Mart de-identified database was queried from 2003 to 2018 to retrospectively examine patients who had undergone LNU/RANU or ORNU with or without NAC and PIC. We evaluated temporal adoption trends, complications, and health care cost analyses. We obtained descriptive statistics and utilized multivariable regression modeling to assess outcomes. A total of n=492 ORNU and n=1618 LNU/RANU procedures were reviewed. The MIS approach was associated with a statistically significant lower risk of intraoperative complications (adjusted Odds Ratio [aOR], 0.48, 95% CI:0.24-0.96), risk of hospitalization costs (aOR: 0.62, 95% CI:0.49-0.78), and shorter hospital stay (aOR: 0.20, 95% CI:0.15-0.26) when compared to ORNU. Overall, adoption of NAC and PIC accounted for only n=81 and n < 37 cases respectively. The implementation of NAC and higher number of cycles were associated with an increased probability of any complication rate (aOR: 2.06, 95% CI:1.26-3.36) and hospital costs (aOR: 2.12, 95% CI:1.33-3.38). MIS has become the approach of choice for RNU in the US. Although recommended by guidelines, neither NAC nor postoperative bladder instillation of chemotherapy has been routinely incorporated into the clinical practice of patients with UTUC.

Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database.The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis.A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC.In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.

Impact of the COVID-19-pandemic on patients with gynecological malignancies undergoing surgery: A Dutch population-based study using data from the ‘Dutch Gynecological Oncology Audit’

ObjectiveThe COVID-19-pandemic caused drastic healthcare changes worldwide. To date, the impact of these changes on gynecological cancer healthcare is relatively unknown. This study aimed to assess the impact of the COVID-19-pandemic on surgical gynecological-oncology healthcare. MethodsThis population-based cohort study included all surgical procedures with curative intent for gynecological malignancies, registered in the Dutch Gynecological Oncology Audit, in 2018–2020. Four periods were identified based on COVID-19 hospital admission rates: ‘Pre-COVID-19’, ‘First wave’, ‘Interim period’, and ‘Second wave’. Surgical volume, perioperative care processes, and postoperative outcomes from 2020 were compared with 2018–2019. ResultsA total of 11,488 surgical procedures were analyzed. For cervical cancer, surgical volume decreased by 17.2% in 2020 compared to 2018–2019 (mean 2018–2019: n = 542.5, 2020: n = 449). At nadir (interim period), only 51% of the expected cervical cancer procedures were performed. For ovarian, vulvar, and endometrial cancer, volumes remained stable. Patients with advanced-stage ovarian cancer more frequently received neoadjuvant chemotherapy in 2020 compared to 2018–2019 (67.7% (n = 432) vs. 61.8% (n = 783), p = 0.011). Median time to first treatment was significantly shorter in all four malignancies in 2020. For vulvar and endometrial cancer, the length of hospital stay was significantly shorter in 2020. No significant differences in complicated course and 30-day-mortality were observed. ConclusionsThe COVID-19-pandemic impacted surgical gynecological-oncology healthcare: in 2020, surgical volume for cervical cancer dropped considerably, waiting time was significantly shorter for all malignancies, while neoadjuvant chemotherapy administration for advanced-stage ovarian cancer increased. The safety of perioperative healthcare was not negatively impacted by the pandemic, as complications and 30-day-mortality remained stable.

Clinical Significance of Breast Cancer Molecular Subtypes and Ki67 Expression as a Predictive Value for Pathological Complete Response following Neoadjuvant Chemotherapy: Experience from a Tertiary Care Center in Lebanon.

Introduction Breast cancer is considered nowadays the most prevalent cancer worldwide. The molecular era has successfully divided breast cancer into subtypes based on the various hormonal receptors. These molecular subtypes play a major role in determining the neoadjuvant chemotherapy to be administered. It was noted that the use of neoadjuvant chemotherapy was associated with higher achievement of pathological complete response. The aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy regimens. Methods Combining dose dense anthracycline-based, regular dose anthracycline-based, and nonanthracycline-based chemotherapy, we observed data from 87 patients with breast cancer who received surgery after administration of neoadjuvant chemotherapy at our institution between January 2015 and July 2018. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer as well as low Ki67 (≤14%) and high Ki67 (>14%) expression groups using immunohistochemistry. Pathologic complete response was the only neoadjuvant chemotherapy outcome parameter. To evaluate variables associated with pathologic complete response, we used univariate analyses followed by multivariate logistic regression. Results 87 patients with breast cancer were classified into different subtypes according to the 12th St. Gallen International Breast Cancer Conference. The response rate to neoadjuvant chemotherapy was significantly different (p = 0.046) between the subgroups. There were significant correlations between pathological complete response (pCR) and ER status (p < 0.0001), HER2 (p = 0.013), molecular subtypes (p = 0.018), T stage (p = 0.024), N stage before chemotherapy (p = 0.04), and type of chemotherapy (p = 0.029). Luminal B type patients had the lowest pCR, followed by luminal A type patients. Conclusion Evaluating molecular subtype's significance in breast cancer prognosis warrants additional studies in our region with extensive data about patient-specific neoadjuvant chemotherapy regimens. Our study was able to reproduce results complementary to those present in the literature in other outcomes.