Receipt Of Neoadjuvant Chemotherapy Research Articles

Factors associated with delays in receipt of neoadjuvant chemotherapy in patients with operable breast cancer.

e13541 Background: Delays in neoadjuvant chemotherapy initiation (NACTI) after breast cancer (BC) diagnosis have been associated with worse outcomes. We evaluated incidence and predictors of delays of NACTI among high clinical risk patients treated with NACT on a national level. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis of non-metastatic BC between 1/1/2010 – 12/31/2020, who were treated with NACT within 180 days of diagnosis. Patients who received neoadjuvant endocrine therapy were excluded. Time to chemotherapy (TTC) in days was recorded. Patients were categorized into sub-cohorts by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) and were lymph node (LN) LN+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Multivariable logistic regression, adjusted for demographic, socioeconomic and tumor characteristics, was used to identify characteristics associated with delays > 60 days from diagnosis to NACTI. Multiple imputation was used for missing data. Results: We identified 145,697 eligible patients, 74% were White, 18% were Black, 3.3% were Asian, and 4.6% were Other/Unknown. Across all racial categories, 9.2% were Hispanic. Median age at diagnosis was 52 years (range 18-90), median TTC was 32 days (range 0-180), and 10% had a delay > 60 days. There were 40,345 patients in the HR+/HER2- cohort, 56,868 in the HER2+ cohort, and 48,484 in the TNBC cohort; 12%, 9.0%, and 8.9% (p <0.001) had a delay in NACTI, respectively. In multivariable analysis among the HR+/HER2- sub-cohort, characteristics associated with delays in NACTI included Black race (OR 1.71, 95%CI 1.57-1.86) and Hispanic ethnicity (OR 1.76, 95%CI 1.60-1.94) compared to White and non-Hispanic patients. Patients with Medicare, Medicaid, or who were uninsured were more likely to be delayed (OR 1.44 95%CI 1.30-1.58, 2.10, 95%CI 1.92-2.29, 2.28, 95%CI 1.99-2.61) compared to those with commercial insurance. Results were similar in the HER2+ and TNBC cohorts, as seen in Table. Conclusions: Among patients with operable BC who received NACT, patients who were Black, Hispanic, had Medicaid or no insurance had as high as a twofold increase in odds of a delay in NACTI. Targeted interventions to address these racial and socioeconomic disparities are necessary to ensure equitable care. Multivariable logistic regression adjusted for demographic, socioeconomic and tumor characteristics variables (n= 145,697). [Table: see text]

Social Vulnerability and Receipt of Neoadjuvant Chemotherapy in Patients Undergoing Radical Cystectomy for Bladder Cancer.

To evaluate the association between a population-level measure of social determinants of health, the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), and receipt of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy. We queried our institutional database for patients with nonmetastatic MIBC treated with radical cystectomy between 2000 and 2022. Patients were assigned an SVI via ZIP code of residence and grouped into quintiles of SVI (i.e. least vulnerable to most vulnerable). Multivariable logistic regression was performed to evaluate the association between SVI and receipt of neoadjuvant chemotherapy, adjusting for age, race, gender, and cancer stage. A sub-analysis was performed to evaluate the association between subthemes of SVI (socioeconomic status, household composition/disability, race/ethnicity/language, and housing/transportation) and receipt of neoadjuvant chemotherapy. Of the 978 patients identified, 490 (50.1%) received neoadjuvant chemotherapy. Patients that received neoadjuvant chemotherapy had a lower SVI, were younger, and had >cT2 stage (all, p<0.05). The most vulnerable patients had lower odds of receiving neoadjuvant chemotherapy (OR 0.61, 0.39 - 0.95) compared to the least vulnerable patients. Analysis of subthemes of SVI demonstrated similar associations by socioeconomic status (OR 0.56, 0.36 - 0.86) and household composition/disability (OR 0.57, 0.33 - 0.99). Adverse social determinants of health, or social vulnerability, is associated with suboptimal and disparate utilization of neoadjuvant chemotherapy in patients with MIBC undergoing radical cystectomy. Strategies for identifying vulnerable populations may allow for more targeted interventions that would improve equity in bladder cancer care.

Income Disparities in Survival and Receipt of Neoadjuvant Chemotherapy and Pelvic Lymph Node Dissection for Muscle-Invasive Bladder Cancer.

Background: Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also primarily been associated with low-income status, as has been reported in other cancers. While the adoption of neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) has improved outcomes, these standard-of-care treatments may be underutilized in lower-income patients. We sought to investigate the economic disparities in NAC and PLND receipt and survival outcomes in MIBC. Methods: Utilizing the National Cancer Database, a retrospective cohort analysis of cT2-4N0-3M0 BCa patients with urothelial histology who underwent RC was conducted. The impact of income level on overall survival (OS) and the likelihood of receiving NAC and PLND was evaluated. Results: A total of 25,823 patients were included. This study found that lower-income patients were less likely to receive NAC and adequate PLND (≥15 LNs). Moreover, lower-income patients exhibited worse OS (Median OS 55.9 months vs. 68.2 months, p < 0.001). Our findings also demonstrated that higher income, treatment at academic facilities, and recent years of diagnosis were associated with an increased likelihood of receiving standard-of-care modalities and improved survival. Conclusions: Even after controlling for clinicodemographic variables, income independently influenced the receipt of standard MIBC treatments and survival. Our findings identify an opportunity to improve the quality of care for lower-income MIBC patients through concerted efforts to regionalize multi-modal urologic oncology care.

Abstract 800: Spatial accessibility of gynecologic oncologists and time to surgery in a diverse cohort of women with ovarian cancer in Northern California

Abstract Introduction: To expand our understanding of factors contributing to racial and ethnic disparities in ovarian cancer outcomes, we examined the association between spatial accessibility of gynecologic oncologists and time from cancer diagnosis to surgery in the KPROCS Study, a diverse cohort of women diagnosed with ovarian cancer between 2000-2018 at Kaiser Permanente Northern California (KPNC). Spatial medical accessibility is a component of healthcare access that captures the proximity and availability of healthcare resources in the area. Methods: Ovarian cancer cases were identified through the KPNC Cancer Registry. Demographic and clinical information was extracted from KPNC databases. Neighborhood characteristics from the California Neighborhoods Data System were linked to the residential addresses of cases at the time of diagnosis. Spatial medical accessibility was measured using the 2-step floating catchment area method based on the location of the infusion centers where KPNC gynecologic oncologists practice and the residence location of cohort members. We used generalized estimating equations with independent correlation structure and robust standard errors to examine the association between spatial accessibility of gynecologic oncologists and time to ovarian cancer surgery, adjusting for year and age at diagnosis, stage, histotype, race, ethnicity, neighborhood socioeconomic status (nSES), and receipt of neoadjuvant chemotherapy. Results: The cohort comprised 4,910 women with ovarian cancer, of whom 3,304 had surgery at KPNC. Of this group, 13% were Hispanic, 14% were non-Hispanic (NH) Asian American women, 5% NH Black women, and 67% NH White women. The proportion of women residing in areas of the lowest spatial accessibility of gynecologic oncologists was highest among NH White women (26%) and women residing in the highest quintile of nSES (29%). The median time from diagnosis to surgery was 4 days (interquartile range 22 days). In adjusted analyses, not including the information on spatial accessibility, the time from diagnosis to surgery was 5.1 days longer (95% CI 1.5, 8.7) for NH Black women than NH White women. After adding information on spatial accessibility, this time did not considerably change, resulting in a 5.3-day (95% CI 1.7, 8.9) difference. In this model, the lowest quintile of spatial accessibility of gynecologic oncologists was associated with a longer time from diagnosis to surgery, but this association was not statistically significant (0.4 days difference, 95% CI -1.3, 2.0). Summary: In our preliminary analyses, spatial accessibility of gynecologic oncologists was not found to be a contributing factor to the disparity in time from diagnosis to surgery between NH Black and NH White women. Further analyses will examine time from diagnosis to chemotherapy overall and stratified by racial and ethnic groups. Citation Format: Ekaterina Chirikova, Pushkar P. Inamdar, Valerie McGuire, Salma Shariff-Marco, Valerie S. Lee, Lindsay J. Collin, Carola T. Sanchez-Diaz, Juraj Kavecansky, C Bethan Powell, Jennifer A. Doherty, Lawrence H. Kushi, Elisa V. Bandera, Scarlett L. Gomez. Spatial accessibility of gynecologic oncologists and time to surgery in a diverse cohort of women with ovarian cancer in Northern California [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 800.

Proximal gastric cancer—time for organ-sparing approach?

IntroductionA steady increase in gastroesophageal junction and proximal gastric cancer (GC) incidence has been observed in the West. Given recent advances in neoadjuvant chemotherapy (NAC), we sought to characterize short- and long-term outcomes of patients with proximal GC who underwent total (TG) versus proximal gastrectomy (PG). MethodsPatients with stage II/III proximal GC who underwent curative intent treatment between 2009 and 2019 were identified using National Cancer Database (NCDB). Multivariable analysis was used to identify oncological outcomes following TG versus PG. ResultsAmong 7,616 patients with GC who underwent surgical resection, PG and TG were performed on 5,246 (68.8%) and 2,370 (31.2%) patients, respectively. Patients who underwent PG were more likely to receive NAC (TG: 52.3% vs. PG: 64.5%)(p<0.001). On pathologic analysis, patients who underwent TG were more likely to have pT4 tumors (TG: 11.7% vs. PG: 3.1%), metastatic lymph nodes (TG: 64.6% vs. PG: 60.4%), and >16 lymph nodes evaluated (TG: 64.1% vs. PG: 53.1%), yet a lower likelihood of negative resection margins (TG: 86.6% vs. PG: 90.0%)(all p<0.001). While gastrectomy procedure type did not impact long-term survival, receipt of NAC was associated with OS among patients who underwent TG (5-year OS, NAC: 43.5% vs. no NAC: 24.6%) and PG (5-year OS, NAC: 43.1% vs. no NAC: 26.7%)(both p<0.001). ConclusionsPG may be an alternative surgical approach to TG in well-selected patients with proximal GC after administration of preoperative systemic chemotherapy.

The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: Data from the International Robotic Cystectomy Consortium

ObjectiveTo assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). MethodsRetrospective review of 988 patients who underwent RARC (2004–2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). ResultsA total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). ConclusionOur data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH.

Abstract A137: Drive time to physicians and outcomes for bladder cancer

Abstract Introduction: Poor geographic access to cancer care providers can delay treatment and limit access to high quality care. Previous research has shown that for patients with bladder cancer, time to cystectomy and receipt of neoadjuvant chemotherapy are associated with improved survival. Travel burden may be an important barrier to timely guideline-concordant treatment and is particularly relevant for residents of rural areas, which are often medically underserved. This study examines the association between drive time to medical oncologists and urologists and clinical outcomes for muscle-invasive bladder cancer (MIBC) patients. Data and Methods: We used information on physician location from the Centers for Medicare and Medicaid Services and patient-level data from the 2010-2016 Pennsylvania Cancer Registry linked to Pennsylvania Healthcare Cost Containment Council (PHC4) inpatient discharge data through 2018. We examined patients in Pennsylvania with a first lifetime bladder cancer diagnosis who underwent radical cystectomy at a non-federal short-term general hospital identified in PHC4. Outcomes examined were surgery within 90 days, receipt of neoadjuvant chemotherapy, 90-day mortality and 90-day readmission. We estimated multivariable linear regression models at the patient level. Our primary exposures were the natural log number of minutes from the patient’s home census tract centroid to the nearest medical oncologist and the nearest urologist. We controlled for patient age, sex, race/ethnicity, tumor size, tumor node involvement, and Elixhauser comorbidity index. We included a control for whether the patient received neoadjuvant chemotherapy in models estimating the association between drive times and cystectomy within 90 days. We also controlled for area-level characteristics, including ZIP code median and area deprivation index quartile. Standard errors were clustered at the county level.Results: The study included 954 patients with MIBC, 1,520 medical oncologists, and 976 urologists in Pennsylvania. Mean (SD) drive time to the nearest oncologist was 17.1 (11.4) minutes and median drive time was 14.4 minutes. Mean drive time to the nearest urologist was 13.9 (9.2) minutes and median drive time was 11.7 minutes. A 30-minute increase in drive time to the nearest urologist was associated with a 12.5 percentage point lower likelihood of undergoing cystectomy within 90 days (95% CI: -24.3 to -0.6). A 30-minute increase in drive time to the nearest oncologist was associated with an 11.9 percentage point lower likelihood of receiving neoadjuvant chemotherapy (95% CI: -23.4 to -0.4). Drive time was not significantly associated with 90-day mortality or readmission within 90 days. Conclusions: Drive time to both oncologists and urologists is associated with timely receipt of guideline-recommended care for patients with MIBC. Understanding the impact of geographic access to medical oncologists and urologists on clinical outcomes for patients with MIBC can inform providers and policymakers in addressing geographic equity in cancer care. Citation Format: Sruthi Muluk, Coleman Drake, Zhaojun Sun, Manisha Bhattacharya, Bruce Jacobs, Lindsay M. Sabik. Drive time to physicians and outcomes for bladder cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A137.

Neoadjuvant Chemotherapy Improves Oncological Outcomes and Long-Term Survival Among Elderly Patients with Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

In the USA, approximately half of newly diagnosed patients with GC are 75 years or older. The objective of the current population-based study was to investigate the impact of neoadjuvant chemotherapy (NAC) on the outcomes of elderly patients with locally advanced GC. Patients aged > 75 years were identified from the National Cancer Database (NCDB). The primary outcome of the study was overall survival (OS). Secondary outcomes included lymph node (LN) harvest, surgical margin status, and 30-day mortality. To minimize the effect of selection bias on the assessed outcome between the two study groups (NAC versus no NAC), propensity score matching (PSM) was performed. After PSM, a total of 1958 patients were included in both groups. NAC utilization increased from 2013 to 2019 (21% versus 42.7%, ptrend < 0.001). On pathologic analysis, patients who received NAC were more likely to have ≥ 16 LNs evaluated (NAC 60.1% versus no NAC 55.5%, p = 0.044) and negative resection margins (NAC 88.6% versus no NAC 83%, p = 0.001). Patients who received NAC were alsoless likely to experience 30-day mortality following resection (NAC 4.1% versus no NAC 7.1%). Receipt of NAC was associated with improved 1-year (73.9% versus 68.3%), 3-year (48.2% versus 43.5%), and 5-year OS (36.9% versus 30.5%) compared with patients who underwent upfront surgery (p = 0.01). Receipt of NAC was associated with improved oncological outcomes among elderly patients undergoing resection for locally advanced GC.

Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy

IntroductionVariant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. Patients and MethodsPatients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. Results225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). ConclusionWhen comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.

Perioperative discordance in mesothelioma cell type after pleurectomy/decortication-a possible detrimental effect of neoadjuvant chemotherapy due to epithelial to mesenchymal transition?

To evaluate the accuracy of preoperative histological assessment, factors affecting the accuracy and the subsequent effect on postoperative survival after surgical treatment for malignant pleural mesothelioma(MPM). We analysed the perioperative course of patients who underwent surgery for MPM in a single institution over a 5-year period. The primary endopoint was to evaluate the proportion of histological discordance between preoperative assessment and postoperative histology, while the secondary end-point was to evaluate its prognostic effect on postoperative survival after surgical treatment. One-hundred and twenty-nine patients were included in this study. Histological discordance between preoperative assessment and postoperative histology was found in 27 of 129 patients(20.9%):epithelial to biphasic/sarcomatoid(negative discordance) in 24, and biphasic to epithelial(positive discordance) in 3(p-value < 0,001).All 24 patients exhibiting epithelial-to-mesenchymal transition(EMT) had received neoadjuvant chemotherapy(p-value : 0,006).In the 34 patients who underwent upfront surgery, only one case(2.9%) of EMT was identified(p-value : 0,127).EMT was not associated with a less invasive method of biopsy(p-value : 0.058) nor with the volume or maximum diameter of the biopsy(p-value : 0,358 and 0,518, respectively) but it was significantly associated with the receipt of neoadjuvant chemotherapy(p-value : 0,006).At median follow-up of 17 months(IQR : 11.0-28.0),50(39%) patients are still alive. Overall survival was significantly reduced in those patients who received neoadjuvant chemotherapy and exhibited discordance(EMT) compared to those who did not : 11(95% CI : 6.2-15.8)months vs 19(95% CI : 14.2 -23.8) months(p-value < 0,001). In addition, there was no difference in overall survival between those who received neoadjuvant chemotherapy and those who had upfront surgery : 16(95% CI : 2.5-19.5)months vs 30(95% CI : 11.6-48.4)months(p-value : 0,203). The association of neoadjuvant chemotherapy with perioperative histological discordance can be explained by EMT, which lead to worse survival. Therefore, there is an argument for the preferential use of upfront surgery in the treatment of otherwise resectable MPM.

Successful Breast Conservation After Neoadjuvant Chemotherapy in Lobular Breast Cancer: The Role of Menopausal Status in Response to Treatment.

While neoadjuvant chemotherapy (NAC) has been shown to increase rates of breast conservation surgery (BCS) for breast cancer, response rates in invasive lobular carcinoma (ILC) appear lower than other histologic subtypes. Some data suggest higher response rates to NAC in premenopausal versus postmenopausal patients, but this has not been studied in ILC. We evaluatedthe rates of successful BCS after NAC in patients with ILC stratified by menopausal status. We analyzed data from a single-institution cohort of 666 patients with stage I-III hormone receptor positive HER-2 negative ILC. We used t-tests, chi-squared tests, and multivariable logistic regression to investigate rates of NAC use, attempted BCS, and associations between NAC and successful BCS by menopausal status. In 217 premenopausal and 449 postmenopausal patients, NAC was used more often in the premenopausal group (15.2% vs. 9.8%, respectively, p = 0.041). Among those who attempted breast conservation (51.3% of pre- and 64.8% of postmenopausal cohorts), NAC was not associated with successful BCS in either group. Interestingly, for postmenopausal patients, receipt of NAC was significantly associated with increased rates of completion mastectomy in those who had positive margins at thefirst attempt at BCS. NAC was not associated with successful BCS in either premenopausal or postmenopausal patients with ILC. Although premenopausal patients were more likely to receive NAC, these data suggest that menopausal status may not be a good predictor of response to chemotherapy. Better predictors of response and more efficacious treatment for patients with ILC are needed.

Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States

ObjectiveTo describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. MethodsWe identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004–December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. ResultsWe observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6–8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07–1.24), and stage IV disease (RR 2.66; 95% CI 2.31–3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65–0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08–1.42). ConclusionNACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.

Impact of geography on receipt of medical oncology consultation and neoadjuvant chemotherapy for triple negative and HER2 positive breast cancer.

1530 Background: Consensus guidelines recommend consideration of neoadjuvant chemotherapy (NAC) for most patients with early-stage triple negative (TN) and HER2 positive (HER2+) breast cancer. Based on our previous work, most patients are not seen by a medical oncologist prior to surgery and do not receive NAC. Although potential barriers are not well understood, distance to cancer centres has been shown to mediate medical oncology referral and use of systemic therapy for other malignancies. We therefore aimed to characterize the impact of region of residence and cancer centre proximity on receipt of pre-treatment medical oncology consultation and NAC for patients with TN and HER2+ breast cancer. Methods: Using linked administrative healthcare datasets in Ontario, Canada, we performed a retrospective population-based geographic analysis of women diagnosed with stage I-III TN or HER2+ breast cancer from 2012-2019. Outcomes were pre-treatment medical oncology consultation and initiation of NAC. We created choropleth maps to assess the spatial distribution of outcomes across census divisions, displaying cancer centres and outcomes by colour gradient using geographic information system analysis. To assess the relationship between distance to the nearest cancer centre and outcomes, we performed a multivariable regression analysis adjusted for sociodemographic and clinical factors, including tumour extent and nodal status. Results: Within the cohort of 12,881 patients, there was no statistically significant relationship between incremental distance to the nearest cancer centre (≤5 vs. 5-10, 10-25, and ≥25 km) and rate of medical oncology consultation or receipt of NAC. Mapping analysis demonstrated high interregional outcome variability, ranging across census divisions from 12.2% to 64.3% for medical oncology consultation rate, and 9.3% to 64.3% for NAC rate. 77.7% of patients referred to medical oncology received NAC. Conclusions: Among patients with TN and HER2+ early breast cancer, rates of medical oncology consultation and NAC were not significantly impacted by distance to cancer centres but varied highly by region. This variability suggests that regional and/or provider practice patterns, rather than distance, may underlie discrepancies in referral for NAC. These findings can inform further studies and interventions aiming to improve equitable access to NAC for patients with TN and HER2+ breast cancer.

Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

5581 Background: Following the publication of randomized trials demonstrating its noninferiority, the use of neoadjuvant chemotherapy (NACT) for the treatment of advanced stage epithelial ovarian cancer has increased substantially in the United States. However, low-grade serous ovarian cancers (LGSOC) respond poorly to chemotherapy compared with high-grade serous carcinoma. For LGSOC, clinical guidelines favor surgical resection prior to adjuvant therapy. This study seeks to describe patterns and temporal trends in the use of NACT for LGSOC. Methods: This cohort study identified women treated for stage III or IV LGSOC in a Commission on Cancer accredited cancer program between January 1, 2004, to December 31, 2020. We fit Poisson regression models to evaluate temporal trends in the use of NACT and cytoreductive outcomes, and to identify factors associated with receipt of NACT. We considered age, race/ethnicity, Charlson Comorbidity Index, year of diagnosis, insurance status, income, facility type, census region, and stage as potentially associated with NACT. Due to the high rate of missingness in data describing cytoreductive outcomes after surgery, we undertook both multiply imputed and complete case analyses. Results: A total of 3,343 patients received treatment for LGSOC during the study period. The mean age at diagnosis was 54.8 year (SD 15.5) and most patients (82%) were white. The most commonly observed upfront treatment strategies were cytoreductive surgery followed by adjuvant chemotherapy (63.7%) and surgery without chemotherapy (19.2%). Treatment with NACT followed by interval cytoreductive surgery (13.0%) or chemotherapy alone (4.1%) were less common. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to a statistically significant annual percent change (APC) of 7.2% (95% CI 5.6-8.9). Increasing decade of age (risk ratio [RR] 1.15; 95% CI 1.09-1.23), increasing calendar year of diagnosis (RR 1.07; 95% CI 1.05-1.08) and stage IV disease (RR 2.66; 95% CI 2.3-3.07) were associated with a higher probability of receiving NACT. Other variables were not associated with receipt of NACT. Among patients who underwent cytoreductive surgery, the proportion who achieved no gross residual disease remained stable over the course of the study period in both complete case (APC 0.5%; 95% CI -1.8 to 0.9) and multiply imputed (APC -0.1%; 95% CI -1.6 to 1.3) analyses. Conclusions: The use of NACT for patients with LGSOC increased substantially from 2004 to 2020. Despite increased utilization of NACT, the rate of complete cytoreduction has not improved over the study period, possibly calling into question the effectiveness of NACT in reducing tumor burden in this setting.

Efficacy and safety of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had measurable residual disease: A post-hoc subgroup analysis of the PRIME study.

5562 Background: Niraparib maintenance therapy significantly prolonged progression-free survival (PFS) versus placebo in patients with newly diagnosed advanced ovarian cancer (aOC), but its antitumor activity remains unclear in those with measurable residual disease (MRD) after first-line platinum-based chemotherapy (1LCT). This study aims to report the efficacy, including antitumor activity, and safety of niraparib maintenance therapy in patients with MRD after 1LCT from the phase 3 PRIME trial (NCT03709316). Methods: In PRIME, adults with newly diagnosed aOC who had received cytoreductive surgery and responded to 1LCT were randomized 2:1 to receive niraparib or placebo with stratification by receipt of neoadjuvant chemotherapy, response to 1LCT, status of germline BRCA mutations, and tumor homologous recombination deficiency status. Tumor assessment was conducted at baseline and every 12 weeks thereafter by blinded independent central review (BICR) according to RECIST, version 1.1. Between 29 June 2018 and 11 November 2019, 384 patients were randomized (255 niraparib, 129 placebo). The data cut-off date was 30 September 2021. This post-hoc analysis reports BICR-assessed objective response rate (ORR) and PFS in patients with MRD at baseline. An initial response was confirmed ≥4 weeks later. Results: In total, 73 (19.0%) patients (47 niraparib, 26 placebo) had MRD at baseline. Baseline characteristics were well balanced between the two MRD groups. Complete and partial responses, both confirmed, were observed in 12 (25.5%) and 15 (31.9%) niraparib-treated patients and 3 (11.5%) and 5 (19.2%) placebo-treated patients, respectively, leading to a confirmed ORR of 57.4% with niraparib and 30.8% with placebo (odds ratio, 3.20; 95% confidence interval [CI], 1.11–9.11). ORRs by biomarker status are provided in the table. Median PFS (95% CI) was 22.3 (8.7–not estimable) months with niraparib versus 8.3 (5.6–11.0) months with placebo (hazard ratio, 0.36; 95% CI, 0.19–0.71). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 28 (59.6%) niraparib-treated patients and 7 (26.9%) placebo-treated patients. TEAEs led to treatment discontinuation in three (6.4%) niraparib-treated patients and one (3.8%) placebo-treated patient. Conclusions: In patients with newly diagnosed aOC who had MRD after 1LCT, niraparib maintenance therapy tended to induce additional antitumor activity and led to a clinically meaningful increase in PFS versus placebo. Clinical trial information: NCT03709316 .[Table: see text]

Gender and postoperative surgical margin status in MIBC: An analysis of the National Cancer Database.

4599 Background: Women with muscle-invasive bladder cancer (MIBC) continue to experience persistent disparities in health outcomes despite accounting for less than 1/3 of newly diagnosed bladder cancer cases. Multiple studies have acknowledged the aggressive profile of female bladder cancer. This study aims to identify tangible areas to intervene and improve the delivery of oncologic care. Methods: The National Cancer Database (NCDB) was queried from 2004-2017 to conduct a retrospective cohort analysis of men and women with MIBC (cT2a-T4). N=41,037 patients with MIBC were reviewed, (30,313 male; 10,724 female). The primary endpoints were OS and surgical margin status. Logistic regression was performed to determine whether female sex conferred differential impact on surgical margin status when controlling for baseline clinical stage, age, receipt of neoadjuvant chemotherapy (NAC), Charleson-Deyo Comorbidity Classification (CDCC), and facility type. Cox proportional hazards assessed the impact of age, gender, margin status, CDCC and NAC on OS. Results: Logistic regression showed that sex, age, baseline clinical stage, CDCC, facility type and NAC were significant predictors of surgical margin status (p&lt;.001). Female sex was found to have a 14.4% higher probability of having positive residual margins (HR 1.144 (95% CI: 1.07-1.23), p&lt;.001). When adjusting for age, margin status, CDCC and NAC, Female gender (OS HR 1.063 (95% CI: 1.03-1.09), p&lt;.001), positive microscopic margins (OS HR 2.0 (95% CI: 1.90-2.10), p&lt;.001) and positive macroscopic margins (OS HR 2.62 (95% CI: 2.40-2.90), p&lt;.001) independently portended poorer OS and necessitated increased adjuvant XRT (p&lt;.001). Unexpected demographic findings included a significantly greater number of females than expected with a median household income &lt;$38,000 (p= 0.047) and a greater number of females in the upper quartile of patients without a HS diploma (p&lt;.001). The median days from diagnosis to definitive surgical treatment was significantly lower compared to males (58 vs 67 days; p&lt;.001). Conclusions: Women with MIBC faced obstacles to getting treatment (less education and lower median income). Despite these hurdles they may be more proactive with their health as seen by a shorter time from diagnosis to the surgical table. However, this proactivity has yet to pay off as women undergoing surgical treatment for MIBC were significantly less likely to have clear margins post-operatively. The urologic community must mirror female patient’s proactivity and further investigate the gender disparity in surgical treatment of MIBC. [Table: see text]

Social determinants of health and utilization of neoadjuvant chemotherapy in patients with triple negative breast cancer (TNBC) in the community oncology setting.

610 Background: TNBC has a higher incidence in African American women compared to European American, often presents at a younger age or more advanced stage, and is associated with worse outcomes. The use of multi-agent neoadjuvant chemotherapy (NC) improves event-free survival and overall survival in patients with early-stage TNBC and is considered standard of care. Race and other social determinants of health (SDOH) have been shown to affect outcomes in patients with TNBC. Differences in use of NC associated with SDOH may be a contributing factor to inferior outcomes. The aim of this study is to determine if SDOH measures affect utilization of NC in patients with early-stage TNBC. Methods: This retrospective observational cross-sectional study examined patient profiles, treatment patterns and SDOH indicators among patients newly diagnosed with early-stage breast cancer in The US Oncology Network. Using iKnowMed EHR data, patients diagnosed with TNBC between 03/31/2017 and 09/30/2021 with stages II-IIIB disease or tumor size ≥2cm (T2 or higher) were included. The initial TNBC diagnosis date was used as the index date for each patient and records were assessed from 6 months pre- to 6 months post-diagnosis for NC initiation, baseline characteristics, and social determinants, including Area Deprivation Index (ADI), a validated measure of socioeconomic status. Results: 3321 patients with TNBC were identified, with a mean age of 58 years; 59% were White, 15% Black, 3% Asian, and 23% other/unknown; and 2139 (64%) received NC. Patients who received NC relative to those who did not were younger (mean 55.9 vs 61.8; p=0.001), had higher BMIs (70% with BMI&gt;25 vs ≤25, p=0.045), and had commercial or Medicaid insurance (67.5% with commercial insurance or Medicaid vs. 52.5% with Medicare; p=0.001). Regional differences were observed, with proportionally fewer patients receiving neoadjuvant chemotherapy in the south US census regions and more in the west. There was no difference in NC use in Black vs White patients (66% vs 64%). No significant differences in receipt of NC were found for race, ethnicity, or ADI. Conclusions: In the community oncology setting, we did not observe inequities in the use of NC based on social determinants analyzed in this study, such as race, ethnicity, and ADI. Poorer outcomes observed in Black patients with TNBC may not be a result of underutilization of NC.

Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation.

Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.

Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer

PurposeTo report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). MethodsPatients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported. ResultsIn 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40–0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56–0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49–0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature. ConclusionsNiraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.

Three-Dimensional Versus Two-Dimensional Laparoscopy in Laparoscopic Liver Resection: A Systematic Review and Meta-Analysis.

Background: Three-dimensional (3D) laparoscopy provides stereopsis and may reduce operating time (OT) and morbidity. However, there is a paucity of literature on its use in laparoscopic liver resection (LLR). This study aims to compare outcomes between 3D and two-dimensional (2D) LLR. Materials and Methods: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched from inception to November 2022. The inclusion criterion was studies comparing intraoperative characteristics and/or postoperative outcomes between 3D and 2D LLR. Studies on the use of 3D image reconstruction techniques for preoperative planning were excluded. Primary outcomes were OT, estimated blood loss (EBL), and overall morbidity. Secondary outcomes were other postoperative complications, need for reoperation, and in-hospital mortality. Results: Four studies with 361 patients (3D: n = 159, 2D: n = 202) were included. There were 65.3% males (overall: n = 236/361). Age, sex, body-mass index, incidence of diabetes mellitus, hepatitis B and/or C carrier, receipt of neoadjuvant chemotherapy, tumor size, and incidence of multiple tumors were comparable between 3D and 2D LLR. No studies reported on Child-Pugh status. One study included only patients with hepatocellular carcinoma, two studies included patients with mixed histopathology, and one study did not report on histopathology. There was no significant difference in OT (mean difference [MD] -31.6 minutes, 95% confidence interval [CI]: -89.7 to 26.5), EBL (MD -454.1 mL, 95% CI: -978.8 to 70.6), need for reoperation (odds ratio [OR] 0.91, 95% CI: 0.18-4.61), and in-hospital mortality (OR 0.52, 95% CI: 0.06-5.50) between 3D and 2D LLR. Overall morbidity was lower in 3D LLR (OR 0.56, 95% CI: 0.32-0.98, P = .04). However, the learning curve (LC) was not described in the included studies and may confound outcomes. Conclusions: 3D LLR may reduce overall postoperative morbidity compared with 2D LLR, but results may be confounded by the lack of standardization of surgeons' experience and the LC of 3D LLR.