Use Of Chemotherapy In Patients Research Articles

Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival

BackgroundThe 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor–positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown.MethodsA patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio (LR) tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry.ResultsRSClin provided significantly more prognostic information than either the clinicopathologic factors (ΔLR chi-square, 86.2; P<0.001) or RS alone (ΔLR chi-square, 131.0; P<0.001). The model was prognostic in an independent cohort for distant recurrence by 10 years after diagnosis (standardized hazard ratio, 1.56; 95% confidence interval, 1.25 to 1.94), was associated with late distant recurrence risk between 5 and 10 years after diagnosis (standardized hazard ratio, 1.78; 95% confidence interval, 1.25 to 2.55), and approximated the observed 10-year distant recurrence risk (Lin concordance, 0.87) and 5- to 10-year distant recurrence risk (Lin concordance, 0.92).ConclusionsThe 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk. (Funded by the National Cancer Institute, National Institutes of Health [U10CA180820, U10CA180794, UG1CA189859, U10CA180868, and U10CA180822] and others.)

Patterns of use of primary and first-line chemotherapy for recurrence among patients with cervical cancer

BackgroundLittle is known about real-world patterns of chemotherapy use in patients with cervical cancer.ObjectiveTo examine the patterns of chemotherapy use in patients with cervical cancerMethodsWe identified patients with cervical cancer...

Impact of the Coronavirus Disease 2019 pandemic on neoadjuvant chemotherapy use in patients diagnosed with epithelial type ovarian cancer.

The Coronavirus Disease 2019 (COVID-19) pandemic posed critical challenges in providing care to ovarian cancer (OC) patients, including delays in OC diagnosis and treatment initiation. To accommodate for delays in OC surgery, the Society of Gynecologic Oncology (SGO) recommended preferential use of neoadjuvant chemotherapy during the pandemic. The purpose of this study was to assess the association of the COVID-19 pandemic with neoadjuvant chemotherapy use in patients diagnosed with OC. This retrospective cohort study included patients diagnosed with stage II-IV ovarian cancer of epithelial subtype between 01/01/2017-06/30/2021 at Kaiser Permanente Southern California (KPSC), a large integrated healthcare system in the United States. Ovarian cancer patients diagnosed between 2017-2020 were identified from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry. Patients diagnosed in 2021 were identified from the electronic medical records (EMR) using ICD-10 diagnosis codes, followed by medical chart review to validate diagnosis and extract information on histology and stage at diagnosis. March 4, 2020 was used as the cut-off to define pre-pandemic and pandemic periods. Patients diagnosed with COVID-19 between OC diagnosis and treatment completion were excluded. Data on neoadjuvant chemotherapy use were extracted from the cancer registry and EMR, supplemented by chart review. Modified Poisson regression was used to evaluate the association of the pandemic with neoadjuvant chemotherapy use. Of 566 OC patients, 160 (28.3%) were diagnosed in the pandemic period. Patients diagnosed in the pandemic period were slightly younger (mean age 62.7 vs 64.9 years, p=0.07) and had a higher burden of Charlson comorbidities (p=0.05) than patients diagnosed in pre-pandemic period. No differences in time to treatment initiation were observed by pandemic periods. Neoadjuvant chemotherapy use was documented in 58.7% patients during the pandemic period compared to 47.3% in pre-pandemic period (p=0.01). After adjusting for covariates, patients diagnosed in the pandemic period were 29% more likely to receive neoadjuvant chemotherapy than patients diagnosed in pre-pandemic period [RR(95%CI): 1.29(1.12-1.49)]. Ovarian cancer patients diagnosed in the COVID-19 pandemic were more likely to receive neoadjuvant chemotherapy than patients diagnosed before the pandemic. Future research on patient outcomes and trends in the post-pandemic period are warranted.

Adjuvant Chemotherapy in Premenopausal Patients With Hormone-Positive Breast Cancer With a Recurrence Score of 16-25: A Retrospective Analysis Using the National Cancer Database.

Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative (HER2-), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database. The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2-. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared. Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]). Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.

Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study

There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Rates of surgery and adjuvant chemotherapy use in patients with stage IB to IIIA non-small cell lung cancer: A provincial population-based study.

134 Background: The current standard of treatment for early-stage (IB to IIIA) non-small cell lung cancer (NSCLC) include surgery and adjuvant chemotherapy. The objective of this study is to identify rates of adherence to guideline recommended surgery and adjuvant chemotherapy treatment for early-stage NSCLC for patients living in Ontario, the most populous province of Canada. Methods: A retrospective population-based study using linked administrative data through ICES was completed that included all adult patients with a diagnosis of stage IB to IIIA NSCLC made from 2010 to 2020 in Ontario. Rates of surgery and chemotherapy completion were calculated using available OHIP (Ontario Health Insurance Plan) billing codes. Logistic multivariate regressions were completed to assess for any predictors for completion of surgery and chemotherapy. Results: A total of 24,237 eligible patients were included. By cancer staging, there were 6,495 (26.8%) stage IB, 7,156 (29.5%) stage II, and 10,586 (43.7%) stage IIIA NSCLC patients. Within 180 days of diagnosis, surgery was completed for 9,929 (41.0%) of patients, by cancer staging were 4090/6495 (63.0%), 3719/7156 (52.0%), and 2120/10586 (20.0%) for IB, II, and IIIA respectively. The median time from diagnosis to surgery was 49 days (IQR 23-77 days). Amongst patients who completed surgery, 3344/9929 (33.7%) underwent at least 1 cycle of adjuvant chemotherapy within 180 days. Having advanced age (p&lt;0.001), high Charlson comorbidity score (p&lt;0.001), and low income (p&lt;0.001) are predictors for poor uptake for both chemotherapy and surgery. Being male also reduces the likelihood of undergoing surgery (p&lt;0.001). Conclusions: In our population-based study, less than half of the patients with early-stage (IB-IIIA) NSCLC underwent surgical resection and chemotherapy. These low treatment rates are concerning and may be contributing to suboptimal outcomes. Our findings indicate that elderly individuals with multiple comorbidities and those with low incomes are at the highest risk of not receiving appropriate chemotherapy and surgery. Our data highlight the need for quality improvement strategies aimed at identifying and enhancing treatment uptake within this patient population.

Tumor size is associated with adjuvant chemotherapy benefit in T1N0M0 triple-negative breast cancer: a multicenter and propensity score matched analysis.

Triple-negative breast cancer (TNBC) is characterized by aggressive phonotypes and relatively poor outcomes. There are controversies on the effect of adjuvant chemotherapy in small (T1N0M0) TNBCs, especially among T1a-b patients. This study evaluated the survival benefit of adjuvant chemotherapy and influential factors in T1N0M0 TNBC patients. All T1N0M0 TNBC patients were identified from the Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB) between January 2009 and December 2021. Propensity score matched (PSM) was applied to create a matched cohort. We used Kaplan-Meier analysis and Cox regression models to evaluate the associations of adjuvant chemotherapy with breast cancer-free interval (BCFI) and overall survival (OS). Stratified analysis according to different influential factors was also performed. In total, 1,113 T1N0M0 TNBC patients (297 T1a, T1b and 816 T1c) were enrolled, including 928 patients with adjuvant chemotherapy and 185 patients without adjuvant chemotherapy. After matching 441 patients by using PSM analysis, 294 patients with chemotherapy and 147 patients without chemotherapy were identified. Patients with or without chemotherapy had similar BCFI (P=0.241) and OS (P=0.509). However, regarding patients with different tumor sizes, adjuvant chemotherapy could significantly improve BCFI in T1c patients (5-year BCFI: 92.1% vs. 79.5%, P=0.035) but not in T1a-b patients (5-year BCFI: 93.6% vs. 94.6%, P=0.546). No significant difference in OS was observed among patients with different tumor sizes. Subgroup analysis found that only tumor size was significantly associated with adjuvant chemotherapy benefit in terms of BCFI (Pinteraction=0.021) and OS (Pinteraction=0.040). The survival benefit of adjuvant chemotherapy was significantly associated with tumor size in T1N0M0 TNBC. Benefit of adjuvant chemotherapy was found in T1c, but not in T1a-b patients. Our findings do not support the routine use of chemotherapy in patients with T1a-bN0 TNBC.

Impact of the COVID-19 pandemic on neoadjuvant chemotherapy use in patients diagnosed with advanced ovarian cancer (2214)

Impact of the COVID-19 pandemic on neoadjuvant chemotherapy use in patients diagnosed with advanced ovarian cancer (2214)

3-year experience of hyperthermic intravesical chemotherapy use in patients with high risk non-muscular-invasive bladder cancer

Cur rently, the search for additional organ-sparing methods of intravesical therapy for non-muscular-invasive bladder cancer (NMIBC) is actively continuing, which could become an effective alternative to standard treatment using the Bacillus Calmette-Guérin (BCG) vaccine. The aim of this work was to analyze the safety profile and long-term results of treatment of patients with the high-risk non-muscular-invasive bladder cancer who received adjuvant intravesical chemotherapy using the Combat BRS HIVEC® device for local hyperthermia (HIVEC® therapy group; n=53) in comparison with patients who received adjuvant therapy after transurethral resection of bladder performed with the Bacillus Calmette-Guérin vaccine (BCG therapy group; n=54). As a result, the median follow-up was 30 months (range 7-36). According to Common Terminology Criteria for Adverse Events (CTCAE) v 5.0, the most relevant side effects in HIVEC®/BCG therapy groups were adverse events grade 1-2: fever – 1%/8%; dysuria – 9%/13%; bladder spasms – 7%/12%; hematuria – 3%/4% and urinary tract infection – 3%/10%. Tumor recurrence was reported in 23 patients receiving intravesical BCG therapy and in 10 patients receiving intravesical hyperthermic chemotherapy (42.6% versus 18.9%, p=0.008). Tumor progression was recorded in 11 patients receiving intravesical BCG therapy and in 4 patients receiving intravesical hyperthermic chemotherapy (20.4% versus 7.5%, p=0.046). The study allows us to conclude that the method of hyperthermic intravesical chemotherapy has a better safety profile compared to intravesical Bacillus Calmette–Guérin vaccine therapy, while such indicators of oncological efficacy as 3-year recurrence-free survival and the incidence of progression were better in the HIVEC® therapy group.

Prognosis and trends in chemotherapy use for patients with stage IA triple-negative breast cancer (TNBC): A population-based study.

510 Background: Outcomes for patients with stage IA TNBC in the modern era remain poorly characterized, and the benefit and utilization of adjuvant chemotherapy (chemo) in this setting remains controversial. Methods: We analyzed data from women diagnosed with pathological stage IA TNBC in the Surveillance, Epidemiology, and End Results (SEER) database during 2010 to 2019. We evaluated the associations of adjuvant chemo with breast-cancer specific survival (BCSS) stratified by tumor size, using multivariate cox models adjusted for tumor size (overall cohort only), age at diagnosis, race, tumor grade, histology, radiation, marital status, income, and rurality. Frequency of chemo use over time was examined by tumor size. Multivariate logistic regression assessed variables associated with chemo administration. Results: In total, we examined data from 8,601 women with stage IA TNBC. Median age at diagnosis was 62 years. Most patients had high-grade tumors (70.1%), ductal histology (92.8%), and received adjuvant chemo (61.6%). Median follow up was 48 months (IQR: 20 – 83). The use of chemo significantly increased during 2010-2019 for both T1b tumors (p for trend = 0.001) and T1c tumors (p for trend &lt; 0.001), with 52.5% and 63% of the patients with T1b and T1c TNBCs receiving chemo in 2010, respectively, compared with 60.5% and 71.1% in 2019. No significant differences were observed in the use of chemo for T1mic (p for trend = 0.567) and T1a (p for trend = 0.637) tumors, with low utilization seen in both cohorts (9.5% overall in T1mic, 22.5% overall in T1a). Variables associated with chemo use included younger age, white race, married status, higher income, more recent diagnosis, higher tumor grade, ductal histology, and larger tumor size (all p &lt; 0.02). Overall, 5-year BCSS was high across T groups ( &gt; 90%; Table). Receiving chemo (vs. none/unknown) was associated with an improved 5-year BCSS (adjusted HR for BCSS = 0.70, p = 0.006). For T1c tumors specifically, adjuvant chemo (vs. none/unknown) was also associated with BCSS (adjusted HR 0.64, p = 0.002). The small number of BCSS events precluded comparisons for other tumor size subgroups. Table shows sample sizes and 5-year BCSS rate by chemo receipt for each T group. Conclusions: In a large population-based cohort of patients with stage IA TNBC, we observed excellent 5-year BCSS outcomes, supporting the good prognosis of this patient population. The use of adjuvant chemo increased over time for T1b and T1c TNBCs, and was associated with improved BCSS for T1c tumors, although evaluation of benefit is limited by the inherent treatment bias in registry data. [Table: see text]

Conventional Therapies of Oral Cancers: Highlights on Chemotherapeutic Agents and Radiotherapy, Their Adverse Effects, and the Cost Burden of Conventional Therapies.

Oral cancer (OC) is increasing worldwide, and it is mostly present to clinic in the late-stage of disease. Cancer of the lips, tongue, hard palate, upper and lower gingiva, buccal mucosa, and retromolar trigone are all included in the category of oral cavity cancer. Disease symptomatology and pathological grading decides the course of treatment. Several treatment modalities either alone in combinations may be utilized for oral squamous cell carcinoma (OSCC), including surgery, radiotherapy (external beam radiotherapy/brachytherapy), and adjuvant systemic therapy (chemotherapy or immunotherapy). Cancer patients also face a greater risk of oral side effects from chemotherapy, such as slowed tissue healing, bone, and salivary gland damage and disintegration, and disruption of the normal bacterial balance in the mouth. Consequently, the economic burden of the salivary gland, oral cavity, and oropharyngeal cancers must be also known for budget allocation, designing different programs and management strategies targeting oral cancers by any healthcare institutes. This article provides a summary of the most recent research that supports the use of chemotherapy for patients with advanced illness both alone and in conjunction with radiation including its adverse events and cost burden for oral cancers.

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population. MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS). ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group. ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.

A novel predictor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors.

e17521 Background: For early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (COUNT) score in guiding the use of concurrent chemotherapy in patients with early-stage cervical cancers during postoperative radiotherapy. Methods: A total of 945 patients with FIGO stage IB-IIA (2009) cervical cancer were retrospectively analyzed in the study from 2009 to 2018. There were 503 patents receiving concurrent chemoradiotherapy, while another 442 patents undergone radiotherapy lonely. Radiotherapy was performed by conformal radiotherapy or intensity-modulated radiotherapy. The concurrent chemotherapy regimen included either cisplatin or paclitaxel. Pre-treatment CONUT score were calculated within 1 weeks before curative resection. Low CONUT group and high CONUT group were defined based on the cutoff value of CONUT score which was determined by the receiver operating characteristic analysis. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses of DFS, local recurrence-free survival and distant metastasis-free survival (DMFS). Results: The median follow-up was 54.6 months (range: 4.8-147.5 months). The optimal cutoff value of CONUT was 3 in the study. For the patients included in the high CONUT group (≥3), the addition of concurrent chemotherapy significantly improved treatment outcomes, and had better 5-year DFS (90.37% vs 70.69%, P &lt; 0.001) and CSS (95.02% vs 78.74%, P = 0.005) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of distant metastasis (6.5% vs 28.1%, P &lt; 0.001). For the patients included in low CONUT group (&lt; 3), there was no difference in prognosis between patients receiving concurrent chemotherapy and not receiving. In the high CONUT group, the multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (HR 3.077; 95% CI: 1.295-6.679, P = 0.011) and DMFS (HR 3.435; 95% CI: 1.506-7.014, P = 0.006). Conclusions: Pre-treatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer patients with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.

A Propensity Score Analysis of Chemotherapy Use in Patients With Resectable Gallbladder Cancer

Gallbladder cancer is uncommon but highly fatal. Surgery remains the only potentially curative treatment for localized or locoregionally advanced gallbladder cancer. The rate of use of neoadjuvant and adjuvant chemotherapy in resectable gallbladder cancer is unknown. To assess factors associated with the use of neoadjuvant and adjuvant chemotherapy in patients with resectable gallbladder cancer and survival outcomes. The National Cancer Database was used to identify 6391 adults who underwent definitive surgical resection for gallbladder cancers between January 1, 2004, and January 1, 2016. Data analysis was performed from January 15 to February 15, 2020. Patients with localized or locoregionally advanced gallbladder cancers (ie, categories cTx-cT4, cN0-2, and cM0) were categorized as receiving neoadjuvant chemotherapy, adjuvant chemotherapy, or surgery alone. Categorical variables were compared using the χ2 test, with 1:3 nearest-neighbor propensity score matching based on neoadjuvant chemotherapy. Survival outcomes between groups were compared using Kaplan-Meier and Cox proportional hazards regression analyses. The use and survival outcomes of adjuvant and neoadjuvant chemotherapy. Of 6391 patients who underwent definitive surgery for gallbladder cancer, 4559 were women (71.3%); median age was 68 (IQR, 59-77) years. A total of 3145 patients (49.2%) received adjuvant chemotherapy, 3145 patients (49.2%) underwent surgery without chemotherapy, and 101 patients (1.6%) received neoadjuvant chemotherapy. Neoadjuvant chemotherapy use was associated with treatment at an academic facility (61 patients [60%] vs 38 patients [38%] treated in a nonacademic facility; P < .001) and in those with private insurance (65 patients [65%] vs 11 patients [11%] with Medicaid insurance; P < .001). Surgery alone was frequently used in older patients (median age, 72 [IQR, 63-81] years vs 59 [IQR, 52-66] years in patients with neoadjuvant chemotherapy; P < .001), those with Medicare insurance (1925 patients [57%] vs 1438 patients [43%] with adjuvant chemotherapy; P < .001), and patients with a higher comorbidity index score (326 patients [62%] vs 197 patients [38%] with adjuvant chemotherapy; P < .001). Adjuvant or neoadjuvant chemotherapy was used more frequently than surgery in patients with node-positive cancer (1482 [67.2%] vs 53 [65.4%] vs 912 [49.7%]). On propensity score matching analysis, adjuvant chemotherapy was associated with longer survival than surgery alone (22 vs 18 months, hazard ratio [HR], 0.78; 95% CI, 0.63-0.96); survival with neoadjuvant chemotherapy was not statistically significant compared with surgery alone and adjuvant chemotherapy groups (27 months, HR, 0.78; 95% CI, 0.58-1.04). However, in patients with node-positive gallbladder cancer, neoadjuvant therapy was associated with longer median overall survival (30 months [95% CI, 24-36 months] vs 14 months [95% CI, 11-17] in patients with surgery alone; P = .002). In this cohort study, use of adjuvant and neoadjuvant chemotherapy was low in patients with surgically resected gallbladder cancers. Chemotherapy was used more frequently than surgery in lymph node-positive disease compared with lymph node-negative disease. Adjuvant chemotherapy was associated with a survival advantage in resectable gallbladder cancer, and neoadjuvant chemotherapy was associated with increased survival in node-positive gallbladder cancers. These findings suggest that adjuvant chemotherapy and neoadjuvant chemotherapy should be considered in treatment of gallbladder cancer.

Abstract P1-08-18: Impact of gene expression profile testing for lymph node positive (LN+) , hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer (BC) patients on the use of adjuvant chemotherapy in a large community cancer center

Abstract Background: Use of gene expression profiling (GEP) is considered standard of care, in deciding use of adjuvant chemotherapy in patients with LN negative breast cancer. However, there are limited data for the use of GEP in LN+ disease. Both Mammaprint™ and Oncotype Dx 21 gene recurrence score™ (RS) have been evaluated in LN+ disease, the data are not as robust as in the LN- population. Based on data from the RXPONDER trial and the MINDACT trial, the NCCN has recently recommended the use of Oncotype Dx to help decide the utility and benefit of adjuvant chemotherapy after resection in LN- , Hormone receptor Positive (HR+), HER2 negative (HER2-) breast cancer patients. Because of the potential major impact of these data on patient management and healthcare utilization, we decided to explore the uptake and implementation of this testing at a large community cancer center in order to assess and report real world data pertaining to this novel standard of care. Methods: Database search of the Electronic Medical Records used at Ironwood Cancer Center, revealed 2455 newly diagnosed patients with early stage breast cancer during the period from 1/1/2018 till 6/1/2021. HIPAA deidentified data was extracted with inclusion criteria of newly diagnosed women with LN+ (1-3 nodes), HR+, and Her2- which yielded 403 patients. Demographics &amp; treatment data: Characteristics included menopausal status (Premenopausal 23%, Post Menopausal 77%), Surgery type (mastectomy 44%, breast conservation surgery 56%), size of primary tumor (0-1 cm 16 %, 1-2 cm 28%, 2-5 cm 43%, and &amp;gt; 5 cm 13%), LNs resected (Range 0-37, Median 4), # of LNs +(1-60%, 2-25%, 3-15%), and Tumor Grade (Grade 1-23%, 2-56%, 3-21%). GEP was performed in 62% of the patients. 49% received adjuvant chemotherapy (61% anthracycline based, 39% non anthracycline based). Of the patients tested, 41% received adjuvant chemotherapy. Adjuvant antihormonal therapy included aromatase inhibitors in 86% and Tamoxifen in 14%. 81% of the pre-menopausal patients received complete ovarian suppression. Results: Logistical Regression analysis in a non linear fashion, R2 data and Chi-square analysis was used to test the statistical significance of the observed relationship with respect to the expected relationship. The data was divided into 6 monthly intervals to allow comparison of the uptake of the test and impact on adjuvant chemotherapy decision making. There was a significant increase in GEP profile testing percentages when these intervals were compared across the years (R2 =0.69). Increase in GEP profiling was associated with lower utilization of adjuvant chemotherapy (R2= 0.84). There was a non-significant decline in the use of adjuvant chemotherapy (Chi2 NS, p value 0.22). Menopausal status, grade/size of tumor did not meet the statistical significance for the likelihood of utilization of the test. Currently multivariate analysis is being performed to examine the interplay between the numerous clinical factors on which the data was collected. This analysis will allow us to decide if we can longitudinally explore recurrence rates in each of these subsets. Conclusion: GEP has seen a significant uptake to help with adjuvant chemotherapy decision making in LN + (1-3) patients in the community cancer center setting over the last 4 years. These real world data also showed that increased testing was associated with decreased chemotherapy use which has translated to lowering health care resources and minimizing patient morbidity. Recommendations from the expert guidelines and clinical trial data have helped accelerate the use of this technology in the decision making to undergo adjuvant chemotherapy in the LN+, HR+, HER2- patients with breast cancer. Citation Format: Nisha Rao Kalmadi, Andrew Brown, Manas Sharma, Mikhail Shtivelband, Joshua Rifkind, Sujith Kalmadi, Rajesh Bagai, Emily Ho, Patricia Clark, Christopher Kellogg, Parvinderjit Khanuja. Impact of gene expression profile testing for lymph node positive (LN+) , hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer (BC) patients on the use of adjuvant chemotherapy in a large community cancer center [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-18.

Abstract P3-14-02: Racial/ethnic differences in the benefit of adjuvant chemotherapy for breast cancer patients with an intermediate risk 21-gene recurrence score

Abstract Background: The Oncotype 21-gene Recurrence Score (RS) is the most commonly ordered genomic biomarker used to inform decisions on adjuvant chemotherapy for patients with estrogen receptor (ER)-positive, HER2-negative early breast cancer. Representation of racial/ethnic minority patients in the population used to develop the assay was poor, with only 5% of study participants identified as Black. This raises concern about the accuracy of the RS in underrepresented populations. In earlier work (Hoskins et al, JAMA Oncology 2021), we showed that the RS has less prognostic accuracy in Black compared with non-Hispanic White (NHW) women. This finding is concerning in light of persistent racial disparities in breast cancer mortality. Here we examine the predictive accuracy of the RS according to race/ethnicity for identifying patients with ER+, axillary node-negative breast cancer who benefit from adjuvant chemotherapy.Methods: We conducted a large, population-based retrospective cohort study of women 18+ years diagnosed with ER+, axillary node-negative breast cancer from 2004 to 2010 using Surveillance, Epidemiology and End Results Oncotype DX Database (2004-2015). This analysis included women with a minimum of 7 yrs follow-up and an RS of 11-25, since this is the group with the most uncertainty regarding the benefit of chemotherapy. Demographic and clinical characteristics were collected from cancer registry data. Propensity score weighted Cox models determined the association between chemotherapy use and breast cancer death. Age, insurance status, tumor grade, tumor size, progesterone receptor status, and RS were included as predictors of the propensity score. Associations between chemotherapy use and breast cancer death were determined using overall, race/ethnicity, and age stratum-specific hazard ratios (HR) and 95% confidence intervals (CI). Results: The analysis included 22,693 NHW, 5,657 Black, and 3,348 Hispanic women. The overall result is consistent with the prospective TAILORx trial, showing greater benefit from chemotherapy in women under age 50. There is a greater reduction in the hazard of breast cancer death associated with chemotherapy use for Black (HR 0.31, 95% CI, 0.15, 0.66) and Hispanic (HR 0.07, 95% CI, 0.02, 0.31) compared with NHW women under age 50 (HR 0.43, 95% CI,0.32, 0.59). In models combining Black and NHW patients, an interaction term for race*chemotherapy was significant (p=0.022), indicating a differential association between chemotherapy use and breast cancer death according to race/ethnicity. Visual comparison of breast cancer mortality curves that plot 7-year breast cancer death rate as a function of the continuous RS, stratified by chemotherapy administration (yes/no), shows that the curves begin to diverge at a lower RS for Black (RS 17) compared with NHW women (RS 24). Conclusions: This observational study found that Black women under age 50 with ER+, axillary node-negative breast cancer and an RS of 11-25 derive significantly more benefit from adjuvant chemotherapy than NHW women. National practice guidelines do not recommend routine use of adjuvant chemotherapy for patients in this risk category, indicating that many Black patients may be undertreated. Results need to be confirmed in prospective studies, but they suggest that RS cut-offs used to recommend adjuvant chemotherapy may need to be modified for racial/ethnic minority women. Hazard of Breast Cancer Death (95% Confidence Interval)Race/EthnicityChemotherapyAll AgesAge &amp;lt; 50Age 50+OverallYes0.71 (0.63, 0.81)0.32 (0.25, 0.41)1.01 (0.87, 1.18)NoRefRefRefNHWYes0.73 (0.62,0.84)0.43 (0.32, 0.59)0.87 (0.74, 1.04)NoRefRefRefBlackYes0.83 (0.60, 1.16)0.31 (0.15, 0.66)1.26 (0.84, 1.89)NoRefRefRefHispanicYes0.33 (0.20, 0.57)0.07 (0.02, 0.31)0.61 (0.33, 1.12)NoRefRefRef Citation Format: Hsiao- Ching Huang, Gregory S. Calip, Jennifer Weiss, Yael Simons, V.K. Gadi, Oana C. Danciu, Garth H. Rauscher, Kent F. Hoskins. Racial/ethnic differences in the benefit of adjuvant chemotherapy for breast cancer patients with an intermediate risk 21-gene recurrence score [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-02.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is > 1cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size. We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated. Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease. Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Impact of Immunoscore on the Management of Stage II Colon Cancer Patients: A Physician Survey.

Adjuvant chemotherapy use in stage II colon cancer is controversial. Current prognostic risk factors do not take the tumor immune microenvironment into account. Consideration of the Immunoscore, which measures the host immune response at the tumor site, may assist clinicians in reducing adjuvant chemotherapy use in patients who are unlikely to benefit from it. This study sought to determine the potential clinical utility of the Immunoscore, via its effect on medical oncologists' recommendations for management of patients with stage II colon cancer. De-identified vignettes of 10 patients with stage II colon cancer were presented to 25 practicing medical oncologists. Each participant completed surveys indicating recommendations for adjuvant chemotherapy and surveillance strategies. An educational session was subsequently conducted, and the same patient profiles were re-presented but included immunoscore results. Participants were again asked to provide their recommendations. A participant was counted as influenced if their responses were altered after immunoscore test results were provided. All but one participant (96%) altered a management recommendation for ≥1 case. For individual cases, a mean of 55% (range, 40-80%) of participants altered their recommendations for adjuvant chemotherapy and/or surveillance. For the immunoscore-high cases (low-risk of recurrence), recommendations for adjuvant chemotherapy use decreased from 60% to 31%. These results indicate a willingness by oncologists to integrate immunoscore information into clinical practice recommendations. Incorporation of immunoscore data resulted in the reduction of nonvalue care in the simulated population. Confirmation in prospective studies is planned.

Circulating tumor cell-driven use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

4523 Background: International guidelines for the treatment of non-metastatic muscle-invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC), which, however, is underutilized in practice. We hypothesized that the absence of circulating tumour cells (CTCs), an established prognostic marker in MIBC, may identify patients with such a favourable prognosis that NAC may be withheld. Methods: The CirGuidance study included adults with clinical stage T2-T4aN0-N1M0 muscle-invasive urothelial carcinoma of the bladder who were fit to undergo radical cystectomy. CTCs were enumerated using the CellSearch system. CTC-negative patients (no CTCs detectable) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC followed by radical surgery, but NAC could be withheld at the discretion of the treating physician. The primary endpoint was the two-year overall survival (OS) in the CTC-negative group, analysed in the intention-to-treat population. The prespecified criterion for trial success was a two-year OS of minimally 75% (95% confidence interval (CI) ±5%) in the CTC-negative group. Results: Of 315 patients screened for eligibility, 273 were enrolled in the study. The median age was 69 years; the median follow-up was 36 months. The two-year OS in the CTC-negative group was 69.5% (n = 203; 95% CI 62.6%-75.5%); in the CTC-positive group it was 58.2% (n = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality (hazard ratio (HR) 1.61, 95% CI 1.05-2.45, p = 0.03) and disease relapse (HR 1.87, 95% CI 1.28-2.73, p = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48), with a two-year OS of 74.8% (95%CI 49.5%-88.8%) versus 52.0% (95% CI 37.2%-65.0%), respectively. Conclusions: The two-year OS in the CTC-negative group did not meet the prespecified criterion for trial success. However, given the trial population’s advanced age and high rate of non-cancer related mortality, the benefit of NAC is likely to be limited in CTC-negative MIBC patients. CTC enumeration at the moment of diagnosis could aid in the decision to prescribe neoadjuvant chemotherapy for a muscle-invasive bladder cancer patient as a criterion in addition to clinical characteristics. Clinical trial information: NL3954.