Significant Differences In Survival Outcomes Research Articles

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer

Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P=0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P=0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

Comparing outcomes in patients with end-stage chronic obstructive pulmonary disease: single versus bilateral lung transplants.

Debate continues on whether a bilateral (BLT) or a single lung transplantation (SLT) is preferred for patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study is to examine the interplay between patient age and transplant type on survival outcomes. We performed a retrospective study of lung transplants for COPD at our centre from February 2012 to March 2020 (n = 186). Demographics and clinical parameters were compared between patients based on their age (≤65 vs >65 years old) and type of transplant (single vs bilateral). Cox proportional hazards regression was also performed. P-values <0.05 were considered significant. Of the 186 patients with COPD who received lung transplants, 71 (38.2%) received BLTs and 115 (61.8%) received SLTs. There was no significant difference in survival outcomes when looking at patients with single versus BLTs (P = 0.870). There was also no difference in survival between the 2 age groups ≤65 versus > 65 years (P = 0.723). The Cox model itself also did not show a statistically significant improvement in survival outcomes (P = 0.126). Lung transplant outcomes in patients with end-stage COPD demonstrated non-inferior results in patients with an SLT compared to patients with a BLT. When we compared the age groups, neither transplant type showed superior survival benefits, suggesting there may be some utility in an SLT in younger recipients.

Stage I Lymphoma: Difference in Survival Outcome By Site of Involvement

Background: Less than half of patients with lymphoma present with stage I or II disease and this presentation may be nodal or extranodal. Stage I lymphoma is commonly treated with chemotherapy with or without radiation therapy (RT), however little is known if primary site of involvement and treatment modalities affect survival outcome.Patients and Methods: TheSurveillance, Epidemiology and End Results (SEER) database was used to evaluate survival outcomes among adult (≥18 yrs) patients diagnosed with stage I lymphoma between 1998 and 2014. We excluded histologic subtypes that develop in extranodal sites such as cutaneous T-cell lymphoma, enteropathy-associated T-cell lymphoma, hepatospenic T-cell lymphoma and extranodal NK-cell lymphoma. We also excluded central nervous system and testicular lymphoma. Overall survival (OS) was calculated from diagnosis to death from any cause using the Kaplan-Meier method. Differences in the survival function between groups were analyzed using the log-rank test. Cox proportional hazards models were used to evaluate associations between patient characteristics and survival.Results: A total of 72095 patients were diagnosed with stage I disease during the study period. The median age of the patients was 66 years (range, 18-104 years). After excluding diseases as described above, diffuse large B-cell lymphoma (DLBCL) was the most common histology (N=24,574), followed by follicular lymphoma (FL, N=13,061), marginal zone lymphoma (MZL, N=9,893), Hodgkin lymphoma (HL, N=5,325) and peripheral T-cell lymphoma (PTCL, with PTCL not otherwise specified, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma, N=2,071). HL was excluded from the analysis with few extranodal diseases. With a median follow up of 69 months, the median OS was 104, 179, 165 and 106 months in patients with DLBCL, FL, MZL and PTCL, respectively. Thirty-seven percent of patients received resection of primary tumor. Thirty-nine percent of patients received neither RT (40% of them received surgical resection) nor chemotherapy, 15% of patients received RT alone, 29% of patients received chemotherapy alone and 17% of patients received combined modality therapy (CMT).Hazard ratios (HR) for OS in stage I extranodal disease compared to stage I nodal disease in each histologic subtype are summarized in Table. Skin origin was associated with longer OS in all histologic subtypes. Breast origin was associated with longer survival in DLBCL and FL. Thyroid origin was associated with longer survival in FL and MZL. Stomach origin was associated with shorter survival in DLBCL, FL and PTCL but not in MZL. Small intestine origin was associated with longer survival in FL but associated with shorter survival in PTCL. Bone origin was associated with shorter survival in FL and PTCL. The difference in HR for site of involvement among histologic subtype is significant; overall, compared to nodal stage I disease, extranodal stage I disease was associated with longer survival in MZL but associated with shorter survival in PTCL.CMT was significantly associated with longer survival in DLBCL while RT alone showed similar survival outcome in FL, MZL and PTCL (Figure). Local control by surgical resection was also associated with significantly longer survival in all histologic subtypes; HR for surgical resection was 0.81 (p<0.001) in DLBCL, 0.83 (p<0.001) in FL, 0.87 (p=0.002) in MZL and 0.85 (p=0.033) in PTCL.Summary: There was a significant difference in survival outcome in stage I lymphoma by site of involvement. RT showed significant impact in survival outcome for patients with stage I FL, MZL and PTCL. [Display omitted] DisclosuresFanale:AMGEN: Membership on an entity's Board of Directors or advisory committees; GENENTECH: Research Funding; MOLECULAR TEMPLATES: Research Funding; TAKEDA: Honoraria, Research Funding; SEATTLE GENETICS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MERCK: Membership on an entity's Board of Directors or advisory committees, Research Funding; ONYX: Research Funding; ADC THERAPEUTICS: Research Funding; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Westin:Apotex: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Nastoupil:Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Karus Therapeutics: Research Funding; TG Therapeutics: Honoraria, Research Funding; Gilead: Honoraria. Neelapu:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Poseida Therapeutics, Inc: Research Funding; Cellectis Inc.: Research Funding; Karus: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Machine Learning and Radiomics Applications in Esophageal Cancers Using Non-Invasive Imaging Methods—A Critical Review of Literature

Simple SummaryNon-invasive imaging modalities are commonly used in clinical practice. Recently, the application of machine learning (ML) techniques has provided a new scope for more detailed imaging analysis in esophageal cancer (EC) patients. Our review aims to explore the recent advances and future perspective of the ML technique in the disease management of EC patients. ML-based investigations can be used for diagnosis, treatment response evaluation, prognostication, and investigation of biological heterogeneity. The key results from the literature have demonstrated the potential of ML techniques, such as radiomic techniques and deep learning networks, to improve the decision-making process for EC patients in clinical practice. Recommendations have been made to improve study design and future applicability.Esophageal cancer (EC) is of public health significance as one of the leading causes of cancer death worldwide. Accurate staging, treatment planning and prognostication in EC patients are of vital importance. Recent advances in machine learning (ML) techniques demonstrate their potential to provide novel quantitative imaging markers in medical imaging. Radiomics approaches that could quantify medical images into high-dimensional data have been shown to improve the imaging-based classification system in characterizing the heterogeneity of primary tumors and lymph nodes in EC patients. In this review, we aim to provide a comprehensive summary of the evidence of the most recent developments in ML application in imaging pertinent to EC patient care. According to the published results, ML models evaluating treatment response and lymph node metastasis achieve reliable predictions, ranging from acceptable to outstanding in their validation groups. Patients stratified by ML models in different risk groups have a significant or borderline significant difference in survival outcomes. Prospective large multi-center studies are suggested to improve the generalizability of ML techniques with standardized imaging protocols and harmonization between different centers.

Surgical Outcomes of Non-Small Cell Lung Cancer in Single-Zone N2 in the Aortopulmonary Zone.

We evaluate the surgical outcome of clinically single-zone N2 lung cancer limited to aortopulmonary zone (AP zone; lymph node #5 or #6). We performed a retrospective analysis of patients with non-small cell lung cancer, in whom mediastinal lymph node metastasis was confined to AP zone. A total of 84 patients who underwent upfront surgery were included in final analysis. Among these patients, pathological nodal outcomes were pN0-1 in 27 patients (32.1%), pN2a in 31 (36.9%), and pN2b in 26 (31.0%). In multivariate analysis, adenocarcinoma (p = 0.005) and staging workup without endobronchial ultrasound-transbronchial needle aspiration (p = 0.002) were independent risk factors for unexpected pN2b. The 5-year overall survival (OS) and disease-free survival (DFS) were 55.9 and 54.4%, respectively. There was no survival difference among patients with pN0-1, pN2a, and pN2b (p = 0.717). In survival analysis, there were no significant risk factors for OS. However, female sex and the ratio of positive lymph nodes to removed lymph nodes were significant risk factors for DFS in multivariate analysis (p = 0.032 and p = 0.009). In this study, cN2a in the AP zone with current diagnostic tool exhibited a relatively high false-positive rate (cN2/pN0-1; 32.1%). However, despite the possibility of pN2b, there were no significant differences in survival outcome according to the pathologic nodal stage.

Plasma pre-treatment T790M relative allelic frequency in patients with advanced EGFR-mutated non-small cell lung cancer predicts treatment response to subsequent-line osimertinib.

BackgroundApproximately half of all patients with advanced EGFR-mutant NSCLC will develop acquired resistance to first or second-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) with a T790M mutation. In the AURA3 trial, patients with a T790M mutation had a response rate of 71% to osimertinib, a third-generation EGFR-TKI. The response to osimertinib may vary according to plasma T790M mutation frequency. Our aim was to determine the effect of plasma T790M mutation load on treatment response to osimertinib in an Australian multi-institutional cohort.MethodsWe performed a retrospective study on patients treated with osimertinib in the second-line setting and beyond between 2016–2018 from ten centres in Australia, who had T790M mutations detected in tumour or plasma. The primary objective was to investigate if there was a difference in disease control rate (DCR) between patients with high vs. low T790M relative allelic frequency (RAF) as detected in plasma, using a 0.3 RAF cut-off, as determined by ddPCR or BEAMing PCR. Secondary objective was to determine the survival outcomes according to high versus low plasma T790M RAF. Additional analyses were performed to investigate the survival outcome for patients with plasma versus tissue T790M positivity.ResultsA total of 139 patients were included in this study. Patients with higher RAF demonstrated higher DCR (74% vs. 36%, P=0.02), however there was no statistically significant difference in survival outcomes in the two groups. Exploratory analysis showed that patients with tissue T790M+ had improved DCR compared with those with plasma T790M+ (89% vs. 68%, P=0.01) and longer progression free survival (median 15.4 vs. 9.7 months; HR 0.51, 95% CI: 0.34 to 0.77, P=0.003) and overall survival (median not reached, HR 0.51, 95% CI: 0.30 to 0.86, P=0.02). Patients who were tissue T790M+ demonstrated superior survival compared to plasma T790M+ after correcting for confounding variables in a multivariate model.ConclusionsDCR was superior in patients with higher plasma T790M mutation load versus lower plasma T790M mutational load, without significant survival benefit. Plasma T790M RAF is a potential predictive biomarker which should be investigated and validated in larger prospective studies.

Assessment of different induction chemotherapy regimens in locally advanced nasopharyngeal carcinoma: Meta-analysis.

A Bayesian network meta-analysis was performed to compare the efficacy and toxicities among different induction chemotherapy regimens in locally advanced nasopharyngeal carcinoma (LA-NPC). Electronic databases were searched for literature up to September 16, 2019. Two researchers independently selected the articles, evaluated the quality of the literature, and extracted and analyzed the data. There were no significant differences in survival outcomes, mucositis, or gastrointestinal adverse events among the four regimens. The probability of GP being the best induction scheme to improve OS was 43.7%. The completion rate of concurrent chemotherapy with the GP regimen was significantly reduced than the other three regimens. The survival outcomes of the four regimens in LA-NPC were comparable. Considering only OS, GP showed the highest probability of improving the survival of LA-NPC, while it also affected the completion of concurrent chemotherapy.

Tumor subtypes and survival in male breast cancer

Male breast cancer is an uncommon disease, and population-based information regarding prognostic factors is limited. Most cases are hormone receptor (HR) positive; however, the association of tumor subtype with overall survival (OS) and breast cancer-specific survival (BCSS) is unclear. Using SEER data, we identified men with invasive breast cancer between 2010 and 2017 with known HR and HER2 status. We examined tumor subtypes by patient characteristics and performed multivariate Cox proportional hazards analyses to determine the associations of each variable with OS and BCSS. We included 2389 men with a median follow-up of 43months (IQR 19-68). Median age was 66years. Tumor subtype distribution was 84.1% HR+/HER2-, 12.7% HR+/HER2+ , 0.8% HR-/HER2+, and 2.3% triple-negative (TN). In univariate analysis, OS at 5years was 76.5% for HR+/HER2-, 65.1% for HR+/HER2+ , 84.2% for HR-/HER2+, and 48.1% for TN (p < 0.0001). Of all subtypes, TN had the worst BCSS (p < 0.0001). Stage, tumor subtype and race were significantly associated with OS and BCSS in multivariate analysis. Adjusted Cox hazard ratios for OS by tumor subtype with HR+/HER2- as reference were 1.55 for HR+/HER2+ (p = 0.001), 1.1 for HR-/HER2+ (p = 0.888), and 3.59 for TN (p < 0.001). We observed significant differences in survival outcomes by tumor subtype. Poor outcomes among men with HER2+ and TN disease suggest possible under-treatment, aggressive tumor biology, and/or more advanced disease at presentation. Studies to better understand the inferior survival for men with these subtypes are warranted and will likely require international collaboration.

Single Lung Transplantation in Patients under 50: Single Center and UNOS Analysis

<h3>Purpose</h3> The lung transplantation (LTx) community continues to investigate single- (SLT) vs. double-lung transplantation (DLT) to predict optimal long-term survival post-LTx. We investigated the survival in younger patients receiving SLT using the current United Network for Organ Sharing (UNOS) database and our single center results. <h3>Methods</h3> A retrospective analysis of both UNOS and single center databases was performed, investigating patients between ages 18 and 50 who received either a SLT or DLT from August 2005 to March 2020 (n=11156; n=48). Similar patients were matched between the two databases (n=96). Survival outcomes were assessed before and after propensity score matching. P-value <0.05 was considered significant. <h3>Results</h3> In the pre-propensity match, the UNOS patient group who received DLT had better survival outcomes than SLT (p<0.001). This was maintained across the combination of both databases (p=0.002). No survival outcome differences were found in the single center group (p=0.317). In post-propensity matching, both database groups were similar in BMI, sex, ischemic times, transplant type, age, length of stay, lung allocation score, and ethnicity. There was no significant difference in survival outcomes based on transplant type (SLT vs. DLT) in the single center (p=0.482), UNOS group (p=0.270), or across the combination of both (p=0.245). Cox regression analysis across the combination of both databases found that longer ischemic times (HR=1.32; p=0.006) and females (HR=2.13; p=0.027) were associated with poorer survival outcomes. <h3>Conclusion</h3> While debate continues on the validity of SLT vs. DLT continues, transplantation type did not affect long-term survival in any patient group. Upon matching, there was no difference in survival for lung transplant patients based on transplant type. These promising newer results support consideration of the use of SLT, which allows for greater distribution of limited donor organs.

Donor Age, Recipient Age and Transplant Type: How Their Interplay Affects Lung Transplants

Purpose There is a hesitancy to use older donor lungs in lung transplants, and to perform them in older patients. To invalidate the use of donor and recipient age as relative contraindications for lung transplantation, we examined both, and factored in transplant type, then analyzed their effects on survival outcomes using propensity matching. Methods Patients were stratified by recipient age ( Results Using 743 lung transplant patients at our single center over 8 years (Feb-2012 to Mar-2020) in the pre-propensity match, there was a significant difference in survival outcomes for the group: ≥50 donor age ≥70 recipient age group in survival when looking at single vs. double lung transplant (p = 0.038). There were no other statistically significant differences in survival based on donor and recipient age, or transplant type. Post-propensity matching, there was no difference in survival based on the interplay between donor and recipient age, for donor group ≥50 (p = 0.092), for donor group Conclusion While donor and recipient age are undoubtedly important factors to consider during lung transplantation, neither of these independently affects long-term survival. Upon matching, there was no differences in survival for lung transplant patients based on transplant type. Older lungs and older patients can result in reasonable post-transplant outcomes.

Impact of Pulmonary Artery Pressure on Survival Outcome of Single- and Double-Lung Transplantation in Chronic Obstructive Pulmonary Disease Patients

<h3>Purpose</h3> It remains unclear whether double lung transplantation (DLT) or single lung transplantation (SLT) is preferred for end-stage chronic obstructive pulmonary disease (COPD) patients. The purpose of this study is to examine the interplay between patient age and pulmonary artery pressure on survival after SLT vs DLT for COPD. <h3>Methods</h3> We performed a single-center retrospective study of lung transplantations for COPD between February 2012 to March 2020 (n=186). Demographics and clinical parameters were compared between patients based on their pulmonary artery pressure (PAP; PAP<25 mmHg vs PAP≥25 mmHg) and type of transplantation (single vs. double). Additionally, survival based on age (≤65 vs. >65 years old) and PAP were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional-hazards regression was also performed. P-value less 0.05 was considered significant. <h3>Results</h3> Of the 186 COPD patients who received lung transplants, 71 (38.2%) received double-lung transplants and 115 (61.8%) received single-lung transplants. Demographics and clinical parameters between the two PAP groups showed significance in: lung allocation score (p=0.002) and BMI at time of transplant (p<0.001). There was no significant difference in survival outcomes between SLT vs. DLT patients (p=0.870). Patients with elevated pulmonary artery pressures (PAP≥25 mmHg) did not have significantly different survival outcomes from patients with normal pressures (PAP<25 mmHg; p=0.16). There was also no difference in survival between the two age groups, ≤65 vs. >65 years (p=0.723). The Cox model itself, also, did not show a statistically significant improvement in evaluating survival outcomes (p=0.126). <h3>Conclusion</h3> Lung transplantation outcomes in end-stage COPD patients demonstrated non-inferior results with SLT compared to DLT. When patients were differentiated based on PA pressure, adopting SLT or DLT did not show any survival differences.

Investigating real-world treatment sequencing outcomes in advanced pancreatic cancer: A purple translational registry analysis.

386 Background: Current standard combination first line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head trials. Data on optimum treatment sequencing is also lacking. Methods: To assess whether first line (1L) treatment with gemcitabine/nab-paclitaxel (Gem/Nab-P)(SEQ1) or FOLFIRINOX (SEQ2) in the palliative treatment setting impacts survival outcomes, data for patients receiving palliative intent combination chemotherapy between 2016 and May 2020 was extracted from PURPLE, a prospective pancreatic cancer registry enrolling consecutive patients across multiple institutions. Results: Of 637 patients, 180 (28%) who received 1L single agent therapy and/or palliative radiotherapy were excluded. Of the remaining 449 patients, 132 (29%) had locally advanced disease (LA PDAC), 67 had local recurrence (15%), and 250 (56%) had de novo metastatic disease (mPDAC). Patients receiving 1L Gem/Nab-P (n=376, 84%) were older (median 67 vs 59 years, P&lt;0.001), had a higher Charlson Comorbidity Index (CCI) (CCI ≥2: 18% vs 3%, Odds Ratio [OR] 8.0, P=0.002), and poorer performance status (ECOG≥2: 10% vs 1%, OR 8.4, P=0.01) compared to the 1L FOLFIRINOX group (n=73, 16%). 140 (37%) patients receiving 1L Gem/Nab-P (SEQ1) and 32 (44%) patients receiving 1L FOLFIRINOX (SEQ2) received second line (2L) chemotherapy. SEQ1 2L regimens included FOLFIRINOX (n=14), FOLFIRI (n=49), FOLFOX (n=35) and 5FU alone (n=3). SEQ2 2L regimens included Gem/Nab-P (n=19), Gem/5FU (n=4), Gem/Cisplatin (n=1) and gemcitabine alone (n=5). Median progression free survival (mPFS) did not differ between patients receiving 1L Gem/Nab-P vs 1L FOLFIRINOX (5.7 vs 5.1 months, P=0.54); nor did median overall survival (mOS; 11.3 vs 12.3 months, P=0.37). In the subset of patients who went on to receive 2L chemotherapy, mPFS in 2L was shorter for SEQ1 compared to SEQ2 (2.9 vs 5.2 months, Hazard Ratio [HR] 1.3, P=0.03) but mOS did not differ (15.9 vs 17.3 months P=0.91). In the subset with LA PDAC, mPFS in 2L was comparable (2.9 vs 3.3 months, P=0.55) but mOS was significantly longer with SEQ1 (22.5 vs 13.8 months, HR 0.50, P=0.01). In mPDAC, mPFS in 2L was shorter with SEQ1 (2.3 vs 5.6 months, HR 1.64, P=0.03), but mOS did not differ by sequence (13 vs 17 months, P=0.23). Conclusions: There were no significant differences in survival outcomes between 1L choices of chemotherapy, despite patients offered 1L FOLFIRINOX (SEQ2) being younger and fitter. Survival differences observed for LA PDAC versus mPDAC will be further explored. Given the multiple potential confounders, randomised clinical trials are needed to make firmer conclusions regarding the optimal initial treatment for each patient subset.

Surgical approach in early stage cervical cancer: the Asian view point

Objective: To examine the current practice of radical hysterectomy for early-stage cervical cancer in Asia after the Laparoscopic Approach to Cervical Cancer (LACC) trial. Methods: A cross-sectional study was conducted in Asia to examine the prevalence and management of women with early-stage cervical cancer. The study was conducted among gynecologic oncologists at leading hospitals in the Asian Society of Gynecologic Oncology Council members. A systematic literature review was performed to examine the association between survival outcomes and surgical approach after the LACC trial. Results: Seven countries participated voluntarily in the study. The incidence, mortality, and centralization of treatment in early-stage cervical cancer were different among the seven countries. The number of specialized centers per population density in Japan was higher than that in the other countries. Minimally invasive surgery (MIS) approach for cervical cancer was common in Korea (56%) and Hong Kong (80-90%), but not in the other countries (2-20%). In the systematic review, there was a significant difference in survival outcomes between MIS and open surgery (recurrence, hazard ratio 1.83, 95% confidence interval 1.27-2.62). MIS without a uterine manipulator or making a vaginal cuff closure produced similar recurrence rates compared with open surgery (MIS without uterine manipulator vs open-surgery: 10.5% vs 10.1%, and MIS with cuff closure vs open-surgery 7.2% vs 10.1%; all P &gt; 0.05). Conclusion: The prevalence of MIS for early-stage cervical cancer varies across Asian regions after the LACC trial. Surgical methods to avoid tumor spillage may be useful for improving survival.

Abstract PO-221: Racial disparities in breast cancer characteristics and outcomes among Hispanic and White patients

Abstract Background: Therapeutic advances in breast cancer (BC) have led to an improved prognosis. However, significant differences in survival outcomes across diverse ethnicities exist. We aim to investigate the differences in demographics, tumor characteristics (cts) and survival outcomes among Hispanic patients (pts) as compared to Non-Hispanic White (NHW) pts. Methods: BC pts diagnosed between 1975-2016 were identified using the Surveillance, Epidemiology, and End Results (SEER) database, and demographic and clinical cts were analyzed. Cox regression models were used for univariate (UV) and multivariable (MV) analyses to evaluate the associations of race with disease-specific survival (DSS) and overall survival (OS) Results: A total of 806,704 (n=720,144 NHW, n=86,560 Hispanic) pts were analyzed. At the time of diagnosis, Hispanic pts were younger [median age 55 years (yrs) vs. 62 yrs], had a higher stage (III/IV=21.3% vs. 16.3%) and a higher grade (grade III/IV=43.3% vs. 35.3%) as compared to NHW pts (p&amp;lt;0.001). Hispanic pts were more likely to present with triple-negative BC (TNBC) (14.2% vs. 11.1%) and Her-2 receptor + BC (6.7% vs. 4.7%) than NHW pts (p&amp;lt;0.001). Hispanic pts were more likely to live in urban areas (95.6% vs. 87.9%) but had similar access to hospitals with oncology services/million population (4.1 vs 4.6) than NHW pts (p&amp;lt;0.001). Hispanic pts were more likely to be uninsured (4% vs.1.1%) with lower odds of undergoing BC surgery (92.8% vs. 95.4%) than NHW pts (p&amp;lt;0.001). On UV analysis, Hispanic pts had a slightly worse DSS [Hazard Ratio (HR) 1.05, 95% CI 1.03-1.07)], but had a better OS (HR 0.84, 95% CI=0.83-0.85) as compared to NHW pts (p&amp;lt;0.0001). On MV analysis controlling for demographic, tumor acts, and disparities in health care access, no significant differences were noted in DSS (HR 0.98, 95% CI=0.96-0.99) and OS (HR 0.99, 95% CI=0.98-1.01) between both groups. However, in pts age&amp;lt;50 yrs, Hispanic pts had a worse DSS (HR 1.17, 95% CI 1.13, 1.20) and OS (HR 1.16, 95% CI 1.13-1.19) than NHW pts. Additionally, worse DSS but not OS was noted in Hispanic pts with hormone receptor+/HER2- BC, pts who received chemotherapy and or surgery and married pts. Conclusions: Our study highlights that Hispanic BC pts appear to have a more aggressive tumor biology than NHW pts with younger age at onset, higher stage, and predominance of TNBC and Her 2+ BC. Although both ethnicities had similar access to health care services, lack of insurance might be a barrier for adequate health care utilization. Despite differences in disease biology, we observed similar survival rates in Hispanic and NHW pts. Interestingly, in pts age&amp;lt;50 yrs, Hispanic pts had a worse DSS and OS than NHW pts. Our findings suggest that racial disparities in outcomes could be related to differences in tumor biology, social status, treatment, and healthcare utilization patterns, especially in younger pts. Further studies are needed to elucidate the causes of racial disparities especially among the younger pt population and develop strategies to mitigate them. Citation Format: Medhavi Gupta, Rohit Gosain, Maithreyi Sarma, Stuthi Perimbeti, Attwood Kristopher, Wenyan Ji, Shipra Gandhi, Yara Abdou. Racial disparities in breast cancer characteristics and outcomes among Hispanic and White patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-221.

Efficacy and Safety Profile of Proteasome Inhibitor Based Drug Regimens for Treatment of Newly Diagnosed AL Amyloidosis: A Systematic Review

Introduction: Light chain amyloidosis (AL) is a plasma cell disorder associated with detrimental manifestations in multiple organ systems of the body. It is estimated that approximately 1275-3200 new cases occur in the United States annually. Proteasome inhibitors (PI), such as bortezomib, carfilzomib, and ixazomib used for multiple myeloma treatment are also used for the treatment of AL amyloidosis. Our aim in this review is to evaluate the efficacy and safety profile of PI-based regimens for the treatment of newly diagnosed AL Amyloidosis (ND-AL). Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive literature search on PubMed, Cochrane, ClinicalTrials.gov, and Embase on June 23rd, 2020. We were able to identify 901 articles, 325 articles from PubMed, 50 from Cochrane, 23 from Clinical Trials.org, and 253 from Embase. After the screening, we selected 11 published studies (n=436) including 5 phase lll trials, 2 phase I/II trials. Results: Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) with or without Daratumumab (Dara): In a Phase lll trial (ANDEROMADA study), Palldini et al. (2020) studied the efficacy of Dara+ CyBorD vs CyBorD in ND-AL pts (n=28). The addition of Dara to CyBorD showed an improved overall hematological response (ORR) in 96% with complete response (CR) in 54% pts at a median follow up of 17.6 months (Table 1). In a retrospective study by Lim et al. (2017), CyBorD was given to ND-AL pts (n=39) which showed an ORR in 63% with very good partial response (VGPR) in 50% pts. In a retrospective study by Diaz-Pallares et al. (2020), CyBord was given to ND-AL pts (n=34) which showed an ORR in 91% with CR, VGPR, and partial response (PR) in 26%, 26%, and 38% pts, respectively. Progression-free survival (PFS) and overall survival (OS) were reported at 26.7 months and 22 months (P=0.06) respectively (Table 1). Bortezomib, Melphalan, Dexamethasone (BMD): In a phase III trial (EMN-03 study), Kastritis et al. (2020) studied the efficacy of BMD vs MD in ND-AL pts (n=109). Addition of B to MD showed an improved ORR: 81% vs 56% (p=0.001) with CR/VGPR in 53% vs 28% pts. No significant difference in survival outcome was observed. In a phase III trial, Kastritis et al. (2015) studied the efficacy of BMD vs MD in ND-AL pts (n=69). Addition of B to MD showed an improved ORR: 75% vs 53% (p=0.075) with CR/VGPR in 56% vs 42% pts (p=0.277). OS and PFS were also improved in BMD group as compared to control group: 83% vs 72% (p= 0.295) and 61% vs 49% (p=0.079) at 2 years, respectively (Table 1). Bortezomib, Melphalan, Prednisolone (BMP): In a retrospective study by Lee et al. (2014), BMP was given to ND-AL pts (n=19) which showed an ORR in 84% pts with CR, VGPR and PR in 37%, 21% and 26% pts, respectively (Table 1). Induction with B based regimens for ASCT: In a Phase lll trial (HOVON 104), Minnema et al. (2019), studied the efficacy of BD induction prior to HDM/ASCT in pts (n=35) with ND-AL. At 6 months, BD induction prior to HDM/ASCT vs No BD Induction prior to HDM/ASCT showed an ORR: 80% vs 80% with an improved CR: 43% vs 5% and VGPR: 54% vs 51%. In a Phase I/II trial by Sanchorawala et al. (2015), BD induction followed by B-HDM conditioning for ASCT was done in pts (n=27) with ND-AL. ORR at 6 months post ASCT was observed in 100% pts with CR and VGPR in 63% and 37% pts, respectively (Table 1). Induction with B based regimen prior to ASCT vs Upfront ASCT: In a retrospective analysis by Scharman et al. (2017), 53 pts who received ASCT were categorized into 3 groups i.e. Upfront ASCT, induction with B based regimen and induction with other regimens. ND-AL Patients (n=34/53) receiving B based induction vs no induction showed an improved ORR: 94% vs 69% (p=0.04). OS also improved in B based induction as compared to no induction group: 87% vs 77% (p=0.22) at 3 years. PFS at 3 years was 61% vs 69%, respectively (Table 1). Conclusions: PI-based regimens have shown favorable outcomes in the treatment of ND-AL and are effective therapeutic options. The most promising results are observed with CyBorD+Dara. The adverse events associated with PI-based therapy are peripheral neuropathy, anemia, thrombocytopenia, and infections. Further prospective clinical trials are warranted for a broader understanding of the safety and efficacy profile of PI-based regimens and correlation with individual pts characteristics. Table Caption: Table 1: Comparative efficacy and safety of proteasome-inhibitor based drug regimens in ND-AL Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Comparison of Survival Rates of Stainless-Steel Crowns Placed with and without Pulpotomy: A Two-Year Retrospective Study.

Aim This study aimed to retrospectively compare the survival outcomes over two years between teeth with proximal dental caries that were restored with stainless-steel crowns to those that were pulpotomized and then restored with a stainless-steel crown in patients who were rehabilitated under general anesthesia. Participants and Methods. The records of 131 patients aged between two to six years who had stainless-steel crowns placed under general anesthesia and had two-year follow-up were screened. 340 teeth with moderate proximal caries on the radiograph (D2) were included in the study. Of these, 164 teeth were treated with a pulpotomy and stainless-steel crown, while 176 teeth were crowned without a pulpotomy. The type of each tooth was compared using the Chi-squared test and Kaplan–Meier survival analysis, and curves were plotted based on the two-year outcomes. Results Treatment: the sample comprised 59 males (mean age 4.73 years, SD ± 1.4 years) and 72 females (mean age 5.2 years, SD ± 2.0 years). The Kaplan–Meier regression model showed no significant difference in survival outcomes between teeth that had been pulpotomized and those that had not (p = 0.283). Conclusion Within the limitations of the current study, we can conclude that performing a pulpotomy does not influence the survival outcome of mild/moderate proximal caries restored with stainless-steel crowns under general anesthesia.

Do predetermined surgical margins compromise oncological safety in computer-assisted head and neck reconstruction?

Computer assisted head and neck reconstruction has gained popularity over the past few years. In computer assisted surgery (CAS), surgical margins are predetermined in virtual surgery and resection guides are designed to be fitted intra-operatively. However, concerns have been raised regarding the oncological safety of predetermined surgical margins. Therefore, the aim of this study was to compare surgical margins, recurrence and survival outcomes in patients underwent CAS and non-CAS in head and neck reconstruction. We retrospectively reviewed the patients underwent oral and maxillofacial malignancies surgical excision and free flap reconstruction from October 2014 to December 2019 by the same chief surgeon. Patients were divided into two groups depending on whether CAS and predetermined surgical margins were adopted. The primary outcome was surgical resection margin and the secondary outcomes included recurrence and survival. A total of 66 subjects were recruited with 37 in the CAS group and 29 in the non-CAS group. The follow-up rate was 100%. The average follow-up time was 24.5months. No significant difference in resection margin was identified between the groups (p=0.387). Tumor staging, margin status, perineural invasion, lymphovascular invasion and extranodal extension were identified as significant factors influencing survival. Both before and after adjustment for these prognostic factors identified, CAS and non-CAS group showed no significant difference in survival outcome. Predetermined surgical margins do not compromise oncological safety in terms of resection margin, disease recurrence and patient survival.

Efficacy of Thiamine in the Treatment of Postcardiac Arrest Patients: A Randomized Controlled Study.

Background Thiamine administration has been shown to improve survival in a postcardiac arrest animal study. We aimed to evaluate the efficacy of thiamine in comatose out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation. Methods A randomized, double-blinded, placebo-controlled study was conducted. Thirty-seven OHCA patients were randomly assigned to receive either thiamine 100 mg every 8 hours or a placebo. The primary outcome was 28-day all-cause mortality. Results Over the course of 2 years, 37 patients were randomized to either receive thiamine (n = 20) or a placebo (n = 17). The primary outcome was not different between the groups: 10/20 (50%) in the thiamine group vs. 8/17 (47.1%) in the placebo group (P=0.93 by the log-rank test). There were no significant differences in secondary outcomes between the groups (good neurological outcome, lactate level, and S100B level). Conclusions In this study, there were no significant differences in survival outcome. Further studies with a larger population are necessary to confirm these results.

BRCA immunohistochemistry for screening of BRCA mutation in epithelial ovarian cancer patients

To evaluate BRCA1/2 immunohistochemistry (IHC) as a screening test for germline BRCA1/2 in epithelial ovarian cancer (EOC), tumor tissue from 105 EOC patients who had germline BRCA mutations, including 9 BRCA1 mutations, 6 BRCA2 mutations and 90 no BRCA mutations, were studied. Paraffin-embedded tissue blocks were stained for BRCA1 and BRCA2. Tumors were indicated as a loss of BRCA expression when neoplastic nuclear stained less than 10%. Loss of BRCA1 and/or BRCA2 expression was found in 36 patients (34.3%). BRCA1 IHC loss was found in 21 patients (20%) while 24 patients (22.9%) had BRCA2 IHC loss. There were no significant differences in patient characteristics between both groups. Loss of BRCA1 expression had 66.7% sensitivity, 84.3% specificity, 28.6% positive predictive value (PPV), and 96.4% negative predictive value (NPV) for detection of germline BRCA1 mutation. Meanwhile, loss of BRCA2 expression had 50% sensitivity, 78.8% specificity, 12.5% PPV, and 96.3% NPV for detection of germline BRCA2 mutation. There was no significant difference in survival outcomes between both groups.Based on high NPV, BRCA IHC may be useful to exclude patients without BRCA dysfunction if IHC showed intact expression. Only patients with BRCA IHC loss should be offered further genetic testing.

Prognostic role of mismatch repair deficiency (MMR-D) in patients receiving first-line fluoropyrimidine and platinum (FP) doublet chemotherapy for metastatic and locally advanced unresectable gastric cancers (GCs).

4566 Background: Although chemotherapy has been suggested to have the potential to cause a detrimental effect on treatment outcomes of localized GC with MMR-D, it remains unclear whether chemotherapy for metastatic/recurrent/unresectable GC with MMR-D would also adversely affect the survival outcomes. Anti PD-1 antibody (Ab) showed remarkable efficacy in patients with MMR-D and is being actively investigated in combination with cytotoxic chemotherapy. Hence, we aim to evaluate the impact of MMR status on treatment outcomes of advanced GC. Methods: We reviewed our database to identify all patients with HER2 negative, metastatic, recurrent, and locally advanced unresectable GC who received FP doublet chemotherapy from January 2015 to August 2018. For those who had an available tumor tissue, MMR protein expression was assessed by immunohistochemistry (IHC) and correlated with clinical characteristics and treatment outcomes. Results: Out of 895 patients identified from the database, 543 underwent IHC testing for MMR. The median age was 58 years (range, 24 – 86) with male comprising 64.0%. Most patients had initially metastatic disease (n = 382, 70.3%) followed by recurrent (n = 127, 23.3%) and locally advanced unresectable disease (n = 34, 6.3%). MMR-D was found in 4.4% (n = 24) and associated with age ≥ 65 years (50% vs. 29.9%; P = 0.04) and signet ring cell histology (0% vs. 17.7%, P = 0.01). According to our prognostic model (Koo DH et al, 2011), only 4.2% of patients with MMR-D were classified as Poor-risk group (vs. 16.8% of patients with MMR-P, p= 0.10). In the Good-risk group, patients with MMR-D (n = 10) had significantly shorter median progression-free survival (PFS, 6.0 vs. 9.0 months, P = 0.05) and overall survival (OS, 10.1 vs 20.9 months, P = 0.047) compared to those with MMR-P (n = 188), while there was no significant difference in survival outcomes depending on MMR status in the Moderate and Poor-risk groups. In multivariate analysis for OS, MMR status was a significant prognostic factor for OS in Good-risk group GC patients. Conclusions: GC patients with MMR-D had poorer median PFS and OS than those with MMR-P on standard cytotoxic chemotherapy in the Good-risk group. Thus, for Good-risk GC patients with MMR-D, anti PD-1 Ab alone might be considered rather than combining cytotoxic chemotherapy. Further investigation with next-generation sequencing is in process to determine underlying molecular mechanisms and will be presented in ASCO 2020.