Community poverty level influences time to first pediatric rheumatology appointment in Polyarticular Juvenile Idiopathic Arthritis

Abstract Background The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. Results A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (< 20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p = 0.038) to be seen by a rheumatologist compared to patients with < 20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ. Conclusion In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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Impact of KRAS mutational status on outcomes in patients with pancreatic cancer (PDAC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4142 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4142-4142

Author(s):

Lucy Xiaolu Ma ◽

Gun Ho Jang ◽

Amy Zhang ◽

Robert Edward Denroche ◽

Anna Dodd ◽

...

Keyword(s):

Proportional Hazards ◽

Advanced Disease ◽

Cox Proportional Hazards ◽

Prognostic Impact ◽

First Line ◽

Kras Mutations ◽

Kaplan Meier ◽

Mutational Status ◽

Translational Research Program ◽

The Impact

4142 Background: KRAS mutations (m) (KRASm) are present in over 90% of pancreatic adenocarcinomas (PDAC) with a predominance of G12 substitutions. KRAS wildtype (WT) PDAC relies on alternate oncogenic drivers, and the prognostic impact of these remains unknown. We evaluated alterations in WT PDAC and explored the impact of specific KRASm and WT status on survival. Methods: WGS and RNAseq were performed on 570 patients (pts) ascertained through our translational research program from 2012-2021, of which 443 were included for overall survival (OS) analyses. This included 176 pts with resected and 267 pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657). The latter cohort underwent biopsies prior to treatment with first line gemcitabine-nab-paclitaxel or mFOLFIRINOX as per physician choice. The Kaplan-Meier and Cox proportional hazards methods were used to estimate OS. Results: KRAS WT PDAC (n = 52) represented 9% of pts, and these cases trended to be younger than pts with KRASm (median age 61 vs 65 years p = 0.1). In resected cases, the most common alterations in WT PDAC (n = 23) included GNASm (n = 6) and BRAFm/fusions (n = 5). In advanced WT PDAC (n = 27), alterations in BRAF (n = 11) and ERBB2/3/4 (n = 6) were most prevalent. Oncogenic fusions (NTRK, NRG1, BRAF/RAF, ROS1, others) were identified in 9 pts. The BRAF in-frame deletion p.486_491del represented the most common single variant in WT PDAC, with organoid profiling revealing sensitivity to both 3rd generation BRAF inhibitors and MEK inhibition. In resected PDAC, multivariable analyses documented higher stage (p = 0.043), lack of adjuvant chemotherapy (p < 0.001), and the KRAS G12D variant (p = 0.004) as poor prognostic variables. In advanced disease, neither WT PDAC nor KRAS specific alleles had an impact on prognosis (median OS WT = 8.5 mths, G12D = 8.2, G12V = 10.0, G12R = 12.0, others = 9.2, p = 0.73); the basal-like RNA subtype conferred inferior OS (p < 0.001). A targeted therapeutic approach following first line chemotherapy was undertaken in 10% of pts with advanced PDAC: MMRd (n = 1), homologous recombination deficiency (HRD) (n = 19), KRASG12C (n = 1), CDK4/6 amplification (n = 3), ERBB family alterations (n = 2), BRAF variants (n = 2). OS in this group was superior (14.7 vs 8.8 mths, p = 0.04), mainly driven by HRD-PDAC where KRASm were present in 89%. Conclusions: In our dataset, KRAS G12D is associated with inferior OS in resected PDAC, however KRAS mutational status was not prognostic in advanced disease. This suggests that improved OS in the WT PDAC population can only be achieved if there is accelerated access to targeted drugs for pts.

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The impact of a faculty development program, the Leadership in Academic Medicine Program (LAMP), on self-efficacy, academic promotion and institutional retention

BMC Medical Education ◽

10.1186/s12909-021-02899-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Judy Tung ◽

Musarrat Nahid ◽

Mangala Rajan ◽

Lia Logio

Keyword(s):

Faculty Development ◽

Proportional Hazards ◽

Development Program ◽

Cox Proportional Hazards ◽

Academic Rank ◽

Faculty Development Program ◽

Kaplan Meier ◽

Significant Difference ◽

Institutional Retention ◽

The Impact

Abstract Background Academic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty, and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention. Method Participants from the 2013–2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests. LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards models were used to examine differences. Results There were significant improvements in almost all self-ratings on program surveys (p < 0.05). Greatest improvements were seen in “understand the promotions process” (36% vs. 94%), “comfortable negotiating” (35% vs. 74%), and “time management” (55% vs. 92%). There were no statistically significant differences in improvements by gender, however women faculty rated themselves lower on all pre-program items compared to men. There was significant difference found in time-to-next promotion (p = 0.003) between LAMP participants and controls. Kaplan-Meier analysis demonstrated that LAMP faculty achieved next promotion more often and faster than controls. Cox-proportional-hazards analyses found that LAMP faculty were 61% more likely to be promoted than controls (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.16–2.23, p-value = 0.004). There was significant difference found in time-to-departure (p < 0.0001) with LAMP faculty retained more often and for longer periods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16–0.34, p < 0.0001). Conclusions LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.

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Thromboembolism (TE) in patients (pts) with bladder cancer treated with checkpoint inhibitors (CPIs).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5042 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5042-5042

Author(s):

Iris Yeong- Fung Sheng ◽

Shilpa Gupta ◽

Chandana A. Reddy ◽

Dana E Angelini ◽

Pauline Funchain ◽

...

Keyword(s):

Bladder Cancer ◽

Upper Limb ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Cleveland Clinic ◽

Cox Proportional Hazards ◽

High Risk Population ◽

Kaplan Meier ◽

Tract Disease ◽

The Impact

5042 Background: Most pts with bladder cancer will be treated with immunotherapy. There is concern for increased TE risk with CPIs in this already high risk population. We present the first analysis of the incidence and outcomes of venous (VTE) and arterial (ATE) thromboembolism in pts with bladder cancer treated with CPIs. Methods: Consecutive pts with bladder cancer treated with CPIs at the Cleveland Clinic from 1/2015 to 12/2019 were identified and TE events noted. Overall survival (OS) was estimated using Kaplan-Meier method and the impact of VTE on OS was evaluated using Cox proportional hazards regression. Results: Of 274 pts, 72% were men (median age 73.3 years, 89% white), 82% had pure UC, 92% had lower tract disease, and 67% had a Bajorin score ≥1 (median KPS 90, 61% visceral metastases), 59% had prior systemic therapy (median 1, range 0-4) and 36% had prior TE (14% ATE, 19% VTE, 0.4% both). At CPI initiation, 24% were on antiplatelet therapy, and 15% on therapeutic anticoagulation. CPI (median doses 5, range 8.5-59) included: 40% atezolizumab, 3% nivolumab, 57% pembrolizumab. VTE occurred in 14% (n = 37), including 8% DVT, 4% PE, 2% both. DVT locations were 56% lower limb, 26% upper limb, 15% visceral vein, 4% visceral+upper limb. 2% (n = 5) had ATE (1% CVA, 0.4% visceral, 0.4% left subclavian). 92% of VTE and all ATE occurred within 6 months of CPI initiation. The incidence of TE was 10.9% (95%CI 6.6%—15.1%) at 6 months and 19.8% (95%CI 13.3%-26.4%) at 12 months. 82% of VTE (mean 6 days) and all ATE (mean 5 days) resulted in hospitalization. Multivariate analysis showed TE (HR 2.296, 95%CI 1.451-3.632, p = 0.0004), Bajorin score 1 (HR 1.490, 95%CI 1.036-2.142, p = 0.0315), and Bajorin score 2 (HR 3.50, 95%CI 2.14-5.74, p < 0.0001) were independently associated with worse OS. Conclusions: CPIs in bladder cancer pts are associated with a high TE risk, especially within six months of initiation. TE is associated with worsened survival. Further investigation into the risk factors for CPI-associated TE is needed to identify if benefits exist from thromboprophylaxis.

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P109 Impact of ethnicity on colorectal cancer incidence in a cohort of colitis-associated dysplasia patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.236 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S201-S202

Author(s):

M Kabir ◽

K Curtius ◽

P Kalia ◽

I Al Bakir ◽

C H R Choi ◽

...

Keyword(s):

Colorectal Cancer ◽

Racial Differences ◽

Proportional Hazards ◽

Hazard Analysis ◽

Cox Proportional Hazards ◽

Time Interval ◽

Low Grade ◽

Kaplan Meier ◽

The Impact

Abstract Background Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC). Methods We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models. Results 408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period. Conclusion In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.

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Impact of Prior Cancer History on Outcomes in Thymoma

10.21203/rs.3.rs-41041/v2 ◽

2020 ◽

Author(s):

Shilong Wu ◽

Mengyang Liu ◽

Weixue Cui ◽

Guilin Peng ◽

Jianxing He

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer History ◽

Treatment Methods ◽

Hazards Model ◽

Kaplan Meier ◽

The Impact

Abstract Background Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research. Method The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not. Results A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However, adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036). Conclusions Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.

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Implications of neuroendocrine tumor and diabetes mellitus on patient outcomes and care: a matched case–control study

Future Science OA ◽

10.2144/fsoa-2020-0190 ◽

2021 ◽

pp. FSO684

Author(s):

Yael N Kusne ◽

Heidi E Kosiorek ◽

Matthew R Buras ◽

Patricia M Verona ◽

Kyle E Coppola ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glycemic Control ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Matched Case ◽

After Cancer ◽

The Impact ◽

Matched Case Control Study ◽

Control Study

Aim: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control. Patients & methods: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005–2017), and survival compared (Kaplan–Meier and Cox proportional hazards). Mixed models compared hemoglobin A1c (HbA1c) and glucose during the year after cancer diagnosis. Results: Three-year overall survival was 72% (95% CI: 60–86%) for DM patients versus 80% (95% CI: 70–92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56–3.16; p = 0.51); mean DM HbA1c, 7.3%. Conclusion: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control.

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Impact of radiotherapy duration on outcomes in patients with esophageal cancer treated with definitive concurrent radiotherapy and chemotherapy on RTOG trials 8501 and 9405.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.119 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 119-119

Author(s):

Christopher Leigh Hallemeier ◽

Jennifer Moughan ◽

Michael G. Haddock ◽

Arnold M. Herskovic ◽

Bruce D. Minsky ◽

...

Keyword(s):

Esophageal Cancer ◽

Proportional Hazards ◽

Negative Impact ◽

Standard Dose ◽

Cox Proportional Hazards ◽

High Dose ◽

Risk Of Death ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

The Impact

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]

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Glucocorticoid receptor (GR) expression in circulating tumor cells (CTCs) to prognosticate overall survival (OS) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with androgen receptor signaling inhibitors (ARSi).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.194 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 194-194 ◽

Cited By ~ 1

Author(s):

David Wise ◽

James Kelvin ◽

Ryon Graf ◽

Nicole A. Schreiber ◽

Brigit McLaughlin ◽

...

Keyword(s):

Protein Expression ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Predictive Biomarker ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Castration Resistant Prostate Cancer ◽

Hazards Model ◽

Kaplan Meier ◽

The Impact

194 Background: Upregulation of GR protein expression in metastatic biopsies from pts with CRPC has previously been shown to correlate with resistance to enzalutamide and has been validated as a therapeutic target in pre-clinical studies. We sought to determine whether upregulated GR protein expression in CTCs from pts with progressing mCRPC predicted clinical outcomes following treatment with enzalutamide (E) or abiraterone (A). Methods: Pre-therapy blood samples from 54 pts with progressing mCRPC were subjected to CTC analysis using the Epic Sciences platform. Samples were examined to identify CK+ (CK+, CD45- cells, with intact nuclei, morph distinct) CTCs for GR protein expression. GR+ CTCs were defined as having expression greater than the 95th percentile of GR expression in the GR negative LNCAP cell line. Kaplan-Meier analysis was used to test the impact of GR+ CTCs on OS following treatment with A or E. A Cox proportional hazards model with CTC number and GR positivity was used in a multivariate analysis. Results: 37 out of 54 pts (69%) had detectable and viable CK+ CTCs. 28 out of 37 pts (76%) had CTCs with upregulated GR staining with a median of 6 GR+/CK+ cells/ml per patient (range 0.7 – 244 cells/ml). The OS of patients with GR+ CTCs treated with ARSi was significantly worse than that of patients without detectable GR+ CTCs (11.4 mo. vs NA, p < 0.01), an effect independent and additive to the presence of viable CTCs, a previously described prognostic biomarker (see Table). Conclusions: GR protein upregulation in CTCs can be detected in a significant percentage of pts with progressing mCRPC and the presence of GR+ CTCs predicts worse OS in response to ARSi. The data supports previously reported pre-clinical data proposing a pathogenic role for GR in mediating resistance to ARSi therapy. Detection of GR in patient CTCs may be a useful predictive biomarker to guide GR-directed therapies. [Table: see text]

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Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis

Scientific Reports ◽

10.1038/s41598-021-93428-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xi Zhang ◽

Long Yu ◽

Jiajie Shi ◽

Sainan Li ◽

Shiwei Yang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Therapy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Antibiotic Administration ◽

Hazards Model ◽

Kaplan Meier ◽

The Impact

AbstractMounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan–Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314–6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016–7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77–17.2, p = 0.003) and OS (HR 7.0395% CI 1.94–25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41–172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39–130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.

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