Impact of metastasectomy in the multimodality approach for BRAFV600E metastatic colorectal cancer (mCRC): The Mayo Clinic experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15045-e15045
Author(s):  
Benny Johnson ◽  
Zhaohui Jin ◽  
Mark J. Truty ◽  
Rory L. Smoot ◽  
Michael L. Kendrick ◽  
...  
Keyword(s):  
Mayo Clinic ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Molecular Data ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Survival Outcomes ◽  
Management Approach ◽  
Free Survival

e15045 Background: BRAF V600E mutations are present in 7% of mCRC patients (pts) and portend a poor prognosis. Data guiding initial treatment decisions are limited. This study investigates the management approach and clinical impact of utilizing metastasectomy for pts with BRAF V600E mCRC. Methods: By using prospective clinical and molecular data from Mayo Clinic, pts with BRAF V600E mCRC were analyzed for clinical characteristics, treatment and survival outcomes. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: 164 pts with BRAF V600E mCRC were identified between 6/1999-8/2015. Complete follow up data were available for 52 pts. Median age of 65 years, 61% female, ECOG PS ≤ 1, 71% of pts had right sided tumors and 28% presented with liver limited metastasis. Only 7% (4/52) received FOLFOXIRI/BEV (average of 8 cycles). Peripheral neuropathy, pending BRAF status , and prior progression on FOLFOX, were the most common reasons documented for avoiding FOLFOXIRI/BEV. FOLFOX/BEV was the most common 1st line regimen used (32% of pts). Median overall survival (mOS) for all 52 pts was 25 months (mo) with median progression free survival (PFS) of 9.3 mo, reflecting worse survival when compared to BRAF wild-type control patients treated at Mayo Clinic (249 pts, mOS: 43 mo). With median follow up of 18.3 mo, 21 pts who underwent metastasectomy had improved OS (29.1mo vs. 22.7mo, HR = 0.33; CI: 0.12-0.78; p = 0.01) and PFS (13.6mo vs. 6.2mo, HR = 0.53, CI: 0.28-0.97; p = 0.03) when compared to the non-metastasectomy cohort, respectively. In multivariate analysis, metastasectomy remained statistically significant for improved survival outcomes (HR 0.52; 95% CI 0.07-1.02; p = 0.02). Median relapse-free survival after metastasectomy was 9.7 mo (95% CI, 5.5 mo-19.5 mo). Only 2 pts remain disease free at the time of last follow up, with 1 pt without recurrent disease for greater than 2 years (28.9 mo). Conclusions: The use of multimodality therapy incorporating metastasectomy for BRAF V600E mCRC is a critical component for enhanced survival outcomes.

scholarly journals Progression-Free Survival Prediction in Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy: Machine Learning versus Traditional Statistics

2021 ◽  
Vol 11 (8) ◽  
pp. 787
Author(s):  
Ronald Wihal Oei ◽  
Yingchen Lyu ◽  
Lulu Ye ◽  
Fangfang Kong ◽  
Chengrun Du ◽  
...  
Keyword(s):  
Machine Learning ◽  
Nasopharyngeal Carcinoma ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Brier Score ◽  
Rank Test ◽  
Survival Prediction ◽  
Free Survival ◽  
Log Rank Test

Background: The Cox proportional hazards (CPH) model is the most commonly used statistical method for nasopharyngeal carcinoma (NPC) prognostication. Recently, machine learning (ML) models are increasingly adopted for this purpose. However, only a few studies have compared the performances between CPH and ML models. This study aimed at comparing CPH with two state-of-the-art ML algorithms, namely, conditional survival forest (CSF) and DeepSurv for disease progression prediction in NPC. Methods: From January 2010 to March 2013, 412 eligible NPC patients were reviewed. The entire dataset was split into training cohort and testing cohort in a ratio of 90%:10%. Ten features from patient-related, disease-related, and treatment-related data were used to train the models for progression-free survival (PFS) prediction. The model performance was compared using the concordance index (c-index), Brier score, and log-rank test based on the risk stratification results. Results: DeepSurv (c-index = 0.68, Brier score = 0.13, log-rank test p = 0.02) achieved the best performance compared to CSF (c-index = 0.63, Brier score = 0.14, log-rank test p = 0.38) and CPH (c-index = 0.57, Brier score = 0.15, log-rank test p = 0.81). Conclusions: Both CSF and DeepSurv outperformed CPH in our relatively small dataset. ML-based survival prediction may guide physicians in choosing the most suitable treatment strategy for NPC patients.

scholarly journals Comparison of Phase 3 Ibrutinib Results Versus Standard of Care in Sweden in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1751-1751 ◽  
Author(s):  
Anders Österborg ◽  
Anna Asklid ◽  
Joris Diels ◽  
Johanna Repits ◽  
Frans Söltoft ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Phase 3 ◽  
Free Survival ◽  
Line Of Therapy

Abstract Background Ibrutinib (Ibr), an oral, first-in-class covalent Bruton's tyrosine kinase inhibitor, showed in the Phase 3 RESONATE trial significantly improved progression-free survival (PFS, hazard ratio [HR] =0.22, p<0.001) and overall survival (OS, HR=0.39,p=0.001) compared with ofatumumab (ofa) in patients with previously treated CLL who were not eligible for chemoimmunotherapy (Byrd et al, NEJM 2013). Long-term follow-up data from a single arm Phase 2 study have also demonstrated that patients treated with ibrutinib have long durable responses with a PFS at 2.5 years of 69% (Byrd et al, Blood 2015). While ofatumumab is a licensed comparator and included in treatment guidelines, some Health Technology Assessment (HTA) bodies require comparisons with a wider range of treatments. In the absence of direct head-to-head comparison of single-agent ibrutinib with other frequently used treatments in this patient population, additional comparative evidence against standard of care as observed in clinical practice can provide useful insights on the relative efficacy of ibrutinib. Naïve (unadjusted) comparisons of outcomes from different sources are prone to bias due to confounding, as treatment assignments were not randomly assigned, and populations can vary in important prognostic factors. The objective of this analysis was to compare the relative efficacy of Ibr versus physician's choice in R/R CLL-patients based on patient-level data from RESONATE pooled with an observational cohort, adjusting for confounders using multivariate statistical modelling. Methods Patient-level data from the Phase 3 RESONATE trial (Ibr: n=195; ofa: n=196) were pooled with data from a retrospective observational study conducted in the Stockholm area in Sweden. This retrospective study collected efficacy and safety data from a detailed, in-depth retrospective review of individual patient files from 148 consecutively identified patients with R/R CLL initiated on second or later line treatment between 2002 and 2013 at the four CLL-treating centers in Stockholm, Sweden, with complete follow-up. Longitudinal follow-up in subsequent treatment lines was available for patients in 3rd (n=91), 4th (n=51), 5th (n=29), and 6+ (n=15) line, and as such individual patients could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. A multivariate cox proportional hazards model was developed to compare PFS and OS between treatments, including line of therapy, age, gender, Binet stage, ECOG, and refractory disease as covariates. Adjusted HRs and 95% CIs are presented vs. Ibr. Results Across all treatment lines, fludarabine-cyclophosphamide (FC) (n=64), chlorambucil (n=59), alemtuzumab (n=33), FC+rituximab (FCR) (n=30), bendamustine+rituximab (BR) (n=28), and other rituximab-based combination chemotherapy (n=28) were the most frequently used treatments. Line of therapy, age and gender, Binet stage, ECOG performance status, and refractory disease were all independent risk factors for worse outcome on both PFS and OS. The adjusted HR for PFS and OS pooled observational data versus Ibr were 6.80 [4.72;9.80] (p<0.0001) and 2.90 [1.80;4.69] (p<0.0001). HR's for PFS/OS versus most frequent treatment regimens ranged between 2.50/1.82 (FCR) and 14.00/5.34 (anti-CD20 Mab). Baseline adjusted results for the Ofa-arm in RESONATE were comparable for both PFS and OS to outcome data from the consecutive historical cohort, however OS outcomes for Ofa were partly confounded by cross-over to Ibr. Conclusions Comparison of results from the Phase 3 RESONATE study with treatments used as part of previous standard of care in a well-defined cohort of consecutive Swedish patients shows that ibrutinib is superior to physician's choice in patients with relapsed/refractory CLL, suggesting a more than 6 fold improvement in PFS and almost 3 fold improvement in OS. Results were consistent across all different physician chosen treatments and provides further evidence that ibrutinib improves both PFS and OS vs current and prior standard of care regimens. Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression) a. Progression-free survival b. Overall survival Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression). / a. Progression-free survival b. Overall survival Disclosures Österborg: Janssen Cilag: Research Funding. Asklid:Janssen Cilag: Research Funding. Diels:Janssen: Employment. Repits:Janssen Cilag: Employment. Söltoft:Janssen Cilag: Employment. Hansson:Jansse Cilag: Research Funding. Jäger:Janssen Cilag: Research Funding.

Association of morphologic response with progression free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 743-743
Author(s):  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Hideyuki Hayashi ◽  
Hiraku Fukushima ◽  
Takashi Kato ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
First Line ◽  
Free Survival ◽  
Contrast Enhanced Ct ◽  
Morphologic Response

743 Background: It was reported that an optimal morphologic response to preoperative chemotherapy was associated with better overall survival (OS) in patients (pts) with colorectal liver metastases (CLM). We investigated association of morphologic response with progression free survival (PFS) in pts with unresectable CLM from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. Pts with CLM underwent contrast-enhanced CT at the start and every 8-weeks of BV-based chemotherapy. In this analysis, three blinded, independent radiologists evaluated images for morphologic response, based on metastases changing from heterogeneous masses with ill-defined margins into homogeneous hypoattenuating lesions with sharp borders. Association of morphologic response and pts characteristics, RR, and PFS were evaluated. PFS was analyzed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 73 pts with CLM were evaluable for morphologic criteria. Eighteen pts (24.7%) had optimal morphologic response (OR), 31 (42.5%) had incomplete (IR), and 24 (32.9%) had no response (NR). The pts characteristics between those with OR, IR and NR were generally balanced. The median TTF was 7.2 months in NR versus 7.2 months in IR versus 6.8 months in OR (HR (OR/NR) = 0.91, HR (OR/IR) = 0.90; p = 0.93). RR was 77.8% in OR versus 64.5% in IR and 58.3% in NR (p = 0.528). The median PFS was 8.3 months in NR versus 8.5 months in IR versus 9.1 months in OR (HR (OR/NR) = 0.72, HR (OR/IR) = 1.04; p = 0.420). Conclusions: In this analysis, morphologic response might not be a prognostic marker in first-line BV-based chemotherapy in pts with CLM.

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Liping Yang ◽  
Jing Gao ◽  
Yan Zhou ◽  
Zhenchao Tao ◽  
Jian He ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Nasopharyngeal Carcinoma ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Optimal Cutoff ◽  
Free Survival

Introduction: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC). Methods: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis. Results: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor. Conclusion: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.

Association of HLA class 1 homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer (NSCLC) treated with PD-1 inhibitor as first-line therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21519-e21519
Author(s):  
Young Kwang Chae ◽  
Dongyup Lee ◽  
Jonghanne Park ◽  
Horyun Choi ◽  
Gahyun Gim ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Survival Outcomes ◽  
Inverse Association ◽  
First Line ◽  
First Line Therapy

e21519 Background: Homozygosity at human leukocyte antigen class I (HLA-I) locus has been reported to be an unfavorable predictive biomarker of second line or beyond immunotherapy in patients with different types of cancer including melanoma and NSCLC. The linkage between HLA-I homozygosity and survival outcomes in NSCLC patients treated with first-line immunotherapy has not been reported. Methods: Next generation sequencing with HLA genotyping was performed for patients with unresectable stage III or IV NSCLC treated with pembrolizumab plus chemotherapy as first line (N = 25). Progression free survival (PFS) was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built and Log-rank test was used to compare unadjusted survival statistics between the groups. Cox Proportional Hazards were then used to adjust for potential confounders; age, sex, and tumor mutation burden status (TMB, above vs. below median). Results: The median follow up time was 259 days [interquartile range,163 to 350]. Among 25 enrollees, 21 patients (84%) were HLA-I heterozygous and 4 patients (16%) were HLA-I homozygous. Treatment response was not available in 6 patients with HLA-I homozygosity. Among 15 patients with HLA-I homozygosity, 4 patients (26.7%) had partial response (PR), 7 patients (46.7%) had stable disease(SD), and 4 patients (26.7%) had progressive disease (PD). Among 4 patients with HLA-I heterozygosity, 1 patient (25%) had PR, 1 patient (25%) had SD, and 2 patients (50%) had PD. The disease control rates (PR and SD) were 73.4% in heterozygous group and 50% in homozygous group. The heterozygous group showed longer median PFS than the homozygous group (19 vs. 9.4 months, Log-rank p = 0.14). Patients with HLA-I homozygosity demonstrated shorter PFS (HR = 2.35, 95% CI = 0.56-9.9, p = 0.25). Adjusted HRs controlled for age, sex, and TMB were 3.6[0.65-20], 2.3[0.55-9.9] and 1.7[0.34-8.6] respectively. Conclusions: We observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line immunotherapy. Further perspective studies to validate such relationship are warranted.

Stereotactic Radiosurgery for Neurofibromatosis 2—Associated Vestibular Schwannomas

Neurosurgery ◽  
2013 ◽  
Vol 74 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Grant W. Mallory ◽  
Bruce E. Pollock ◽  
Robert L. Foote ◽  
Matthew L. Carlson ◽  
Colin L. Driscoll ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nerve Function ◽  
Facial Nerve Function ◽  
Free Survival ◽  
Kaplan Meier

Abstract BACKGROUND: Management of neurofibromatosis type 2 (NF2)—associated vestibular schwannomas (VSs) remains controversial. Stereotactic radiosurgery (SRS) with conventional dosing is less effective for NF2-related VS compared with sporadic lesions. OBJECTIVE: To evaluate optimal SRS dose parameters for NF2-related VS and to report long-term outcomes. METHODS: A prospective database was reviewed and outcome measures, including radiographic progression, American Academy of Otolaryngology—Head and Neck Surgery hearing class, and facial nerve function, were analyzed. Progression-free survival was estimated with Kaplan-Meier methods. Associations between tumor progression and radiosurgical treatment parameters, tumor volume, and patient age were explored with the use of Cox proportional hazards regression. RESULTS: Between 1990 and 2010, 26 patients with 32 NF2-related VSs underwent SRS. Median marginal dose and tumor volume were 14 Gy and 2.7 cm3, respectively. Twenty-seven tumors (84%) showed no growth (median follow-up, 7.6 years). Kaplan-Meier estimates for 5- and 10-year progression-free survival were 85% and 80%, respectively. Cox proportional hazards demonstrated a significant inverse association between higher marginal doses and tumor progression (hazard ratio, 0.49; 95% confidence interval, 0.17-0.92; P = .02). Audiometric data were available in 30 ears, with 12 having class A/B hearing before SRS. Only 3 maintained serviceable hearing at the last follow-up. Four underwent cochlear implantation. Initially, 3 achieved open-set speech recognition, although only 1 experienced long-term benefit. Facial nerve function remained stable in 50% of cases. CONCLUSION: Higher marginal doses than commonly prescribed for sporadic VS were associated with improved tumor control in patients with NF2. Hearing outcomes were poor even when contemporary reduced marginal doses were used. However, SRS allows an anatomically preserved cochlear nerve and may permit hearing rehabilitation with cochlear implantation. Further consideration should be given to optimum dosing to achieve long-term control while maximizing functional outcomes.

Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1001-1001
Author(s):  
Dennis J. Slamon ◽  
Patrick Neven ◽  
Stephen K. L. Chia ◽  
Guy Heinrich Maria Jerusalem ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Term Survival ◽  
Free Survival ◽  
Hazards Model

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]

scholarly journals Influence of Smoking Habits on the Prevalence of Dental Caries: A Register-Based Cohort Study

2021 ◽  
Author(s):  
Miguel A. de Araújo Nobre ◽  
Ana M. Sezinando ◽  
Inês C. Fernandes ◽  
Andreia C. Araújo
Keyword(s):  
Dental Caries ◽  
Proportional Hazards ◽  
Smoking Habit ◽  
Cox Proportional Hazards ◽  
Radiographic Examination ◽  
Rank Test ◽  
Significance Level ◽  
Cumulative Survival ◽  
Caries Lesions

Abstract Objective The study aimed to evaluate the influence of smoking habit on the prevalence of dental caries lesions in a follow-up study. Materials and Methods A total of 3,675 patients (2,186 females and 1,489 males) with an average age of 51.4 years were included. Outcome measures were the incidence of dental caries defined as incipient noncavitated, microcavitated, or cavitated lesions which had been diagnosed through clinical observation with mouth mirror and probe examination evaluating change of texture, translucency, and color; radiographic examination through bitewing radiographs; or secondary caries through placement of a new restoration during the follow-up of the study. Statistical Analysis Cumulative survival (time elapsed with absence of dental caries) was estimated through the Kaplan–Meier product limit estimator with comparison of survival curves (log-rank test). A multivariable Cox proportional hazards regression model was used to evaluate the effect of smoking on the incidence of dental caries lesions when controlled to age, gender, systemic status, frequency of dental hygiene appointments, and socioeconomic status. The significance level was set at 5%. Results Eight hundred sixty-three patients developed caries (23.5% incidence rate). The cumulative survival estimation was 81.8% and 48% survival rate for nonsmokers and smokers, respectively (p < 0.001), with an average of 13.5 months between the healthy and diseased state diagnosis. Smokers registered a hazard ratio for dental caries lesions of 1.32 (p = 0.001) when controlled for the other variables of interest. Conclusion Within the limitations of this study, it was concluded that smoking habit might be a predictor for dental caries.

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

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.

Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bradley Alexander McGregor ◽  
Daniel M. Geynisman ◽  
Mauricio Burotto ◽  
Camillo Porta ◽  
Cristina Suarez Rodriguez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Objective Response ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Wald Test ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Published Data ◽  
Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

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