scholarly journals Long-term Outcomes of Endoscopic Resection Versus Open Surgery for Locally Advanced Sinonasal Malignancies in Combination With Radiotherapy

2021 ◽  
Author(s):  
Qian Liu ◽  
Xiaodong Huang ◽  
Xuesong Chen ◽  
Jianghu Zhang ◽  
Jingbo Wang ◽  
...  
Keyword(s):  
Endoscopic Resection ◽  
Open Surgery ◽  
Proportional Hazards ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Surgery Group ◽  
Sinonasal Malignancies ◽  
Endoscopic Group

Abstract Objective:To compare the long-term oncological outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies.Methods:Data for continuous patients with sinonasal epithelial tumors treated in our center between Jan 1999 and Dec 2016 were retrospectively reviewed. Those who received surgery (endoscopic or open surgery) combined with radiotherapy were identified, and 1:1 matching with propensity scores was performed. The primary endpoints of overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. The local recurrence rate (LRR) was assessed by competing risk analysis.Results:We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS and LRR were 69.9%, 58.6%, and 24.5% in the endoscopic group and 64.6%, 54.4%, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that surgical approach was not associated with lower OS, PFS or LRR. Age, histopathology and stage were independent risk factors for OS.Conclusion:For patients with locally advanced sinonasal carcinoma, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

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.

Exposure-response (E-R) analysis of rilotumumab (R, AMG 102) plus epirubicin/cisplatin/capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric or esophagogastric junction (G/EGJ) cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2535-2535 ◽  
Author(s):  
Min Zhu ◽  
Rui Tang ◽  
Sameer Doshi ◽  
Kelly S. Oliner ◽  
Steven Kathman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Safety Data ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Linear Regression Models ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Covariate Effects

2535 Background: R is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), the only known MET receptor ligand. In a double-blind, placebo-controlled, phase 2 trial of 121 pts with G/EGJ cancer, R (7.5 or 15 mg/kg) + ECX showed trends for improved overall survival (OS) and progression-free survival (PFS) compared to ECX alone (placebo, P). Methods: E-R analyses were performed using pharmacokinetic (PK), biomarker, efficacy, and safety data. A population PK model was used to evaluate covariate effects (eg, demographics, ECX, and MET status) on R PK and predict individual R exposure (trough steady-state Cmin [C]). The effect of C on OS/PFS was evaluated with Kaplan-Meier estimates and Cox proportional hazards models. Covariate effects for OS/PFS were evaluated with multivariate analysis. The relationships between adverse events of interest (AEs), lab values, and C were analyzed with descriptive statistics and linear regression models. Results: R showed linear PKs that were unaffected by ECX or MET levels. Pts who received R + ECX were divided into low C (CL) and high C (CH) groups by the median C (94 µg/mL). Median PFS was 4.2, 4.5, and 6.9 months in the P, CL, and CH groups; median OS was 8.9, 9.5, and 13.3 months. Improved OS/PFS in CH and improved PFS in CH and CL groups (vs P) were seen after adjusting for baseline covariates. Pts with tumors that expressed high MET levels (METHigh: > 50% cells positive) showed greater improvement in OS in the CH vs CL group. No improvement in OS was seen in METLow pts (CH and CL groups) compared to placebo (see Table). No relationship was seen between R exposure and AEs or lab values. Conclusions: Higher R exposure was associated with improved OS/PFS in METHigh pts without increased toxicity, supporting further study of R + ECX in G/EGJ cancer. [Table: see text]

scholarly journals Perioperative Geriatric Assessment as A Predictor of Long-Term Hepatectomy Outcomes in Elderly Patients with Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 842
Author(s):  
Masaki Kaibori ◽  
Hideyuki Matsushima ◽  
Morihiko Ishizaki ◽  
Hisashi Kosaka ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Geriatric Assessment ◽  
Proportional Hazards ◽  
Prognostic Indicator ◽  
Cox Proportional Hazards ◽  
Rate Of Change ◽  
Score Change ◽  
Comorbidity Burden ◽  
Reduction Group

This retrospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for recurrence-free survival (RFS) and overall survival (OS) after hepatectomy in 100 consecutive patients aged ≥70 years with hepatocellular carcinoma. Patients had geriatric assessments of cognition, nutritional and functional statuses, and comorbidity burden, both preoperatively and at six months postoperatively. The rate of change in each score between preoperative and postoperative assessments was calculated by subtracting the preoperative score from the score at six months postoperatively, then dividing by the score at six months postoperatively. Patients with score change ≥0 comprised the maintenance group, while patients with score change <0 comprised the reduction group. The change in Geriatric 8 (G8) score at six months postoperatively was the most significant predictive factor for RFS and OS among the tested geriatric assessments. Five-year RFS rates were 43.4% vs. 6.7% (maintenance vs. reduction group; HR, 0.19; 95%CI, 0.11–0.31; p < 0.001). Five-year OS rates were 73.8% vs. 17.8% (HR, 0.12; 95%CI, 0.06–0.25; p < 0.001). Multivariate Cox proportional hazards analysis showed that perioperative maintenance of G8 score was an independent prognostic indicator for both RFS and OS. Perioperative changes in G8 scores can help forecast postoperative long-term outcomes in these patients.

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Oded Jacobi ◽  
Yosef Landman ◽  
Daniel Reinhorn ◽  
Oded Icht ◽  
Michal Sternschuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Negative Relationship ◽  
Progression Free Survival ◽  
Significant Negative Correlation ◽  
Cox Proportional Hazards ◽  
Diabetic Patients

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ<sup>2</sup> tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

Reduction in Short- and Long-term Pneumonia Rate With Laryngoplasty for Unilateral Vocal Fold Paralysis

2021 ◽  
pp. 019459982110151
Author(s):  
Cheng-Ming Hsu ◽  
Yao-Te Tsai ◽  
Geng-He Chang ◽  
Yao-Hsu Yang ◽  
Tuan-Jen Fang ◽  
...  
Keyword(s):  
Lower Incidence ◽  
Vocal Fold ◽  
Proportional Hazards ◽  
Vocal Fold Paralysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Voice Therapy ◽  
Unilateral Vocal Fold Paralysis ◽  
Short And Long Term

Objective To examine the association of laryngoplasty, voice therapy, and pneumonia rate in patients with unilateral vocal fold paralysis (UVFP). Study Design Population-based retrospective cohort study. Setting Data were collected from the LHID2000 (Longitudinal Health Insurance Database 2000), containing the information of 1 million randomly selected patients in Taiwan. Methods In the LHID2000, we identified 439 patients having new diagnoses of UVFP from 1997 to 2013. We grouped the aforementioned patients according to UVFP treatment and probed the occurrence of pneumonia: 305 patients underwent laryngoplasty or voice therapy, and 134 patients did not undergo treatment. Follow-up procedures were executed for the enrollees until death or December 31, 2013, representing the end of the study period. We assessed the association of UVFP treatment and pneumonia by executing Cox proportional hazards regression. Results The pneumonia cumulative incidence was significantly higher among enrolled patients without treatment than in those receiving treatment ( P < .001). The pneumonia incidence was significantly lower in patients receiving UVFP treatment (hazard ratio, 0.49; 95% CI, 0.27-0.88; P = .018), as validated by the Cox proportional hazards model after adjustment. Patients undergoing laryngoplasty with or without voice therapy had a significantly lower incidence of pneumonia at 6 months and 1, 3, and 5 years, whereas those undergoing voice therapy alone did not. Conclusion Laryngoplasty was associated with a lower incidence of short- and long-term pneumonia in patients with UVFP. Physicians should encourage patients with UVFP at risk of aspiration to receive prompt evaluation as well as treatment.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Inter-pregnancy interval and later pediatric cardiovascular health of the offspring – a population-based cohort study

2020 ◽  
pp. 1-5
Author(s):  
Majdi Imterat ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Gali Pariente
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cardiovascular Morbidity ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Inter Pregnancy Interval

Abstract Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

Differential response rates in early-phase cancer clinical trials (EPCCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3133-3133
Author(s):  
Rozana Abdul Rahman ◽  
Neethu Billy Graham Mariam ◽  
Hitesh Mistry ◽  
Sreeja Aruketty ◽  
Matt Church ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Sustained Response ◽  
Phase Ii Trials ◽  
Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković
Keyword(s):  
Hodgkin Lymphoma ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Relative Dose Intensity ◽  
Cox Proportional Hazards Models ◽  
Stage Disease ◽  
Stage Iv Disease

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

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