Browsing by Author "Wang, Xiaofei"
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Item Open Access Associations between body mass index, weight loss and overall survival in patients with advanced lung cancer.(Journal of cachexia, sarcopenia and muscle, 2022-12) Oswalt, Cameron; Liu, Yingzhou; Pang, Herbert; Le-Rademacher, Jennifer; Wang, Xiaofei; Crawford, JeffreyBackground
Weight loss (WL) has been associated with shorter survival in patients with advanced cancer, while obesity has been associated with longer survival. Integrating body mass index (BMI) and WL provides a powerful prognostic tool but has not been well-studied in lung cancer patients, particularly in the setting of clinical trials.Methods
We analysed patient data (n = 10 128) from 63 National Cancer Institute sponsored advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) trials. Risk matrices were created using BMI and WL percentage, which were divided into 'grades' based on median survival. Relationships between survival, BMI and WL percentage were examined using Kaplan-Meier estimators and Cox proportional hazards (PH) models with restricted cubic splines.Results
For NSCLC, a twofold difference was noted in median survival between the BMI > 28 and WL ≤ 5% group (13.5 months) compared with the BMI < 20 and WL > 5% group (6.6 months). These associations were less pronounced in SCLC. Kaplan-Meier curves showed significant survival differences between grades for both NSCLC and SCLC (log-rank, P < 0.0001). In Stage IV NSCLC, Cox PH analyses with restricted cubic splines demonstrated significant associations between BMI and survival in both WL ≤ 5% (P = 0.0004) and >5% (P = 0.0129) groups, as well as in WL > 5% in Stage III (P = 0.0306). In SCLC, these relationships were more complex.Conclusions
BMI and WL have strong associations with overall survival in patients with advanced lung cancer, with a greater impact seen in NSCLC compared with SCLC. The integration of a BMI/WL grading scale may provide additional prognostic information and should be included in the evaluation of therapeutic interventions in future clinical trials in advanced lung cancer.Item Open Access Characteristics of toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced non-small cell lung cancer: a pooled analysis based on individual patient data of CALGB/Alliance trials.(Translational cancer research, 2022-10) Yang, Lexie Zidanyue; He, Qihua; Zhang, Jianrong; Ganti, Apar Kishor; Stinchcombe, Thomas E; Pang, Herbert; Wang, XiaofeiBackground
For patients with locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy is the foundational treatment strategy. Adding induction chemotherapy did not achieve a superior efficacy but increased the burden from toxicity. Accordingly, we retrospectively investigated the toxicity patterns through pooling individual patient data of the Cancer and Leukemia Group B (CALGB)/Alliance trials.Methods
We included a total of 637 patients with unresectable stage III NSCLC who received induction chemotherapy with a platinum doublet and concurrent chemoradiotherapy and experienced at least one adverse event (AE) in CALGB 9130, 9431, 9534, 30105, 30106 and 39801 trials. The following toxicity occurrence patterns were evaluated: top 10 most frequent AEs, AE distribution by grade, rate of treatment discontinuation due to AEs, associations of AE occurrence with patient characteristics and treatment phase, the time to the first grade ≥3 AE occurrence and its associations with patient characteristics and treatment phase.Results
The occurrence of AEs was the main reason accounting for treatment discontinuation (60 of 637 among all patients; 18 of 112 patients who experienced the induction phase only; 42 of 525 patients who experienced both phases). All patients experienced a total of 11,786 AEs (grade ≥3: 1,049 of 5,538 in induction phase, 1,382 of 6,248 in concurrent phase). Lymphocytes and white blood count were of top 3 grade ≥3 AEs that patients experienced the most in the either phase. Multivariable analysis found AE occurrence was associated with age ≥65 [any grade: odds ratio (OR) =1.44, 95% confidence interval (CI): 1.12-1.86] and the concurrent phase (grade ≥3: OR =1.86, 95% CI: 1.41-2.47; any grade: OR =1.47, 95% CI: 1.19-1.81). Patients in the concurrent phase were more likely and earlier to develop grade ≥3 AEs than those in the induction phase [hazard ratio (HR) =4.37, 95% CI: 2.52-7.59].Conclusions
The report provides a better understanding regarding the toxicity occurrence patterns in concurrent chemoradiotherapy after induction chemotherapy.Item Open Access Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.(BMC pulmonary medicine, 2019-11) Giovacchini, Coral X; Kessler, Edward R; Merrick, Christopher M; Gao, Junheng; Wang, Xiaofei; Wahidi, Momen M; Shofer, Scott L; Cheng, George Z; Mahmood, KamranBACKGROUND:Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS:We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS:During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS:Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.Item Open Access Endpoint surrogacy in oncology Phase 3 randomised controlled trials.(British journal of cancer, 2020-08) Zhang, Jianrong; Pilar, Meagan R; Wang, Xiaofei; Liu, Jingxia; Pang, Herbert; Brownson, Ross C; Colditz, Graham A; Liang, Wenhua; He, JianxingEndpoint surrogacy is an important concept in oncology trials. Using a surrogate endpoint like progression-free survival as the primary endpoint-instead of overall survival-would lead to a potential faster drug approval and therefore more cancer patients with an earlier opportunity to receive the newly approved drugs.Item Open Access Impact of Esophageal Motion on Dosimetry and Toxicity With Thoracic Radiation Therapy.(Technology in cancer research & treatment, 2019-01) Gao, Hao; Kelsey, Chris R; Boyle, John; Xie, Tianyi; Catalano, Suzanne; Wang, Xiaofei; Yin, Fang-FangPURPOSE:To investigate the impact of intra- and inter-fractional esophageal motion on dosimetry and observed toxicity in a phase I dose escalation study of accelerated radiotherapy with concurrent chemotherapy for locally advanced lung cancer. METHODS AND MATERIALS:Patients underwent computed tomography imaging for radiotherapy treatment planning (CT1 and 4DCT1) and at 2 weeks (CT2 and 4DCT2) and 5 weeks (CT3 and 4DCT3) after initiating treatment. Each computed tomography scan consisted of 10-phase 4DCTs in addition to a static free-breathing or breath-hold computed tomography. The esophagus was independently contoured on all computed tomographies and 4DCTs. Both CT2 and CT3 were rigidly registered with CT1 and doses were recalculated using the original intensity-modulated radiation therapy plan based on CT1 to assess the impact of interfractional motion on esophageal dosimetry. Similarly, 4DCT1 data sets were rigidly registered with CT1 to assess the impact of intrafractional motion. The motion was characterized based on the statistical analysis of slice-by-slice center shifts (after registration) for the upper, middle, and lower esophageal regions, respectively. For the dosimetric analysis, the following quantities were calculated and assessed for correlation with toxicity grade: the percent volumes of esophagus that received at least 20 Gy (V20) and 60 Gy (V60), maximum esophageal dose, equivalent uniform dose, and normal tissue complication probability. RESULTS:The interfractional center shifts were 4.4 ± 1.7 mm, 5.5 ± 2.0 mm and 4.9 ± 2.1 mm for the upper, middle, and lower esophageal regions, respectively, while the intrafractional center shifts were 0.6 ± 0.4 mm, 0.7 ± 0.7 mm, and 0.9 ± 0.7 mm, respectively. The mean V60 (and corresponding normal tissue complication probability) values estimated from the interfractional motion analysis were 7.8% (10%), 4.6% (7.5%), 7.5% (8.6%), and 31% (26%) for grade 0, grade 1, grade 2, and grade 3 toxicities, respectively. CONCLUSIONS:Interfractional esophageal motion is significantly larger than intrafractional motion. The mean values of V60 and corresponding normal tissue complication probability, incorporating interfractional esophageal motion, correlated positively with esophageal toxicity grade.Item Open Access Radiomics analysis using stability selection supervised component analysis for right-censored survival data.(Computers in biology and medicine, 2020-09) Yan, Kang K; Wang, Xiaofei; Lam, Wendy WT; Vardhanabhuti, Varut; Lee, Anne WM; Pang, Herbert HRadiomics is a newly emerging field that involves the extraction of massive quantitative features from biomedical images by using data-characterization algorithms. Distinctive imaging features identified from biomedical images can be used for prognosis and therapeutic response prediction, and they can provide a noninvasive approach for personalized therapy. So far, many of the published radiomics studies utilize existing out of the box algorithms to identify the prognostic markers from biomedical images that are not specific to radiomics data. To better utilize biomedical images, we propose a novel machine learning approach, stability selection supervised principal component analysis (SSSuperPCA) that identifies stable features from radiomics big data coupled with dimension reduction for right-censored survival outcomes. The proposed approach allows us to identify a set of stable features that are highly associated with the survival outcomes in a simple yet meaningful manner, while controlling the per-family error rate. We evaluate the performance of SSSuperPCA using simulations and real data sets for non-small cell lung cancer and head and neck cancer, and compare it with other machine learning algorithms. The results demonstrate that our method has a competitive edge over other existing methods in identifying the prognostic markers from biomedical imaging data for the prediction of right-censored survival outcomes.Item Open Access Sample size calculation for studies with grouped survival data.(Statistics in medicine, 2018-06-10) Li, Zhiguo; Wang, Xiaofei; Wu, Yuan; Owzar, KourosGrouped survival data arise often in studies where the disease status is assessed at regular visits to clinic. The time to the event of interest can only be determined to be between two adjacent visits or is right censored at one visit. In data analysis, replacing the survival time with the endpoint or midpoint of the grouping interval leads to biased estimators of the effect size in group comparisons. Prentice and Gloeckler developed a maximum likelihood estimator for the proportional hazards model with grouped survival data and the method has been widely applied. Previous work on sample size calculation for designing studies with grouped data is based on either the exponential distribution assumption or the approximation of variance under the alternative with variance under the null. Motivated by studies in HIV trials, cancer trials and in vitro experiments to study drug toxicity, we develop a sample size formula for studies with grouped survival endpoints that use the method of Prentice and Gloeckler for comparing two arms under the proportional hazards assumption. We do not impose any distributional assumptions, nor do we use any approximation of variance of the test statistic. The sample size formula only requires estimates of the hazard ratio and survival probabilities of the event time of interest and the censoring time at the endpoints of the grouping intervals for one of the two arms. The formula is shown to perform well in a simulation study and its application is illustrated in the three motivating examples.Item Open Access The impact of lowering the study design significance threshold to 0.005 on sample size in randomized cancer clinical trials.(Journal of clinical and translational science, 2024-01) Leung, Tiffany H; Ho, James C; Wang, Xiaofei; Lam, Wendy W; Pang, Herbert HThe proposal of improving reproducibility by lowering the significance threshold to 0.005 has been discussed, but the impact on conducting clinical trials has yet to be examined from a study design perspective. The impact on sample size and study duration was investigated using design setups from 125 phase II studies published between 2015 and 2022. The impact was assessed using percent increase in sample size and additional years of accrual with the medians being 110.97% higher and 2.65 years longer respectively. The results indicated that this proposal causes additional financial burdens that reduce the efficiency of conducting clinical trials.Item Open Access Trends and age, sex, and race disparities in time to second primary cancer from 1990 to 2019.(Cancer medicine, 2023-12) Leung, Tiffany H; El Helali, Aya; Wang, Xiaofei; Ho, James C; Pang, HerbertBackground
Despite the growth in primary cancer (PC) survivors, the trends and disparities in this population have yet to be comprehensively examined using competing risk analysis. The objective is to examine trends in time to second primary cancer (SPC) and to characterize age, sex, and racial disparities in time-to-SPC.Methods
A retrospective analysis was conducted based on Surveillance, Epidemiology, and End Results (SEER). Two datasets for this study are (1) the discovery dataset with patients from SEER-8 (1990-2019) and (2) the validation dataset with patients from SEER-17 (2000-2019), excluding those in the discovery dataset. Patients were survivors of lung, colorectal, breast (female only), and prostate PCs.Results
The 5-year SPC cumulative incidences of lung PC increased from 1990 to 2019, with the cumulative incidence ratio being 1.73 (95% confidence intervals [CI], 1.64-1.82; p < 0.001). Age disparities among all PCs remained from 2010 to 2019, and the adjusted HRs (aHRs) of all PCs were above 1.43 when those below 65 were compared with those 65 and above. Sex disparity exists among colorectal and lung PC survivors. Racial disparities existed among non-Hispanic (NH) Black breast PC survivors (aHR: 1.11; 95% CI: 1.07-1.17; p < 0.001). The types of SPC vary according to PC and sex.Conclusions
Over the past three decades, there has been a noticeably shortened time-to-SPC among lung PC survivors. This is likely attributed to the reduced number of lung cancer deaths due to advancements in effective treatments. However, disparities in age, sex, and race still exist, indicating that further effort is needed to close the gap.