The impact of quantitative CT-based tumor volumetric features on the outcomes of patients with limited stage small cell lung cancer.
ABSTRACT: INTRODUCTION:Limited stage small cell lung cancer (LS-SCLC) has a poor prognosis. Additional prognostic markers are needed for risk-stratification and treatment intensification. This study compares quantitative CT-based volumetric tumor measurements versus International Association for the Study of Lung Cancer (IASLC) TNM staging to predict outcomes. MATERIALS & METHODS:A cohort of 105 patients diagnosed with LS-SCLC and treated with chemoradiation (CRT) from 2000 to 2013 were analyzed retrospectively. Patients were staged by the Union for International Cancer Control (UICC) TNM Classification, 8th edition. Tumor volumes and diameters were extracted from radiation planning CT imaging. Univariable and multivariable models were used to analyze relationships between CT features and overall survival (OS), locoregional recurrence (LRR), in-field LRR, any progression, and distant metastasis (DM). RESULTS:Median follow-up was 21.3?months. Two-year outcomes were as follows: 38% LRR, 31% in-field LRR, 52% DM, 62% any progression, and 47% OS (median survival 16.5?months). On univariable analysis, UICC T-stage and N-stage were not associated with any clinical outcome. UICC overall stage was only statistically associated with in-field LRR. One imaging feature (3D maximum tumor diameter) was found to be significantly associated with LRR (HR 1.10, p =?0.003), in-field LRR (HR 1.10, p =?0.007), DM (HR 1.10, p =?0.02), any progression (HR 1.10, p =?0.008), and OS (HR 1.10, p =?0.03). On multivariable analysis, this feature remained significantly associated with all outcomes. CONCLUSION:For LS-SCLC, quantitative CT-based volumetric tumor measurements were significantly associated with outcomes after CRT and may be better predictors of outcome than TNM stage.
Project description:BACKGROUND AND PURPOSE:The relationship between tumor-node-metastasis (TNM) stage and patterns of failure in limited-stage small cell lung cancer (LS-SCLC) remains unclear. We hypothesized that TNM stage predicts brain metastasis risk, and could inform the use of prophylactic cranial irradiation. MATERIAL AND METHODS:We reviewed 283 patients with stage I-IIIB SCLC. Competing-risks regression was used to analyze local, distant, and brain failure. Multivariate analysis was used to evaluate the effect of treatment and clinical factors on failure and OS. RESULTS:Patients with stage I or II SCLC (35% of cohort) had significantly better survival and lower risk of distant and brain metastasis, compared with stage III patients. The 5-year cumulative incidence of brain metastasis for stage I/II and III were 12% and 26%, respectively. Stage had no correlation with local failure. On multivariate analysis, stage was independently prognostic for survival, distant metastasis risk, and brain metastasis risk. CONCLUSIONS:TNM staging predicts likelihood of distant metastasis, brain metastasis, and survival in LS-SCLC. This supports the routine use of TNM staging in clinical practice. The lower risk of brain metastasis in stage I and II SCLC suggests that prophylactic cranial irradiation could play a more limited role in treatment of early-stage disease.
Project description:PURPOSE:The eighth edition of the TNM classification of malignant tumors for the first time includes an official staging system for thymic epithelial tumors (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging is critical for the management of TETs, and determining stage accurately from imaging has the potential to improve clinical outcomes. We examine preoperative computed tomography (CT) characteristics of TETs associated with AJCC/UICC pathologic TNM stage. MATERIALS AND METHODS:In this retrospective study, patients were included if they met all the following criteria: (1) diagnosis of TET, (2) had primary curative intent surgery performed at Stanford University, and (3) had available preoperative CT imaging for review. Tumor pathology was staged according to the eighth edition TNM classification. Fifteen CT scan features were examined from each patient case according to the International Thymic Malignancy Interest Group standard report terms in a blinded manner. A Lasso-regularized multivariate model was used to produce a weighted scoring system predictive of pathologic TNM stage. RESULTS:Examining the 54 patients included, the following CT characteristics were associated with higher pathologic TNM stage when using the following scoring system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score of 6), pleural nodule (score of 2), lobulated contour (score of 2), and heterogeneous internal density (score of 1). Area under the receiver operating characteristic curve was 0.76. CONCLUSIONS:TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.
Project description:Recently, the correlation between the efficacy of platinum-based chemotherapy and ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a lot of investigations have been conducted, whereas conflicting results were presented. Therefore, we performed the present meta-analysis of eligible studies to derive a more precise evaluation of the association between ERCC1 expression and the clinical outcome in SCLC patients receiving platinum-based chemotherapy. A literature search for relevant studies was conducted in the electronic databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC patients treated by platinum-based chemotherapy, and evaluated the relationship between ERCC1 expression and the clinical outcomes [including overall response rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk. A total of nine studies including 1129 patients were included in final analysis. Our analysis indicated that positive/high ERCC1 expression was associated with unfavorable OS (HR?=?1.18, 95%CI?=?1.02-1.37) and PFS (HR?=?1.46, 95%CI?=?1.14-1.88). Subgroup analysis according to disease stage suggested the significant relationship was found in limited stage (LS-SCLC), but not in extensive stage (ES-SCLC). However, no significant association was found between ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a prognostic factor in SCLC patients receiving platinum-based chemotherapy, especially for LS-SCLC.
Project description:Background:Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear. Methods:This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016. Results:According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4-22.2) months in the M1b group vs 7.3 (95% CI 5.7-8.9) months in the M1c group (P<0.001). Multivariate analysis showed that in addition to the known prognostic factors such as performance status, serum albumin, and lactate dehydrogenase, M descriptor was a prognostic factor (HR 1.95, 95% CI 1.38-2.77; P<0.001). Conclusion:The 8th TNM classification has a prognostic value in SCLC. Similarly to NSCLC, treatment approaches should be considered on the basis of the 8th TNM classification, especially stage IVA separate from stage IVB in ED-SCLC patients.
Project description:Results of PET/CT examinations are communicated as text-based reports which are frequently not fully structured. Incomplete or missing staging information can be a significant source of staging and treatment errors. We compared standard text-based reports to a manual full 3D-segmentation-based approach with respect to TNM completeness and processing time. TNM information was extracted retrospectively from 395 reports. Moreover, the RIS time stamps of these reports were analyzed. 2995 lesions using a set of 41 classification labels (TNM features + location) were manually segmented on the corresponding image data. Information content and processing time of reports and segmentations were compared using descriptive statistics and modelling. The TNM/UICC stage was mentioned explicitly in only 6% (n=22) of the text-based reports. In 22% (n=86), information was incomplete, most frequently affecting T stage (19%, n=74), followed by N stage (6%, n=22) and M stage (2%, n=9). Full NSCLC-lesion segmentation required a median time of 13.3?min, while the median of the shortest estimator of the text-based reporting time (R1) was 18.1?min (p=0.01). Tumor stage (UICC I/II: 5.2?min, UICC III/IV: 20.3?min, p < 0.001), lesion size (p < 0.001), and lesion count (n=1: 4.4?min, n=12: 37.2?min, p < 0.001) correlated significantly with the segmentation time, but not with the estimators of text-based reporting time. Numerous text-based reports are lacking staging information. A segmentation-based reporting approach tailored to the staging task improves report quality with manageable processing time and helps to avoid erroneous therapy decisions based on incomplete reports. Furthermore, segmented data may be used for multimedia enhancement and automatization.
Project description:The International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) TNM staging system of nasopharyngeal carcinoma (NPC) is the most important system for survival prediction. The TNM 7th edition UICC/AJCC TNM staging system for NPC was adopted in January 2009, and is now internationally recommended. In comparison with the TNM 6th edition, there were several revisions in the new edition staging system. This study aims to evaluate the prognostic value of the TNM 7th edition for NPC patients in comparison with the TNM 6th edition.Clinical data of 2,629 NPC patients from the Sun Yat-sen University Cancer Center between January 2006 and December 2010 were retrospectively collected and all the patients were restaged according to the criteria of the TNM 6th edition and TNM 7th edition UICC/AJCC staging manual. Univariate and multivariate COX proportional hazards analyses were applied to evaluate the prognostic values between adjacent stage categories of the TNM 6th edition and TNM 7th edition.In comparison with the TNM 6th edition, a significant alteration of the distribution of N categories was observed when the TNM 7th edition was applied (?2?=?20.589, P<0.001), with 119 (119/670, 17.8%) patients up-staging from N0 to N1. With regard to T and overall stage, 37 (37/561, 6.6%) patients were down-staged from T2a with the TNM 6th edition to T1 with the TNM 7th edition, and finally two patients were up-staged to overall stage II (2/118, 1.7%). Moreover, the survival curves were significantly segregated (P<0.05) between T1 and T2 as well as N1 and N2 with the TNM 7th edition.The TNM 7th edition led to a significant alteration in the distribution of N categories and it is superior to the TNM 6th edition in predicting the frequency of overall survival and distant metastasis-free survival.
Project description:BACKGROUND:Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited-stage small cell lung cancer (LS-SCLC). Many patients with LS-SCLC are elderly with comorbidities. METHODS:Individual patient data were collected from 11 phase 2 or 3 trials for LS-SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression-free survival (PFS), the rate of severe adverse events, and off-treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients). RESULTS:Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18-1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03-1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently. CONCLUSIONS:Elderly patients with LS-SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.
Project description:<h4>Background</h4>The aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC).<h4>Methods</h4>184 SCLC patients' primary tumour samples were analyzed for ERCCI, BRCA1, ATP7B, PKM2 TOPOI, TOPOIIA, TOPOIIB and C-MYC mRNA expression. All patients were treated with cisplatin-etoposide.<h4>Results</h4>The patients' median age was 63 years and 120 (65%) had extended stage, 75 (41%) had increased LDH serum levels and 131 (71%) an ECOG performance status was 0-1. Patients with limited stage, whose tumours expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPOI (p=0.008), TOPOIIA (p=0.002) and TOPOIIB (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPOIIA (p=0.021) and TOPOIIB (p=0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high TOPOIIB expression had a negative impact on Os (p=0.035). The favorable expression signature expression signature (low expression of ERCC1, PKM2, TOPOIIA and TOPOIIB) was correlated with significantly better PFS and Os in both LS-SCLC (p<0.001 and p=0.007, respectively) and ES-SCLC (p=0.007 and (p=0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; p=0.002 and HR: 3.14; p=0.021) and Os (HR: 4.35; p=0.001and HR: 3.32; p=0.019) in both limited and extended stage, respectively.<h4>Conclusions</h4>Single gene's expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPOIIA and TOPOIIB may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.
Project description:Background: Considerable modifications have been introduced in the new edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system. Based on the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, this study aimed to compare the 7th and 8th editions of the AJCC/UICC TNM staging system for patients with papillary thyroid microcarcinoma (PTMC) and follicular variant papillary thyroid microcarcinoma (FVPTMC). Methods: A Data from 2004 to 2014 of 39,032 patients registered in the SEER database were included. The 7th and 8th editions of the AJCC/UICC staging system were compared in terms of TNM staging, age cutoff, and clinical staging. Patient survival was evaluated using Kaplan-Meier and multivariable Cox proportional hazards models. The American Thyroid Association (ATA) risk stratification system was integrated with the AJCC/UICC staging system for further investigation. Receiver operating characteristic (ROC) curves, Harrell's C-index, Akaike information criterion (AIC), and the Bayesian information criterion (BIC) were used to assess the models' performances. Results: Revised TNM categories, age cutoff, and clinical staging in the 8th edition resulted in reclassification of the overall stage. Applying the 8th edition, 1,278 stage III and 425 stage IV patients were reclassified as stage I; 950 stage III and 459 stage IV patients were reclassified as stage II; 77 stage IV patients were reclassified as stage III; and only 88 patients remained in stage IV. All patients in stage I, according to the 7th edition, remained in this stage when using the 8th edition. Patients classified into higher stages (III and IV) in the 8th edition showed a worse prognosis than those classified into same stages in the 7th edition. The 8th edition proved to be a better model with higher prognostic efficacy survival (higher AUC and C-index, lower AIC and BIC) than the 7th edition. When integrated with the ATA risk stratification system, the 8th edition still showed better discriminative power for patients in the higher risk group. Conclusion: Based on the SEER database, the 8th edition of the AJCC/UICC staging system has better prognostic efficacy than the 7th edition for patients with PTMC and FVPTMC.
Project description:Purpose: To estimate the outcomes of definitive concurrent chemoradiotherapy (CCRT) for bulky or advanced-stage cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Patients and methods: We enrolled patients who had been diagnosed as having cervical SCC or ADC and received definitive CCRT. A Cox regression analysis was performed to determine the hazard ratio (HR) and 95% confidence intervals (95% CI); independent predictors were stratified or controlled for in the analysis, and the endpoint was all-cause mortality among patients with cervical SCC and ADC who received CCRT. Propensity score matching was performed to create well-balanced groups. Results: we enrolled 3258 patients who had International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IVA cervical cancer without distant metastasis. Among them, 2927 patients with cervical SCC and 331 patients with cervical ADC received definitive CCRT. The results of multivariate Cox regression analysis indicated that ADC, advanced FIGO stage, no intracavitary brachytherapy, old age, earlier year of diagnosis, and higher comorbidity scores were significant independent poor prognostic factors of all-cause mortality in patients with cervical cancer who received definitive CCRT. Patients with cervical ADC who received definitive CCRT had higher all-cause mortality, locoregional recurrence (LRR), and distant metastasis (DM) (adjusted HR [95% CI]: 2.10 [1.79-2.46], 1.79 [1.35-2.37], and 1.97 [1.54-2.53] for all-cause mortality, LRR, and DM, respectively) compared with patients with cervical SCC who received CCRT. Conclusion: Definitive CCRT in patients with cervical ADC resulted in lower overall survival, higher LRR, and higher DM rate compared with patients with cervical SCC.