To assess the impact of cell type, age, and gender in addition to pathologic tumor, node, metastasis (TNM) stage in surgically managed stage I-IIIA non-small cell lung cancer (NSCLC) cases from the ...international staging database of the International Association for the Study of Lung Cancer.
From the 67,725 cases of NSCLC submitted to the staging database, 9137 surgically managed cases were selected for which all the following variables were available: pathologic stage, age, gender, and specific histologic cell type. Performance status and smoking history were examined in subsets. Methods used were Cox proportional hazards regression and recursive partitioning and amalgamation (RPA) analyses.
Pathologic TNM stage, age, and gender were all independently prognostic for survival. The bronchioloalveolar carcinoma (BAC) subtype had superior survival over other cell types despite the potential for heterogeneity in this group. Adjusted comparisons revealed a small survival advantage for squamous cell carcinomas over non-BAC adenocarcinoma histology and also over large cell, though the effect appeared to be limited to the male patients. RPA revealed the importance of TNM stage primarily, and age was prognostic within stage groups. Cell type was not found to add prognostic value in the RPA analysis. Prognostic groups were formed based on the RPA output, and the prognostic value of these groupings was validated using the North American Surveillance, Epidemiology, and End Results Registries. Performance status and smoking history were prognostic in the subsets where data were available. Effects of other variable were not influenced by the inclusion of smoking status in regression models.
Age and gender are confirmed as important prognostic factors in surgically resected NSCLC. Cell type is less important, although the small population of cases classified as BAC have a survival advantage over other histologies, and there may be a small survival advantage for squamous cell carcinomas over non-BAC adenocarcinomas. Imbalances between stage, gender, and cell type at presentation may lead to a misleading result with respect to cell type in unadjusted analyses. Pathologic TNM category is the most important prognostic factor in this analysis.
Background Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single-institution studies suggest that volumetric computed tomography (CT) is more accurate but ...labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage), and the prognostic significance of semiautomated volumetric CT. Methods Six institutions electronically submitted to an established multicenter database clinical and pathologic data for patients with MPM who had operations. Institutional radiologists reviewed preoperative CT scans for quality and then submitted by electronic network (AG Mednet, www.agmednet.com ) to the biostatistical center. Two reference radiologists blinded to clinical data performed semiautomated tumor volume calculations using Vitrea Enterprise 6.0 software (Vital Images, Minnetonka, MN) and then submitted readings to the biostatistical center. Study end points included feasibility of the network, interobserver variability for volumetric CT, correlation of tumor volume to pTN stages, and overall survival (OS). Results Of 164 patients, the CT scans for 129 were analyzable and read by reference radiologists. Most tumors were less than 500 cm3 . A small bias was observed between readers because one provided consistently larger measurements than the other (mean difference, 47.9; p = .0027), but for 80%, the absolute difference was 200 cm3 or less. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by three groups with average volumes of 91.2, 245.3, and 511.3 cm3 associated with median OS of 37, 18, and 8 months, respectively. Conclusions For the first time, a multicenter network was established and initial correlations of tumor volume with pTN stages and OS are shown. A larger multicenter international study is planned to confirm the results and refine correlations.
The lack of an official-stage classification system for thymic malignancies is an issue that hampers progress in this rare disease. A collaborative effort by the International Association for the ...Study of Lung Cancer and the International Thymic Malignancies Interest Group is underway to develop proposals for such a system. A database of more than 10,000 cases worldwide has been assembled to provide a solid basis for analysis. This report outlines the structure of the effort and the process that has been designed.
Analysis of the International Association for the Study of Lung Cancer database revealed that for patients with completely resected, node-negative, non–small-cell lung cancer (NSCLC), increasing ...tumor size was associated with worsening survival. This analysis was performed to determine the effect of size on prognosis in patients in the same database but who were treated with radiotherapy or chemoradiotherapy.
Patients were eligible if they had pathologically confirmed NSCLC, no evidence of distant metastases, intended treatment was radical radiotherapy (minimum 50 Gy) or combined chemotherapy and radiotherapy, no surgery, and tumor diameter was available.
Eight hundred and sixty-eight patients were available for analysis. Patient characteristics were: sex (men) 65.3%; median age 64 years (range, 32–88); Eastern Cooperative Oncology Group performance status 0: 55%, 1: 33%, 2 or more: 5%; chemotherapy 74%; no chemotherapy 18%; weight loss less than 5 %: 70%, and more than 5%: 25%. Primary tumor size was categorized according to tumor, node, metastasis 7th edition. On univariate analysis, the following factors were prognostic for survival: age (continuous) (p = 0.0035); performance status of 1 or more (p = 0.0021); weight loss less than 5% (p < 0.0001); chemotherapy (p = 0.0189); and primary tumor size (continuous) (p = 0.0002). Sex and clinical nodal stage were not significant. On multivariate analysis, age and weight loss remained significant factors for survival, as was tumor size less than 3 cm.
In patients treated with radiotherapy with or without chemotherapy, tumor size less than 3 cm was associated with longer survival than larger tumors. Evidence of the effect of size on prognosis above this was weak. Five-year survival of more than 10% was observed in all four size categories.
Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients ...with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification.
Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification.
Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status.
The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging.
Purpose: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation ...induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting.
Methods and Materials: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m
2 i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m
2 (days 1–14, 29–42, and 57–70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m
2 i.v., doxorubicin 50 mg/m
2 i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy.
Results: Among 56 eligible patients, 93% had SWOG performance status 0–1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimun follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary fibrosis (including one Grade 3) and six cases of pneumonitis (including one Grade 3).
Conclusion: Concomitant chemoradiation with oral etoposide as part of a platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is not better than our prior best group-wide experience. The progression-free and overall survival are similar to published trials utilizing short-course i.v. etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent advantage to prolonged exposure to etoposide, and toxicity resulted in an inferior therapeutic index compared to programs with shortened exposure.
Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high‐dose ...therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan‐based tandem autotransplants (median follow‐up, 5 years). Negative consequences for both overall survival (OS) and event‐free survival (EFS) in the presence of any CA were confirmed, especially when detected within 3 months of HDT. In the context of standard prognostic factors (SPF), ‘MM‐MDS’ (MM karyotype that contains, in addition, CA typical of MDS) imparted a poor OS and EFS, after adjusting for any CA and all individual CA. One‐year mortality was also high, especially for the MM‐MDS subgroup with trisomy 8 within a MM signature karyotype (87%vs 34% in its absence, P < 0·001). No patient remained event free 5 years post transplant in the presence of these baseline high‐risk CA. However, certain trisomies (e.g. chromosomes 7 and 9) and del 20 had favourable clinical consequences. The higher risk that is associated with CA compared with SPF justifies routine cytogenetic studies in all patients with MM at diagnosis and whenever additional treatment decisions are considered, such as in planning HDT either for initial response consolidation, at the time of primary unresponsiveness to induction therapy, or at relapse.
PDF
