Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize ...abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel (11Cdocetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of 11Cdocetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs.
► Drug delivery to tumors can be measured using PET and radiolabeled drugs ► The anti-angiogenic drug bevacizumab induces a rapid decline in tumor perfusion ► In NSCLC patients, drug delivery decreased within 5 hr after bevacizumab ► Bevacizumab did not improve delivery of chemotherapy to tumors
Purpose Patients with squamous non-small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and ...safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were randomly assigned (1:1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population.
The current Lung Cancer Stage Classification system is the seventh edition, which took effect in January 2010. This article reviews the definitions for the TNM descriptors and the stage grouping in ...this system.
For more than 50 years, small cell lung cancer (SCLC) has been staged mainly as either limited or extensive stage disease. Small published series of resected SCLC have suggested that the tumor, node, ...metastases (TNM) pathologic staging correlates with the survival of resected patients. Recent analysis of the 8088 cases of SCLC in the International Association for the Study of Lung Cancer (IASLC) database demonstrated the usefulness of clinical TNM staging in this malignancy. The IASLC data bank contains an unprecedented number of resected SCLC cases with pathologic staging information. This analysis was undertaken to examine the impact of the TNM system on the pathologic staging of SCLC and to assess the new IASLC proposals in this subtype of lung cancer.
Using the IASLC database, survival analyses were performed for resected patients with SCLC. Prognostic groups were compared, and the new IASLC TNM proposals were applied to this population and to the Surveillance, Epidemiology, and End Results (SEER) database.
The IASLC database contained 349 cases of resected SCLC where pathologic TNM staging was available. Survival after resection correlated with both T and N category with nodal status having a stronger influence on survival. Stage groupings using the 6th edition of TNM clearly identify patient subgroups with different prognoses. The IASLC proposals for the 7th edition of TNM classification also apply to this population and to the SEER database.
This analysis further strengthens our previous recommendation to use TNM staging for all SCLC cases.
Background Until now, many investigators have focused on describing right ventricular (RV) dysfunction in groups of patients with pulmonary arterial hypertension (PAH), but very few have addressed ...the deterioration of RV function over time. The aim of this study was to investigate time courses of RV geometric changes during the progression of RV failure. Methods Forty-two patients with PAH were selected who underwent right-sided heart catheterization and cardiac MRI at baseline and after 1-year follow-up. Based on the survival after this 1-year run-in period, patients were classified into two groups: survivors (26 patients; subsequent survival of > 4 years) and nonsurvivors (16 patients; subsequent survival of < 4 years). Four-chamber cine imaging was used to quantify RV longitudinal shortening (apex-base distance change), RV transverse shortening (septum-free wall distance change), and RV fractional area change (RVFAC) between end diastole and end systole. Results Longitudinal shortening, transverse shortening, and RVFAC measured at the beginning of the run-in period and 1 year later were significantly higher in subsequent survivors than in nonsurvivors ( P < .05). Longitudinal shortening did not change during the run-in period in either patient group. Transverse shortening and RVFAC did not change during the run-in period in subsequent survivors but did decrease in subsequent nonsurvivors ( P < .05). This decrease was caused by increased leftward septal bowing. Conclusions Progressive RV failure in PAH is associated with a parallel decline in longitudinal and transverse shortening until a floor effect is reached for longitudinal shortening. A further reduction of RV function is due to progressive leftward septal displacement. Because transverse shortening incorporates both free wall and septum movements, this parameter can be used to monitor the decline in RV function in end-stage PAH.
Small cell lung cancer (SCLC) is usually classified using the limited and extensive definition. The tumor, node, metastasis (TNM) classification should also be applicable to SCLC, but it has only ...been reported in small surgical series. The current analysis looks to the impact of the TNM system on the clinical staging of SCLC and of the new International Association for the study of Lung Cancer (IASLC) proposals.
Using the IASLC database, survival analyses were performed for clinically staged patients. Prognostic groups were compared, and the new IASLC TNM proposals were applied to this population and to the Surveillance, Epidemiology, and End Results (SEER) database.
The IASLC database contained 12,620 eligible cases of small cell histology. TNM staging was available for 8088 patients. Survival was directly correlated to both T and N category. Differences were more pronounced in patients without mediastinal or supraclavicular nodal involvement. Stage grouping using the sixth edition of TNM also differentiates survival except between IA and IB. Patients with pleural effusion regardless of the cytology have an intermediate prognosis between limited and extensive disease. The IASLC proposals for the seventh edition of the TNM classification also apply to this series of SCLC and to the SEER database.
TNM staging is recommended for SCLC, and stratification by stage I-III should be incorporated in clinical trials of early-stage disease. Further studies are needed to clarify the impact of pleural effusion and the extent of N3 disease.
The seventh edition of the TNM Classification of Malignant Tumors is due to be published early in 2009. In preparation for this, the International Association for the Study of Lung Cancer established ...its Lung Cancer Staging Project in 1998. The recommendations of this committee for changes to the T, N, and M descriptors have been published. This report contains the proposals for the new stage groupings.
Data were contributed from 46 sources in more than 19 countries. Adequate data were available on 67,725 cases of non-small cell lung cancer treated by all modalities of care between 1990 and 2000. The recommendations for changes to the T, N, and M descriptors were incorporated into TNM subsets. Candidate stage groupings were developed on a training subset and tested in a validation subset.
The suggestions include additional cutoffs for tumor size, with tumors >7 cm moving from T2 to T3; reassigning the category given to additional pulmonary nodules in some locations; and reclassifying pleural effusion as an M descriptor. In addition, it is suggested that T2b N0 M0 cases be moved from stage IB to stage IIA, T2a N1 M0 cases from stage IIB to stage IIA, and T4 N0–1 M0 cases from stage IIIB to stage IIIA.
Such changes, if accepted, will involve a reassessment of existing treatment algorithms. However, they are based on an intensive and validated analysis of the largest database to date. The proposed changes would improve the alignment of TNM stage with prognosis and, in certain subsets, with treatment.
Aims
This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH).
Methods and results
In 64 ...patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan-Meier survival curves, survival was lower in patients with an inframedian SV index ≤ 25 mL/m2, a supramedian RV end-diastolic volume index ≥ 84 mL/m2, and an inframedian LVEDV≤40 mL/m2.
Conclusions
The RV contains prognostic information in IPAH. A large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.
To analyze all nonlymphatic metastatic components (T4 and M1) of the current TNM system of lung cancer, with the objective of providing suggestions for the next edition of the TNM classification for ...lung cancer.
Data on 100,809 patients were submitted to the International Association for the Study of Lung Cancer International Database. Of these, 5592 selected T4M0 and M1 patients fulfilled the inclusion criteria for the analysis. Specific categories of clinically staged T4 (lesions not continuous with the primary tumor) and M1 cases were compared with respect to overall survival using Kaplan–Meier survival estimates and comparisons via Cox regression analysis. Relevant findings were validated internally by geographic area and type of database and were validated externally by the North American Surveillance, Epidemiology and End Results Registries.
Median survival for cT4M0 with malignant pleural effusion was significantly worse than that of other cT4M0 patients (8 months versus 13 months) and was more comparable with M1 cases with metastases to the contralateral lung only (10 months). M1 cases with metastases outside the lung/pleura had a significantly poorer prognosis than those with metastases confined to the lung, with a median survival of 6 months.
Revisions to the TNM classification system for lung cancer should include grouping cases with malignant pleural effusions and cases with nodules in the contralateral lung in the M1a category, and cases with distant metastases should be designated M1b. In addition, cases with nodule(s) in the ipsilateral lung (nonprimary lobe), currently staged M1, should be reclassified as T4M0, in accordance with the recommendations of the T descriptor subcommittee of the IASLC international staging committee.
PDF
