Jeremy Gorelick

Cost-effectiveness of CT screening in the National Lung Screening Trial.

BACKGROUND The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST. METHODS We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions. RESULTS As compared with no screening, screening with low-dose CT cost an additional

Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial

1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were

Pretreatment FDG-PET Metrics in Stage III Non–Small Cell Lung Cancer: ACRIN 6668/RTOG 0235

52,000 per life-year gained (95% CI, 34,000 to 106,000) and

The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health

81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses. CONCLUSIONS We estimated that screening for lung cancer with low-dose CT would cost

Utility of preoperative ferumoxtran-10 MRI to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN 6671/GOG 0233

81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

MRI prior to systematic lymphadenectomy in patients with locally advanced cervical cancer.

PURPOSE In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. RESULTS Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. CONCLUSION Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Metabolic Tumor Volume on FDG-PET Predicts Clinical Outcomes Following Chemoradiation Therapy for Locally-Advanced Non-small Cell Lung Cancer: A Secondary Analysis of ECOG-ACRIN 6668 / RTOG 0235

BACKGROUND ACRIN 6668/RTOG 0235 evaluated the prognostic value of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) uptake before and after definitive, concurrent, platinum-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). In this secondary analysis, we evaluate volumetric pretreatment PET measures as predictors of clinical outcomes. METHODS Patients with stage III NSCLC underwent FDG-PET prior to treatment. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic lesions on each scan. For each patient, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA) for all contoured lesions were recorded. Cox proportional hazards regression models were used to evaluate clinical variables and PET metrics as predictors of overall survival (OS) and locoregional control (LRC). Time-dependent covariables were added to the models when necessary to address nonproportional hazards. All statistical tests were two-sided. RESULTS Complete data were available for 214 patients in the OS analysis and 189 subjects in the LRC analysis. In multivariable analysis incorporating clinical and imaging data available prior to treatment, MTV was an independent predictor of OS (HR = 1.04 per 10 cm(3) increase, 95% CI = 1.03 to 1.06, P < .001). High MTV was also associated with increased risk of locoregional failure at baseline (HR = 1.16 per 10 cm(3) increase, 95% CI = 1.08 to 1.23, P < .001) and at six months (HR = 1.05 per 10 cm(3) increase, 95% CI = 1.02 to 1.07, P < .001) but not at 12 months or later time points. CONCLUSION Pretreatment MTV is a predictor of clinical outcomes for NSCLC patients treated with chemoradiotherapy. Quantitative PET measures may serve as stratification factors in clinical trials for this patient population and may help guide novel trial designs.

Correlation of 18F-fluoride PET response to dasatinib in castration-resistant prostate cancer bone metastases with progression-free survival: Preliminary results from ACRIN 6687.

INTRODUCTION Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings. METHODS Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit ≥ 6 months). RESULTS During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with ≥1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up. CONCLUSIONS A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions.

Effects of dasatinib on prostate cancer bone metastases and normal bone measured by 18F-fluoride PET: Preliminary results from ACRIN 6687

Highlights • We evaluated the added value of a USPIO agent (Ferumoxtran-10) to MRI evaluation of LN metastasis in loco-regionally advanced cervical cancer in a multicenter trial.• There was no significant difference in the accuracy of f-10 MRI as compared to standard MRI to detect LN metastasis in advanced cervical cancer (P > 0.05).• F-10 MRI increased sensitivity of MRI to detect metastasis in small (<8 mm) LNs but at the expense of lower specificity.• Mean size of the largest metastatic focus in the LN on pathology was 13.7 mm in the abdomen and 18.8 mm in the pelvis (P = 0.018).

The effects of physician-delivered brief smoking cessation on ACRIN/NLST participants’ smoking behaviors.

5042 Background: Surgical evaluation of lymph node (LN) metastases has served as the gold standard for comparison of imaging modalities in locally advanced cervical cancers. It has been suggested that contemporary techniques such as MRI be relied upon for treatment planning and, specifically, extended-field radiation (EFRT) without pathologic confirmation. METHODS As part of a prospective, multicenter clinical trial conducted by ACRIN/GOG, patients (pts) with histologically confirmed, stage IB2, IIA≥4 cm, or IIB-IVA) cervical carcinoma underwent MRI prior to systematic pelvic (PLN) and abdominal (PALN) lymphadenectomy. LNs ≤ 1 cm were bisected while those > 1 cm were serially sectioned into 5 mm sections and a slide was made from each section. For positive & negative predictive values (PPV & NPV) of PALN on MRI, patients were grouped into those with MRI reports of both (+) PLN & PALN (G1), (+) PLN but (-)PALN (G2), and those with both (-) PLN & PALN (G3). RESULTS 33 pts are included in this analysis. Stage distribution was 12 1B2, 3 2A, 15 2B, 3 3B. 29 were squamous, 3 adeno, and 1 rhabdomyosarcoma. 94 (+) and 659 (-) LNs were removed. (+) LNs were found in the PALN in 12 (36%) and in the PLN in 22 (67%) pts. Two pts had PALN but not PLN metastases. The mean size of the long axis of the largest (+) (N=60) and (-) (N=209) LNs removed did not differ (18.7±9.3 vs. 18.7±11.6 mm; p=0.47). The size of the largest focus of metastasis within a LN ranged from 2-50 mm and was statistically larger in PLN compared to PALN (18 vs. 14 mm; p=0.02). The mean number of LNs counted by pathology was greater than the number reported on MRI (p <0.0001). For the above defined groups, the PPV for PALN in G1 was 0.61 (95% CI 0.48-0.73), the NPV for PALN in G2 was 0.66 (95% CI 0.55-0.75), and the NPV for PALNs in G3 was 0.86 (95% CI 0.76-0.92). CONCLUSIONS PALN metastases are common in locally advanced cervical cancer. The NPV of MRI for PALN among pts reported to have negative PLN & PA LN on MRI is high enough that surgical evaluation and EFRT is not necessary. For all others, the PPV & NPV of MRI is too low to determine the need for EFRT without first performing surgical evaluation. This study was supported by NCI funding to the GOG (grants CA 27469 and CA 37517) and to ACRIN (grants U01 CA079778 and U01 CA080098).