Yee C. Ung

Randomized, Double-Blind, Placebo-Controlled Trial of Erythropoietin in Non–Small-Cell Lung Cancer With Disease-Related Anemia

PURPOSE Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC). PATIENTS AND METHODS A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks. RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment. CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.

Positron Emission Tomography-Computed Tomography Compared with Invasive Mediastinal Staging in Non-small Cell Lung Cancer: Results of Mediastinal Staging in the Early Lung Positron Emission Tomography Trial

Introduction: Patients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. 18Fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment. Methods: In this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy. Results: All 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48–85%), and specificity was 94% (95% CI, 88–97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43–80%) and 95% (95% CI, 90–98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure. Conclusions: PET-CT assessment of the mediastinum is associated with a clinically relevant false-positive result. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT.

Positron Emission Tomography with 18Fluorodeoxyglucose in Radiation Treatment Planning for Non-small Cell Lung Cancer: A Systematic Review

Introduction: This article summarizes the available evidence on the role of 18fluorodeoxy-d-glucose positron emission tomography (PET) and PET-computed tomography in radiation treatment (RT) planning for non-small cell lung cancer. Methods: Relevant studies were identified through a systematic review of the medical literature between January 1996 and May 2010. Medline, EMBASE, and the Cochrane databases were searched. Results: Twenty-eight nonrandomized prospective and retrospective studies and one randomized trial reported in abstract form were identified. There were no guidelines, systematic reviews, or meta-analyses found in the search. There are no data available that demonstrate an impact of PET-based RT planning on survival or local recurrence rates. Nineteen studies reported changes in gross tumor volume, and 11 studies reported changes in planning target volume. The limited data suggest that PET in RT planning is more likely to decrease the dose to the esophagus, but the data on the dose to lung tissue are mixed. In two studies that evaluated the effect of PET on total RT dose administered to patients, the RT dose increased by approximately 15 Gy and tumor control probability increased by 8.6% and 17.7% (p = 0.026). In 12 studies, PET detected distant metastases in 8 to 25% of patients and resulted in a change from curative to palliative RT intent in 8 to 41% of patients. Conclusions: The inclusion of PET imaging in the planning process produces modifications in RT planning that may be beneficial. These changes include a change in treatment intent from radical to palliative and substantial modifications of the gross tumor volume and planning target volume. It is not certain that these changes result in better clinical outcomes, but ongoing evaluation of PET for this purpose is warranted.

How equitable is access to treatment for lung cancer patients? A population-based review of treatment practices in Ontario

Aim: Guideline concordance is one of the metrics used by the Cancer Quality Council of Ontario and Cancer Care Ontario to assess the quality of cancer care and to drive quality improvement. Materials & Methods: The rates for lung cancer surgical resection and concordance with the Cancer Care Ontario postoperative adjuvant chemotherapy (AC) guideline were assessed by health region during two time periods (2010–2011 and 2012–2013) according to five equity measures (age, sex, neighborhood income, location of residence and size of immigrant population). Results: Of the patients with stage I/II NSCLC, 52.2% to 63.0% underwent surgical resection in the province of Ontario, Canada; for patients with stage IIIA disease, the rate was 26.4%. The probability of a surgical resection decreased substantially with age; only 26.9% of those with potentially resectable (stage I–IIIA) disease over 80 years underwent surgery. The use of postoperative AC increased modestly over the time of the study but the rate of use varied widely by health region (34.6 to 84.6%). Patients in rural areas were as likely to receive AC as urban dwellers; however, older aged patients (≥65 years) and those from the lowest income neighborhoods were significantly less likely to receive AC. Conclusion: Surgical rates and the use of AC vary by health region in Ontario and by age and level of neighborhood income despite universal access in a publicly funded health care system. The reasons for this variance are unclear but warrant further study. Presented in part at the 15th World Conference on Lung Cancer, Sydney, Australia, 27–30 October 2013