Radical Treatment of Non-Small-Cell Lung Cancer Patients with Synchronous Oligometastases Long-Term Results of a Prospective Phase II Trial (Nct01282450)

BackgroundStage IV non–small-cell lung cancer (NSCLC) patients with oligometastases (< 5 metastatic lesions) may experience long-term survival when all macroscopic tumor sites are treated radically, but no prospective data on NSCLCs with synchronous oligometastases are available.MethodsA prospective single-arm phase II trial was conducted. The main inclusion criteria were pathologically proven NSCLC stage IV with less than five metastases at primary diagnosis, amendable for radical local treatment (surgery or radiotherapy). The study is listed in clinicaltrials.gov, number NCT01282450.ResultsForty patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age was 62.1 ± 9.2 years (range, 44–81). Twenty-nine (74%) had local stage III; 17 (44%) brain, seven (18%) bone, and four (10%) adrenal gland metastases. Thirty-five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients received chemotherapy as part of their primary treatment. Median overall survival (OS) was 13.5 months (95% confidence interval 7.6–19.4); 1-, 2-, and 3-year OS was 56.4%, 23.3%, and 17.5%, respectively. Median progression-free survival (PFS) was 12.1 months (95% confidence interval 9.6–14.3); 1-year PFS was 51.3%, and both 2- and 3-year PFS was 13.6%. Only two patients (5%) had a local recurrence. No patient or tumor parameter, including volume and 18F-deoxyglucose uptake was significantly correlated with OS or PFS. The treatment was well tolerated.ConclusionIn this phase II study, long-term PFS was found in a subgroup of NSCLC patients with synchronous oligometastases when treated radically. Identification of this favorable subgroup before therapy is needed

Treatment with curative intent of stage III non-small cell lung cancer patients of 75years: A prospective population-based study

AbstractBackgroundThere is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC).MethodsPatients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included.FindingsOne thousand and two patients with stage III were diagnosed, of which 237 were 75years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6–18.7) versus 5.2months (4.3–6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment.Patients who received only radiotherapy with curative intent had a median OS of 11.1months (95% confidence interval [95% CI] 6.4–15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0months (95% CI 12.2–23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation.InterpretationIn this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates

Long-term survival of stage T4N0-1 and single station IIIA-N2 NSCLC patients treated with definitive chemo-radiotherapy using individualised isotoxic accelerated radiotherapy (INDAR)

Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal station IIIA-N2 are two stage III sub-groups for which the outcome of non-surgical therapy is not well known. We investigated the results of individualised isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting.Analysis of NSCLC patients included in 2 prospective trials (NCT00573040 and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum-based chemotherapy. Overall survival (OS) was updated and calculated from date of diagnosis (Kaplan-Meier). Toxicity was scored following CTCAEv3.0. To allow comparison with other articles the subgroups were also analysed separately for toxicity, progression free and overall survival.83 patients (42 T4N0-1 and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty-seven percent of patients received sequential CRT and 63% received concurrent CRT. At a median follow-up of 48 months the median OS for T4N0-1 patients was 34 months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a median follow-up of 50 months the median OS was 26 months with 2- and 5-year survival rates of 53% and 24%, respectively.Chemo-radiation using INDAR yields promising survival results in patients with single-station stage IIIA-N2 or T4N0-1 NSCLC

Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer

Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 +/- 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P =. 026) and performance status (P = .016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival

¹⁸FDG-PET-CT in the follow-up of non-small cell lung cancer patients after radical radiotherapy with or without chemotherapy:An economic evaluation

Background: The optimal follow-up strategy of non-small cell lung cancer (NSCLC) patients after curative intent therapy is still not established. In a recent prospective study with 100 patients, we showed that a FDG-PET-CT 3 months after radiotherapy (RT) could identify progression amenable for curative treatment in 2% (95% confidence interval (CI): 1-7%) of patients, who were all asymptomatic. Here, we report on the economic evaluation of this study. Patients and methods: A decision-analytic Markov model was developed in which the long-term cost-effectiveness of 3 follow-up strategies was modelled with different imaging methods 3 months after therapy: a PET-CT scan; a chest CT scan; and conventional follow-up with a chest X-ray. A probabilistic sensitivity analysis was performed to account for uncertainty. Because the results of the prospective study indicated that the advantage seems to be confined to asymptomatic patients, we additionally examined a strategy where a PET-CT was applied only in the subgroup of asymptomatic patients. Cost-effectiveness of the different follow-up strategies was expressed in incremental cost-effectiveness ratios (ICERs), calculating the incremental costs per quality adjusted life year (QALY) gained. Results: Both PET-CT- and CT-based follow-up were more costly but also more effective than conventional follow-up. CT-based follow-up was only slightly more effective than conventional follow-up, resulting in an incremental cost-effectiveness ratio (ICER) of € 264.033 per QALY gained. For PET-CT-based follow-up, the ICER was € 69.086 per QALY gained compared to conventional follow-up. The strategy in which a PET-CT was only performed in the asymptomatic subgroup resulted in an ICER of € 42.265 per QALY gained as opposed to conventional follow-up. With this strategy, given a ceiling ratio of € 80.000, PET-CT-based follow-up had the highest probability of being cost-effective (73%). Conclusions: This economic evaluation shows that a PET-CT scan 3 months after (chemo)radiotherapy with curative intent is a potentially cost-effective follow-up method, and is more cost-effective than CT alone. Applying a PET-CT scan only in asymptomatic patients is probably as effective and more cost-effective. It is worthwhile to perform additional research to reduce uncertainty regarding the decision concerning imaging in the follow-up of NSCLC.</p

¹⁸FDG-PET-CT in the follow-up of non-small cell lung cancer patients after radical radiotherapy with or without chemotherapy:An economic evaluation

Background: The optimal follow-up strategy of non-small cell lung cancer (NSCLC) patients after curative intent therapy is still not established. In a recent prospective study with 100 patients, we showed that a FDG-PET-CT 3 months after radiotherapy (RT) could identify progression amenable for curative treatment in 2% (95% confidence interval (CI): 1-7%) of patients, who were all asymptomatic. Here, we report on the economic evaluation of this study. Patients and methods: A decision-analytic Markov model was developed in which the long-term cost-effectiveness of 3 follow-up strategies was modelled with different imaging methods 3 months after therapy: a PET-CT scan; a chest CT scan; and conventional follow-up with a chest X-ray. A probabilistic sensitivity analysis was performed to account for uncertainty. Because the results of the prospective study indicated that the advantage seems to be confined to asymptomatic patients, we additionally examined a strategy where a PET-CT was applied only in the subgroup of asymptomatic patients. Cost-effectiveness of the different follow-up strategies was expressed in incremental cost-effectiveness ratios (ICERs), calculating the incremental costs per quality adjusted life year (QALY) gained. Results: Both PET-CT- and CT-based follow-up were more costly but also more effective than conventional follow-up. CT-based follow-up was only slightly more effective than conventional follow-up, resulting in an incremental cost-effectiveness ratio (ICER) of € 264.033 per QALY gained. For PET-CT-based follow-up, the ICER was € 69.086 per QALY gained compared to conventional follow-up. The strategy in which a PET-CT was only performed in the asymptomatic subgroup resulted in an ICER of € 42.265 per QALY gained as opposed to conventional follow-up. With this strategy, given a ceiling ratio of € 80.000, PET-CT-based follow-up had the highest probability of being cost-effective (73%). Conclusions: This economic evaluation shows that a PET-CT scan 3 months after (chemo)radiotherapy with curative intent is a potentially cost-effective follow-up method, and is more cost-effective than CT alone. Applying a PET-CT scan only in asymptomatic patients is probably as effective and more cost-effective. It is worthwhile to perform additional research to reduce uncertainty regarding the decision concerning imaging in the follow-up of NSCLC.</p