Cost-utility analysis of short- versus long-course palliative radiotherapy in patients with non-small-cell lung cancer.

BACKGROUND: Radiotherapy can effectively palliate the symptoms of poor-prognosis patients with non-small-cell lung cancer. However, controversy remains about whether short-course or more protracted radiotherapy schedules provide better value for the money. We conducted a societal cost-utility analysis of a Dutch multicenter randomized trial with 1-year follow-up that compared the efficacy of radiotherapy schedules consisting of 10 fractions of 3 Gy (10 x 3 Gy) versus two fractions of 8 Gy (2 x 8 Gy) in 297 patients with inoperable stage IIIA/B or stage IV non-small-cell lung cancer. this trial found that the 10 x 3-Gy group had better survival than the 2 x 8-Gy group. METHODS: Lifetime quality-adjusted life-years (QALYs) were estimated using the EuroQol questionnaire. Lifetime societal costs were estimated using a model estimated based on data from cost questionnaires filled out by a subset of patients (n = 56). Differences were analyzed statistically using two-sided nonparametric bootstrapping. RESULTS: Compared with the 2 x 8-Gy group, the 10 x 3-Gy group accrued statistically significantly more QALYs (20.0 versus 13.2 weeks; difference = 6.8 weeks, 95% confidence interval [CI] = 0.1 to 13.5 weeks, P = .05), which was mainly due to the statistically significantly better survival (38.1 versus 27.4 weeks; difference = 10.7 weeks, 95% CI = 0.9 to 20.6 weeks, P = .03) without a statistically significant difference with respect to the average valuation of health (P = .27). Total radiotherapy and radiotherapy-related costs were estimated at 5236 dollars for the 10 x 3-Gy group and 2512 dollars for the 2 x 8-Gy group (difference = 2724 dollars, 95% CI = 2501 dollars to 2947 dollars, P<.001). The 39% increase in life expectancy in the 10 x 3-Gy group as compared with the 2 x 8-Gy group was associated with a 30% increase in survival-related nonradiotherapy costs (11,254 dollars versus 8651 dollars, difference 2602 dollars, 95% CI = -357 dollars to 5562 dollars, P = .09). The cost-utility ratio for the 10 x 3-Gy schedule versus the 2 x 8-Gy schedule was estimated at 40,900 dollars per QALY (95% CI = 19,400 dollars to 1,100,000 dollars per QALY). CONCLUSIONS: In these poor-prognosis non-small-cell lung cancer patients, the estimated cost-utility ratio for the palliative 10 x 3-Gy schedule was acceptable according to current economic standards. However, the additional costs for the protracted schedule were justified not by improved quality of life but by longer survival.

Quality assurance of thoracic radiotherapy in EORTC 08941: a randomised trial of surgery versus thoracic radiotherapy in patients with stage IIIA non-small-cell lung cancer (NSCLC) after response to induction chemotherapy.

The aim of this study was to investigate the improvement of quality of radiotherapy and compliance to the protocol amendment of EORTC study 08941. The radiotherapy-specific data were analysed from 154 patients with stage IIIA-N2 Non-Small-Cell Lung Cancer who were actually irradiated after response to 3 cycles of platinum-based induction chemotherapy. The parameters of quality, assessed in 93 patients before and in 61 after protocol amendment, included: time interval between last chemotherapy course and start of thoracic radiotherapy, the use of a 3-D planning CT, dose and fractionation scheme to the primary tumour, the involved and uninvolved mediastinum, duration of radiotherapy and toxicity. A significant improvement of all quality parameters was noted, except for the overall treatment time, which decreased slightly. Protocol amendment resulted in an improvement of the quality and the compliance of most observed parameters, at the cost of some increase in overall treatment time. The latter reflects logistical problems rather than poor compliance.

Reduction of observer variation using matched CT-PET for lung cancer delineation: a three-dimensional analysis.

PURPOSE: Target delineation using only CT information introduces large geometric uncertainties in radiotherapy for lung cancer. Therefore, a reduction of the delineation variability is needed. The impact of including a matched CT scan with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and adaptation of the delineation protocol and software on target delineation in lung cancer was evaluated in an extensive multi-institutional setting and compared with the delineations using CT only. METHODS AND MATERIALS: The study was separated into two phases. For the first phase, 11 radiation oncologists (observers) delineated the gross tumor volume (GTV), including the pathologic lymph nodes of 22 lung cancer patients (Stages I-IIIB) on CT only. For the second phase (1 year later), the same radiation oncologists delineated the GTV of the same 22 patients on a matched CT-FDG-PET scan using an adapted delineation protocol and software (according to the results of the first phase). All delineated volumes were analyzed in detail. The observer variation was computed in three dimensions by measuring the distance between the median GTV surface and each individual GTV. The variation in distance of all radiation oncologists was expressed as a standard deviation. The observer variation was evaluated for anatomic regions (lung, mediastinum, chest wall, atelectasis, and lymph nodes) and interpretation regions (agreement and disagreement; i.e., >80% vs. <80% of the radiation oncologists delineated the same structure, respectively). All radiation oncologist-computer interactions were recorded and analyzed with a tool called "Big Brother." RESULTS: The overall three-dimensional observer variation was reduced from 1.0 cm (SD) for the first phase (CT only) to 0.4 cm (SD) for the second phase (matched CT-FDG-PET). The largest reduction in the observer variation was seen in the atelectasis region (SD 1.9 cm reduced to 0.5 cm). The mean ratio between the common and encompassing volume was 0.17 and 0.29 for the first and second phases, respectively. For the first phase, the common volume was 0 in 4 patients (i.e., no common point for all GTVs). In the second phase, the common volume was always >0. For all anatomic regions, the interpretation differences among the radiation oncologists were reduced. The amount of disagreement was 45% and 18% for the first and second phase, respectively. Furthermore, the mean delineation time (12 vs. 16 min, p<0.001) and mean number of corrections (25 vs. 39, p<0.001) were reduced in the second phase compared with the first phase. CONCLUSION: For high-precision radiotherapy, the delineation of lung target volumes using only CT introduces too great a variability among radiation oncologists. Implementing matched CT-FDG-PET and adapted delineation protocol and software reduced observer variation in lung cancer delineation significantly with respect to CT only. However, the remaining observer variation was still large compared with other geometric uncertainties (setup variation and organ motion).

Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: a 'Big Brother' evaluation.

BACKGROUND AND PURPOSE: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. PATIENTS AND METHODS: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. RESULTS: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P = 0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm2), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm2), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. CONCLUSIONS: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between observers concerning the delineation style were large. This study led to recommendations on how to improve delineation accuracy by adapting the delineation protocol (guidelines for L/W use) and delineation software (double window with lung and mediastinum L/W settings at the same time, enforced use of coronal and sagittal views) and including FDG-PET information (lymph nodes and atelectasis).

Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer.

PURPOSE: A national multicenter randomized study compared the efficacy of 2 x 8 Gy versus our standard 10 x 3 Gy in patients with inoperable stage IIIA/B (with an Eastern Cooperative Oncology Group score of 3 to 4 and/or substantial weight loss) and stage IV non-small-cell lung cancer. PATIENTS AND METHODS: Between January 1999 and June 2002, 297 patients were eligible and randomized to receive either 10 x 3 Gy or 2 x 8 Gy by external-beam irradiation. The primary end point was a patient-assessed score of treatment effect on seven thoracic symptoms using an adapted Rotterdam Symptom Checklist. Study sample size was determined based on an average total symptom score difference of more than one point over the initial 39 weeks post-treatment. The time course of symptom scores were also evaluated, and other secondary end points were toxicity and survival. RESULTS: Both treatment arms were equally effective, as the average total symptom score over the initial 39 weeks did not differ. However, the pattern in time of these scores differed significantly (P < .001). Palliation in the 10 x 3-Gy arm was more prolonged (until week 22) with less worsening symptoms than in 2 x 8-Gy. Survival in the 10 x 3-Gy arm was significantly (P = .03) better than in the 2 x 8-Gy arm with 1-year survival of 19.6% (95%CI, 14.1% to 27.3%) v 10.9% (95%CI, 6.9% to 17.3%). CONCLUSION: The 10 x 3-Gy radiotherapy schedule is preferred over the 2 x 8-Gy schedule for palliative treatment, as it improves survival and results in a longer duration of the palliative response.

Hypofractionated external beam radiotherapy as retreatment for symptomatic non-small-cell lung carcinoma: an effective treatment?

PURPOSE: To evaluate prospectively the efficacy, toxicity, and duration of the palliative effect of retreatment with external beam radiotherapy in symptomatic patients with recurrent non-small-cell lung cancer. METHODS AND MATERIALS: Twenty-eight symptomatic patients with local recurrence of non-small-cell lung cancer underwent repeated treatment after previous radiotherapy (equivalent dose, 46-60 Gy). Reirradiation consisted of two fractions of 8 Gy on Days 1 and 8 with two opposed beams using 6-18-MV photon beams at the site of pulmonary recurrence. The physician scored symptom resolution. RESULTS: Relief of hemoptysis and superior vena cava syndrome could be obtained in all assessable cases (100%). Treatment was less effective for coughing (67%) and dyspnea (35%). The overall median duration of this palliative effect was 4 months. Palliation in almost all patients lasted more than one-half of their remaining life span. The Karnofsky performance score improved in 45% of assessable cases. One patient had Grade 2 esophagitis. Complications consisted of tumor-related fatal hemoptysis in 5 patients (17%) and 1 death from bronchoesophageal fistula (4%). CONCLUSION: External beam hypofractionated reirradiation can be effective as a palliative treatment for local complaints in non-small-cell lung cancer. The complication rate of reirradiation was acceptably low.