Jan F. Ubbels

Pulmonary oligometastases: Metastasectomy or stereotactic ablative radiotherapy?

BACKGROUND AND PURPOSE Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We analysed consecutive patients referred via a university-hospital based multidisciplinary team. MATERIAL AND METHODS Patients were offered PME as first choice and SABR in case they were considered to be less suitable surgical candidates. Overall survival was the primary endpoint. Secondary endpoints were progression-free-survival, local control of treated metastases, and freedom-from-failure of a local-only treatment strategy without systemic therapy. RESULTS From 2007 until 2010, 110 patients were treated and analysed (PME, n=68; SABR, n=42). Median follow-up time was 43 months (minimally, 25). Estimated overall survival rates at one, three, and five years were 87%, 62%, and 41% for PME, and 98%, 60%, and 49% for SABR, respectively (logrank-test, p=0.43). Local control at two years was 94% for SABR and 90% for PME. Progression-free survival was 17% at three years, but 43% of the patients still had not failed a local-only treatment strategy. CONCLUSIONS Although SABR was second choice after PME, survival after PME was not better than after SABR. Prospective comparative studies are clearly required to define the role of both, SABR and PME in OMD.

Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

PURPOSE To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. METHODS AND MATERIALS Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. RESULTS Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. CONCLUSION In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

Optimizing dose prescription in stereotactic body radiotherapy for lung tumours using Monte Carlo dose calculation

PURPOSE To define a method of dose prescription employing Monte Carlo (MC) dose calculation in stereotactic body radiotherapy (SBRT) for lung tumours aiming at a dose as low as possible outside of the PTV. METHODS AND MATERIALS Six typical T1 lung tumours - three small, three large - were constructed centrally, peripherally in the lung, and nearby the thoracic wall, respectively. For each of these, five treatment plans employing dynamic conformal arc technique were made in which the dose was prescribed to encompass the PTV with the prescription isodose level (PIL) set in a range between 50% and 80% of the isocenter dose. Three shells of respectively 10mm thickness around the PTV were constructed to assess the dose in the tissues directly adjacent to the PTV. RESULTS The PTV was nicely covered (mean 98.8%+/-0.9%) with favourable conformity indices (mean 1.09+/-0.1). Mean doses around the PTVs were 73% (+/-1.3%), 76% (+/-3.5%), and 85% (+/-5.1%) of the prescribed dose in shell 1 for PIL50%, PIL65%, and PIL80%, respectively; 40% (+/-2.6%), 44% (+/-5.1%), 54% (+/-9.3%) in shell 2; and 24% (+/-1.9%), 26% (+/-3.6%), 33% (+/-6.8%) in shell 3. All normal tissue doses including the integral dose were also consistently worst for PIL80%. Monitor units were 30% higher for PIL65%, and 70% higher for PIL50%, compared with PIL80%. CONCLUSIONS To improve normal tissue sparing the dose should be prescribed at an isodose lower than 80% of the isocenter dose in SBRT when using conformal arc technique with MC dose calculation.

Dose-volume-response analysis in stereotactic radiotherapy for early lung cancer

BACKGROUND AND PURPOSE Japanese and Western approaches to stereotactic ablative radiotherapy (SABR) are considerably different, particularly with respect to dose prescription and reporting, which makes comparisons of Japanese versus European or American results challenging. Using individual patient data, the aim of this study was to analyze the dose-local-control relationship and its impact on survival. MATERIAL AND METHODS Patients receiving SABR for single-lesion early stage NSCLC in Osaka (OM) or Groningen (GN) were analyzed. Doses were recalculated using state-of-the-art dose calculation algorithms and expressed as biologically effective dose (BED) at PTV margin. Survival, local control (LC), and effect of treatment failure in operable and inoperable patients on survival were analyzed. RESULTS Between 2006 and 2010, 383 patients were included. The BED at PTV periphery was 102 Gy₁₀ (±21) in GN and 83 Gy₁₀ (±5) in OM. Unadjusted overall survival (OS) was better in OM (72% vs 52%; p<0.001), but GTVs and performance status (PS) were also significantly more favorable in OM. Adjusted for GTV and PS, OS was not different between institutions (HR 0.88; p=0.47). LC was better in GN (93% vs 84%; p<0.05). Local control predicted survival in operable patients: Adjusted for GTV and PS, the HR of local failure for OS was 7.5 (2-27; p=0.003) for operable, and 1.1 (0.7-1.9; p=0.6) for inoperable patients. CONCLUSIONS Sufficient dose is crucial for local control, which was a significant factor for survival for operable patients.

Long-term Outcome of Surgery or Stereotactic Radiotherapy for Lung Oligometastases

ABSTRACT Local treatment for pulmonary oligometastases (one to five lesions) using metastasectomy or stereotactic ablative radiotherapy (SABR) was investigated in a cohort that received multidisciplinary tumor board–based treatment decisions. The first choice of treatment was surgery; SABR was recommended in cases of adverse clinical factors. Propensity score–adjusted and unadjusted overall survival was the primary end point; local control and time to failure of a local‐only treatment strategy were also analyzed. With a minimum follow‐up time of 5.8 years, the 5‐year overall survival rate was 41% for surgery (n = 68) and 45% for SABR (n = 42). Again not different for the two modalities, 40% of patients were free from failure of a local‐only treatment strategy, and 20% were free from any progression at 5 years. The 5‐year local control rate was 83% for SABR and 81% for surgery. Despite treatment selection clearly disadvantaging SABR against surgery, even unadjusted outcome was not better when pulmonary oligometastases were surgically removed rather than irradiated.

An instrument dedicated for modelling of pulmonary radiotherapy

BACKGROUND AND PURPOSE Radiotherapy plays a pivotal role in lung cancer treatment. Selection of patients for new (radio)therapeutic options aiming at improving outcomes requires reliable and validated prediction models. We present the implementation of a prospective platform for evaluation and development of lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional predictive modelling. MATERIALS AND METHODS ProPED-LUNG was designed to comprise relevant baseline and follow up data of patients receiving pulmonary radiotherapy with curative intent. Patient characteristics, diagnostic and staging information, treatment parameters including full dose-volume-histograms, tumour control, survival, and toxicity are scored. Besides physician-rated data, a range of patient-rated data regarding symptoms and health-related quality-of-life are collected. RESULTS After 18 months of accrual, 315 patients have been included (accrual rate, 18 per month). Of the first hundred patients included, 70 received conformal (chemo)radiotherapy and 30 underwent stereotactic radiotherapy. Compliance at 3 and 6 months follow-up was 96-100% for patient-rated, and 81-94% for physician-rated assessments. For data collection, 0.4 FTE were allocated in a 183 FTE department (0.2%). CONCLUSIONS ProPED-LUNG is feasible with high compliance rates and yields a large amount of high quality prospective disease-related, treatment-related, patient- and physician-rated data which can be used to evaluate new developments in pulmonary radiotherapy.