Max Dahele

Radiographic changes after lung stereotactic ablative radiotherapy (SABR) - Can we distinguish recurrence from fibrosis? A systematic review of the literature

BACKGROUND Changes in lung density on computed tomography (CT) are common after stereotactic ablative radiotherapy (SABR) and can confound the early detection of recurrence. We performed a systematic review to describe post-SABR findings on computed tomography (CT) and positron-emission tomography (PET), identify imaging characteristics that predict recurrence and propose a follow-up imaging algorithm. METHODS A systematic review was conducted of studies providing detailed radiologic descriptions of anatomic and metabolic lung changes after SABR. Our search returned 824 studies; 26 met our inclusion criteria. Data are presented according to PRISMA guidelines. RESULTS Acute changes post-SABR predominantly appear as consolidation or ground glass opacities. Late changes often demonstrate a modified conventional pattern of fibrosis, evolving beyond 2years after treatment. Several CT features, including an enlarging opacity, correlate with recurrence. Although PET SUVmax may rise immediately post-SABR, an SUVmax⩾5 carries a high predictive value of recurrence. CONCLUSIONS CT density changes are common post-SABR. The available evidence suggests that recurrent disease should be suspected if high-risk CT changes are seen with SUVmax⩾5 on PET. Further studies are needed to validate the predictive values of such metrics, and for advanced analysis of CT changes to allow early detection of potentially curable local recurrence.

Stereotactic Body Radiotherapy for Medically Inoperable Lung Cancer: Prospective, Single-Center Study of 108 Consecutive Patients

PURPOSE To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. METHODS AND MATERIALS Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. RESULTS The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. CONCLUSIONS Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.

Radiological Changes After Stereotactic Radiotherapy for Stage I Lung Cancer

Introduction: Stereotactic body radiation therapy (SBRT) is entering routine clinical use for selected patients with early-stage non-small cell lung cancer. Post-SBRT radiological changes are commonly seen on follow-up computed tomography (CT) imaging and can cause diagnostic dilemmas. The aim of this study is to describe the incidence, radiological severity, and long-term morphology of these changes. Methods: CT scans from patients treated between 2003 and June 2008 were eligible for evaluation if radiological follow-up had been performed at our center for at least 2 years, and there was no definite evidence of local recurrence. Timing, incidence, morphology, and severity of lung changes were determined. Results: CT scans from 61 patients (68 lesions) with a median follow-up of 2.5 years were evaluated. Within 6 months, 54% of lesions were associated with additional radiological abnormalities, and this figure reached 99% after 36 months. Most changes were scored as mild to moderate, and although the median time to first observation was 17 weeks, 25% appeared ≥1 year post-SBRT. In 47% of lesions, the morphology or severity of changes continued to evolve more than 2 years posttreatment. Conclusions: Mild-moderate radiological changes are common after lung SBRT. Some degree of late change is nearly universal, and it often continues to evolve more than 2 years post-SBRT. Clinicians should be aware of these radiological findings, which need to be distinguished from the uncommon cases of local failure post-SBRT.

Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): Study protocol for a randomized phase II trial

BackgroundStereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone.MethodsAfter stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy.DiscussionThis study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.Trial registrationClinicaltrials.gov identifier: NCT01446744

Evaluation of a Knowledge-Based Planning Solution for Head and Neck Cancer

PURPOSE Automated and knowledge-based planning techniques aim to reduce variations in plan quality. RapidPlan uses a library consisting of different patient plans to make a model that can predict achievable dose-volume histograms (DVHs) for new patients and uses those models for setting optimization objectives. We benchmarked RapidPlan versus clinical plans for 2 patient groups, using 3 different libraries. METHODS AND MATERIALS Volumetric modulated arc therapy plans of 60 recent head and neck cancer patients that included sparing of the salivary glands, swallowing muscles, and oral cavity were evenly divided between 2 models, Model(30A) and Model(30B), and were combined in a third model, Model60. Knowledge-based plans were created for 2 evaluation groups: evaluation group 1 (EG1), consisting of 15 recent patients, and evaluation group 2 (EG2), consisting of 15 older patients in whom only the salivary glands were spared. RapidPlan results were compared with clinical plans (CP) for boost and/or elective planning target volume homogeneity index, using HI(B)/HI(E) = 100 × (D2% - D98%)/D50%, and mean dose to composite salivary glands, swallowing muscles, and oral cavity (D(sal), D(swal), and D(oc), respectively). RESULTS For EG1, RapidPlan improved HI(B) and HI(E) values compared with CP by 1.0% to 1.3% and 1.0% to 0.6%, respectively. Comparable D(sal) and D(swal) values were seen in Model(30A), Model(30B), and Model60, decreasing by an average of 0.1, 1.0, and 0.8 Gy and 4.8, 3.7, and 4.4 Gy, respectively. However, differences were noted between individual organs at risk (OARs), with Model(30B) increasing D(oc) by 0.1, 3.2, and 2.8 Gy compared with CP, Model(30A), and Model60. Plan quality was less consistent when the patient was flagged as an outlier. For EG2, RapidPlan decreased D(sal) by 4.1 to 4.9 Gy on average, whereas HI(B) and HI(E) decreased by 1.1% to 1.5% and 2.3% to 1.9%, respectively. CONCLUSIONS RapidPlan knowledge-based treatment plans were comparable to CP if the patients OAR-planning target volume geometry was within the range of those included in the models. EG2 results showed that a model including swallowing-muscle and oral-cavity sparing can be applied to patients with only salivary gland sparing. This may allow model library sharing between institutes. Optimal detection of inadequate plans and population of model libraries requires further investigation.

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: a planning study and early clinical data.

BACKGROUND AND PURPOSE Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc, RA) and conventional intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n=3), while group 2 had PTVs encompassing the entire vertebra (n=4). Finally, RA delivery parameters in four patients were assessed. RESULTS Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V(10-partial cord) for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min. CONCLUSIONS Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.

Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): Patient outcomes and prognostic factors

OBJECTIVES Metastatic non-small cell lung carcinoma (NSCLC) generally carries a poor prognosis, and systemic therapy is the mainstay of treatment. However, extended survival has been reported in patients presenting with a limited number of metastases, termed oligometastatic disease. We retrospectively reviewed the outcomes of such patients treated at two centers. MATERIALS AND METHODS From September 1999-July 2012, a total of 61 patients with 1-3 synchronous metastases, who were treated with radical intent to all sites of disease, were identified from records of two cancer centers. Treatment was considered radical if it involved surgical resection and/or delivery of radiation doses ≥13 × 3 Gy. RESULTS Besides the primary tumor, 50 patients had a solitary metastasis, 9 had two metastases, and 2 had three metastases. Locations of metastases included the brain (n = 36), bone (n = 11), adrenal (n = 4), contralateral lung (n = 4), extra-thoracic lymph nodes (n = 4), skin (n = 2) and colon (n = 1). Only one patient had metastases in two different organs. Median follow-up was 26.1 months (m), median overall survival (OS) was 13.5m, median progression free survival (PFS) was 6.6m and median survival after first progression (SAFP) was 8.3m. The 1- and 2-year OS were, 54% and 38%, respectively. Significant predictors of improved OS were: smaller radiotherapy planning target volume (PTV) (p = 0.004) and surgery for the primary lung tumor (p < 0.001). Factors associated with improved SAFP included surgery for the primary lung tumor, presence of brain metastases, and absence of bone metastases. No significant differences in outcomes were observed between the two centers. CONCLUSION Radical treatment of selected NSCLC patients presenting with 1-3 synchronous metastases can result in favorable 2-year survivals. Favorable outcomes were associated with intra-thoracic disease status: patients with small radiotherapy treatment volumes or resected disease had the best OS. Future prospective clinical trials, ideally randomized, should evaluate radical treatment strategies in such patients.

Stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC): Is FDG-PET a predictor of outcome?

BACKGROUND AND PURPOSE Distant metastases are the dominant mode of failure after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). The primary study objective was to evaluate if the maximum standardized uptake value (SUV(max)) on pre-treatment FDG-PET/CT predicted clinical outcomes. Secondary objectives were to correlate 3-month post-SBRT SUV(max) and change in SUV(max) with outcomes. MATERIALS AND METHODS Consecutive patients with medically inoperable early-stage NSCLC and an FDG-PET/CT scan before (n=82) and 3 months after (n=62) SBRT. RESULTS Median follow up was 2 years. On univariate analysis baseline SUV(max) predicted for distant failure (p=0.0096), relapse free survival (RFS) (p=0.037) and local failure (p=0.044). On multivariate analysis baseline SUV(max) predicted for RFS (p=0.037). Baseline SUV(max) of above 5 was the most statistically significant cut off point for predicting distant failure (p=0.0002). Baseline SUV(max) ≥4.75 (median) was correlated with a higher risk of distant failure (p=0.012) and poorer RFS (p=0.04). Patients with a post-SBRT SUV(max) ≥2 and a reduction of <2.55 had a significantly higher rate of distant failure. CONCLUSIONS Pre-SBRT SUV(max) on FDG-PET/CT correlated most strongly with distant failure. A cut off of ≥5 was the most significant. Post-SBRT SUV(max) ≥2 and a reduction of <2.55 were associated with a higher risk of distant failure.

Fast Arc Delivery for Stereotactic Body Radiotherapy of Vertebral and Lung Tumors

PURPOSE Flattening filter-free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. METHODS AND MATERIAL Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions. RESULTS No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion. CONCLUSION The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.

Management of early-stage non-small cell lung cancer using stereotactic ablative radiotherapy: Controversies, insights, and changing horizons

The use of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer is growing rapidly, particularly since it has become the recommended therapy for unfit patients in current European and North American guidelines. As three randomized trials comparing surgery and SABR closed prematurely because of poor accrual, clinicians are faced with a dilemma in individual patient decision-making. Radiation oncologists, in particular, should be aware of the data from comparative effectiveness studies that suggest similar survival outcomes irrespective of local treatment modality. The necessity of obtaining a pathological diagnosis, particularly in frail patients prior to treatment remains a challenge, and this topic was addressed in recent European recommendations. Awareness of the high incidence of a second primary lung cancer in survivors, as well as other competing causes of mortality, is needed. The challenges in distinguishing focal scarring from recurrence after SABR also need to be appreciated by multidisciplinary tumor boards. With a shift in focus toward patient-centered decision-making, clinicians will need to be aware of these new developments and communicate effectively with patients, to ensure that treatment decisions are reflective of patient preferences. Priorities for additional research in the area are proposed.