We investigated the dosimetric impact of the interplay effect during RapidArc stereotactic body radiation therapy for lung tumors using flattening filter-free (FFF) beams with different dose rates.
...Seven tumors with motion ≤20 mm, treated with 10-MV FFF RapidArc, were analyzed. A programmable phantom with sinusoidal longitudinal motion (30-mm diameter "tumor" insert; period = 5 s; individualized amplitude from planning 4-dimensional computed tomography) was used for dynamic dose measurements. Measurements were made with GafChromic EBT III films. Plans delivered the prescribed dose to 95% of the planning target volume, created by a 5-mm expansion of the internal target volume. They comprised 2 arcs and maximum dose rates of 400 and 2400 MU/min. For 2400 MU/min plans, measurements were repeated at 3 different initial breathing phases to model interplay over 2 to 3 fractions. For 3 cases, 2 extra plans were created using 1 full rotational arc (with contralateral lung avoidance sector) and 1 partial arc of 224° to 244°. Dynamic and convolved static measurements were compared by use of gamma analysis of 3% dose difference and 1 mm distance-to-agreement.
For 2-arc 2400 MU/min plans, maximum dose deviation of 9.4% was found in a single arc; 7.4% for 2 arcs (single fraction) and <5% and 3% when measurements made at 2 and 3 different initial breathing phases were combined, simulating 2 or 3 fractions. For all 7 cases, >99% of the area within the region of interest passed the gamma criteria when all 3 measurements with different initial phases were combined. Single-fraction single-arc plans showed higher dose deviations, which diminished when dose distributions were summed over 2 fractions. All 400 MU/min plans showed good agreement in a single fraction measurement.
Under phantom conditions, single-arc and single-fraction 2400 MU/min FFF RapidArc lung stereotactic body radiation therapy is susceptible to interplay. Two arcs and ≥2 fractions reduced the effect to a level that appeared unlikely to be clinically significant.
An analysis of patterns of care in the USA showed high adherence to guidelines; 98% of radiation oncologists recommended prophylactic cranial irradiation for patients with extensive-stage small-cell ...lung cancer with response to systemic chemotherapy.10 Are there other explanations for the absence of a survival benefit in the Japanese study? Interestingly, in the EORTC study, the opposite was observed, and the more frequent use of second-line or third-line chemotherapy after prophylactic cranial irradiation might have contributed to the survival benefit.2 Although side-effects that could be caused by chemotherapy were more frequent and severe in the prophylactic cranial irradiation group of the Japanese study, grade 3 or higher toxicity was rarely observed.3 In the EORTC study, temporary effects of prophylactic cranial irradiation on hair loss and fatigue were seen, but not on global quality of life.11 The investigators of the Japanese study have to be complimented for assessing cognitive functioning; no significant differences between groups were seen, possibly because of the small number of patients analysed. PCI Overview Collaborative Group, N Engl J Med, Vol. 341, 1999, 476-484 2 BJ Slotman, C Faivre-Finn, G Kramer, Prophylactic cranial irradiation in extensive small-cell lung cancer, N Engl J Med, Vol. 357, 2007, 664-672 3...
Stereotactic 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 for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions.
One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival.
This 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 4-10 oligometastatic lesions.
Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018.
The use of stereotactic ablative radiotherapy (SABR) in centrally located early-stage lung tumors has been associated with increased toxicity. We studied outcomes after delivery of risk-adapted SABR ...of central tumors.
SABR was delivered in eight fractions of 7.5 Gy to 63 such patients between 2003 and 2009. Of these, 37 patients had a tumor at a central hilar location, whereas 26 patients had tumors abutting the pericardium or mediastinal structures. Survival outcomes were compared with patients with peripheral tumors treated during the same time period using fewer fractions of SABR.
Median follow-up was 35 months. Late grade III toxicity was limited to chest wall pain (n = 2) and increased dyspnoea (n = 2). No grade IV/V toxicity was observed, but grade V toxicity could not be excluded with certainty in nine patients who died of cardiopulmonary causes. Distant metastases were the predominant cause of death; cardiovascular deaths were not associated with a paracardial tumor location. No significant differences in outcomes were observed between these 63 patients and 445 other SABR patients treated for peripheral early-stage lung tumors. Three-year local control rates were 92.6% and 90.2% (p = 0.9). Three-year overall survival rates were 64.3% and 51.1% with median survival rates of 47 and 36 months, in favor of the group of patients with central tumors (p = 0.09).
Use of risk-adapted SABR delivered in eight fractions of 7.5 Gy did not result in excess toxicity for centrally located early-stage lung tumors, and clinical outcomes were comparable with those seen for peripheral lesions.
Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy ...(SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749 ; ROSEL: NCT00687986 ). Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0–47·3) for the SABR group and 35·4 months (18·9–40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio HR 0·14 95% CI 0·017–1·190, log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0·69 95% CI 0·21–2·29, log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three 10% chest wall pain, two 6% dyspnoea or cough, and one 3% fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four 15% patients), chest pain (four 15% patients), and lung infections (two 7%). Interpretation SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Funding Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
Abstract
BACKGROUND
Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence.
OBJECTIVE
To conduct a systematic review and provide an ...objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases.
METHODS
Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases.
RESULTS
Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone.
For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery.
CONCLUSION
A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus.
Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected ...to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC.
In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of ≥3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter.
Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild, with grade ≥3 radiation pneumonitis and rib fractures in 2% and 3%, respectively.
Patients with potentially operable disease who underwent primary SABR had a median OS that exceeded 5 years. This finding supports ongoing randomized clinical trials comparing surgery and SABR in cases of operable stage I NSCLC.
Summary The incidence of brain metastases in patients with lung cancer has increased as a result of improved local and systemic control and better diagnosis from advances in brain imaging. Because ...brain metastases are responsible for life-threatening symptoms and serious impairment of quality of life, resulting in shortened survival, prophylactic cranial irradiation has been proposed in both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) to try to improve incidence of brain metastasis, survival, and eventually quality of life. Findings from randomised controlled trials and a meta-analysis have shown that prophylactic cranial irradiation not only reduces the incidence of brain metastases in patients with SCLC and with non-metastatic NSCLC, but also improves overall survival in patients with SCLC who respond to first-line treatment. Although prophylactic cranial irradiation is potentially associated with neurocognitive decline, this risk needs to be balanced against the potential benefit in terms of brain metastases incidence and survival. Several strategies to reduce neurotoxicity are being investigated.
The purpose of this study was to compare intensity-modulated radiation therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with regard to patient-rated xerostomia, Radiation ...Therapy Oncology Group (RTOG) acute and late xerostomia and health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma (HNSCC).
Included were 241 patients with HNSCC treated with bilateral irradiation +/- chemotherapy. Since 2000, all patients treated with HNSCC were included in a program, which prospectively assessed acute and late morbidity according to the RTOG and HRQoL on a routine basis at regular intervals. Before October 2004, all patients were treated with 3D-CRT (N = 150). After clinical implementation in October 2004, 91 patients received IMRT. In this study, the differences regarding RTOG toxicity, xerostomia, and other items of HRQoL were analyzed.
The use of IMRT resulted in a significant reduction of the mean dose of the parotid glands (27 Gy vs. 43 Gy (p < 0.001). During radiation, Grade 2 RTOG xerostomia was significantly less with IMRT than with 3D-CRT. At 6 months, the prevalence of patient-rated moderate to severe xerostomia and Grade 2 or higher RTOG xerostomia was significantly lower after IMRT versus 3D-CRT. Treatment with IMRT also had a positive effect on several general and head and neck cancer-specific HRQoL dimensions.
IMRT results in a significant reduction of patient- and observer-rated xerostomia, as well as other head and neck symptoms, compared with standard 3D-CRT. These differences translate into a significant improvement of the more general dimensions of HRQoL.
OBJECTIVE The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously ...untreated spinal metastases. METHODS The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language. RESULTS A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16-24 Gy/1 fraction (fx), 24 Gy/2 fx, 24-27 Gy/3 fx, and 30-35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported. CONCLUSION There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.
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