Abstract We report quality of life and indirect costs from patient reported outcomes from the ROSEL randomized control trial comparing stereotactic ablative radiotherapy (SABR, also known as ...stereotactic body radiotherapy or SBRT) versus surgical resection for medically operable stage IA non-small cell lung cancer. ROSEL closed prematurely after accruing and randomizing 22 patients. This exploratory analysis found the global health related quality of life and indirect costs to be significantly favorable and cheaper, with SABR.
Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived ...radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC. Preclinical evidence demonstrates that RCC cells are sensitive to ablative doses of radiotherapy (≥8-10 Gy). Trials in the setting of intracranial and extracranial oligometastases, as well as primary RCC, have demonstrated excellent tumour control using this approach. Additionally, an awareness of the capacity of high-dose radiation to stimulate antitumour immunity has resulted in novel combinations of SABR with immunotherapies. Here we describe the historical application of conventional radiotherapy, the current biological understanding of the effects of radiation, and the clinical evidence supporting the use of ablative radiotherapy in RCC. We also explore emerging opportunities to combine systemic targeted agents or immunotherapies with radiation. Radiotherapy, although once an overlooked approach, is moving towards the forefront of RCC treatment.
Abstract Background and purpose Early detection of local recurrences following stereotactic ablative radiotherapy (SABR) for lung cancer may allow for curative salvage treatment, but recurrence can ...be difficult to distinguish from fibrosis. We studied the clinical performance of CT imaging high-risk features (HRFs) for detecting local recurrence. Materials and methods Patients treated with SABR for early stage lung cancer between 2003 and 2012 who developed pathology-proven local recurrence ( n = 12) were matched 1:2 to patients without recurrences ( n = 24), based on baseline factors. Serial CT images were assessed by blinded radiation oncologists. Previously reported HRFs were (1) enlarging opacity at primary site; (2) sequential enlarging opacity; (3) enlarging opacity after 12-months; (4) bulging margin; (5) loss of linear margin and (6) air bronchogram loss. Results All HRFs were significantly associated with local recurrence ( p < 0.01), and one new HRF was identified: cranio-caudal growth ( p < 0.001). The best individual predictor of local recurrence was opacity enlargement after 12-months (100% sensitivity, 83% specificity, p < 0.001). The odds of recurrence increased 4-fold for each additional HRF detected. The presence of ⩾3 HRFs was highly sensitive and specific for recurrence (both >90%). Conclusion The systematic assessment of post-SABR CT images for HRFs enables the accurate prediction of local recurrence.
High-energy transmission beams (TBs) are currently the main delivery method for proton pencil beam scanning ultrahigh dose-rate (UHDR) FLASH radiotherapy. TBs place the Bragg-peaks behind the target, ...outside the patient, making delivery practical and achievement of high dose-rates more likely. However, they lead to higher integral dose compared to conventional intensity-modulated proton therapy (IMPT), in which Bragg-peaks are placed within the tumor. It is hypothesized that, when energy changes are not required and high beam currents are possible, Bragg-peak-based beams can not only achieve more conformal dose distributions than TBs, but also have more FLASH-potential.
This works aims to verify this hypothesis by taking three different Bragg-peak-based delivery techniques and comparing them with TB and IMPT-plans in terms of dosimetry and FLASH-potential for single-fraction lung stereotactic body radiotherapy (SBRT).
For a peripherally located lung target of various sizes, five different proton plans were made using "matRad" and inhouse-developed algorithms for spot/energy-layer/beam reduction and minimum monitor unit maximization: (1) IMPT-plan, reference for dosimetry, (2) TB-plan, reference for FLASH-amount, (3) pristine Bragg-peak plan (non-depth-modulated Bragg-peaks), (4) Bragg-peak plan using generic ridge filter, and (5) Bragg-peak plan using 3D range-modulated ridge filter.
Bragg-peak-based plans are able to achieve sufficient plan quality and high dose-rates. IMPT-plans resulted in lowest OAR-dose and integral dose (also after a FLASH sparing-effect of 30%) compared to both TB-plans and Bragg-peak-based plans. Bragg-peak-based plans vary only slightly between themselves and generally achieve lower integral dose than TB-plans. However, TB-plans nearly always resulted in lower mean lung dose than Bragg-peak-based plans and due to a higher amount of FLASH-dose for TB-plans, this difference increased after including a FLASH sparing-effect.
This work indicates that there is no benefit in using Bragg-peak-based beams instead of TBs for peripherally located, UHDR stereotactic lung radiotherapy, if lung dose is the priority.
•Delivery of single-fraction SABR to lung tumors on a 0.35T MR-linac resulted in a 3-year local control rate of 97%.•Only 1 patient (2%) developed grade ≥3 toxicity, which was chest wall ...pain.•MR-guided SABR delivered using repeated breath-holds and with automatic beam gating, achieves good tumor control and low toxicity.
Magnetic resonance imaging (MR)-guided radiotherapy permits continuous intrafraction visualization and use of automatic triggered beam delivery, with use of smaller planning target volumes (PTV). We report on long-term clinical outcomes following MR-guided single fraction (SF) lung SABR on a 0.35 T linac.
Details of patients treated with SF-SABR for lung tumors were accessed from an ethics approved institutional database. A breath-hold 3D MR simulation scan was performed using a true FISP sequence, followed by a breath-hold 3D CT scan. The gross tumor volume (GTV) was first contoured on the breath-hold CT scan, which was then compared with contours on the 3D MR scan, before the GTV was finalized. SABR plans used step-and-shoot IMRT beams to a PTV derived by adding a 5 mm margin to the breath-hold GTV, and a 3 mm gating window was used. SABR was delivered during repeated breath-holds, using automatic beam gating with continuous visualization of the GTV in a sagittal MR plane.
Between 2018-2022, 50 consecutive patients were treated, and 69% had a primary non-small cell lung cancer. Median PTV was 11.2 cc (range 3.9-53.5); 80% of GTV’s were located ≤2.5cm from the chest wall. Prescribed doses were 34Gy (in 58%), 30Gy (32%), or between 20-28Gy (10%). After a median follow-up of 18.1 months (95% CI 12.8-23.5), the 2-year survival was 82% (89% for primary NSCLC and 62% for metastases). After a median follow-up of 16.1 months (95% CI 11.2-21.1), local recurrences developed in 2 patients (4%). The 3-year local control rate was 97%, and just 1 patient developed grade ≥3 toxicity (chest wall pain).
MR-guided SF-SABR delivery to lung tumors on a 0.35 T linac, using repeated breath-holds with automatic beam gating, achieves good tumor control and low toxicity.
To investigate the generic and condition-specific health-related quality of life (HRQL) of patients with low-grade glioma (LGG).
A total of 195 patients with LGG, which was diagnosed, on average, 5.6 ...years before the study, were compared with 100 patients with hematologic (non-Hodgkin's) lymphoma and chronic lymphatic leukemia cancer (NHL/CLL) and 205 general population controls who were comparable with patients with LGG at the group level for age, sex, and education (healthy controls). Generic HRQL was assessed with the Short Form-36 (SF-36) Health Survey, and condition-specific HRQL was assessed with the Medical Outcomes Study cognitive function questionnaire and the European Organisation for Research and Treatment of Cancer brain cancer module. Objective neurocognitive functioning was assessed with a standardized battery of neuropsychological tests.
No statistically significant differences were observed between patients with LGG and patients with NHL/CLL in SF-36 scores. Patients with LGG scored significantly lower than healthy controls on six of eight scales and on the mental health component score of the SF-36. Approximately one quarter of patients with LGG reported serious neurocognitive symptoms. Female sex, epilepsy burden, and number of objectively assessed neurocognitive deficits were associated significantly with both generic and condition-specific HRQL. Clinical variables, including the time since diagnosis, tumor lateralization, extent of surgery, and radiotherapy, did not show a consistent relationship with HRQL.
Patients with LGG experienced significant problems across a broad range of HRQL domains, many of which were not condition-specific. However, the neurocognitive deficits and epilepsy that were relatively prevalent among patients with LGG were associated with negative HRQL outcomes and, thus, contributed additionally to the vulnerability of this population of patients with cancer.
This review provides an overview of the use of stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. The local control rates after SABR are generally >90%. Whether this also ...translates into a significant improvement in overall survival is the subject of ongoing studies. New exciting opportunities including the integration of SABR with targeted and immune therapies as well as some competing treatment strategies are discussed.
Volumetric modulated arc therapy (RapidArc; Varian Medical Systems, Palo Alto, CA) allows fast delivery of stereotactic radiotherapy for Stage I lung tumors. We investigated discrepancies between the ...calculated and delivered dose distributions, as well as the dosimetric impact of leaf interplay with breathing-induced tumor motion.
In 20 consecutive patients with Stage I lung cancer who completed RapidArc delivery, 15 had tumor motion exceeding 5 mm on four-dimensional computed tomography scan. Static and dynamic measurements were performed with Gafchromic EBT film (International Specialty Products Inc., Wayne, NJ) in a Quasar motion phantom (Modus Medical Devices, London, Ontario, Canada). Static measurements were compared with calculated dose distributions, and dynamic measurements were compared with the convolution of static measurements with sinusoidal motion patterns. Besides clinical treatment plans, additional cases were optimized to create excessive multileaf collimator modulation and delivered on the phantom with peak-to-peak motions of up to 25 mm. γ Analysis with a 3% dose difference and 2- or 1-mm distance to agreement was used to evaluate the accuracy of delivery and the dosimetric impact of the interplay effect.
In static mode film dosimetry of the two-arc delivery in the phantom showed that, on average, fewer than 3% of measurements had γ greater than 1. Dynamic measurements of clinical plans showed a high degree of agreement with the convolutions: for double-arc plans, 99.5% met the γ criterion. The degree of agreement was 98.5% for the plans with excessive multileaf collimator modulations and 25 mm of motion.
Film dosimetry shows that RapidArc accurately delivers the calculated dose distribution and that interplay between leaves and tumor motion is not significant for single-fraction treatments when RapidArc is delivered with two different arcs.
As patients with centrally located lung tumors are at increased risk of toxicity with stereotactic ablative radiation therapy (SABR), we performed stereotactic magnetic resonance (MR)-guided adaptive ...radiation therapy (SMART) for such patients. We retrospectively analyzed the benefits of daily on-table plan adaptation.
Twenty-five patients with central lung tumors underwent a total of 182 fractions of video-assisted, respiration-gated SMART on the MRIdian (ViewRay, Inc). Risk-adapted fractionation was used to deliver 60 Gy in 8 fractions (n = 20) or 55 Gy in 5 fractions (n = 5). For each fraction, daily MR-guided setup and on-table plan reoptimization, based on planning target volume (PTV) coverage and organ-at-risk (OAR) constraints, was performed. Gated breath-hold delivery was performed under continuous MR guidance. Benefits of daily plan reoptimization were studied by comparing 168 "predicted" plans, which are the calculated baseline plans on the anatomy of the day, with the reoptimized treatment plans.
The reoptimized plan was chosen for treatment in 92% of fractions. On-table plan adaptation improved PTV coverage in 61% of fractions by achieving superior coverage by the prescription dose (V
) and a higher median dose (D
). Mean increase in PTV V
was 4.6% (P < .01) with a median of 91.2% and 95.0% in predicted and reoptimized plans, respectively. The benefits of on-table adaptation persisted in an analysis restricted to fractions in which the PTV change was ≤1 cm
compared with baseline. On-table plan adaptation reduced the number of OAR planning constraint violations (P < .05). Maximum OAR doses remained mostly stable, with on-table reoptimization avoiding excessive OAR doses in selected cases.
On-table plan reoptimization during breath-hold MR-guided SABR for central lung tumors improves target coverage while avoiding excessive OAR doses. The SMART approach may widen the therapeutic window of SABR in high-risk patients with central lung tumors.
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