Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Spine Stereotactic Body Radiation Therapy Without Immobilization: Detailed Analysis of Intrafraction Motion Using High-Frequency kV Imaging During Irradiation.

PURPOSE: Spine stereotactic body radiation therapy (SBRT) requires high positioning accuracy and a stable patient to maximize target coverage and reduce excessive irradiation to organs at risk. Positional verification during spine SBRT delivery helps to ensure accurate positioning for all patients. We report our experience with noninvasive 3-dimensional target position monitoring during volumetric modulated arc therapy of spine metastases in nonimmobilized patients positioned using only a thin mattress and simple arm and knee supports. METHODS AND MATERIALS: Fluoroscopic planar kV images were acquired at 7 frames/s using the on-board imaging system during volumetric modulated arc therapy spine SBRT. Template matching and triangulation were used to track the target in vertical, longitudinal, and lateral directions. If the tracking trace deviated >1 mm from the planned position in ≥1 direction, treatment was manually interrupted and 6-dimensional cone beam computed tomography (CBCT)-based couch correction was performed. Tracking data were used to retrospectively analyze the target position. Positional data, agreement with CBCT, correlation between position of the couch and direction of any positional correction, and treatment times were analyzed. RESULTS: In total, 175 fractions were analyzed. Delivery was interrupted 83 times in 66 fractions for a deviation >1 mm. In 97% of cases the difference between tracking data and subsequent clinical shift performed after the CBCT match was ≤0.5 mm. Lateral/longitudinal shift performed after intervention correlated with the couch roll/pitch at the start of treatment (correlation coefficient, -0.63/0.53). Mean (SD; range) time between start of first imaging and end of the last arc was 15.2 minutes (5.1; 7.6-36.3). CONCLUSIONS: Spine tracking during irradiation can be used to prompt an intervention CBCT scan and repositioning so that a spine SBRT target deviates by ≤1 mm from the planned position, even in nonimmobilized patients. kV tracking and CBCT are in good agreement. The data support verification CBCT after all 6 degrees-of-freedom positional corrections in nonimmobilized spine SBRT patients.

Differential Sensitivity to Ionizing Radiation in Gemcitabine-Resistant and Paclitaxel-Resistant Pancreatic Cancer Cells.

PURPOSE: Chemoresistance remains a major challenge in treating pancreatic ductal adenocarcinoma (PDAC). Although chemoradiation has proven effective in other tumor types, such as head and neck squamous cell carcinoma, its role in PDAC and effect on acquired chemoresistance have yet to be fully explored. In this study, we investigated the sensitivity of gemcitabine-resistant (GR) and paclitaxel-resistant (PR) PDAC cells to ionizing radiation (IR) and their underlying mechanisms. METHODS AND MATERIALS: GR and PR clones were generated from PANC-1, PATU-T, and SUIT2-007 pancreatic cancer cell lines. Cell survival after radiation was assessed using clonogenic assay, sulforhodamine B assay, apoptosis, and spheroid growth by bioluminescence. Radiation-induced DNA damage was assessed using Western blot, extra-long polymerase chain reaction, reactive oxygen species production, and immunofluorescence. Autophagy and modulation of the Hippo signaling pathway were investigated using proteomics, Western blot, immunofluorescence, and reverse-transcription quantitative polymerase chain reaction. RESULTS: In both 2- and 3-dimensional settings, PR cells were more sensitive to IR and showed decreased ß-globin amplification, indicating more DNA damage accumulation compared with GR or wild-type cells after 24 hours. Proteomic analysis of PR PATU-T cells revealed that the protein MST4, a kinase involved in autophagy and the Hippo signaling pathway, was highly downregulated. A differential association was found between autophagy and radiation treatment depending on the cell model. Interestingly, increased yes-associated protein nuclear localization and downstream Hippo signaling pathway target gene expression were observed in response to IR. CONCLUSIONS: This was the first study investigating the potential of IR in targeting PDAC cells with acquired chemoresistance. Our results demonstrate that PR cells exhibit enhanced sensitivity to IR due to greater accumulation of DNA damage. Additionally, depending on the specific cellular context, radiation-induced modulation of autophagy and the Hippo signaling pathway emerged as potential underlying mechanisms, findings with potential to inform personalized treatment strategies for patients with acquired chemoresistance.

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy or Stereotactic Radiotherapy?

BACKGROUND: Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups. METHODS: We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics. RESULTS: The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26-67) in the surgery group and 46 months (IQR: 30-79) in the SABR group. Median OS was 58 months (CI: 20-94) in the metastasectomy group and 70 months (CI: 29-111) in the SABR group (p = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR (p = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3-26) in the metastasectomy group and 10 months (CI: 6-13) in the SABR group (p = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR (p < 0.001). Lower BED Gy10 was correlated with an increased likelihood of recurrence (p = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR (p = 0.22). CONCLUSION: In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.

Clinical outcomes of MR-guided adrenal stereotactic ablative radiotherapy with preferential sparing of organs at risk.

Background and purpose: The optimal stereotactic ablative radiotherapy (SABR) doses for adrenal tumors are unknown. Some trials have specified that organ at risk (OAR) dose constraints should take priority over target coverage. We performed a retrospective review of the outcomes of MR-guided adrenal SABR (MRgRT) delivered with OAR sparing. Materials and methods: Patients who underwent adrenal MRgRT between 2016 and 2023 were identified from our Ethics-approved institutional database. Dose ranged between 8 and 24 Gy per fraction, delivered in 1-5 fractions. A 3 mm margin was added to the breath-hold gross tumor volume (GTV) to derive a PTV. Plan were delivered to an 'optimized' PTV that was generated by excluding any overlap with OARs. Results: Adrenal SABR was performed in 107 patients (114 metastases). The commonest scheme used 5 fractions of 10 Gy (53.5 %); 82 % of plans delivered a BED10 ≧ 80 Gy. Systemic therapy was administered within 3 months preceding or following SABR in 53.5 % of patients. Grade 3 acute toxicity (CTCAE v5.0) occurred in 0.9 % of patients, and 4.4 % reported late toxicity, consisting of adrenal insufficiency and a vertebral collapse. Median follow-up was 13.8 months (range, 0.0-73.4 months). Local progression occurred in 7.4 % of evaluable patients. PTV underdosage was frequent, with a coverage compromise index (D99/prescription dose) of < 0.90 in 52 % of all plans. Recurrences were independent of the prescription doses. Conclusion: MRgRT for adrenal metastases is well tolerated with high local control rates despite prioritizing OAR sparing over PTV coverage. Studies using deformable dose accumulation may lead to a better understanding of dose-response relationship with adaptive SABR.

Dose distribution prediction for head-and-neck cancer radiotherapy using a generative adversarial network: influence of input data.

Purpose: A three-dimensional deep generative adversarial network (GAN) was used to predict dose distributions for locally advanced head and neck cancer radiotherapy. Given the labor- and time-intensive nature of manual planning target volume (PTV) and organ-at-risk (OAR) segmentation, we investigated whether dose distributions could be predicted without the need for fully segmented datasets. Materials and methods: GANs were trained/validated/tested using 320/30/35 previously segmented CT datasets and treatment plans. The following input combinations were used to train and test the models: CT-scan only (C); CT+PTVboost/elective (CP); CT+PTVs+OARs+body structure (CPOB); PTVs+OARs+body structure (POB); PTVs+body structure (PB). Mean absolute errors (MAEs) for the predicted dose distribution and mean doses to individual OARs (individual salivary glands, individual swallowing structures) were analyzed. Results: For the five models listed, MAEs were 7.3 Gy, 3.5 Gy, 3.4 Gy, 3.4 Gy, and 3.5 Gy, respectively, without significant differences among CP-CPOB, CP-POB, CP-PB, among CPOB-POB. Dose volume histograms showed that all four models that included PTV contours predicted dose distributions that had a high level of agreement with clinical treatment plans. The best model CPOB and the worst model PB (except model C) predicted mean dose to within ±3 Gy of the clinical dose, for 82.6%/88.6%/82.9% and 71.4%/67.1%/72.2% of all OARs, parotid glands (PG), and submandibular glands (SMG), respectively. The R2 values (0.17/0.96/0.97/0.95/0.95) of OAR mean doses for each model also indicated that except for model C, the predictions correlated highly with the clinical dose distributions. Interestingly model C could reasonably predict the dose in eight patients, but on average, it performed inadequately. Conclusion: We demonstrated the influence of the CT scan, and PTV and OAR contours on dose prediction. Model CP was not statistically different from model CPOB and represents the minimum data statistically required to adequately predict the clinical dose distribution in a group of patients.

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS: 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION: SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.

Local control and toxicity after magnetic resonance imaging (MR)-guided single fraction lung stereotactic ablative radiotherapy.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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 ≤2.5 cm from the chest wall. Prescribed doses were 34 Gy (in 58%), 30 Gy (32%), or between 20-28 Gy (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). CONCLUSION: 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.

Stereotactic Body Radiotherapy for Lung Oligo-metastases: Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

PURPOSE: A systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases served as the basis for development of this International Stereotactic Radiosurgery Society (ISRS) practice guideline. METHODS: In accordance with PRISMA guidelines, a systematic review was performed of retrospective series with ≥50 patients/lung metastases, prospective trials with ≥25 patients/lung metastases, analyses of specific high-risk situations, and all randomized trials published between 2012 and July 2022 in the MEDLINE or Embase database using the key words "lung oligometastases", "lung metastases", "pulmonary metastases", "pulmonary oligometastases", "stereotactic body radiation therapy (SBRT)" and "stereotactic ablative body radiotherapy (SBRT)". Weighted random effects models were used to calculate pooled outcomes estimates. RESULTS: Of the 1884 articles screened, 35 analyses (27 retrospective-, 5 prospective, and 3 randomized trials) reporting on treatment of >3600 patients and >4650 metastases were included. The median local control was 90 % (Range: 57-100 %) at 1 year and 79 % (R: 70-96 %) at 5 years. Acute toxicity ≥3 was reported for 0.5 % and late toxicity ≥3 for 1.8 % of patients. A total of 21 practice recommendations covering the areas of staging & patient selection (n = 10), SBRT treatment (n = 10), and follow-up (n = 1) were developed, with agreements rates of 100 %, except for recommendation 13 (83 %). CONCLUSION: SBRT represents an effective definitive local treatment modality combining high local control rates with low risk of radiation-induced toxicities.

Deep learning-based markerless lung tumor tracking in stereotactic radiotherapy using Siamese networks.

BACKGROUND: Radiotherapy (RT) is involved in about 50% of all cancer patients, making it a very important treatment modality. The most common type of RT is external beam RT, which consists of delivering the radiation to the tumor from outside the body. One novel treatment delivery method is volumetric modulated arc therapy (VMAT), where the gantry continuously rotates around the patient during the radiation delivery. PURPOSE: Accurate tumor position monitoring during stereotactic body radiotherapy (SBRT) for lung tumors can help to ensure that the tumor is only irradiated when it is inside the planning target volume. This can maximize tumor control and reduce uncertainty margins, lowering organ-at-risk dose. Conventional tracking methods are prone to errors, or have a low tracking rate, especially for small tumors that are in close vicinity to bony structures. METHODS: We investigated patient-specific deep Siamese networks for real-time tumor tracking, during VMAT. Due to lack of ground truth tumor locations in the kilovoltage (kV) images, each patient-specific model was trained on synthetic data (DRRs), generated from the 4D planning CT scans, and evaluated on clinical data (x-rays). Since there are no annotated datasets with kV images, we evaluated the model on a 3D printed anthropomorphic phantom but also on six patients by computing the correlation coefficient with the breathing-related vertical displacement of the surface-mounted marker (RPM). For each patient/phantom, we used 80% of DRRs for training and 20% for validation. RESULTS: The proposed Siamese model outperformed the conventional benchmark template matching-based method (RTR): (1) when evaluating both methods on the 3D phantom, the Siamese model obtained a 0.57-0.79-mm mean absolute distance to the ground truth tumor locations, compared to 1.04-1.56 mm obtained by RTR; (2) on patient data, the Siamese-determined longitudinal tumor position had a correlation coefficient of 0.71-0.98 with the RPM, compared to 0.07-0.85 for RTR; (3) the Siamese model had a 100% tracking rate, compared to 62%-82% for RTR. CONCLUSIONS: Based on these results, we argue that Siamese-based real-time 2D markerless tumor tracking during radiation delivery is possible. Further investigation and development of 3D tracking is warranted.

Impact of imperfection in medical imaging data on deep learning-based segmentation performance: An experimental study using synthesized data.

BACKGROUND: Clinical data used to train deep learning models are often not clean data. They can contain imperfections in both the imaging data and the corresponding segmentations. PURPOSE: This study investigates the influence of data imperfections on the performance of deep learning models for parotid gland segmentation. This was done in a controlled manner by using synthesized data. The insights this study provides may be used to make deep learning models better and more reliable. METHODS: The data were synthesized by using the clinical segmentations, creating a pseudo ground-truth in the process. Three kinds of imperfections were simulated: incorrect segmentations, low image contrast, and artifacts in the imaging data. The severity of each imperfection was varied in five levels. Models resulting from training sets from each of the five levels were cross-evaluated with test sets from each of the five levels. RESULTS: Using synthesized data led to almost perfect parotid gland segmentation when no error was added. Lowering the quality of the parotid gland segmentations used for training substantially lowered the model performance. Additionally, lowering the image quality of the training data by decreasing the contrast or introducing artifacts made the resulting models more robust to data containing those respective kinds of data imperfection. CONCLUSION: This study demonstrated the importance of good-quality segmentations for deep learning training and it shows that using low-quality imaging data for training can enhance the robustness of the resulting models.

Radiation Therapy and Indigenous Peoples in Canada and Australia: Building Paths Toward Reconciliation in Cancer Care Delivery.

Indigenous peoples represent approximately 5% of the world's population and reside in over 90 countries worldwide. They embody a rich diversity of cultures, traditions, languages and relationships with the land that are shared through many generations and that are distinct from those of the settler societies within which they now live. Many Indigenous peoples have a shared experience of discrimination, trauma, and violation of rights, rooted in complex sociopolitical relationships with settler societies that are still ongoing. This results in continuing social injustices and pronounced disparities in health for many Indigenous peoples around the globe. Indigenous peoples exhibit a significantly higher cancer incidence, mortality, and poorer survival compared to non-Indigenous peoples. Cancer services, including radiotherapy, have not been designed to support the specific values and needs of Indigenous populations, resulting in poorer access to cancer services for Indigenous peoples globally across the entire cancer care spectrum. Specific to radiotherapy, available evidence demonstrates disparities in radiotherapy uptake between Indigenous and non-Indigenous patients. Radiotherapy centres are also located disparately further away from Indigenous communities. Studies are limited by a lack of Indigenous-specific data to help inform effective radiotherapy delivery. Recent Indigenous-led partnerships and initiatives have helped to address existing gaps in cancer care, and radiation oncologists play an important role in supporting such efforts. In this article, we present an overview of access to radiotherapy for Indigenous peoples in Canada and Australia, with a focus on strengthening cancer care delivery through education, partnerships, and research.

Same-day adaptive palliative radiotherapy without prior CT simulation: Early outcomes in the FAST-METS study.

BACKGROUND AND PURPOSE: Standard palliative radiotherapy workflows involve waiting times or multiple clinic visits. We developed and implemented a rapid palliative workflow using diagnostic imaging (dCT) for pre-planning, with subsequent on-couch target and plan adaptation based on a synthetic computed tomography (CT) obtained from cone-beam CT imaging (CBCT). MATERIALS AND METHODS: Patients with painful bone metastases and recent diagnostic imaging were eligible for inclusion in this prospective, ethics-approved study. The workflow consisted of 1) telephone consultation with a radiation oncologist (RO); 2) pre-planning on the dCT using planning templates and mostly intensity-modulated radiotherapy; 3) RO consultation on the day of treatment; 4) CBCT scan with on-couch adaptation of the target and treatment plan; 5) delivery of either scheduled or adapted treatment plan. Primary outcomes were dosimetric data and treatment times; secondary outcome was patient satisfaction. RESULTS: 47 patients were enrolled between December 2021 and October 2022. In all treatments, adapted treatment plans were chosen due to significant improvements in target coverage (PTV/CTV V95%, p-value < 0.005) compared to the original treatment plan calculated on daily anatomy. Most patients were satisfied with the workflow. The average treatment time, including consultation and on-couch adaptive treatment, was 85 minutes. On-couch adaptation took on average 30 min. but was longer in cases where the automated deformable image registration failed to correctly propagate the targets. CONCLUSION: A fast treatment workflow for patients referred for painful bone metastases was implemented successfully using online adaptive radiotherapy, without a dedicated CT simulation. Patients were generally satisfied with the palliative radiotherapy workflow.

Evaluation of a workflow for cone-beam CT-guided online adaptive palliative radiotherapy planned using diagnostic CT scans.

PURPOSE: Single-visit radiotherapy (RT) is beneficial for patients requiring pain control and can limit interruptions to systemic treatments. However, the requirement for a dedicated planning CT (pCT)-scan can result in treatment delays. We developed a workflow involving preplanning on available diagnostic CT (dCT) imaging, followed by online plan adaption using a cone-beam CT (CBCT)-scan prior to RT-delivery, in order to account for any changes in anatomy and target position. METHODS: Patients previously treated with palliative RT for bone metastases were selected from our hospital database. Patient dCT-images were deformed to treatment CBCTs in the Ethos platform (Varian Medical Systems) and a synthetic CT (sCT) generated. Treatment quality was analyzed by comparing a coverage of the V95% of the planning/clinical target volume and different organ-at-risk (OAR) doses between adapted and initial clinical treatment plans. Doses were recalculated on the CBCT and sCT in a separate treatment planning system. Adapted plan doses were measured on-couch using an anthropomorphic phantom with a Gafchromic EBT3 dosimetric film and compared to dose calculations. RESULTS: All adapted treatment plans met the clinical goals for target and OARs and outperformed the original treatment plans calculated on the (daily) sCT. Differences in V95% of the target volume coverage between the initial and adapted treatments were <0.2%. Dose recalculations on CBCT and sCT were comparable, and the average gamma pass rate (3%/2 mm) of dosimetric measurements was 98.8%. CONCLUSIONS: Online daily adaptive RT using dCTs instead of a dedicated pCT is feasible using the Ethos platform. This workflow has now been implemented clinically.

Radiobiological Aspects of FLASH Radiotherapy.

Radiotherapy (RT) is one of the primary treatment modalities for cancer patients. The clinical use of RT requires a balance to be struck between tumor effect and the risk of toxicity. Sparing normal tissue is the cornerstone of reducing toxicity. Advances in physical targeting and dose-shaping technology have helped to achieve this. FLASH RT is a promising, novel treatment technique that seeks to exploit a potential normal tissue-sparing effect of ultra-high dose rate irradiation. A significant body of in vitro and in vivo data has highlighted a decrease in acute and late radiation toxicities, while preserving the radiation effect in tumor cells. The underlying biological mechanisms of FLASH RT, however, remain unclear. Three main mechanisms have been hypothesized to account for this differential FLASH RT effect between the tumor and healthy tissue: the oxygen depletion, the DNA damage, and the immune-mediated hypothesis. These hypotheses and molecular mechanisms have been evaluated both in vitro and in vivo. Furthermore, the effect of ultra-high dose rate radiation with extremely short delivery times on the dynamic tumor microenvironment involving circulating blood cells and immune cells in humans is essentially unknown. Therefore, while there is great interest in FLASH RT as a means of targeting tumors with the promise of an increased therapeutic ratio, evidence of a generalized FLASH effect in humans and data to show that FLASH in humans is safe and at least effective against tumors as standard photon RT is currently lacking. FLASH RT needs further preclinical investigation and well-designed in-human studies before it can be introduced into clinical practice.

Practical considerations of single-fraction stereotactic ablative radiotherapy to the lung.

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations.

Local Treatment of the Primary Tumor for Patients With Metastatic Cancer (PRIME-TX): A Meta-Analysis.

PURPOSE: Local treatment of the primary tumor for patients with metastases is controversial, and prospective data across many disease sites have conflicting conclusions regarding benefits. METHODS AND MATERIALS: A comprehensive search was conducted in PubMed/MEDLINE including randomized controlled trials (RCTs) published in the past 50 years. Inclusion criteria were multi-institutional RCTs of patients with metastatic disease receiving systemic therapy randomized to addition of local treatment to the primary tumor. Two primary outcome measures, overall survival (OS) and progression-free survival (PFS), were quantitatively assessed using random effects, and meta-analyses were conducted using the inverse variance method for pooling. Secondary endpoints were qualitatively assessed and included toxicity and patient-reported quality of life. Exploratory analyses were performed by treatment type and volume of disease. RESULTS: Eleven studies comprising 4952 patients were included (1558 patients received radiation therapy and 913 patients received surgery as primary tumor treatment). OS and PFS were not significantly improved from treatment of the primary (OS: hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.80-1.05; PFS: HR, 0.88; 95% CI, 0.72-1.07). Assessment of primary local treatment modality demonstrated a significant difference in summary effect size on PFS between trials using surgery (HR, 1.15; 95% CI, 0.99-1.33) compared with radiation therapy (HR, 0.73; 95% CI, 0.56-0.96) as the local treatment modality (P = .005). In low metastatic burden patients, radiation therapy was associated with significantly improved OS (HR, 0.67; 95% CI, 0.52-0.85), but surgery was not associated with improved OS compared with no local treatment (HR, 1.12; 95% CI, 0.94-1.34). CONCLUSIONS: In RCTs conducted to date enrolling a variety of cancer types with variable metastatic burden, there is no consistent improvement in PFS or OS from the addition of local therapy to the primary tumor in unselected patients with metastatic disease. Carefully selected patients may derive oncologic benefit and should be discussed in tumor boards. Future prospective studies should aim to further optimize patient selection and the optimal systemic and local therapy treatment types.