Management of oligometastatic head and neck squamous cell carcinoma: A systematic review.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer worldwide. It is mainly discovered in a locally advanced stage, but it is estimated that 40% of recurrences after the treatment of the primary disease will be in a metastatic form, with one third being oligometastatic. There is no clear consensus regarding the treatment of oligometastatic HNSCC, whether it being local treatment, systemic treatment or a combination of both. We put together a systematic review using the Preferred Reporting Item for Systematic review and Meta-Analysis (PRISMA) method to gather all pertinent articles approaching the therapeutic management of oligometastatic HNSCC, especially in the metachronous setting. Out of 344 articles, 21 articles fit our inclusion criteria and were deemed pertinent to help answer the question of our review. Eight studies included only head and neck cancers (HNC) and the other 13 tackled multiple histologies including HNC. Stereotactic body radiotherapy (SBRT) was the treatment of choice for oligometastatic HNSCC with good local control rates and manageable toxicity. Most included studies were retrospective and not randomized. The association of local treatment and systemic treatment was difficult to assess as treatment protocols were not always standardized. There is crucial need for more prospective randomized trials that compare all treatments and sequences as some patients with a high risk of developing polymetastatic disease could derive benefit form a more intensified approach.

CT-Guided Adaptive Radiotherapy for the Treatment of Technically Challenging Oligometastatic Disease: A Case Report.

There is a growing interest in the application of stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic cancers. This increasing appeal of SBRT has highlighted the need for more sophisticated radiotherapy techniques that allow high doses of radiation to be delivered to multiple sites while limiting the exposure of neighboring healthy tissue. A major obstacle to achieving this aim has been the occurrence of interfraction target variability: the tendency of both the tumor and the surrounding tissue to undergo day-to-day non-synchronous shifts in position. Such changes in the conformation of the tumor field often compromise the effectiveness of conventional SBRT prescribed for a fixed target. We report a case of oligometastatic pelvic disease where the challenge of an unusually mobile tumor was overcome with the use of a novel technique employing cone beam CT (CBCT)-based online adaptive radiotherapy (OART). The Phase I "Adaptive Radiation for Abdominopelvic Metastases (ARAM)" clinical trial was designed to determine if OART can achieve dosing targets superior to those attained using conventional radiotherapy techniques. In this case, CT adaptive planning enabled the treatment of a pelvic target prescribed per protocol to 45Gy that would otherwise have not been amenable to treatment with conventional SBRT planning. Adaptive plans showed significant improvements in target coverage while respecting critical organ constraints, resulting in a total treatment V35Gy of 89.3% and V45Gy of 52.8%, whereas the scheduled plan would have achieved V35Gy of 67.4% and V45Gy of 13.6%. Treatment times were variable (38.1-96.7 mins), and correlated with the magnitude of daily translation which ranged from 4 to 7 cm of total linear translation. The patient tolerated treatment without any adverse events. These results demonstrate a novel application of CBCT-guided OART that allowed for the administration of ablative treatment to an unexpectedly mobile target unamenable to conventional SBRT. CBCT-guided OART currently requires increased treatment time, a need which might be reduced by optimization of daily contouring. The phase 1 clinical trial NCT05880667 is ongoing and may provide further evidence that CBCT-guided OART can meet the technical challenges posed by radiotherapy for oligometastatic abdominal and pelvic disease.

The impact of progression-directed therapy on survival in metastatic castration-refractory prostate cancer: MEDCARE phase 3 trial.

BACKGROUND: Metastatic castration-refractory prostate cancer (mCRPC) presents a therapeutic challenge despite advancements in treatment. Once mCRPC is attained, patients face limited survival prospects. Next-line systemic treatment (NEST) is the standard of care for progressive mCRPC, encompassing various therapeutic options with associated toxicity and costs. In patients with oligoprogressive mCRPC, data suggest that progression-directed therapy (PDT), such as metastasectomy or stereotactic body radiotherapy, delays the initiation of NEST. METHODS AND DESIGN: The MEDCARE phase III trial aims to assess the impact of PDT on overall survival (OS) in oligoprogressive mCRPC. In this multicentric, randomised, prospective trial, we aim to randomise 246 patients in 1:1 allocation ratio between the standard-of-care therapy (surveillance or NEST) or PDT while continuing the current systemic treatment. Patients will be stratified based on number of progressive lesions (one vs ≥one), location of progressive lesions (local recurrence, N or M1a vs M1b or M1c) and previous systemic therapy (palliative androgen-deprivation therapy [pADT] vs pADT + androgen receptor-targeted agent or patients who received docetaxel in the past). The primary endpoint is OS, and the secondary endpoints include quality of life, radiographic progression-free survival (PFS), modified PFS, prostate cancer-specific survival and PDT-induced toxicity. DISCUSSION: This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

Randomized phase III study comparing re-irradiation stereotactic body radiotherapy and conventional radiotherapy for painful spinal metastases: Japan Clinical Oncology Group study JCOG2211 (RESCORE study).

Bone metastases are often associated with pain and can occur in various types of cancer, significantly affecting patients' quality of life. Despite the high response rates to initial conventional radiotherapy in patients with painful spinal metastases, recurrence and inadequate response still occur. Thus, the development of a highly effective strategy for pain recurrence is crucial to improving the quality of life in patients with advanced metastatic cancer. This randomized phase III trial aims to confirm the superiority of re-irradiation with stereotactic body radiotherapy (24 Gy in 2 fractions) over conventional radiotherapy (8 Gy in a single fraction) in achieving a complete pain response at 12 weeks in patients with previously irradiated painful spinal metastases. A total of 158 patients from 33 hospitals will be enrolled in Japan over 3.5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs1030240172 (https://jrct.niph.go.jp/latest-detail/jRCT1030240172).

Comparative analysis of clinical treatment outcomes: Breath-hold vs. free-breathing techniques in liver stereotactic body radiotherapy.

INTRODUCTION: The aim of this study was to clarify the safety and efficacy of breath-hold irradiation in liver stereotactic body radiotherapy (SBRT). METHODS: A retrospective analysis was conducted on 57 consecutive patients who received SBRT for hepatocellular carcinoma or liver metastases between 2013 and 2021. Breath-hold irradiation was implemented for patients treated after April 2020. RESULTS: The median follow-up period for all patients was 16.4 months (IQR: 7.36-20.9). The 2-year overall survival rate was 64.4% (95% CI: 47.4-77.2), and the local control rate was 84.3% (95% CI: 69.7-92.3) for all patients. The 1-year overall survival was 80.0% (95% CI: 60.8-90.5) versus 82.0% (95% CI: 53.5-93.9) in the free-respiratory (FR) group versus the breath-hold (BH) group, respectively (P = 0.60). The 1-year local control rates were 78.1% (95% CI: 57.5-89.5) in the FR group and 95.7% (95% CI: 72.9-99.4) in the BH group, respectively (P = 0.16). Radiation-induced liver injury, defined by an escalation of ≥2 in Child-Pugh score, was observed in four patients within each group (FR 13% vs. BH 15%). There were no gastrointestinal adverse events of Grade 3 or higher. CONCLUSION: Breath-hold irradiation can be safely administered and has demonstrated clinical potential in improving local control. Further research into dose escalation using breath-hold techniques is warranted.

Split-Course Adaptive Radioimmunotherapy for Oligometastatic Non-Small Cell Lung Cancer (SiCARIO): A Case Report.

Current treatment paradigms for oligometastatic non-small cell lung cancer (NSCLC) utilize systemic chemotherapy alone or in combination with immune checkpoint inhibitors (ICIs). The addition of ICIs in NSCLC has led to significant improvements in survival; however, recurrence remains common. New methods are needed to enhance anti-tumor immune responses and improve patient outcomes. Here, we present the first case of utilization of the Ethos OART platform to deliver multi-site pulsed hypofractionated radiotherapy in a patient with oligometastatic disease on the single arm prospective clinical trial SiCARIO (Split-Course Adaptive Radioimmunotherapy in Oligometastatic NSCLC, NCT05501665). A 67-year-old man with stage IV NSCLC with metastases to bilateral adrenal glands, retroperitoneum, and mesentery was prescribed treatment of 40 Gy in 5 fractions on SiCARIO in combination with SOC chemoimmunotherapy. A multi-target single isocenter approach was utilized to treat nine distinct targets in five total isocenters. Treatment plans were generated using an isotopic approach prioritizing organ at risk (OAR) constraints with the goal of minimum coverage of at least 30 Gy in 5 fractions. CBCT was acquired with each fraction to generate new targets and OAR contours based on anatomic changes with the patient on the treatment table. A comparison of an adapted plan to a base plan was performed online with a selection of superior plans based on target coverage and OAR constraints. The adapted plan was deemed superior for all but 1 fraction of a single isocenter for this patient. The discussion will focus primarily on the bilateral adrenal isocenter, where bulk tumor shrinkage of greater than 80% was observed in this patient with corresponding significant dosimetric benefits. This case demonstrates a potential clinical benefit of OART in multi-metastasis RT. Further data is needed to confirm the safety and efficacy of this approach. Enrollment is ongoing.

Transition of Online Adaptive Stereotactic Radiotherapy for Pancreatic Cancer From Magnetic Resonance-Guided Linear Accelerator (MR-Linac) to State-of-the-Art Cone-Beam Computed Tomography (CBCT).

Pancreatic cancer is one of the most challenging tumor sites to treat safely and effectively with radiotherapy due to the anatomical location and aggressiveness of the disease. One modality that has shown promising results, which our institution has been employing, is online adaptive stereotactic radiotherapy using a magnetic resonance-guided linear accelerator (MR-linac). However, due to unforeseen circumstances regarding our MR-linac, it was necessary for our institution to use an alternative treatment technique. In this case report, we describe our experience using our ring-gantry linac equipped with an advanced cone-beam computed tomography (CBCT) system to treat a 61-year-old patient with advanced pancreatic cancer with CBCT-guided online adaptive stereotactic radiotherapy. In a short time period of four weeks, we prepared for this case by training with the surface scanning motion management system and developing procedures for planning and adaptation. The patient was prescribed 24 Gy in three fractions, with a risk-adapted approach using strict organ-at-risk (OAR) constraints. Daily CBCT was used for online adaptation of the plan, and the superior plan (non-adapted or adapted) was selected for treatment. For this patient, the adapted plan was chosen for all three fractions, due to OAR constraints being violated in the non-adapted plan. In summary, we found that for this patient, high-quality CBCT guidance for daily re-contouring, in combination with motion management, enabled the use of daily adaptive radiotherapy to safely deliver stereotactic radiotherapy. The results from this case report are promising, and CBCT-guided online adaptive stereotactic radiotherapy for pancreatic cancer warrants further investigation in more patients.

Adaptive Stereotactic Body Radiation Therapy in the Management of Oligometastatic Uterine Leiomyosarcoma: A Clinical Case Report.

Safe delivery of stereotactic body radiation therapy (SBRT) to large (>5 cm) oligometastatic abdominopelvic tumors can often be challenging, especially in tumors that require a higher biologically effective dose (BED) for tumor control. Adaptive stereotactic body radiation therapy (A-SBRT) involves inter-fraction and real-time replanning while the patient is on the treatment table, potentially allowing for improved dose coverage and greater sparing of critical structures. Our case report illustrates the benefit of CT-based A-SBRT in the treatment and management of an oligometastatic uterine leiomyosarcoma patient with a rapidly enlarging pelvic recurrence. A 60-year-old female presented to the radiation oncology clinic for treatment of an enlarging, right pelvic oligometastatic leiomyosarcoma. She was prescribed 35 Gy in five fractions. Planning prioritized the sparing of nearby small bowels while maximizing coverage of the planning target volume (PTV). On treatment day, two plans were calculated, the initial plan recalculated on the current CBCT (scheduled plan) and a plan reoptimized using current contours (adapted plan), and the more appropriate one was chosen for delivery. The adapted plan was chosen for all five fractions, with the adapted plan offering better small bowel sparing in five fractions and better target coverage in four fractions, delivering a total of 34 Gy to 95% of the PTV while limiting the small bowel to a maximum point dose of 37 Gy. At approximately six months out from treatment, the patient showed continued radiographic response and resolved acute Grade 1 gastrointestinal toxicity. This case study therefore demonstrates the successful treatment of a large oligometastatic abdominopelvic tumor using CT-based A-SBRT and builds on previous experience treating abdominal cases adaptively.

Optimizing target and diaphragmatic configuration, and dosimetric benefits using continuous positive airway pressure in stereotactic ablative radiotherapy for lung tumors.

PURPOSE: This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. MATERIALS AND METHODS: We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. RESULTS: Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm3 vs. 4.09 cm3; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm3 vs. 22.52 cm3, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. CONCLUSION: This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management.

Stereotactic body radiotherapy versus lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity matching score analysis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the survival benefit of Stereotactic Body Radiotherapy (SBRT) versus lenvatinib as first-line therapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: 147 HCC patients with PVTT were included in this retrospective study, 70 were treated with SBRT and 77 of were treated with lenvatinib. Propensity score matching (PSM) analysis was employed to balance the differences in baseline characteristics between the two groups. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between the two groups. In addition, the safety of patients in both groups was also evaluated. RESULTS: After PSM, 38 patients were matched in each of the two groups. The median OS was 14.5 (95% CI: 10.1-18.9) and 11.1 (95% CI: 9.3-12.9) months in the SBRT and lenvatinib groups, respectively (P = 0.014). The median PFS was 6.8 (95% CI: 5.1-8.5) and 5.0 (95% CI: 3.0-7.0) months, respectively (P = 0.010). The 1-, 2-years OS rates in the two groups were 65.8% vs. 39.5% and 31.6% vs. 10.5%, respectively. The 6-, 12-months PFS rates in the two groups were 57.9% vs. 44.7% and 28.9% vs. 10.5%, respectively. In addition, the SBRT group had a better ORR than the lenvatinib group (52.6% vs. 23.7%, P = 0.009). Patients with good response to SBRT had better survival. Cox proportional hazard model showed that SBRT was an important prognostic factor for OS and PFS. The incidence of hypertension (34.2% vs. 0%) was higher in the LEN group, however, both treatment modalities were well tolerated in the two groups of patients. CONCLUSION: In HCC patients with PVTT, SBRT had a better survival benefit than Lenvatinib treatment as first-line therapy.

Uninvolved liver dose prediction in stereotactic body radiation therapy for liver cancer based on the neural network method.

BACKGROUND: The quality of a radiotherapy plan often depends on the knowledge and expertise of the plan designers. AIM: To predict the uninvolved liver dose in stereotactic body radiotherapy (SBRT) for liver cancer using a neural network-based method. METHODS: A total of 114 SBRT plans for liver cancer were used to test the neural network method. Sub-organs of the uninvolved liver were automatically generated. Correlations between the volume of each sub-organ, uninvolved liver dose, and neural network prediction model were established using MATLAB. Of the cases, 70% were selected as the training set, 15% as the validation set, and 15% as the test set. The regression R-value and mean square error (MSE) were used to evaluate the model. RESULTS: The volume of the uninvolved liver was related to the volume of the corresponding sub-organs. For all sets of R-values of the prediction model, except for Dn0 which was 0.7513, all R-values of Dn10-Dn100 and Dnmean were > 0.8. The MSE of the prediction model was also low. CONCLUSION: We developed a neural network-based method to predict the uninvolved liver dose in SBRT for liver cancer. It is simple and easy to use and warrants further promotion and application.

Prognostic Index for Liver Radiation (PILiR).

A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child-Pugh Score (CPS) (p = 0.002), serum albumin (p = 0.039), and presence of extrahepatic disease (p = 0.012) were significant predictors of early death on multivariable analysis and were included in the PILiR (total score 0 to 5). Median survival was 23.8, 9.1, 4.5, and 2.6 months for patients with 0, 1-2, 3, and 4-5 points, respectively. In the HCC dataset, CPS (p < 0.001) and gross tumor volume (p = 0.013) were predictive of early death. In the metastatic dataset, serum albumin (p < 0.001) and primary disease site (p = 0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, and 0.80, respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.

The Role of Stereotactic Body Radiotherapy (SBRT) in Oligoprogressive Renal Cell Carcinoma (RCC) Treated with ICIs-TKIs: A Retrospective Multicentric Study.

BACKGROUND: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine-kinase inhibitor (TKI). METHODS: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI-TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6-12-18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. RESULTS: After a median follow-up of 24 months, 6-12-18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. CONCLUSIONS: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs-TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Impact of instrumentation material on local recurrence: a case-matched series using carbon fiber-PEEK vs. titanium.

PURPOSE: Spine metastases are a major burden of oncologic care, contributing to substantial morbidity. A well-established treatment paradigm for patients with metastatic epidural spinal cord compression includes separation surgery followed by stereotactic body radiotherapy (SBRT). Innovations in implant technology have brought about the incorporation of Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) instrumentation for spinal fixation. We present our experience of CFR-PEEK instrumentation, comparing outcomes and complication profiles with a matched cohort of titanium instrumented cases for spine metastatic disease. METHODS: Oncology patients who underwent spinal fusion for metastatic spine disease from 2012 to 2023 were retrospectively reviewed. Ninety-nine cases with CFR-PEEK fusions were case-control matched with 50 titanium controls (2:1 ratio) based upon primary tumor type and spinal instability neoplastic score (SINS) location. Demographic, clinical, radiographic and progression free survival (PFS) were analyzed. RESULTS: In the study years, 263 patients underwent spinal decompression and fusion, for which 148 patients met predetermined inclusion criteria. Of these, 49 had titanium instrumentation, and 99 had CFR-PEEK. Complication profiles, including hardware failure and infection were similar between the groups. There was no significant difference in PFS between all CFR-PEEK and titanium patients (143 days versus 214 days; p = 0.41). When comparing patients in which recurrence was noted, CFR-PEEK patients had recurrence detected two times earlier than titanium patients (94 days versus 189 days; p = 0.013). CONCLUSION: In this case matched cohort, CFR-PEEK demonstrated decreased overall PFS suggestive of earlier local recurrence identification. Long-term studies are warranted for better evaluation of the impact on survival and systemic disease progression.

Increased Dose in Spine Stereotactic Radiosurgery for Metastatic Disease: Are We Underestimating the Risks?

Background and Objectives: The recently published Spine Stereotactic Radiosurgery (SSRS) ESTRO guidelines advise against treating spinal metastatic disease with a single dose equal to or smaller than 18 Gy, prioritizing local control over the potential for complications. This study aims to assess the necessity and validity of these higher dose recommendations by evaluating the outcomes and experiences with lower radiation doses. Materials and Methods: A retrospective evaluation of SSRS patients treated at a single institute was conducted. The outcomes and complications of this cohort were compared to the current literature and the data supporting the new ESTRO guidelines. Results: A total of 149 treatment sessions involving 242 spinal levels were evaluated. The overall local control rate was 91.2%. The mean radiation dose for the local control group compared to the local failure group was similar (17.5 vs. 17.6 Gy, not significant). The overall complication rate was 6%. These results are consistent with previous publications evaluating SSRS for metastatic spinal disease. Conclusions: SSRS dose escalation may increase local control efficacy but comes with a higher risk of complications. The evidence supporting the strong recommendations in the recent ESTRO guidelines is not robust enough to justify a universal application. Given the palliative nature of treatment for metastatic patients, dose determination should be individualized based on patient conditions and preferences, with a detailed discussion about the risk-benefit ratio of increased doses and the level of evidence supporting these recommendations.

CT-Guided Online Adaptive Radiotherapy Delivered via Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) for a Bulky Thoracic and Abdominal Mass in Oligometastatic Renal Cell Carcinoma.

In the context of oligometastatic renal cell carcinoma (RCC), local treatment with stereotactic body radiotherapy (SBRT) may improve oncologic outcomes. However, the location and size can often pose a technical challenge in standard SBRT delivery, and the dose is potentially limited by nearby organs at risk (OARs). Online adaptive radiotherapy (oART) improves radiation delivery by personalizing high-dose fractions to account for daily stochastic variations in patient anatomy or setup. The oART process aims to maximize tumor control and enhances precision by tailoring to a more accurate representation of a patient in near-real time. The proceeding re-optimization can mitigate the uncertainty inherent in the traditional radiation delivery workflow and precludes the need for larger margins that account for anatomical variations and setup errors. Here, we describe a case of oligometastatic RCC with a bulky (>300 cm3) pleural-based left lower lobe mass extending into the upper abdomen treated via personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR). Three fractions were delivered four weeks apart allowing for tumor shrinkage of these bulky lesions, and oART permitted on-table adaptation of the plan without traditional re-simulation and re-planning required during off-line adaptive radiotherapy. The plan was designed for the Ethos linear accelerator (Varian Medical Systems, Inc., Palo Alto, CA, USA). The prescription dose was 36 Gray (Gy) in three fractions, and the adapted plan was selected in each treatment over the scheduled plan due to better target coverage and reversal of OAR dose violations. The adapted plan met all OAR dose constraints, and it achieved higher target coverage in the first two PULSAR fractions compared to the scheduled plan. In the third fraction, the cumulative point dose was approaching the maximum heart tolerance, and target coverage was accordingly compromised based on clinical judgment. There was evidence of tumor regression throughout the course of treatment, and the patient did not develop any significant radiation-related toxicities. Follow-up imaging has demonstrated the overall stable size of her lesion without any evidence of disease progression. Our case reflects the benefit of adaptive SBRT delivery to a bulky mass near multiple OARs in the setting of oligometastatic RCC. The adapted plan allowed for prioritization of critical structures on a fraction-by-fraction basis while preserving the therapeutic intent of SBRT. Further integration of advanced imaging techniques, optimal disease-specific systemic immunotherapies or targeted therapies, and refinement of patient selection will be crucial in identifying which patients would most benefit from an adaptive approach.

Stereotactic body radiotherapy boost as an alternative to brachytherapy for cervical cancer: A scoping review.

PURPOSE: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer. MATERIAL AND METHODS: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety. RESULTS: Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3-5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78-92 %, and 81-92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50-77 %, and 50-69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14 %) and gastrointestinal (0-26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %. CONCLUSION: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness.

Elective pelvic nodal irradiation in the setting of ultrahypofractionated versus moderately hypofractionated and conventionally fractionated radiotherapy for prostate cancer: Outcomes from 3 prospective clinical trials.

Background and purpose: Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate. Materials and methods: Between 2011-2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35-40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0). Results: Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6-94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5-19.8 %) for CFRT, 6.5 % (0.8-12.2 %) MHRT, and 1.8 % (0-5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities. Conclusion: ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

Single preoperative radiation therapy with delayed surgery for low-risk breast cancer: Oncologic outcome, toxicity and cosmesis of the SPORT-DS phase I trial.

BACKGROUND: A novel approach using single-fraction preoperative partial breast irradiation (PBI) for low-risk breast cancer is under study. We sought to investigate the rate of pathologic response (pR), toxicities and cosmetic results related to this new treatment strategy. METHODS: Women of 65 years or older with stage I unifocal luminal A breast cancer were eligible for inclusion in this phase I prospective trial. Patients received a single 20 Gy dose of PBI followed by breast-conserving surgery (BCS) 3 months later. The primary endpoint was the pR rate, and the secondary endpoints were radiation therapy-related toxicity and cosmetic results. RESULTS: Thirteen patients were treated, with a median age of 71. Eleven patients (84.6 %) had pR with a median residual cellularity of 1 % (range: 0-10 %). At median follow-up of 48.5 months, no recurrences or cancer-related deaths were recorded. Acute radiation therapy-related toxicity were limited to grade 1 dermatitis and breast pain. At the 1-year follow-up, there were one grade 2 fat necrosis and two grade 3 toxicities (wound infection and hematoma). Only grade 1 toxicities remained at 2 years, but one grade 2 toxicity (fibrosis/induration) developed by the 3-year follow-up. Three-year patient-reported cosmetic outcomes were good or excellent in 60 % of patients. CONCLUSIONS: Single-fraction preoperative PBI preceding BCS for low-risk breast cancer is feasible, relatively well tolerated and leads to a high level of pR. The 3-month interval after PBI seems to place surgery in a post-radiation inflammatory phase. Further delay between PBI and surgery could improve pR and cosmetic outcome. NCT03917498.