Feasibility of surface-guidance combined with CBCT for intra-fractional breath-hold motion management during Ethos RT.

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs. METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP direction) on optical surface imaging was used for manually triggering intra-fractional CBCT acquisition and treatment beam irradiation during breath-hold (seven patients for the end of exhalation and three patients for the end of inhalation). Two inter-fractional CBCTs at the ends of exhalation and inhalation in each fraction were acquired to verify the primary direction and range of the tumor/imaging-surrogate (donut-shaped fiducial) motion. Intra-fractional CBCTs were used to quantify the residual motion of the tumor/imaging-surrogate within the pre-configured breath-hold window in the AP direction. Fifty fractions of Ethos RT were delivered under surface image-guidance: Thirty-two fractions with CT-STAR (adaptive RT) and 18 fractions with CT-SBRT (non-adaptive RT). The residual motion of the tumor was quantified by determining variations in the tumor centroid position. The dosimetric impact on target coverage was calculated based on the residual motion. RESULTS: We used 46 fractions for the analysis of intra-fractional residual motion and 43 fractions for the inter-fractional motion analysis due to study constraints. Using the image registration method, 43 pairs of inter-fractional CBCTs and 100 intra-fractional CBCTs attached to dose maps were analyzed. In the motion range study (image registration) from the inter-fractional CBCTs, the primary motion (mean ± std) was 16.6 ± 9.2 mm in the SI direction (magnitude: 26.4 ± 11.3 mm) for the tumors and 15.5 ± 7.3 mm in the AP direction (magnitude: 20.4 ± 7.0 mm) for the imaging-surrogate, respectively. The residual motion of the tumor (image registration) from intra-fractional breath-hold CBCTs was 2.2 ± 2.0 mm for SI, 1.4 ± 1.4 mm for RL, and 1.3 ± 1.3 mm for AP directions (magnitude: 3.5 ± 2.1 mm). The ratio of the actual dose coverage to 99%, 90%, and 50% of the target volume decreased by 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.05, respectively. The mean percentage of the target volume covered by the prescribed dose decreased by 2.8 ± 4.4%. CONCLUSION: We demonstrated the intra-fractional motion-managed treatment strategy in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT. While the controlled residual tumor motion measured at 3.5 mm exceeded the predetermined setup value of 2 mm, it is important to note that this motion still fell within the clinically acceptable range defined by the PTV margin of 5 mm. Nonetheless, additional caution is needed with intra-fractional motion management in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT.

Circumferential Resection Margin as Predictor of Nonclinical Complete Response in Nonoperative Management of Rectal Cancer.

BACKGROUND: Short-course radiation therapy and consolidation chemotherapy with nonoperative intent has emerged as a novel treatment paradigm for patients with rectal cancer, but there are no data on the predictors of clinical complete response. OBJECTIVE: Evaluate the predictors of clinical complete response and survival. DESIGN: Retrospective cohort. SETTINGS: National Cancer Institute-designated cancer center. PATIENTS: Patients with stage I to III rectal adenocarcinoma treated between January 2018 and May 2019 (n = 86). INTERVENTIONS: Short-course radiation therapy followed by consolidation chemotherapy. MAIN OUTCOME MEASURES: Logistic regression was performed to assess for predictors of clinical complete response. The end points included local regrowth-free survival, regional control, distant metastasis-free survival, and overall survival. RESULTS: A positive (+) circumferential resection margin by MRI at diagnosis was a significant predictor of nonclinical complete response (OR: 4.1, p = 0.009) when adjusting for CEA level and primary tumor size. Compared to patients with a negative (-) pathologic circumferential resection margin, patients with a positive (+) pathologic circumferential resection margin had inferior local regrowth-free survival (29% vs 87%, p < 0.001), regional control (57% vs 94%, p < 0.001), distant metastasis-free survival (43% vs 95%, p < 0.001), and overall survival (86% vs 95%, p < 0.001) at 2 years. However, the (+) and (-) circumferential resection margin by MRI subgroups in patients who had a clinical complete response both had similar regional control, distant metastasis-free survival, and overall survival of more than 90% at 2 years. LIMITATIONS: Retrospective design, modest sample size, short follow-up, and the heterogeneity of treatments. CONCLUSIONS: Circumferential resection margin involvement by MRI at diagnosis is a strong predictor of nonclinical complete response. However, patients who achieve a clinical complete response after short-course radiation therapy and consolidation chemotherapy with nonoperative intent have excellent clinical outcomes regardless of the initial circumferential resection margin status. See Video Abstract at http://links.lww.com/DCR/C190 . EL MARGEN DE RESECCIN CIRCUNFERENCIAL COMO PREDICTOR NO CLNICO DE RESPUESTA COMPLETA EN EL MANEJO CONSERVADOR DEL CNCER DE RECTO: ANTECEDENTES:La radioterapia de corta duración y la quimioterapia de consolidación en el manejo conservador, han surgido como un nuevo paradigma de tratamiento, para los pacientes con cáncer de recto, lastimosamente no hay datos definitivos sobre los predictores de una respuesta clínica completa.OBJETIVO:Evaluar los predictores de respuesta clínica completa y de la sobrevida.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro oncológico designado por el NCI.PACIENTES:Adenocarcinomas de recto estadio I-III tratados entre 01/2018 y 05/2019 (n = 86).INTERVENCIONES:Radioterapia de corta duración seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó una regresión logística para evaluar los predictores de respuesta clínica completa. Los criterios de valoración incluyeron la sobrevida libre de recidiva local, el control regional, la sobrevida libre de metástasis a distancia y la sobrevida general.RESULTADOS:Un margen de resección circunferencial positivo (+) evaluado por imagenes de resonancia magnética nuclear en el momento del diagnóstico fue un predictor no clínico muy significativo de respuesta completa (razón de probabilidades/ OR: 4,1, p = 0,009) al ajustar el nivel de antígeno carcinoembrionario y el tamaño del tumor primario. Comparando con los pacientes que presetaban un margen de resección circunferencial patológico negativo (-), los pacientes con un margen de resección circunferencial patológico positivo (+) tuvieron una sobrevida libre de recidiva local (29% frente a 87%, p < 0,001), un control regional (57% frente a 94%, p < 0,001), una sobrevida libre de metástasis a distancia (43% frente a 95%, p < 0,001) y una sobrevida global (86% frente a 95%, p < 0,001) inferior en 2 años de seguimiento. Sin embargo, los subgrupos de margen de resección circunferencial (+) y (-) evaluados por imágenes de resonancia magnética nuclear en pacientes que tuvieron una respuesta clínica completa tuvieron un control regional similar, una sobrevida libre de metástasis a distancia y una sobrevida general >90% en 2 años de seguimiento.LIMITACIONES:Diseño retrospectivo, tamaño modesto de la muestra, seguimiento corto y heterogeneidad de tratamientos.CONCLUSIONES:La afectación del margen de resección circunferencial evaluado por resonancia magnética nuclear al momento del diagnóstico es un fuerte factor predictivo no clínico de respuesta completa. Sin embargo, los pacientes que logran una respuesta clínica completa después de un curso corto de radioterapia y quimioterapia de consolidación como manejo conservador tienen excelentes resultados clínicos independientemente del estado del margen de resección circunferencial inicial. Consulte Video Resumen en http://links.lww.com/DCR/C190 . (Traducción-Dr. Xavier Delgadillo ).

The impact of tumor size and histology on local control when utilizing high-dose-rate interstitial brachytherapy for gynecologic malignancies.

OBJECTIVE: To report long-term results of an outpatient template-based high-dose-rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies. METHODS: Patients treated between 2006 and 2020 at an academic hospital with outpatient template based HDR ISBT without spinal or general anesthesia were reviewed. Patients who had previously received HDR ISBT were excluded. Baseline patient, tumor, and treatment characteristics, such as tumor size, histology, and/or total EQD2 including prior external beam radiation therapy (EBRT) were recorded. Local control and overall survival were estimated using the Kaplan-Meier method, and factors associated with local control and overall survival were evaluated using Cox regression analyses. RESULTS: 150 patients received HDR ISBT for a gynecologic tumor and the median follow-up time was 2.98 years (0.89-4.82). Of those, 74/150 (49%) were treated definitively, 69/150 (46%) were treated for tumor recurrence/persistence, and 7/150 (5%) were treated for durable palliation. Median tumor size was 3.00 cm (1.50-4.00). 124/150 (83%) patients received EBRT prior to HDR ISBT. Median HDR ISBT dose was 18 Gy delivered in eight fractions. Local control was 71% (64%-79%), 58% (50%-68%), and 57% (48%-67%) at one, three, and five years, respectively. On multivariate analysis, non-endometrial adenocarcinoma histology (HR = 2.423, 95% CI = 1.011-5.808, p = 0.047) and tumor size ≥ 3 cm (HR = 2.903, 95% CI 1.053-3.441, p = 0.033) were associated with lower local control. CONCLUSIONS: The majority of patients who received outpatient-based twice daily HDR ISBT had long-term local control. Larger tumor size and non-endometrial adenocarcinoma histology were detrimental to local control.

Overall survival in patients with FIGO stage IVA cervical cancer.

OBJECTIVE: FIGO stage IVA cervical cancer is a unique diagnosis that conveys a poor prognosis. Despite the use of PET/CT for staging, concurrent chemotherapy, and image-guided brachytherapy, overall survival (OS) in these patients is low. Treatment requires aggressive use of radiotherapy and chemotherapy. We report results of a prospective observational cohort study for patients with de novo stage IVA cervical cancer treated at a single institution. METHODS: Patients with a new diagnosis of stage IVA cervical cancer treated at an academic institution between 1997 and 2020 were prospectively monitored. Staging was retroactively assigned using the 2018 FIGO staging system. All patients had a PET/CT prior to treatment and were treated with definitive intent radiotherapy with or without chemotherapy. The primary outcome of interest was OS. Secondary outcomes were local control, progression-free survival (PFS), and disease-specific survival (DSS). RESULTS: 32 patients with de novo stage IVA cervical cancer were treated with definitive intent radiotherapy. Median follow-up time was 4.27 years (1.31-10.35). 22/32 (69%) of patients received brachytherapy as a part of their definitive treatment, and 28/32 (88%) received chemotherapy concurrently with radiotherapy. 14/32 (44%) of patients had no evidence of disease at last follow-up. The 5-year local control, PFS, DFS, and OS estimates were 79%, 49%, 53%, and 48%, respectively. On multivariate analysis, complete metabolic response was associated with a statistically significant improvement in PFS (HR = 0.256, 95% CI = 0.078-0.836, p = 0.024) and OS (HR = 0.273, 95% CI 0.081-0.919). CONCLUSIONS: These data demonstrate a robust OS in patients with stage IVA cervical cancer when treated with definitive chemoradiotherapy.

Early prostate-specific antigen response post-abiraterone as predictor of overall survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: Abiraterone is an important agent in the treatment of advanced prostate cancer. Early changes in prostate-specific antigen while on abiraterone in patients with metastatic castrate-resistant prostate cancer potentially have financial and health implications for patients. Limited data is available on early prostate-specific antigen change and subsequent survival given phase III trials did not measure prostate-specific antigen changes before 12 weeks. METHODS: A single-center retrospective study was performed. Metastatic castrate-resistant prostate cancer patients treated with abiraterone (without prior enzalutamide) at Tulane Cancer Center were reviewed with a focus on early prostate-specific antigen decline and relationship to overall survival. RESULTS: A total of 110 patients were analyzed for prostate-specific antigen response of ≥ 30 and > 50% at 4, 8, and 12 weeks. A prostate-specific antigen response of either > 30% or > 50% at 4, 8, or 12 weeks was associated with improved overall survival at all time points except > 50% decline at 8 weeks. Multivariate analysis indicated, for all time points, that early prostate-specific antigen declines were predictive of overall survival. The neutrophil to lymphocyte ratio and docetaxel pretreatment also were predictive in many, but not all, of the multivariate analyses. CONCLUSIONS: A > 30% or > 50% prostate-specific antigen decline at 4, 8, or 12 weeks provides important information regarding subsequent overall survival for patients with metastatic castrate-resistant prostate cancer. While these data require validation with a large, multi-institutional trial, they can provide physicians with information regarding prognosis and the timing of expected outcomes. These data affirms the notion that prostate-specific antigen responses as early as 4 weeks after abiraterone initiation can be used to inform both patients and physicians about metastatic castrate-resistant prostate cancer outcomes after initiating treatment with this important but costly therapeutic choice.

Cone-Beam Computed Tomography (CBCT)-Guided Adaptive Boost Radiotherapy for a Patient With Locally Advanced Cervical Cancer Ineligible for Brachytherapy.

Brachytherapy is a critical component of locally advanced cervical cancer treatment, and patients ineligible for brachytherapy historically have poor outcomes. Delivery of boost with stereotactic body radiation therapy (SBRT) has been studied, though toxicity is a concern. Recent case reports have explored adaptive radiation boost, which can adjust plans for inter-fraction motion using magnetic resonance guidance. Herein, we report the first patient with locally advanced cervical cancer ineligible for brachytherapy who was treated with a cone-beam computed tomography (CBCT)-guided adaptive boost following completion of chemoradiation. A 71-year-old female with locally advanced cervical cancer was treated with chemoradiation and was deemed ineligible for a brachytherapy boost due to tumor size, geometry, and a fistula with a tumor in the bladder. She was prescribed a boost to the primary tumor of 25 Gy in five fractions using CBCT-guided adaptive radiation following the completion of chemoradiation. A simulation was performed using a non-contrast CT fused with a mid-chemoradiation magnetic resonance imaging (MRI) scan to create an initial plan. For each treatment fraction, kilovoltage CBCTs were acquired, contours of organs at risk (OARs) were adjusted to reflect anatomy-of-the-day, and an adapted plan was generated. The initial and adapted plans were compared using dose-volume histogram objectives, and the adapted plan was used if it resolved OAR constraint violations or improved target coverage. The use of the initial treatment plan would have resulted in constraint violations for the rectum, sigmoid, and bladder in all fractions. The adapted plans achieved hard constraints in all fractions for all four critical OARs. The mean total treatment time across all five fractions was 58 minutes. This case demonstrates the feasibility of a CBCT-guided adaptive boost approach and the dosimetric benefits of plan adaptation in this setting. Though larger-scale and longer-term data are needed, CBCT-guided adaptive radiation may present a feasible alternative modality to deliver boost doses for brachytherapy-ineligible patients.

The impact of an Advanced Practice Radiation Therapist contouring for a CBCT-based adaptive radiotherapy program.

We successfully implemented an APRT specializing in CBCT-guided online adaptive contouring. These data show statistical improvements in contouring time with APRT-led vs non-APRT led ART contouring, suggesting that an APRT specifically trained to manage the ART process may reduce physician workload and patient treatment time.

The Use of MR-Guided Radiation Therapy for Liver Cancer.

The role of radiotherapy in the management of primary and metastatic liver malignancies has expanded in recent years due to advances such as IGRT and SBRT. MRI-guided radiotherapy (MRgRT) has arisen as an excellent option for the management of hepatocellular carcinoma, cholangiocarcinoma, and liver metastases due to the ability to combine improved hepatic imaging with conformal treatment planning paradigms like adaptive radiotherapy and advanced motion management techniques. Herein we review the data for MRgRT for liver malignancies, as well as describe workflow and technical considerations for the 2 commercially available MRgRT delivery platforms.

Feasibility of simulation free abdominal stereotactic adaptive radiotherapy using an expedited pre-plan workflow.

Background and Purpose: Improved hounsfield-unit accuracy of on-board imaging may lead to direct-to-unit treatment approaches We aimed to demonstrate the feasibility of using only a diagnostic (dx) computed tomography (CT)-defined target pre-plan in an in silico study of simulation-free abdominal stereotactic adaptive radiotherapy (ART). Materials and Methods: Eight patients with abdominal treatment sites (five pancreatic cancer, three oligometastases) were treated using an integrated adaptive O-Ring gantry system. Each patient's target was delineated on a dxCT. The target only pre-plan served primarily to seed the ART process. During the ART session, all structures were delineated. All simulated cases were treated to 50 Gy in 5 fractions to a planning target optimization structure (PTV_OPT) to allow for dose escalation within the planning target volume. Timing of steps during this workflow was recorded. Plan quality was compared between ART treatment plans and a plan created on a CT simulation scan using the traditional planning workflow. Results: The workflow was feasible in all attempts, with organ-at-risk (OAR) constraints met in all fractions despite lack of initial OAR contours. Median absolute difference between the adapted plan and simulation CT plan for the PTV_Opt V95% was 2.0 %. Median absolute difference in the D0.5 cm3 between the adapted plan and simulation CT plan was -0.9 Gy for stomach, 1.2 Gy for duodenum, -5.3 Gy for small bowel, and 0.3 Gy for large bowel. Median end-to-end workflow time was 63 min. Conclusion: The workflow was feasible for a dxCT-defined target-only pre-plan approach to stereotactic abdominal ART.

The First Reported Case of Treating the Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR).

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. He was prescribed 55 Gy in five fractions with CT-STAR. A simulation was performed using four-dimensional CT, and patients were planned for treatment at end-exhale breath-hold. Treatment plans were generated using a strict isotoxicity approach, which prioritized organ at risk (OAR) constraints over target coverage. During treatment, daily CBCTs were acquired and used to generate adapted contours and treatment plans based on the patient's anatomy-of-the-day, all while the patient was on the treatment table. The initial and adapted plans were compared using dose-volume histograms, and the superior plan was selected for treatment. The adapted plan was deemed superior and used for treatment in three out of five fractions. The adapted plan provided improved target coverage in two fractions and resolved an OAR hard constraint violation in one fraction. We report the successful treatment of a patient with ultra-central NSCLC utilizing CT-STAR. This case report builds on previously published in silico data to support the viability and dosimetric advantages of CT-STAR in the ablative treatment of this challenging tumor location. Further data are needed to confirm the toxicity and efficacy of this technique.

Dosimetric predictors of acute and late gastrointestinal toxicities in stereotactic online adaptive magnetic resonance-guided radiotherapy (SMART) for locally advanced pancreatic adenocarcinoma.

BACKGROUND AND PURPOSE: A retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART). MATERIALS AND METHODS: 147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR multicollinearity. A receiver operator curve (ROC) analysis was performed for the combined averages of significant toxicity groups to identify critical volumes per dose levels. RESULTS: 18 of 147 patients experienced Gr2+ GI toxicity. 17 Gr2+ duodenal toxicities were seen; the most significant predictor was a V33Gy odds ratio (OR) of 1.69 per cc (95 % CI 1.14-2.88). 17 Gr2+ small bowel (SB) toxicities were seen; the most significant predictor was a V33Gy OR of 1.60 per cc (95 % CI 1.01-2.53). The AUC was 0.72 for duodenum and SB. The optimal duodenal cut-point was 1.00 cc (true positive (TP): 17.8 %; true negative (TN); 94.9 %). The SB cut-point was 1.75 cc (TP: 16.7 %; TN: 94.3 %). No stomach or large bowel dose toxicity predictors were identified. CONCLUSIONS: For LAPC treated with SMART, the dose-volume threshold of V33Gy for duodenum and SB was associated with Gr2+ toxicities. These metrics can be utilized to guide future dose-volume constraints for patients undergoing upper abdominal SBRT.

Ablative radiotherapy for colorectal liver metastases and intrahepatic cholangiocarcinoma.

The role of radiation therapy in the management of liver cancers, both primary and metastatic, has changed drastically over the past several decades. Although conventional radiation was limited by technology, the advent of advanced image-guided radiotherapy and the rise in evidence for and popularity of stereotactic body radiotherapy have expanded the indications for radiation in these two distinct disease types. Magnetic resonance imaging-guided radiation therapy, daily online adaptive radiotherapy, and proton radiotherapy are some of many modern radiotherapy techniques that allow for increasingly efficacious treatment of intrahepatic disease while simultaneously allowing for increased normal tissue sparing, including sparing of the normal liver and the radiosensitive luminal gastrointestinal tract. Modern radiation therapy should be considered along with approaches such as surgical resection and radiofrequency ablation for the management of liver cancers of diverse histologies. Herein we describe the use of modern radiotherapy in two example settings, colorectal liver metastases and intrahepatic cholangiocarcinoma, and how external beam radiotherapy provides options within multidisciplinary discussions to elect optimal patient-specific treatments.

An Analysis of Major Target Deviations in Craniospinal Irradiation Treatment Plans for Patients With Intermediate-Risk Medulloblastoma Within a Phase 3 Clinical Trial (Children's Oncology Group Study ACNS0331).

Purpose: Craniospinal irradiation remains an essential and yet difficult part of the treatment of patients with medulloblastoma. Whereas technological advances offer promise of increased conformity, realiance on advanced technology is not without risk, and it remains critical to carefully delineate targets. We describe examples of target deviations (TDs) in craniospinal irradiation treatment plans for postoperative patients with medulloblastoma in a phase 3 clinical trial (ACNS 0331). Methods and Materials: The principal investigator independently performed a review of the treatment plans and portal films of enrolled patients and evaluated the plans for TDs. TDs of dose, dose uniformity, and volume were defined as major or minor deviations. Major TDs scored as protocol violations. The effect of major TDs on event-free survival (EFS) and overall survival (OS) was evaluated using the stratified Cox proportional hazards model. Results: Of the 549 patients enrolled, 461 were available for this analysis. Thirty-two (7%) plans did not have data sufficient for TD evaluation. Major TDs were found in 32 of the 461 plans (7%). Of those, 21 were deviations of target volume alone, 7 were deviations of target dose alone, and 4 were deviations of both target volume and dose. The 25 patients with TDs of volume involved 29 sites. The most common major TDs of volume involved the brain (9 of 29) and the posterior fossa (9 of 29). On Cox proportional hazards modeling, the presence of a major TD did not statistically significantly affect EFS (hazard ratio, 0.98; 95% confidence interval, 0.45-2.11; P = .9541) or OS (hazard ratio, 1.10; 95% confidence interval, 0.51-2.38; P = .8113). Conclusions: Although intensity modulated radiation therapy and proton therapy are promising in improving conformity and sparing organs at risk, technology does not substitute for careful anatomic definition of target volumes. The study was not powered to evaluate the effect of TDs on EFS and OS; therefore, the statistical analysis presented in this study must be interpreted with caution.

Simulation-Free Radiation Therapy: An Emerging Form of Treatment Planning to Expedite Plan Generation for Patients Receiving Palliative Radiation Therapy.

Purpose: Herein we report the clinical and dosimetric experience for patients with metastases treated with palliative simulation-free radiation therapy (SFRT) at a single institution. Methods and Materials: SFRT was performed at a single institution. Multiple fractionation regimens were used. Diagnostic imaging was used for treatment planning. Patient characteristics as well as planning and treatment time points were collected. A matched cohort of patients with conventional computed tomography simulation radiation therapy (CTRT) was acquired to evaluate for differences in planning and treatment time. SFRT dosimetry was evaluated to determine the fidelity of SFRT. Descriptive statistics were calculated on all variables and statistical significance was evaluated using the Wilcoxon signed rank test and t test methods. Results: Thirty sessions of SFRT were performed and matched with 30 sessions of CTRT. Seventy percent of SFRT and 63% of CTRT treatments were single fraction. The median time to plan generation was 0.88 days (0.19-1.47) for SFRT and 1.90 days (0.39-5.23) for CTRT (P = .02). The total treatment time was 41 minutes (28-64) for SFRT and 30 minutes (21-45) for CTRT (P = .02). In the SFRT courses, the maximum and mean deviations in the actual delivered dose from the approved plans for the maximum dose were 4.1% and 0.07%, respectively. All deliveries were within a 5% threshold and deemed clinically acceptable. Conclusions: Palliative SFRT is an emerging technique that allowed for a statistically significant lower time to plan generation and was dosimetrically acceptable. This benefit must be weighed against increased total treatment time for patients receiving SFRT compared with CTRT, and appropriate patient selection is critical.

A pilot study of same-day MRI-only simulation and treatment with MR-guided adaptive palliative radiotherapy (MAP-RT).

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3-5 toxicities occurred.

Knowledge-based adaptive planning quality assurance using dosimetric indicators for stereotactic adaptive radiotherapy for pancreatic cancer.

INTRODUCTION: We aimed to develop knowledge-based tools for robust adaptive radiotherapy (ART) planning to determine on-table adaptive DVH metric variations or planning process errors for stereotactic pancreatic ART. We developed volume-based dosimetric identifiers to identify deviations of ART plans from simulation plans. MATERIALS AND METHODS: Two patient cohorts who were treated on MR-Linac for pancreas cancer were included in this retrospective study; a training cohort and a validation cohort. All patients received 50 Gy in 5 fractions. PTV-OPT was generated by subtracting the critical organs plus a 5 mm-margin from PTV. Several metrics that potentially can identify failure-modes were calculated including PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5%. The difference between each DVH metric in each adaptive plan with the DVH metric in simulation plan was calculated. The 95% confidence interval (CI) of the variations in each DVH metric was calculated for the patient training cohort. Variations in DVH metrics that exceeded the 95% CI for all fractions in training and validation cohort were flagged for retrospective investigation for root-cause analysis to determine their predictive power for identifying failure-modes. RESULTS: The CIs for the PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5% were ± 13%, ± 5%, ± 0.1, ± 0.03, respectively. We estimated the positive predictive value and negative predictive value of our method to be 77% and 89%, respectively, for the training cohort, and 80% for both in the validation cohort. DISCUSSION: We developed dosimetric indicators for ART planning QA to identify population-based deviations or planning errors during online adaptive process for stereotactic pancreatic ART. This technology may be useful as an ART clinical trial QA tool and improve overall ART quality at an institution.

Prospective In Silico Evaluation of Cone-Beam Computed Tomography-Guided StereoTactic Adaptive Radiation Therapy (CT-STAR) for the Ablative Treatment of Ultracentral Thoracic Disease.

Purpose: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage. Methods and Materials: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico. Initial, nonadaptive plans (PI) were created based on simulation images and simulated adaptive plans (PA) were based on study CBCTs. 55 Gy/5 fractions was prescribed, with OAR constraint prioritization over PTV coverage under a strict isotoxicity approach. PI were applied to patients' anatomy of the day and compared with daily PA using dose-volume histogram metrics, with selection of superior plans for simulated delivery. Feasibility was defined as completion of the end-to-end adaptive workflow while meeting strict OAR constraints in ≥80% of fractions. CT-STAR was performed under time pressures to mimic clinical adaptive processes. Results: Seven patients were accrued, 6 with intraparenchymal tumors and 1 with a subcarinal lymph node. CT-STAR was feasible in 34 of 35 simulated fractions. In total, 32 dose constraint violations occurred when the PI was applied to anatomy-of-the-day across 22 of 35 fractions. These violations were resolved by the PA in all but one fraction, in which the proximal bronchial tree dose was still numerically improved through adaptation. The mean difference between the planning target volume and gross total volume V100% in the PI and the PA was -0.24% (-10.40 to 9.90) and -0.62% (-11.00 to 8.00), respectively. Mean end-to-end workflow time was 28.21 minutes (18.02-50.97). Conclusions: CT-STAR widened the dosimetric therapeutic index of ultracentral thorax SBRT compared with nonadaptive SBRT. A phase 1 protocol is underway to evaluate the safety of this paradigm for patients with ultracentral early-stage NSCLC.

First treatments for Lattice stereotactic body radiation therapy using magnetic resonance image guided radiation therapy.

Two abdominal patients were treated with Lattice stereotactic body radiation therapy (SBRT) using magnetic resonance guided radiation therapy (MRgRT). This is one of the first reported treatments of Lattice SBRT with the use of MRgRT. A description of the treatment approach and planning considerations were incorporated into this report. MRgRT Lattice SBRT delivered similar planning quality metrics to established dosimetric parameters for Lattice SBRT. Increased signal intensity were seen in the MRI treatments for one of the patients during the course of treatment.

Clinical outcomes of patients with unresectable primary liver cancer treated with MR-guided stereotactic body radiation Therapy: A Six-Year experience.

Purpose: Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) with optional online adaptation has shown promise in delivering ablative doses to unresectable primary liver cancer. However, there remain limited data on the indications for online adaptation as well as dosimetric and longer-term clinical outcomes following MRgSBRT. Methods and Materials: Patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CCA) who completed MRgSBRT to 50 Gy in 5 fractions between June of 2015 and December of 2021 were analyzed. The necessity of adaptive techniques was evaluated. The cumulative incidence of local progression was evaluated and survival and competing risk analyses were performed. Results: Ninety-nine analyzable patients completed MRgSBRT during the study period and 54 % had planning target volumes (PTVs) within 1 cm of the duodenum, small bowel, or stomach at the time of simulation. Online adaptive RT was used in 53 % of patients to correct organ-at-risk constraint violation and/or to improve target coverage. In patients who underwent adaptive RT planning, online replanning resulted in superior target coverage when compared to projected, non-adaptive plans (median coverage ≥ 95 % at 47.5 Gy: 91 % [IQR: 82-96] before adaptation vs 95 % [IQR: 87-99] after adaptation, p < 0.01). The median follow-up for surviving patients was 34.2 months for patients with HCC and 10.1 months for patients with CCA/cHCC-CCA. For all patients, the 2-year cumulative incidence of local progression was 9.8 % (95 % CI: 1.5-18 %) for patients with HCC and 9.0 % (95 % CI: 0.1-18) for patients with CCA/cHCC-CCA. Grade 3 through 5 acute and late clinical gastrointestinal toxicities were observed in < 10 % of the patients. Conclusions: MRgSBRT, with the option for online adaptive planning when merited, allows delivery of ablative doses to primary liver tumors with excellent local control with acceptable toxicities. Additional studies evaluating the efficacy and safety of MRgSBRT in the treatment of primary liver cancer are warranted.

Initial clinical experience building a dual CT- and MR-guided adaptive radiotherapy program.

Introduction: Our institution was the first in the world to clinically implement MR-guided adaptive radiotherapy (MRgART) in 2014. In 2021, we installed a CT-guided adaptive radiotherapy (CTgART) unit, becoming one of the first clinics in the world to build a dual-modality ART clinic. Herein we review factors that lead to the development of a high-volume dual-modality ART program and treatment census over an initial, one-year period. Materials and Methods: The clinical adaptive service at our institution is enabled with both MRgART (MRIdian, ViewRay, Inc, Mountain View, CA) and CTgART (ETHOS, Varian Medical Systems, Palo Alto, CA) platforms. We analyzed patient and treatment information including disease sites treated, radiation dose and fractionation, and treatment times for patients on these two platforms. Additionally, we reviewed our institutional workflow for creating, verifying, and implementing a new adaptive workflow on either platform. Results: From October 2021 to September 2022, 256 patients were treated with adaptive intent at our institution, 186 with MRgART and 70 with CTgART. The majority (106/186) of patients treated with MRgART had pancreatic cancer, and the most common sites treated with CTgART were pelvis (23/70) and abdomen (20/70). 93.0% of treatments on the MRgART platform were stereotactic body radiotherapy (SBRT), whereas only 72.9% of treatments on the CTgART platform were SBRT. Abdominal gated cases were allotted a longer time on the CTgART platform compared to the MRgART platform, whereas pelvic cases were allotted a shorter time on the CTgART platform when compared to the MRgART platform. Our adaptive implementation technique has led to six open clinical trials using MRgART and seven using CTgART. Conclusions: We demonstrate the successful development of a dual platform ART program in our clinic. Ongoing efforts are needed to continue the development and integration of ART across platforms and disease sites to maximize access and evidence for this technique worldwide.