Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy.

PURPOSE: The purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis. METHODS: Forty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments. RESULTS: BV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN. CONCLUSION: The use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.

Evaluation of Nutritional Status and Anxiety Levels in Patients Applying to the Radiation Oncology Outpatient Clinic during the COVID-19 Pandemic: Turkish Society for Radiation Oncology Group Study (TROD 12:02).

Cancer patients often face malnutrition, which negatively affects their response to cancer treatment. This study aims to analyze the effects of the COVID-19 pandemic on nutritional status and anxiety in cancer patients with different types and stages of cancer. This is a cross-sectional cohort study that includes 1,252 patients with varying cancer types from 17 radiation oncology centers. The nutritional risk scores (NRS-2002) and coronavirus anxiety scale (CAS) scores of all patients were measured. NRS-2002 ≥ 3 and CAS ≥ 5 were accepted as values at risk. Of all patients, 15.3% had NRS-2002 ≥ 3. Breast cancer was the most prevalent cancer type (24.5%) with the lowest risk of nutrition (4.9%, p < 0.001). Nutritional risk was significantly higher in patients with gastrointestinal cancer, head and neck cancer, and lung cancer (p < 0.005) and in patients with stage IV disease (p < 0.001). High anxiety levels (CAS ≥ 5) were significantly related to voluntary avoidance and clinical postponement of hospital visits due to the pandemic (p < 0.001), while clinical postponement was particularly frequent among patients with NRS-2002 < 3 (p = 0.0021). Fear and anxiety in cancer patients with COVID-19 cause hesitations in visiting hospitals, leading to disrupted primary and nutritional treatments. Thus, nutritional monitoring and treatment monitoring of cancer patients are crucial during and after radiotherapy.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Factors influencing local control after MR-guided stereotactic body radiotherapy (MRgSBRT) for adrenal metastases.

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal gland metastases, but it is technically challenging and there are concerns about toxicity. We performed a multi-institutional pooled retrospective analysis to study clinical outcomes and toxicities after MR-guided SBRT (MRgSBRT) using for adrenal gland metastases. Methods and Materials: Clinical and dosimetric data of patients treated with MRgSBRT on a 0.35 T MR-Linac at 11 institutions between 2016 and 2022 were analyzed. Local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Results: A total of 255 patients (269 adrenal metastases) were included. Metastatic pattern was solitary in 25.9 % and oligometastatic in 58.0 % of patients. Median total dose was 45 Gy (range, 16-60 Gy) in a median of 5 fractions, and the median BED10 was 100 Gy (range, 37.5-132.0 Gy). Adaptation was done in 87.4 % of delivered fractions based on the individual clinicians' judgement. The 1- and 2- year LPFS rates were 94.0 % (95 % CI: 90.7-97.3 %) and 88.3 % (95 % CI: 82.4-94.2 %), respectively and only 2 patients (0.8 %) experienced grade 3 + toxicity. No local recurrences were observed after treatment to a total dose of BED10 > 100 Gy, with single fraction or fractional dose of > 10 Gy. Conclusions: This is a large retrospective multi-institutional study to evaluate the treatment outcomes and toxicities with MRgSBRT in over 250 patients, demonstrating the need for frequent adaptation in 87.4 % of delivered fractions to achieve a 1- year LPFS rate of 94 % and less than 1 % rate of grade 3 + toxicity. Outcomes analysis in 269 adrenal lesions revealed improved outcomes with delivery of a BED10 > 100 Gy, use of single fraction SBRT and with fraction doses > 10 Gy, providing benchmarks for future clinical trials.

Magnetic Resonance Imaging-Guided Radiation Therapy for Early-Stage Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Lymphoid neoplasia derived from mucosa-associated lymphoid tissue (MALT; also abbreviated as MALToma) is most commonly seen in the stomach. Radiotherapy (RT) is indicated in early-stage disease as a standard of care. With the advent of RT techniques, large field irradiation was replaced by involved site and involved field approaches. Magnetic resonance imaging-guided online adaptive RT (MRgRT) has the advantage of better soft tissue visualization, adaptive planning before each fraction, and online tumor tracking during treatment; hence, it could be a safe and effective choice for gastric MALToma patients. Herein, we investigated the interfractional changes in target and the impact of MRgRT on daily dosimetry in a gastric MALToma case. A patient diagnosed with MALToma who failed to respond to antibacterial treatment was referred to our clinic for RT. He was found to be suitable for MRgRT. We treated the patient with MRgRT in 20 fractions to a total dose of 30 Gy. Reoptimized adaptive plans were generated before each fraction since the coverages of the original plan were inadequate in each fraction. The patient showed good compliance and tolerated the treatment well. To our knowledge, this is the first documented case of a gastric MALToma treated with MRgRT. MRgRT is safe and feasible for this patient group with improved target coverage using small planning target volume margins. Without online adaptive planning, the target coverages would be inadequate and we would risk surrounding tissues to get higher doses.

Magnetic Resonance Image-Guided Hypofractionated Ablative Radiation Therapy for Hepatocellular Carcinoma With Tumor Thrombus Extending to the Right Atrium.

Hepatocellular carcinoma (HCC) presenting with tumor thrombus (TT) and inferior vena cava (IVC)/right atrium (RA) infringement point to an advanced-stage disease that is deemed inoperable. Stereotactic body radiotherapy is an emerging treatment option for this group of patients with promising outcomes in recent studies that are comparable to conventional treatment methods, namely, transarterial chemoembolization and transarterial radioembolization. Here, we report a case of HCC with RA extension through the IVC. The patient was referred to our clinic for treatment options, and he was found suitable for magnetic resonance imaging-guided radiotherapy (MRgRT). We treated the patient with MRgRT in five fractions to a total dose of 40 Gray. The tumor was tracked during the treatment sessions, and adaptive treatment planning was performed before each fraction. The patient tolerated the treatment well with no acute grade 3-4 toxicities. The last follow-up showed that the patient had a complete biochemical response and is now a candidate for an orthotopic liver transplant. To our knowledge, this report is the first to document the MRgRT treatment of an HCC with TT and RA extension. MRgRT is safe and feasible for this patient group and can be an effective bridging therapy for liver transplants.

Stereotactic Radiotherapy for Adrenal Metastases: A Multi-Institutional Review of Patient Characteristics and Outcomes - Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10-004).

INTRODUCTION: This study aimed to report the outcomes of stereotactic body radiotherapy (SBRT) for adrenal metastasis in a retrospective multi-institutional cohort. METHODS: The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods. RESULTS: The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median biologically effective dose (BED)10 was 61 Gy. The overall LC rate was 83%, and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival, overall survival (OS), and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and <4-cm lesion and PFS with a fraction dose ≥8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity, and late toxicity was observed in 3 patients, including one grade 5. CONCLUSION: A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients, and systemic treatment options are needed to be improved.

Magnetic resonance image-guided hypofractionated ablative radiation therapy for extrahepatic cholangiocarcinoma: Plan adaptation in changing anatomy.

Extrahepatic cholangiocarcinoma is an aggressive malignancy of biliary duct epithelium which typically has a poor prognosis. Although surgical resection improves overall survival, many patients are deemed medically inoperable or have unresectable tumors. Herein, we report a case of an 84-year-old Caucasian male who was diagnosed with medically inoperable extrahepatic cholangiocarcinoma. Magnetic resonance image-guided hypofractionated ablative radiotherapy was administered which has the advantages of superior soft tissue resolution, better visualization of the target and organ at risk, daily online adaptive planning and continuous cine MR tracking of the target during irradiation. Concomitant chemotherapy was used. On the first fraction the patient presented with a broken arm that forced the patient take a treatment position much different than the one used for simulation CT and planning. The patient was able to finish the treatment without the need of another simulation by adapting the plan according to the new anatomy. The patient is being followed up until today and is alive with no evidence of disease.

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity.

OBJECTIVE: Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response. METHODS: 50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. RESULTS: The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. CONCLUSION: In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. ADVANCES IN KNOWLEDGE: MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.

Patient-Reported Tolerance of Magnetic Resonance-Guided Radiation Therapy.

PURPOSE: Magnetic resonance-guided radiation therapy (MRgRT) has been incorporated into a growing number of clinical practices world-wide, however, there is limited data on patient experiences with MRgRT. The purpose of this study was to prospectively evaluate patient tolerance of MRgRT using patient reported outcome questionnaires (PRO-Q). METHODS: Ninety patients were enrolled in this prospective observational study and treated with MRgRT (MRIdian Linac System, ViewRay Inc. Oakwood Village, OH, United States) between September 2018 and September 2019. Breath-hold-gated dose delivery with audiovisual feedback was completed as needed. Patients completed an in-house developed PRO-Q after the first and last fraction of MRgRT. RESULTS: The most commonly treated anatomic sites were the abdomen (47%) and pelvis (33%). Respiratory gating was utilized in 62% of the patients. Patients rated their experience as positive or at least tolerable with mean scores of 1.0-2.8. The most common complaint was the temperature in the room (61%) followed by paresthesias (57%). The degree of anxiety reported by 45% of the patients significantly decreased at the completion of treatment (mean score 1.54 vs. 1.36, p = 0.01). Forty-three percent of the patients reported some degree of disturbing noise which was improved considerably by use of music. All patients appreciated their active role during the treatment. CONCLUSION: This evaluation of PROs indicates that MRgRT was well-tolerated by our patients. Patients' experience may further improve with adjustment of room temperature and noise reduction.

Multichannel Film Dosimetry for Quality Assurance of Intensity Modulated Radiotherapy Treatment Plans Under 0.35 T Magnetic Field.

Purpose To evaluate the intensity modulated radiotherapy (IMRT) quality assurance (QA) results of the multichannel film dosimetry analysis with single scan method by using Gafchromic™ EBT3 (Ashland Inc., Covington, KY, USA) film under 0.35 T magnetic field. Methods Between September 2018 and June 2019, 70 patients were treated with ViewRay MRIdian® (ViewRay Inc., Mountain View, CA) linear accelerator (Linac). Film dosimetry QA plans were generated for all IMRT treatments. Multichannel film dosimetry for red, green and blue (RGB) channels were compared with treatment planning system (TPS) dose maps by gamma evaluation analysis. Results The mean gamma passing rates of RGB channels are 97.3% ± 2.26%, 96.0% ± 3.27% and 96.2% ± 3.14% for gamma evaluation with 2% DD/2 mm distance to agreement (DTA), respectively. Moreover, the mean gamma passing rates of RGB channels are 99.7% ± 0.41%, 99.6% ± 0.59% and 99.5% ± 0.67% for gamma evaluation with 3% DD/3 mm DTA, respectively. Conclusion The patient specific QA using Gafchromic™ EBT3 film with multichannel film dosimetry seems to be a suitable tool to implement for MR-guided IMRT treatments under 0.35 T magnetic field. Multichannel film dosimetry with Gafchromic™ EBT3 is a consistent QA tool for gamma evaluation of the treatment plans even with 2% DD/2 mm DTA under 0.35 T magnetic field presence.

New horizons from novel therapies in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience.

Objectives Improved soft-tissue visualization, afforded by magnetic resonance imaging integrated into a radiation therapy linear accelerator-based radiation delivery system (MR-linac) promises improved image-guidance. The availability of MR-imaging can facilitate on-table adaptive radiation planning and enable real-time intra-fraction imaging with beam gating without additional exposure to radiation. However, the novel use of magnetic resonance-guided radiation therapy (MRgRT) in the field of radiation oncology also potentially poses challenges for routine clinical implementation. Herein the early experience of a single institution, implementing the first MRgRT system in the country is reported. We aim to describe the workflow and to characterize the clinical utility and feasibility of routine use of an MR-linac system. Methods The ViewRay MRIdian MR-linac system consists of a split-magnet 0.35 T MR-imaging scanner with a double focused multi-leaf collimator (MLC) equipped 6MV linear accelerator. Unique to the system are the control console integrated on-table adaptive radiation therapy (oART) planning capabilities as well as automated beam gating based on real-time intra-fraction MR imaging. From the first day of clinical implementation, oART was performed according to physicians' discretion when medically indicated. All fractions were delivered under real-time imaging with soft tissue-based automated beam gating with individualized gating boundary settings. Patients actively assisted in breath-hold beam gating with the help of custom designed prismatic glasses allowing sight of a computer monitor mounted on the back wall just behind the MRI system bore. Patient demographics and treatment experience, indications for MRgRT including diagnosis and disease site, radiation dose prescribed and fractionation scheme, utilization of oART, respiratory gating settings, as well as duration of each treatment phase were analyzed. Results Between September 2018 and May 2019, 72 patients with 84 tumor sites were treated with MRgRT in 500 total fractions. Median patient age was 66 years (range: 28-83 years). Among 84 tumor sites, the most frequently treated regions were upper abdominal and pelvic (n = 36, 43% and n = 29, 34%, respectively). The most common diagnosis was prostate cancer, with 14 patients treated. In 69 patients (93.2%) oART was used at least once during a treatment course. Twenty-nine targets (43.1%) with significant breathing-related motion were treated in breath-hold with patient visual feedback. Median prescribed dose was 36.25 Gy (range: 24-70 Gy) in median five fractions (range: 3-28 fractions). A gating boundary of 3 mm around a gating region of interest (gROI) was most commonly used (range: 3-5 mm) with 95% of the gROI (range: 93-97%) required to be within the gating boundary for the beam to automatically engage. Mean total treatment time was 47 min (range: 21-125 min) and mean beam-on time was 16.7 min (range: 6-62 min). Conclusions MRgRT afforded by an MR-linac system has been successfully implemented into routine clinical use at our institution as the first system of its kind in Turkey. While the overall number of patients treated and fractions delivered is still limited, we have demonstrated the feasibility of both on-table adaptive radiation therapy as well as automated real-time beam gating on a daily basis in acceptable time schedules.

Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases.

PURPOSE: Renal cell carcinoma (RCC) and melanoma have been considered 'radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. RESULTS: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. CONCLUSION: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.