The Importance of Radiation Planning Guidelines in Spinal Stereotactic Body Radiotherapy.

Introduction: Stereotactic body radiotherapy (SBRT) is a well-established treatment for spinal metastases. Official guidelines for radiation planning were published and revised by several groups. Here, we present real-world data about the importance of adhering to those guidelines. Case Report: A 42-year-old metastatic colon cancer patient presented with oligometastatic disease to L3 vertebra and underwent SBRT treatment. Due to lack of adhering to official guidelines both in dose regiment and in volume definition, he progressed locally and required re-treatment. Conclusions: SBRT is a well-known established choice for oligometastatic spinal lesions. Thorough evaluation of imaging and adherence to clinical guidelines are crucial for achieving a high local control rate and reducing the likelihood of re-irradiation and associated complications.

Total dose, fraction dose and respiratory motion management impact adrenal SBRT outcome.

Purpose/Objectives: Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites. However, the optimal radiation dose for long-term local control of adrenal metastases has yet to be determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control. Materials/Methods: After IRB approval, a retrospective data review of patients treated with SBRT for adrenal metastases at a medical center in Israel between 2015 and 2021 was conducted. A biological effective dose was calculated using an alpha beta ratio of 10. Kaplan Meier and Cox regression were calculated using SPSS software to describe the hazard ratio for local control and survival. Results: 83 cases of adrenal SBRT were identified. The average age was 67 (range 42-92 years old). Non-small cell lung cancer was the primary site in 44 % of patients. A total of 70 % of the patients had oligometastatic disease (less than five lesions), and the rest were polymetastatic, responding to systemic therapy with oligo progression in the adrenal. The average gross tumor volume (GTV) was 42 ml. Respiratory control was applied in 88 % of cases; 49.3 % used 4-D/ITV, and 38.5 % used breath-hold or continuous positive airway pressure (CPAP) with free breathing. On multivariable analysis, Dose above 75 Gy (biological effective Dose) (HR = 0.41, p = 0.031), Dose above 8 Gy per fraction (HR = 0.53p = 0.038), and breath-holds or CPAP (HR = 0.65, p = 0.047) were significant for local control. From multivariable analysis, we computed a predicted nomogram curve using seven clinical parameters to evaluate local control odds. Conclusion: In this single institution series reported to date, we found unilateral adrenal SBRT safe, yet bilateral treatment harbors a risk of adrenal insufficiency. Biological effective Dose > 75 Gy (BED), motion management with breath-hold or CPAP, and Dose per fraction > 8 Gy were the enhanced local controls. We propose a nomogram to help in decision-making regarding total Dose and Dose per fraction when treating adrenal SBRT.

Treatment-Induced Bone Marrow Enhancement at MRI in Breast Cancer Patients Receiving Granulocyte-Colony Stimulating Factor Adjunct to Chemotherapy.

RATIONALE AND OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) induces the reconversion of fatty bone marrow to hematopoietic bone marrow. The bone marrow changes are detectable as signal intensity changes at MRI. The aim of this study was to evaluate sternal bone marrow enhancement following G-CSF and chemotherapy treatment in women with breast cancer. MATERIALS AND METHODS: This retrospective study included breast cancer patients who received neoadjuvant chemotherapy with adjunct G-CSF. The signal intensity of sternal bone marrow at MRI on T1-weighted contrast-enhanced subtracted images was measured before treatment, at the end of treatment, and at 1-year follow-up. The bone marrow signal intensity (BM SI) index was calculated by dividing the signal intensity of sternal marrow by the signal intensity of the chest wall muscle. Data were collected between 2012 and 2017, with follow-up until August 2022. Mean BM SI indices were compared before and after treatment, and at 1-year follow-up. Differences in bone marrow enhancement between time points were analyzed using a one-way repeated measures ANOVA. RESULTS: A total of 109 breast cancer patients (mean age 46.1 ± 10.4 years) were included in our study. None of the women had distal metastases at presentation. A repeated-measures ANOVA determined that mean BM SI index scores differed significantly across the three time points (F[1.62, 100.67] = 44.57, p < .001). At post hoc pairwise comparison using the Bonferroni correction BM SI index significantly increased between initial assessment and following treatment (2.15 vs 3.33, p < .001), and significantly decreased at 1-year follow-up (3.33 vs 1.45, p < .001). In a subgroup analysis, while women younger than 50 years had a significant increase in marrow enhancement after G-CSF treatment, in women aged 50 years and older, the difference was not statistically significant. CONCLUSION: Treatment with G-CSF as an adjunct to chemotherapy can result in increased sternal bone marrow enhancement due to marrow reconversion. Radiologists should be aware of this effect in order to avoid misinterpretation as false marrow metastases.

Deep inspiratory breath hold assisted by continuous positive airway pressure ventilation for lung stereotactic body radiotherapy.

PURPOSE: Continuous positive airway pressure (CPAP) ventilation hyperinflates the lungs and reduces diaphragmatic motion. We hypothesized that CPAP could be safely combined with deep inspiratory breath hold (CPAP-DIBH) during lung stereotactic radiotherapy (SBRT). MATERIAL AND METHODS: Patients with stage-1 lung cancer or lung metastasis treated with CPAP-DIBH SBRT between 3/2017-5/2021 were analyzed retrospectively. Patient characteristics, treatment parameters, duration of breath holds in all sessions and tolerance to CPAP-DIBH were recorded. Local control (LC) was assessed from CT or PET-CT imaging. The distances between the tumor and mediastinal organs at risk (OAR) in centrally located tumors using either free breathing (FB) or CPAP-DIBH were compared. Toxicity was graded retrospectively. RESULTS: Forty-five patients with 71 lesions were treated with CPAP-DIBH SBRT. Indications for CPAP-DIBH were prior radiation (35/71, 65%), lower lobe location (34/71, 48%), multiple lesions (26/71, 36.6%) and proximity to mediastinal OAR (7/71, 10%). Patient characteristics were: F:M 43%: 57%; mean gross tumor volume 4.5cm3 (SD 7.9), mean planning target volume 20cm3 (SD 27), primary: metastatic lesions (7%:93%). Mean radiation dose was 52.5 Gray (SD3.5). Mean lung volume was 5292cm3 (SD 1106). Mean duration of CPAP-DIBH was 41.3s (IQR 31-46.8). LC at 2 years was 89.5% (95% CI 76-95.5). In patients with central lesions, the distance between the tumor and mediastinal OAR increased from 0.84cm (SD 0.65) with FB to 1.23cm (SD 0.8) with CPAP-DIBH (p=0.002). Most patients tolerated CPAP well and completed all treatments after starting therapy. Three patients did not receive treatment: 2 were unable to tolerate CPAP and 1 had syncope (pre-existing). Toxicity was grade 2 in 4/65 (6%) and grade 3 in 1/65 (1.5%). There was no grade 2 or higher esophageal or tracheal toxicities. CONCLUSION: CPAP-DIBH assisted lung SBRT was tolerated well and was associated with minimal toxicity and favorable LC. This technique may be considered when treating multiple lung lesions, lesions located in the lower lobes or adjacent to mediastinal OAR.

Radiotherapy may augment response to immunotherapy in metastatic uveal melanoma patients.

Introduction: Uveal melanoma (UM) is a subtype of melanoma arising from the ocular region. Despite various local therapies available, a significant portion of patients develop distant metastases, primarily to the liver. While cutaneous melanoma is very sensitive to immunotherapy, UM is known to be less responsive and patients were excluded from pivotal clinical trials. To date, there is no standard first line therapy for metastatic UM and clinical trial participation is encouraged. While UM is considered a radio-resistant tumor, there is a role for radiotherapy (RT) as palliative treatment and possibly for immune sensitization. This a retrospective analysis aimed at addressing the role of combination checkpoint inhibitors (ICI) with RT as a synergistic treatment in metastatic UM patient. We hypothesized that concurrent RT would improve the clinical response to immunotherapy. Methods: Retrospective chart review of patients with metastatic UM treated with ICI at Ella Lemelbaum Institute between 2015 and 2021. Patients' electronic medical records were analyzed for baseline characteristics, response rate and survival data. Patients were grouped according to receipt of concomitant RT. Study was approved by local IRB and statistical analyses done using Stata V.17. Results: Thirty-nine patients were treated with immunotherapy. Fifty percent were treated with anti-programmed cell death (PD)-1 and 50% with anti-PD1- anti CTLA4 combination therapy. Nine patients were treated concomitantly with immunotherapy and external beam RT or with stereotactic body RT (group A) and 29 patients were treated with immunotherapy alone (group B). Overall response rate was significantly higher in group A (44% versus 10%, p = 0.004). Median progression-free survival was longer for patients in group A (22 months versus 3 m, Hazard Ratio (HR) = 0.37, p = 0.036). Median overall survival was also longer for group A (26 months versus 7.5 m, HR = 0.34, p = 0.03). Toxicity was comparable between the groups. Conclusions: RT may improve response to immunotherapy with ICI in metastatic UM patients and may confer an advantage in survival. Further prospective, larger studies are warranted.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

CHA2 DS2 -VASc score and clinical outcomes of patients with chest pain discharged from internal medicine wards following acute coronary syndrome rule-out.

BACKGROUND: Chest-pain patients deemed safe for discharge from internal medicine wards might still be at risk for adverse outcomes. HYPOTHESIS: CHA2 DS2 -VASc score improves risk stratification of low-risk chest-pain patients discharged after acute coronary syndrome (ACS) rule-out. METHODS: We accessed medical records of patients who were admitted to internal medicine wards at a single medical center during 2010-2016 and discharged following an ACS rule-out. Patients were classified according to CHA2 DS2 -VASc score: 0-1 (low), 2-3 (intermediate), >3 (high). Primary endpoint was occurrence of ACS at 1 year; 30-day and 1-year all-cause mortality (ACM) were secondary outcomes. RESULTS: Of 12 449 patients, 7057 (57%) had low, 3781 (30%) intermediate, and 1611 (13%) high CHA2 DS2 -VASc scores. Compared with a low score, intermediate and high scores were associated with significantly increased risk for 1-year ACS during the first year (OR: 2.89, 95% CI: 1.91-4.37, P < 0.01 and OR: 4.84, 95% CI: 3.02-7.74, P < 0.01, respectively). Each 1-point increase in CHA2 DS2 -VASc was associated with a 37% increased risk for 1-year ACS. A higher CHA2 DS2 -VASc score was associated with significantly higher 30-day ACM. Hazard ratios for 30-day ACM were 1.9 (95% CI: 1.1-3.4, P = 0.03) and 4.4 (95% CI: 2.4-7.9, P < 0.01) for intermediate and high CHA2 DS2 -VASc scores, respectively, compared with a low score. Each 1-point increase in CHA2 DS2 -VASc score was associated with 43% increased risk for 30-day mortality. CONCLUSIONS: High CHA2 DS2 -VASc score (>3) was associated with adverse outcomes among chest-pain patients discharged from internal medicine wards following ACS rule-out.