Effect Of Stereotactic Body Radiotherapy Research Articles

Quality of Life in Patients with Locally Advanced Pancreatic Cancer During Stereotactic Radiotherapy Combined with Heat-Killed Mycobacterium Obuense Vaccination.

Background: New treatment options for patients with locally advanced pancreatic cancer (LAPC) have proven to be safe but, in addition, may have an effect on the patient's quality of life. Objectives: To evaluate the effect of stereotactic body radiotherapy (SBRT) combined with intradermal heat-killed mycobacterium obuense (IMM-101) vaccination on health-related quality of life (HRQoL), pain, and sleep, in patients with LAPC. Design: Prospective cohort study. Setting/Participants: In total, 42 Dutch patients with LAPC were included after completion of at least four cycles of (m) leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX). Measurements: Quality of life was assessed with the EORTC QLQ-C30. Patients completed the Richard Campbell Sleep Questionnaire (RCSQ) for five consecutive nights and wore simultaneously a GENEActiv tri-axial accelerometer, which registered sleep duration and sleep efficiency. The Numeric Rating Scale was used to assess pain intensity during treatment. Data were collected at the baseline visit [i.e., at inclusion in the study after (m)FOLFIRINOX treatment] and at week 8 (i.e., 6 weeks after start date of SBRT and after four IMM-101 vaccinations). Results: Univariable linear mixed model analysis revealed significant improvement for EORTC QLQ-C30 items "cognitive functioning" and "emotional functioning." Outcomes on RCSQ subscales and "RCSQ total score" did not significantly change. In the multivariable model, with "Global HRQoL scale" and "RCSQ total score" as outcomes, we did not find a significant change during treatment. Conclusion: In this prospective cohort study, we found that SBRT combined with IMM-101, in patients with LAPC, is well tolerated and does not negatively affect HRQoL, sleep quality, and pain.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. clinicaltrials.gov, identifier NCT04431674.

Revolutionizing localized prostate cancer treatment: Stereotactic radiotherapy "Moroccan experience".

Prostate cancer is the most common urological cancer, and its incidence is increasing. Radical prostatectomy and radiotherapy are theprimary treatments for localized forms. Stereotactic Body RadioTherapy (SBRT), a new and innovative therapy, has been validated for some cancer localizations but not yet for localized prostate cancer. Our study aims to report the efficacy and tolerance results of SBRT for localized prostate cancer. This is a retrospective study of 27 patients with localized prostate cancer (CaP) who were treated with SBRT in our department from 2017 to 2021 using transponders for tumor tracking. The dose was 36.25 Gy delivered in five fractions of 7.25 Gy. The delineation and doses of organs at risk were determined based on the recommendations of the SFRO and the TG101 report of medical physics. All patients were treated using a latest-generation linear accelerator (True Beam STXÒ). Acute toxicities were observed in 33.3% of cases, with 22.2% grade 1 or 2 genitourinary (GU) and no grade 3 while 11.1% gastrointestinal (GI) toxicities were reported as grade 1-2 (7.4%) and one case grade 3 (3.7%). Late grade 1 or 2 GU toxicity was observed in 14.84% of cases, with no reports of late GI toxicity. After a 26-month follow-up period, the biochemical failure-free survival rate was 92.6%. The results of our study are consistent with the existing literature and support the safety and effectiveness of SBRT as a treatment option for localized prostate cancer (CaP). In the United States, both ASTRO and the NCCN recognize SBRT as a valid treatment option for localized CaP. Ongoing phase III trials are being conducted to further substantiate these long-term results and to establish SBRT as the future standard of care for localized CaP.

Retrospective study on the toxicity induced by stereotactic body radiotherapy: overview of the reunion experience on prostate cancer in elderly patients.

Prostate cancer is the fourth most commonly diagnosed cancer among men worldwide. Various tools are used to manage disease such as conventional radiotherapy. However, it has been demonstrated that large prostate volumes were often associated with higher rates of genitourinary and gastrointestinal toxicities. Currently, the improvements in radiotherapy technology have led to the development of stereotactic body radiotherapy, which delivers higher and much more accurate radiation doses. In order to complete literature data about short-term outcome and short-term toxic effects of stereotactic body radiotherapy, we aimed to share our experience about gastrointestinal and genitourinary toxicities associated with stereotactic body radiotherapy in prostate cancer in patients over 70 years old. We retrospectively reviewed the medical records of elderly patients with prostate cancer treated between 2021 and 2022. The elderly patients were treated with a non-coplanar robotic stereotactic body radiotherapy platform using real-time tracking of implanted fiducials. The prostate, with or without part of the seminal vesicles, was treated with a total dose of 36.25 Gy delivered in five fractions, each fraction being administered every other day. We analyzed a total of 80 elderly patients, comprising 38 low-, 37 intermediate- and 5 high-risk patients. The median follow-up duration was 12 months. We did not observe biochemical/clinical recurrence, distant metastasis, or death. Grade 2 acute genitourinary toxicity was observed in 9 patients (11.25%) and Grade 2 acute gastrointestinal toxicity in 4 patients (5.0%). We did not observe any grade 3 or more acute or late toxicities. Over the follow-up period, we noted a low frequency of gastrointestinal and genitourinary toxicities induced by stereotactic body radiotherapy in the context of prostate cancer in elderly patients. Therefore, stereotactic body radiotherapy seems to represent a promising treatment option for elderly patients, with acceptable acute toxicity.

Late radiation-related lymphopenia after prostate stereotactic body radiation therapy plus or minus supplemental pelvic irradiation.

Prior studies suggest lymphopenia following radiation therapy may impact toxicity and cancer control. Chronic radiation-related lymphopenia (RRL) has been noted in prostate cancer patients treated with conventionally fractionated pelvic radiation therapy. The impact of utilizing hypofractionated high integral dose therapies such as stereotactic body radiation therapy (SBRT) on RRL is less well characterized. This prospective study sought to evaluate the impact of prostate SBRT plus or minus supplemental pelvic nodal radiation (PNI) on RRL. Between 2012 and 2023, serial serum absolute lymphocyte counts (ALCs) were measured in 226 men treated at MedStar Georgetown with robotic SBRT using the CyberKnife® (CK) (36.25 Gy in 5 fractions) alone or CK (19.5 Gy in 3 fractions) followed by supplemental PNI using VMAT (37.5-45.0 Gy in 15-25 fractions) per an institutional protocol (IRB#: 2012-1175). Baseline ALC (k/μL) was measured 1-2 hours prior to robotic SBRT and at each follow-up appointment (1, 3, 6, 9, 12, 18, and 24 months post-treatment). Lymphopenia was graded using the CTCAEv.4: Grade 1 (0.8-1.0 k/μL), Grade 2 (0.5-0.8 k/μL), Grade 3 (0.2-0.5 k/μL) and Grade 4 (<0.2 k/μL). To compare two different treatment groups, the Wilcoxon signed-rank test was used. A p-value of < 0.05 determined statistical significance. Of 226 patients (SBRT alone: n = 169, SBRT + PNI: n = 57), the median age was 72 years and 45% of patients were non-white. Baseline lymphopenia was uncommon and of low grade. In the SBRT alone group, the baseline ALC of 1.7 k/μl decreased by 21% to 1.4 k/μL at 3 months and then stabilized. 38% of these men experienced lymphopenia in the two years following SBRT, however, no patient presented with Grade 3 lymphopenia. Patients who received SBRT + PNI had a lower baseline ALC (1.5 k/μl), and a significantly greater decrease in ALC relative to individual baseline value throughout the 2-year follow-up period, decreasing by 57% to 0.6 k/μL at 3 months and recovering to a 36% decrease from baseline (1.0 k/μL) at 24 months. Notably, 12% of the men treated with SBRT + PNI experienced Grade 3 lymphopenia. No patient in either cohort experienced Grade 4 lymphopenia. The low incidence of high-grade lymphopenia within this elderly patient population further supports the safety of prostate SBRT plus or minus PNI for the treatment of prostate cancer. However, RRL was more severe when PNI was utilized. The effect of SBRT and PNI on lymphocytes in prostate cancer patients could act as a model for other cancers, specifically those involving treatment with immunomodulatory agents. Future studies should focus on the clinical implications of RRL and the effects of specifically irradiating lymphoid tissues on lymphocyte biology.

The Effect of Stereotactic Body Radiotherapy (SBRT) Dose-Fraction (fx) Schema on Non-Small Cell Lung Cancer (NSCLC)

Stereotactic body radiotherapy (SBRT) dose-fraction (fx) schema for non-small cell lung cancer (NSCLC) varies at different centers and commonly involves 3 to 5 fx. Additionally, the frequency of treatment per week, or treatment schedules (TS), can also differ. We sought to evaluate and compare the effect of different dose-fx schemas on overall survival (OS). We retrieved data from the National Cancer Database. Patient eligibility included early-stage NSCLC with cT1-2 N0M0 disease treated with SBRT using 3-5f x regimens. Demographics and clinical characteristics were identified. Biologically effective dose (BED) and total dose (TD) were calculated. TD included following: 45-60 Gy for 3 fx, 48-60 Gy for 4 fx, and 50-60 Gy for 5 fx. TS was classified as one of the following: daily, every other day, twice per week, or prolonged (less frequently than twice weekly). Non-prolonged TS was defined as daily, every other day, and twice per week. OS was calculated from the date of end of RT to the date of death and censored at the date of last contact. Kaplan Meier method was used to estimate OS and log-rank tests were used to compare the difference between groups. TS was compared pairwise within each individual fx-group. Univariable Cox proportional models with robust standard errors to account for within institution correlations were used to investigate the association between BED, TD, TS, fx-group and OS. Within each fx-group, BED was also assessed and compared. A total of 3244 patients were identified, with median age 73. 48% were males and 52% females. 601 (19%) patients received 3 fx, 884 (27%) received 4 fx, and 1759 (54%) received 5 fx treatments. For the overall cohort, median and mean BEDs were 112 and 119, respectively. TS did not show a difference in OS among each individual fx group. Overall, prolonged vs non-prolonged schedules also did not show a difference in OS (p = 0.64). OS was superior in the 3 fx group compared to 4 and 5 fx groups, with median survival times of 61.5 vs 53.7 vs 52.6 months, respectively (p = 0.046). Overall, an increase in BED reduced risk of death (HR = 0.97 per 10-units, CI: 0.94-0.99, p = 0.04). When stratified by fx, each 10 unit rise in BED for those treated with 5 fx reduced the risk of death by 8% (HR = 0.92, CI: 0.87-0.97, p<0.01). However, increasing BED was not associated with change in OS for 3 fx (HR = 1.00, CI: 0.93-1.08, p = 0.93) and 4 fx (HR = 1.08, p = 0.08) regimens. Patients who received BED greater than the median (BED>112) had improved OS compared to those receiving BED£112 (HR = 0.86, p = 0.047). When evaluating the 5 fx-group individually, BED >100 (median of 5fx group) had superior OS compared to £100 (HR = 0.80, p = 0.02). Three-fraction regimens have superior OS compared to 4 and 5 fx regimens. Higher BED improves OS in 5 fx regimens. Treatment schedule variations among individual fx-groups does not impact OS.

A Novel Strategy to Enhance Radiotherapy Efficacy: Results from the Prospective Phase I Clinical Trial of MR-Guided Focused Ultrasound-Stimulated Microbubbles (MRgFUS+MB) Treatment for Breast Cancer

Preclinical in vitro and in vivo studies have demonstrated that tumor cell death can be enhanced 10- to 40-fold when radiotherapy (RT) is combined with focused-ultrasound (FUS)-stimulated microbubbles (MB) treatment. MBs are gas microspheres used as intravascular contrast agents. The acoustic exposure of MBs within the target volume causes bubbles cavitation that induces perturbation of tumor vasculature. This activates apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy, which would otherwise require high-dose radiotherapy (>8-10 Gy/fraction) to be activated. Subsequent irradiation of an MB-sensitized tumor causes increased anoxic tumor killing, which occurs in addition to canonical RT-induced DNA damage. Given the compelling results of preclinical data, we conducted a phase I clinical trial of magnetic resonance (MR)-guided FUS-stimulated MBs (MRgFUS+MB) treatment for breast cancer patients (pts). We report the safety and efficacy results of this new radio enhancement treatment. This is a single-center, single-arm, investigator-initiated phase 1 clinical trial (NCT04431674). We included pts with stage I-IV breast cancer with tumor in situ for whom breast or chest wall RT was deemed adequate by a multidisciplinary team. Pts were excluded if they had contraindications for contrast-enhanced MR or MB administration. Pts underwent 2-3 MRgFUS+MB treatments throughout the RT course. We used an MR-coupled FUS-device operating at 500 KHz and 540 kPa peak negative pressure to deliver the treatment. The FUS sonicated intravenously administrated MB within the MR-guided target volume. Pts were monitored for 30-min post-procedure and subsequently treated with RT. The primary outcome was acute toxicity per Common Terminology for Adverse Events V5.0. Secondary outcomes were radiological response at 3 months and local control (LC) at 1 year. Kaplan-Meier method was used to estimate local control. All pts signed a written consent form before study participation. We enrolled 18 females with 20 primary breast cancer treated with MRgFUS+MB therapy. The median age was 60 years (range, 44-90). The molecular subtypes consisted of basal-like (n = 3/20), luminal (n = 11/20), and HER2-enriched (n = 6/20). The prescribed dose was 20 Gy/5 fractions (n = 8/20), 30-35 Gy/5 fractions (n = 7/20), 30-40 Gy/10 fractions (n = 3/20), and 66 Gy/33 fractions (n = 2/20). The median follow-up was 9 months (range, 0.3-29). All pts completed the planned MRgFUS+MB treatments. The only MRgFUS+MB treatment-related toxicity consisted of Grade 1 allergic reaction (mild cough) 30 minutes after the last MB injection. All worst acute toxicities were radiation dermatitis (Grade 3 = 2/20, Grade 2 = 2/20, Grade 1 = 14/20). At 3 months, 75% had partial (n = 6/20) or complete (n = 9/20) response, with a single progression. The LC rate at 1 year was 86%. MRgFUS+MB was a safe and efficient treatment that provided durable responses.

Effects of stereotactic body radiotherapy for clinical outcomes of patients with liver metastasis and hepatocellular carcinoma: A retrospective study.

This retrospective clinical study described the treatment efficacy and safety of stereotactic body radiotherapy (SBRT) for patients of hepatocellular carcinoma (HCC) and liver metastasis tumors. The therapeutic effect and prognosis of patients with liver cancer treated with stereotactic body radiation therapy (SBRT) at the Fudan University Shanghai Cancer Center (Shanghai, China) between July 2011 and December 2020 were retrospectively analyzed. Overall survival (OS), local control (LC) rates and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and the log-rank test. Local progression was defined as tumor growth after SBRT on dynamic computed tomography follow-up. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4. A total of 36 patients with liver cancer were enrolled in the present study. The prescribed dosages (14 Gy in 3 fractions or 16 Gy in 3 fractions) were applied for SBRT treatments. The median follow-up time was 21.4 months. The median OS time was 20.4 [95% confidence interval (CI): 6.6-34.2] months, and the 2-year OS rates for the total population, HCC group and liver metastasis group were 47.5, 73.3 and 34.2%, respectively. The median PFS time was 17.3 (95% CI: 11.8-22.8) months and the 2-year PFS rates for the total population, HCC group and liver metastasis group were 36.3, 44.0 and 31.4%, respectively. The 2-year LC rates for the total population, HCC group and liver metastasis group were 83.4, 85.7 and 81.6%, respectively. The most common grade IV toxicity for the HCC group was liver function impairment (15.4%), followed by thrombocytopenia (7.7%). There were no grade III/IV radiation pneumonia or digestive discomfort. The present study aimed to explore a safe, effective and non-invasive treatment method for liver tumors. At the same time, the innovation of the present study is to find a safe and effective prescription dose of SBRT in the absence of consensus on guidelines.

Translational study for stereotactic body radiotherapy against non-small cell lung cancer, including oligometastases, considering cancer stem-like cells enable predicting clinical outcome from in vitro data

BackgroundCurative effects of stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) have been evaluated using various biophysical models. Because such model parameters are empirically determined based on clinical experience, there is a large gap between in vitro and clinical studies. In this study, considering the heterogeneous cell population, we performed a translational study to realize the possible linkage based on a modeling approach. MethodsWe modeled cell-killing and tumor control probability (TCP) considering two populations: progeny and cancer stem-like cells. The model parameters were determined from in vitro survival data of A549 and EBC-1 cells. Based on the cellular parameters, we predicted TCP and compared it with the corresponding clinical data from 553 patients collected at Hirosaki University Hospital. ResultsUsing an all-in-one developed model, the so-called integrated microdosimetric-kinetic (IMK) model, we successfully reproduced both in vitro survival after acute irradiation and the 3-year TCP with various fractionation schemes (6–10 Gy per fraction). From the conventional prediction without considering cancer stem cells (CSCs), this study revealed that radioresistant CSCs play a key role in the linkage between in vitro and clinical outcomes. ConclusionsThis modeling study provides a possible generalized biophysical model that enables precise estimation of SBRT worldwide.

Two-institution results of Stereotactic Body Radiation Therapy (SBRT) for treating adrenal gland metastases from liver cancer

ObjectiveStereotactic Body Radiation Therapy (SBRT) has been found beneficial for adrenal gland metastases (AGMs) with a high local control rate and low toxicity. The role of SBRT for AGMs in patients with liver cancer has not been well-discussed before. We, therefore, report our two-institution experience to further elaborate on the feasibility and effectiveness of SBRT in the treatment of AGMs from liver cancer.MethodsA total of 23 liver cancer patients (19 males, 4 females) with 24 AGMs treated by SBRT from July 2006 to April 2021 were retrospectively included in this study. Toxicity was assessed based on clinical adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The effectiveness was assessed based on local control (LC), progression-free survival (PFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Univariate analyses were compared by log-rank test. The relevant covariates were evaluated using Cox proportional hazards models.ResultsThe median dose was 40 Gy in 5 fractions, with the corresponding median biological effective dose (BED10, α/β = 10 Gy) of 72 Gy. The median overall follow-up time was 15.4 months (range: 4.2–70.6 months). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 25.0%, 20.8%, 33.3%, and 20.8%, respectively. All 6 patients with AGMs accompanying symptoms had varying degrees of alleviation after SBRT. The 0.5-, 1-year and 2-year LC rates were 87.5%, 77.8%, and 77.8%, respectively. The 0.5-, 1-year and 2-year OS rates were 95.5%, 66.8%, and 41.1%, respectively. The treatments were all tolerated with only one patient reporting a grade-3 hepatic injury. The univariate analysis concluded that only gross tumor volume (GTV) < 34.5 ml (p = 0.039) was associated with a favorable LC rate. After multivariate analysis, favorable predictors correlated with OS were GTV < 34.5 ml (p = 0.043), systemic therapy (p = 0.017), and without additional organ metastasis after SBRT (p = 0.009).ConclusionOur results suggest that SBRT is a safe and effective technique to treat AGM from liver cancer, especially for small GTV (< 34.5ml). Moreover, the small metastatic lesion volume, fewer metastatic lesions, and intervention of systemic therapy are more likely to improve OS.

Observation on the Clinical Effect of Stereotactic Body Radiotherapy in Patients with Oligometastatic Tumors

Objective: To observe the efficacy and safety of stereotactic body radiotherapy (SBRT) in the treatment of extracranial oligometastases. Method: A retrospective analysis of 70 patients with extracranial oligometastasis of malignant tumors who underwent SBRT in our hospital (Shaanxi Provincial People’s Hospital) from January 2019 to December 2021 with ? 5 metastases, ?3 metastatic organs, and metastases with diameters of ? 5 cm. According to the clinical data of patients, the dose-fractionation mode of SBRT is mainly determined according to the pathology of the primary tumor, the location of the metastatic tumor, and the important structures around the tumor. The local control, survival and adverse reactions were observed. Results: A total of 219 oligometastatic lesions in 70 patients were treated with SBRT. The median follow-up time was 24 months (12–40 months). The local control rate (LCR) of all target lesions assessed 3 months after radiotherapy was 94.1%; the 1-, 2-, and 3-year LCRs were 88.6%, 74.6%, and 64.9%, respectively. The median progression-free survival (PFS) was 11.8 months (95% CI, 8.9–14.7 months), and the 1- and 2-year PFS rates were 48.6% and 32.6%, respectively; the median overall survival (OS) was 31.9 month (95% CI 26.0-37.8 months), the 1-year OS rate was 84.3%. The local control time, PFS, and OS of patients with metastases ? 3 cm were significantly better than those with metastases &gt; 3 cm, and the differences were statistically significant (P &lt; 0.05). Acute adverse reactions after SBRT treatment in oligometastatic patients were mainly bone marrow suppression and gastrointestinal reactions, with incidence rates of 48.98% and 30.61%, respectively; chronic adverse reactions were mainly pain (bone, muscle), radiation enteritis, and radiation pneumonitis, with incidence rates of 38.57%, 30.00%, and 24.29%, respectively. The treatment-related adverse reactions were mainly grade 1, which were all improved after symptomatic treatment, except for one patient with bone metastases from lung cancer who had grade 4 myelosuppression. No grade 4 or 5 adverse events occurred in the other patients. Conclusion: The application of SBRT in the treatment of extracranial oligometastases is safe, effective, and has high tolerability.

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm

BackgroundTo describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm. MethodsWe used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity. ResultsOf 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HROS: 0.78, 95% CI: 0.68-0.89, HRLCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HROS: 0.81, 95% CI: 0.72-0.93, HRLCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71). ConclusionFor patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.

Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer.

Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16-CD11b+HLA-DRlow myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.

The Potential Therapeutic Effects of Carbon Ion Beams and X-Rays on Mice with Heart Failure: Preliminary Results

<h3>Purpose/Objective(s)</h3> In general, the heart has been recognized as an organ at risk because of adverse events associated with irradiation. However, in recent years, beneficial effects of stereotactic body radiotherapy on refractory arrhythmias have been reported. Therefore, this study investigated the effects of radiation on the diseased heart. <h3>Materials/Methods</h3> A mouse model with cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) was irradiated with 30 Gy X-rays or carbon ion beams at 2 weeks after pressure overload and then underwent echocardiography. Fractional shortening (FS) was used to assess cardiac function and left ventricular end-diastolic diameter (LVDd) was used to assess cardiac enlargement. Mice were sacrificed at 4 weeks after irradiation, and heart weight and fibrosis of the myocardium were assessed. <h3>Results</h3> Each group comprised four mice, except for the group that underwent TAC and X-ray irradiation, which comprised five mice. The average values are described. Two weeks after TAC, FS had decreased from 50.9% to 31.3%, and LVDd had increased from 2.6 mm to 3.7 mm. This confirmed that the TAC procedure was successful. In the control group, the FS change ratio (before irradiation versus 4 weeks after irradiation) was 1.06 (50.0% to 53.1%) in non-irradiated mice, 1.18 (51.7% to 60.9%) in mice irradiated with X-rays, and 1.11 (53.1% to 58.7%) in mice irradiated with carbon ion beams. Meanwhile, the LVDd change ratio (before irradiation versus 4 weeks after irradiation) was 1.01 (2.9 mm to 2.9 mm) in non-irradiated mice, 0.90 (2.7 mm to 2.5 mm) in mice irradiated with X-rays, and 0.85 (2.8 mm to 2.4 mm) in mice irradiated with carbon ion beams. In the TAC group, the FS change ratio (before irradiation versus 4 weeks after irradiation) was 0.75 (29.4% to 22.3%) in non-irradiated mice, 1.01 (35.1% to 35.5%) in mice irradiated with X-rays, and 1.36 (29.4% to 39.9%) in mice irradiated with carbon ion beams. Meanwhile, the LVDd change ratio (before irradiation versus 4 weeks after irradiation) was 0.92 (3.8 mm to 3.5 mm) in non-irradiated mice, 0.73 (3.4 mm to 2.5 mm) in mice irradiated with X-rays, and 0.67 (3.8 mm to 2.5 mm) in mice irradiated with carbon ion beams. In the control group, irradiation did not significantly improve cardiac function, but cardiac enlargement was significantly improved by carbon ion beams (P=0.036) and tended to be improved by X-rays (P=0.094). In the TAC group, cardiac function was significantly improved by carbon ion beams (P=0.041) but not by X-rays (P=0.212). Furthermore, cardiac enlargement was significantly improved by carbon ion beams (P=0.036) and tended to be improved by X-rays (P=0.080). Irradiation did not significantly affect heart weight or fibrosis in the control or TAC group. <h3>Conclusion</h3> Irradiation had no observed adverse effects on normal or failing hearts. In the TAC group, irradiation improved cardiac function and enlargement.

Health related quality of life outcomes following stereotactic body radiotherapy in patients with oligo-metastatic disease: A systematic review and individual patient data meta-analysis

IntroductionPublished health-related quality of life (HRQOL) outcomes are lacking in patients treated for oligo-metastatic disease (OMD). The aim of this systematic review and individual patient data meta-analysis is to determine the effect of stereotactic body radiotherapy (SBRT) on HRQOL outcomes of patients with OMD. MethodsStudies screened included adults with extra-cranial OMD, defined as ≤ 5 metastases, SBRT intended as definitive treatment, and HRQOL as primary or secondary outcome. Primary outcome was change in HRQOL at 12-months from baseline in patients with OMD who received SBRT (versus not), reported as standardized mean difference (SMD). ResultsA total of 7556 publications were identified, four studies met inclusion criteria (2 single arm interventional studies and 2 randomised controlled trials [RCTs]), and individual patient data was available from 3 studies (175 patients). In the two RCTs, there was no SS difference in the SMD between patients who received SBRT and those that did not (0.09 [95 % CI −0.32, 0.5], P = 0.66). On meta-analysis of patients (N = 107) who received SBRT the SMDwas −0.23 (95 % CI [−0.42, −0.04], versus −0.25 (95 % CI [−0.57, 0.07]) in those who did not (N = 37) receive SBRT, demonstrating a small deterioration from baseline. ConclusionIn patients with OMD, there is no difference in HRQOL at 12-months from baseline between patients who received SBRT and those that did not. However, a small HRQOL deterioration was found in both groups of patients. More in-depth analysis of relevant HRQOL domains, in the setting of OMD, is required to better understand the potential impact of SBRT.

Oesophagopericardial fistula as a late complication of stereotactic radiotherapy for recurrent ventricular tachycardia.

Severe adverse effects of stereotactic body radiotherapy (SBRT) for recurrent ventricular tachycardias (VTs) have not been reported. We describe the late complication of SBRT (25 Gy, CyberKnife, Accuray) in a 67-year-old patient with previous arterial coronary revascularization, including gastroepiploic artery, and subsequent recurrent VTs despite catheter ablation. He developed radiation oesophagitis 18 days after SBRT, which resolved on antiulcer therapy, and 6 months later was admitted for severe symptomatic ulcer. Despite intensive treatment, he died because of bleeding oesophagopericardial fistula. Post-mortem macroscopic picture shows the myocardial substrate in the inferior wall (black arrows) and adjacent oesophagopericardial fistula through the parietal pericardium (open arrows). Inset depicts radiosurgical treatment plan with coloured isodose lines. Our case illustrates that SBRT may be complicated even in a long-term course, and oesophagopericardial fistula could be one of the potential complications. Therefore, the risk/benefit of SBRT for VT should be always carefully considered, and long-term follow-up...

The prognostic value of circulating lymphocyte counts and ABO blood group in lung cancer stereotactic body radiation therapy: a retrospective study

BackgroundClinically, there is a lack of simple and feasible indicators to predict the efficacy of stereotactic body radiation therapy (SBRT). Circulating lymphocyte counts (CLCs) is considered to be related to curative effect in conventional radiotherapy of lung cancer, and blood groups are also associated with the survival. In this study, we investigate the prognostic value of CLCs and ABO blood groups in lung cancer patients treated with SBRT.MethodsWe retrospectively analyzed 191 patients who were treated with lung cancer SBRT in Taizhou Hospital of Zhejiang Province from September 2014 to December 2018. The medical record system of Taizhou Hospital was used to collect relevant clinical data, such as stage, CLC, ABO blood groups and other important clinical co-variates. The effects of SBRT were evaluated by patient reexamination image data and telephone follow-up. The RECIST 1.1 standard was used to evaluate the short-term efficacy in the first, third, and sixth months after SBRT. Progression-free survival (PFS) was defined as the time from the day of SBRT to disease progression or death from any cause. Overall survival (OS) was measured from the day of SBRT until the last follow-up or death. Survival curves and univariate, multivariate logistic-regression analyses were used to expound the prognostic factors for local control (LC), PFS, and OS of lung cancer SBRT patients.ResultsUnivariate and multivariate analysis results showed that post-SBRT CLCs were independent factors for the short-term efficacy 3 and 6 months after lung cancer SBRT [hazard ratio (HR) =0.249, P=0.037; HR =0.347, P=0.012]. Survival analyses showed that the PFS and OS of lung cancer SBRT patients with A blood type was significantly shorter than that in the other three non-A blood groups (PFS: 6.5 vs. 10 months, HR =1.535, P=0.020; OS: 24 vs. 41 months, HR =1.578, P=0.048). Moreover, the patients with high post-SBRT CLCs in the non-A blood group had the longest PFS and OS after lung cancer SBRT (HR =0.551, P=0.043).ConclusionsLung cancer SBRT patients with high-post-SBRT CLCs and non-A blood groups seem to exhibits best curative effect, which represent a potential opportunity to improve the clinical management of these patients. The mechanisms of this association deserve further verification and investigation.

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy.

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.

Radiation-Induced Changes in VentricularMyocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia.

Stereotactic body radiotherapy (SBRT) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias (VTs) in patients with structural heart disease. This case series is the first postmortem immunohistochemical analysis of morphologic changes in the myocardium early and late after SBRT. The present findings are in line with experimental observations on apoptosis followed by fibrosis. This may explain why the effect of SBRT on VT is not predominantly immediate. Together with observation of early recurrences after SBRT for VT, these data suggest that this strategy may have rather delayed antiarrhythmic effects.

Circulating Tumor Cell Assay Enables Prediction of Recurrence Following Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: An Interpretable Machine Learning Study

Despite the effectiveness of stereotactic body radiotherapy (SBRT) in the local control of early-stage non-small cell lung cancer (ES-NSCLC), recurrence rates remain high. Such results may be improved with selection of high-risk patients for intensified treatment, e.g., early salvage radiotherapy or adjuvant systemic therapy/immunotherapy. We previously reported that a high level of circulating tumor cell (CTC) assay counts is prognostic for increased recurrence risks. In this study, based on the same patient cohort, we aimed to determine a threshold of CTC counts using the explainable boosting machine (EBM), a new interpretable machine learning model.Our dataset comprised de-identified patients (n = 92) with biopsy-proven or clinically presumed ES-NSCLC, enrolled between August 2013 and October 2018. All patients received SBRT to a median dose of 50 Gy. Peripheral blood samples for CTC assays were collected for each patient during pre-treatment, on-treatment (between the first and last fraction), and post-treatment at follow-up intervals of 1, 3, 6, 12, 18 and 24 months. EBM is a recently developed open-source machine learning model. It is an efficient implementation of the generalized additive model with pairwise interactions (GA2M), which yields high intelligibility without sacrificing accuracy. We used the explainable boosting classifier from EBM to predict recurrence risks, including any local, nodal or distant failures during the 2-year follow-up. In addition to the CTC counts, we selected the following clinicopathologic parameters known before the time of treatment as training features: gender, race, body mass index, smoker status, pack-years, age at enrollment, tumor size, stage, histology, and fractionation. The dataset was stratified by the recurrence label, and 5-fold split into 80% training set and 20% testing set.EBM was trained on each feature in a round-robin fashion via sequential gradient boosting. The model scored the pre-treatment CTC count (PreCTC) and tumor size as the most important features, with 9.7% and 9.3% of overall score. AJCC Stage and T Stage were scored lower at 3.7% each. The average area under the curve (AUC) was 0.713 ± 0.099. From the model, we extracted the 2-year recurrence risks as a function of PreCTC, with a peak found at 6.EBM correctly scored PreCTC as the most influential feature for predicting recurrence, in agreement with our previous findings; additionally, we extracted a PreCTC threshold of 6 for clinical stratification of ES-NSCLC patients. These results illustrate how EBM may be a useful innovative tool for machine-learning aided translation of clinical data sets.