Effect Of Stereotactic Body Radiotherapy Research Articles

A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population.

BackgroundTo investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients.MethodsFrom January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients.ResultsData from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively.ConclusionsDisease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.

Stereotactic body radiotherapy prolongs the progression-free survival and delays the change of systemic therapy regimen in patients with lung oligoprogressive metastatic colorectal cancer.

To analyze the effect of stereotactic body radiotherapy (SBRT) on colorectal cancer (CRC) patients with lung oligoprogression (OP). Patients with lung OP from CRC treated by SBRT at our center were included in this retrospective analysis. The progression-free survival (PFS), change of systemic therapy (CST), local control (LC), and overall survival (OS) were analyzed. Cumulative incidence was used to report CST, and the Kaplan-Meier method was used to evaluate PFS and LC. A total of 17 patients with 38 lung OP lesions treated by SBRT from October 2012 to December 2018 were involved. All patients had undergone radical resection for primary CRC and administered with standard systemic therapy regimens (seven for the first line and 10 for the second line). Among them, nine (52.9%) had received targeted therapy before SBRT, 14 (82.4%) patients underwent chemotherapy, and 12 received targeted therapy after SBRT. Six patients (35.3%) underwent CST after a median time of 5.2 months (range: 1.7-27.5 months). The median follow-up was 9.9 months, and the 1-year OS rate for all patients was 73.5%. Progression was observed in of 14 of 17 patients (82.4%), and the 6-month PFS for all patients was 25.9%. Univariate analysis indicated that only targeted therapy before SBRT was a beneficial prognostic indicator for 6-month PFS (P=.026) and N-PFS (P=.013). The 1-year LC for all 38 lesions was 77.8%, and during and after SBRT, no grade 3 or higher toxicities were observed. SBRT combined with systemic therapy made partial CRC patients with lung OP avoid the progress within 6 months and delayed the need for CST to 5.2 months, and targeted therapy before SBRT was a positive indicator of PFS.

Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II

PurposeAssessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). Patients and methodsThe subjects were 16 patients who underwent SBRT for solitary HCC ≤3cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8–43 (median: 28) months, ages from 59–85 (median: 65) years. ResultsChanges in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself. ConclusionsThis is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.

The effects of stereotactic body radiotherapy on peripheral natural killer and CD3+CD56+ NKT-like cells in patients with hepatocellular carcinoma

BackgroundBoth natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. MethodsTwenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. ResultsThe peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. ConclusionsSBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.

Analyses of local control and survival after stereotactic body radiotherapy for pulmonary oligometastases from colorectal adenocarcinoma.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan–Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P < 0.01), type B calculation algorithm (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.04). A longer OS was associated with no history of local therapy for oligometastases (P = 0.04), a more recent period of SBRT (2010–15, P = 0.02), tumor located in the upper or middle lobe (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.01). In conclusion, OS after SBRT was good, but LC rate was relatively low. The use of high biological effective radiation doses can improve both LC and OS outcomes.

Effectiveness of stereotactic body radiotherapy for portal vein tumor thrombosis in patients with hepatocellular carcinoma and underlying chronic liver disease.

Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. This study included 24 patients. The initial prescription dose was 45Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6%vs 71.4%, P<.001; presence of hepatic toxicity vs absence: 0%vs 81.1%, P=.002). Overall, SBRT, especially in combination with TACE, is an effective treatment for patients with HCC and PVTT. An optimal dose schedule must be followed to reduce hepatic toxicity while maintaining tumor response.

Radiofrequency ablation versus stereotactic body radiotherapy for painful osseous metastases: A comparative correlation meta-analysis of pain relief.

e24156 Background: Osseous metastases (OMs), a common cause of cancer pain, are only partially palliated by analgesics. Stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are increasingly used, but the comparative effectiveness of SBRT vs. RFA for OMs has not been adequately evaluated. Herein we analyzed palliative benefits of SBRT and RFA in terms of pain relief from OMs. Methods: A systematic review was performed for all studies reporting palliative outcomes of SBRT (defined as five or fewer fractions of radiation) or RFA for palliation of OMs. Studies not reporting pain palliation were excluded. Random effects model determined the net Pearson correlation (R2) for post-SBRT and post-RFA pain reduction over time. The pooled correlation coefficient and 95% confidence interval were calculated using Fisher r-to- z transformation. Risk of bias was assessed using sunset plots; heterogeneity was assessed using I2 and meta-regression. Results: Seven full-text articles assessed a total of 1100 SBRT patients and 22 full-text articles assessed a total of 557 RFA patients. No studies directly compared SBRT to RFA. All included studies collected data on pain related to OM disease pre- and post-therapy. The scales used included the visual analog scale (2 SBRT, 15 RFA), brief pain inventory (4 SBRT, 4 RFA), numeric rating scale (0 SBRT, 2 RFA), QLQ-15 (1 SBRT, 0 RFA), or the memorial pain index card (0 SBRT, 1 RFA). Mean SBRT dose and fractions were 17.3 gy and 2.6. Median follow-up was 24 weeks for SBRT and 18 weeks for RFA, with median pain reduction of 59% (R2=0.83, 95%CI:0.80-0.87, I2=58.63%) and 64% (R2=0.52, 95%CI:0.41-0.62, I2=48.16%) respectively. Meta-regression by number of fractions and reporting metric fully accounted for heterogeneity in the SBRT and RFA data respectively. Sunset plots did not indicate significant publication bias. Conclusions: The published literature is predominately non-randomized, limiting the evidence level. Pain reduction and durability post-SBRT or post-RFA are comparable. Pre-SBRT or RFA therapies may obscure the full effect of either treatment modality. SBRT and RFA for painful OMs are associated with pain relief in a majority of patients, but the durability of this relief and the comparative efficacy of SBRT vs. RFA for this purpose has been inadequately reported in the literature. Future, combinatorial therapies as opposed to single-modality approaches may help to increase overall pain relief and durability as well as efficaciously palliating treatment-resistant patients.

&lt;p&gt;Celiac Plexus Block After Stereotactic Body Radiotherapy Improves Pain Relief in Locally Advanced Pancreatic Cancer&lt;/p&gt;

PurposeThis study evaluated the analgesic effect of stereotactic body radiotherapy (SBRT) in combination with celiac plexus block (CPB), relative to SBRT alone, in locally advanced pancreatic cancer (LAPC) patients.Patients and MethodsWe reviewed medical records of all patients with LAPC, who received SBRT between 1 January 2017 to 31 August 2019 at our center. The average numeric rating scale (NRS) of ≥3 was used in all patients at admission. We recorded average and worst NRS in a 24-hour period, and daily narcotic doses before SBRT, followed by weekly for 1 month and monthly for 3 months.ResultsA total of 23 patients in the SBRT group and 12 under SBRT+CPB who met the inclusion criteria were enrolled. All patients in the SBRT+CPB group received CPB within 10 days after SBRT. Pain intensity and narcotic consumption were comparable in both groups at initial assessment. However, a significant decrease (P < 0.05) in average NRS was recorded in the SBRT+CPB group relative to SBRT at 2, 3 and 4 weeks after SBRT. A comparison of daily narcotic consumption with baseline values showed a significant decrease in the SBRT+CPB group at 3 and 4 weeks after SBRT (P < 0.05), while no significant differences were observed in the SBRT group.ConclusionCPB after SBRT appears to be an effective therapeutic option in patients with LAPC and warrants further evaluation with increased number of patients in prospective clinical trials.

The effect of stereotactic body radiotherapy (SBRT) using flattening filter-free beams on cardiac implantable electronic devices (CIEDs) in clinical situations.

PurposeThis study focused on determining risks from stereotactic radiotherapy using flattening filter‐free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs.MethodsA retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6‐MV and 10‐MV FFF beams. First, a repetition‐rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single‐fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom.ResultsBetween 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep‐rate tests, inappropriate sensing occurred, starting at a rep‐rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT‐SBRT with a 10‐MV FFF beam were observed.ConclusionsThe study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG‐203. Correspondingly, it was found that for FFF beams although there is small risk from dose‐rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high‐dose rate to CIEDs positioned in close vicinity of the PTV may present issues.

A Phase I Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination with Transarterial Chemoembolization for Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is indicated in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Stereotactic body radiation therapy (SBRT) is increasingly being used in HCC. Preclinical studies show that moderate radiation doses (5-10 Gy) induce acute changes in tumor permeability and perfusion. Thus, we hypothesize that SBRT followed by TACE within 24 hours promotes sensitization to TACE. In this prospective phase I trial, we evaluated the feasibility, safety, tolerability, and functional magnetic resonance imaging (MRI) changes associated with single-fraction SBRT followed by TACE within 24 hrs. Patients with HCC, 1-3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hrs. Secondary endpoints included safety, tolerability, tumor perfusion changes via dynamic-contrast enhanced (DCE) MRI (at 6 or 24 hrs after SBRT), overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS). Tumor response and progression were graded using modified RECIST criteria. The uni-directional exchange rate constants kep (interstitial space to blood plasma) and kpe (blood plasma to interstitial space) were reported as measures of vascular permeability/perfusion. A total of 16 patients were enrolled, and all but one patient received SBRT. Within 24 hours, 13 of these 15 patients successfully underwent TACE. The median age was 64 years (range 48 to 79) and 84.6% of patients were males. Median tumor size was 5.6 cm (range 2.0 to 12.0). Median follow up for living patients is 12.6 months. Crude ORR and CBR are 58% and 75%, respectively. Median OS, PFS, and FFLP are 14.2 months, 6 months, and 5.3 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity are 85% and 38%, respectively. There were no grade 3 or 4 toxicities. One patient died due to TACE-related hemorrhage 4 days after TACE (grade 5). Regarding DCE-MRI metrics, kpe showed a rapid increase within 6 hrs post-SBRT (mean +300.0%, range -6% to +1030%, p=0.01), but a decrease by 24 hrs (mean -34%, range -75% to +17%, p=0.05). A similar trend was also observed for kep, with an increase within 6 hrs post-SBRT (mean +61.3%, range -50% to +218%, p=0.07) and return to near baseline by 24 hrs (mean +21%, range -29% to +155%, p=0.23). Single-fraction SBRT followed by TACE within 24 hrs is a feasible and tolerable strategy for intermediate-stage HCC. DCE-MRI analysis revealed significant acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination, and the effects of SBRT on the HCC microenvironment.

Preliminary Study of the Effect of Stereotactic Body Radiotherapy (SBRT) on the Immune System in Lung Cancer Patients Unfit for Surgery: Immunophenotyping Analysis.

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA− regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients.

Organs at Risk Considerations for Thoracic Stereotactic Body Radiation Therapy: What Is Safe for Lung Parenchyma?

Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors. This study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed. Ninety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20Gy (V20) <10% to 15%. To allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT.

Pain flare, complexity and analgesia in bone oligometastases treated with stereotactic body radiation therapy.

The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS≥2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n=18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n=23), pain control was obtained in 62% of patients at 1year; median time to pain progression after SBRT was 29months (CI95% 6-52months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30months, p=0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies.

The safety and effectiveness of stereotactic body radiotherapy for central versus ultracentral lung tumors

Background and purposeRecent studies have postulated that patients undergoing lung stereotactic body radiotherapy (SBRT) for ultracentral tumors have higher toxicity and mortality rates than those with central tumors. Our aim was to compare the outcomes after lung SBRT for central versus ultracentral tumors in our own series. Material and methodsThis was a retrospective review of patients with primary and metastatic lung tumors treated with SBRT from 1 September 2009 to 30 June 2015. Patients were included if they were treated with five-fraction SBRT to central or ultracentral tumors. Central tumors were defined as tumors where the closest point was within 2 cm of (but not abutting) the proximal bronchial tree, or within 2 cm of (whether abutting or not) mediastinal structures. Ultracentral tumors were defined as tumors abutting the proximal bronchial tree. The 2-year overall survival (OS), 2-year local failure (LF), and 2-year grade ≥3 toxicity rates were compared between patients with central and ultracentral tumors. ResultsA total of 107 patients were included in this study. There were no significant differences in 2-year OS between the two groups, with 2-year OS 57.7% for central tumors, and 50.4% for ultracentral tumors (p = 0.10). There were no significant differences in 2-year LF between the two groups, with 2-year LF 3.4% for central tumors and 4.3% for ultracentral tumors (p = 0.92). There were no significant differences in 2-year grade ≥3 toxicity rate for the two groups, with 3.5% with central tumors and 8.7% with ultracentral tumors (p = 0.23). ConclusionsThere were no significant differences in OS, LF, or grade ≥3 toxicity between patients with central and ultracentral lung tumors. Although these results indicate that SBRT for ultracentral tumors may be safe, caution should be applied in selecting and treating these patients until the completion of large prospective trials.

Treatment-Related Mortality Among Early-Stage NSCLC Patients Undergoing Surgery Versus SBRT

The comparative effectiveness of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (esNSCLC) continues to be debated. Perioperative surgical mortality may give SBRT patients an early survival advantage. We endeavored to compare near-term mortality in a large esNSCLC population between patients undergoing surgery or SBRT in an analysis of the National Cancer Database (NCDB). NCDB was queried for patients with T1-T2a N0 M0 NSCLC diagnosed from 2004 to 2013 undergoing either SBRT or surgery. Thirty-day and 90-day post-treatment mortality was calculated by subtracting the time from diagnosis to treatment initiation from duration of follow-up and compared between SBRT and various surgical approaches. Patients were segmented into similarly sized age quartiles. Multivariate logistic regression (MVA) was performed to determine associations between odds of mortality and demographic, facility-specific, and clinical factors. Propensity-score matching (PSM) was also performed to derive a 3:1 (surgery:SBRT) matched cohort in order to compare odds of mortality between surgery and SBRT by univariate logistic regression. We identified 76,623 surgery patients, of whom 77.7% received lobectomy, and 8,216 SBRT patients, who received a median dose of 51 Gy. Surgical patients experienced increased mortality as compared to those undergoing SBRT at both 30 days (2.1% vs 0.7%) and 90 days (3.6% vs 2.9%), differences most pronounced among patients older than 75 (Table 1). On MVA, each surgical modality was associated with increased mortality versus SBRT at 30 days (odds ratio [OR] for sublobar resection 2.76, 95% CI 2.08-3.68; OR for lobectomy 3.52, 95% CI 2.70-4.60; OR for pneumonectomy 14.1, 95% CI 10.1-19.8; all P < 0.001) and at 90 days (OR for sublobar resection 1.36, 95% CI 1.16-1.61; OR for lobectomy 1.58, 95% CI 1.37-1.83; OR for pneumonectomy 5.59, 95% CI 4.46-7.01; all P < 0.001). Among a PSM cohort of 28,248 patients, surgical patients continued to experience increased mortality at both 30 days (2.5% vs 0.7%; OR 3.43, 95% CI 2.57-4.56; P < 0.001) and 90 days (4.2% vs 2.8%; OR 1.53, 95% CI 1.31-1.79; P < 0.001). We identified greater mortality in the near-term post-treatment period in a modern cohort of esNSCLC patients undergoing surgery versus SBRT. These findings may guide management of esNSCLC, particularly for older patients and those at greatest risk of perioperative morbidity, and underscore the importance of multidisciplinary evaluation.Abstract 1154; Table 1Age QuartileSublobar ResectionLobectomyPneumonectomyAll SurgerySBRT30-Day Mortality Rates (%)<620.70.85.31.00.762-681.31.47.21.50.469-751.72.410.92.40.8>752.93.913.83.70.890-Day Mortality Rates (%)<621.31.48.11.62.762-682.32.411.02.61.969-753.24.216.04.22.7>755.46.521.36.43.5 Open table in a new tab

Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

BackgroundFor prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.Methods/designThis German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.DiscussionThe HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.Study statusThe study is ongoing and currently recruiting patients.Trial registrationRegistration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015.

Curative effect of stereotactic body radiotherapy for unresectable massive primary liver cancer.

The aim of this study was to evaluate the curative effect of gamma knife stereotactic body radiotherapy (SBRT) for unresectable massive primary liver cancer. A total of 69 patients with unresectable massive (>10 cm) primary liver cancer who were treated by SBRT at the Department of Radiation Oncology of the 323 Hospital of People's Liberation Army (Xi'an, China) between October, 2006 and October, 2010, were analyzed. According to the Union for International Cancer Control TNM staging guidelines, the patients were graded as stage T1 (n=8), T2 (n=12), T3 (n=21) and T4 (n=28). None of the patients had lymph node metastasis, whereas 45 patients had portal vein tumor thrombosis. The Child-Pugh class was A (n=49), B (n=15) and C (n=5). The visible tumor volume ± standard deviation was 810±213 cm3. The patients received a total radiation dose of 50-60 Gy, with a dose fractionation of 4-6 Gy/fx, administered for a total of 9-12 times, 2-5 times/week. A total of 8 patients succumbed to the disease within 3 months after gamma knife treatment and were not included in the evaluation of the curative effect. The total effectiveness rate was 59.0% (36/61) and the median survival was 17.4 months for all the patients included in the study. The 1-, 2-, and 3-year overall survival rates were 71, 30 and 22%, respectively. In conclusion, SBRT appears to be effective for unresectable massive primary liver cancer.

Effect of Stereotactic Body Radiotherapy on the Growth Kinetics and Enhancement Pattern of Primary Renal Tumors.

The objective of our study was to assess the growth rate and enhancement of renal masses before and after treatment with stereotactic body radiotherapy (SBRT). This retrospective study included all patients with renal masses who underwent SBRT during a 5-year period. Orthogonal measurements of renal masses were obtained on pre- and posttreatment CT or MRI. Pre- and posttreatment growth rates were compared for renal mass diameter and volume using the t test. Pre- and posttreatment tumor enhancement values were compared for tumors that underwent multiphasic contrast-enhanced MRI. Forty patients underwent SBRT for the treatment of 41 renal tumors: clear cell renal cell carcinomas (RCCs) (n = 16), papillary RCCs (n = 6), oncocytic neoplasms (n = 8), unclassified RCCs (n = 2), urothelial carcinoma (n = 1), and no pathologic diagnosis (n = 8). The mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). Three hundred thirty-eight pre- and posttreatment imaging studies were analyzed: 214 MRI studies and 124 CT studies. The mean pre- and posttreatment lengths of observation were 416 days (range, 2-1800 days) and 561 days (83-1366 days), respectively. The mean pretreatment tumor growth rate of 0.68 cm/y decreased to -0.37 cm/y post treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm(3)/y before treatment decreased to -5.35 cm(3)/y after treatment (p = 0.002). Local control-defined as less than 5 mm of growth-was achieved in 38 of 41 (92.7%) tumors. The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 showed progression in one tumor (2.4%), stability in 31 tumors (75.6%), partial response in eight tumors (19.5%), and complete response in one tumor (2.4%). No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days). Renal tumors treated with SBRT show statistically significant reductions in growth rate and tumor size after treatment but do not show statistically significant differences in enhancement in the initial (mean, 142 days) posttreatment period.

Stereotactic body radiotherapy with helical TomoTherapy for medically inoperable early stage primary and second-primary non-small-cell lung neoplasm: 1-year outcome and toxicity analysis.

This study investigated the effectiveness of stereotactic body radiotherapy with helical TomoTherapy (T-SBRT) for treating medically inoperable primary and second-primary early stage non-small-cell lung neoplasm (SPLN) and evaluated whether the movement of organizing pneumonia (OP) within the irradiation field (IF) can be detected via analysis of radiological changes. Patients (n = 16) treated for 1 year (2011-12) at our hospital by T-SBRT at a total dose of 60 Gy in five fractions were examined retrospectively. Outcome and toxicity were recorded and were separately described for SPLN. CT scans were reviewed by a single radiologist. Of the 16 patients, 5 (31.3%) had primary lung malignancies, 10 (62.5%) had SPLN, and 1 case (6.3%) had isolated mediastinal metastasis of lung neoplasm. Pathological evidence was obtained for 72.2% of all lesions. The median radiological follow-up was 11 months (10.5 months for SPLN). For all cases, the 6- and 12-month survival rates were 100% and 77.7% (100% and 71.4%, respectively, for SPLN), and the 6- and 12-month locoregional control rates were 100% in all cases. 2 (12.5%) of 16 patients developed grade 3 late transient radiation pneumonitis following steroid therapy and 1 (6.3%) presented asymptomatic infiltrates comparable to OP opacities. T-SBRT seems to be safe and effective. Mild OP is likely associated with radiation-induced anomalies in the IF, identification of migrating opacities can help discern relapse of radiation-induced opacities.

Stereotactic Body Radiation Therapy: A Review of Applications and Outcomes

Radiotherapy is a versatile tool used in the treatment of various types of benign and malignant neoplasms. However, conventional radiation therapy for cancerous conditions often results in collateral damage to healthy tissues due to involvement of oversized radiation fields. Over the last decade one type of precision based radiation treatment has developed. This new treatment, known as Stereotactic Radiosurgery (SRS), involves highly accurate beams of high-energy radiation that are used to destroy abnormal cells by permanently damaging their DNA. As technology progressed stereotactic cranial radiosurgery developed into a successful method for certain tumorous conditions of the head and skull. The success of stereotactic cranial radiosurgery led to further radiation application research to widen the spectrum of treatable conditions to include those located extracranially. The result of this continued research led to the development of stereotactic body radiation therapy (SBRT), a radiotherapy technique based upon principles of SRS that is used to treat small or moderate sized tumors of the body with a limited number of treatments. Stereotactic body radiation therapy combines the use of the latest tumor imaging technology as well as precision based radiation delivery mechanisms to overcome physiological barriers of normal radiation therapy such as movement of tumors in tissues. The net effect of SBRT is that a dose of radiation much larger than normal can be administered in a very precise manner, over smaller time frame, bringing about a dramatic tumor response. In this review the authors will attempt to briefly cover the subject of stereotactic body radiation therapy as well as its applications and effectiveness.