Role Of Stereotactic Body Radiation Therapy Research Articles

Abstract PO2-05-11: Patient Perspectives on the Value of Stereotactic Body Radiotherapy (SBRT) in the Management of Breast Cancer: The PERSPECTIVE Study

Abstract Background: Oligometastatic disease describes limited metastases amenable to local therapy such as stereotactic body radiotherapy (SBRT). Within the UK National Health Service (NHS), SBRT is a standard of care for up to 3 metachronous sites of oligometastatic breast cancer (OMBC), offering high local control rates with low toxicity. The SABR-COMET study demonstrated improved progression-free survival (PFS) and overall survival (OS) with SBRT compared to standard of care in a number of oligometastatic cancers, including breast cancer [1]. Conversely, the NRG-002 trial results suggest no PFS or OS improvement with the addition of SBRT to standard systemic therapy in OMBC [2]. The OS data for this study are yet to mature and in the meantime the results of other prospective studies are awaited. As patients’ attitudes and perspectives govern their preferences around treatment decisions, it is vital to understand whether PFS and OS are the most important considerations for patients. This study aims to explore patients’ perspective on the role of SBRT in breast cancer management. Their views will help inform future trial endpoints and support clinicians to support patients with their decision making and expectations. Methods: We conducted an exploratory qualitative study with focus groups and individual interviews, to understand participants knowledge, views and opinions on SBRT in treating breast cancer. All patients were asked to watch an educational video about SBRT in advance of participating in the interviews. An interview guide with open-ended questions was developed. Breast cancer patients were recruited using a purposive sampling matrix based on the patients age, presence of metastatic disease and previous experience with radiotherapy. Each focus group had at least two moderators and all interviews were digitally recorded and then transcribed. The data were managed and coded using NVivo version 12 and analysed using a thematic analysis approach. Results: A total of 18 breast cancer patients participated in this study, with 7 (39%) having primary disease and 11 (61%) with metastatic disease. The study included two focus groups (group one = 5 patients; group two = 9 patients) and four individual interviews conducted between May and June 2023. The participants had a median age of 54 years (range 38-74). The majority of participants (83%) had previous experience with radiotherapy, with 4 (27%) having received SBRT previously for their OMBC. Only 2 (2%) patients who had not previously received SBRT were aware of it before participating in this study. Most of the patients (78%) were Caucasian and 72% had attained at least an undergraduate degree level of education. Throughout the study, three main themes emerged: theme 1 - participants experience with radiotherapy; theme 2 - interests and considerations regarding SBRT (including desired treatment outcomes) and theme 3 - willingness to consider SBRT in absence of a survival benefit. Extending their life was unanimously described as the most important desired outcome of SBRT, followed by quality of life. Other desired treatment outcomes expressed included reduction of tumour size, minimal collateral damage/side effects, relief of symptoms, avoidance of recurrence and increase in time to change of systemic therapy. Conclusion: In our study, while extension of life was a desired treatment outcome of SBRT for OMBC, all participants expressed willingness to consider SBRT for its potential benefits in local control and durable pain control, even in absence of a survival benefit.

The role of stereotactic body radiotherapy (SBRT) in the treatment of recurrent / progressive lung lesions after primary treatment

The role of stereotactic body radiotherapy (SBRT) in the treatment of recurrent / progressive lung lesions after primary treatment

MRI Guided Adaptive Radiotherapy (MRgART) in Primary and Metastatic Liver Lesions

The role of stereotactic body radiotherapy (SBRT) in the management of primary hepatic and metastatic tumors has increased significantly over the past few years. MR-Linac is rapidly gaining evidence in the delivery of ablative doses using MR guided adaptive radiotherapy (MRgART) with improved accuracy and dose coverage to the lesions. We report local control and toxicity of patients with primary and metastatic liver lesions treated with MR guided adaptive SBRT. All patients were treated with MRgART on the Unity 1.5T MR Linacs at two institutions and consented to the ADAPT-MRL study (1). A 4DCT and MRI with abdominal compression were obtained at simulation and the primary MRI sequence used for online treatment included a T2 3D navigated scan. A balanced turbo field echo (btFFE) 2D cine motion scan was also acquired at every fraction to determine movement of the tumor to aid in internal target volume margin. All plans were treated with SBRT prescribed to 3-5 alternate daily fractions. Acute toxicity was reported according to Common Terminology Criteria for Adverse Events version 5 (CTCAE) v.5. Patient demographics, prescribed dose fractionation, acute toxicity and clinical response at 6 months were analyzed. Clinical response to treatment was measured according to RECIST criteria 1.1. Between February 2021 to January 2023 a total of 30 patients were treated with 149 fractions to the liver. Patients were majority male (70%) with a median age of 66 (range 36-83). 16 patients were treated for primary hepatocellular carcinoma (HCC) of the liver and 14 patients for metastatic liver lesions. The median prescribed dose was 48 Gy (range 30-50Gy) in median 5 fractions (range (3-5 fractions). All patients completed treatment with no interruptions. The mean time from 'patient setup' to 'beam-off' was 52.6 minutes (range 37-73 minutes). Data on acute toxicity at 3 month follow up was available for 28 patients. Of these patients 7/28 (25%) had grade 1 or 2 toxicity and no >/ = grade 3 toxicity was reported. Clinical response at 6 months was available for 18 patients and showed complete response in 44% (8/18), partial response in 22% (4/18), stable disease in 22% (4/18) and progressive disease in 11.1% (2/18). Our experience on MRgART to the liver has shown good local control and minimal acute toxicity in the treatment of primary and metastatic liver lesions. We continue to collect data on patient reported outcomes, clinical response and toxicity to determine the feasibility and safety of this system.

Ten-Year Outcomes of Stereotactic Body Radiotherapy for Oligometastatic Breast Cancer: Does Synchronous Oligometastatic Breast Cancer Benefit?

AimsThe benefit of stereotactic body radiotherapy (SBRT) in metachronous oligometastatic breast cancer (OMBC) has previously been described and its use in current clinical practice is established. The role of SBRT in the management of synchronous OMBC remains uncertain. The aim of this study was to compare outcomes of SBRT-treated synchronous OMBC with those of SBRT-treated metachronous OMBC. Materials and methodsThis was a retrospective analysis of consecutive extracranial OMBC patients treated with SBRT at a single institution between 2011 and 2022. Kaplan–Meier methods were used to calculate progression-free survival (PFS), overall survival, local control and distant control. Log-rank tests were used to test any differences. Cox regression was used for univariate and multivariate analyses to identify predictive factors. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. ResultsIn total, 74 OMBC patients with 113 lesions were analysed. The median follow-up was 20 months (range 0–98). Seventy per cent of patients presented metachronously and 30% synchronously. 30 Gy in three fractions was most commonly prescribed, resulting in a median biologically effective dose (BED at α/β = 10) of 60 Gy (range 35.7–112.5 Gy). Forty-nine per cent of patients switched systemic therapy post-SBRT (median time to switch: 14 months, range 0–79). Two patients (2%) experienced grade 3 acute toxicities with no grade ≥4 toxicities. At 2 years overall survival was 92.4% and PFS 39.0%, local control 85.9% and distant control 37.0%. For metachronous and synchronous disease, respectively, 2-year local control rates were 86.5% and 85.8% and PFS rates were 35.3% and 48.3%. The median PFS of metachronous and synchronous disease were 18 months and 17 months, respectively (P = 0.86). Predictive factors on multivariate analysis were treated site for overall survival, change in systemic therapy post-SBRT for PFS and BED for local control. ConclusionOur data confirm SBRT as a well-tolerated treatment for OMBC with excellent local control rates regardless of metachronous or synchronous presentation. There is no suggestion that survival outcomes are inferior for synchronous disease. Further prospective studies are required to validate this finding.

Stereotactic body radiotherapy in oligoprogressive metastatic castration-resistant prostate cancer during abiraterone or enzalutamide.

This monocentric, single-arm, retrospective study investigated the role of stereotactic body radiotherapy in patients with metastatic castration resistant prostate cancer who experienced oligoprogression during androgen receptor targeted agents. We retrospectively enrolled metastatic castration resistant prostate cancer patients treated with androgen receptor targeted agents between December 2016 and January 2022. All patients experienced an oligoprogression (defined as the appearance and/or the progression of ⩽5 bone or nodal or soft tissue metastases) during treatment with androgen receptor targeted agents and received stereotactic body radiotherapy upon oligoprogressive sites, preserving the androgen receptor targeted agents. Further stereotactic body radiotherapy upon new metastatic sites was permitted. Patients showing visceral metastases or receiving palliative radiotherapy were excluded. Progressive disease at >5 metastatic sites or the appearance of visceral metastases led to a change of the systemic treatment. Primary endpoints were 36-month survival rate and 36-month rate of patients receiving treatment with androgen receptor targeted agents. Secondary endpoints were local disease control, biochemical response and safety. We analyzed data from 30 patients. The 36-month survival rate was 90% (27 patients); 36-month rate of patients who were still on treatment with androgen receptor targeted agents was 50%. 20 of 30 patients had performed imaging control after a single course of stereotactic body radiotherapy: overall response rate was 50%, while clinical benefit was 93%. No ⩾G2 adverse events related to stereotactic body radiotherapy were recorded. Stereotactic body radiotherapy in oligoprogressive metastatic sites during androgen receptor targeted agent treatment resulted in a feasible and effective treatment to delay the start of next-line systemic treatment and prolong overall survival in metastatic castration resistant prostate cancer. Longer follow-up and further prospective studies are necessary to confirm our preliminary results.

Stereotactic Body Radiation Therapy (SBRT) in a Standardized Neoadjuvant Therapy Pathway for Pancreatic Cancer across a Geographically Large and Diverse Healthcare System

<h3>Purpose/Objective(s)</h3> The role of SBRT as part of a neoadjuvant therapy pathway (NATP) is actively being defined in the setting of growing multidisciplinary approach to pancreatic cancer (PC). A standardized approach to neoadjuvant therapy (NAT) has been shown to improve outcomes. We evaluated whether patients who received SBRT as part of our standardized NATP had better outcomes than patients in our institution who were not enrolled in our NATP. <h3>Materials/Methods</h3> The NATP was established at Northwell Health in June 2019, consisting of a single-day pancreas multi-disciplinary clinic (PMDC) visit, followed by neoadjuvant chemotherapy with interval scans and PMDC re-reviews prior to consideration of radiation and/ or surgical resection. Prior to consideration for resection, SBRT was standardized for borderline resectable PC (BRPC) and locally advanced PC (LAPC) patients after completion of chemotherapy. We retrospectively analyzed patients undergoing neoadjuvant SBRT in the last 5 years prior and after the establishment of NATP. Primary endpoints included resection rates, quality assurance (QA) measures and overall survival (OS). Kaplan-Meier analysis was used to estimate OS. <h3>Results</h3> A total of 38 non-metastatic patients were identified between January 2017 and December 2021 undergoing neoadjuvant SBRT after completion of at least 1 cycle of chemotherapy with 19 (50%) enrolled in the newly established NATP. Between NATP and non-NATP SBRT, mean age was 66.3 vs 63.3 years (p=.519) and additional baseline characteristics listed in Table 1 were comparable. SBRT BED (10) was 87.4Gy in NATP vs 68.8Gy in non-NATP (p<0.001). NATP patients underwent surgery at 47% vs. 26% in non-NATP (p=.179). Median OS was 19.7 months for all patients undergoing SBRT, with median follow-up (FU) of 13.0 mo (IQR: 9.2-18.8 mo). With Median FU of 10.0 mo vs 18.5 mo (p<0.001), NATP Median OS was 16.0 mo vs. non-NATP 22.8 mo (p=0.157). Surgery was the only significant predictor of OS, Median OS 28.3 mo vs. 18.5 mo (p=0.047). Implementation of NATP showed QA improvements in time of biopsy to start of chemotherapy (NATP 21 days (d) vs. 28 d) and time of radiation to surgery (NATP 35 d vs. 68d). <h3>Conclusion</h3> Implementation of a NATP with standardized incorporation of SBRT increased the percentage of PC patients who underwent timely radiation therapy and surgical resection. Further follow-up is required for assessing OS benefit. A standardized NATP increases access for patients to radiation therapy and sets the groundwork for multi-disciplinary care in PDAC.

The Current Role of Stereotactic Body Radiation Therapy (SBRT) in Hepatocellular Carcinoma (HCC).

Simple SummaryThe role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to bridging transplantation and treating oligometastases from HCC in combination with immune checkpoint inhibitors. Major guidelines suggest that SBRT be regarded as a substitute therapy to conventional therapies, such as surgery, ablative therapies, transarterial chemoembolization, and systemic therapy. Further investigations are expected to establish the rationale for using SBRT in each situation.The role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to pre-transplantation and the treatment of oligometastases from HCC in combination with immune checkpoint inhibitors (ICI). In early-stage HCC, many promising prospective results of SBRT have been reported, although SBRT is not usually indicated as a first treatment potion in localized HCC according to several guidelines. In the treatment of portal vein or inferior vena cava tumor thrombi, several reports using various dose-fraction schedules have shown relatively good response rates with low toxicities and improved survival due to the rapid advancements in systemic therapy. Although SBRT is regarded as a substitute therapy when conventional bridging therapies to transplantation, such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), are not applicable or fail in controlling tumors, SBRT may offer advantages in patients with borderline liver function who may not tolerate TACE or RFA, according to several reports. For oligometastases, the combination of SBRT with ICI could potentially induce an abscopal effect in patients with HCC, which is expected to provide the rationale for SBRT in the treatment of oligometastatic disease in the near future.

Transcriptomic profiling identifies genomic markers associated with benefit from stereotactic body radiation therapy (SBRT) in oligoprogressive metastatic renal cell carcinoma (mRCC).

4555 Background: Addition of SBRT to systemic therapy in oligoprogressive mRCC has been shown to prolong the duration of systemic treatment (Cheung et al Eur Urol 2021; De et al BJUI 2021). To date, the genomic predictors of benefit are unknown. We hypothesized that hypoxia-related genes would be associated with lesser benefit from SBRT. Methods: We retrospectively identified patients (pts) with mRCC who had oligoprogressive disease (progression of &lt; 5 sites) while on systemic treatment and received SBRT without any systemic treatment change or interruption. Clinicopathologic characteristics, whole exome and transcriptome sequencing (Ashion Analytics) data were collected. Duration of systemic therapy (DOT) was quantified as systemic treatment duration prior to oligoprogression (DOT[P]) and after completion of SBRT (DOT[S]). The ratio of DOT[S]/DOT[P] was calculated and patients with a ratio ≥ 1.0 were considered to derive greater benefit from SBRT. The frequency of specific DNA alterations and RNA expression of pts above and below a DOT[S]/DOT[P] threshold of 1.0 was compared using a two-tailed Fischer’s exact and student’s t-test, respectively. Results: In this study, 23 mRCC pts who had oligoprogression during systemic treatment and received SBRT were identified. Within this cohort 16 pts (69.6%; M:F, 12:4) had available genomic data. Median age was 70 years and the most common histology was clear cell (87.5%). At the time of oligoprogression 11 pts (68.8%) were on immunotherapy, 4 pts (25.0%) were on targeted therapy. Median DOT[S] and DOT[P] were 12.6 months (range,0.7-46.3) and 13.4 months (range, 0.5-26.9), respectively, with a median DOT[S]/DOT[P] ratio of 1.4 (range,0.01-3.8). The most commonly mutated genes were VHL (56.3%), PBRM1 (37.5%), and SETD2 (37.5%). Alterations in VHL, PBRM1 and SETD2 were seen in 66.7% vs 42.9%, 33.3% vs 43.9%, and 44.4% vs 28.6% in patients with greater vs lesser benefit from SBRT, respectively (p≥0.05for each). Transcriptomic analysis was available in 9 pts and 1580 genes were noted to be differentially expressed between the groups (p &lt; 0.05). Limiting scope to cancer genes in the COSMIC database, pts with lesser benefit from SBRT had higher expression of CDKN1B, CNBP, and FOXO3 whereas pts with greater benefit had higher expression of RNF43, POLD1 and PBRM1 (p &lt; 0.05 for each). Gene set enrichment analysis showed a trend towards increased expression of hypoxia related genes in pts with lesser benefit. Conclusions: Our data align with existing studies supporting the role of SBRT in oligoprogressive mRCC. In addition, while clinical benefit from SBRT appears to be independent of DNA-level alterations, transcriptomic analysis revealed significant differences in gene expression. Hypoxia-associated signatures may be associated with lesser benefit from radiotherapy.

Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients

Breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS). One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24months. Median NEST 8months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p = < 0.01). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression < 6months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED) > 70Gy10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p = 0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p = 0.02). SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified.

The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma.

Targeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT. We examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated. Median age was 67years (range 31-83years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1months, median OS was 49.1months and the median PFS was 18.3months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade ≥ 3 acute and late toxicities. The SBRT to oligometastatic sites is an effective and safe treatment option for ≤ 5 metastases in RCC patients by providing favorable survival and delaying NEST change.

Role of stereotactic body radiotherapy for early-stage non-small-cell lung cancer in patients borderline for surgery due to impaired pulmonary function.

Stereotactic body radiotherapy (SBRT) is recommended only for inoperable patients with early-stage (e-stage) non-small-cell lung cancer (NSCLC). We compared outcomes between surgery and SBRT in patients borderline for surgery due to impaired pulmonary function (PF). We reviewed single-institution retrospective data of 578 patients with clinically T1-2N0M0 NSCLC treated by surgery or SBRT between 2004 and 2014, and extracted a cohort with borderline impaired PF for surgery, which was defined as predicted postoperative (PPO) forced expiratory volume in 1 s (FEV1 ) of<50% and ≥30%. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared between surgery and SBRT using propensity score-matching (PSM) to avoid bias. Among a total of 116 eligible patients with a median PPO FEV1 of 45%, PSM identified 25 patients from each group with similar characteristics. The median age, pretreatment FEV1 , and follow-up durations for the surgery and SBRT groups were 75 and 74 years, 58% and 56%, and 56 and 60 months, respectively. The 5-year OS, CSS, and DFS rates of the surgery versus SBRT groups were 60%versus 63%, 76%versus 81%, and 52%versus 48%, respectively (p=0.97, 0.81, and 0.99). The surgical mortality was 4.0%, but no treatment-related death was observed after SBRT. The incidence of ≥ grade 2 adverse events after surgery was double that after SBRT (40%versus 20%, p=.22). Our study suggests that SBRT is a reasonable option for patients with e-stage NSCLC and impaired PF who are considered borderline candidates for surgery.

Role of Stereotactic Body Radiotherapy (SBRT) in the Treatment of Oligo Metastatic Colorectal Cancer: Analysis of a Large Multi-Institutional Database

In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective local treatment for oligometastatic cancers. However, it has been suggested that colorectal cancers may represent a more radioresistant histology, even to the high doses used in SBRT. Here, we report local recurrence rates, progression free-survival, and overall survival of patients with oligometastatic CRC treated with SBRT using a large multi-institutional data-base.We collected data retrospectively from six cancer centers with a high volume of SBRT treatments from Jan 1 2008 to December 31, 2016. Our primary outcome was local recurrence while secondary outcomes included overall survival (OS), local recurrence free survival, progression free survival, oligo-progression, and widespread progression. Time-to event outcomes were estimated using the Kaplan-Meier method. Univariable regression analysis was performed to determine the relationship between patient, tumor and treatment variables and outcomes. Variables significant on univariable screen were entered into a multivariable model. All analysis was performed in R (R Foundation for Statistical Computing, version 4.0.2) RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions that were treated with SBRT. The mean age was 70.7 ± 12.2 years, 58% of patients were male with a median follow-up of 25.5 months. The most common site of metastasis was the lung (n = 133, 56.6%) with a total of 239 (62.7%) lesions. The median time to local recurrence was not reached with the 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year probability of 76.1% and 35.9% respectively. On multivariable analysis, a BED10 of ≥100 Gy (HR 0.67, 95% CI 0.45-0.99) and the presence of lung (HR 0.53, 95% CI 0.34-0.82) or lymph node metastasis as opposed to liver metastasis (HR 0.31, 95% CI 0.13-0.74) were associated with improved local control. Larger total PTV size (≥17.5cc) was associated with worse overall survival (HR 2.62, 95% CI 1.45-4.72), progression free survival (HR 2.01, 95% CI 1.39-2.90) and widespread progression (HR = 2.82, 95% CI: 1.63-4.88). Use of prior systemic therapy before SBRT was also adversely associated with widespread progression (HR = 1.90, 95% CI: 1.22-2.95).This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is appreciably lower than what has historically been demonstrated in other cancer primary sites. These results suggest that an increase in BED should be considered if feasible and safe, in order to optimize local control. Increased overall PTV size may also be an indicator for the need for systemic therapy in addition to SBRT.

Role of Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer in Borderline Patients for Surgery due to Impaired Pulmonary Function

Stereotactic body radiotherapy (SBRT) is recommended only for inoperable patients with early stage (e-stage) non-small cell lung cancer (NSCLC). We compared outcomes between surgery and SBRT in borderline patients for surgery due to impaired pulmonary function (PF).In our institution, operable patients (i.e., sufficient PF and no serious comorbidity) were generally selected for surgery after discussion among the multidisciplinary team. The inoperable patients decided after discussion among the multidisciplinary team and those who refused surgery were usually selected for SBRT. The total dose of 44 or 48 Gy for tumors with a maximum diameter < 1.5 cm, 48 or 50 Gy for tumors of 1.5-3 cm, and 52 Gy for tumors > 3 cm was prescribed to the isocenter of the planning target volume. Surgery included lobectomy, sub lobar resection (SLR), and wedge resection (WR) by video-assisted thoracic surgery or open thoracotomy at the thoracic surgeons' discretion. We reviewed single-institutional retrospective data of 578 patients with clinically T1-2N0M0 NSCLC treated by surgery or SBRT between 2004 and 2014, and extracted a cohort with borderline impaired PF for surgery, which was defined as predicted postoperative (PPO) forced expiratory volume in 1 second (FEV1) of < 50% and ≥ 30%. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared between surgery and SBRT using propensity score-matching (PSM) to avoid bias.Among a total of 116 eligible patients with a median PPO FEV1 of 45%, PSM identified 25 patients from each group with similar characteristics. After PSM, 17 (68%), 3 (12%), and 5 (20%) patients underwent lobectomy, SLR, and WR, respectively. The median age, pretreatment FEV1, and follow-up durations for the surgery and SBRT groups were 75 and 74 years, 58% and 56%, and 56 and 60 months, respectively. The 5-year OS, CSS, and DFS rates of the surgery vs SBRT groups were 60% vs 63%, 76% vs 81%, and 52% vs 48%, respectively (P = 0.97, 0.81, and 0.99). Among the matched patients, one patient died of massive hemorrhage during lobectomy. The 90-day surgical mortality was 4.0% (1 of 25), but no treatment-related death was observed after SBRT. In the surgery group after PSM, 10 (40%) patients had grade 2 or greater adverse events. In the SBRT group after PSM, 5 (20%) patients had treatment-related grade 2 or greater adverse events. After PSM, the incidence of grade 2 or greater adverse events in the surgery group was twice as high as that in the SBRT group, but this difference was not significant by the χ2 test (40% vs 20%, P = 0.22).Although surgery and SBRT had similar survivals, fewer adverse events were observed after SBRT. Our current study suggests that SBRT is a reasonable option for impaired PF patients borderline for surgery in e-stage NSCLC. However, a prospective study of this specific population is warranted in order to improve patient selection for SBRT or surgery.

The Role of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic and Oligoprogressive Gynecologic Malignancies: A Multi-Institutional Pooled Analysis

The optimal use of stereotactic body radiotherapy (SBRT) for the diverse group of patients with gynecologic malignancies has not been clearly defined. This multi-institutional pooled analysis aims to characterize the use of SBRT for different primary disease types and indications within the gynecologic cancer population.Patients treated with SBRT at three institutions with oligometastatic (OM) disease (5 or fewer sites), oligoprogressive (OP) disease (limited areas of progression with controlled systemic disease), or progression in an eloquent area were included. Descriptive statistics were used to report patient and treatment characteristics and toxicity. Local recurrence-free survival (LRFS), distant progression-free survival (DPFS), salvage chemotherapy-free survival (CFS, excluding patients on systemic therapy at time of SBRT) and overall survival (OS) probabilities following SBRT were calculated using Kaplan-Meier methods. Associations with disease and tumor factors were examined using Cox regression methods.One hundred forty-four patients (144) with gynecologic cancers were treated with SBRT to 206 lesions. The median age was 61 (range 46-86) and median follow up was 16.6 months (range 0.5-106.8). Patients had cancers of the uterus (n = 101), ovary (n = 67), cervix (n = 27), and vulva or vagina (n = 8). Lesions were considered OM (n = 124), OP (n = 68), or progressive in an eloquent area (n = 14). Treatment was delivered to lesions in the pelvis (n = 50), lung (n = 40), para-aortic region (n = 37), abdomen or liver (n = 36), bone (n = 31), and distant nodes (n = 10). SBRT dose ranged from 20-60Gy (median 40Gy) in 2-5 fractions. Twenty-three (11.1%) lesions recurred locally after SBRT. Median LRFS was 23.9 months (95% CI 20.2-27.5), DPFS was 10.7 months (95% CI 10.7-16.9), and OS 22.9 months (95% CI 12.8-31.3). LRFS was 73.0% and 47.8%, DPFS was 44.2% and 19.6%, and OS was at 72.9% and 46.6% 1 and 2 years respectively. Twenty-nine percent of patients received salvage systemic therapy, and median CFS was 14.1 months (95% CI 10.4-17.8). On multi-variable analysis, only higher BED (OR 0.98, P = 0.013) was associated with LRFS. Primary disease type, tumor size, dose of radiotherapy, nodal versus non-nodal target, and DFI were not significantly associated with OS or DPFS on MVA.This large cohort of patients receiving SBRT for oligometastatic and oligoprogressive gynecologic cancers had excellent tumor control, and promising DPFS and OS. Local control appears to be related to SBRT dose. SBRT may have the potential to delay time to initiation of chemotherapy or targeted therapies in select gynecologic cancer populations. Further prospective studies are required to determine which primary disease types benefit most from SBRT, and to establish the optimal sequencing of SBRT with other oncologic treatments.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study

BackgroundNivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined. ObjectiveOur aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients. Design, setting, and participantsThe NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT. InterventionThe patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients. Outcome measurements and statistical analysisWe hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety. Results and limitationsSixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9–7.1) and median OS 20 mo (95% CI, 17–not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose. ConclusionsWe did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease. Patient summaryNivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

Radiation therapy for prostate cancer: What's the best in 2021.

Radiotherapy is highly involved in the management of prostate cancer. Its features and potential applications experienced a radical evolution over last decades, as they are associated to the continuous evolution of available technology and current oncological innovations. Some application of radiotherapy like brachytherapy have been recently enriched by innovative features and multidisciplinary dedications. In this report we aim to put some questions regarding the following issues regarding multiple aspects of modern application of radiation oncology: the current application of radiation oncology; the modern role of stereotactic body radiotherapy (SBRT) for both the management of primary lesions and for lymph-nodal recurrence; the management of the oligometastatic presentations; the role of brachytherapy; the aid played by the application of the organ at risk spacer (spacer OAR), fiducial markers, electromagnetic tracking systems and on-line Magnetic Resonance guided radiotherapy (MRgRT), and the role of the new opportunity represented by radiomic analysis.

Hepatocellular carcinoma patients with portal vein thrombosis treated with robotic radiosurgery: Interim results of a prospective study.

This is a prospective study evaluating the role of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) in Indian patients suffering from hepatocellular carcinoma with portal vein thrombosis (HCC-PVT). Patients with inoperable HCC-PVT, good performance score (PS), and liver function are accrued for treatment on CK (version M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring, and the gross tumor volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per-risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy, and the duodenum max of ≤24 Gy). Seventy-two HCC-PVT accrued till date (mean age 63 years [38-76 years], 96% male; Child-Pugh [CP] A 84%, B 9%; Barcelona-Clinic Liver Cancer [BCLC] C 96%; PS0-1: 80%, Karnofsky performance score [KPS]>70: 88%; co-morbidities 42%; infective 12%, alcohol intake 31%, adjuvant sorafenib 39%). CP scores 5, 6, 7, and 8 were in 35%, 32%, 8%, and 18%, respectively. Focal disease with portal vein thrombus (PVT) in 21%, liver involvement >50% and <50% in 46% and 32%. Liver cancer study group of Japan staging-based portal vein invasion VP2, VP3, and VP4 in 22%, 29%, and 40%. Cancer of the Liver Italian Programm (CLIP) scores 1, 2, 3, 4, and 5 were in 8%, 26%, 31%, 26%, and 7%, respectively. Mean follow-up was 7.3 months (median 6 months, standard deviation [SD] 6; range 3-30 months). Mean actuarial overall survival (OS) was 11.4 months (SE 1.587; 95% CI: 8-14.2 months). Six months and 12 months actuarial OS 55% and 38%, respectively. At last follow-up, 25/69 (36%) were alive and 44/69 (64%) were dead. Among 54 patients evaluated for response assessment, 23 (30%) had radiological confirmed PVT response, 1 (3%) had response of IVC thrombus, and 30 (42%) had no or minimal response to SBRT. Actuarial OS in responders and non-responders were 14.4 months (95% CI 9.4-19.2) and 7.4 months (95% CI 4.9-9.7), p-value: 0.022. Six and 12 months survival in responders and non-responders were 65.7% and 37% and 49% and 24.6%, respectively. Post-SBRT, 4 (12%) patients underwent transarterial chemoembolization (TACE) 3 patients (8%) and 1 patient (4%) transarterial radioembolization (TARE). Post-CK, (<4 weeks) 2 patients (4%) had decompensation. PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Current usage of stereotactic body radiotherapy for oligometastatic prostate cancer in Korea: patterns of care survey (KROG 19-08).

BackgroundGrowing evidence suggests that metastasis-directed therapy and/or prostate-directed therapy may benefit patients with oligometastatic prostate cancer (OMPC). Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastases in various cancers. The purpose of this study was to investigate the current patterns of curative-intent SBRT for OMPC in Korea.MethodsA 20-item questionnaire was sent to 326 radiation oncologists in 93 institutions in Korea. Only 1 physician per institution was required to complete the survey. Subsequently, the second survey consisting of 3 clinical scenarios was sent to 64 physicians with clinical experience in SBRT: case 1, cT4N0M1 (direct invasion to two pelvic bones); case 2, cT2N0M1 (three bone metastases); and case 3, solitary spine metastasis after radical prostatectomy.ResultsSeventy-six physicians from 93 institutions (82%) answered the first survey. The multidisciplinary team approach was practiced in 16 institutions (21%). Most physicians (75%) agreed on the definition of oligometastases as limited lesions and/or organs ≤5: 25% agreed with low-volume disease according to CHAARTED trial. During the last year, 49 physicians (64%) treated OMPC patients with curative intent. Sixty four physicians (84%) had a clinical experience with SBRT: 48 (75%) stated that both dose and fraction number should be considered when defining SBRT, whereas others (25%) stated that only fraction size should be considered. Fifty-five faculties (86%) answered the second survey. Physicians agreed with oligometastases in 89% for case 1, in 80% for case 2, and in 100% for case 3. The rate of SBRT application was the highest in case 3 (70%).ConclusionsThere was diversity in the patterns of SBRT for OMPC in Korea. Additional prospective studies are necessary to strengthen evidence regarding role of SBRT in OMPC.

Ultra-central lung tumors: safety and efficacy of protracted stereotactic body radiotherapy

Background For patients with early stage or medically inoperable lung cancer, stereotactic body radiotherapy (SBRT) is a general accepted and effective treatment option. The role of SBRT in ultra-central tumors remains controversial. The aim of this single-center retrospective analysis was to evaluate the safety and efficacy of protracted SBRT with 60 Gy in 12 fractions (with a biological effective dose (BED10) of 90–150 Gy) for patients with ultra-central lung tumors. Materials and methods Patients with ultra-central lung tumors treated in our institution with 60 Gy in 12 fractions from January 2012 until April 2020 were included. Ultra-central tumors were defined as planning target volume (PTV) abutting or overlapping the main bronchi and/or trachea and/or esophagus. Data regarding patient-, tumor-, and treatment-related characteristics were evaluated. Results A total of 72 patients met the criteria for ultra-central tumor location. The PTV abutted the main bronchus, trachea or esophagus in 79%, 22% and 28% of cases, respectively. At a median follow-up of 19 months, 1- and 2-year local control rates were 98% and 85%, respectively. Overall survival rates at 1 and 2 years were 77% and 52%, respectively. Grade 3 or higher toxicity was observed in 21%, of which 10 patients (14% of total) died of bronchopulmonary hemorrhage. A significant difference between patients with or without grade ≥3 toxicity was found for the mean dose (D mean) to the main bronchus (p = 0.003), where a D mean BED3 of ≥91 Gy increased the risk of grade ≥3 toxicity significantly. Discussion A protracted SBRT regimen of 60 Gy in 12 fractions for ultra-central lung tumors leads to high local control rates with toxicity rates similar to previous series, but with substantial risk of fatal bronchopulmonary hemorrhage. Therefore, possible risk factors of bronchopulmonary hemorrhage such as dose to the main bronchus should be taken into account.

Stereotactic radiotherapy in intrahepatic cholangiocarcinoma: A systematic review.

Among biliary tract cancers, intrahepatic cholangiocarcinoma (ICC) has different characteristics compared with those in other sites. Current guidelines suggest several treatment options for ICC, including stereotactic body radiation therapy (SBRT). However, the role of SBRT in locally advanced ICC is unclear. The aim of the present study was to present a systematic review on the efficacy and safety of SBRT in ICC. A systematic review based on the PRISMA methodology was performed. Only papers reporting outcomes in terms of overall survival (OS) after SBRT in inoperable patients with ICC were included. Secondary aims were local control (LC), progression-free survival (PFS) and treatment-related toxicity. Six papers (145 patients) were included in the present analysis. SBRT was frequently used as a salvage treatment, since 28.6-66.7% of patients received previous systemic or local treatments. The median SBRT dose was 45 Gy delivered in 3-5 fractions. The median follow-up was 16 months, and median OS time was 14 months (range, 10-48 months). In one of the included studies, SBRT was significantly superior in terms of OS compared with both chemoradiation and trans-arterial-radio-embolization. The 1-year LC rate was 85% in one study, and 1-year PFS rates were 50 and 68% in two studies, respectively. Toxicity was generally not reported in detail or was reported including other sites of biliary cancers. Overall, limited evidence was available on the efficacy of SBRT in ICC, which should be further investigated in prospective studies with a larger number of patients. However, based on the available data, SBRT seems to produce similar results compared with other ICC treatments, with the advantage of being a very short and non-invasive therapy. Therefore, SBRT should be considered in selected patients with ICC.