Stereotactic Body Radiotherapy For Oligometastases Research Articles

Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy.

Over the past two decades, it has been established that cancer patients with oligometastases, i.e., only a few detectable metastases confined to one or a few organs, may benefit from an aggressive local treatment approach such as the application of high-precision stereotacticbody radiotherapy (SBRT). Specifically, some studies have indicated that achieving long-term local tumor control of oligometastases is associated with prolonged overall survival. This motivates investigations into which factors may modify the dose-response relationship of SBRT by making metastases more or less radioresistant. One such factor relates to the uptake of the positron emission tomography tracer 2-deoxy-2-[18F]fluoro-D-glucose (FDG) which reflects the extent of tumor cell glycolysis or the Warburg effect, respectively. Here we review the biological mechanisms how the Warburg effect drives tumor cell radioresistance and metastasis and draw connections to clinical studies reporting associations between high FDG uptake and worse clinical outcomes after SBRT for oligometastases. We further review the evidence for distinct metabolic phenotypes of metastases preferentially seeding to specific organs and their possible translation into distinct radioresistance. Finally, evidence that obesity and hyperglycemia also affect outcomes after SBRT will be presented. While delivered dose is the main determinant of a high local tumor control probability, there might be clinical scenarios when metabolic targeting could make the difference between achieving local control or not, for example when doses have to be compromised in order to spare neighboring high-risk organs, or when tumors are expected to be highly therapy-resistant due to heavy pretreatment such as chemotherapy and/or radiotherapy.

Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study.

IntroductionStereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer.Materials and MethodsWe conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment.FindingsForty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 – 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported.ConclusionThe PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries.

Stereotactic body radiotherapy (SBRT) is increasingly used in metastasized patients receiving targeted/immunotherapy. Information on safety and effectivity of concurrent SBRT and targeted/immunotherapy remains limited, resulting in alack of consensus on treatment strategies. This study aimed to investigate how SBRT-experienced centers in German-speaking countries combine both therapies. Patterns-of-care of combined treatment with SBRT and targeted/immunotherapy were assessed in 27radiation oncology centers (19German, 1Austrian and 7Swiss centers). Asurvey was performed to analyze the details of SBRT, SBRT planning and combined modality treatment. Consensus was defined as ≥75% agreement among participants. Most participants (60%) were university centers. SBRT for oligometastases has been performed since the year 2008 (median, range 1997-2016), since then amedian of 140 cases (5-1100) of SBRT have been performed. In all, 67% performed concurrent SBRT and targeted agents. BRAF inhibitors and VEGF/EGFR inhibitors (bevacizumab [90%], erlotinib [11%], sorafenib [19%], lapatinib [4%]) were considered acontraindication. Bevacizumab was never given simultaneously with SBRT; other agents were given concurrently in 7-52% of centers. Amajority (59%) paused targeted agents 1week before/after SBRT. Only 1center reduced SBRT dose when combined with targeted agents. Although evidence for safety and efficacy of concurrent SBRT and targeted agents is limited, it is regularly performed outside of clinical trials. The survey showed consensus not to combine SBRT with antiangiogenic agents, especially bevacizumab. Furthermore, SBRT with concurrent BRAF inhibitors should be practiced with caution and BRAF inhibitors should be paused at least 1week before SBRT.

Multisite stereotactic body radiotherapy for metastatic non-small-cell lung cancer: Delaying the need to start or change systemic therapy?

ObjectivesThe purpose of this study was to review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic non-small-cell lung cancer (NSCLC) from a large academic institution. Materials and methodsMetastatic NSCLC patients treated with extracranial SBRT were identified from an institutional database. Treatment indications were: (1) oligometastases, (2) oligoprogression, and (3) local control of dominant tumors. Endpoints included overall survival (OS), progression-free survival (PFS), time to starting/changing systemic therapy (SCST), and local failure (LF). Univariate and multivariable analyses were performed to look for predictive factors. Results108 patients with 165 tumors were treated. SBRT was delivered for oligometastases in 66 patents, for oligoprogression in 20 patients, and for local control in 22 patients. Median OS and PFS for all patients were 27.3 months and 4.4 months, respectively, with treatment indication being the only predictive factor on multivariable analysis (patients with oligometastases having the highest median OS and PFS of 39.3 months and 7.6 months respectively). Cumulative incidence of SCST was only 21.5% at 1 year after SBRT, with larger tumor size and positivity for EGFR/ALK mutation being predictive of higher rates of SCST on multivariable analysis. LF was 15.6% at 1 year, with larger tumor size and exposure to previous systemic therapy being predictive of higher rates of LF on multivariable analysis. ConclusionPatients treated with SBRT for oligometastases have better OS and PFS than those treated for oligoprogression or for local control of dominant tumors. Use of SBRT may delay the need for SCST. Larger tumors and previous exposure to systemic therapy were predictive of higher rates of LF.

Comparison of survival and prognostic factors in patients treated with stereotactic body radiotherapy for oligometastases or oligoprogression

Background and purposeClinical challenges arise in the oligoprogressive (OP) state with little evidence to support the use of ablative strategies. Our aim is to report on outcomes and prognostic variables following stereotactic body radiotherapy (SBRT) for OP and oligometastases (OM). Material and methodsOverall (OS) and progression-free survivals (PFS) were calculated for 163 patients for 209 lesions (106 OM and 57 OP) treated with SBRT over 9 years. OS and PFS comparisons were calculated using the Kaplan–Meier actuarial survival and log rank methods. Uni, multi-variate analyses and cumulative incidences of local failure were performed using the Cox modelling and Gray’s test respectively. ResultsThe median OS and PFS was 37 and 15 months versus 21.7 and 6.4 months in the OM and OP groups respectively (P = 0.02 and P = 0.01). Performance status (⩾2 HR 2.95) and number of metastases (1/2 vs ⩾3 HR 1.88) were independent prognosticators for survival. The 1/2-year PFS were 55%/25% versus 22%/6% in the OM and OP cohorts. Patterns of first relapse were four times higher outside the irradiated field and OP status (p = 0.03), ⩾3 metastasis (p = 0.002) and concurrent systemic therapy (p = 0.001) conferred a greater risk. Time to second-line treatment was 20 vs 11 months in the OM and OP groups (P = 0.001). ConclusionSurvival and distant relapse following SBRT to OM/OP is determined by the extent of metastatic disease and performance status. Future research should address the benefit of integrating SBRT with systemic therapies to allow deferral or continuation of therapeutic agents.

Stereotactic Radiotherapy for Oligometastases in Lymph Nodes-A Review.

In recent years, the concept of oligometastases has become accepted and reports on stereotactic body radiotherapy as a treatment method have been published. Lesions in the brain, lung, and liver have been reported as target lesions. However, lymph node oligometastases could be a good candidate for stereotactic body radiotherapy as well. In this study, the usability of stereotactic body radiotherapy for oligometastases to lymph nodes is assessed by researching for each primary site. As a result, we could consider that stereotactic body radiotherapy could be almost well applied for lymph node oligometastases from the breast, gynecological organs, and prostate. However, doubts remain concerning the usefulness of stereotactic body radiotherapy for cervical node metastases from head and neck cancer or for mediastinal node metastases from lung or esophageal cancer since late toxicities have occurred with a large radiation dose at hypofractionation to major vessels or the central respiratory tract, especially in patients with irradiation histories. In addition, high-dose irradiation is required to control lymph node metastases from colorectal cancer due to its radioresistance, and severe late adverse events would therefore occur in adjacent organs such as the gastrointestinal tract. In cases of lymph node oligometastases with a primary tumor in the stomach or esophagus, stereotactic body radiotherapy should be used limitedly at present because this patient population is not so large and these metastases are often located close to organs at risk. Because of the varied status of recurrence and varied conditions of patients, it is difficult to determine the optimal dose for tumor control. It might be reasonable to determine the treatment dose individually based on dose constraints of adjacent organs. The oligometastatic state is becoming more frequently identified with more sensitive methods of detecting such oligometastases. In addition, there seems to be another type of oligometastases, so-called induced oligometastases, following successful systemic treatment. To determine the optimal indication of stereotactic body radiotherapy for lymph node oligometastases, further investigation about the mechanisms of oligometastases and further clinical studies including a phase III study are needed.

Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists.

Stereotactic body radiotherapy (SBRT) is often used to treat patients with oligometastases (OM). Yet, patterns of SBRT practice for OM are unknown. Therefore, we surveyed radiation oncologists internationally, to understand how and when SBRT is used for OM. A 25-question survey was distributed to radiation oncologists. Respondents using SBRT for OM were asked how long they have been treating OM, number of patients treated, organs treated, primary reason for use, doses used, and future intentions. Respondents not using SBRT for OM were asked reasons why SBRT was not used and intentions for future adoption. Data were analyzed anonymously. We received 1007 surveys from 43 countries. Eighty-three percent began using SBRT after 2005 and greater than one third after 2010. Eighty-four percent cited perceived treatment response/durability as the primary reason for using SBRT in OM patients. Commonly treated organs were lung (90%), liver (75%), and spine (70%). SBRT dose/fractionation schemes varied widely. Most would offer a second course to new OM. Nearly all (99%) planned to continue and 66% planned to increase SBRT for OM. Of those not using SBRT, 59% plan to start soon. The most common reason for not using SBRT was lack of clinical efficacy (48%) or lack of necessary image guidance equipment (34%). Radiation oncologists are increasingly using SBRT for OM. The main reason for not using SBRT for OM is a perceived lack of evidence demonstrating clinical advantages. These data strengthen the need for robust prospective clinical trials (ongoing and in development) to demonstrate clinical efficacy given the widespread adoption of SBRT for OM.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up*

Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns.Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6–7 common responses), moderate (4–5), low (2–3), or no agreement.Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2–5) and three within a single organ (range 2–5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up.Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.

Stereotactic Body Radiotherapy for Oligometastases Confined to the Para-Aortic Region: Clinical Outcomes and the Significance of Radiotherapy Field and Dose

We retrospectively reviewed 88 patients with oligometases in the para-aortic region from any controlled primary tumor site who were treated with stereotactic body radiotherapy (SBRT). The 5-year local control, disease-free survival, and overall survival rates were 83%, 31%, and 41%, respectively. A 90% tumor-control probability was predicted at a biological effective dose of 90 Gy. Severe gastrointestinal toxicities (grade ≥3) were observed in 2 of 88 patients (1%). The results of this study are limited by the retrospective nature of the study but could serve as the background and rationale for future prospective trials on SBRT-based treatment for oligometastses.

Survival and prognostic factors in 321 patients treated with stereotactic body radiotherapy for oligo-metastases

Background and purposeTo establish a model to predict survival after SBRT for oligo-metastases in patients considered ineligible for surgical resection (SR) and radiofrequency ablation (RFA). Material and methodsOverall survival (OS) rates were estimated in 321 patients treated for 587 metastases with SBRT over 13years. Patients were treated for a variety of metastasis types with colorectal cancer (CRC) being the most frequent (n=201). ResultsWith a median follow-up time of 5.0years, the median OS was 2.4years (95% CI 2.3–2.7) and the survival rates were 80%, 39%, 23% and 12% at 1, 3, 5 and 7.5years after SBRT, respectively. WHO performance status (PS) (0–1) (HR 0.49; p<0.001), solitary metastasis (HR 0.75; p=0.049), metastasis ⩽30mm (HR 0.53; p<0.001), metachronous metastases (HR 0.71; p=0.02) and pre-SBRT chemotherapy (HR 0.59; p<0.001) were independently related to favorable OS. Median OS rates were 7.5, 2.8, 2.5, 1.7 and 0.8years with 0, 1, 2, 3, ⩾4 unfavorable prognostic factors, respectively. The treatment-related morbidity was moderate. However, three deaths were possibly treatment-related. ConclusionPrognostic factors may predict long-term survival in patients with oligo-metastases treated with SBRT.

Stereotactic body radiation therapy for abdominal and pelvic oligometastases: Dosimetric targets for safe and effective local control

PurposeTo investigate correlates and predictors of outcomes of stereotactic body radiation therapy (SBRT) for patients with abdominal and pelvic oligometastases from different primary tumors. Methods and materialsWe evaluated outcomes of 38 consecutive patients with 44 unresectable nodal and soft-tissue oligometastases in the abdominal pelvic region who were treated with SBRT between November 2008 and April 2014. Thirty-two patients had solitary lesions and 6 patients had 2 lesions. The median prescription dose was 40 Gy (24-50 Gy) delivered in 4-5 fractions. The median gross tumor volume was 18.7 mL (0.7-194.1 mL). We evaluated tumor response, local control (LC), and overall survival (OS) rates as well as acute and chronic toxicities. ResultsAt a median follow-up of 19 months (0.9-53.4 months), tumor responses were: complete response 31.8%, partial response 38.6%, standard deviation 20.5%, and progressive disease 9.1%. The overall 1- to 2-year LC and OS rates were 100%/75.1% (95% confidence interval [CI], 54.4%-88.4%) and 95.2% (95% CI, 82.8%-98.8%)/88.9% (95% CI, 68.1%-95.1%), respectively. On univariate analysis, increasing SBRT dose, smaller gross tumor volume, and asymptomatic lesions were associated with improved LC (P = .01, P<.001, and P = .01, respectively). On multivariate analysis, advanced original primary disease stage predicted for worse OS (P = .001). One patient developed a colovesicular fistula at 20.9 months in the setting of local tumor progression with a volume of bowel receiving 20 Gy (V20Gy) = 26.9 mL. The overall mean bowel V20Gy achieved was 16 ± 22.9 mL. Another patient had grade 2 proctitis at 13 months after SBRT. Pain relief was achieved in 81.8% of patients with symptomatic lesions (N = 11). ConclusionsOur results suggest that SBRT doses 40-50 Gy in 5 fractions (biological effective dose 72-100 Gy10) with bowel V20Gy ≤20 mL are efficacious and associated with minimal toxicity for abdominal pelvic nodal and soft-tissue oligometastases. Palliation of symptoms is achievable in most patients with symptomatic lesions. SBRT for oligometastases may be a good alternative to systemic therapy in selected patients.

EP-1390: Lung stereotactic body radiotherapy for oligometastases of colorectal tumors: First outcomes

EP-1390: Lung stereotactic body radiotherapy for oligometastases of colorectal tumors: First outcomes

Stereotactic body radiotherapy for oligometastases.

The management of metastatic solid tumours has historically focused on systemic treatment given with palliative intent. However, radical surgical treatment of oligometastases is now common practice in some settings. The development of stereotactic body radiotherapy (SBRT), building on improvements in delivery achieved by intensity-modulated and image-guided radiotherapy, now allows delivery of ablative doses of radiation to extracranial sites. Many non-randomised studies have shown that SBRT for oligometastases is safe and effective, with local control rates of about 80%. Importantly, these studies also suggest that the natural history of the disease is changing, with 2-5 year progression-free survival of about 20%. Although complete cure might be possible in a few patients with oligometastases, the aim of SBRT in this setting is to achieve local control and delay progression, and thereby also postpone the need for further treatment. We review published work showing that SBRT offers durable local control and the potential for progression-free survival in non-liver, non-lung oligometastatic disease at a range of sites. However, to test whether SBRT really does improve progression-free survival, randomised trials will be essential.