Incidence and imaging characteristics of difficult to detect retrospectively identified brain metastases in patients receiving repeat courses of stereotactic radiosurgery.

PURPOSE: During stereotactic radiosurgery (SRS) planning for brain metastases (BM), brain MRIs are reviewed to select appropriate targets based on radiographic characteristics. Some BM are difficult to detect and/or definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, reviewing the initial planning MRI would reveal early evidence of lesions that developed into metastases requiring SRS. METHODS: Patients undergoing two or more courses of SRS to BM within 6 months between 2016 and 2018 were included in this single-institution, retrospective study. Brain MRIs from the initial course were reviewed for lesions at the same location as subsequently treated metastases; if present, this lesion was classified as a "retrospectively identified metastasis" or RIM. RIMs were subcategorized as meeting or not meeting diagnostic imaging criteria for BM (+ DC or -DC, respectively). RESULTS: Among 683 patients undergoing 923 SRS courses, 98 patients met inclusion criteria. There were 115 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were associated with RIMs found in a prior MRI. 58% of RIMs were + DC. 17 (15%) of subsequent courses consisted solely of metastases associated with + DC RIMs. CONCLUSION: Radiographic evidence of brain metastases requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. Most RIMs were + DC, and some subsequent SRS courses treated only + DC RIMs. These findings suggest enhanced BM detection might enable earlier treatment and reduce the need for additional SRS.

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy.

BACKGROUND: Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. MATERIALS AND METHODS: We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation-treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable-adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). RESULTS: Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow-up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24-1.03; P-interaction = .002), though neither association reached statistical significance. Similar patterns of ADT-stratified associations were observed for PPAT and SFA. CONCLUSIONS: Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

Current multidisciplinary management of brain metastases.

Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late-stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new and emerging systemic therapies and advancements in radiation oncology and neurosurgery. Current therapies include stereotactic radiosurgery, whole-brain radiation therapy, surgical resection, laser-interstitial thermal therapy, systemic cytotoxic chemotherapy, targeted agents, and immune-checkpoint inhibitors. Determining the optimal treatment for a specific patient has become increasingly individualized, emphasizing the need for multidisciplinary discussions of patients with BM. Recognizing and addressing the sequelae of BMs and their treatment while maintaining quality of life and neurocognition is especially important because survival for patients with BMs has improved. The authors present current and emerging treatment options for patients with BM and suggest approaches for managing sequelae and disease recurrence.

Survival Advantage With Adjuvant Chemotherapy for Locoregionally Advanced Rectal Cancer: A Veterans Health Administration Analysis.

BACKGROUND: Adjuvant chemotherapy (AC) after chemoradiation (CRT) and surgery for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States. This study examined the role, optimal regimen, and duration of AC using data from the largest integrated health system in the United States. PATIENTS AND METHODS: Using the Veterans Affairs Central Cancer Registry, patients with stage II-III rectal cancer diagnosed in 2001 through 2011 who received neoadjuvant CRT and surgery with or without AC were identified. Kaplan-Meier analysis, log-rank tests, and propensity score (PS) adjustment analysis were used to assess survival. RESULTS: A total of 866 patients were identified; 417 received AC and 449 did not (observation [OBS] group). Median follow-up was 109 months. Median disease-specific survival (DSS) was not reached. Six-year DSS was 73.7%; 79.5% for the AC group versus 68.0% for the OBS group. PS-matched analysis for DSS favored AC (P=.0002). Median overall survival (OS) was 90.8 months. Six-year OS was 56.7%; 64.3% for AC versus 49.6% for OBS. In PS-matched analysis, median OS was 117.4 months for AC and 74.3 months for OBS (P<.0001). A DSS advantage was seen when comparing ≥4 months with <4 months of AC (P=.023). No difference in DSS or OS was seen with single-agent versus multiagent AC. CONCLUSIONS: In this population of patients with LARC treated with neoadjuvant CRT and surgery, OS and DSS were improved among those treated with AC versus OBS. DSS benefits were seen with ≥4 months of AC. No additional benefit was observed with multiagent therapy. In the absence of phase III data, these findings support the use of AC for LARC.

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria.

OBJECTIVE. The purpose of this study was to investigate whether, compared with traditional criteria, the modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapeutics (iRECIST) improves prediction of local tumor control and survival in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS. Fifty-one HCC lesions (mean size, 3.1 cm) treated with SBRT in 41 patients (mean age, 67 years) were retrospectively included. Each patient underwent CT or MRI before SBRT and at least once after SBRT. Best overall response was categorized using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), iRECIST, World Health Organization (WHO) criteria, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Lesions were then classified as local tumor control (i.e., stable disease, partial response, or complete response) or local treatment failure (i.e., progressive disease) by each tumor response criteria. Proportions of local tumor control were compared using the McNemar exact test. The 1-year overall survival was estimated using the Kaplan-Meier method. RESULTS. The median follow-up after SBRT was 21.0 months. The local tumor control rate was 94.1% (48/51) by iRECIST, 88.2% (45/51) by RECIST 1.1, 72.5% (37/51) by WHO criteria, 80.4% (41/51) by mRECIST, and 72.5% (37/51) by EASL criteria. The local tumor control rate was significantly higher according to iRECIST compared with WHO (p = 0.0010) and EASL (p = 0.0225) criteria. The 1-year survival rate for patients with local tumor control according to iRECIST (86.4%) was higher (although not statistically significant) compared with the 1-year survival rate for patients with local tumor control according to the other response criteria. CONCLUSION. iRECIST may provide more robust interpretation of HCC response after SBRT, yielding improved prediction of local tumor control and 1-year survival rates compared with traditional criteria.

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

BACKGROUND: Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. METHODS: The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. RESULTS: Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. CONCLUSIONS: US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434-1441. © 2016 American Cancer Society.

Radiation therapy for oligometastatic non-small cell lung cancer.

Interest has been increasing in the treatment of non-small cell lung cancer (NSCLC) patients with limited or oligometastatic disease. Surgery has historically been used to remove non-small cell lung cancer metastases, but recent developments including advanced radiotherapy planning and delivery techniques, often called stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR), has been associated with high rates of treated metastasis control. Therefore, given common comorbid disease, often precluding surgery, an increasing number of oligometastatic NSCLC patients are receiving radiation for ablation of all disease. Early results have reported favorable survival for some, with improved median survival, and approximately 25 % alive long term. Patients with fewer metastases, those treated to all known cancerous sites, and longer disease-free intervals tend to have better outcomes. While promising, better clinical criteria are needed to optimize patient selection. The biologic underpinnings of the oligometastatic state are beginning to be demonstrated with specific microRNAs being associated with limited or no progression both in human samples and murine models. Clinical trials are ongoing to improve the techniques used to deliver radiotherapy for NSCLC oligometastases. Ideally, randomized studies will need to be conducted to demonstrate the utility of these treatments suggested by the uncontrolled studies to date. In lieu of these, data presented here may help guide clinicians as to appropriate patient selection.

Irradiation and immunotherapy: From concept to the clinic.

In recent years, an increased understanding of T-cell-regulatory mechanisms has led to the development of a novel class of immune-checkpoint inhibitors that have robust clinical activity against a broad array of malignancies-even those that historically were not believed to be sensitive to immune therapy. With this, there has been renewed interest in the potential for synergy with more traditional forms of anticancer therapy like radiation therapy (RT). The role of RT in palliation or as definitive treatment for certain malignancies has been well established. Yet, in recent years, the concept has come to light that RT could be an attractive partner for use in combination with other immunotherapies. The effects of RT include not only control of an irradiated tumor but also multiple immunomodulatory effects on both the tumor and the microenvironment, priming tumors for an immune-mediated response. Herein, the authors summarize relevant preclinical data and rationale supporting the synergy of combined RT and immunotherapy and highlight recent clinical work on promising combination strategies. Cancer 2016;122:1659-71. © 2016 American Cancer Society.

Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).

BACKGROUND: The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. METHODS: Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. RESULTS: Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. CONCLUSIONS: A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society.

Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy.

PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.

Stereotactic body radiotherapy: a critical review for nonradiation oncologists.

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease.

Palliative radiotherapy for prostate cancer.

Radiotherapy is an effective tool for the palliation of symptoms commonly caused by prostate cancer. The majority of painful bone metastases respond equally well to single or multiple fractions of external radiotherapy. Retreatment with a second course of radiation induces pain responses in approximately 50% of patients. For more diffuse metastases, either hemibody radiation or systemic radiopharmaceuticals can reduce pain, and radium-223 is associated with improved survival in men with castration-resistant prostate cancer. Hematuria, bladder outlet obstruction, and rectal compression are all improved with palliative radiotherapy. The ability of stereotactic body radiation therapy to reduce pain compared with standard external radiation is being investigated, as is its role in treating those with limited metastatic disease.

Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: a secondary analysis of RTOG 0415.

BACKGROUND: While moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC) is commonly delivered by intensity modulated radiation therapy, IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in this context. We conducted a secondary analysis of the phase III RTOG 0415 trial comparing survival and toxicity outcomes for low-risk PC following MHRT with IMRT versus 3D-CRT. METHODS: RTOG 0415 was a phase III, non-inferiority trial randomizing low-risk PC patients to either MHRT or conventionally fractionated radiation with stratification by RT technique. A secondary analysis for differences in overall survival (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. RESULTS: 1079 patients received the allocated intervention with a median follow up of 5.8 years. 79.1% of patients were treated with IMRT and radiation technique was balanced between arms. Across all patients, RT technique was not associated with significant differences in BRFS, OS, or rates of acute and late toxicities. For patients completing MHRT, there was a difference in the late GU toxicity distribution between 3D-CRT and IMRT but no difference in late grade 2 or greater GU or GI toxicity. Stratifying patients by RT technique and fractionation, no significant differences were observed in the minimal clinically important difference (MCID) in EPIC urinary and bowel scores following RT. CONCLUSIONS: RT technique did not impact clinical outcomes following MHRT for low-risk PC. Despite different late GU toxicity distributions in patients treated with MHRT by IMRT or 3D-CRT, there was no difference in late Grade 2 or greater GU or GI toxicity or patient reported toxicity. Increases in late GU and GI toxicity following MHRT compared to CFRT, as demonstrated in the initial publication of RTOG 0415, do not appear related to a 3D-CRT treatment technique.

Determinants of Symptomatic Intracranial Progression After an Initial Stereotactic Radiosurgery Course.

Purpose: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance of neurologic symptoms at the time of ITCP is poorly understood. Methods and Materials: This was a multi-institutional, retrospective cohort study from 2015 to 2020, including all patients with brain metastases completing an initial course of SRS. The primary outcome was overall survival (OS) by presence of neurologic symptoms at ITCP. OS, freedom from ITCP (FF-ITCP), and freedom from symptomatic ITCP (FF-SITCP) were assessed via Kaplan-Meier method. Cox proportional hazard models tested parameters impacting FF-ITCP and FF-SITCP. Results: Among 1383 patients, median age was 63.4 years, 55% were female, and common primaries were non-small cell lung (49%), breast (15%), and melanoma (9%). At a median follow-up of 8.72 months, asymptomatic and symptomatic ITCP were observed in 504 (36%) and 194 (14%) patients, respectively. The majority of ITCP were distant ITCP (79.5%). OS was worse with SITCP (median, 10.2 vs 17.9 months, P < .001). SITCP was associated with clinical factors including total treatment volume (P = .012), melanoma histology (P = .001), prior whole brain radiation therapy (P = .003), number of brain metastases (P < .001), interval of 1 to 2 years from primary and brain metastasis diagnosis (P = .012), controlled extracranial disease (P = .042), and receipt of pre-SRS chemotherapy (P = .015). Patients who were younger and received post-SRS chemotherapy (P = .001), immunotherapy (P < .001), and targeted or small-molecule inhibitor therapy (P < .026) had better FF-SITCP. Conclusions: In this cohort study of patients with brain metastases completing SRS, neurologic symptoms at ITCP is prognostic for OS. This data informs post-SRS surveillance in clinical practice as well as future prospective studies needed in the modern management of brain metastases.

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy.

Role of radiation in oligometastases and oligoprogression in metastatic non-small cell lung cancer: consensus and controversy.

INTRODUCTION: The oligometastatic state in non-small cell lung cancer (NSCLC) has recently become well-established. However, the specific definition of oligometastases remains unclear. Several smaller randomized studies have investigated the safety and efficacy of radiation as metastasis-directed therapy (MDT) in oligometastatic NSCLC, which have led the way to larger studies currently accruing patients globally. AREAS COVERED: This review covers the definitions of 'oligometastases' and explains why the oligometastatic state is becoming increasingly relevant in metastatic NSCLC. This includes the rationale for MDT in oligometastatic NSCLC, specifically reviewing stereotactic body radiation therapy (SBRT) as a treatment strategy. This review details many randomized trials that support radiation as MDT and introduces trials that are currently accruing patients. Finally, it explores some of the controversies that warrant further investigation. EXPERT OPINION: Radiation treatment, specifically SBRT, has been shown to be safe, convenient, and cost-effective as MDT. As systemic therapy, including targeted agents and immunotherapy, continues to improve, the precise role(s) and timing of radiation therapy may evolve. However, radiation therapy as MDT will continue to be an integral part of treatment in patients with oligometastatic NSCLC.