To SABR or Not to SABR? Indications and Contraindications for Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage, Oligometastatic, or Oligoprogressive Non–Small Cell Lung Cancer

doi:10.1016/j.semradonc.2014.11.005

Seminars in Radiation Oncology

Volume 25, Issue 2, April 2015, Pages 78-86

https://doi.org/10.1016/j.semradonc.2014.11.005 Get rights and content

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for early-stage non–small cell lung cancer. Although direct comparisons from randomized trials are not available, rates of both primary tumor control and distant metastasis are similar between SABR and surgery. Overall survival is lower after SABR compared with surgery, largely reflecting that a primary selection criterion for SABR has been medical inoperability because of decreased cardiopulmonary function and other comorbidities that lead to decreased survival independent of non–small cell lung cancer. Survival outcomes between SABR and surgery are much more similar in propensity-matched cohorts. Newer potential indications for SABR include treatment of operable patients; of oligometastatic lung cancer, in which SABR has emerged as an alternative to metastasectomy; and of oligoprogressive lung cancer, an attractive concept especially as improved personalized systemic therapies emerge, and prospective trials are currently being conducted in these settings. Although toxicity in modern series is low, SABR is clearly capable of producing fatal complications, and understanding the risk factors and approaches for mitigating them has been emerging in recent years. Thus, appropriate patient selection is a vital, evolving, and controversial topic.

Section snippets

Historical Perspective

Based on reports from the Karolinska Hospital in Sweden published in the 1990s describing the application of stereotactic radiotherapy to extracranial targets, a practice that evolved from stereotactic radiosurgery (SRS) for intracranial targets and was pioneered decades earlier at the same institution,¹ groups worldwide, including from the Netherlands,² Japan,3, 4, 5 Korea,⁶ Germany,7, 8 and the United States,9, 10 began treating non–small cell lung cancer (NSCLC) and other lung tumors with

SABR for Oligometastatic Lung Cancer

The concept of oligometastatic disease was first proposed nearly 20 years ago as a putatively distinct disease stage lying within the cancer spectrum between locoregional and widely disseminated cancer.¹⁰⁰ Generally speaking, oligometastatic cancer is considered a potentially curable disease state wherein a patient may or may not have disseminated micrometastatic disease controlled by systemic therapies and 1-5 gross lesions that could potentially be addressed definitively with local

Conclusion

SABR plays an essential role in the treatment of patients with early-stage NSCLC who are unfit for surgery, whereas for OLC, itself a controversial subject, the role for surgery or SABR is unclear. Prospective trials are needed to further define the role for SABR in treating these diseases and to refine the process of patient selection.

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Cited by (21)

Stereotactic Body Radiation Therapy for Oligoprogressive and Oligorecurrent Non–Small-Cell Lung Cancer
2023, Clinical Lung Cancer
The role of stereotactic body radiation therapy (SBRT) in oligoprogressive non–small-cell lung cancer (NSCLC) is controversial. We evaluated whether SBRT in a subset of patients with oligoprogressive or oligorecurrent NSCLC offers a durable response, obviating the need to change systemic therapy.
A retrospective analysis of 168 NSCLC patients who underwent SBRT for oligoprogressive or oligorecurrent disease was performed. Oligoprogression was defined as progression in ≤5 lesions during or after systemic therapy following an initial complete or partial response. Oligorecurrence was defined as progression while off systemic therapy. Progression-free survival (PFS), overall survival (OS) and time to next treatment or death (TNT-D) were estimated.
Median age was 68 years. Sixty-seven percent of patients were on systemic therapy at the time of progression. Progression at the primary site was present in 31% of the patients. The number of sites of metastatic progression was 0 to 2 in 76% and 3 to 5 in 24% of the patients. Two-year OS and PFS were 56% (95%CI 46%-64%) and 14% (95%CI 8%-21%), respectively. Median TNT-D was 9 months (95%CI 6-11). No grade 4 or 5 toxicity was seen. In multivariable analysis, patients with 3 to 5 sites of metastatic progression had worse OS (HR 2.6, 95%CI 1.5-4.3, P < .001) and shorter TNT-D (HR 1.7, 95%CI 1.1-2.5, P = .01) than those with 0 to 2 sites.
SBRT is a safe and viable treatment option for oligoprogressive and oligorecurrent NSCLC. Patients with 0 to 2 sites had better OS and longer TNT-D compared to those with 3 to 5 lesions.
Clinical Factors That Affect Fiducial Tracking in Robotic SABR for Lung Tumors
2023, Advances in Radiation Oncology
SABR is a treatment option for patients with lung tumors that employs fiducials to track tumors during the breathing cycle. Currently, there is a paucity of data on how relative fiducial location and patient clinical characteristics affect fiducial tracking and clinical outcomes. This study aimed to identify factors that reduce the number of fiducials tracked with respiratory motion management during SABR.
An institutional review board–approved retrospective review was performed of patients receiving robotic SABR for lung tumors at our institution from 2016 to 2019. Clinical data including demographics, medical history, treatment data, and follow-up were collected. Fiducial geometries were obtained with Velocity contouring software and MATLAB. Mann-Whitney U, χ², and t tests were completed using MedCalc.
A total of 73 patients with 77 treatments were identified. The χ² analysis revealed that chronic obstructive pulmonary disease was associated with having 3 or more fiducials tracked (P = .034). Tumors in lower lobes were associated with higher rates of uncertainty errors (P = .015). The number of fiducials tracked had no effect on local tumor control or overall survival, with a median of 36 months of follow-up. A total of 28 treatments had fiducial centroid data available for geometric analysis. The most common tracking errors were rigid body error (RBE; 57%) and spacing errors (36.4%). Spacing errors had a shorter average minimum interfiducial distance than nonspacing errors (1.0 cm vs 1.7 cm, respectively; P = .017). RBE treatments had a longer average maximum distance than non-RBE treatments (4.0 cm vs 3.0 cm; P = .022).
Greater motion in lower lobes can contribute to certain tracking errors that prevent more fiducials from being tracked. Maintaining interfiducial distance between experimentally determined guidelines may limit spacing errors and RBEs, the 2 most common tracking errors. An increased number of patients in a data set may result in stronger correlations between patient and tumor factors and outcomes.
Optimal and actual rates of Stereotactic Ablative Body Radiotherapy (SABR) utilisation for primary lung cancer in Australia
2022, Clinical and Translational Radiation Oncology
Citation Excerpt :
Centrally located tumours remain a controversial issue with some guidelines precluding the use of SABR, while others recommend using more protracted dose schedules based on data from RTOG-0813 [51]. Similarly, there is a lack of consensus regarding tumours > 5 cm, most RTOG trials have excluded such lesions, though large retrospective studies have not reported significantly increased toxicity [56,57]. ASTRO/ASCO guidelines allow SABR use for such tumours provided that maximum dose constraints are respected [2], while Australian guidelines do not recommend its use in such cases [45].
Radiotherapy utilisation rates considerably vary across different countries and service providers, highlighting the need to establish reliable benchmarks against which utilisation rates can be assessed. Here, optimal utilisation rates of Stereotactic Ablative Body Radiotherapy (SABR) for lung cancer are estimated and compared against actual utilisation rates to identify potential shortfalls in service provision.
An evidence-based optimal utilisation model was constructed after reviewing practice guidelines and identifying indications for lung SABR based on the best available evidence. The proportions of patients likely to develop each indication were obtained, whenever possible, from Australian population-based studies. Sensitivity analysis was performed to account for variations in epidemiological data. Practice pattern studies were reviewed to obtain actual utilisation rates.
A total of 6% of all lung cancer patients were estimated to optimally require SABR at least once during the course of their illness (95% CI: 4–6%). Optimal utilisation rates were estimated to be 32% for stage I and 10% for stage II NSCLC. Actual utilisation rates for stage I NSCLC varied between 6 and 20%. For patients with inoperable stage I, 27–74% received SABR compared to the estimated optimal rate of 82%.
The estimated optimal SABR utilisation rates for lung cancer can serve as useful benchmarks to highlight gaps in service delivery and help plan for more adequate and efficient provision of care. The model can be easily modified to determine optimal utilisation rates in other populations or updated to reflect any changes in practice guidelines or epidemiological data.
Novel Radiation Therapy Paradigms and Immunomodulation: Heresies and Hope
2020, Seminars in Radiation Oncology
Citation Excerpt :
For most solid tumors, to reach potentially curative doses while avoiding intolerable collateral damage to normal tissues, typical conventionally fractionated radiation therapy (CFRT) regimens involve small doses of 1.8-2 Gy fractions per day, 5 days per week, over 6-8 weeks with total doses of 60-80 Gy. The emergence of stereotactic radiosurgery for intracranial tumors1 and later stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy, for other body sites2,3 defied the conventional wisdom of the time with the use of extremely hypofractionated regimens, such as large single-fraction treatments of up to 25-34 Gy or up to 60 Gy in 3-8 fractions over 1-2 weeks. This departure from established fractionation dogma is possible only in the setting of limited volume targets and highly conformal dose delivery, producing therapeutic index through physical separation of ablative doses from normal tissues and achieving unprecedented local tumor control outcomes in this setting.4
Radiation therapy benefits the majority of patients across the spectrum of cancer types. However, both local and distant tumor recurrences limit its clinical success. While departing from the established tenet of fractionation in clinical radiotherapy, ablative-intensity hypofractionated radiotherapy, especially stereotactic radiosurgery and stereotactic ablative radiotherapy, has emerged as an alternative paradigm achieving unprecedented rates of local tumor control. Direct tumor cell killing has been assumed to be the primary therapeutic mode of action of such ablative radiation. But with increasing recognition that tumor responses also depend on the immunostimulatory or immunosuppressive status of the tumor microenvironment, the immunologic effect of ablative radiotherapy is emerging as a key contributor to antitumor response. More recently, novel radiation modalities, such as spatially fractionated radiotherapy and ultrahigh dose rate FLASH irradiation, that venture even further from conventional paradigms have shown promise of increasing the therapeutic index of radiation therapy with the potential of immunomodulation. Here, we review the immunomodulatory impact of novel radiation therapy paradigms, heretofore considered radiobiological heresies, a deeper understanding of which is imperative to realizing fully their potential for more curative cancer therapy.
Treatment, no treatment and early death in Danish stage I lung cancer patients
2019, Lung Cancer
Citation Excerpt :
Surgery was associated with the best short-term prognosis, probably due to both an effective treatment modality and selection of younger patients with a good lung function and a favourable performance status into this treatment group. The weakened association between the surgical and oncological treatment and one-year mortality in the adjusted analysis supports this mechanism, and is in accordance with the findings of several other retrospective studies as concluded in a review by Shultz et al [18]. Not surprisingly, the palliative group had significantly higher one-year mortality as compared to the group that received curatively intended oncologic therapy.
Stage I lung cancer is curable with surgery as the treatment of choice. Other effective and curative treatments exist. Nevertheless, some patients only receive palliative treatment and some receive no treatment at all.
Using the Danish Lung Cancer Registry (DLCR), we assessed treatment distribution for a population-based Danish cohort of stage I lung cancer patients diagnosed from 2011 to 2014. We assessed one-year mortality according to treatment. Furthermore, in a nested case-control study based on data from medical records, we assessed the reason for not undergoing treatment among patients in favourable performance status (PS) with no treatment registration in the DLCR.
We identified 2985 patients, 68% (n = 2021) were treated surgically and 17% (n = 508) were managed with curative oncological therapy. The unadjusted odds ratio (OR) for death within one year was 2.5 (95% CI, 1.8–3.3) for the oncologically managed vs. the surgically treated. After adjusting for age, lung function and PS, the OR was 1.2 (95% CI, 0.8–1.9).
Among 129 patients with a PS of 0–1 and no treatment registration, we established the reason for not undergoing treatment in 122 (95%). The majority (70%) were misclassified and did either not have lung cancer, had more advanced disease or were curatively treated. The 36 (30%) patients that did not undergo treatment, had a lower prevalence of adenocarcinomas (17 vs. 51%, p = 0.003), more comorbidites (median Charlson comorbidity index score 2 vs. 1, p < 0.001) and high alcohol intake (19 vs. 7%, p = 0.04) as compared to surgically treated controls. The primary reasons for no treatment were; comorbidity, patient decision and disease progression.
Difference in outcome between the two major treatment groups was confounded by age, lung function and PS. Comorbidity, high alcohol intake and histology were associated with not undergoing curative treatment in spite of a favourable PS.
Tumors that mimic diffuse parenchymal lung disease
2019, Difficult to Diagnose Rare Diffuse Lung Disease
A differential diagnosis for diffuse parenchymal lung disease can in some cases include primary tumors (such as lung cancer and carcinoid and nonepithelial tumors, including lymphoma) and metastatic lung tumors, because these often mimic the nontumor pathology of the lung tissue. CT findings typical of interstitial lung diseases, such as ground-glass opacity, reticular changes, and multiple cysts in the lungs, can also occur in some tumor processes. The similar CT semiotics of some tumor and nontumor lung lesions can give rise to errors, especially in an initial diagnosis based on clinical and X-ray characteristics of the infiltrative process in the lung tissue. In this chapter, we consider the features of the lung tumors that most often mimic diffuse pulmonary diseases.

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^☆: Conflicts of interest and source of funding: B.W.L. and M.D. have received research support from Varian Medical Systems. B.W.L. has received research support from RaySearch Laboratories and speaking honoraria from Varian Medical Systems. D.B.S. has nothing to disclose.

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Invited ReviewTo SABR or Not to SABR? Indications and Contraindications for Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage, Oligometastatic, or Oligoprogressive Non–Small Cell Lung Cancer☆

Section snippets

Historical Perspective

SABR for Oligometastatic Lung Cancer

Conclusion

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lung Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Thorac Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lung Cancer

Radiother Oncol

J Thorac Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Pract Radiat Oncol

J Thorac Oncol

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

J Thorac Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

J Thorac Oncol

Semin Radiat Oncol

Int J Radiat Oncol Biol Phys

Lung Cancer

Ann Oncol

J Thorac Cardiovasc Surg

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Lung Cancer

J Thorac Cardiovasc Surg

J Vasc Interv Radiol

Chest

Chest

Radiother Oncol

J Thorac Oncol

Int J Radiat Oncol Biol Phys

Lung Cancer

Int J Radiat Oncol Biol Phys

Clin Lung Cancer

Clin Lung Cancer

Invited Review
To SABR or Not to SABR? Indications and Contraindications for Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage, Oligometastatic, or Oligoprogressive Non–Small Cell Lung Cancer☆