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Modern evidence and future prospects of external body radiation therapy for lung oligometastases of breast cancer

ABSTRACT: After Hellman and Weichselbaum defined “Oligometastasis” in 1995, several local therapies for lung oligometastases including surgical resection and external body radiation therapy were reported that improved local control (LC) and progression-free survival, overall survival, and quality of life. This suggests that oligometastases is a potentially curable state. Modern advances in radiation therapy such as stereotactic body radiation therapy (SBRT) in which high dose coverage of target lesion without exposure of normal organ is possible, and are widely used to treat solitary or a limited number of primary lung cancer and metastases. Several reports showed that SBRT was a useful treatment method for lung oligometastases, and the LC rate of SBRT was 80–90% in 2 years and less invasive than surgical resection. SBRT is a safe and effective especially for small and peripheral lung metastases. However, if the metastatic lesion is big or centrally located, careful treatment is necessary to prevent radiation pneumonitis. After SBRT, it is sometimes difficult to differentiate local recurrence and pulmonary injury, especially in the early phase. However, it is important to detect local recurrence especially in patients who require further local therapy such as surgical resection and re-irradiation or systemic therapy. The diagnosis can be improved by determining the natural course after SBRT and local recurrence with computed tomography imaging and 18F-fluorodeoxyglucose positron emission tomography, respectively. Moreover, radiation therapy may have both local and systemic effects that are related to the enhancement of immune-response after radiation. Currently, several trials evaluating the benefits of SBRT for oligometastatic breast cancer are underway. However, the adaption of SBRT for lung metastases including other treatment strategies should be carefully discussed by the radiation oncologist and a multi-disciplinary team comprising a breast surgeon, medical oncologist, diagnostic radiologist, and radiation oncologist, among others.

SUBMITTER: Wada Y

PROVIDER: S-EPMC8799217 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Stereotactic body radiation therapy (SBRT) also referred to as stereotactic ablative radiotherapy (SABR), is a technique which has emerged over the past two decades due to improvements in radiation technology. Unlike conventional external beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically delivered in one to eight fractions, is a technique whereby potentially ablative doses of radiotherapy (usually 7.5-20 Gy per fraction) can be delivered with steeper dose gradients and sub millimetre precision, minimising risk to surrounding normal tissues. The potential benefits of excellent tumor control with low toxicity has led to the increasing use of SBRT in a number of clinical situations. Due to compelling evidence, SBRT is now the treatment of choice for medically inoperable patients with peripherally located stage I non-small cell lung cancer (NSCLC). Controversy remains however as to its efficacy and safety for central or ultra-central lung tumors. The evidence base supporting the use of SBRT as a novel treatment for spinal metastases and oligometastases is rapidly expanding but challenges remain in these difficult patient populations. In an era where targeted therapy and improved systemic treatments for stage IV cancer have resulted in increased disease-free survival, and our knowledge of the oligometastatic state is ever expanding, using SBRT to treat metastatic disease and gain durable local control is increasingly desirable. Several randomized trials are currently underway and are sure to provide valuable information on the benefit and utility of SBRT across many tumor sites including early-stage NSCLC, spinal metastases and oligometastatic disease. Recognizing the evolving role of SBRT in clinical practice, this paper provides a critical review of recent developments in each of these areas particularly highlighting the challenges facing clinicians and discusses potential areas for future research.

Project description:BackgroundTo investigate the effect of stereotactic body radiation therapy (SBRT) on pulmonary oligometastases and to analyze the clinical factors and dose parameters affecting local recurrence-free survival (LRFS) and overall survival (OS).MethodsThis study retrospectively enrolled a total of 84 patients (148 lesions) treated in our department from May 2015 to November 2018. Pulmonary oligometastases was defined as up to 5 metastatic lesions in the lung and with both the primary tumor and any extra-thoracic metastases being controlled. Patients receiving a BED10 (biological effective dose, α/β =10) of SBRT ≥75 Gy and a dose/fraction ≥4 Gy were enrolled. The patient group consisted of 52 men (61.9%) and 32 women (38.1%), with a median age 56 years (range, 29-80 years). Median tumor diameter was 1.71cm (range, 1.2-5.0 cm). The BED10 was 75-119 Gy in 4-15 fractions. Univariate and multivariate Cox regression analyses were performed on factors predicting the outcomes.ResultsAll patients completed the treatment as planned, and the median follow-up time was 20.3 months. The median OS for the entire group was 34.3 months, with an actuarial 1-, 2-, 3- and 5-year OS of 74.7%, 59.4%, 49.7%, and 36.8%, respectively. Among the 148 lesions in the whole group, 19 (12.8%) lesions had local recurrence (LR). The median LRFS time for all patients was 56.9 months. The LRFS rate was 93.6%, 83.5%, 81.4%, and 76.6% at 1, 2, 3, and 5 years, respectively. No patient developed acute grade 3 or 4 toxicity. On univariate analysis, age ≥63 years old, primary site of colorectal cancer, BED10 <85.2 Gy, pathological type of adenocarcinoma, planning target volume (PTV) min BED10 <76.6 Gy, and gross tumor volume (GTV) ≥8.8 cc, were significantly associated with poorer LRFS. Multivariate analysis showed that age ≥63 years old, primary site of colorectal cancer, and PTV min BED10 <76.6 Gy were significant risk factors affecting LRFS.ConclusionsSBRT is feasible for pulmonary oligometastasis with favorable local control and minimal toxicity. Multiple dose parameters, instead of a prescription dose only, in combination with clinical parameters, should be considered for optimal local control.

Project description:AimsTo evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials.MethodsA retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated.ResultsThe median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment-LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported.ConclusionOur study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.

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Modern evidence and future prospects of external body radiation therapy for lung oligometastases of breast cancer

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