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Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

ABSTRACT:

Background

Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).

Methods

Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.

Results

361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.

Conclusions

We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

SUBMITTER: Hong JC

PROVIDER: S-EPMC5896920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundResearch in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken.MethodsThis is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment.DiscussionIf a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials.Trial registrationClinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021.Protocol version1.1 on December 9, 2021.

Project description:ImportanceThe oligometastatic paradigm postulates that patients with a limited number of metastases can be treated with ablative local therapy to each site of disease with curative intent. Stereotactic ablative radiotherapy (SABR) is a radiation technique that has become widely used in this setting. However, prospective data are limited and are mainly from single institutional studies.ObjectiveTo conduct a meta-analysis to characterize the safety and clinical benefit of SABR in oligometastatic cancer.Data sourcesA comprehensive search was conducted in PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cumulative Index to Nursing and Allied Health Literature on December 23, 2019, that included prospective clinical trials and review articles that were published within the past 15 years.Study selectionInclusion criteria were single-arm or multiarm prospective trials including patients with oligometastatic cancer (ie, ≤5 sites of extracranial disease), and SABR was administered in less than or equal to 8 fractions with greater than or equal to 5 Gy/fraction.Data extraction and synthesisThe Population, Intervention, Control, Outcomes and Study Design; Preferred Reporting Items for Systematic Reviews and Meta-analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify eligible studies. Study eligibility and data extraction were reviewed by 3 authors independently. Random-effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted.Main outcomes and measuresSafety (acute and late grade 3-5 toxic effects) and clinical benefit (1-year local control, 1-year overall survival, and 1-year progression-free survival).ResultsTwenty-one studies comprising 943 patients and 1290 oligometastases were included. Median age was 63.8 years (interquartile range, 59.6-66.1 years) and median follow-up was 16.9 months (interquartile range, 13.7-24.5 months). The most common primary sites were prostate (22.9%), colorectal (16.6%), breast (13.1%), and lung (12.8%). The estimate for acute grade 3 to 5 toxic effect rates under the random-effects models was 1.2% (95% CI, 0%-3.8%; I2 = 50%; 95% CI, 3%-74%; and τ = 0.20%; 95% CI, 0.00%-1.43%), and the estimate for late grade 3 to 5 toxic effects was 1.7% (95% CI, 0.2%-4.6%; I2 = 54%; 95% CI, 11%-76%; and τ = 0.25%; 0.01%-1.00%). The random-effects estimate for 1-year local control was 94.7% (95% CI, 88.6%-98.6%; I2 = 90%; 95% CI, 86%-94%; and τ = 0.81%; 95% CI, 0.36%-2.38%]). The estimate for 1-year overall survival was 85.4% (95% CI, 77.1%-92.0%; I2 = 82%; 95% CI, 71%-88%; and τ = 0.72%; 95% CI, 0.30%-2.09%) and 51.4% (95% CI, 42.7%-60.1%; I2 = 58%; 95% CI, 17%-78%; and τ = 0.20%; 95% CI, 0.02%-1.21%) for 1-year progression-free survival.Conclusions and relevanceIn this meta-analysis, SABR appears to be relatively safe in patients with oligometastatic cancer with clinically acceptable rates of acute and late grade 3 to 5 toxic effects less than 13% and with clinically acceptable rates of 1-year local control overall survival, and progression-free survival. These findings are hypothesis generating and require validation by ongoing and planned prospective clinical trials.