Original StudyRadiosensitivity of Colon and Rectal Lung Oligometastasis Treated With Stereotactic Ablative Radiotherapy
Introduction
According to the International Agency for Research on Cancer, colorectal cancer (CRC) represent about 10% of all newly diagnosed cancers in 2015, and is the third most common cause of cancer mortality worldwide.1 Early metastatic progression of CRC may present with oligometastatic disease, defined as 3 to 5 slowly progressive metastases.2 Oligometastatic disease is potentially curable with local therapy such as surgery, radiofrequency, or stereotactic ablative radiotherapy (SABR).2 In surgically resected liver metastasis, patients with CRC have 5-year overall survival (OS) rates of 50% to 60%.3, 4, 5 This local therapeutic approach can also be applied to oligometastastic lung lesions, such as treatment with surgery,6 radiofrequency,7 or SABR. SABR is a noninvasive high-precision external beam radiation therapy recognized as a safe and effective treatment for primary and metastatic lung lesions.2, 8, 9 Previous studies have demonstrated > 90% local control rates with biologically effective doses (BED) > 100 Gy.9, 10, 11, 12 These studies often analyzed treatments of non–small-cell lung cancer and metastatic lesions of various histologies together. It has been reported that colorectal histology is associated with worse local control versus other histologies,12 although it remains unclear whether a difference in outcome exists between rectal and colon carcinoma.
The aim of this study is to identify factors predictive for tumor response, local control (LC), metastasis-free survival (MFS), progression-free survival (PFS), and overall survival (OS) in patients with CRC with oligometastatic disease in the lung treated with SABR. KRAS status was analyzed as a potential prognostic factor for LC, MFS, OS and tumor response. Because rectal histology was found as a deleterious factor for local control, detailed comparison between rectal and colon lesions was also performed.
Section snippets
Patient Selection
This study is a retrospective monocentric cohort study, which includes patients treated from September 2007 to November 2014. Inclusion criteria were as follows: histologically proven colon or rectal cancer; at least 1 lung metastasis; tumor size less than 7 cm. Exclusion criteria were as follows: presence of other active cancer; more than 5 progressive metastases either at cancer diagnosis, after treatment of the primary tumor or after chemotherapy in the metastatic setting.
Treatment
The treatment
Characteristic of Patients and Lesions
A total of 87 lesions from 53 patients were treated with SABR. The characteristics of both patients and lesions are shown in Table 1.
The majority of patients had 1 lung metastasis (n = 34) treated with SABR, and the remaining had 2 (n = 8), 3 (n = 8), 4 (n = 2), or 5 (n = 1) lung metastases treated. The median maximal size of the irradiated tumors was 16 mm (range, 3-70 mm).
Toxicity Profile
There were no grade 3 to 5 early or late toxicities in this study. A detailed analysis of minor side effects (grade 1-2)
Discussion
This retrospective study describes factors associated with disease control and survival after SABR for lung oligometastasis arising from CRC.
After a median follow-up of 33 months, we found good outcomes with colorectal lesions treated with SABR, including: a 2-year LC rate of 78.2%, a 1-year MFS rate of 29.2%, and an estimated 5-year OS rate of 58.3%. The treatment was well-tolerated with no grade 3-5 toxicities.
Filippi et al17 previously reported the treatment of 26 patients and 59 lesions.
Conclusions
This study confirms an excellent survival in patients with oligometastatic CRC treated with SABR for lung metastases. The LC rate is high with a median BED prescription of 180 Gy. In this cohort, patients with rectal primary tumors had a higher risk of local relapse, without influence on MFS rate or OS. This detriment was not dependent on treatment or tumor characteristics, but may be due to an unknown biological factor, as previously hypothesized with radiofrequency ablation.7 In this study, a
Disclosure
The authors have stated that they have no conflicts of interest.
References (29)
- et al.
Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial
Lancet Oncol
(2013) - et al.
Single-center multidisciplinary management of patients with colorectal cancer and resectable synchronous liver metastases improves outcomes
Clin Res Hepatol Gastroenterol
(2013) - et al.
Pooled analysis of the surgical treatment for colorectal cancer liver metastases
Crit Rev Oncol Hematol
(2015) - et al.
Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases
Ann Oncol
(2015) - et al.
Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy
Radiother Oncol
(2016) - et al.
Predictive factors for local control in primary and metastatic lung tumours after four to five fraction stereotactic ablative body radiotherapy: a single institution's comprehensive experience
Clin Oncol (R Coll Radiol)
(2014) - et al.
Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study
Int J Radiat Oncol Biol Phys
(2012) - et al.
Colorectal histology is associated with an increased risk of local failure in lung metastases treated with stereotactic ablative radiation therapy
Int J Radiat Oncol Biol Phys
(2015) - et al.
Cancer Radiother
(2007) - et al.
Stereotactic radiosurgery for lung tumors: preliminary report of a phase I trial
Ann Thorac Surg
(2003)
Stereotactic ablative radiation therapy as first local therapy for lung oligometastases from colorectal cancer: a single-institution cohort study
Int J Radiat Oncol Biol Phys
Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases: a pooled analysis of the German working group “stereotactic radiotherapy”
Lung Cancer
Lung stereotactic ablative body radiotherapy: a large scale multi-institutional planning comparison for interpreting results of multi-institutional studies
Phys Med
Study of 201 non-small cell lung cancer patients given stereotactic ablative radiation therapy shows local control dependence on dose calculation algorithm
Int J Radiat Oncol Biol Phys
Cited by (31)
Stereotactic Body Radiotherapy for Management of Pulmonary Oligometastases in Stage IV Colorectal Cancer: A Perspective
2023, Clinical Colorectal CancerManagement of Oligometastatic Colorectal Cancer
2023, Surgical Clinics of North AmericaLocal Therapies in Advanced Colorectal Cancer
2022, Hematology/Oncology Clinics of North AmericaCitation Excerpt :SABR has also been shown to be an effective treatment of pulmonary metastases from CRC with select published series summarized in Table 2. Overall, local control rates of 80% to 90% at 1 year have been reported with minimal toxicity.31–33 Data from several series have shown that CRC lung metastases treated with SABR have a higher rate of local failure compared with other histologies and improved local control can be achieved by delivering a higher biologically effective dose.34,35
Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy
2020, Radiotherapy and OncologyCitation Excerpt :KRAS mutation has recently been shown to be a prognostic biomarker of worse survival outcomes in metastatic colorectal cancer in a large meta-analysis of first line randomised chemotherapy trials [26], an analogous situation to those referred for SBRT. Kinj et al found that KRAS mutation was associated with inferior metastasis free survival, but not OS, following SBRT in lung metastases [14]. In a randomised phase II trial of proton therapy for liver metastases KRAS mutants and TP53 mutants had worse local control than wild type patients [24].
Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document
2020, Radiotherapy and Oncology