Elsevier

Clinical Colorectal Cancer

Volume 16, Issue 3, September 2017, Pages e211-e220
Clinical Colorectal Cancer

Original Study
Radiosensitivity of Colon and Rectal Lung Oligometastasis Treated With Stereotactic Ablative Radiotherapy

https://doi.org/10.1016/j.clcc.2016.08.003Get rights and content

Abstract

Introduction

Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR.

Material and Methods

This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014.

Results

We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1- and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site (P = .001) and > 2 metastases (P = .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P = .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P = .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P = .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume ≥ 3266 mm3 (P = .03) and > 2 metastases (P = .04).

Conclusion

In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome.

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)

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    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].

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