Clinical Investigation
Clinical Outcome of Hypofractionated Stereotactic Radiotherapy for Abdominal Lymph Node Metastases

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Purpose

We report the medium-term clinical outcome of hypofractionated stereotactic body radiotherapy (SBRT) in a series of patients with either a solitary metastasis or oligometastases from different tumors to abdominal lymph nodes.

Methods and Materials

Between January 2006 and June 2009, 19 patients with unresectable nodal metastases in the abdominal retroperitoneal region were treated with SBRT. Of the patients, 11 had a solitary nodal metastasis and 8 had a dominant nodal lesion as part of oligometastatic disease, defined as up to five metastases. The dose prescription was 45 Gy to the clinical target volume in six fractions. The prescription had to be downscaled by 10% to 20% in 6 of 19 cases to keep within dose/volume constraints. The first 11 patients were treated with three-dimensional conformal techniques and the last 8 by volumetric intensity-modulated arc therapy. Median follow-up was 1 year.

Results

Of 19 patients, 2 had a local progression at the site of SBRT; both also showed concomitant tumor growth at distant sites. The actuarial rate of freedom from local progression was 77.8% ± 13.9% at both 12 and 24 months. Eleven patients showed progressive local and/or distant disease at follow-up. The 12- and 24-month progression-free survival rates were 29.5% ± 13.4% and 19.7% ± 12.0%, respectively. The number of metastases (solitary vs. nonsolitary oligometastases) emerged as the only significant variable affecting progression-free survival (p < 0.0004). Both acute and chronic toxicities were minimal.

Conclusions

Stereotactic body radiotherapy for metastases to abdominal lymph nodes was shown to be feasible with good clinical results in terms of medium-term local control and toxicity rates. Even if most patients eventually show progressive disease at other sites, local control achieved by SBRT may be potentially significant for preserving quality of life and delaying further chemotherapy.

Introduction

Stereotactic body radiotherapy (SBRT) has proved its efficacy in several patient populations with primary and metastatic limited tumors (1). In particular, SBRT may be appropriate for selected patients with oligometastatic disease, defined as fewer than five lesions (2). Abdominal SBRT has been reported with reference mainly to primary and secondary liver tumors, as well as pancreatic and renal tumors (1). Stereotactic body radiotherapy for metastases to abdominal lymph nodes has rarely been reported, with only three articles reporting on it as a specific topic 3, 4, 5 and with it most often comprising a few cases in mixed series 6, 7, 8, 9, 10. In one article reporting the outcome of SBRT for isolated lymph node recurrence from prostate cancer, the target lesion was within the pelvis in most cases, which poses different technical problems (11).

The rationale for administering SBRT with a curative intent to patients with limited nodal metastatic disease may be the same as that in selected patients with liver or lung metastases. Whereas most patients with metastases to abdominal nodes are unfit for surgery, it is known that in the setting of limited metastatic burden, SBRT leads to local control rates higher than 70% to 80% 1, 10, which may turn into increased survival and better quality of life. Conversely, conventionally fractionated non-stereotactic radiotherapy is generally believed to attain poorer results, because doses are limited by normal tissue tolerance. Actually, few published data do exist on local control rates of conventional radiotherapy in this context. Although several articles dealt with conventional radiotherapy of isolated para-aortic lymph node recurrence from cervix cancer, most of them reported only survival rates 12, 13, 14, 15. A 33% to 50% rate of progressive disease in the para-aortic lymph node–treated area was reported in two studies 16, 17.

Between January 2006 and June 2009, 19 patients with unresectable nodal metastases in the abdominal region were treated with SBRT. We have previously reported early results in a series of 15 patients with abdominal nodal metastases, including 12 treated by SBRT alone with three-dimensional conformal radiotherapy (CRT) techniques (18). In that series no major toxicity was observed, and 6-month local control was achieved in 10 of 12 cases. Because in 6 of 12 cases our standard dose of 45 Gy in 6 fractions had to be downscaled by 10% to 20% to keep within dose/volume constraints for organs at risk (OARs), we also investigated the potential role of volumetric intensity-modulated arc therapy given by RapidArc (Varian Medical Systems, Palo Alto, CA) in this patient population (19). RapidArc has been investigated previously for some other clinical cases 20, 21, 22, 23, 24, 25, showing significant improvements over other advanced techniques. Because we also found advantages in dose distribution in this setting, since November 2008, SBRT to abdominal nodes has been delivered by volumetric intensity-modulated radiotherapy.

This retrospective study is an update of our previous report. Our aim was to evaluate the clinical effectiveness of SBRT for patients with solitary or nonsolitary oligometastases to abdominal lymph nodes. Medium-term (12–24 months) local control and acute and late toxicity were considered as the main endpoints.

Section snippets

Patient selection

From October 2005 to June 2009 at Istituto Clinico Humanitas, Rozzano, Italy, 80 patients were treated by linear accelerator–based hypofractionated SBRT to abdominal targets, including liver, pancreatic, and lymph nodal lesions. Since January 2006, 29 consecutive patients with unresectable nodal metastases in the abdominal region were treated. Six patients treated with a single-dose SBRT boost after external beam fractionated radiation over an extended volume are not the subject of this report.

Patient population

The comparison between the CRT and RapidArc groups (11 and 8 patients, respectively) showed a rather well-balanced distribution of patient and tumor variables (Table 1). Given the small numbers, no formal statistic was applied to check the balancing. An unbalancing between the two groups is evident in the median duration of follow-up, obviously caused by different time periods. Similarly, the subgroup of 6 patients with downscaling of total dose did not show any specific difference in

Discussion

Locally curative treatment of oligometastases is regarded as an important resource for improving survival in a clinically significant subset of cancer patients 1, 2. In this framework, SBRT for patients with oligometastatic disease in abdominal lymph nodes may play a major role. Early data from our series showed promising local control rates. However, a dose reduction was needed in several cases because of the close proximity of the CTV to the gastrointestinal OARs, where severe radiation

Conclusions

Hypofractionated SBRT for metastases to abdominal lymph nodes was feasible and able to provide good clinical results, supporting its role in aggressively treating selected cases with limited metastatic disease. A more prolonged follow-up will be required to confirm our results in the long term. Even if most patients eventually show progressive disease at other sites, local control achieved by SBRT may be potentially significant for quality of life and delaying further chemotherapy. In the

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    Conflict of interest: Dr. Cozzi acts as Scientific Advisor to Varian Medical Systems, Palo Alto, California. The other authors have no conflict of interest.

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