Clinical Investigation
Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

https://doi.org/10.1016/j.ijrobp.2009.10.046Get rights and content

Purpose

To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT).

Methods and Materials

From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5–30 Gy).

Results

Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy.

Conclusions

Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

Introduction

In 2008, nearly 149,000 patients in the United States were diagnosed with colorectal cancer (1). Although adjuvant therapy has decreased the risk of pelvic relapse 2, 3, the consequences of local relapse are devastating 4, 5. Locoregional relapse of colon cancer occurs relatively frequently with tumor penetration through the bowel wall and regional lymph node involvement 6, 7, 8, 9, 10. Relapse in presacral or para-aortic lymph nodes is observed in patients with node-positive disease.

Locoregional relapse after resection of colorectal cancer is associated with a poor prognosis; median survival is 11 to 15 months 5, 11, 12, 13, and generally fewer than 5% of patients survive for 5 years 5, 11, 14, 15. Palliative therapies for pelvic recurrence are of limited effectiveness, especially for patients surviving longer than a few months. Additional radiation therapy often is not recommended for patients with relapse in previously irradiated fields.

Since 1981, curative-intent therapy at our institution has included intraoperative electron radiation therapy (IOERT) for patients with locally advanced malignancies. We have previously reported preliminary results of IOERT-containing regimens for patients with recurrent rectal cancer 16, 17 or locally advanced relapse of colorectal cancer 18, 19. The current study evaluated survival, patterns of relapse, and prognostic factors of patients with recurrent colorectal cancer.

Section snippets

Methods and Materials

The Mayo Clinic institutional review board approved this study. From April 1981 through January 2008, 607 patients with recurrent colorectal cancer underwent surgical resection and concurrent IOERT. All had locally advanced recurrence in the primary tumor bed or in regional pelvic or para-aortic lymph nodes. Patient characteristics are shown in Table 1. The median time from primary diagnosis to diagnosis of recurrence was 27 months.

External-beam radiation therapy (EBRT) was included in the

Survival

Survival estimates for the 607 patients are shown in Fig. 1. Median survival was 36 months. The 5- and 10-year survival estimates were 30% and 16%, respectively. Univariate analysis of potential prognostic factors for survival (Table 2) showed that longer length of time to relapse from diagnosis of primary disease, EBRT dose, IOERT dose, biologically equivalent dose, tumor volume, sex, and tumor histology were not associated with greater survival.

Prognostic factors with p values less than 0.10

Discussion

The medical literature offers little guidance for curative-intent therapy for patients with locoregional relapse of colorectal cancer. Most reports are single-institution retrospective analyses with inherent selection biases. Since 1981, a curative-intent approach, including the use of intraoperative electrons as a component of therapy, has been used relatively uniformly at our institution. Although retrospective in nature, the current analysis was accomplished using a prospectively defined

Conclusion

Long-term survival was observed for many patients with recurrent colorectal cancer treated with chemoradiation, resection, and IOERT. Prior EBRT was not a contraindication to this approach. Survival was higher for patients with R0 resection, patients with no prior chemotherapy, and patients treated more recently. Long-term survival was observed even for patients with R1 or R2 resection. For patients without prior EBRT, 50.4 Gy in 28 fractions with concomitant fluoropyrimidine, followed by

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    Portions of this article have been published in abstract form: Int J Radiat Oncol Biol Phys 2008;72(Suppl):S70.

    Conflict of interest: none.

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