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OBJECTIVE(S):
Patients with colorectal cancer fixed to critical structures (e.g., IVC and pelvic sidewall) are considered “unresectable” and treated with palliative therapy. Our objective was to determine in what manner aggressive neoadjuvant external beam radiotherapy (EBRT), chemotherapy, surgical resection, and intraoperative radiotherapy (IORT) impacts recurrence and survival in patients with unresectable primary colorectal cancer.
METHODS:
One-hundred forty-six patients (65% males) with unresectable colon (40) and rectal (106) cancer were treated with EBRT, chemotherapy, surgical resection, and IORT. Final surgical margins were close, but negative in 100 patients (68%), microscopically positive in 28 (19%), and grossly positive in 18 (13%). Kaplan-Meier method was used to visualize survival and recurrence curves; groups were compared using the log-rank test.
RESULTS:
Five-year outcomes are shown in Table 1. Median overall survival (years) favored patients with age <58 (7.6 vs. 3.6; p=0.0012), those receiving adjuvant chemotherapy (9.4 vs. 3.9; p=0.0019), and those with negative or microscopic margins (6.3 vs. 1.9; p=0.0006). There were no peri-operative deaths. Fifteen complications occurred in 12 patients (8%) within 30 days of surgery/IORT. One-hundred nineteen long-term complications occurred in 77 patients (53%), most commonly peripheral neuropathy (19%), bowel obstruction (14%), and ureteral obstruction (12%).
CONCLUSIONS:
Aggressive multimodality therapy for unresectable primary colorectal cancer results in excellent local disease control and a 5-year overall survival rate of 52% with no operative mortality and acceptable peri-operative morbidities.

Table 1: 5 year Outcomes (Median Survival 3.7 years)

5 year Outcome
Overall survival	52%
Disease-free survival	43%
Freedom from central recurrence (IORT field)	98%
Freedom from local recurrence (EBRT field)	86%
Freedom from distant recurrence	51%

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