In our study, the primary rectal tumor was treated with combined CRT, whereas the distant lesions were treated only with chemotherapy. This chemotherapy regimen, consisting of oxaliplatin plus capecitabine, was expected to improve the overall tumor response, especially for lesions outside the irradiation field. We found that 50% of distant tumors responded to treatment and that this was due solely to weekly chemotherapy, similar to the response to FOLFOX or FOLFIRI in patients with stage IV colorectal cancer . Nine of 32 patients (28.1%) received definitive therapy after CRT and CT, a percentage similar to other studies using FOLFOX [5, 6]. Moreover, 30 of these 32 patients experienced progression-free local control after CRT, better than the outcome from chemotherapy alone . Therefore, our preliminary results supported the hypothesis that first-line CRT followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone.
Intensified CRT may significantly increase toxicities, which would have a negative impact on subsequent CT. To reduce toxicities, we therefore used the IMRT technique to decrease doses delivered to the surrounding normal organs, including the bowel, bladder and femoral head. For example, use of the IMRT decreased the volume of 45 Gy to the small bowel decreased by more than 64% . Moreover, a comparison of IMRT with 3DCRT in 10 patients found that IMRT had similar target coverage with reduced doses to the small bowel, bladder, pelvic bones and femoral heads . These findings were supported by our results, showing toxicities using IMRT were acceptable and most patients could be treated according to the original CT schedule.
We found that 9 of our 32 patients received definitive treatment, including the removal of all visible masses, and that these patients had a longer PFS and OS. Remove of all visible tumors is critical. Further analysis, however, showed that 5 of these 9 patients experienced distant relapse during follow up. The high distant failure rate was partly due to the initial tumor burden, with most patients having more than 3 distant lesions at initial diagnosis. Total surgical resection after neoadjuvant therapy has been based on the reduction or disappearance of these lesions. However, pCR and cCR rates were not identical, with consistencies of only 50% to 75%. Therefore, recurrence in situ would occur in 40% to 74% of patients whose liver metastases showed a cCR [19, 20]. Furthermore, most relapses in our patients occurred after the completion of 6 months of chemotherapy, similar to the results of previous trials [21, 22]. Since residual tumor cells may reproduce after the completion of chemotherapy, maintenance chemotherapy may be essential in increasing the disease-free interval in stage IV patients, despite having undergone a “curative surgery”.