<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2019-0046_s_006_w2aab3b8c78b1b7b1aab1c16b1Aa"><h3>Background</h3><p>In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence.</p></sec><sec id="j_raon-2019-0046_s_007_w2aab3b8c78b1b7b1aab1c16b2Aa"><h3>Patients and methods</h3><p>Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8–10 weeks after completition of CRT.</p></sec><sec id="j_raon-2019-0046_s_008_w2aab3b8c78b1b7b1aab1c16b3Aa"><h3>Results</h3><p>From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p &lt; 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR.</p></sec><sec id="j_raon-2019-0046_s_009_w2aab3b8c78b1b7b1aab1c16b4Aa"><h3>Conclusions</h3><p>Total neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.</p></sec></abstract>

BackgroundIn the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence.Patients and methodsPatients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8–10 weeks after completition of CRT.ResultsFrom November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR.ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.

Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia

Radiology and Oncology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

BackgroundIn the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total...

Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia

Article Category: Research Article

Published Online: Oct 25, 2019

Page range: 465 - 472

Received: Jul 01, 2019

Accepted: Aug 13, 2019

DOI: https://doi.org/10.2478/raon-2019-0046

© 2019 Mojca Tuta, Nina Boc, Erik Brecelj, Mirko Omejc, Franc Anderluh, Ajra Secerov Ermenc, Ana Jeromen Peressutti, Irena Oblak, Bojan Krebs, Vaneja Velenik, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.