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

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.

Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation

“…The current findings are consistent with previous publications demonstrating relatively high rates of primary tumour response and compliance with chemotherapy for TNT in comparison with standard neoadjuvant treatment 25–27 . At the time of introduction of our protocol there was a paucity of level 1 evidence for TNT, given the four randomized controlled trials had not been published in full yet 11–13,28 .…”

“…The current findings are consistent with previous publications demonstrating relatively high rates of primary tumour response and compliance with chemotherapy for TNT in comparison with standard neoadjuvant treatment. [25][26][27] At the time of introduction of our protocol there was a paucity of level 1 evidence for TNT, given the four randomized controlled trials had not been published in full yet. [11][12][13]28 To account for this, we employed an integrated approach across disciplines with justification based on level 2 data, ethics committee approval, and rigorous prospective data collection with frequent reporting of outcomes.…”

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

“…After analysing the results of treatment of this high-risk group of patients in two previous Slovenian studies, we reported 10.5% of pCR in 2011-2013 and 20% in 2014-2015[ 24 , 30 , 31 ]. Preoperative treatment was more intensive than standard treatment in both studies.…”

The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer

“…All patients received concomitant CRT, and 54 patients received consolidation chemotherapy. As a result, the pCR rate was 23.3% in 60 patients who were operated [ 11 ]. Only grade 1 and 2 toxicity were observed due to intensive treatment.…”