Neoadjuvant bevacizumab and chemoradiotherapy in locally advanced rectal cancer: early outcome and technical impact on toxicity

Abstract

BackgroundWe aimed to evaluate early clinical and pathological results for treating locally advanced rectal cancer with bevacizumab and neoadjuvant concurrent chemoradiotherapy using the technique of prone-position volumetric modulated arc therapy and to compare the toxicity of volumetric modulated arc therapy with that of supine-position four-field box radiotherapy.MethodsTwelve patients with stage IIA to IVA rectal adenocarcinoma, treated with neoadjuvant concurrent chemoradiotherapy (45 Gy in 25 fractions to the rectal tumor and pelvic lymphatics) and bevacizumab, were prospectively enrolled. Chemotherapy included FOLFOX (leucovorin, fluorouracil, and oxaliplatin) (n =11) and 5-fluorouracil (n =1). All patients received prone-position volumetric modulated arc therapy. A historical cohort treated with supine-position box radiotherapy, including six other patients treated with bevacizumab-based concurrent chemoradiotherapy in our hospital, was used for comparison. Setup errors, toxicities, and potential biomarkers were evaluated.ResultsAll patients completed neoadjuvant concurrent chemoradiotherapy and underwent total mesorectal excision. Four (33.3%) patients had pathological complete response. Significantly more grade 2 or 3 diarrhea was associated with the supine-box technique (5/6 versus 2/12, P =0.01). The magnitude of setup errors was similar between the supine-box and prone volumetric modulated arc therapy techniques. The estimated 2-year survival and 2-year failure-free survival rates were 100% and 72.9% in the prone volumetric modulated arc therapy group and 66.7% and 66.7% in the supine box group, respectively.ConclusionsThe early clinical outcome has been encouraging. Volumetric modulated arc therapy in prone-positioned patients was technically advantageous and reduced bowel toxicity.

The efficacy and safety of adding bevacizumab in neoadjuvant therapy for locally advanced rectal cancer patients: A systematic review and meta-analysis

“…The initial database search and manual screening of references retrieved 9987 records, of which 6491 were removed as duplicates, leaving 3496 records which proceeded on to title and abstract screening. 39 potential candidates underwent full-text review, of which 27 [ [10] , [11] , [12] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] ] were adequate for inclusion, with 12 studies deemed inadequate for various reasons shown in Fig. 1 .…”

“…Of note, among the eligible studies, five [ 5 , 11 , 17 , 18 ] explored the role of TNT. Concerning the countries/districts where these trials were conducted, seven [ 16 , 17 , 19 , 22 , 30 , 33 , 35 ] were in Japan, five [ 10 , 14 , 37 , 41 , 42 ] in the United States of America, four in China (two [15] , [18] in the mainland, two [21] , [32] in Taiwan), four [12] , [29] , [31] , [34] in Spain, two [ 38 , 43 ] in Italy, one [11] in France, one [36] in Germany, one [40] in Greece, one [39] in Slovenia, and one [20] in the United Kingdom. The detailed baseline characteristics and data regarding endpoints of interest from the included studies are shown in Table 1 .…”

The efficacy of adding targeted agents to neoadjuvant therapy for locally advanced rectal cancer patients: a meta‐analysis

“…A total of 32 studies were ultimately included, after ruling out 16 ineligible investigations which failed to meet the inclusion and exclusion criteria for this meta‐analysis. The included studies consisted of 21 for the VEGF inhibitor, bevacizumab , and 11 for EGFR inhibitors (eight for cetuximab , one for nimotuzumab and two for panitumumab ). These included one randomized clinical trial (RCT) and three clinical controlled trials (CCT) , but we only analyzed cohorts which tested the addition of targeted agents to their neoadjuvant therapy regimens for this meta‐analysis.…”

“…These included one randomized clinical trial (RCT) [54] and three clinical controlled trials (CCT) [34,53,55], but we only analyzed cohorts which tested the addition of targeted agents to their neoadjuvant therapy regimens for this meta-analysis. There were also two bevacizumab-relevant studies [22,52] consisting of two arms with bevacizumab in their neoadjuvant regimens, and we included all four cohorts for the meta-analysis. Additionally, there was one study [49] consisting of two cohorts testing addition of bevacizumab, one in the neoadjuvant setting and the other in the postoperative setting, and we included only the former.…”

Preliminary results of preoperative chemoradiotherapy with consolidating chemotherapy in patients with locally advanced rectal cancer

“…Применение химиотерапии в режиме консолидации после завершения химиолучевой терапии и немногочисленные опубликованные по этому направлению сообщения демонстрируют высокие результаты по уровню достижения полного лечебного патоморфоза [9,10,12]. Лечебный патоморфоз и патологическая стадия опухолевого процесса тесно связана с отдаленными результатами лечения [3,5,36,19,29]. ретроспективный анализ Capirci et al результатов лечения 566 пациентов, у которых был достигнут полный лечебный патоморфоз в опухоли, показал увеличение до 85% и 90% пятилетней безрецидивной и общей выживаемости, а также снижение локальных рецидивов до 1,6% и отдаленных метастазов до 8,9% [3].…”