Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

Voogt, E L K; Schaap, Dennis P.; Berg, Kim; Nieuwenhuijzen, Grard A. P.; Bloemen, Johanne G.; Creemers, G.J.; Willems, Jeroen; Cnossen, Jeltsje S.; Peulen, Heike M.U.; Lijnschoten, Gesina van; Burger, Jacobus W. A.; Rutten, H.J.T.

doi:10.1016/j.ejso.2021.05.017

Cited by 12 publications

(8 citation statements)

References 44 publications

(29 reference statements)

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Section: Discussionsupporting

confidence: 90%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Bedrikovetski

Fitzsimmons

Perry

et al. 2022

ANZ Journal of Surgery

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Background This study aimed to assess short‐term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. Methods A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two‐schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non‐operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. Results Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty‐three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non‐operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy‐related toxicity, with no treatment related mortality. Conclusion Early results with a defined two‐schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

Bedrikovetski

Fitzsimmons

Perry

et al. 2022

ANZ Journal of Surgery

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“…Effect of neoadjuvant therapy on improved survival has been demonstrated in numerous publications [ 33 – 35 ]. However, besides these advantages, short- and long-term disadvantages of neoadjuvant therapy should also be mentioned.…”

Section: Discussionmentioning

confidence: 99%

Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer

Paszt¹,

Ottlakán²,

Ábrahám³

et al. 2022

Pathol. Oncol. Res.

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Background: During the last decade, one of the most important treatment options for locally advanced, potencially resectable rectal tumours was neoadjuvant chemoradiotherapy (CRT) followed by surgery.Methods: Effects of the neoadjuvant treatment on surgical outcomes were retrospectively analysed in 185 patients with stage T2–T4 and N0–2, resectable rectal tumour among two patient groups defined by radiosensitizer agents. Group 1 (n = 94) involved radiotherapy (RT) with 50.4 Gy total dose (25 × 1.8 Gy + 3 × 1.8 Gy tumour bed boost), and intravenous 5-fluorouracil (5-FU) (350 mg/m2) with leucovorin (20 mg/m2) on the 1–5 and 21–25 days, while Group 2 (n = 91) RT and orally administrated capecitabine (daily 2 × 825 mg/m2) on RT days. Surgery was carried out after 8–10 weeks. Side effects, perioperative complications, type of surgery, number of removed regional lymph nodes, resection margins and tumour regression grade (TRG) were analysed.Results: More favourable side effects were observed in Group 2. Despite the same rate of diarrhoea (Group 1 vs. Group 2: 54.3% vs. 56.0%), Grade 2–3 diarrhoea ratio was lower (p = 0.0352) after capecitabine (Group 2). Weight loss occurred in 17.0% and 2.2% (p = 0.00067), while nausea and vomiting was described in 38.3% and 15.4% (p = 0.00045) with 5-FU treatment and capecitabine respectively. Anaemia was observed in 33.0% and 22.0% (p = 0.0941). Complete tumour regression occurred in 25.3% after oral- and 13.8% after intravenous treatment (p = 0.049). Ratio of sphincter preservation was higher with laparoscopy than open surgery (72.3% vs. 39.7%) (p = 0.00001).Conclusion: The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and overall clinical outcome, with increased rate of complete tumour regression.

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“…A 10% CR rate is assumed in patients diagnosed with hr-LARC, treated with chemoradiotherapy alone prior to surgery [ 30 , 32 ]. Based on the available literature and a retrospective analysis of patients from our own institution a CR rate of 20% is hypothesised after neoadjuvant chemotherapy and chemoradiotherapy for hr-LARC [ 30 , 32 , 33 ]. A 5% significance level and a 90% power, resulted in a total of 121 required patients.…”

Section: Methodsmentioning

confidence: 99%

“…As an alternative, the addition of neoadjuvant chemotherapy to the current treatment regimen has been suggested [26][27][28][29]. A matched casecontrol study observed an improved complete response (CR) rate of 28% compared to 9% (p = 0.013) with the addition of doublet chemotherapy to neoadjuvant treatment in patients with unfavourable LARC, defined as any cT4 rectal cancer, or cT2/3 rectal cancer with extramural venous invasion (EMVI), and/or tumour deposits, and/or cN2 disease on magnetic resonance imaging (MRI) [30]. These results on CR are in line with those of three recently published, phase III randomised controlled trials in LARC [28,31,32].…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk (“ugly”) locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT)

et al. 2022

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Background The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. Methods This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. Discussion This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. Trial registration Clinicaltrials.gov: NCT04838496, registered on 02–04-2021 Netherlands Trial Register: NL9790. Protocol version Version 3 dd 11–4-2022.

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Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

Cited by 12 publications

References 44 publications

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

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

Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer

Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk (“ugly”) locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT)

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