Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial

Masi, Gianluca; Vivaldi, Caterina; Fornaro, Lorenzo; Buccianti, P; Sainato, A.; Marcucci, Lorenzo; Martignetti, Angelo; Urso, Emanuele Damiano Luca; Castagna, Maura; Fontanini, Gabriella; Bergamo, Francesca; Musettini, Gianna; Urbani, Lucio; Sensi, Elisa; Balestri, Riccardo; Montrone, S.; Pasqualetti, Francesco; Cremolini, Chiara; Paolo, Antonello Di; Zagonel, Vittorina; Falcone, Alfredo

doi:10.1016/j.ejca.2019.01.006

Cited by 32 publications

(22 citation statements)

References 35 publications

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“…The traditional treatment method for such patients is the "sandwich mode" (radiotherapy-surgery-chemotherapy), which reduces the local recurrence rate from 35% to 10%, while the distant metastasis rate remains approximately 25%. To reduce the distant metastasis rate of RC, its treatment mode has been changed to total neoadjuvant therapy (TNT) (3)(4)(5)(6)(7). Adjuvant chemotherapy (AT) is now only recommended if there are high risk factors for stage II colon cancer (8).…”

Section: Introductionmentioning

confidence: 99%

A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy

Zhang

Wang

2021

Front. Oncol.

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BackgroundThe perioperative treatment model for locally advanced rectosigmoid junction cancer (LARSC) has not been finalized; whether this model should refer to the treatment model for rectal cancer remains controversial.MethodsWe screened 10,188 patients with stage II/III rectosigmoid junction adenocarcinoma who underwent surgery between 2004 and 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Among them, 4,960 did not receive adjuvant chemotherapy, while 5,228 did receive adjuvant chemotherapy. Propensity score matching was used to balance the two groups for confounding factors, and the Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to identify independent prognostic factors and build a predictive nomogram of survival for LARSC. X-tile software was used to divide the patients into three groups (low, medium, and high) according to their risk scores. 726 patients in our hospital were included for external validation.ResultsLARSC patients did not show a benefit from neoadjuvant radiotherapy (P>0.05). After further excluding patients who received neoadjuvant radiotherapy, multivariate analysis found that age, grade, tumor size, T stage, and log odds of positive lymph nodes were independent prognostic factors for patients without adjuvant chemotherapy and were included in the nomogram. The C-index of the model was 0.690 (95% confidence interval: 0.668–0.712). We divided the patients into low, moderate, and high risk subgroups based on prediction scores of the nomogram. We found that adjuvant chemotherapy did not improve the prognosis of low risk patients, while moderate and high risk patients benefited from adjuvant therapy. External validation data found that moderate, and high risk patients also benefited from AT.ConclusionDirect surgery plus adjuvant chemotherapy may be the best perioperative treatment for LARSC. Moreover, adjuvant chemotherapy is only recommended for moderate and high risk patients as it did not benefit low risk patients.

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Section: Introductionmentioning

confidence: 99%

A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy

Zhang

Wang

2021

Front. Oncol.

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“…Avoiding the last scheduled dose of oxaliplatin significantly reduced pathological response in a recent study [64]. We cannot assess the contribution of oxaliplatin in our cohort, but we notice that oxaliplatin is part of current total neoadjuvant therapy for rectal cancer where induction chemotherapy is used before radiation [65][66][67][68]. Giving more chemotherapy before surgery was recently documented in two large randomized studies and several phase II studies, yielding pCR rates around 30% for total neoadjuvant therapy versus 14% for standard radiochemotherapy in a meta-analysis [69][70][71].…”

Section: Discussionmentioning

confidence: 83%

Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas

Schem

Pfeffer

Ott

et al. 2022

Cancers

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Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5–42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6–8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.

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“…The detrimental effect on the mucosa, mostly with hypofractionated high dose regimens, seemed to be true notwithstanding the order and time between the radiotherapy and bevacizumab. However, there are also other publications revealing the safety of bevacizumab and radiotherapy combinations 42,43 . Aside from its antiangiogenic effect to improve tumor response, bevacizumab has been increasingly used to clinically control, stabilize, and hopefully revert the clinically symptomatic radiation-induced brain necrosis [44][45][46][47] .…”

Section: Discussionmentioning

confidence: 99%

Simulations on the efficacy of radiotherapy with different time schemes of antiangiogenic therapy

Tuzer

Yιlmaz

Ünlü

2021

Preprint

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The combination of radiotherapy and antiangiogenic agents has been suggested to be potent in tumor growth control compared to the application of antiangiogenic therapy or radiotherapy alone. Since radiotherapy is highly dependent on the oxygen level of the tumor area, antiangiogenic agents are utilized for the reoxygenation of tumor vasculature. We present a mathematical framework to investigate the efficacy of radiotherapy combined with antiangiogenic treatment. The framework consists of tumor cells, vasculature, and oxygenation levels evolving with time to mimic a tumor microenvironment. Non-linear partial differential equations (PDEs) are employed to simulate each component of the framework. Different treatment schemes are investigated to see the changes in tumor growth and oxygenation. To test combination schedules, radiation monotherapy, neoadjuvant, adjuvant, and concurrent cases are simulated. The efficiency of each therapy scheme on tumor growth control, the changes in tumor cell density, and oxygen levels shared by tumor cells are represented. The simulation results indicate that the application of radiotherapy after antiangiogenic treatment is more efficient in tumor growth control compared to other therapy schemes. The present study gives an insight into the possible interaction and timing of the combination of radiotherapy and antiangiogenic drug treatment.

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Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial

Cited by 32 publications

References 35 publications

A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy

A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy

Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas

Simulations on the efficacy of radiotherapy with different time schemes of antiangiogenic therapy

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