A perspective on the current treatment strategies for locally advanced rectal cancer

Avallone, Antonio; Aloj, Luigi; Aprile, Giuseppe; Rosati, Gerardo; Budillon, Alfredo

doi:10.1016/j.biocel.2015.06.002

Cited by 3 publications

(5 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although, preoperative multimodality treatment advances have remarkably improved the outcomes of patients with locally advanced rectal cancer (LARC), there is still a clear need to optimize the management of these patients (1). The evidence that LARC represents a widely heterogeneous group of tumors with different prognostic features has prompted to pursue different risk-adapted treatment strategies in order to maximize benefit and minimize toxicity of treatment (1).…”

Section: Introductionmentioning

confidence: 99%

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

There is an unmet need for predictive biomarkers of the clinical benefit of antiangiogenic drugs. The aim of the present study was to prospectively evaluate the value of 18 F-FDG-PET/CT performed during and after preoperative chemoradiotherapy with bevacizumab for the prediction of complete pathologic tumor regression and survival in magnetic resonance imaging (MRI)-defined high-risk locally advanced rectal cancer (LARC) patients. Methods Sixty-one patients treated in a non-randomized phase II study (BRANCH) with concomitant or sequential (4 days before chemoradiotherapy) administration of bevacizumab with preoperative chemoradiotherapy were included. 18 F-FDG PET/CT was performed at baseline, 11 days after the beginning of chemoradiotherapy (early) and before surgery (late). Metabolic changes were compared with pathological complete (TRG1) vs incomplete (TRG2-5) tumor regression, progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curves were calculated for those 18 F-FDG-PET/CT parameters that significantly correlated with TRG1. Results Early total lesion glycolysis (TLG-early) and its percent change compared to baseline (ΔTLG-early) could discriminate TRG1 from TRG2-5. Only ROC analysis of ΔTLG-early showed an area under curve (AUC) > 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4% specificity) for identifying TRG1. Late metabolic assessment could not discriminate between the two groups. After a median follow-up of 98 months (range 77-132) metabolic responders (ΔTLG-early ≥ 59.5%) demonstrated a significantly higher 10-year PFS (89.3% vs 63.6%, p=0.02) and CSS (92.9% vs 72.6%, p=0.04) compared to incomplete metabolic responders. Conclusion Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy and provide further support for the use of early 18 F-FDG-PET/CT evaluation to predict pathological response and survival in the preoperative treatment of patients with LARC. ΔTLG-early showed the best accuracy in predicting TRG and may be particularly useful in guiding treatment modifying decisions during preoperative chemoradiotherapy based on expected response. Preoperative Radiochemotherapy with Bevacizumab in High RiskLocally Advanced F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival to 18 http://jnm.snmjournals.org/content/early/2019/03/14/jnumed.118.222604 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

show abstract

Section: Introductionmentioning

confidence: 99%

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Colorectal cancer (CRC) is the third most common cancer in males and females with an estimated worldwide annual incidence of 1.3 million [ 1 , 2 ] and with rectal cancer representing a 30% of its totality [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although the introduction of total mesorectal excision and preoperative radiotherapy (RT) have been revolutionary and resulted in improved local control after curative resection for rectal cancer, local relapses and distant metastasis still occur and remain a cause of recurrence worldwide [ 6 ]. This is particularly true for the “high risk” locally advanced rectal cancer (LARC) patients, also defined as the “ugly” subgroup [ 3 ]. Therefore several strategies have attempted to improve local control and reduce distant recurrence adding new cytotoxic agents into the standard treatment strategy, but this is still an ongoing challenging process [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…This is particularly true for the “high risk” locally advanced rectal cancer (LARC) patients, also defined as the “ugly” subgroup [ 3 ]. Therefore several strategies have attempted to improve local control and reduce distant recurrence adding new cytotoxic agents into the standard treatment strategy, but this is still an ongoing challenging process [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53

Terranova-Barberio

Pecori

Roca

et al. 2017

J Exp Clin Cancer Res

Self Cite

View full text Add to dashboard Cite

BackgroundRecurrence with distant metastases has become the predominant pattern of failure in locally advanced rectal cancer (LARC), thus the integration of new antineoplastic agents into preoperative fluoropyrimidine-based chemo-radiotherapy represents a clinical challenge to implement an intensified therapeutic strategy.The present study examined the combination of the histone deacetylase inhibitor (HDACi) valproic acid (VPA) with fluoropyrimidine-based chemo-radiotherapy on colorectal cancer (CRC) cells.MethodsHCT-116 (p53-wild type), HCT-116 p53−/− (p53-null), SW620 and HT29 (p53-mutant) CRC cell lines were used to assess the antitumor interaction between VPA and capecitabine metabolite 5′-deoxy-5-fluorouridine (5′-DFUR) in combination with radiotherapy and to evaluate the role of p53 in the combination treatment. Effects on proliferation, clonogenicity and apoptosis were evaluated, along with γH2AX foci formation as an indicator for DNA damage.ResultsCombined treatment with equipotent doses of VPA and 5′-DFUR resulted in synergistic effects in CRC lines expressing p53 (wild-type or mutant). In HCT-116 p53−/− cells we observed antagonist effects. Radiotherapy further potentiated the antiproliferative, pro-apoptotic and DNA damage effects induced by 5′-DFUR/VPA combination in p53 expressing cells.ConclusionsThese results highlighted the role of VPA as valuable candidate to be added to preoperative chemo-radiotherapy in LARC. On these bases we launched the ongoing phase I/II study of VPA and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer (V-shoRT-R3).Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0647-5) contains supplementary material, which is available to authorized users.

show abstract

“…Despite the introduction of the screening programs, several patients are diagnosed in a locally advanced stage. Preoperative radio-chemotherapy (pCRT) associated with total mesorectal excision (TME) is the standard care procedure for locally advanced rectal cancer (LARC) [2, 3]. TME is linked to morbidity and complications, therefore in clinical practise there is an increase of conservative treatment strategies application for patients with substantial tumor regression after pCRT and “wait and see” policy for patients with complete pathological regression.…”

Section: Introductionmentioning

confidence: 99%

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

Petrillo

Granata

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

PurposeTo investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).Methods75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated.Results55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR.ConclusionsCRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR.

show abstract

A perspective on the current treatment strategies for locally advanced rectal cancer

Cited by 3 publications

References 64 publications

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

Contact Info

Product

Resources

About

A perspective on the current treatment strategies for locally advanced rectal cancer

Cited by 3 publications

References 64 publications

18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

Contact Info

Product

Resources

About

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

¹⁸F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer