Prediction of Response to Neoadjuvant Therapy in Rectal Cancer

NCT ID: NCT02439086

Last Updated: 2015-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-09-30

Brief Summary

The purpose of this study is to determine whether 18F-FDG-PET-CT and texture analysis of MRI performed 9 weeks after Neoadjuvant Chemo-radiotherapy in patients with locally advanced rectal cancer has the ability to identify patients with Complete Response.

Detailed Description

In recent years, treatment with NCRT has revolutionised management of LARC. In addition to downstaging the tumour in 62% of cases, half of which decrease by more than 1 T stage; pathological complete response (pCR), with no viable tumour cells left in resected specimens, was demonstrated in up to 30% of patients. Only 3% of patients showed progressive disease. It has recently been shown that those with pathological complete response survive longer than those with partial response, with figures for 5-year disease free survival quoted between 83 and 91% for pCR; versus 65% for non pCR. Furthermore, it has been argued that those tumours which are sensitive to radiotherapy have a favourable biological tumour profile, with fewer propensities to recur or to metastasise than aggressive non-radiosensitive tumours. The key is to accurately be able to identify patients who exhibit complete response to radiotherapy, or to predict those who might show complete response.

Positron Emission Tomography (18-F-FDG-PET-CT) as a tumour biomarker after radiotherapy has been shown to be able to predict patients who have responded to chemo radiotherapy, with a sensitivity of 79% and specificity of 88%. Texture Analysis (TA) assesses the aggressiveness of the tumour by assessing intra-tumoural heterogeneity. It has already been shown to be effective in assessing biological characteristics of solid tumours, including the oesophagus, breast, and liver.

The aim of this study is to utilise these two novel molecular imaging techniques to identify rectal cancer patients who have responded completely from neoadjuvant chemo-radiotherapy. Parameters will be calculated as changes in measurable variables from baseline to post treatment scans.

Pilot data The watch-and-wait approach could potentially reduce treatment-related toxicity in selected rectal cancer patients who have a clinical complete response (cCR) after chemoradiation. The "watch & wait" protocol has been adopted from studies performed in Brazil, United Kingdom, and the Netherlands.

Studies indicate that accurate assessment of response to neoadjuvant therapy is the key to selecting patients who will benefit from the watch & wait approach. Therefore, determining the modality with highest accuracy and cost-effectiveness has been the holy grail of managing locally advanced rectal cancers.

A study performed by our Chief Investigator on the efficiency and accuracy of 18-F-FDG-PET-CT has concluded that PET-CT has a proven role and is cost effective in monitoring therapy and in detecting recurrence in colorectal cancers; as this technology combines picomolar sensitivity with high-resolution CT imaging. It has therefore shown to be more sensitive than plain CT imaging in detecting recurrence and monitoring response to therapy. In other studies, the reported accuracy for PET-CT in determining responsiveness to NCRT was around 80%. Baseline PET-CT and subsequent PET-CT parameters, including SUV-based measurements, have been shown to be highly accurate in determining responses to NCRT.

Texture Analysis is a biomarker technique that measures heterogeneity within solid tumours. Textural parameters (coefficient of variation [COV], skewness, and kurtosis) applied on PET-CT images has been shown to be able to predict response to NCRT, and to predict survival. A pilot study performed at our institution has indeed showed that textural parameters performed on pelvic MRI were associated with improved overall survival and disease- free survival.

Study hypothesis

• PET-CT restaging done at 9 weeks rather than 6 weeks will be a more accurate predictor in assessing response to NCRT.
• Texture analysis of rectal MRI scans is a strong biomarker in assessing tumour response and identifying patients with Complete Response.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Long Course Radiotherapy

all patients diagnosed with rectal cancer, amenable for neoadjuvant chemoradiotherapy, who agree to participate in this study will undergo 2 PET-CT scans: at baseline and 9 weeks after commencing therapy.

Group Type: EXPERIMENTAL

PET-CT Scan

Intervention Type: DEVICE

patients will have 2 PET CT scans: one before radiotherapy, and one 9 weeks after.

Interventions

PET-CT Scan

patients will have 2 PET CT scans: one before radiotherapy, and one 9 weeks after.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients with biopsy-proven confirmed rectal cancer
• MRI stage: T3/T4 and/or N1/N0.
• No contraindication to MRI and PET-CT.

Exclusion Criteria

• Contraindication to MRI and/or PET-CT.
• Inability to consent.
• Severe claustrophobia.
• Distant metastases.
• Synchronous tumour.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anglia Ruskin University

OTHER

Sponsor Role: collaborator

Colchester General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Medhat Alaker

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tan Arulampalam, MD

Role: PRINCIPAL_INVESTIGATOR

ICENI Centre director

Locations

Colchester General Hospital

Colchester, , United Kingdom

Countries

United Kingdom

Central Contacts

Medhat S Alaker, MCh, MD(Res)

Role: CONTACT

medhat.alaker@nhs.net

+447746147851

Tan Arulampalam, MD

Role: CONTACT

laptan1@yahoo.org.uk

01206742456

References

Arulampalam TH, Costa DC, Loizidou M, Visvikis D, Ell PJ, Taylor I. Positron emission tomography and colorectal cancer. Br J Surg. 2001 Feb;88(2):176-89. doi: 10.1046/j.1365-2168.2001.01657.x.

Reference Type: BACKGROUND

PMID: 11167864 (View on PubMed)

Bundschuh RA, Dinges J, Neumann L, Seyfried M, Zsoter N, Papp L, Rosenberg R, Becker K, Astner ST, Henninger M, Herrmann K, Ziegler SI, Schwaiger M, Essler M. Textural Parameters of Tumor Heterogeneity in (1)(8)F-FDG PET/CT for Therapy Response Assessment and Prognosis in Patients with Locally Advanced Rectal Cancer. J Nucl Med. 2014 Jun;55(6):891-7. doi: 10.2967/jnumed.113.127340. Epub 2014 Apr 21.

Reference Type: BACKGROUND

PMID: 24752672 (View on PubMed)

HABR-GAMA, A., PEREZ, R., LYNN, P., SãO JULIãO, G. and GAMA RODRIGUES, J., 2012. Selective non-operative management of distal rectal cancer: The Watch & Wait Protocol. In: R. SCHIESSEL and P. METZGER, eds, Springer Vienna, pp. 43-53.

Reference Type: BACKGROUND

Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.

Reference Type: BACKGROUND

PMID: 15383798 (View on PubMed)

Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.

Reference Type: BACKGROUND

PMID: 20692872 (View on PubMed)

Niccoli-Asabella A, Altini C, De Luca R, Fanelli M, Rubini D, Caliandro C, Montemurro S, Rubini G. Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery. Biomed Res Int. 2014;2014:952843. doi: 10.1155/2014/952843. Epub 2014 May 4.

Reference Type: BACKGROUND

PMID: 24877151 (View on PubMed)

Aker M, Ganeshan B, Afaq A, Wan S, Groves AM, Arulampalam T. Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer. Dis Colon Rectum. 2019 Feb;62(2):163-170. doi: 10.1097/DCR.0000000000001224.

Reference Type: DERIVED

PMID: 30451764 (View on PubMed)

Other Identifiers

TBA (ethics)

Identifier Type: -

Identifier Source: org_study_id