Prediction of Response to Neoadjuvant Therapy in Rectal Cancer
Information source: Colchester General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Rectal Neoplasms
Intervention: PET-CT Scan (Device)
Phase: N/A
Status: Not yet recruiting
Sponsored by: Colchester General Hospital Official(s) and/or principal investigator(s): Tan Arulampalam, MD, Principal Investigator, Affiliation: ICENI Centre director
Overall contact: Medhat S Alaker, MCh, MD(Res), Phone: +447746147851, Email: medhat.alaker@nhs.net
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.
Clinical Details
Official title: Prediction of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic
Primary outcome: Accuracy of Texture analysis PET-CT
Secondary outcome: Correlation between tumour response parameters to survival.Accuracy of Texture analysis MRI
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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Medhat S Alaker, MCh, MD(Res), Phone: +447746147851, Email: medhat.alaker@nhs.net
Colchester General Hospital, Colchester CO4 5JL, United Kingdom
Additional Information
Related publications: 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. Review. Bundschuh RA, Dinges J, Neumann L, Seyfried M, Zsótér 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 ¹⁸F-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. 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. 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. Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suárez 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. 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.
Starting date: September 2015
Last updated: May 8, 2015
|