Cancers 2022 Jul 28
MORPHEUS Phase II-III Study: A Pre-Planned Interim Safety Analysis and Preliminary Results.
Abstract
Background
We explored image-guided adaptive endorectal brachytherapy patients electing non-operative management for rectal cancer. We present the first pre-planned interim analysis.
Methods
In this open-label phase II-III randomized study, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with 5-FU/Capecitabine. They were randomized 1:1 to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A) or three weekly adaptive brachytherapy (IGAEBT) boosts totaling 30 Gy (Arm B). Patient characteristics and toxicity are presented using descriptive analyses; TME-free survival between arms with the intention to treat the population is explored using the Kaplan-Meier method.
Results
A total of 40 patients were in this analysis. Baseline characteristics were balanced; acute toxicities were similar. Complete clinical response (cCR) was 50% (n = 10/20) in Arm A and 90% in Arm B (n = 18/20). Median follow-up was 1.3 years; 2-year TME-free survival was 38.6% (95% CI: 16.5-60.6%) in the EBRT arm and 76.6% (95% CI: 56.1-97.1%) in the IGAEBT arm.
Conclusions
Radiation intensification with IGAEBT is feasible. This interim analysis suggests an improvement in TME-free survival when comparing IGAEBT with EBRT, pending confirmation upon completion of this trial.
Related Questions
In a patient with rectal cancer, when would you consider brachytherapy monotherapy or brachytherapy boost after CRT?
For a patient with cT2N0 disease, the most appropriate use of brachytherapy would be sequential with pelvic radiotherapy, the bulk of data being with long-course CRT. Brachy can either be done prior to CRT or sequenced afterwards. We routinely use brachytherapy in appropriate candidates in our pract...
What treatment sequence do you follow for patients with rectal cancer who are candidates for both PROSPECT and TNT/Watch and wait?
Thanks for this question. I am not sure whether this is up to us. This is up to our patients to choose which modality they would like to omit (radiation vs surgery). I would point out that a good quality MRI rectum should be performed to r/o any T4/N2 disease or potential requirement for APR. Otherw...
Should we be shrinking rectal cancer fields?
I think this is a good point. However, I think we need to consider the nuances of the question. First PROSPECT included: patients that "had cT2N+, cT3N-, cT3N+ rectal cancers deemed appropriate for neoadjuvant therapy prior to low anterior resection with TME. Patients with distal, T4 tumors, threate...
What is the optimal treatment for a locally advanced rectal cancer on the anterior wall abutting the prostate in a medically inoperable patient with a remote history of LDR brachytherapy for low risk prostate cancer?
I would start with chemotherapy if that is an option and tailor RT dose to some extent based on response. If there is great response even local excision can be evaluated? Rectal and urethral complications are high and I have seen patients developing these complications even with 45 to 50.4 Gy preop ...