External beam radiation treatment (EBRT) is a popular method for treating prostate cancer (CaP) involving destroying tumor cells with ionizing radiation. Following EBRT, biochemical failure has been linked with disease recurrence. However, there is a need for methods for evaluating early treatment related changes to allow for an early intervention in case of incomplete disease response. One method for looking at treatment evaluation is to detect changes in MRI markers on a voxel-by-voxel basis following treatment. Changes in MRI markers may be correlated with disease recurrence and complete or partial response. In order to facilitate voxel-by-voxel imaging related treatment changes, and also to evaluate morphologic changes in the gland post treatment, the pre- and post-radiated MRI must first be brought into spatial alignment via image registration. However, EBRT induces changes in the prostate volume and distortion to the internal anatomy of the prostate following radiation treatment. The internal substructures of the prostate, the central gland (CG) and peripheral zone (PZ), may respond to radiation differently, and their resulting shapes may change drastically. Biomechanical models of the prostate that have been previously proposed tend to focus on how external forces affect the surface of the prostate (not the internals), and assume that the prostate is a volume-preserving entity. In this work we present DoCD, a biomechanical model for automatically registering pre-, post-EBRT MRI with the aim of expressly modeling the (1) changes in volume, and (2) changes to the CG and PZ. DoCD was applied to a cohort of 30 patients and achieved a root mean square error of 2.994 mm, which was statistically significantly better a traditional biomechanical model which did not consider changes to the internal anatomy of the prostate (mean of 5.071 mm).

Background

We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers.

Methods

Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1.

Findings

The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable.

Interpretation

Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.