Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

OBJECTIVES: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. METHODS: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. RESULTS: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). CONCLUSIONS: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

Randomized phase II trial of cisplatin, etoposide, and radiation followed by gemcitabine alone or by combined gemcitabine and docetaxel in stage III A/B unresectable non-small cell lung cancer.

PURPOSE: Southwest Oncology Group 9504 demonstrated the feasibility and potential benefit of docetaxel consolidation after etoposide, cisplatin, and radiotherapy in patients with locally advanced non-small cell lung cancer. Our study assessed consolidation with either gemcitabine alone or with docetaxel after identical chemoradiation as used in Southwest Oncology Group 9504. METHODS: Patients with stage III non-small cell lung cancer and good performance status were included. Treatment consisted of concurrent cisplatin 50 mg/m on days 1 and 8 plus etoposide 50 mg/m on days 1 to 5 for two 28-day cycles plus radiotherapy (62 Gy, 2 Gy daily in 31 fractions over 7 weeks), followed by randomization to either gemcitabine 1000 mg/m on days 1 and 8 (G) or gemcitabine 1000 mg/m on days 1 and 8 plus docetaxel 75 mg/m on day 1 (GD) every 21 days for three cycles. RESULTS: Eighty-three patients were entered, 81 received induction therapy, and 64 were randomized (32 in each arm). Grade 3 or four events, including neutropenia (56.3% vs. 28.1%, p = 0.03), anemia (18.8% vs. 3.1%, p = 0.05), and fatigue (15.6% vs. 6.3%, p = NS), were more frequent with GD compared with G. Among all patients, median survival from registration was 20.8 months (95% confidence interval: 16.4-33.8), and 2-year survival was 46.7% (95% confidence interval: 35.6-57.1). From randomization, median progression-free survival was 5.4 months for G and 13.4 months for GD, and median survival was 16.1 months for G and 29.5 months for GD. Two-year survival rates were 40.6% for G and 55.7% for GD. CONCLUSION: The doublet, as expected, resulted in more toxicity, particularly myelosuppression and fatigue. Survival associated with the GD treatment arm of this trial exceeds that of previously reported trials.

Dosimetric comparison of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: evaluation of the impact on daily dose coverage.

PURPOSE: To investigate the dosimetric impact of using 4D CT and multiphase (helical) CT images for treatment planning target definition and the daily target coverage in hypofractionated stereotactic body radiotherapy (SBRT) of lung cancer. MATERIALS AND METHODS: For 10 consecutive patients treated with SBRT, a set of 4D CT images and three sets of multiphase helical CT scans, taken during free-breathing, end-inspiration and end-expiration breath-hold, were obtained. Three separate planning target volumes (PTVs) were created from these image sets. A PTV(4D) was created from the maximum intensity projection (MIP) reconstructed 4D images by adding a 3mm margin to the internal target volume (ITV). A PTV(3CT) was created by generating ITV from gross target volumes (GTVs) contoured from the three multiphase images. Finally, a third conventional PTV (denoted PTV(conv)) was created by adding 5mm in the axial direction and 10mm in the longitudinal direction to the GTV (in this work, GTV=CTV=clinical target volume) generated from free-breathing helical CT scans. Treatment planning was performed based on PTV(4D) (denoted as Plan-1), and the plan was adopted for PTV(3CT) and PTV(conv) to form Plan-2 and Plan-3, respectively, by superimposing "Plan-1" onto the helical free-breathing CT data set using modified beam apertures that conformed to either PTV(3CT) or PTV(conv). We first studied the impact of PTV design on treatment planning by evaluating the dosimetry of the three PTVs under the three plans, respectively. Then we examined the effect of the PTV designs on the daily target coverage by utilizing pre-treatment localization CT (CT-on-rails) images for daily GTV contouring and dose recalculation. The changes in the dose parameters of D(95) and D(99) (the dose received by 95% and 99% of the target volume, respectively), and the V(p) (the volume receiving the prescription dose) of the daily GTVs were compared under the three plans before and after setup error correction. RESULTS: For all 10 patients, we found that the PTV(4D) consistently resulted in the smallest volumes compared with the other PTV's (p=0.005). In general, the plans generated based PTV(3CT) could provide reasonably good coverage for PTV(4D), while the reverse can only achieve 90% of the planned values for PTV(3CT). The coverage of both PTV(4D) and PTV(3CT) in Plan-3 generally reserves the original planned values in terms of D(95), D(99), and V(p,) with the average ratios of 0.996, 0.977, and 0.977, respectively, for PTV(3CT), and 1.025, 1.025, and 1.0, respectively, for PTV(4D). However, it increased the dose significantly to normal lung tissue. Additionally, the plans generated using the PTV(4D) presented an equivalent daily target coverage compared to the plans generated using the PTV(3CT) (p=0.953) and PTV(conv) (p=0.773) after setup error correction. Consequently, this minimized the dose to the surrounding normal lung. CONCLUSION: Compared to the conventional approach using helical images for target definition, 4D CT and multiphase 3D CT have the advantage to provide patient-specific tumor motion information, based on which such designed PTVs could ensure daily target coverage. 4D CT-based treatment planning further reduces the amount of normal lung being irradiated while still providing a good target coverage when image guidance is used.

Benefit of three-dimensional image-guided stereotactic localization in the hypofractionated treatment of lung cancer.

PURPOSE: The aim of this study was to investigate the benefit of image-guided stereotactic localization in the hypofractionated treatment for medically inoperable non-small-cell lung cancer. METHODS AND MATERIALS: A stereotactic body localizer (SBL) system was used for patient immobilization, reliable image registration among multiphase computed tomography (CT) scanning, and image-guided stereotactic localization. Three sets of CT scans were taken (free breathing, and breath holding at the end-tidal inspiration and expiration, respectively) to contrast target motion. Target delineation was performed on all 3 sets of images and the combination of the targets forms an internal target volume (ITV). In this retrospective study of treatment dose verification, we performed image fusion between the simulation CT scan and each pretreatment CT scan to obtain the same target and critical structure information. The same treatment plans were reloaded onto each pretreatment CT scan with their respective stereotactic coordinate system. The changes in dose distributions were assessed by dose-volume histograms of the planning target volume (PTV) and the critical structures before and after isocenter corrections which were prompted by image-guided stereotactic localization. We compared D95, D99, and V95 for the PTV and internal target volume, and V20 and V30 for the ipsilateral lung. RESULTS: Our retrospective study for 10 patients with 40 dose reconstructions showed that the average D95, D99, and V95 of the PTVs are 92.1%, 88.1%, and 95.8% of the planned values before isocenter corrections. With the corrections, all of these values are improved to 100% of the planned values. CONCLUSIONS: Three-dimensional image guidance is crucial for stereotactic radiotherapy of lung tumors.

Stereotactic IMRT for prostate cancer: setup accuracy of a new stereotactic body localization system.

The purpose of this work is to prospectively assess the setup accuracy that can be achieved with a stereotactic body localizer (SBL) in immobilizing patients for stereotactic intensity-modulated radiotherapy (IMRT) for prostate cancer. By quantifying this important factor and target mobility in the SBL, we expect to provide a guideline for selecting planning target volume margins for stereotactic treatment planning. We analyzed data from 40 computed tomography (CT) studies (with slice thickness of 3 mm) involving 10 patients with prostate cancer. Each patient had four sets of CT scans during the course of radiotherapy. For the purpose of this study, all four sets of CT scans were obtained with the patients immobilized in a customized body pillow formed by vacuum suction. Unlike other immobilization devices, this system consists not only of a customized body pillow, but also of a fixation sheet used to suppress patient respiratory motion, a stereotactic body frame to provide stereotaxy, and a carbon fiber base board to which both the body cushion and the frame are affixed. We identified four bony landmarks and measured their coordinates in the stereotactic body frame on each set of CT scans. The displacements of the bony landmarks from their corresponding positions on the simulation scan (first CT scan) were analyzed in three dimensions in terms of overall, systematic, and random categories. The initial planned isocenter was also marked on the patients' skin with fiducials for each CT study. The distance from each bony landmark to the fiducial-based isocenter was measured and compared among the four sets of CT scans. The deviations in distances were also compared to those measured from the landmarks to the stereotactic frame center, in order to determine the effectiveness of the rigid body frame in positioning patients with prostate cancer. Target inter-fraction motion in this system was also studied for five patients by measuring the deviations in distances from the target geometric center to the bony landmarks. Our results showed that the overall setup accuracy had standard deviations (SDs) of 2.58 mm, 2.41 mm, and 3.51 mm in lateral (LAT), anterior-posterior(AP), and superior-inferior (SI) directions, respectively. The random component had SDs of 1.72 mm, 2.06 mm, and 2.79 mm, and the systematic component showed SDs of 0.92 mm, -0.27 mm, and 0.90 mm in these three directions. In terms of three-dimensional vector, the mean displacement over 116 measurements was 3.0 mm with an SD of 1.29 mm. Compared to the rigid reference, the skin-mark-based reference was less reliable for patient repositioning in terms of reproducing known bony landmark positions. The mean target mobility relative to the bony landmarks was 2.22 +/- 3.45 mm, 0.17 +/- 1.11 mm, and 0.11 +/- 2.69 mm in the AP, LAT, and SI directions, respectively. In conclusion, the body immobilization system has the ability to immobilize prostate cancer patients with satisfactory setup accuracy for fractionated extracranial stereotactic radiotherapy. A rigid frame system serves as a reliable alignment reference in terms of repositioning patients into the planning position, while skin-based reference showed larger deviations in repositioning patients.