Effects of remedies made in patient setup process on residual setup errors and margins in head and neck cancer radiotherapy based on 2D image guidance.

AIM: Patient setup errors were aimed to be reduced in radiotherapy (RT) of head-and-neck (H&N) cancer. Some remedies in patient setup procedure were proposed for this purpose. BACKGROUND: RT of H&N cancer has challenges due to patient rotation and flexible anatomy. Residual position errors occurring in treatment situation and required setup margins were estimated for relevant bony landmarks after the remedies made in setup process and compared with previous results. MATERIALS AND METHODS: The formation process for thermoplastic masks was improved. Also image matching was harmonized to the vertebrae in the middle of the target and a 5 mm threshold was introduced for immediate correction of systematic errors of the landmarks. After the remedies, residual position errors of bony landmarks were retrospectively determined from 748 orthogonal X-ray images of 40 H&N cancer patients. The landmarks were the vertebrae C1-2, C5-7, the occiput bone and the mandible. The errors include contributions from patient rotation, flexible anatomy and inter-observer variation in image matching. Setup margins (3D) were calculated with the Van Herk formula. RESULTS: Systematic residual errors of the landmarks were reduced maximally by 49.8% (p ≤ 0.05) and the margins by 3.1 mm after the remedies. With daily image guidance the setup margins of the landmarks were within 4.4 mm, but larger margins of 6.4 mm were required for the mandible. CONCLUSIONS: Remarkable decrease in the residual errors of the bony landmarks and setup margins were achieved through the remedies made in the setup process. The importance of quality assurance of the setup process was demonstrated.

Evaluation of overall setup accuracy and adequate setup margins in pelvic image-guided radiotherapy: comparison of the male and female patients.

We evaluated adequate setup margins for the radiotherapy (RT) of pelvic tumors based on overall position errors of bony landmarks. We also estimated the difference in setup accuracy between the male and female patients. Finally, we compared the patient rotation for 2 immobilization devices. The study cohort included consecutive 64 male and 64 female patients. Altogether, 1794 orthogonal setup images were analyzed. Observer-related deviation in image matching and the effect of patient rotation were explicitly determined. Overall systematic and random errors were calculated in 3 orthogonal directions. Anisotropic setup margins were evaluated based on residual errors after weekly image guidance. The van Herk formula was used to calculate the margins. Overall, 100 patients were immobilized with a house-made device. The patient rotation was compared against 28 patients immobilized with CIVCO's Kneefix and Feetfix. We found that the usually applied isotropic setup margin of 8mm covered all the uncertainties related to patient setup for most RT treatments of the pelvis. However, margins of even 10.3mm were needed for the female patients with very large pelvic target volumes centered either in the symphysis or in the sacrum containing both of these structures. This was because the effect of rotation (p ≤ 0.02) and the observer variation in image matching (p ≤ 0.04) were significantly larger for the female patients than for the male patients. Even with daily image guidance, the required margins remained larger for the women. Patient rotations were largest about the lateral axes. The difference between the required margins was only 1mm for the 2 immobilization devices. The largest component of overall systematic position error came from patient rotation. This emphasizes the need for rotation correction. Overall, larger position errors and setup margins were observed for the female patients with pelvic cancer than for the male patients.

Estimation of adequate setup margins and threshold for position errors requiring immediate attention in head and neck cancer radiotherapy based on 2D image guidance.

BACKGROUND: We estimated sufficient setup margins for head-and-neck cancer (HNC) radiotherapy (RT) when 2D kV images are utilized for routine patient setup verification. As another goal we estimated a threshold for the displacements of the most important bony landmarks related to the target volumes requiring immediate attention. METHODS: We analyzed 1491 orthogonal x-ray images utilized in RT treatment guidance for 80 HNC patients. We estimated overall setup errors and errors for four subregions to account for patient rotation and deformation: the vertebrae C1-2, C5-7, the occiput bone and the mandible. Setup margins were estimated for two 2D image guidance protocols: i) imaging at first three fractions and weekly thereafter and ii) daily imaging. Two 2D image matching principles were investigated: i) to the vertebrae in the middle of planning target volume (PTV) (MID_PTV) and ii) minimizing maximal position error for the four subregions (MIN_MAX). The threshold for the position errors was calculated with two previously unpublished methods based on the van Herk's formula and clinical data by retaining a margin of 5 mm sufficient for each subregion. RESULTS: Sufficient setup margins to compensate the displacements of the subregions were approximately two times larger than were needed to compensate setup errors for rigid target. Adequate margins varied from 2.7 mm to 9.6 mm depending on the subregions related to the target, applied image guidance protocol and early correction of clinically important systematic 3D displacements of the subregions exceeding 4 mm. The MIN_MAX match resulted in smaller margins but caused an overall shift of 2.5 mm for the target center. Margins ≤ 5mm were sufficient with the MID_PTV match only through application of daily 2D imaging and the threshold of 4 mm to correct systematic displacement of a subregion. CONCLUSIONS: Adequate setup margins depend remarkably on the subregions related to the target volume. When the systematic 3D displacement of a subregion exceeds 4 mm, it is optimal to correct patient immobilization first. If this is not successful, adaptive replanning should be considered to retain sufficiently small margins.

No additional benefit of adding ifosfamide to docetaxel in castration-resistant metastatic prostate cancer.

BACKGROUND: In the treatment of many types of cancer, combination chemotherapy has been shown to be better than single-agent chemotherapy. The aim of our phase I-II clinical trial was to assess the efficacy and toxicity of docetaxel-ifosfamide combination chemotherapy in patients with castration-resistant metastatic prostate cancer (CRPC). PATIENTS AND METHODS: A total of 31 patients were enrolled to receive first-line chemotherapy consisting of 40-60 mg/m(2) docetaxel followed by 3.0 g/m(2) ifosfamide with mesna. All drugs were administered intravenously. The maximum duration of the chemotherapy was six cycles. The median age of the patients was 70 (range 58-82) years. Prostate specific antigen (PSA) responses were determined according to the PSA working group guidelines and all toxicities, time-to-progression and overall survival were determined according to the WHO criteria. RESULTS: The objective PSA response rate was 32% in 11/31 patients. The mean PSA value at baseline was 300 (range 2.5-1577) µg/l. The overall median survival was 14.1 months; 15 patients were alive at a median follow-up time of 18 months. The observed side-effects were as expected, with grade 3-4 neutropenia developing in 38% of the cycles, whereas febrile neutropenia occurred in only 12% of the patients. The median number of administered cycles was 4.8. No acute hypersensitivity reactions were observed. Transient renal insufficiency developed in two patients, thus necessitating dose reductions. CONCLUSION: The combination of docetaxel and ifosfamide seems to be well-tolerated and has some activity in patients with CRPC. However, newer docetaxel-based combination chemotherapy regimens need to be further developed in other to provide more efficacious and well-tolerated treatment options for earlier phases of CRPC.