Factors associated with improved biochemical response to neoadjuvant androgen deprivation therapy before definitive radiation therapy in prostate cancer patients.

BACKGROUND: In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients. METHODS: We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011. RESULTS: A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001). CONCLUSIONS: Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.

Utilization of custom electron bolus in head and neck radiotherapy.

Conventional methods of treating superficial head and neck tumors, such as the wedge pair technique or the use of multiple electron fields of varying energies, can result in excellent tumor control. However, in some cases, these techniques irradiate healthy tissue unnecessarily and/or create hot and cold spots in junction regions, particularly in patients with complex surface contour modification or varying planning target volume (PTV) thickness. The objective of this work is to demonstrate how bolus electron conformal therapy can be used for these patients. Two patients treated using this technique are presented. The first patient was diagnosed with malignant fibrous histiocytoma involving the right ear concha and was treated with 12-MeV electrons. The second patient was diagnosed with acinic cell carcinoma of the left parotid gland and was treated with 20-MeV electrons after having undergone a complete parotidectomy. Each patient's bolus was designed using bolus design tools implemented in an in-house treatment-planning system (TPS). The bolus was fabricated using a computer-controlled milling machine. As part of the quality assurance process to ensure proper fabrication and placement of the bolus, the patients underwent a second computed tomography (CT) scan with the bolus in place. Using that data, the final dose distribution was computed using the Philips Pinnacle(3) TPS (Philips Medical Systems, Andover, MA). Results showed that the 90% isodose surface conformed well to the PTV and that the dose to critical structures such as cord, brain, and lung was well below tolerance limits. Both patients showed no evidence of disease six months post-radiotherapy. In conclusion, electron bolus conformal therapy is a viable option for treating head and neck tumors, particularly patients having a variable thickness PTV or surface anatomy with surgical defects.

Enhanced dynamic wedge factors at off-axis points in asymmetric fields.

Several recent reports have described methods for calculating enhanced dynamic wedge factors (EDWFs). Many of these reports use the monitor-unit (MU) fraction method to predict EDWFs as a function of field size. Although simple in approach, MU fraction methods do not produce accurate EDWFs in large or asymmetric fields. A recently described technique, based on the MU fraction method works well for large and asymmetric fields, but only when the calculation point is in the center of the field. Other existing methods based on beam-segment superposition do not have this limitation. These beam summation methods, however, are difficult to implement in routine clinical MU calculation schemes. In this paper, we present a simple calculation method that estimates EDWFs at off-axis calculation points in both symmetric and asymmetric fields. Our method, which also is based on the MU fraction method, similarly uses empirically determined field-size corrections but also applies wedged-field profiles to estimate EDWFs that are independent of calculation-point location and field symmetry. EDWF measurements for a variety of field sizes and calculation-point locations for both 6- and 18-MV x-ray beams were performed to validate our calculations and those of our ADAC Pinnacle3 Treatment Planning System. The disagreement between the calculated and measured EDWFs over the useful clinical range of field sizes and calculation-point locations was less than 2%. The worst disagreement was 3% and occurred at a point 8.5 cm from the center of an asymmetric 25 (wedged direction)x20 cm2 60 degrees-wedged field. Detailed comparisons of measurements with calculations and wedge factors obtained from the ADAC Pinnacle3 Treatment Planning System will be presented. In addition, the strengths and weaknesses of this calculation method will be discussed.

A Monte Carlo dosimetry-based evaluation of the 7Li(p,n)7Be reaction near threshold for accelerator boron neutron capture therapy.

Advanced methods of boron neutron capture therapy (BNCT) use an epithermal neutron beam in conjunction with tumor-targeting boron compounds for irradiation of glioblastomas and metastatic melanomas. A common neutron-producing reaction considered for accelerator-based BNCT is 7Li(p,n)7Be, whose cross section increases very rapidly within several tens of keV of the reaction threshold at 1.88 MeV. Operation in the proton energy region near threshold will have an appreciable thick target neutron yield, but the neutrons produced will have relatively low energies that require little moderation to reach the epithermal range desirable for BNCT. Because of its relatively low projected accelerator cost and the portability of the neutron source/target assembly, BNCT based on the near-threshold technique is considered an attractive candidate for widespread hospital use. A systematic Monte Carlo N-Particle (MCNP) investigation of the dosimetric properties of near-threshold neutron beams has been performed. Results of these studies indicate that accelerator proton energies between 1.93 and 1.99 MeV, using 5 cm of H2O moderator followed by thin 6Li and Pb shields, can provide therapeutically useful beams with treatment times less than one hour and accelerator currents less than 5 mA.