Bart Frizzell

Randomized Trial to Assess the Impact of Venlafaxine and Soy Protein on Hot Flashes and Quality of Life in Men With Prostate Cancer

PURPOSE Hot flashes occur in approximately 80% of androgen-deprived men. Few intervention studies have been conducted to relieve hot flashes in men. PATIENTS AND METHODS Eligible androgen-deprived men were randomly assigned to one of four daily regimens (2 × 2 factorial design) for 12 weeks: milk protein powder and placebo pill, venlafaxine and milk protein powder, soy protein powder and placebo pill, or venlafaxine and soy protein powder. The primary end point was hot flash symptom severity score (HFSSS), defined as number of hot flashes times severity. The secondary end point was quality of life (QoL), assessed by using the Functional Assessment of Cancer Therapy-Prostate. RESULTS In all, 120 men age 46 to 91 years participated. Most were white (78%) and overweight or obese (83%). Toxicity was minimal. Neither venlafaxine nor soy protein alone or in combination had a significant effect on HFSSS. Soy protein, but not venlafaxine, improved measures of QoL. CONCLUSION In androgen-deprived men, neither venlafaxine nor soy proved effective in reducing hot flashes. Interventions that appear effective for decreasing hot flashes in women may not always turn out to be effective in men.

Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

PURPOSE Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. METHODS AND MATERIALS A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. RESULTS There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. CONCLUSIONS SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

Dietary and Serum Lycopene Levels in Prostate Cancer Patients Undergoing Intensity-Modulated Radiation Therapy

Tomato products, good sources of lycopene, may lower the incidence of prostate cancer, but data on the effectiveness of lycopene supplementation during radiation therapy are lacking. This study aimed to evaluate the tolerance and acceptance of three different amounts (4, 8, or 12 oz) of tomato juice (TJ) and their effect on serum lycopene during radiotherapy in 20 men with localized prostate cancer. Participants were randomized into a control group or one of three intervention groups who consumed TJ daily during treatment. Dietary lycopene intake was estimated using the National Cancer Institute (NCI) Diet History Questionnaire, and gastrointestinal tolerance of TJ was evaluated using the NCI Cancer Therapy Evaluation Program: Common Toxicity Criteria v 2.0. Serum and TJ lycopene levels were measured by liquid chromatography-mass spectrometry. TJ was well tolerated without any gastrointestinal side effects, and increased serum lycopene levels were observed in the 8 and 12 oz groups from baseline to endpoint. No correlation between serum and dietary lycopene was detected. Despite no reported change in dietary intake, non-significant weight loss was observed in the control group but not the intervention group participants. A significant positive correlation between serum lycopene, weight, and body mass index, and a negative correlation between serum lycopene and piror nutritional supplement use was detected. Weight change should be monitored and evaluated during treatment. Larger clinical trials are needed to validate the use of TJ to increase serum/dietary lycopene intake and correlate with side effects during radiotherapy in men with prostate cancer.

A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer

Background. Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. Methods. We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. Results. After 12 weeks, patients on JP had significantly higher serum α-carotene (P = .009), β-carotene (P < .0001), and lutein (P = .003) but did not differ significantly in p27 (P = .23) or Ki-67 (P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. Conclusions. Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.

Urinary Specific Gravity (USG) as an Assessment Tool for the Management of Dehydration in Head and Neck Cancer Patients Receiving Chemo-Radiation with Weekly Cisplatin

Background: Concomitant chemo-radiation therapy (CRT) with cisplatin is the mainstay of treatment for patients with locally advanced head and neck cancer. Nephrotoxicity is a well-documented adverse effect of cisplatin, which is exacerbated by dehydration, a common complication in this group of patients. This study prospectively assessed the utility of urine specific gravity (USG) as a guide for fluid replacement, and its preventive effect in cisplatin induced nephrotoxicity. Methods: Patients with head and neck cancer who received CRT with weekly cisplatin at our institution were included in the analysis. All patients received 1 L normal saline (NS) with 1 g of magnesium and 10 mEq of potassium pre and post cisplatin. USG was measured weekly, patients with USG>1.020 was considered dehydrated and received 2 L NS twice weekly. Those patients with USG>1.025 while on the twice-weekly regimen were deemed very dehydrated and received 2 L NS daily. The primary objective was renal toxicity of any grade. Results: 44 patients were identified and completed CRT in less than 7.5 weeks. Eighteen of 44 patients (41%) had initial USG>1.020 and were started on NS twice weekly. By week 5, 44 of 44 patients (100%) needed supplemental fluid hydration with only 4 of 44 (9%) requiring daily IV fluids (IVF). No patient experienced renal toxicity of any grade. Five patients (11%) had grade I hypomagnesemia. Conclusion: USG is a very sensitive marker of dehydration and can be used as a guide for fluid replacement which can minimize cisplatin induced nephrotoxicity in this population.

Impact of bladder volume on radiation dose to the rectum in the definitive treatment of prostate cancer.

BACKGROUND AND OBJECTIVE Our group created and routinely reviewed a dedicated prostate intensity-modulated radiation therapy (IMRT) delivery program. Previously, a retrospective review of our experience demonstrated that a larger bladder volume reduced radiation dose to the rectum. We conducted an observational study to confirm this relationship. METHODS Men receiving definitive radiation for prostate cancer were eligible for the study. Eligible patients received 2 computed axial tomography (CT) scans on the day of their planning CT scan: 1 with a full bladder and 1 with an empty bladder. On each CT data set, the prostate, rectum, bladder, penile bulb, and femoral heads were contoured. 2 IMRT plans were completed on each dataset: 1 by a medical dosimetrist and 1 by a medical physicist. The study plans targeted the prostate to 79.2 Gray (Gy) while respecting predefined dose tolerances to the other contoured structures. Rectal doses were compared on empty and full bladder CT data sets. RESULTS From June 29, 2010 to December 14, 2011, 17 full bladder data sets and 15 empty bladder data sets were available for analysis. Median change in bladder volume was 63 ml. Full vs empty bladder set-up was associated with a statistically significant reduction in the mean rectal dose of 25.41 Gy vs 27.6 Gy (𝑃 = .031). LIMITATIONS Small sample size and small variations in bladder volumes. CONCLUSIONS A greater bladder volume resulted in a reduced mean dose to the rectum irrespective of planning method.