Novel portable apparatus for outpatient high-dose-rate (HDR) brachytherapy in penile cancer.

BACKGROUND: Penile squamous cell carcinoma (PSC) is traditionally treated with surgical resection with significant morbidity. Penile sparing approaches, such as brachytherapy, require expertise, prolonged inpatient stays, poor patient convenience, and heterogenous plans with variable long-term toxicity. In this study, we describe the protocol for novel portable apparatus created for PSC, allowing outpatient hybrid interstitial/surface brachytherapy, improving homogeneity and patient convenience. METHODS: A portable brachytherapy apparatus was developed utilizing a foley catheter, prostate template, 6F interstitial catheters, 5 mm bolus, and a jock strap. The apparatus allowed for internal and external catheter placement housed in a jock strap to allow mobility and defecation without affecting the implant. High-dose-rate brachytherapy was performed as an outpatient. RESULTS: The apparatus was then used on a 62-year-old male with cT2pN0M0 (stage IIA) PSC with bilateral glans and urethral meatus involvement, who elected for definitive brachytherapy (4000cGy in 10 fractions over 5-days). Given external dwell positions, heterogeneity correction of the template was calculated (AAPM TG186) with <2% variation. Patient had minimal impact on his active lifestyle during treatment and had complete clinical response at 3-months. Grade 2 skin desquamation resolved at 2-months, with no necrosis. At 6-months, he was able to resume sexual intercourse, and at 12-months, he remained disease-free with sexual and urinary function intact. CONCLUSIONS: Novel portable implant allows for improved patient convenience, reduced inpatient stay, capable of optimizing dosimetry with hybrid brachytherapy. This outpatient treatment allows the opportunity to increase fractionation, offering high local-control and lower toxicity. Future studies utilizing this apparatus for more fractionated regimens with further lower dose-per-fraction (∼3 Gy/fraction) is recommended.

Implications of staged reconstruction and adjuvant brachytherapy in the treatment of recurrent soft tissue sarcoma.

PURPOSE: Prior studies illustrated a reduction in wound complications with the use of staged reconstruction (SR) and negative pressure wound therapy when treating soft tissue sarcoma (STS) with surgical resection followed by high-dose-rate adjuvant brachytherapy. The purpose of this study is to compare the outcomes of SR and immediate reconstruction (IR) brachytherapy in recurrent STS. METHODS AND MATERIALS: A retrospective review of 40 patients with recurrent STS of the local extremity and trunk treated with resection followed by adjuvant brachytherapy alone. Margin status was defined as positive (SM(+)) if there was microscopic involvement (R1) or ≤1 mm margin and negative (SM(-)) if >1 mm margin was obtained. SR and IR were compared regarding toxicity, local control, and limb preservation. RESULTS: Median followup was 27 months. When comparing the SR (n = 22) and IR (n = 18) cohorts, there was a significantly lower final SM(+) rate in SR (32% vs. 83%, p < 0.01). A 2-year local control benefit seen with SR (80% vs. 34%; p = 0.012) and a final SM(-) (81% vs. 39%; p = 0.023). SR was associated with less toxicity on multivariate analysis, including a 90% decrease in persistent edema, an 80% decrease in wound dehiscence, and a 94% decrease in nonhealing wounds, when compared to IR. Ten of 31 (32%) extremity cases required eventual amputation from either chronic wound complications (n = 4) or local recurrence (n = 6). SR predicted for a benefit in 2-year limb preservation (88% vs. 50%; p = 0.008). CONCLUSION: In our series, the treatment with SR brachytherapy resulted in less morbidity and an improved final SM(-) rate. This technique translated to an improvement in both local control and limb preservation of recurrent STS.

Health-related quality-of-life changes due to high-dose-rate brachytherapy, low-dose-rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.

PURPOSE: To compare urinary, bowel, and sexual health-related quality-of-life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy, low-dose-rate (LDR) brachytherapy, or intensity-modulated radiation therapy (IMRT) monotherapy for prostate cancer. METHODS AND MATERIALS: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2700-2800 cGy in two fractions (n = 85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n = 249), or IMRT monotherapy to 7400-8100 cGy in 37-45 fractions (n = 79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an international prostate symptoms score questionnaire, an expanded prostate cancer index composite-26 bowel questionnaire, and a sexual health inventory for men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pretreatment and at 1, 3, 6, 9, 12, and 18 months posttreatment. RESULTS: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months after irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months after treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients after treatment. CONCLUSIONS: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.

A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer patients treated with high-dose rate brachytherapy±intensity modulated radiation therapy.

BACKGROUND AND PURPOSE: We sought to analyze the effect of polyethylene glycol (PEG) hydrogel on rectal doses in prostate cancer patients undergoing radiotherapy. MATERIALS AND METHODS: Between July 2009 and April 2013, we treated 200 clinically localized prostate cancer patients with high-dose rate (HDR) brachytherapy±intensity modulated radiation therapy. Half of the patients received a transrectal ultrasound (TRUS)-guided transperineal injection of 10mL PEG hydrogel (DuraSeal™ Spinal Sealant System; Covidien, Mansfield, MA) in their anterior perirectal fat immediately prior to the first HDR brachytherapy treatment and 5mL PEG hydrogel prior to the second HDR brachytherapy treatment. Prostate, rectal, and bladder doses and prostate-rectal distances were calculated based upon treatment planning CT scans. RESULTS: There was a success rate of 100% (100/100) with PEG hydrogel implantation. PEG hydrogel significantly increased the prostate-rectal separation (mean±SD, 12±4mm with gel vs. 4±2mm without gel, p<0.001) and significantly decreased the mean rectal D2 mL (47±9% with gel vs. 60±8% without gel, p<0.001). Gel decreased rectal doses regardless of body mass index (BMI). CONCLUSIONS: PEG hydrogel temporarily displaced the rectum away from the prostate by an average of 12mm and led to a significant reduction in rectal radiation doses, regardless of BMI.

High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy.

PURPOSE: To evaluate the use of high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy ± IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7 cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5 ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040 cGy in 25-28 fractions to the prostate bed followed by two 950 cGy HDR brachytherapy fractions separated by 1-2 weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800 cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy ± IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study.

Providing a fast conversion of total dose to biological effective dose (BED) for hybrid seed brachytherapy.

Optimization of permanent seed implant brachytherapy plans for treatment of prostate cancer should be based on biological effective dose (BED) distributions, since dose does not accurately represent biological effects between different types of sources. Currently, biological optimization for these plans is not feasible due to the amount of time necessary to calculate the BED distribution. This study provides a fast calculation method, based on the total dose, to calculate the BED distribution. Distributions of various numbers of hybrid seeds were used to calculate total dose distributions, as well as BED distributions. Hybrid seeds are a mixture of different isotopes (in this study (125)I and (103)Pd). Three ratios of hybrid seeds were investigated: 25/75, 50/50, and 75/25. The total dose and BED value from each voxel were coupled together to produce graphs of total dose vs. BED. Equations were then derived from these graphs. The study investigated four types of tissue: bladder, rectum, prostate, and other normal tissue. Equations were derived from the total dose - BED correspondence. Accuracy of conversion from total dose to BED was within 2 Gy; however, accuracy of conversion was found to be better for high total dose regions as compared to lower dose regions. The method introduced in this paper allows one to perform fast conversion of total dose to BED for brachytherapy using hybrid seeds, which makes the BED-based plan optimization practical. The method defined here can be extended to other ratios, as well as other tissues that are affected by permanent seed implant brachytherapy (i.e., breast).

Calculating prescription doses for new sources by biologically effective dose matching.

PURPOSE: In current clinical practice, single isotopes, such as (125)I or (103)Pd, are used as single sources in prostate seed implants. A mixture of two radionuclides in the seeds has been proposed for prostate cancer treatment. This study investigates a method for determining the prescription dose for these new seeds using the biological effective dose (BED). METHODS: Ten prostate cancer cases previously treated using single radionuclide seeds were selected for this study. The BED distribution for these cases was calculated. Plans using other radionuclides were then calculated based on this BED distribution. Prescription values could then be obtained for the calculated plans. The method was verified by calculating the prescription dose for (103)Pd and (125)I and comparing to clinical values. The method was then applied to a hybrid seed that consisted of a mixture of (125)I and (103)Pd radionuclides, which deliver equal dose to 1cm from the source in water (50/50D@1 cm). A prescription BED value was also calculated. RESULTS: A prescription BED of 110 Gy was found to correlate to a prescription dose of 145, 120, and 137 Gy for (125)I, (103)Pd, and 50/50D@1 cm hybrid seeds, respectively. CONCLUSION: The method introduced in this article allows one to calculate the prescription dose for new and novel sources in brachytherapy. The method was verified by calculating a prescription dose for (125)I and (103)Pd radionuclides that coincides with values used clinically.

Dose reduction study in vaginal balloon packing filled with contrast for HDR brachytherapy treatment.

PURPOSE: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. METHODS AND MATERIALS: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken with each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. RESULTS: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 ± 0.002 for contrast/saline solution and 0.808 ± 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 ± 0.010 and 0.781 ± 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. CONCLUSIONS: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.

Energy dependence of commercially available diode detectors for in-vivo dosimetry.

The energy dependence of commercially available diode detectors was measured for nominal accelerating potential ranging between Co-60 and 17 MV. The measurements were performed in a liquid water phantom at 5 cm depth for 10 x 10 cm2 collimator setting and source-to-detector distance of 100 cm. The response (nC/Gy) was normalized to Co-60 beam after corrections for the dose rate and temperature dependences for each diode. The energy dependence, calculated by taking the percent difference between the maximum and minimum sensitivity normalized to Co-60 beam, varied by 39% for the n-type Isorad Red, 26% for the n-type Isorad Electron, 19% for the QED Red (p-type), 15% for the QED Electron (p-type), 11% for the QED Blue (p-type), and 6% for the EDP10 diode for nominal accelerating potential between Co-60 and 17 MV. It varied by 34% for the Isorad-3 Gold #1 and #2, 35% for the Veridose Green, 15% for the Veridose Yellow, 9% for the Veridose Electron, 21% for the n-type QED Gold, 24% for the n-type QED Red, 3% for the EDP23G, 2% for the PFD (photon field detector), 7% for the EDP103G, and 16% for the EDP203G for nominal accelerating potential between Co-60 and 15 MV. The magnitude of the energy dependence is verified by Monte Carlo simulation. We concluded that the energy dependence does not depend on whether the diode is n- or p-type but rather depends mainly on the material around the die such as the buildup and the geometry of the buildup material. As a result, the value of the energy dependence can vary for each individual diode depending on the actual geometry and should be used with caution.

A dosimetric analysis of unstranded seeds versus customized stranded seeds in transperineal interstitial permanent prostate seed brachytherapy.

PURPOSE: This study aimed to retrospectively analyze the dosimetric and toxicity results from 272 patients with localized prostate cancer treated consecutively using loose or stranded radioactive seeds by transrectal ultrasound-guided transperineal permanent prostate seed brachytherapy. METHODS AND MATERIALS: Two hundred seventy-two patients with localized prostate cancer treated between February 2002 and June 2004 were analyzed. All patients were treated with radioactive iodine-125 or palladium-103 using unstranded or loose seeds (USS) (159 patients) or customized stranded seeds (CSS) at variable spacing (5-50 mm) (113 patients) (Vari-Strand; BrachySciences, Oxford, CT). A single experienced brachytherapist performed all implants. RESULTS: There was a slight improvement in the dosimetric parameter D90 between the CSS (101.9%) and USS (99.3%) groups (p = 0.041). However, overall implant quality based on Radiation Therapy Oncology Group (RTOG) guidelines was similar between both groups. CONCLUSIONS: We conclude that the D90 value calculated for CSS is statistically improved when compared to the USS cohort, but without a clinically significant difference. There was no difference in the toxicity scores in either group. Overall quality between groups is comparable in our institution.

Dose rate and SDD dependence of commercially available diode detectors.

The dose-rate dependence of commercially available diode detectors was measured under both high instantaneous dose-rate (pulsed) and low dose rate (continuous, Co-60) radiation. The dose-rate dependence was measured in an acrylic miniphantom at a 5-cm depth in a 10 x 10 cm2 collimator setting, by varying source-to-detector distance (SDD) between at least 80 and 200 cm. The ratio of a normalized diode reading to a normalized ion chamber reading (both at SDD=100 cm) was used to determine diode sensitivity ratio for pulsed and continuous radiation at different SDD. The inverse of the diode sensitivity ratio is defined as the SDD correction factor (SDD CF). The diode sensitivity ratio increased with increasing instantaneous dose rate (or decreasing SDD). The ratio of diode sensitivity, normalized to 4000 cGy/s, varied between 0.988 (1490 cGy/s)-1.023 (38,900 cGy/s) for unirradiated n-type Isorad Gold, 0.981 (1460 cGy/s)-1.026 (39,060 cGy/s) for unirradiated QED Red (n type), 0.972 (1490 cGy/s)-1.068 (38,900 cGy/s) for preirradiated Isorad Red (n type), 0.985 (1490 cGy/s)-1.012 (38,990 cGy/s) for n-type Pt-doped Isorad-3 Gold, 0.995 (1450 cGy/s)-1.020 (21,870 cGy/s) for n-type Veridose Green, 0.978 (1450 cGy/s)-1.066 (21,870 cGy/s) for preirradiated Isorad-p Red, 0.994 (1540 cGy/s)-1.028 (17,870 cGy/s) for p-type preirradiated QED, 0.998 (1450 cGy/s)-1.003 (21,870 cGy/s) for the p-type preirradiated Scanditronix EDP20(3G), and 0.998 (1490 cGy/s)-1.015 (38,880 cGy/s) for Scanditronix EDP10(3G) diodes. The p-type diodes do not always show less dose-rate dependence than the n-type diodes. Preirradiation does not always reduce diode dose-rate dependence. A comparison between the SDD dependence measured at the surface of a full scatter phantom and that in a miniphantom was made. Using a direct adjustment of radiation pulse height, we concluded that the SDD dependence of diode sensitivity can be explained by the instantaneous dose-rate dependence if sufficient buildup is provided to eliminate electron contamination. An energy independent empirical formula was proposed to fit the dose-rate dependence of diode sensitivity.

Temperature dependence of commercially available diode detectors.

Temperature dependence of commercially available n- and p-type diodes were studied experimentally under both high instantaneous dose rate (pulsed) and low dose rate (continuous) radiation. The sensitivity versus temperature was measured at SSD = 80 or 100 cm, 10 x 10 cm2, and 5 cm depth in a 30 x 30 x 30 cm3 water phantom between 10 degrees C and 35 degrees C. The response was linear for all the diode detectors. The temperature coefficient (or sensitivity variation with temperature, svwt) was dose rate independent for preirradiated diodes. They were (0.30 +/- 0.01)%/degrees C, (0.36 +/- 0.03)%/degrees C, and (0.29 +/- 0.08)%/degrees C for QED p-type, EDP p-type, and Isorad n-type diodes, respectively. The temperature coefficient for unirradiated n-type diodes was different under low dose rate [(0.16 to 0.45)%/degrees C, continuous, cobalt] and high instantaneous dose rate [(0.07 +/- 0.02)%/degrees C, pulsed radiation]. Moreover, the temperature coefficient varies among individual diodes. Similarly, the temperature coefficient for a special unirradiated QED p-type diode was different under low dose rate (0.34%/degrees C, cobalt) and high instantaneous dose rate [(0.26 +/- 0.01)%/degrees C, pulsed radiation]. Sufficient preirradiation can eliminate dose rate dependence of the temperature coefficient. On the contrary, preirradiation cannot eliminate dose rate dependence of the diode sensitivity itself.