Desmond A. O’Farrell

Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma.

PURPOSE When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. METHODS AND MATERIALS 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasm), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. RESULTS Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P = 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD. CONCLUSION This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume.

A practical method to achieve prostate gland immobilization and target verification for daily treatment

PURPOSE A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

A prospective trial of real-time magnetic resonance-guided catheter placement in interstitial gynecologic brachytherapy.

PURPOSE To present outcome and toxicity results of the first real-time intraoperative MRI-guided interstitial approach to gynecologic cancer. METHODS AND MATERIALS From February 2004 to December 2006, 25 patients with gynecologic malignancies were enrolled and treated in a prospective clinical trial of real-time MRI-guided interstitial brachytherapy. This was followed by a confirmatory CT imaging scan. Statistical analyses included Kaplan-Meier estimates for overall and relapse-free survival. RESULTS MRI visualization of needles during placement permitted accurate placement with no inadvertent insertions. This prevented unnecessary normal-tissue perforation as confirmed by CT simulation. With a mean followup of 3.8 years (range, 2-6.8), 1-, 2-, and 3-year overall survival rates were 80%, 60% and 43%, respectively; corresponding relapse-free survival rates were 79%, 65%, and 59%, respectively. Actuarial acute toxicity rates for any grade were 0% at 0-14 days and 80% (all grade 1) at 14-90 days. Long-term (>180 days) actuarial toxicity rates were 8% gastrointestinal, 4% bladder and 4% vaginal. CONCLUSIONS Real-time MRI guidance during insertion of interstitial needles followed by 3D-planning maximized opportunities for tumor targeting and sparing of normal tissues. Although image guidance requires additional anesthesia time, clinical outcomes indicate potential for a successful reduction in toxicity using 3D image-guided in addition to 3D image-planned brachytherapy.

American Brachytherapy Society (ABS) consensus statement for sarcoma brachytherapy.

PURPOSE To present recommendations for the use of brachytherapy (BT) in patients with soft tissue sarcoma (STS). METHODS A group of practitioners with expertise and experience in sarcoma BT formulated recommendations for BT in STS based on clinical experience and literature review. RESULTS The indications for adjuvant BT are discussed. There is no consensus on the use of BT alone or in combination with external beam radiation therapy (EBRT), but factors that influence the selection of this modality include tumor grade and size, prior surgeries, and tumor recurrence. Low-dose-rate, high-dose-rate, and pulsed-dose-rate radiation are all acceptable BT modalities to use for STS. Recommendations are made for patient selection, techniques, dose rates, and dosages. Outcome data and toxicity data are reviewed. CONCLUSIONS BT is a useful component of the treatment of STS. The advantages of BT are the targeted dose distribution, low integral dose, and short treatment times. Ultimately the clinician should select the modality or combination of modalities that are most familiar to the treatment team and suitable to the patient.

Independent brachytherapy plan verification software: Improving efficacy and efficiency

BACKGROUND AND PURPOSE To compare the pre-treatment brachytherapy plan verification by a physicist assisted by custom plan verification software (SAV) with those performed manually (MV). MATERIALS AND METHODS All HDR brachytherapy plans used for treatment in 2013, verified using either SAV or MV, were retrospectively reviewed. Error rate (number of errors/number of plans) was measured and verification time calculated. All HDR brachytherapy safety events recorded between 2010 and 2013 were identified. The rate of patient-related safety events (number of events/number of fractions treated) and the impact of SAV on the underlying errors were assessed. RESULTS Three/106 errors (2.8%) were found in the SAV group and 24/273 (8.8%) in the MV group (p=0.046). The mean ±1 standard deviation plan verification time was 8.4±4.0min for SAV and 11.6±5.3 for MV (p=0.006). Seven safety events out of 4729 fractions delivered (0.15%) were identified. Four events (57%) were associated with plan verification and could have been detected by SAV. CONCLUSIONS We found a safety event rate in HDR brachytherapy of 0.15%. SAV significantly reduced the number of undetected errors in HDR treatment plans compared to MV, and reduced the time required for plan verification.

Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma using surface-mold computer-optimized high-dose-rate brachytherapy.

PurposeThe objective of this study was to evaluate the palliative treatment benefit of surface-mold computer-optimized high-dose-rate brachytherapy (SMBT) for in-transit cutaneous metastases of Merkel cell carcinoma (MCC). MethodsTen patients with in-transit cutaneous MCC metastases were treated with SMBT at the Dana-Farber/Brigham & Women’s Cancer Center between 2006 and 2012. ResultsThe median age at diagnosis was 76 years (range, 63–87 years). Seven patients had in-transit metastases on the lower extremities (70%), 2 patients on the head and neck (20%), and 1 patient on an upper extremity (10%). A total of 152 metastatic MCC lesions were treated with SMBT. All SMBT-treated lesions resolved clinically within a few weeks of therapy. The median follow-up was 34 months (range, 22–85 months). Two of 152 treated lesions recurred during the study period for a local control rate of 99%. Eight patients (80%) developed additional in-transit metastases outside the original SMBT fields. Five of these 8 patients underwent additional SMBT. At study conclusion, 3 patients (30%) are alive without disease, 3 patients (30%) are alive with disease, and 4 patients (40%) died of MCC. DiscussionSurface-mold computer-optimized high-dose-rate brachytherapy offers effective and durable palliation for cutaneous metastases of MCC, although it does not appear to alter disease course.

Equivalent uniform dose for accelerated partial breast irradiation using the MammoSite applicator

INTRODUCTION This study aims to quantify the radiobiology of the MammoSite applicator and examine whether there is a relationship between equivalent uniform dose (EUD) and radiotherapy-associated toxicity. METHODS AND MATERIALS A previously-published version of the linear quadratic (LQ) model, designed to address the impact of dose-gradients in brachytherapy applications, was used to determine the biological effective dose (BED), equivalent dose in 2 Gray per fraction (EQD2) and EUD for the most common fractionation scheme for the MammoSite catheter (34 Gy in 10 fractions prescribed to 1cm from the balloon surface), using a range of balloon sizes in a series of patients treated with single or multiple dwell positions. Toxicity from the MammoSite catheter was assessed and statistical associations with the calculated EUDs were investigated. RESULTS The acute- and late-toxicity EUDs respectively range from 34.8-39.4 Gy and 33.4-37.6 Gy, with EUD decreasing as balloon diameter increases and/or the number of dwell positions increases. There was a positive association between EUD and hyperpigmentation and telangiectasia. CONCLUSIONS For APBI using the Mammosite applicator, EUD is higher than the marginal prescription dose and, for the dose-fractionation patterns considered here, was associated with acute and late skin toxicity. EUD is a potentially useful parameter to characterize non-uniform dose distributions related to brachytherapy treatments. Further evaluation in future studies is warranted.

Palliative Therapy for Recalcitrant Cutaneous T-Cell Lymphoma of the Hands and Feet With Low-Dose, High Dose-Rate Brachytherapy

Importance Cutaneous T-cell lymphoma (CTCL) of the hands and feet can be challenging to treat and cause significant disability for patients. Although CTCL is a highly radiosensitive tumor, the complex topography of acral surfaces presents challenges to achieving homogeneous superficial dosing of traditional electron beam therapy. In addition, traditional dosing may result in substantial acute cutaneous toxic effects. Recent reports demonstrate that low-dose palliative radiotherapy may be as effective as traditional regimens in CTCL. High dose-rate (HDR) brachytherapy allows for control of the depth of radiation penetration over complex curved surfaces. This study investigated the role of low-dose HDR brachytherapy for acral CTCL lesions. Observations Six patients with a total of 8 acral CTCL lesions received low-dose HDR brachytherapy during a 3-year period. Rapid improvement and clinical clearance were observed in all treated lesions with minimal to no acute cutaneous toxic effects. During a mean follow-up period of 15.8 months, 1 lesion recurred locally; the remaining 7 lesions had sustained clinical remission. No long-term sequelae were observed. Conclusions and Relevance This case series demonstrates that low-dose HDR brachytherapy provides excellent palliation for local control of acral CTCL lesions, offering homogeneous, controlled dosing for complex topographic sites with minimal to no cutaneous toxic effects.

Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis

Purpose In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. Material and methods The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. Results The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. Conclusions The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

SU-G-201-04: Can the Dynamic Library of Flap Applicators Replace Treatment Planning in Surface Brachytherapy?

PURPOSE Contemporary brachytherapy treatment planning systems-(TPS) include the applicator model libraries to improve digitization; however, the library of surface-flap-applicators-(SFA) is not incorporated into the commercial TPS. We propose the dynamic library-(DL) for SFA and investigate if such library can eliminate applicator reconstruction, source activation and dose normalization. METHODS DL was generated for the SFA using the C++class libraries of the Visualization Toolkit-(VTK) and Qt-application framework for complete abstraction of the graphical interface. DL was designed such that the user can initially choose the size of the applicator that corresponds to the one clinically placed to the patient. The virtual applicator-(VA) has an elastic property so that it can be registered to the clinical CT images with a real applicator-(RA) on it. The VA and RA matching is performed by adjusting the position and curvature of the VA. The VA does not elongate or change its size so each catheter could always be at a distance of 5mm from the skin and 10mm apart from the closest catheter maintaining the physical accuracy of the clinical setup. Upon the applicator placement, the dwell positions were automatically activated, and the dose is normalized to the prescription depth. The accuracy of source positioning was evaluated using various applicator sizes. RESULTS The accuracy of the applicator placement was in the sub-millimeter range. The time-study reveals that up to 50% of the planning time can be saved depending on the complexity of the clinical setup. Unlike in the classic approach, the planning time was not highly dependent on the applicator size. CONCLUSION The practical benefits of the DL of the SFA were demonstrated. The time demanding planning processes can be partially automated. Consequently, the planner can dedicate effort to fine tuning, which can result in the improvement of the quality of treatment plans in surface brachytherapy.