A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs.

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue "pocket" for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.

CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands.

Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.

ASTRO Radiation Therapy Summary of the ASCO-ASTRO-SSO Guideline on Management of Hereditary Breast Cancer.

PURPOSE: To develop a summary of recommendations regarding locoregional management of patients with breast cancer and germline mutations in breast cancer susceptibility genes based on the American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology Guideline on Management of Hereditary Breast Cancer. METHODS: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an expert panel to develop recommendations based on a systematic review of the literature and a formal consensus process. A total of 58 articles met the eligibility criteria and formed the evidentiary basis for the locoregional therapy recommendations. Additionally, 6 randomized controlled trials of systemic therapy also met eligibility criteria. RESULTS: A joint evidence-based guideline was developed by a multidisciplinary panel, which has been separately published. From this guideline, the radiation-oncologist authors of the panel extracted pertinent surgical and radiation-specific recommendations of findings that are hereby presented. CONCLUSIONS: Patients with newly diagnosed breast cancer and BRCA1/2 mutations may be considered for breast conserving therapy (BCT), expecting similar rates of local control of the index cancer as noncarriers. The significant risk of contralateral breast cancer in these women (especially younger women), coupled with the higher risk of new cancers in the ipsilateral breast, warrant discussion of bilateral mastectomy. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or contralateral breast cancer events from radiation exposure in BRCA1/2 carriers. Patients with mutations in moderate-risk genes should be offered BCT as one choice after appropriate counseling. Radiation therapy should not be withheld in ATM carriers if BCT is planned. For patients with germline TP53 mutations, mastectomy is advised and radiation therapy is contraindicated except for those with a significant risk of locoregional recurrence.

Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes. METHODS: The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process. RESULTS: Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria. RECOMMENDATIONS: Patients with newly diagnosed BC and BRCA1/2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.

Dosimetric evaluation of multilumen intracavitary balloon applicator rotation in high-dose-rate brachytherapy for breast cancer.

The objective of this work is to evaluate dosimetric impact of multilumen balloon applicator rotation in high-dose-rate (HDR) brachytherapy for breast cancer. Highly asymmetrical dose distribution was generated for patients A and B, depending upon applicator proximity to skin and rib. Both skin and rib spacing was ≤ 0.7 cm for A; only rib spacing was ≤ 0.7 cm for B. Thirty-five rotation scenarios were simulated for each patient by rotating outer lumens every 10° over ± 180° range with respect to central lumen using mathematically calculated rotational matrix. Thirty-five rotated plans were compared with three plans: 1) original multidwell multilumen (MDML) plan, 2) multidwell single-lumen (MDSL) plan, and 3) single-dwell single-lumen (SDSL) plan. For plan comparison, planning target volume for evaluation (PTV_EVAL) coverage (dose to 95% and 90% volume of PTV_EVAL) (D95 and D90), skin and rib maximal dose (Dmax), and normal breast tissue volume receiving 150% (V150) and 200% (V200) of prescribed dose (PD) were evaluated. Dose variation due to device rotation ranged from -5.6% to 0.8% (A) and -6.5% to 0.2% (B) for PTV_EVAL D95; -5.2% to 0.4% (A) and -4.1% to 0.7% (B) for PTV_EVAL D90; -2.0 to 18.4% (A) and -7.8 to 17.5% (B) for skin Dmax; -11.1 to 22.8% (A) and -4.7 to 55.1% (B) of PD for rib Dmax, respectively. Normal breast tissue V150 and V200 variation was < 1.0 cc, except for -0.1 to 2.5cc (B) of V200. Furthermore, 30° device rotation increased rib Dmax over 145% of PD: 152.9% (A) by clockwise 30° rotation and 152.5% (B) by counterclockwise 30° rotation. For a highly asymmetric dose distribution, device rotation can outweigh the potential benefit of improved dose shaping capability afforded by multilumen and make dosimetric data worse than single-lumen plans unless it is properly corrected.

Pacemaker/implantable cardioverter-defibrillator dose in balloon high-dose-rate brachytherapy for breast cancer treatment.

PURPOSE: To retrospectively report pacemaker (PM)/implantable cardioverter-defibrillator (ICD) dose in balloon high-dose-rate (HDR) brachytherapy and provide distance-dose graph and table to approximately estimate the maximal device dose. METHODS AND MATERIALS: For 3 patients (A, B, and C), PM/ICD was retrospectively contoured on planning computed tomography images and its maximal dose was extracted from a dose-volume histogram. The surface of 1cm expansion from balloon was prescribed to 34Gy and the inverse square law was dominant factor in dose calculation. Therefore, the maximal PM/ICD dose was approximately estimated from the distance-dose graph or table and compared with that of the treatment plan. RESULTS: The minimal device-balloon surface distance was 10.9, 18.4, and 4.3cm for patient A, B, and C, respectively. The maximal dose estimated from the proposed table/graph was 2.1 vs. 1.61Gy for patient A, 0.87 vs. 0.49Gy for patient B, and 8.9 vs. 9.14Gy for patient C compared with that from the treatment plan. CONCLUSIONS: Depending on the location of PM/ICD relative to the tumor bed, balloon HDR brachytherapy is feasible if the maximal dose is less than or equal to the dose limit. The proposed distance-dose graph and/or table enable to approximately predict the maximal device dose based on the measurement of minimal distance between lumpectomy and the device before balloon implantation for the suitability of balloon HDR brachytherapy.

A comprehensive analysis of cardiac dose in balloon-based high-dose-rate brachytherapy for left-sided breast cancer.

PURPOSE: To investigate radiation dose to the heart in 60 patients with left-sided breast cancer who were treated with balloon-based high-dose-rate brachytherapy using MammoSite or Contura applicators. METHODS AND MATERIALS: We studied 60 consecutive women with breast cancer who were treated with 34 Gy in 10 twice-daily fractions using MammoSite (n = 37) or Contura (n = 23) applicators. The whole heart and the left and right ventricles were retrospectively delineated, and dose-volume histograms were analyzed. Multiple dosimetrics were reported, such as mean dose (D(mean)); relative volume receiving 1.7, 5, 10, and 20 Gy (V1.7, V5, V10, and V20, respectively); dose to 1 cc (D(1cc)); and maximum point dose (D(max)). Biologic metrics, biologically effective dose and generalized equivalent uniform dose were computed. The impact of lumpectomy cavity location on cardiac dose was investigated. RESULTS: The average ± standard deviation of D(mean) was 2.45 ± 0.94 Gy (range, 0.56-4.68) and 3.29 ± 1.28 Gy (range, 0.77-6.35) for the heart and the ventricles, respectively. The average whole heart V5 and V10 values were 10.2% and 1.3%, respectively, and the heart D(max) was >20 Gy in 7 of 60 (11.7%) patients and >25 Gy in 3 of 60 (5%) patients. No cardiac tissue received ≥30 Gy. The V1.7, V5, V10, V20, and D(mean) values were all higher for the ventricles than for the whole heart. For balloons located in the upper inner quadrant of the breast, the average whole heart D(mean) was highest. The D(mean), biologically effective dose, and generalized equivalent uniform dose values for heart and ventricles decreased with increasing minimal distance from the surface of the balloon. CONCLUSIONS: On the basis of these comprehensive cardiac dosimetric data, we recommend that cardiac dose be routinely reported and kept as low as possible in balloon-based high-dose-rate brachytherapy treatment planning for patients with left-sided breast cancer so the correlation with future cardiac toxicity data can be investigated.

Objective method to report planner-independent skin/rib maximal dose in balloon-based high dose rate (HDR) brachytherapy for breast cancer.

PURPOSE: An objective method was proposed and compared with a manual selection method to determine planner-independent skin and rib maximal dose in balloon-based high dose rate (HDR) brachytherapy planning. METHODS: The maximal dose to skin and rib was objectively extracted from a dose volume histogram (DVH) of skin and rib volumes. A virtual skin volume was produced by expanding the skin surface in three dimensions (3D) external to the breast with a certain thickness in the planning computed tomography (CT) images. Therefore, the maximal dose to this volume occurs on the skin surface the same with a conventional manual selection method. The rib was also delineated in the planning CT images and its maximal dose was extracted from its DVH. The absolute (Abdiff = [D(max) Man - D (max)DVH]) and relative (Rediff[%] = 100 x ([D(max)Man-D(max)DVH])/D(max)DVH) maximal skin and rib dose differences between the manual selection method (D(max)Man) and the objective method (D(max)DVH) were measured for 50 balloon-based HDR (25 MammoSite and 25 Contura) patients. RESULTS: The average +/- standard deviation of maximal dose difference was 1.67% +/- 1.69% of the prescribed dose (PD). No statistical difference was observed between MammoSite and Contura patients for both Abdiff and Rediff[%] values. However, a statistically significant difference (p value < 0.0001) was observed in maximal rib dose difference compared with maximal skin dose difference for both Abdiff (2.30% +/- 1.71% vs 1.05% +/- 1.43%) and Rediff[%] (2.32% +/- 1.79% vs 1.21% +/- 1.41%). In general, rib has a more irregular contour and it is more proximally located to the balloon for 50 HDR patients. Due to the inverse square law factor, more dose difference was observed in higher dose range (D(max) > 90%) compared with lower dose range (D(max) < 90%): 2.16% +/- 1.93% vs 1.19% +/- 1.25% with p value of 0.0049. However, the Rediff[%] analysis eliminated the inverse square factor and there was no statistically significant difference (p value = 0.8931) between high and low dose ranges. CONCLUSIONS: The objective method using volumetric information of skin and rib can determine the planner-independent maximal dose compared with the manual selection method. However, the difference was < 2% of PD, on average, if appropriate attention is paid to selecting a manual dose point in 3D planning CT images.

Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy.

OBJECTIVES: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. METHODS: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. RESULTS: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. CONCLUSIONS: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

Local control and visual acuity following treatment of medium-sized ocular melanoma using a contact eye plaque: a single surgeon experience.

PURPOSE: To evaluate the outcomes of choroidal melanoma in (CM) patients treated with (125)I episcleral plaque brachytherapy and to compare our single surgeon results with the multi-institutional Collaborative Ocular Melanoma Study (COMS). METHODS AND MATERIALS: A review was performed of all CM patients treated with (125)I episcleral plaque brachytherapy by ophthalmologist in accordance with established COMS guidelines. RESULTS: The records of 35 patients were reviewed. The median longest basal tumor diameter and apical tumor height was 13.5 and 7.8mm, respectively. Median dose to the apex was 8609 cGy at a median dose rate of 92 cGy/h. At a median followup of 45 months, 35 patients had local control and 33 had successful organ preservation. At 5 years, the local control rate was 100%, and the eye preservation rate was 94%. Five patients developed hepatic metastasis at a median of 58 months, and 2 succumbed from disease. The 5-year survival rate was 84%, and the 5-year rate of death with histopathologically confirmed metastasis was 15%. Of the 22 patients with at least 3 years of followup, 68% had a visual acuity in the treated eye of 20/200 or worse. CONCLUSION: Excellent local control, eye preservation rates, and survival outcomes following (125)I episcleral plaque application for CM can be optimized by having an experienced ophthalmologist place the plaques. Additionally, hepatic metastasis can occur more than 5 years postimplant regardless of local control; therefore, longer systemic staging should be considered.

Evaluation of the interfractional biological effective dose (BED) variation in MammoSite high dose rate brachytherapy.

The objective of this work is to evaluate the interfractional biological effective dose (BED) variation in MammoSite high dose rate (HDR) brachytherapy. Dose distributions of 19 patients who received 34 Gy in 10 fractions were evaluated. A method was employed to account for nonuniform dose distribution in the BED calculation. Furthermore, a range of alpha/beta values was utilized for specific clinical end points: fibrosis, telangiectasia, erythema, desquamation and breast carcinoma. Two scenarios were simulated to calculate the BED value using: i) the same dose distribution of fraction 1 over fractions 2-10 (constant case, CC), and ii) the actual delivered dose distribution for each fraction 1-10 (interfractiondose variation case, IVC). Although the average BED difference (IVC - CC) was < 0.7 Gy for all clinical endpoints, the range of difference for fibrosis and telangiectasia reached -11% to +3% and -9% to +9% for one of the patients, respectively. By disregarding high inhomogeneity in HDR brachytherapy, the conventional BED calculation tends to overestimate the BED for fibrosis by 16% on average, while it underestimates the BED for erythema (7.6%) and desquamation (10.2%). In conclusion, the BED calculation accounting for the nonuniform dose distribution provides a more clinically relevant description of the clinical delivered dose. Though the average BED difference was clinically insignificant, the maximum difference of BED for late effects can differ by a single fractional dose (10%) for a specific patient due to the interfraction dose variation in MammoSite treatment.

Comparison of single and multiple dwell position methods in MammoSite high dose rate (HDR) brachytherapy planning.

The purpose of this study is to dosimetrically compare two plans generated using single dwell position method (SDPM) and multiple dwell position methods (MDPM) in MammoSite high dose rate (HDR) brachytherapy planning for 19 breast cancer patients. In computed tomography (CT) image-based HDR planning, a surface optimization technique was used in both methods. Following dosimetric parameters were compared for fraction 1 plans: %PTV_EVAL (planning target volume for plan evaluation) coverage, dose homogeneity index (DHI), dose con-formal index (COIN), maximum dose to skin and ipsilateral lung, and breast tissue volume receiving 150% (V150[cc]) and 200% (V200[cc]) of the prescribed dose. In addition, a plan was retrospectively generated for each fraction 2-10 to simulate the clinical situation where the fraction 1 plan was used for fractions 2-10 without modification. In order to create nine derived plans for each method and for each of the 19 patients, the catheter location and contours of target and critical structures were defined on the CT images acquired prior to each fraction 2-10, while using the same dwell-time distribution as used for fraction 1 (original plan). Interfraction dose variations were evaluated for 19 patients by comparing the derived nine plans (each for fractions 2-10) with the original plan (fraction 1) using the same dosimetric parameters used for fraction 1 plan comparison. For the fraction 1 plan comparison, the MDPM resulted in slightly increased %PTV_EVAL coverage, COIN, V150[cc] and V200[cc] values by an average of 1.2%, 0.025, 0.5 cc and 0.7cc, respectively, while slightly decreased DHI, maximum skin and ipsilateral lung dose by an average of 0.003, 3.2 cGy and 5.8 cGy, respectively. For the inter-fraction dose variation comparison, the SDPM resulted in slightly smaller variations in %PTV_EVAL coverage, DHI, maximum skin dose and V150[cc] values by an average of 0.4%, 0.0005, 0.5 cGy and 0.2 cc, respectively, while slightly higher average variations in COIN, maximum ipsilateral lung dose and V200[cc] values by 0.0028, 0.2 cGy and 0.2 cc, respectively. All differences were too small to be clinically significant. Compared to the MDPM, the SDPM combined with a surface optimization technique can generate a clinically comparable fraction 1 treatment plan with a similar interfraction dose variation if a single source is carefully positioned at the center of the balloon catheter.

Investigation of interfraction variations of MammoSite balloon applicator in high-dose-rate brachytherapy of partial breast irradiation.

PURPOSE: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. METHODS AND MATERIALS: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV_EVAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV_EVAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. RESULTS: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% +/- 1.6% and -0.1 +/- 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm(3)) to Fraction 1 (0.8 cm(3)). The PTV_EVAL volume change was insignificant. The average variation for the %PTV_EVAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% +/- 2.4%, -0.35 +/- 2.4%, and -0.34 +/- 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 +/- 0.47 and -0.16 +/- 0.29 Gy, respectively. CONCLUSION: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant.

Tolerance of the aorta using intraoperative iodine-125 interstitial brachytherapy in cancer of the lung.

PURPOSE: A retrospective review to assess the efficacy and morbidity of surgical resection and (125)I interstitial lung brachytherapy placed in approximation to the aorta. METHODS AND MATERIALS: The records and postoperative films of 278 patients who had undergone intrathoracic (125)I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non-small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with (125)I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of (125)I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2cc (mean surface area=34.4cm(2)) and the mean prescribed dose was 114Gy (range, 85-120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. RESULTS: All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1-117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. CONCLUSIONS: Interstitial (125)I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non-small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000cGy over the permanent life of the interstitial implant. Interstitial (125)I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.

Dosimetric comparison of partial and whole breast external beam irradiation in the treatment of early stage breast cancer.

A dosimetric comparison was performed on external-beam three-dimensional conformal partial breast irradiation (PBI) and whole breast irradiation (WBI) plans for patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol at our institution. Twenty-four consecutive patients were treated with either PBI (12 patients) or WBI (12 patients). In the PBI arm, the lumpectomy cavity was treated to a total dose of 38.5 Gy at 3.85 Gy per fraction twice daily using a four-field noncoplanar beam setup. A minimum 6 h interval was required between fractions. In the WBI arm, the whole breast including the entirety of the lumpectomy cavity was treated to a total dose of 50.4 Gy at 1.8 Gy per fraction daily using opposed tangential beams. The lumpectomy cavity volume, planning target volume for evaluation (PTV_EVAL), and critical structure volumes were contoured for both the PBI and WBI patients. Dosimetric parameters, dose volume histograms (DVHs), and generalized equivalent uniform dose (gEUD) for target and critical structures were compared. Dosimetric results show the PBI plans, compared to the WBI plans, have smaller hot spots in the PTV_EVAL (maximum dose: 104.2% versus 110.9%) and reduced dose to the ipsilateral breast (V50: 48.6% versus 92.1% and V100: 10.2% versus 50.5%), contralateral breast (V3: 0.16% versus 2.04%), ipsilateral lung (V30: 5.8% versus 12.7%), and thyroid (maximum dose: 0.5% versus 2.0%) with p values < or = 0.01. However, similar dose coverage of the PTV_EVAL (98% for PBI and 99% for WBI, on average) was observed and the dose difference for other critical structures was clinically insignificant in both arms. The gEUD data analysis showed the reduction of dose to the ipsilateral breast and lung, contralateral breast and thyroid. In addition, preliminary dermatologic adverse event assessment data suggested reduced skin toxicity for patients treated with the PBI technique.