Virtual planning of multicatheter brachytherapy implants for accelerated partial breast irradiation.

Over the last decade, increasing numbers of breast cancer patients are being treated using interstitial radioactive implants (brachytherapy). Multiple catheters are placed in the breast using a free-hand or template-guided approach. The configuration of the catheters and their relation to the tumor target volume are crucial to effective treatment. Catheter insertion requires a high level of experience to produce an implant of excellent quality. Construction of optimal catheter configuration prior to the procedure (virtual planning) would reduce the dependence of implant quality on the skill of the physician. Currently available commercial planning systems do not allow for virtual planning. We have developed software which inputs the target anatomy for a prospective patient and matches it to a previously-delivered catheter configuration from an institutional implant library. The archived catheter arrangement is then customized to fit the new target volume. The user can actually explore the implications of variations in catheter number and spatial arrangement. This may significantly improve the quality of implants that would otherwise be designed strictly based on a physician's prior experience. In an academic environment, this new resource could lead to better, faster results in the treatment of breast cancer.

Quantifying the effect of intrafraction motion during breast IMRT planning and dose delivery.

Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.

Brachytherapy in the treatment of breast cancer.

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Biologic treatment planning for high-dose-rate brachytherapy.

PURPOSE: Interstitial brachytherapy treatment plans are conventionally optimized with respect to total target dose and dose homogeneity, which does not account for the biologic effects of dose rate. In an HDR implant, with a stepping source, the dose rate dramatically changes during the course of treatment, depending on location, as the source moves from dwell position to dwell position. These widely varying dose rates, together with the related sequencing of the dwell positions, may impart different biologic effects at points receiving the same total dose. This study applies radiobiologic principles to account for the potential biologic impact of dose delivery at varying dose rates within an HDR implant. METHODS AND MATERIALS: The model under study uses a generalized version of the linear-quadratic (LQ) cell kill formula to calculate the surviving fraction of cells subjected to HDR irradiation. Using a planar interstitial HDR implant with the dwell times optimized to produce a homogeneous dose distribution along a reference plane parallel to the implant plane, surviving fractions were compared at selected reference points subjected to the same total dose. Biologic effect homogeneity was compared to dose homogeneity by plotting the effects at the reference points. The effects were examined with LQ parameters alpha, beta, and sublethal repair time T(1) varied over a range typical of human cells. RESULTS: In a region in which dose is relatively uniform, surviving fraction for some values of the model parameters are found to vary by as much as an order of magnitude due to differences in the HDR irradiation profiles at different dose points. This effect is more pronounced for shorter repair times and smaller alpha/beta ratios, and increases with increasing total irradiation time. CONCLUSION: Conventional HDR treatment planning currently considers dose distribution as the primary indicator of clinical effect. Our results demonstrate that plans optimized to maximize homogeneity within a target volume may not reflect the effect of the sequential nature of HDR dose delivery on cell kill. Biologic effect modeling may improve our understanding and ability to predict the adverse effects of our treatment, such as fat necrosis and fibrosis. Accounting for irradiation history and repair kinetics in the evaluation of HDR brachytherapy plans may add an important new dimension to our planning capabilities.

Interstitial high-dose-rate brachytherapy boost: the feasibility and cosmetic outcome of a fractionated outpatient delivery scheme.

PURPOSE: To evaluate the feasibility, potential toxicity, and cosmetic outcome of fractionated interstitial high dose rate (HDR) brachytherapy boost for the management of patients with breast cancer at increased risk for local recurrence. METHODS AND MATERIALS: From 1994 to 1996, 18 women with early stage breast cancer underwent conventionally fractionated whole breast radiotherapy (50-50.4 Gy) followed by interstitial HDR brachytherapy boost. All were considered to be at high risk for local failure. Seventeen had pathologically confirmed final surgical margins of less than 2 mm or focally positive. Brachytherapy catheter placement and treatment delivery were conducted on an outpatient basis. Preplanning was used to determine optimal catheter positions to enhance dose homogeneity of dose delivery. The total HDR boost dose was 15 Gy delivered in 6 fractions of 2.5 Gy over 3 days. Local control, survival, late toxicities (LENT-SOMA), and cosmetic outcome were recorded in follow-up. In addition, factors potentially influencing cosmesis were analyzed by logistic regression analysis. RESULTS: The minimum follow-up is 40 months with a median 50 months. Sixteen patients were alive without disease at last follow-up. There have been no in-breast failures observed. One patient died with brain metastases, and another died of unrelated causes without evidence of disease. Grade 1-2 late toxicities included 39% with hyperpigmentation, 56% with detectable fibrosis, 28% with occasional discomfort, and 11% with visible telangiectasias. Grade 3 toxicity was reported in one patient as persistent discomfort. Sixty-seven percent of patients were considered to have experienced good/excellent cosmetic outcomes. Factors with a direct relationship to adverse cosmetic outcome were extent of surgical defect (p = 0.00001), primary excision volume (p = 0.017), and total excision volume (p = 0.015). CONCLUSIONS: For high risk patients who may benefit from increased doses, interstitial HDR brachytherapy provides a convenient outpatient method for boosting the lumpectomy cavity following conventional whole breast irradiation without overdosing normal tissues. The fractionation scheme of 15 Gy in 6 fractions over 3 days is well tolerated. The volume of tissue removed from the breast at lumpectomy appears to dominate cosmetic outcome in this group of patients.

Internal mammary node coverage: an investigation of presently accepted techniques.

PURPOSE: Recent publications have generated a renewed interest in regional nodal treatment to include the ipsilateral supraclavicular and internal mammary nodes (IMN). The purpose of this study is to evaluate three presently accepted treatment techniques for coverage of the intact breast and ipsilateral lymph node regions and to construct recommendations regarding the utilization of these techniques. METHODS AND MATERIALS: Anatomic data were obtained from five randomly selected patients with computerized tomography (CT) in treatment position. Three patients presented with cancer of the left breast and two with cancer of the right. Using the Pinnacle 3-D planning system, normal tissue volumes of breast, ipsilateral lung, heart, sternum, and the IMN target were delineated for each patient. Three accepted techniques used to treat ipsilateral breast, internal mammary and supraclavicular nodes (extended tangents, 5-field, partly wide tangents) were configured and compared to a supraclavicular field matched to standard tangential fields. A dosage of 50 Gy in 25 fractions was prescribed to the target volume. Dose-volume histograms (DVH) were generated and analyzed with regard to target volume coverage and lung/heart volumes treated. RESULTS: All of the treatment techniques covering IMN include at least 10% more lung and heart volume than that covered by standard tangential fields. The relative lung and heart volumes treated with each technique were consistent from patient to patient. The 5-field technique clearly treats the largest volume of normal tissue; however, most of this volume receives less than 50% of the dose prescribed. The percent of heart and ipsilateral lung treated to 20 Gy, 30 Gy, and 40 Gy have been calculated and compared. Due to the increase in chest wall thickness and depth of IMN superiorly, complete coverage was not achieved with any technique if the IMN target extended superiorly into the medial supraclavicular field where dose fall-off resulted in a significant underdosing at depth. For the same anatomic reasons, the 5-field technique underdosed 10-15% of the IMN target volume in 4 of the 5 cases. This technique also yielded a greater dose heterogeneity, which was not seen with the other techniques evaluated and correlated with the change of anterior chest wall thickness. CONCLUSIONS: Anatomic variation in chest wall thickness and IMN depth strongly suggests the routine use of multislice CT planning to ensure complete coverage of the target volume and optimal sparing of normal tissue. All of the techniques can be constructed to look acceptable at central axis. To cover the superior most aspect of the IMN chain either high tangential fields, a supraclavicular field photon beam of energy >6 MV, or an AP/PA supraclavicular setup should be considered. The 5-field technique has the most difficulty in compensating for the increased depth of the IMN in the superior aspect of the tangent fields with up to +/-40% variation of the dose noted in isolated areas within the target volume. Based on our evaluation, the partly wide tangent technique offers many advantages. It provides optimal coverage of the target volume, reduces coverage of normal tissue volumes to an acceptable level, and is easily reproducible with a high degree of dose homogeneity throughout the target.

Cosmetic outcome in patients receiving an interstitial implant as part of breast-conservation therapy.

PURPOSE: To study factors related to breast cosmetic outcome in patients treated with an interstitial implant as part of breast-conservation therapy. MATERIALS AND METHODS: One hundred fifty-six patients with stage I or II breast carcinoma who received 50 Gy of external-beam irradiation followed by a 20-Gy interstitial boost were examined. The dose homogeneity index (DHI) was calculated for each evaluable implant and was examined in light of other patient-, treatment-, and tumor-related variables previously demonstrated to affect cosmesis. RESULTS: Of the variables examined, both the DHI (P = .021) and the total excision volume (P = .019) were significantly related to cosmetic outcome (excellent vs less than excellent) in a univariate model. In the multivariate analysis, only the total excision volume remained significant (P = .032). The mean total excision volume +/- SD in patients with excellent cosmetic outcome (81.8 cm3 +/- 84.0) was significantly less than that in patients with less than excellent cosmetic outcome (120 cm3 +/- 84). The probability of excellent cosmetic outcome linearly increased with an increase in DHI. The mean DHI was 0.74 +/- 0.12 for the cases with excellent cosmetic outcome and 0.68 +/- 0.10 for those with less than excellent cosmetic outcome. CONCLUSION: To achieve optimal cosmesis, DHI should be maximized. The volume of tissue removed, however, remains the most significant determinant.

Optimization of planar high-dose-rate implants.

PURPOSE: Brachytherapy has long been used to deliver localized radiation to the breast and other cancer sites. For interstitial implants, proper source positioning is critical in obtaining satisfactory dose distributions. The present work examines techniques for optimizing source guide placement in high-dose-rate (HDR) biplanar implants, and examines the effects of suboptimal catheter placement. METHODS AND MATERIALS: Control of individual dwell times in HDR implants allows a high degree of dose uniformity in planes parallel to the implant planes. Biplanar HDR implants can be considered optimized when the dose at the implant center is equal to the dose at the symmetric target boundaries. It is shown that this optimal dose uniformity is achieved when the interplanar separation is related to the target thickness T through the direct proportionality, s = T/square root2. To quantify the significance of source positioning, the average dose and a related quantity, equivalent uniform dose (EUD), were calculated inside the treatment volume for two conditions of suboptimal catheter geometry. In one case, the interplanar spacing was varied from 1 cm up to the target thickness T, while a second study examined the effects of off-center placement of the implant planes. RESULTS: Both the average dose and EUD were minimized when the interplanar spacing satisfied the relationship s = T/square root2. EUD, however, was significantly smaller than the average dose, indicating a reduced relative cell killing in the high dose regions near the dwell points. It was also noted that in contrast to the average dose, the EUD is a relatively weak function of catheter misplacement, suggesting that the biological consequences of suboptimal implant geometry may be less significant than is indicated by the increase in average dose. CONCLUSION: A concise formula can be used to determine the interplanar separation needed for optimal dose uniformity in Manchester-type implants. Deviations from optimal source geometry result in an increase in the average dose inside the treatment volume, but the weaker dependence of the EUD suggests that the surviving fraction of cells may not be not strongly affected by suboptimal source geometry.

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation.

PURPOSE: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. METHODS AND MATERIALS: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. RESULTS: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively. CONCLUSION: Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Electron/photon matched field technique for treatment of orbital disease.

PURPOSE: A number of approaches have been described in the literature for irradiation of malignant and benign diseases of the orbit. Techniques described to date do not deliver a homogeneous dose to the orbital contents while sparing the cornea and lens of excessive dose. This is a result of the geometry encountered in this region and the fact that the target volume, which includes the periorbital and retroorbital tissues but excludes the cornea, anterior chamber, and lens, cannot be readily accommodated by photon beams alone. To improve the dose distribution for these treatments, we have developed a technique that combines a low-energy electron field carefully matched with modified photon fields to achieve acceptable dose coverage and uniformity. METHODS AND MATERIALS: An anterior electron field and a lateral photon field setup is used to encompass the target volume. Modification of these fields permits accurate matching as well as conformation of the dose distribution to the orbit. A flat-surfaced wax compensator assures uniform electron penetration across the field, and a sunken lead alloy eye block prevents excessive dose to the central structures of the anterior segment. The anterior edge of the photon field is modified by broadening the penumbra using a form of pseudodynamic collimation. Direct measurements using film and ion chamber dosimetry were used to study the characteristics of the fall-off region of the electron field and the penumbra of the photon fields. From the data collected, the technique for accurate field matching and dose uniformity was generated. RESULTS: The isodose curves produced with this treatment technique demonstrate homogeneous dose coverage of the orbit, including the paralenticular region, and sufficient dose sparing of the anterior segment. The posterior lens accumulates less than 40% of the prescribed dose, and the lateral aspect of the lens receives less than 30%. A dose variation in the match region of +/-12% is confronted when an unmodified photon field edge is matched with the fall-off of the electron field at the 50% isodose lines. By modifying the penumbra, the dose variation is reduced to +/-2%. Treatment setup accuracy is essential. CONCLUSIONS: The electron/photon matched field technique offers a uniform isodose distribution for treatment of the orbit that has not been previously achieved. With this technique a homogeneous dose can be delivered to the entire orbit while avoiding a significant dose to the anterior segment and minimizing the risk of morbidity.

Intracranial hemangioblastomas: CT and MR findings.

The CT and magnetic resonance (MR) findings in eight patients with 10 biopsy-proven intracranial hemangioblastomas were reviewed. Three of these patients had von Hippel-Lindau (VHL) syndrome. Nine tumors were infratentorial, seven were cystic, and five had well-defined mural nodules. The only three solid tumors, the only brain stem tumor, and the only supratentorial tumor in this series occurred in VHL patients. Magnetic resonance detected a single tumor missed by CT, and no lesion seen on CT was missed by MR. The tumor nodule, when present, was identified in every case using MR, although it was usually more apparent on contrast-enhanced CT. In three cases MR was better than CT in defining the margins of posterior fossa tumors. Serpentine vessels were well seen as flow voids against high signal cyst or tumor on T2-weighted images, but contrast-enhanced CT also demonstrated them. Magnetic resonance was found superior to CT for the detection of intracranial hemangioblastomas, and complementary in their characterization.