Vijay R. Kini

The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy

PURPOSE We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. METHODS AND MATERIALS Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with (192)Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. RESULTS Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. CONCLUSION In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed.

Irradiation of the tumor bed alone after lumpectomy in selected Patients with early-stage breast cancer treated with breast conserving therapy

We present the interim findings of our in‐house protocol treating the tumor bed alone after lumpectomy with low‐dose‐rate (LDR) interstitial brachytherapy in selected patients with early‐stage breast cancer treated with breast conserving therapy (BCT).

Active breathing control (ABC) for Hodgkin’s disease: reduction in normal tissue irradiation with deep inspiration and implications for treatment☆

PURPOSE Active breathing control (ABC) temporarily immobilizes breathing. This may allow a reduction in treatment margins. This planning study assesses normal tissue irradiation and reproducibility using ABC for Hodgkins disease. METHODS AND MATERIALS Five patients underwent CT scans using ABC obtained at the end of normal inspiration (NI), normal expiration (NE), and deep inspiration (DI). DI scans were repeated within the same session and 1-2 weeks later. To simulate mantle radiotherapy, a CTV1 was contoured encompassing the supraclavicular region, mediastinum, hila, and part of the heart. CTV2 was the same as CTV1 but included the whole heart. CTV3 encompassed the spleen and para-aortic lymph nodes. The planning target volume (PTV) was defined as CTV + 9 mm. PTVs were determined at NI, NE, and DI. A composite PTV (comp-PTV) based on the range of NI and NE PTVs was determined to represent the margin necessary for free breathing. Lung dose-mass histograms (DMH) for PTV1 and PTV2 and cardiac dose-volume histograms (DVH) for PTV3 were compared at the three different respiratory phases. RESULTS ABC was well-tolerated by all patients. DI breath-holds ranged from 34 to 45 s. DMHs determined for PTV1 revealed a median reduction in lung mass irradiated at DI of 12% (range, 9-24%; n = 5) compared with simulated free-breathing. PTV2 comparisons also showed a median reduction of 12% lung mass irradiated (range, 8-28%; n = 5). PTV3 analyses revealed the mean volume of heart irradiated decreased from 26% to 5% with deep inspiration (n = 5). Lung volume comparisons between intrasession and intersession DI studies revealed mean variations of 4%. CONCLUSION ABC is well tolerated and reproducible. Radiotherapy delivered at deep inspiration with ABC may decrease normal tissue irradiation in Hodgkins disease patients.

Dose-volume analysis for quality assurance of interstitial brachytherapy for breast cancer

PURPOSE/OBJECTIVE The use of brachytherapy in the management of breast cancer has increased significantly over the past several years. Unfortunately, few techniques have been developed to compare dosimetric quality and target volume coverage concurrently. We present a new method of implant evaluation that incorporates computed tomography-based three-dimensional (3D) dose-volume analysis with traditional measures of brachytherapy quality. Analyses performed in this fashion will be needed to ultimately assist in determining the efficacy of breast implants. METHODS AND MATERIALS Since March of 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. Eight patients treated with high-dose-rate (HDR) brachytherapy who had surgical clips outlining the lumpectomy cavity and underwent computed tomography (CT) scanning after implant placement were selected for this study. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system. The lumpectomy cavity, target volume (lumpectomy cavity plus a 1-cm margin), and entire breast were outlined on each axial slice. Once all volumes were entered, the programmed HDR brachytherapy source positions and dwell times were imported into the 3D planning system. Using the tools provided by the 3D planning system, the implant dataset was then registered to the visible implant template in the CT dataset. The distribution of the implant dose was analyzed with respect to defined volumes via dose-volume histograms (DVH). Isodose surfaces, the dose homogeneity index, and dosimetric coverage of the defined volumes were calculated and contrasted. All patients received 32 Gy to the entire implanted volume in 8 fractions of 4 Gy over 4 days. RESULTS Three-plane implants were used for 7 patients and a two-plane implant for 1 patient. The median number of needles per implant was 16.5 (range 11-18). Despite visual verification by the treating physician that surgical clips (with an appropriate margin) were within the boundaries of the implant needles, the median proportion of the lumpectomy cavity that received the prescribed dose was only 87% (range 73-98%). With respect to the target volume, a median of only 68% (range 56-81%) of this volume received 100% of the prescribed dose. On average, the minimum dose received by at least 90% of the target volume was 22 Gy (range 17.3-26.9), which corresponds to 69% of the prescribed dose. CONCLUSION Preliminary results using our new technique to evaluate implant quality with CT-based 3D dose-volume analysis appear promising. Dosimetric quality and target volume coverage can be concurrently analyzed, allowing the possibility of evaluating implants prospectively. Considering that target volume coverage may be suboptimal even after radiographically verifying accurate implant placement, techniques similar to this need to be developed to ultimately determine the true efficacy of brachytherapy in the management of breast cancer.

The role of regional nodal irradiation in the management of patients with early-stage breast cancer treated with breast-conserving therapy

PURPOSE To determine the incidence of regional nodal failure (RNF) and indications for regional nodal irradiation (RNI) in patients with Stage I and II breast cancer treated with breast-conserving therapy (BCT). METHODS AND MATERIALS Four hundred fifty-six patients with Stage I/II breast cancer were treated with BCT at William Beaumont Hospital. All patients underwent excisional biopsy and 288 (63%) were reexcised. A Level I/II ipsilateral axillary lymph node dissection was performed on 431 patients (95%). Pathologically involved nodes were found in 106 (23%) cases (69 with one to three nodes and 37 with > or = four nodes involved). All patients received whole breast irradiation (median dose 50 Gy) and 415 (91%) were boosted to the tumor bed (median total dose 60.4 Gy). Three hundred and sixty (79%) patients received breast alone irradiation and 96 (21%) also received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. RESULTS With a median follow-up of 83 months, 15 patients developed a RNF for a 5- and 8-year actuarial rate of 3 and 4%, respectively. The 5- and 8-year actuarial rates of axillary failure (AF) were 0.7 and 1.0%, respectively. The incidence of RNF or AF was not affected by the use of RNI in N0 or N1 patients with one to three positive nodes. Only in patients with four or more positive nodes was there a trend towards improved regional control with RNI (p = 0.09). However, patient numbers were extremely small, and this improvement was limited to a reduction in the rate of failure in the supraclavicular fossa (SCF) (20 vs. 0%, p = 0.04). Multiple clinical, pathologic, and treatment related factors were analyzed for an association with AF. On univariate analysis, AF was associated with the number of lymph nodes excised (p < 0.0001) estrogen receptor status (p = 0.0016), and pathologic node status (p = 0.0021). CONCLUSIONS Regional nodal failure as the first site of failure is uncommon in patients with early-stage breast cancer treated with BCT with < or = three positive lymph nodes and appears unaffected by RNI. For patients with four or more positive lymph nodes, a trend towards improved RNF was noted with RNI, primarily in the SCF. However, patient numbers were extremely small in all subsets analyzed. Additional studies are needed to further define the need for RNI in these patients and help determine other factors associated with RNF.

Implementation of 3D-virtual brachytherapy in the management of breast cancer: a description of a new method of interstitial brachytherapy.

PURPOSE We present the initial description of a new technique of interstitial breast brachytherapy in which a computer-generated image of an implant template is applied virtually to serial-computed tomography (CT) scan images of a patients breast. Optimal placement of the virtual template around the CT images of the proposed target volume provides the physician with a preplan for improved positioning of implant needles around the actual target volume intraoperatively. METHODS AND MATERIALS Since March of 1993, 110 patients with early-stage breast cancer were entered onto a protocol of low or high dose rate brachytherapy as the sole radiation modality for part of their breast-conserving therapy. To improve the accuracy and reproducibility of target volume coverage in patients with a closed lumpectomy cavity, 11 of these implants were performed using the virtual brachytherapy technique. The virtual implant procedure was performed by first placing radiopaque skin markers on the breast surface for reference on the CT image and ultimately as intraoperative landmarks for the placement of implant needles. A CT scan of the breast was then performed and the target volume outlined on each CT scan slice by the physician. A virtual image of the brachytherapy template was then positioned around the CT image of the target volume to achieve an idealized implant with optimal coverage. The projected entrance and exit points of all needles on the skin of the breast (from the idealized virtual implant) were then identified (by perspective rendering of multiple 3D views) and hard-copy images taken to the operating room. The implant was then constructed by referencing the virtual implant images (needle entrance and exit points) to the radiopaque skin markers on the breast. After the implant was completed, a CT scan of the breast with the template catheters or needles in position was taken for comparison of the actual target volume coverage with the virtual implant generated preoperatively. RESULTS Intraoperative ultrasound was used to check the real-time position of the afterloading needles in reference to the chest wall and posterior border of the target volume. No adjustment of needles was required in any of the 11 patients. Assessment of target volume coverage between the virtual implant and the actual CT image of the implant showed excellent agreement. In each case, all target volume boundaries specified by the physician were adequately covered. The total number of implant planes, intertemplate separation, and template orientation were identical between the virtual and real implant. CONCLUSION We conclude that 3D virtual brachytherapy may offer an improved technique for accurately performing interstitial implants of the breast with a closed lumpectomy cavity in selected patients. Although preliminary results show excellent coverage of the desired target volume, additional patients will be required to establish the reproducibility of this technique and its practical limitations.

A comprehensive review of prostate cancer brachytherapy: defining an optimal technique

PURPOSE A comprehensive review of prostate cancer brachytherapy literature was performed to determine if an optimal method of implantation could be identified, and to compare and contrast techniques currently in use. METHODS AND MATERIALS A MEDLINE search was conducted to obtain all articles in the English language on prostate cancer brachytherapy from 1985 through 1998. Articles were reviewed and grouped to determine the primary technique of implantation, the method or philosophy of source placement and/or dose specification, the technique to evaluate implant quality, overall treatment results (based upon pretreatment prostate specific antigen, (PSA), and biochemical control) and clinical, pathological or biochemical outcome based upon implant quality. RESULTS A total of 178 articles were identified in the MEDLINE database. Of these, 53 studies discussed evaluable techniques of implantation and were used for this analysis. Of these studies, 52% used preoperative ultrasound to determine the target volume to be implanted, 16% used preoperative computerized tomography (CT) scans, and 18% placed seeds with an open surgical technique. An additional 11% of studies placed seeds or needles under ultrasound guidance using interactive real-time dosimetry. The number and distribution of radioactive sources to be implanted or the method used to prescribe dose was determined using nomograms in 27% of studies, a least squares optimization technique in 11%, or not stated in 35%. In the remaining 26%, sources were described as either uniformly, differentially, or peripherally placed in the gland. To evaluate implant quality, 28% of studies calculated some type of dose-volume histogram, 21% calculated the matched peripheral dose, 19% the minimum peripheral dose, 14% used some type of CT-based qualitative review and, in 18% of studies, no implant quality evaluation was mentioned. Six studies correlated outcome with implant dose. One study showed an association of implant dose with the achievement of a PSA nadir < or = 0.5. Two studies showed an improvement in biochemical control with a D90 (dose to 90% of the prostate volume) of 120 to 140 Gy or higher, and 2 additional studies found an association of clinical outcome with implant dose. One study correlated implant quality with biopsy results. Of the articles, 33 discussed evaluable treatment results, but only 16 reported findings based upon pretreatment PSA and biochemical control. Three- to 5-year biochemical control rates ranged from 48% to 100% for pretreatment PSAs < or = 4, 55% to 90% for PSAs between 4 and 10, 30% to 89% for PSAs > 10, < or = 20 and < 10% to 100% for PSAs > 20. Due to substantial differences in patient selection criteria (e.g., median Gleason score, clinical stage, pretreatment PSA), number of patients treated, median follow-up, definitions of biochemical control, and time points for analysis, no single technique consistently produced superior results. CONCLUSIONS Our comprehensive review of prostate cancer brachytherapy literature failed to identify an optimal treatment approach when studies were analyzed for treatment outcome based upon pretreatment PSA and biochemical control. Although several well-designed studies showed an improvement in outcome with total dose or implant quality, the numerous techniques for implantation and the varied and inconsistent methods to specify dose or evaluate implant quality suggest that standardized protocols should be developed to objectively evaluate this treatment approach. These protocols have recently been suggested and, when implemented, should significantly improve the reporting of treatment data and, ultimately, the efficacy of prostate brachytherapy.

Improving the dosimetric coverage of interstitial high-dose-rate breast implants.

PURPOSE/OBJECTIVE We performed a retrospective computed tomography (CT)-based three-dimensional (3D) dose-volume analysis of high-dose-rate (HDR) interstitial breast implants to evaluate the adequacy of lumpectomy cavity coverage, and then designed a simple, reproducible algorithm for dwell-time adjustment to correct for underdosage of the lumpectomy cavity. METHODS AND MATERIALS Since March 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. In this protocol, all patients received 32 Gy in 8 fractions of 4 Gy over 4 days. Eleven patients treated with HDR brachytherapy who underwent CT scanning after implant placement were included in this analysis. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system, and the relevant tissue volumes were outlined on each axial slice. The implant dataset, including the dwell positions and dwell times, were imported into the 3D planning system and then registered to the visible implant template in the CT dataset. The calculated dose distribution was analyzed with respect to defined volumes via dose-volume histograms. Due to the variability of lumpectomy cavity coverage discovered in this 3D quality assurance analysis, dwell times at selected positions were adjusted in an attempt to improve dosimetric coverage of the lumpectomy cavity. Using implant data from 5 cases, a dwell-time adjustment algorithm was designed and was then tested on 11 cases. In this algorithm, a point P was identified using axial CT images, which was representative of the underdosed region within the cavity. The distance (d) from point P to the nearest dwell position was measured. A number of dwell positions (N) nearest to point P were selected for dwell time adjustment. The algorithm was tested by increasing the dwell times of a variable number of positions (N = 1, 3, 5, 7, 10, and 20) by a weighting factor (alpha), where alpha = f(d) and alpha > 1, and subsequently performing 3D dose-volume analysis to evaluate the improvement in lumpectomy cavity coverage. RESULTS Before adjustment in the 11 implants, the median proportion of the lumpectomy cavity and target volume that received at least the prescription dose was 85% and 68%, respectively. After dwell-time adjustment, lumpectomy cavity coverage was significantly improved in all 11 cases. The median distance from point P to the nearest dwell position (d) was 1.4 cm (range 0.9-1.9). The median volume of the lumpectomy cavity receiving 32 Gy increased from 85.3% in the actual implant to 97.0% (range 74-100%) by increasing the dwell time of a single dwell position by a median factor (alpha) of 12.2 according to the above algorithm. With N = 3, the median proportion of the cavity volume receiving 32 Gy was improved to 97.5% (range 77-100%), with a median alpha of 5.7. Further improvement in lumpectomy cavity coverage was relatively small by increasing additional dwell times. In addition, with N = 20, the median absolute volume of breast tissue receiving 150% of the prescription dose was 70.3 cm3 compared to 26.3 cm3 in the actual implant; whereas with N = 1 or N = 3, this median volume was only 35.9 and 42.0 cm3, respectively. CONCLUSION Lumpectomy cavity coverage sometimes appears suboptimal with interstitial HDR breast brachytherapy using our current technique. A simple dwell-time increase at only 1-3 dwell positions can compensate for some underdosage without creating significant regions of overdosage. Using simple methodology, a single reference point representing the underdosed region can be utilized for initial selection of the dwell positions to be increased.

Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy

BACKGROUND We retrospectively reviewed our institutions experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. METHODS Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. RESULTS A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age < or =35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age < or = 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age < or = 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. CONCLUSION In patients with early-stage breast cancer treated with BCT, age < or = 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence.

Long term results with breast‐conserving therapy for patients with early stage breast carcinoma in a community hospital setting

Prospective randomized trials and retrospective reviews from academic centers have documented the success of breast‐conserving therapy (BCT) for patients with early stage breast carcinoma. The authors retrospectively reviewed the outcome of BCT for early stage breast carcinoma to determine the success of BCT at the study institution, a 1000‐bed community hospital.