Intraoperative planning and evaluation of permanent prostate brachytherapy: report of the American Brachytherapy Society.

PURPOSE: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP). METHODS AND MATERIALS: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique. RESULTS: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints. CONCLUSION: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial.

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

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.

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.

Iridium-192 transperineal interstitial brachytherapy for locally advanced or recurrent gynecological malignancies.

PURPOSE: To assess treatment outcome for patients with locally advanced or recurrent gynecological malignancies treated with continuous low-dose-rate (LDR) remote afterloading brachytherapy using the Martinez Universal Perineal Interstitial Template (MUPIT). MATERIALS AND METHODS: Between 7/85 and 6/94, 69 patients with either locally advanced or recurrent malignancies of the cervix, endometrium, vagina, or female urethra were treated by 5 different physicians using the MUPIT with (24 patients) or without (45 patients) interstitial hyperthermia. Fifty-four patients had no prior treatment with radiation and received a combination of external beam irradiation (EBRT) and an interstitial implant. The combined median dose was 71 Gy (range 56-99 Gy), median EBRT dose was 39 Gy (range 30-74 Gy), and the median implant dose was 32 Gy (range 17-40 Gy). Fifteen patients with prior radiation treatment received an implant alone. The total median dose including previous EBRT was 91 Gy (range 70-130 Gy) and the median implant dose was 35 Gy (range 25-55 Gy). RESULTS: With a median follow-up of 4.7 yr in survivors, the 3-yr actuarial local control (LC), disease-specific survival (DSS), and overall survival (OS) for all patients was 60%, 55%, and 41% respectively. The clinical complete response rate was 78% and in these patients the 3-year actuarial LC, DSS, and OS was 78%, 79%, and 63% respectively. On univariate analysis for local control, disease volume and hemoglobin were found to be statistically significant. On multivariate analysis, however, only disease volume remained significant (p = 0.011). There was no statistically significant difference in local control whether patients had received any prior treatment with radiation (p = 0.34), had recurrent disease (p = 0.13), or which physician performed the implant (p = 0.45). The grade 4 complication rate (small bowel obstruction requiring surgery, fistulas, soft tissue necrosis) for all patients was 14%. With a dose rate less than 70 cGy/hour, the grade 4 complication rate was 3% vs. 24% with dose rate > or = 70 cGy/hour (p = 0.013). CONCLUSION: Patients with locally advanced or recurrent gynecological malignancies treated with the remote afterloader LDR MUPIT applicator can expect reasonable rates of local control that are not operator-dependent. Complication rates with this approach are acceptable and appear to be related to the dose rate.

Use of three-dimensional radiation therapy planning tools and intraoperative ultrasound to evaluate high dose rate prostate brachytherapy implants.

PURPOSE: We performed a pilot study to evaluate the quality of high dose rate (HDR) prostate implants using a new technique combining intraoperative real-time ultrasound images with a commercially available 3-dimensional radiation therapy planning (3D RTP) system. METHODS AND MATERIALS: Twenty HDR prostate implants performed by four different physicians on a phase I/II protocol were evaluated retrospectively. Radiation therapy (RT) consisted of pelvic external beam RT (EBRT) to a dose of 46 Gy in 2-Gy fractions over 5 weeks and 2 HDR implants (prescribed dose of 950 cGy per implant). Our in-house real-time geometric optimization technique was used in all patients. Each HDR treatment was delivered without moving the patient. Ultrasound image sets were acquired immediately after needle placement and just prior to HDR treatment. The ultrasound image sets, needle and source positions and dwell times were imported into a commercial computerized tomography (CT) based 3D RTP system. Prostate contours were outlined manually caudad to cephalad. Dose-volume histograms (DVHs) of the prostate were evaluated for each implant. RESULTS: Four patients with stage T2a carcinoma, 4 with stage T2b, and 3 with stage T1c were studied. The median number of needles used per implant was 16 (range 14-18). The median treated volume of the implant (volume of tissue covered by the 100% isodose surface) was 82.6 cc (range 52.6-96.3 cc). The median target volume based on the contours entered in the 3D RTP system was 44.83 cc (range 28.5-67.45 cc). The calculated minimum dose to the target volume was 70% of the prescribed dose (range 45-97%). On average 92% of the target volume received the prescribed dose (range 75-99 %). The mean homogeneity index (fraction of the target volume receiving between 1.0 to 1.5 times the prescribed dose) was 80% or 0.8 (range 0.55-0.9). These results compare favorably to recent studies of permanent implants which report a minimum target volume dose of 43% (range 29-50%) and an average of 85% of the target volume (range 76-92%) receiving the prescribed dose. CONCLUSIONS: The feasibility of evaluating HDR prostate implants using ultrasound images (acquired immediately prior to treatment) with a commercially available 3D RTP system was established. The dosimetric characteristics of these HDR implants appear to be substantially different compared to permanent implants. These developments allow quantitative evaluation of the dosimetric quality of HDR prostate treatments. Future studies will examine any correlation between the dosimetric quality of the implant and clinical/biochemical outcomes.

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 patient's 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.

The use of ultrasonography in the localization of the lumpectomy cavity for interstitial brachytherapy of the breast.

PURPOSE: To determine the value of breast ultrasonography (US) in defining the lumpectomy cavity for patients treated with interstitial brachytherapy. METHODS AND MATERIALS: In March 1993, a protocol of low dose rate (LDR) interstitial brachytherapy as the sole radiation modality in selected patients with early breast cancer was initiated at William Beaumont Hospital. To date, 60 patients have been entered in this protocol, and 38 have undergone US assisted placement of interstitial brachytherapy needles. The lumpectomy cavity was outlined in all dimensions and corresponding skin marks were placed for reference at time of implantation. These US dimensions were compared to the physician's clinical estimate of the location of the lumpectomy cavity, the patient's presurgical mammogram, and the position of the surgical scar. In the intraoperative setting, the dimensions of the lumpectomy cavity were also obtained and the placement of the deep plane of interstitial needles was verified by US. RESULTS: The full extent of the lumpectomy cavity was underestimated by clinical examination (physical exam, operative report, mammographic information and location of the surgical scar) in 33 of 38 patients (87%). The depth to the chest wall was also incorrectly estimated in 34 (90%) patients when compared to US examination. Intraoperatively, US was performed in nine patients and was useful in verifying the accurate placement of the deepest plane of interstitial brachytherapy needles. In 7 of 9 patients (75%), clinical placement of needles did not ensure adequate coverage of the posterior extent of the lumpectomy cavity as visualized by intraoperative US. CONCLUSIONS: In breast cancer patients considered for interstitial brachytherapy, US appears to be a more accurate means of identifying the full extent of the lumpectomy cavity when compared to clinical estimates. In addition, US allows real-time verification of needle placement in the intraoperative setting.

Low-dose-rate brachytherapy as the sole radiation modality in the management of patients with early-stage breast cancer treated with breast-conserving therapy: preliminary results of a pilot trial.

PURPOSE: We present the preliminary 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). METHODS AND MATERIALS: Since March 1, 1993, 60 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation only using an interstitial LDR implant with iodine-125. Patients were eligible if the tumor was < or = 3 cm, margins were > or = 2 mm, there was no extensive intraductal component, the axilla was surgically staged, and a postoperative mammogram was performed. Implants were placed using a standardized template either at the time of reexcision or shortly after lumpectomy. A total of 50 Gy was delivered at 0.52 Gy/h over a period of 96 h to the lumpectomy bed plus a 2-cm margin. Perioperative complications, cosmetic outcome, and local control were assessed. RESULTS: The median follow-up for all patients is 20 months. Three patients experienced minimal perioperative pain that required temporary nonnarcotic analgesics. There have been four postoperative infections which resolved with oral antibiotics. No significant skin reactions related to the implant were noted and no patient experienced impaired would healing. Early cosmetic results reveal minimal changes consisting of transient hyperpigmentation of the skin at the puncture sites and temporary induration in the tumor bed. Good to excellent cosmetic results were noted in all 19 patients followed up a minimum of 24 months posttherapy. To date, 51 women have obtained 6-12-month follow-up mammograms and no recurrences have been noted. All patients currently have no physical signs of recurrence, and no patient has failed regionally or distantly. CONCLUSION: Treatment of the tumor bed alone with LDR interstitial brachytherapy appears to be well tolerated, and early results are promising. Long-term follow-up of these patients is necessary to establish the equivalence of this treatment approach compared to standard BCT, however.

The impact of temporary iodine-125 interstitial implant boost in the primary management of squamous cell carcinoma of the oropharynx.

BACKGROUND: To define the impact of interstitial boost of the oropharynx on local control and complications using iodine-125 (I-125) brachytherapy. METHODS: Between October 1986 and September 1991, 19 patients with cancer of the oropharynx received treatment at William Beaumont Hospital. Primary tumors consisted of 13 base of tongue, 4 tonsillar, and 2 pharyngeal wall lesions. All patients received 45-66 Gy (median, 54 Gy) external beam irradiation to the primary and regional nodes, followed by an interstitial implant of 22-32 Gy (median, 25 Gy) with I-125. RESULTS: Median follow-up was 58 months (range, 12-89 months). Three patients failed within the tumor bed, for a 5-year actuarial rate of local control of 83% (T1/T2, 82%; T3/T4, 86%). Two of the three local failures were salvaged surgically, for an overall 5-year actuarial local control rate of 94%. The 5-year actuarial overall survival rate was 64%. Complications included one case of soft tissue ulceration and two cases of osteoradionecrosis, all managed conservatively. CONCLUSIONS: Patients with cancer of the oropharynx judged to be candidates for boosts with interstitial implants can be effectively treated with I-125. Local control was excellent, and complications were minimal.

Long-term outcome with interstitial brachytherapy in the management of patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We reviewed our institution's experience with interstitial implant boosts to determine their long-term impact on local control and cosmetic results. METHODS AND MATERIALS: Between January 1, 1980 and December 31, 1987, 390 women with 400 cases of Stage I and II breast cancer were managed with breast-conserving therapy (BCT) at William Beaumont Hospital. All patients were treated with an excisional biopsy and 253 (63%) underwent reexcision. Radiation consisted of 45-50 Gy external beam irradiation to the whole breast followed by a boost to the tumor bed to at least 60 Gy using either electrons [108], photons [15], or an interstitial implant [277] with either 192Ir [190] or 125I [87]. Long-term local control and cosmetic outcome were assessed and contrasted between patients boosted with either interstitial implants, electrons, or photons. RESULTS: With a median follow-up of 81 months, 25 patients have recurred in the treated breast for a 5- and 8-year actuarial rate of local recurrence of 4 and 8%, respectively. There were no statistically significant differences in the 5- or 8-year actuarial rates of local recurrence using either electrons, photons, or an interstitial implant. Greater than 90% of patients obtained a good or excellent cosmetic result, and no statistically significant differences in cosmetic outcome were seen whether electrons, photons, or implants were used. CONCLUSIONS: We conclude that patients with Stage I and II breast cancer undergoing BCT and judged to be candidates for boosts can be effectively managed with LDR interstitial brachytherapy. Long-term local control and cosmetic outcome are excellent and similar to patients boosted with either electrons or photons.

Intraoperative optimization of needle placement and dwell times for conformal prostate brachytherapy.

PURPOSE: Traditionally, transperineal prostate brachytherapy has been heavily operator dependent. To overcome this limitation, a treatment planning method was developed for intraoperative planning, guidance, and evaluation. In this setting, reliability, speed, and ease of understanding are primary considerations. This planning method has been implemented for ultrasound guided implants of the prostate, but can be extended for use in other body sites. METHODS AND MATERIALS: The length and cross-section of the target (prostate) and location of urethra and rectum are determined intraoperatively from live ultrasound imaging. The planning program then automatically generates a "reference plan" containing needle locations, dwell times, and the resulting isodose distribution. As needles are placed, this information is corrected to account for any deviation of needle placement or movement of the prostate. Once all needles are in place, the normalization is adjusted to reconcile remaining hot-spots with coverage of the target volume. Optimization is performed in three separate stages. Each stage works to enhance only a subset of the implant parameters. (a) Pattern Optimization attempts to find the most appropriate placement for the needles or catheters. It is based on the transverse contour of the target volume. Needles are placed uniformly around the perimeter, and interior needle positions are determined from the cross-sectional area and shape. Critical structures such as the urethra are explicitly avoided. This step provides the overall framework for the implant, and is not generally repeated. (b) Relative Dwell Time Optimization selects relative dwell times that will give the best uniformity of dose. It works by setting the relative dwell time in each source position inversely proportional to the dose delivered to that point by the other source positions. It is used in the reference plan, and is repeated as each needle is inserted. This provides dosimetric feedback to the physician, who can judge the effect of deviations from the reference plan. (c) Relative Volume Optimization is an interactive method for fine tuning the normalization based upon volume analysis. The volume analysis is presented in tabular and graphical form, both being updated rapidly as the normalization is adjusted. The information is formatted to help the operator judge coverage and uniformity. Special functions are provided that allow the operator to "jump" to special normalization values based on several indices of uniformity or uniformity/coverage. RESULTS: This system overcomes some conventional brachytherapy limitations. Rather than depend on the operator's intuitive judgement of where the needles should be placed, a global plan is generated and validated with full dose calculations. Immediate feedback is provided concerning the adequacy of placement and avoidance of critical structures. This information is provided in terms of actual tissue doses to the target volume and critical structures using point doses, isodose distributions, and volume analysis. Since the new method was introduced in January 1994, 33 implants have been performed. The needle placement method has been reliable in the clinic, with different doctors producing similar results on subsequent fractions for the same patient. CONCLUSION: The method of decomposing the optimization problem into several simple steps is capable of rapidly, consistently, and reliably designing conformal treatment plans of high uniformity. Operator dependence has been significantly reduced. We are adapting the method for other anatomic sites.

Concurrent treatment planning for outpatient high dose rate prostate template implants.

PURPOSE: Since November of 1991, we have treated locally advanced (B2-C) prostate cancer using external beam radiotherapy integrated with outpatient high dose rate interstitial implant boost as part of a Phase II clinical trial. This required (a) rapid, automated planning; (b) incorporation of image data and (c) dose optimization. METHODS AND MATERIALS: A treatment planning system was designed which integrates imaging and needle guidance with source reconstruction and dose display. All components of treatment planning (reconstruction, optimization, dose prescription, dose display) are largely automated. A rectal reference point was defined which was reproducible and easily verified. No pretreatment planning was required. RESULTS: As of November 1992, 83 treatments were delivered using this system. Intra-operative treatment decisions were made possible due to the speed and ease of interpretation of the system. The system has proven satisfactory in the operating room. Rectal doses were calculated for all patients, and ranged from 35-79% of the prescribed dose, with a mean of 58%. The first echelon of a Phase II escalating dose trial has been completed, with 22 patients treated over a period of 1 year. CONCLUSION: Outpatient high dose rate brachytherapy appears to be a practical means of boosting locally advanced prostate cancer patients. Rapid treatment planning is possible incorporating on-line ultrasound images to allow immediate dose optimization to be performed during and after implant placement.

The clinical advantages of I-125 seeds as a substitute for Ir-192 seeds in temporary plastic tube implants.

In August of 1986 at William Beaumont Hospital, Iodine-125 (I-125) seeds were introduced in the clinical practice as a substitute for Iridium-192 (Ir-192) seeds in patients undergoing temporary plastic tube interstitial implants. Through February 1988, 108 I-125 implants were performed in 105 patients. Acute and chronic toxicity was indistinguishable from Ir-192. However, improved radiation safety and a dynamic dosimetric program have resulted from this endeavor. Because of the multiple clinical advantages of I-125, we feel that this should be considered the isotope of choice in temporary interstitial plastic tube implants.

The utilization of I-125 seeds as a substitute for Ir-192 seeds in temporary interstitial implants: an overview and a description of the William Beaumont Hospital technique.

In August of 1986, the Department of Radiation Oncology at William Beaumont Hospital (WBH) initiated the routine use of high activity I-125 seeds as a substitute for Ir-192 seeds in temporary implants where the afterloading plastic tube technique was used. Through March 6, 1987, 42 temporary I-125 implants were performed as a boost for curative therapy (38 breasts, 2 sarcomas, 2 tongues). Thus far, we have observed no differences in acute toxicity. Sources ranging from 2 to 5 mCi were utilized. The advantages of I-125 are as follows: (a) Easy to shield; (b) Radiation safety; (c) Decreased exposure to sensitive organs in close proximity to the implanted site; (d) Dosimetric advantages both intrinsic and extrinsic; and (e) Any private room can be used for these patients allowing a central brachytherapy ward to be established. While the advantages were obvious, we anticipated potential disadvantages and shortcomings and these will be discussed in detail. Furthermore because of significant differences in tube and ribbon construction, the I-125 afterloading plastic tube technique has important differences from that technique used with Ir-192. These modifications must be fully understood to maintain the integrity of the I-125 seed-ribbon afterloading tube assembly. A detailed description of the technique will be emphasized.

Pelvic lymphadenectomy combined with transperineal interstitial implantation of iridium-192 and external beam radiotherapy for locally advanced prostatic carcinoma: technical description.

Regardless of the treatment modality, control of locally advanced extracapsular prostatic cancer remains a therapeutic challenge. At the Mayo Clinic, we have recently developed a combined approach for surgically staged patients employing interstitial irradiation with 192 Iridium via a transperineal template. The Martinez Universal Perineal Interstitial Template (MUPIT-II) and moderate doses of external beam irradiation. The procedure consists of: 1) preoperative single dose external beam irradiation to decrease potential for tumor seeding or showering of malignant cells during MUPIT-II placement; 2) adequate surgical staging through a bilateral retroperitoneal lymphadenectomy; 3) transperineal interstitial implantation of the tumor and retropubic palpation of the needles to verify proper position; 4) intraoperative X rays are taken and used for documentation of needle position as well as for calculation and optimization of the implant dose distribution with the aid of a computerized system; 5) moderate doses of external beam irradiation postoperatively to the prostate with adequate margins. Our favorable preliminary results obtained in 18 patients treated with the above approach warrant the continuation of this trial. Details of this technique are presented.

Acute toxicity and preliminary therapeutic results of pelvic lymphadenectomy combined with transperineal interstitial implantation of 192IR and external beam radiotherapy for locally advanced prostate cancer.

We have developed a combined modality approach for treatment of locally advanced prostate cancer consisting of: surgical staging with lymphadenectomy; transperineal placement of afterloading needles for a course of 192Ir brachytherapy; and a course of moderate-dose external beam irradiation to tight prostatic fields. The flexibility of the treatment permits adaptation of the dose to any tumor configuration. A total of 23 patients have been treated to date; 18 are available for treatment review and 14 for acute toxicity analysis. Significant morbidity has occurred in only 2 patients, 1 with a pelvic hematoma and 1 with hematoma in the wound. Local tumor response has been excellent in all but 1 patient. A good degree of symptomatic improvement was observed at the three-month follow-up. This approach appears to be safe and effective at this time. A brief review of the technique and the rationale for its use are also presented.

Management of malignant airway obstruction: clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser.

Fourteen patients with malignant airway obstruction have had 21 placements of a flexible nylon catheter for afterloading Iridium-192 using the flexible fiberoptic bronchoscope. Prescribed therapy was completed in 13 patients (18 courses). All patients had prior full-dose external irradiation, and no effective surgical or chemotherapeutic options remained. While many have had a trial of neodymium-YAG (yttrium-aluminum-garnet) laser therapy alone, eight patients received laser treatment one to three weeks prior to planned brachytherapy to provide immediate relief of symptoms and/or facilitate access and safe catheter placement. Most patients (64%) had recurrent squamous cell lung cancer. A dose of 3000 cGy is currently specified to 5 mm and 10 mm in the bronchus and trachea, respectively. Nine of the 13 treated patients have had follow-up bronchoscopy at approximately three months post-treatment with improvement documented in seven and progression in two patients. One patient was clinically improved without follow-up bronchoscopy, and three patients have had insufficient follow-up. A single patient treated with laser and 6000 rad at 5 mm developed a bronchoesophageal fistula. No other complication has been observed. The technique is simple and safe with the use of laser therapy when needed and appears to offer effective palliation in most patients even when standard therapy is exhausted.

Combination of external beam irradiation and multiple-site perineal applicator (MUPIT) for treatment of locally advanced or recurrent prostatic, anorectal, and gynecologic malignancies.

We have devised a single after-loading applicator, the Martinez Universal Perineal Interstitial Template (MUPIT), which has been used in combination with external beam irradiation to treat 104 patients with either locally advanced or recurrent malignancies of the cervix, vagina, female urethra, prostate, or anorectal region. Twenty-six patients treated for prostate cancer are excluded because of their short follow-up. Local failure developed in 13 of the 78 remaining patients (16.6%)--major complications developed in 4 patients (5.1%). Follow-up has been 1 year to 7 1/2 years; 60/78 patients have been followed for more than 2 years. All local recurrences and complications occurred before 18 months. The device consists of two acrylic cylinders, an acrylic template with an array of holes that serve as guides for trocars, and a cover plate. In use, the cylinders are placed in the vagina and/or rectum or both and then fastened to the template so that a fixed geometric relationship among the tumor volume, normal structures, and source placement is preserved throughout the course of the implantation. Appropriate computer programs have been developed to calculate the dose from these implants. The advantages of the system are (a) greater control of the placement of sources relative to the tumor volume and critical structures, as a result of the fixed geometry provided by the template and cylinders, and (b) improved dose-rate distributions obtained by means of computerized optimization of the source placement and strength during the planning phase. We conclude that the local control rate (83.4%) with low morbidity (5.1%) achieved with the combination of external beam irradiation and MUPIT applicator in these patients with locally advanced malignancies represents an improvement over previous published results with other applicators.