Dosimetric feasibility and acute toxicity in a prospective trial of ultrashort-course accelerated partial breast irradiation (APBI) using a multi-lumen balloon brachytherapy device.

BACKGROUND: Shorter courses of APBI, including single-fraction intraoperative therapy, are under active investigation. We designed a prospective trial to identify and address the potential radiobiological and logistical shortcomings of single-fraction APBI. METHODS: We designed a single-arm, multi-institutional, prospective phase II trial that sequentially treats 3 cohorts of women (each n = 30) with 3 progressively hypofractionated schedules. Eligible women were age ≥50 years with unifocal invasive or in situ tumors ≤3.0 cm, excised with negative margins, and with negative lymph nodes and positive hormone receptors. We defined strict dosimetric criteria for appropriateness. RESULTS: A total of 30 patients were enrolled at the 7 Gy × 4 fractions dose-level and followed for 6 months. The median skin dose as a percent of prescription dose (PD) was 84 % (40-100), and the median rib dose was 71 % (16-119). Also, 95 % of the PTV_eval received a median of 95 % of PD (range 85-103). The V150 (range 14-48 cc) and V200 (range 0-29 cc) criteria were met in all cases. One breast infection occurred and was treated; 2 cases of symptomatic fat necrosis and 2 cases of symptomatic seromas occurred. CONCLUSION: Short-course APBI is dosimetrically feasible using the Contura MLB and appears to be tolerable in terms of acute toxicities. Our approach is based on well-defined radiobiological parameters and allows for an abbreviated course of treatment that is guided by full pathological review and the ability to objectively achieve and validate acceptable dosimetric criteria in each case. We have opened enrollment to the next schedule of 8.25 Gy for 3 fractions.

The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema.

We performed a multi-institutional analysis to evaluate the ability of bioimpedance spectroscopy (BIS) to capture the impact of lymphedema treatment compared with observation alone in the management of breast cancer related lymphedema (BCRL). We utilized a retrospective review of 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional treatment. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second (subset) analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to undergoing loco-regional treatment (n=32). When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) in the period following intervention (for treated patients). For the subset of patients with elevated L-Dex scores postoperation, the change in L-Dex score following BCRL treatment was significantly reduced (-5.8 v. 0.1, p=0.001) compared with the group observed that had elevated postsurgical L-Dex scores. In this analysis, BIS was able to detect early onset lymphedema and subsequently significant changes (reductions) in L-Dex scores directly related to intervention for BCRL compared with observation alone.

Six-year analysis of treatment-related toxicities in patients treated with accelerated partial breast irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy registry trial.

BACKGROUND: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity. RESULTS: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections. CONCLUSIONS: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Local control, toxicity, and cosmesis in women younger than 50 enrolled onto the American Society of Breast Surgeons MammoSite Radiation Therapy System registry trial.

BACKGROUND: The American Society of Breast Surgeons enrolled women onto a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System (RTS) breast brachytherapy device. This report examines local recurrence (LR), toxicity, and cosmesis as a function of age in women enrolled onto the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50 years of age. Fisher's exact test was performed to correlate age (<50 vs. > or = 50 years) with toxicity and with cosmesis. The association of age with LR failure times was investigated by fitting a parametric model. RESULTS: Women younger than 50 were more likely to develop fat necrosis: 4.6% (6 of 130) vs. 1.8% (24 of 1319) (P = .0456). Other toxicities were comparable. At 2 years, cosmesis was excellent or good in 87% of assessable women aged <50 years (n = 74) and in 94% of assessable older women (n = 751) (P = .0197). At 3 years, this difference disappeared: excellent or good in 90% (56 of 62) of younger women vs. 93% (573 of 614) of older women (P = .2902). The crude LR rate for the group was 1.7% (25 of 1449). There was no statistically significant difference in LR as a function of age. In women <50, 3.1% (4 of 130) developed a LR; in the older patients, 1.6% (21 of 1319) developed LR (3-year actuarial LR rates, 2.9% vs. 1.7%, respectively; P = .2284). CONCLUSIONS: Accelerated partial breast irradiation with the MammoSite RTS results in low toxicity and produces similar cosmesis and local control at 3 years in women younger than 50 when compared with older women.

Impact of young age on outcome in patients with ductal carcinoma-in-situ treated with breast-conserving therapy.

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to determine the impact of patient age on outcome. PATIENTS AND METHODS: From 1980 to 1993, 146 patients were treated with BCT for DCIS. All patients underwent excisional biopsy, and 64% underwent re-excision. All patients received whole-breast irradiation to a median dose of 45 Gy. Ninety-four percent of patients received a boost to the tumor bed, for a median total dose of 60.4 Gy. All slides on every patient were reviewed by one pathologist. The median follow-up period was 7.2 years. RESULTS: Seventeen patients developed an ipsilateral local recurrence, for 5- and 10-year actuarial rates of 10.2% and 12.4%, respectively. The 10-year rate of ipsilateral failure was 26.1% in patients younger than 45 years of age versus 8.6% in older patients (P =.03). On multivariate analysis, young age was independently associated with recurrence of the index lesion (true recurrence/marginal miss ¿TR/MM failures), regardless of how it was analyzed (eg, < 45 years of age or as a continuous variable). In addition, young patients had a dramatically higher 10-year rate of invasive TR/MM failures (19.9% v 3.2%). In a separate multivariate analysis for the development of invasive TR/MM failures, only patient age and predominant nuclear grade were independently associated with recurrence. The relationship between excision volume and outcome was analyzed in the 95 patients who underwent re-excision. The 5-year actuarial rate of TR/MM failure was significantly worse only in young patients with smaller (< 40 mL) re-excision volumes (33.3% v 9.1%; P =.02). In a separate multivariate analysis of only these 95 patients (25 of whom were < 45 years of age), the volume of re-excision had the strongest association with outcome (P =.05). Patient age was no longer associated with local recurrence. CONCLUSION: These findings suggest that young patients with DCIS have a significantly greater risk of local recurrence after BCT that is independent of other previously defined risk factors. Our data also suggest that the extent of resection may in part be related to the less optimal results that are observed in these patients.

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.

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.

Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma.

We retrospectively analyzed the likelihood of regional nodal failure (RNF) for 1,624 patients with stage I or II invasive breast carcinoma treated with conservative surgery and radiotherapy (RT) at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. The median follow-up time was 77 months. RNF was the first site of failure for 38 of the 1,624 patients (2.3%). The incidence of axillary failure for patients undergoing axillary dissection (AXD) who were irradiated to the breast only was 2.1% (nine of 420) for patients with negative nodes and 2.1% (one of 47) for patients with one to three positive nodes. The incidence of supraclavicular failure in these two groups was 1.9% (eight of 420) and 0% (zero of 47), respectively. The incidences of axillary and supraclavicular failure in patients without clinically suspicious axillary involvement who did not have AXD but were treated with RT were 0.8% (three of 355) and 0.3% (one of 364), respectively. Despite various combinations of salvage surgery, RT, and systemic therapy, only 47% of patients (18 of 38) achieved complete regional control after nodal relapse. We conclude that RNF is uncommon in patients treated to the breast alone following an adequate AXD when the axillary nodes are negative or when one to three nodes are positive. RNF is also uncommon in patients with a clinically uninvolved axilla treated with nodal RT without AXD. Symptoms of RNF can be controlled in most but not all patients. Further study is needed to determine if the benefits of RT in preventing a small number of symptomatic RNF outweigh the potential toxicity for any subgroup of patients.

Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer.

PURPOSE: This analysis was performed to clarify the relationship of young age at diagnosis to the pathologic features of the tumor and prognosis in patients with early-stage breast cancer. PATIENTS AND METHODS: We retrospectively analyzed data from 1,398 patients with American Joint Committee on Cancer Staging stage I or II breast cancer treated by breast-conserving therapy between 1968 and 1985. One hundred seven patients were younger than 35 years at the time of diagnosis. The median follow-up duration for the 1,032 survivors was 99 months. RESULTS: Patients younger than 35 years had a significantly higher overall recurrence rate (P = .002), as well as a greater risk for developing distant metastases (P = .03), when compared with older patients. The cancers in younger patients more commonly showed factors associated with a worse prognosis (including grade 3 histology, lymphatic vessel invasion [LVI], necrosis, and estrogen receptor [ER] negativity) as compared with older patients. In a proportional hazards model that included clinical and treatment-related variables, as well as these pathologic features, age younger than 35 years remained a significant predictor for time to recurrence (relative risk [RR], 1.70), time to distant failure (RR, 1.60), and overall mortality (RR, 1.50). CONCLUSION: Breast cancer patients younger than 35 years have a worse prognosis than older patients. This difference is only partially explained by a higher frequency of adverse pathologic factors seen in younger patients.

Accelerated treatment of breast cancer.

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of adequate follow-up in defining treatment success after external beam irradiation for prostate cancer.

PURPOSE: We reviewed our institution's experience treating patients with localized prostate cancer with external beam radiation therapy (RT) to determine how differences in the length of follow-up affect the determination of treatment outcome using the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Panel Definition of biochemical failure (BF). METHODS AND MATERIALS: From January 1987 through December 1997, 1109 patients with localized prostate cancer were treated with definitive external beam RT at William Beaumont Hospital, Royal Oak, Michigan. All patients received external beam RT to a median total prostate dose of 66.6 Gy (range: 59.4-70.4 Gy). A total of 1096 patients (99%) had sufficient prostate-specific antigen (PSA) follow-up to determine their biochemical status. To test the impact of differences in follow-up on the calculation of BF, 389 patients with at least 5 years of PSA follow-up were selected as the reference group for the initial analysis. BF was then retrospectively determined using the Consensus Panel definition at yearly intervals, ignoring the remainder of each patient's follow-up. The median follow-up for this group of patients was 6.6 years (range: 5.0-11.6 years). In a second analysis, patient cohorts were randomly selected with varying median PSA follow-up intervals in order to more accurately represent a population whose follow-up is distributed continuously over a defined range. Seven cohorts were randomly selected with 200 patients in each cohort. Cohorts were individually identified such that half of the patients (100) had 2 years or less follow-up than the stated time point for analysis and half (100) had up to 2 years more follow-up than the time point chosen for analysis. For example, in the cohort with a median follow-up of 3 years, 100 patients with a PSA follow-up from 1 to 3 years were randomly selected, and 100 patients with a follow-up from 3 to 5 years were randomly selected, thus generating a median follow-up of 3 years for this cohort (range: 1 to 5 years). This process was repeated five times for five random samples of seven cohorts each. Biochemical failure was calculated according to the Consensus Panel definition. RESULTS: In the first analysis, significantly different rates of biochemical control (varying by 6-21%) were calculated for the same actuarial year chosen for analysis depending only upon the length of follow-up used. For example, the 3-year actuarial rate of biochemical control (BC) varied from 71% when calculated with 3 years of follow-up versus 50.4% with 7 years (p < 0.01). These differences in actuarial rates of BC were observed in all subsets of patients analyzed (e.g., PSA < 10, Gleason < or = 6, n = 132,p < 0.001; PSA < 10, Gleason > or = 7, n = 33, p = 0.03; PSA > or = 10, Gleason < or = 6, n = 109, p < 0.001; and PSA > or = 10, Gleason > or = 7, n = 72, p = 0.002). The absolute magnitude of the difference in actuarial rates of BC was greatest during years 2 (range 18-30%), 3 (range 16-25%), and 4 (range 15-24%) after treatment. In the second analysis using median PSA follow-ups (as defined above), statistically significant differences in actuarial rates of BC were again observed. For example, the 3-year actuarial rate of BC varied from 74.8% with a median follow-up of 2 years versus 49.2% with a median follow-up of 6 years. These dramatic differences in BC were still observed beyond 5 years. CONCLUSION: When the ASTRO Consensus Panel definition of BF is used to calculate treatment success with external beam RT for prostate cancer, adequate follow-up is critical. Depending upon the length of time after treatment, significantly different rates of BC (varying by 15% to 30%) can be calculated for the same time interval chosen for analysis. These results suggest that data should only be reported if the length of follow-up extends at least beyond the time point at which actuarial results are examined for the majority of patients.

Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better?

PURPOSE: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship. METHODS AND MATERIALS: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded. RESULTS: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] > or = 10, Gleason score [GS] > or = 7, or tumor stage > or = T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified. CONCLUSIONS: Although RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefitting most, and the optimal dose remain to be defined.

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.

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 use of iodine-125 seeds as a substitute for iridium-192 seeds in temporary interstitial breast implants.

PURPOSE: We have previously reported that the use of iodine-125 seeds in temporary plastic tube interstitial implants may be more advantageous than iridium-192 seeds due to less patient and personnel radiation exposure, reduced shielding requirements, and significant dosimetric advantages. The impact of this isotope on the rate of local control and cosmetic outcome in patients with early stage breast cancer treated with interstitial implants for their irradiation "boost" remains to be defined. METHODS AND MATERIALS: We reviewed the treatment outcome of 402 consecutive cases of Stage I and II breast cancer undergoing breast conserving therapy between 1/1/80 and 12/31/87. All patients underwent excisional biopsy and received 45-50 Gy to the entire breast followed by a boost to the tumor bed using either electrons (104 patients), photons (15 patients), or an interstitial implant with either iridium-192 (197 patients) or iodine-125 (86 patients) to at least 60 Gy. Iodine-125 implants were primarily performed in patients with significant risk factors for local recurrence (71%) or in patients with large breasts (17%). Local tumor control and cosmetic outcome were assessed and contrasted between patients boosted with each modality. RESULTS: With a median follow-up of 59.3 months, 18 (4.5%) patients developed a recurrence of the tumor in the treated breast (4.4% 5-year actuarial rate). No statistically significant differences in the 5-year actuarial rate of local recurrence were noted between patients boosted with either iodine-125 (3.0%), iridium-192 (3.8%), electrons (5.4%), or photons (0%). Likewise, no significant differences in the percentage of patients obtaining good/excellent cosmetic results were noted between iodine-125 (93%), iridium-192 (88%), electrons (90%), or photons (82%). CONCLUSION: We conclude that patients with Stage I and II breast cancer undergoing breast conserving therapy and judged to be candidates for boosts with interstitial implants can be effectively treated with iodine-125 seeds. Use of this isotope results in less patient and personnel irradiation exposure and a better dose distribution than iridium-192, since dose optimization can be routinely employed. Overall, local control and cosmetic outcome have been excellent and are similar to either iridium-192, electrons, or photons.

Adaptive modification of treatment planning to minimize the deleterious effects of treatment setup errors.

PURPOSE: Using daily setup variation measured from an electronic portal imaging device (EPID), radiation treatment of the individual patient can be adaptively reoptimized during the course of therapy. In this study, daily portal images were retrospectively examined to: (a) determine the number of initial days of portal imaging required to give adequate prediction of the systematic and random setup errors; and (b) explore the potential of using the prediction as feedback to reoptimize the individual treatment part-way through the treatment course. METHODS AND MATERIALS: Daily portal images of 64 cancer patients, whose treatment position was not adjusted during the course of treatment, were obtained from two independent clinics with similar setup procedures. Systematic and random setup errors for each patient were predicted using different numbers of initial portal measurements. The statistical confidence of the predictions was tested to determine the number of daily portal measurements needed to give reasonable predictions. Two treatment processes were simulated to examine the potential opportunity for setup margin reduction and dose escalation. The first process mimicked a conventional treatment. A constant margin was assigned to each treatment field to compensate for the average setup error of the patient population. A treatment dose was then prescribed with reference to a fixed normal tissue tolerance, and then fixed in the entire course of treatment. In the second process, the same treatment fields and prescribed dose were used only for the initial plan and treatment. After several initial days of treatments, the treatment field shape and position were assumed to be adaptively modified using a computer-controlled multileaf collimator (MLC) in light of the predicted systematic and random setup errors. The prescribed dose was then escalated until the same normal tissue tolerance, as determined in the first treatment process, was reached. RESULTS: The systematic setup error and the random setup error were predicted to be within +/-1 mm for the former and +/-0.5 mm for the latter at a > or = 95% confidence level using < or = 9 initial daily portal measurements. In the study, a large number of patients could be treated using a smaller field margin if the adaptive modification process were used. Simulation of the adaptive modification process for prostate treatment demonstrates that additional treatment dose could be safely applied to 64% of patients. CONCLUSION: The adaptive modification process represents a different approach for use of on-line portal images. The portal imaging information from the initial treatments is used as feedback for reoptimization of the treatment plan, rather than adjustment of the treatment setup. Results from the retrospective study show that the treatment of individual patient can be improved with the adaptive modification process.

Effects of treatment setup variation on beam's eye view dosimetry for radiation therapy using the multileaf collimator vs. the cerrobend block.

PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy.

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, we retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002). A case:control analysis was performed to determine if the volume of lung irradiated (as determined using central lung distance [CLD]) was related to the risk of developing radiation pneumonitis. Three control patients were matched to each case of radiation pneumonitis based on age, side of lesion, chemotherapy (including sequencing), use of a third field, and year treated. Lung volumes were similar in the radiation pneumonitis cases and controls. We conclude that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy). Over the limited range of volumes treated, lung volume was not associated with an increased risk of radiation pneumonitis.

Are cosmetic results following conservative surgery and radiation therapy for early breast cancer dependent on technique?

To assess the cosmetic results in relation to treatment technique, we retrospectively reviewed the results for 1159 Stage I-II breast cancer patients treated with conservative surgery and radiotherapy between 1970-1985. All patients underwent gross excision followed by radiation therapy including an implant or electron beam boost. The total dose to the primary site was greater than or equal to 60 Gy. Because of technical modifications introduced over time after 1981, the population was divided arbitrarily into two cohorts: 504 patients treated through 1981 and 655 treated between 1982-1985. Median follow-up time for surviving patients in the two cohorts were 107 months and 67 months, respectively. Cosmetic outcome was evaluated by the examining physician and scored as excellent, good, fair or poor. Excellent results at 5 years were scored in 59% of early cohort patients and 74% of the latter cohort (p = 0.002). Acceptable results (either good or excellent) were seen in 84% and 94%, respectively (p = 0.02). In the latter cohort, the likelihood of achieving an excellent result, but not an acceptable result, was significantly related to the volume of resected breast tissue and the use of chemotherapy. The number of fields (three-field technique, provided that fields are precisely matched, compared to tangents only) and boost type (implant vs electrons) did not influence the cosmetic outcome. We conclude that our current technique using breast RT to 45-46 Gy and a boost to the primary site of 16-18 Gy is associated with a high likelihood of acceptable cosmetic results and that this likelihood is not diminished by the use of adjuvant chemotherapy, a large breast resection, the use of a third field, or boost type.