Richard C. Matter

Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy

PURPOSE To present our clinical experience using intensity-modulated radiation therapy (IMRT) to improve dose uniformity and treatment efficacy in patients with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS A total of 281 patients with Stage 0, I, and II breast cancer treated with breast-conserving therapy received whole breast RT after lumpectomy using our static, multileaf collimator (sMLC) IMRT technique. The technical and practical aspects of implementing this technique on a large scale in the clinic were analyzed. The clinical outcome of patients treated with this technique was also reviewed. RESULTS The median time required for three-dimensional alignment of the tangential fields and dosimetric IMRT planning was 40 and 45 min, respectively. The median number of sMLC segments required per patient to meet the predefined dose-volume constraints was 6 (range 3-12). The median percentage of the treatment given with open fields (no sMLC segments) was 83% (range 38-96%), and the median treatment time was <10 min. The median volume of breast receiving 105% of the prescribed dose was 11% (range 0-67.6%). The median breast volume receiving 110% of the prescribed dose was 0% (range 0-39%), and the median breast volume receiving 115% of the prescribed dose was also 0%. A total of 157 patients (56%) experienced Radiation Therapy Oncology Group Grade 0 or I acute skin toxicity; 102 patients (43%) developed Grade II acute skin toxicity and only 3 (1%) experienced Grade III toxicity. The cosmetic results at 12 months (95 patients analyzable) were rated as excellent/good in 94 patients (99%). No skin telengiectasias, significant fibrosis, or persistent breast pain was noted. CONCLUSION The use of intensity modulation with our sMLC technique for tangential whole breast RT is an efficient method for achieving a uniform and standardized dose throughout the whole breast. Strict dose-volume constraints can be readily achieved resulting in both uniform coverage of breast tissue and a potential reduction in acute and chronic toxicities. Because the median number of sMLC segments required per patient is only 6, the treatment time is equivalent to conventional wedged-tangent treatment techniques. As a result, widespread implementation of this technology can be achieved with minimal imposition on clinic resources and time constraints.

Breast conservation therapy. Severe breast fibrosis after radiation therapy in patients with collagen vascular disease

Two patients with collagen vascular disease (rheumatoid arthritis and scleroderma) had extremely poor cosmetic results after breast radiation therapy (RT). The patient with rheumatoid arthritis received 5251 cGy at 210 cGy per day, followed by a 1600 cGy iridium‐192 implant boost. Between 8 and 11 months post‐RT she had severe breast fibrosis, retraction, and pain that required a mastectomy for relief. The patient with scleroderma received 5040 cGy at 180 cGy per day without a boost. Between 1 and 4 months post‐RT the systemic symptoms of scleroderma progressed and the breast became hard and retracted. Both rheumatoid arthritis and scleroderma are chronic systemic diseases characterized by severe inflammation and an autoimmune component. The presence of scleroderma at or before treatment should be considered a contraindication to breast RT, whereas the presence of active rheumatoid arthritis should be considered a relative contraindication. An autoimmune mechanism will be presented to explain both the fibrosis and the systemic progression of collagen vascular disease that was observed.

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.

OUTCOME AND PROGNOSTIC FACTORS FOR LOCAL RECURRENCE IN MAMMOGRAPHICALLY DETECTED DUCTAL CARCINOMA IN SITU OF THE BREAST TREATED WITH CONSERVATIVE SURGERY AND RADIATION THERAPY

PURPOSE We have retrospectively reviewed our institutions experience treating a predominantly mammographically detected population of ductal carcinoma in situ (DCIS) patients with conservative surgery and radiation therapy (CSRT) to determine outcome and prognostic factors for local recurrence. METHODS AND MATERIALS Between January 1, 1982 and December 31, 1988, 52 consecutive cases of DCIS of the breast were treated with CSRT at William Beaumont Hospital. Forty-six (88%) were mammographically detected nonpalpable lesions. All patients underwent at least an excisional biopsy and 28 (54%) were reexcised. The axilla was surgically staged in 41 (79%) and all were N0. The entire breast was irradiated to 45-50 Gy over 5-6 weeks. The tumor bed was boosted in 49 (94%) so that the minimum dose was 60 Gy. The three patients not boosted received a minimum dose of 50 Gy to the entire breast. Pathologic materials were reviewed by one of the authors. RESULTS The predominant DCIS pattern was comedo in 40%, cribriform in 28%, solid in 17%, and micropapillary in 15%. The predominant nuclear grade was Grade I in 51%, Grade II in 49%, and Grade III in 0%. The median follow-up is 68 months. There have been three recurrences in the treated breast at a median time to failure of 30 months. The 5- and 8-year actuarial local recurrence rate is 6%. One patient recurred with invasive ductal cancer at 28 months, and the other two recurrences were DCIS at 30 and 50 months. All three patients were treated with salvage mastectomy. The patient who recurred locally with an invasive cancer developed metastasis and died at 64 months. The 5- and 8-year actuarial cause-specific survival rates are 100% and 97%, respectively. The following pathologic factors were analyzed for an association with local recurrence: predominant DCIS histology, predominant nuclear grade, and highest nuclear grade. Of these, the predominant nuclear grade was the best predictor of local recurrence (p = 0.070). No clinical or treatment related factor analyzed was associated with local recurrence. CONCLUSION Our results indicate that excellent local control (94%) at 8 years is obtainable after CSRT in a mammographically detected population of patients with DCIS. The predominant nuclear grade was the only factor found that may be associated with local recurrence.

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 institutions 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.

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL The multileaf collimator prescription preparation system developed by us acquires prescription images from different sources, including film scanner and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

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.

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.