Charles E. Leonard

Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control

PURPOSE To determine if a delay of irradiation to the intact breast for administration of adjuvant chemotherapy results in increased local recurrence in breast cancer. PATIENTS AND METHODS The records of 262 women with 264 cases of breast cancer were reviewed. Group I contained 105 patients treated with conservative surgery, chemotherapy, and radiotherapy. Group II contained 157 patients (used as a concurrent control) treated with conservative surgery and radiotherapy only. Eighty-nine percent of subjects in group I received all chemotherapy before radiotherapy. Fifty-eight percent of patients received hormone therapy. Seventy-one percent of patients had negative surgical margins, and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10, 9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%), > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5. RESULTS Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local [5%]). There were no significant differences in local recurrence (group I, four [4%]; group II, eight [5%]; difference not significant). There were no significant differences in local recurrence in any surgery-radiotherapy interval within each group. Although we found marginal increases in the percentage of local recurrences in group I patients (with prolonged surgery-radiotherapy intervals) who had positive margins, positive lymph nodes, and tumor size more than 2 cm versus group II (without prolonged surgery-radiotherapy intervals), these results were not significant. CONCLUSION We could not identify any surgery-radiotherapy interval that resulted in increased local recurrence if radiotherapy was delayed for administration of adjuvant chemotherapy in breast cancer patients. Because of the heterogenous population of breast cancer patients, our results also support the need for further study to determine the optimum integration of radiotherapy and chemotherapy in the management of the conservatively treated breast.

Use of ultrasound to guide radiation boost planning following lumpectomy for carcinoma of the breast

PURPOSE To determine if sonographic localization of the breast lumpectomy site is feasible and useful in boost planning. METHODS AND MATERIALS The operative beds following lumpectomy were localized by ultrasound in 22 patients (15-infiltrating ductal, 7-ductal carcinoma in situ; size: .4-2.0 cm). Twelve patients had two ultrasound examinations on different days for a total of 34 examinations. Twenty-one patients had their course of boost electron therapy planned using ultrasound to guide field placement. While the patient was in the treatment position, the surgical scar was placed at the machines isocenter. With the electron cone in place, the ultrasound transducer was placed within the cone on top of the surgical scar. The biopsy site was localized and the light field maneuvered so that its central axis would follow the axis of the transducer, transecting both the scar and biopsy site. RESULTS The operative bed was highly visible in 26 ultrasound examinations, visible in 7, and subtly visible in 1. Every biopsy site showed some hypoechoic area but most appeared as the mixed hypoechoic pattern. Ultrasound appearances were mixed or mostly hypoechoic (28), anechoic with irregular walls (4), and echoic (hypoechoic compared to parenchyma) (2). In two cases the surgeon placed surgical clips in the operative bed, and in both cases several of these clips could be identified at the margins of the operative bed as hyperechoic foci with shadowing. The mean depth of the operative bed was 21 mm (range 17-36 mm). In 12 patients, two ultrasound examinations were performed on different days, and the mean depth difference between these scans was 2 mm with a range of 0-5 mm. Among patients with two scans we found that both the location and appearance of the operative bed was highly reproducible. CONCLUSION Ultrasound can successfully be used to localize the biopsy site and facilitate boost field placement in patients treated with lumpectomy and radiation.

CLINICAL EXPERIENCE WITH IMAGE-GUIDED RADIOTHERAPY IN AN ACCELERATED PARTIAL BREAST INTENSITY-MODULATED RADIOTHERAPY PROTOCOL

PURPOSE To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. METHODS AND MATERIALS Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. RESULTS All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). CONCLUSIONS This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume.

Predictors for Clinical Outcomes After Accelerated Partial Breast Intensity-Modulated Radiotherapy

PURPOSE To correlate the treatment planning parameters with the clinical outcomes in patients treated with accelerated partial breast intensity-modulated radiotherapy. METHODS AND MATERIALS A total of 105 patients with Stage I breast cancer were treated between February 2004 and March 2007 in a Phase II prospective trial and had detailed information available on the planning target volume (PTV), ipsilateral breast volume (IBV), PTV/IBV ratio, lung volume, chest wall volume, surgery to radiotherapy interval, follow-up interval, breast pain, and cosmesis. The first 7 of these patients were treated to 34 Gy, and the remaining 98 were treated to 38.5 Gy. All patients were treated twice daily for 5 consecutive days. Univariate and multivariate analyses were performed. RESULTS The median follow-up was 13 months. No recurrences or deaths were observed. Of the 105 patients, 30 reported mild or moderate breast pain in their most recently recorded follow-up visit. The irradiated lung volume (p < 0.05) and chest wall volume receiving >35 Gy (p < 0.01) were associated with pain. The PTV, but not the PTV/IBV ratio, also correlated with pain (p < 0.01 and p = 0.42, respectively). A total of 72 patients reported excellent, 32 reported good, and 1 reported poor cosmesis. Physician-rated cosmesis reported 90 excellent and 15 good. None of the tested variables correlated with the cosmetic outcomes. CONCLUSION Radiotherapy to the chest wall (chest wall volume receiving >35 Gy) and to lung correlated with reports of mild pain after accelerated partial breast intensity-modulated radiotherapy. Also, the PTV, but not the PTV/IBV ratio, was predictive of post-treatment reports of pain.

Excision only for tubular carcinoma of the breast.

Abstract:  The purpose of this study was to assess the rationale of excision only (without breast irradiation) in patients with small (≤3 cm) tubular/well‐differentiated breast cancers. A total of 44 patients with pure tubular invasive breast cancer who have undergone complete excision only and have had a minimum 1‐year follow‐up were identified from the Colorado Cancer Registry and assessed for recurrence rates as well as median local disease‐free and overall survival. Treatment dates were October 1972 to April 2001. The median age was 67 years (range 40–96 years). The median tumor size was 6.5 mm (range 2–30 mm). All patients had a complete excision with negative margins. Staging was as follows: T1N0 (11), T1Nx (27), T2N0 (1), T1N1 (3); 2 were unable to be staged accurately. After a median follow‐up of 5.4 years (range 1.1–26.3 years) there were only two local recurrences in the ipsilateral breast (at 7.6 and 8.8 years), for a crude local control rate of 96% (2/44). Both patients were salvaged, are alive, and currently have no evidence of disease (NED) at last follow‐up of 9 and 13.3 years. Actuarial 5‐ and 10‐year local control rates were 100% and 87%. Actuarial 5‐ and 10‐year overall and disease‐free survivals were 80% and 52%, and 100% and 91%. Twenty‐five patients had more than 5 years of follow‐up. The median follow‐up for this group was 9.1 years (range 5.1–26.3 years) and both recurrences were in this group. Although the number of cases in this report is small, it represents the largest total and longest follow‐up for tubular breast cancer cases after excision alone. This report suggests that breast irradiation could be omitted after conservative surgery in older patients with smaller (≤3 cm) tubular/well‐differentiated breast cancers. However, due to the retrospective nature of our report, we cannot categorically make this recommendation. 

Clinical observations of axillary involvement for tubular, lobular, and ductal carcinomas of the breast

Recently, there has been much interest in identifying primary breast cancer characteristics which have predictive value for axillary metastases. We studied breast cancer patients to determine variables associated with the incidence/extent of axillary involvement and to construct a modeled analysis.

Mediastinoscopy incisional metastasis. A radiotherapeutic approach.

Tumor seeding of the mediastinoscopy tract has been described. Although it is a rare occurrence, it can present the radiation oncologist with a therapeutic dilemma. Two cases of mediastinoscopy scar recurrences are reported. Their response to treatment and a review of previous cases are included.

External Beam Accelerated Partial Breast Irradiation Yields Favorable Outcomes in Patients with Prior Breast Augmentation

Purpose: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT. Materials and Methods: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria. Results: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2–58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm3. The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%. Conclusion: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted.

Accelerated Partial Breast Intensity-Modulated Radiotherapy in Women Who Have Prior Breast Augmentation

PURPOSE To examine the outcome of breast cancer patients who have prior breast augmentation treated with lumpectomy followed by accelerated partial breast external intensity-modulated radiotherapy (APBIMRT) with image-guided radiotherapy (IGRT). METHODS AND MATERIALS Four patients with previous elective subpectoral breast augmentation were enrolled on this APBIMRT trial. These four patients were treated with 10 equal twice daily 3.85 Gy fractions over 5 consecutive days (total dose of 38.5 Gy) using APBIMRT and IGRT. Patients were assessed for pain and cosmetic outcome (physician and a patient self-assessment). RESULTS At last follow-up, two patients reported an excellent cosmetic results (at 2 years and at 8 months, respectively), one reported good cosmetic results (at 2 years), and one reported poor cosmetic results (at 20 months). Physicians rated the cosmetic outcomes as excellent in two (CEL; at 2 years and 8 months, respectively), good in one (CEL; at 20 months) and excellent in one (KTH; at 2 years). Three patients reported no breast/chest wall pain (two at 2 years and one at 1 year) and the fourth reported mild pain (at 20 months). The mean percent volume of ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose was 7.28%, 17.55%, 24.33%, and 33.1%, respectively. The mean breast, planning target volume (PTV), and implant volumes were 399.88 cc, 43.55 cc, and 313.36 cc, respectively. The mean breast prosthesis/total volume (breast tissue plus prosthesis) ratio was 44.55%. The mean PTV/ipsilateral breast and PTV/total volume ratios were 11.1% and 6.1%, respectively. CONCLUSION The results show that a regimen of APBIMRT with IGRT is possible in patients who have prior breast augmentation.

Lumpectomy and breast radiotherapy in breast cancer patients with a family history of breast cancer, ovarian cancer, or both.

This article presents an outcomes review of breast cancer patients identified from the cancer registries of four area hospitals. These patients had family histories of breast cancer, ovarian carcinoma, or both and were treated with conservative surgery and radiation to the involved breast. Patients were as follows: group 1, one first‐degree relative ( n = 165, one synchronous bilateral breast cancer); group 2, ≥2 first‐degree relatives ( n = 21); group 3, one second‐degree relative ( n = 20); and group 4, ≥2 second‐degree relatives ( n = 18). The total of patients and breast cancer events was 224 and 225, respectively. Group 5 was a subgroup of 53 patients with a substantial risk (>10%) of a BRCA1 or BRCA2 mutation. After a median follow‐up of 3.9 years, 5 patients had local failure (2%), and 5 developed a contralateral breast cancer (2%). There were no significant differences in local failure rates between groups (p = 1.0): group 1, 5 of 166 (3%); group 2, 0 of 21 (0%); group 3, 0 of 20 (0%); and group 4, 0 of 18 (0%). Local failure for group 5 was 2% (1 of 53). Four of 143 patients (3%) with a minimum 3 years of follow‐up (median, 5.6 years) had local failure, and 5 (4%) developed a contralateral breast cancer. A univariate analysis was statistically significant for differentiation only (well, 0 of 67; moderately, 1 of 57 [1.8%]; poor, 3 of 26 [11.5%], p = 0.008). Overall survival for groups 1–4 did not differ significantly. Although follow‐up has been relatively short, we have not found that breast cancer patients with various degrees of family histories of breast/ovarian carcinoma have had a detrimental outcome when treated with conservative therapy.