Sally B. Cheston

Repeat Computed Tomography Simulation to Assess Lumpectomy Cavity Volume During Whole-Breast Irradiation

PURPOSE To determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease. PATIENTS AND METHODS Forty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2. RESULTS The median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume. CONCLUSIONS Patients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.

Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

PURPOSE The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. METHODS AND MATERIALS A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status ≥ 60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m(2) divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m(2) increments until the MTD was reached. When ≥ 2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m(2). A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. RESULTS A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m(2). One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m(2). CONCLUSIONS The MTD of tamoxifen was 100 mg/m(2) when given concurrently with temozolomide 75 mg/m(2) and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

Preoperative radiation therapy significantly increases patient eligibility for accelerated partial breast irradiation using 3D-conformal radiotherapy.

Introduction:Three-dimensional-conformal radiation (3D-CRT) is the most common approach used in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 for accelerated partial breast irradiation (APBI). Administration of APBI-3D-CRT in the preoperative (preop) setting has been shown to decrease the planning target volume. The impact of this decrease on patient eligibility for APBI has not been evaluated in a comparative manner. Materials and Methods:Forty patients with 41 previously treated breast cancers (⩽4 cm) were analyzed. A spherical preop tumor volume was created using the largest reported radiographic dimension and centered within the contoured lumpectomy cavity. Plans were created and optimized using the preop tumor volume and postoperative lumpectomy cavity using NSABP B-39 guidelines. The primary end point was to evaluate for differences in patient eligibility and normal tissue exposure. Results:Thirty-five tumors (85%) in the preop versus 19 tumors (46%) in the postoperative setting were eligible for 3D-CRT-APBI using NSABP B-39 criteria (P=0.0002). The most common reason for ineligibility was due to >60% of the ipsilateral breast volume receiving 50% of the dose. Other reasons included dose to the contralateral breast, heart, and ipsilateral lung. Preop 3D-CRT-APBI was associated with statistically significant improvements in dose sparing to the heart, ipsilateral normal breast tissue, contralateral breast, chest wall, ipsilateral lung, and skin. Conclusions:Dosimetrically, the use of preop radiation would increase patient eligibility for 3D-CRT-APBI and decrease dose to normal tissues, which will potentially decrease toxicity and improve cosmesis. These results provide the basis for a recently activated prospective study of preop 3D-CRT-APBI.

Radiation Therapy in the Elderly with Early Stage Breast Cancer: Review and Role of New Technology

In 2013, breast cancer affected 232,340 women in the US. Of these diagnoses, 52% were in women aged 65 and older. Although age is a risk factor for the development of breast cancer, women diagnosed at an older age generally have a more favorable prognosis due to often less aggressive tumor biology. Elderly women tend to have higher rates of hormone receptor positive tumors and also tumors with lower proliferative indices (Ki-67). Despite these favorable prognostic factors, breast cancer specific mortality has only decreased at a rate of 1.1% per year for women aged 75+ in comparison to 2.4% per year for women aged <50. It has been hypothesized that this is related to under-treatment of elderly patients due to increased comorbidities which can limit treatment options as well as social influences such as distance to treatment facilities and lack of transportation. Older women are less likely to be offered standard treatment including surgery, radiotherapy, chemotherapy and endocrine therapy regardless of their breast cancer stage.

Effect of reduction mammoplasty on acute radiation side effects and use of lumpectomy cavity boosts

PURPOSE Reduction mammoplasty (RM) during breast-conserving surgery is popular among women with large-volume breasts because it reduces redundant breast folds and may decrease skin-related morbidity from radiation therapy. However, RM may obscure the lumpectomy cavity (LC) and pose challenges to administering an LC boost, potentially affecting local control. We investigated the impact of RM on acute side effects and use of LC boosts. METHODS AND MATERIALS The records of 645 consecutive women treated with whole-breast irradiation at an urban university and 2 community practices between January 2012 and December 2014 were reviewed on an institutional review board-approved study. The primary endpoint was grade ≥3 radiation dermatitis; the secondary endpoint was use of LC boost. Student 2-sample t tests, Pearson χ2 tests, Fisher exact tests, and univariate and multivariable logistic regression analyses were performed. RESULTS Forty-three (7%) RMs were performed in 650 treated breasts. No significant differences in grade 3 toxicities were identified among RM and non-RM patients. LC boost was delivered to 474 breasts. Fewer (16/43) RM patients received LC boosts compared with non-RM patients (458/607), P = .0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multifocal disease, higher body mass index, larger planning treatment volumes, and conventional fractionation (P < .05). CONCLUSIONS RM was associated with decreased use of LC boost without significant differences in acute toxicities. Further investigation to delineate LCs in patients undergoing RM or identify alternative strategies for delivering LC dose is needed.

What is the impact of reduction mammoplasty for women undergoing breast-conserving surgery for breast cancer?

49 Background: Reduction mammoplasty (RM) at time of breast conserving surgery (BCS) is an increasingly popular procedure that reduces redundant breast folds and skin toxicity from whole breast irradiation (WBI). However, the tissue manipulation may obscure the lumpectomy cavity (LC) and hinder the ability to deliver a radiation boost to the LC, potentially impacting local control. We studied the impact of RM on acute radiation side effects and the use of LC boost. METHODS From Jan 2012 to Dec 2014, 652 consecutive women with DCIS or Stage I-III invasive cancer were treated with curative intent BCS and WBI at an urban university and 2 community practices. We reviewed the charts on an IRB-approved study with the primary endpoint of ≥ grade 3 radiation dermatitis scored via the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Secondary endpoint was the use of LC boost. Tested variables included age, race, body mass index, menopausal status, multi-focal disease, stage, tumor grade, receptor status, chemotherapy administered, specimen volume, 3D or intensity modulated radiation, fractionation, nodal irradiation, and planning treatment volume (PTV). Students t-tests and Pearsons chi-square tests were utilized. RESULTS Forty-three (7%) of 652 patients underwent RM. Larger volumes of tissue were removed from the RM patients (median 366.5 g v 35.3 g, P= 0.0001). No grade 4 toxicities and few (2-3%) grade 3 toxicities were seen, P= 1.00. Narcotic use was similar (4-5%), P= 0.70. A LC boost was used in 476 (73%) patients; RM significantly decreased the use of a boost [16/43 (37%) v 460/609 (76%)], P= 0.0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multi-focal disease, higher BMI, nodal irradiation, and conventional fractionation (P< 0.05). Subgroup analysis of the patients with available PTVs (67%) revealed similar volumes (P= 0.16). CONCLUSIONS RM was associated with a decrease in the use of LC boost without significant differences in acute toxicities; however, the result is not surprising given that PTVs were similar. Further investigation is needed to better delineate LCs in patients undergoing RM to increase the use of LC boosts.