A. Dhople

Comparative Analysis of the Post-Lumpectomy Target Volume Versus the Use of Pre-Lumpectomy Tumor Volume for Early-Stage Breast Cancer: Implications for the Future

PURPOSE Three-dimensional conformal accelerated partial breast irradiation (APBI-3D-CRT) is commonly associated with the treatment of large amounts of normal breast tissue. We hypothesized that a planning tumor volume (PTV) generation based on an expansion of the pre-lumpectomy (pre-LPC) intact tumor volume would result in smaller volumes of irradiated normal breast tissue compared with using a PTV based on the post-lumpectomy cavity (post-LPC). Use of PTVs based on the pre-LPC might also result in greater patient eligibility for APBI-3D-CRT. METHODS AND MATERIALS Forty-one early-stage breast cancers were analyzed. Preoperative imaging was used to determine a pre-LPC tumor volume. PTVs were developed in the pre- and post-LPC settings as per National Surgical Breast and Bowel Project (NSABP)-B39 guidelines. The pre- and post-LPC PTV volumes were compared and eligibility for APBI-3D-CRT determined using NSABP-B39 criteria. RESULTS The post-LPC PTV exceeded the pre-LPC PTV in all cases. The median volume for the pre- and post-LPC PTVs were 93 cm(3) (range, 24-570 cm(3)) and 250 cm(3) (range, 45-879 cm(3)), respectively, p <0.001. The difference between pre- and post-LPC PTVs represented a median of 165 cc (range, 21-482 cc) or 16% (range, 3%-42%) of the whole breast volume. Three of 41 vs. 13 of 41 cases were ineligible for APBI-3D-CRT when using the pre- and post-LPC PTVs, respectively. CONCLUSION PTVs based on pre-LPC tumor expansion are likely associated with reduced amounts of irradiated normal breast tissue compared with post-LPC PTVs, possibly leading to greater patient eligibility for APBI-3D-CRT. These findings support future investigation as to the feasibility of neoadjuvant APBI-3D-CRT.

Optimal beam arrangement for stereotactic body radiation therapy delivery in lung tumors.

Abstract Purpose. To compare the different beam arrangement and delivery techniques for stereotactic body radiation therapy (SBRT) of lung lesions using the criteria of Radiation Therapy Oncology Group (RTOG) 0236 protocol. Material and methods. Thirty-seven medically inoperable lung cancers were evaluated with various planning techniques including multiple coplanar multiple static beams, multiple non-coplanar static beams and arc delivery. Twelve plans were evaluated for each case, including five plans using coplanar fixed beams, six plans using non-coplanar fixed beams and one plan using arc therapy. These plans were compared using the target prescription isodose coverage, high and low dose volumes, and critical organ dose-volume limits. Results. The prescription isodose coverage, high dose evaluation criteria and dose to critical organs were similar among treatment delivery techniques. However, there were differences in low dose criteria, especially in the ratio of the volume of 50% isodose of the prescription dose to the volume of planning treatment volume (R50%). The R50% in plans using non-coplanar static beams was lower than other plans in 30 of 37 cases (81%). Conclusion. Based on the dosimetric criteria outlined in RTOG 0236, the treatment technique using non-coplanar static beams showed the most preferable results for SBRT of lung lesions.

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.

SU‐FF‐T‐656: 4D IMRT Planning Using a Direct Aperture Morphing Method

Purpose: To propose a 4D IMRT planning method that accounts for both rigid and non‐rigid respiration related target motion based on the 4DCT datasets. Methods and Materials: The set of MLC aperture sequences optimized on a reference phase of 4DCT is morphed to the rest of the phases according to the anatomical changes of the target projection in the beams eye view (BEV) at each beam angle, and thus ensured the continuity of the MLC aperture between adjacent phases. This method does not need complex computation or couch motion, only simple geometric relationship of target projection between different phases are employed. Three different planning schemes were evaluated. 1) Individually optimize each breathing phase should theoretically generate the best dose distributions, although such plans cannot be delivered because the apertures in different plans are not connected geometrically. This scheme is used as a benchmark of plan quality for the other schemes. 2) Optimize treatment for a reference phase and shift the optimized apertures to other phases based on a rigid‐body image registration. 3) The proposed scheme of optimizing treatment for a reference phase and deforming the optimized apertures to other phases based on the deformation and translation of target contours. Results: Direct aperture morphing method (scheme 3) illustrated comparable plan quality compared to scheme1; and demonstrated the improved target coverage and conformity compared to the scheme2 that only considers the rigid motion and comparable dose in normal tissue. Conclusion: Direct aperture morphing method can be used for 4D IMRT planning and it has equal or better plan quality compared to the method that only considers the rigid body motion.

Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early stage breast cancer: implications for the future.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #5134 Purpose: Accelerated partial breast irradiation (APBI) is increasingly being utilized for the treatment of early stage breast cancer. Planning target volume (PTV) generation with this approach is based on the post-lumpectomy cavity volume (post-LPC) and is often associated with treatment of large amounts of normal breast tissue which can result in patient ineligibility for external beam APBI (EB-APBI). In malignancies such as soft tissue sarcomas, neoadjuvant radiation therapy (RT) has been shown to be associated with smaller volumes of tissue irradiated compared to adjuvant RT. However, neoadjuvant RT has not been attempted in the setting of APBI. We hypothesized that a PTV generation based on an expansion of the pre-lumpectomy (pre-LP) intact tumor volume would result in a significant reduction in the volume of irradiated normal breast tissue compared to the current approach of using the post-LPC. We further hypothesize that the use of EB-APBI utilizing the pre-LP tumor will result in greater patient eligibility for APBI. Materials and Methods: 40 patients with 41 early stage breast cancers previously treated with breast conserving lumpectomy and RT were analyzed. Pre-operative imaging and pathology reports were used to determine a pre-LP tumor volume. A sphere, the diameter of which was the largest determined radiographic dimension, representing the pre-LP tumor volume was placed in the center of the previously contoured and treated lumpectomy cavity. PTVs were developed for the pre-LP tumor volume and the post-LPC volume as per the NSABP-B39 protocol guidelines. The pre-LP and post-LPC PTV volumes were compared. Suitability for APBI was analyzed using criteria set forth by NSABP-B39 guidelines. Results: For all patients, the pre-LP PTV was smaller than the post-LPC PTV. The median volume for the pre and post-LPC PTVs were 93 cc (range 24 – 570 cc) and 250 cc (range 45 – 879 cc), respectively. Paired t-test analysis demonstrated the pre-LP PTV to be significantly smaller than the post-LPC PTV, p < 0.001. The average difference between pre-LP and post-LPC PTVs represented 173 cc (range 21 – 482 cc) or 18% (range 3 - 42%) of the whole breast volume. Based on our analysis, only 3 of 41 cases were ineligible for EB-APBI when using the pre-LP tumor volume, (2 based on pathologic criteria and 1 based on dose/volume constraints) while 13 of 41 cases were ineligible when using the post-LPC PTV (2 based on pathologic criteria and 11 based on dose/volume constraints). Conclusion: PTVs based on the pre-LP tumor expansion are likely to be associated with a significantly reduced amount of normal breast tissue irradiated compared to post-LPC PTVs potentially leading to improved breast cosmesis, decreased dose to critical structures and decreased toxicities. Additionally, eligibility for EB-APBI would potentially increase if administered in the pre-lumpectomy setting. The findings from this study support future investigation as to the implications and feasibility of neoadjuvant APBI. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5134.