Lindsay C. Brown

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis

UNLABELLED The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. PATIENT SUMMARY This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival.

Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

PURPOSE To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. METHODS AND MATERIALS Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. RESULTS Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastases were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. CONCLUSIONS For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.

Stereotactic body radiotherapy for metastatic and recurrent ewing sarcoma and osteosarcoma

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma (n = 19) or ES (n = 8). The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.

Benefits, risks, and safety of external beam radiation therapy for breast cancer.

Breast cancer is a common and complex disease often necessitating multimodality care. Breast cancer may be treated with surgical resection, radiotherapy (RT), and systemic therapy, including chemotherapy, hormonal therapy, and targeted therapies, or a combination thereof. In the past 50 years, RT has played an increasingly significant role in the treatment of breast cancer, resulting in improvements in locoregional control and survival for women undergoing mastectomy who are at high risk of recurrence, and allowing for breast conservation in certain settings. Although radiation provides significant benefit to many women with breast cancer, it is also associated with risks of toxicity, including cardiac and pulmonary toxicity, lymphedema, and secondary malignancy. RT techniques have advanced and continue to evolve dramatically, offering increased precision and reproducibility of treatment delivery and flexibility of treatment schedule. This increased sophistication of RT offers promise of improved outcomes by maintaining or improving efficacy, reducing toxicity, and increasing patient access and convenience. A review of the role of radiation therapy in breast cancer, its associated toxicities and efforts in toxicity reduction is presented.

Once-daily radiation therapy for inflammatory breast cancer.

PURPOSE Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. METHODS AND MATERIALS A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. RESULTS Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). CONCLUSIONS Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.

Analysis of automatic match results for cone-beam computed tomography localization of conventionally fractionated lung tumors.

PURPOSE To evaluate the dependence of an automatic match process on the size of the user-defined region of interest (ROI), the structure volume of interest (VOI), and changes in tumor volume when using cone-beam computed tomography (CBCT) for tumor localization and to compare these results with a gold standard defined by a physicians manual match. METHODS AND MATERIALS Daily CBCT images for 11 patients with lung cancer treated with conventionally fractionated radiation therapy were retrospectively matched to a reference CT image using the Varian On Board Imager software (Varian, Palo Alto, CA) and a 3-step automatic matching protocol. Matches were performed with 3 ROI sizes (small, medium, large), with and without a structure VOI (internal target volume [ITV] or planning target volume [PTV]) used in the last step. Additionally, matches were performed using an intensity range that isolated the bony anatomy of the spinal column. All automatic matches were compared with a manual match made by a physician. RESULTS The CBCT images from 109 fractions were analyzed. Automatic match results depend on ROI size and the structure VOI. Compared with the physicians manual match, automatic matches using the PTV as the structure VOI and a small ROI resulted in differences ≥ 5 mm in 1.8% of comparisons. Automatic matches using no VOI and a large ROI differed by ≥ 5 mm in 30.3% of comparisons. Differences between manual and automatic matches using the ITV as the structure VOI increased as tumor size decreased during the treatment course. CONCLUSIONS Users of automatic matching techniques should carefully consider how user-defined parameters affect tumor localization. Automatic matches using the PTV as the structure VOI and a small ROI were most consistent with a physicians manual match, and were independent of volumetric tumor changes.

Separating the dosimetric consequences of changing tumor anatomy from positional uncertainty for conventionally fractionated lung cancer patients

PURPOSE To separate the dosimetric consequences of changing tumor volume from positional uncertainty for patients undergoing conventionally fractionated lung radiation therapy (RT) and to quantify which factor has a larger impact on dose to target volumes and organs at risk (OAR). METHODS AND MATERIALS Clinical treatment plans from 20 patients who had received conventionally fractionated RT were retrospectively altered by replacing tumor and atelectasis with lung equivalent tissue in the treatment planning system calculations. To simulate positional uncertainty, the isocenter was shifted in both the altered and original plans by 2 and 5 mm in 6 directions. Rotational uncertainty was introduced by rotating each computed tomographic image set by ± 3 degrees about a superior-inferior axis extending through patient center. Additionally, after rotation the isocenter was translated back to its original point within the patient to evaluate whether purely translational corrections could minimize dosimetric consequences due to rotations. RESULTS Dosimetric statistics for each altered plan were compared with the original. Average changes in the planning target volume (PTV) receiving 95% of prescription dose (PTV V95%) resulting from changing tumor anatomy alone were approximately 0.1%. Average changes in PTV V95% resulting from positional uncertainty were greater (0.2%-4.2%) but were largely independent of whether or not the original tumor volume was present. For 3 patients, increases in volumes receiving 110% of the prescription dose were seen but were largely limited to within the PTV. Translational corrections for patient rotations were effective in minimizing differences in target coverage but had less effect on reducing the maximum spinal cord dose. CONCLUSIONS Anatomic changes alone, such as reductions in tumor volume and atelectasis, had minimal effect on the overall dose distribution. Greater dosimetric consequences were seen with positional uncertainty. With accurate patient localization, replanning during the course of treatment for conventionally fractionated lung cancer patients may not be necessary.

Vaginal brachytherapy for early-stage carcinosarcoma of the uterus

OBJECTIVE Uterine carcinosarcoma (CS) is an aggressive malignancy and the optimal adjuvant treatment is not well-established. We report outcomes with vaginal brachytherapy (VB) for women with early-stage CS. METHODS AND MATERIALS A multi-institutional retrospective study of Stage I-II CS treated with hysterectomy, surgical staging, and adjuvant high-dose-rate VB without external-beam pelvic radiotherapy was performed. Rates of vaginal control, pelvic control, locoregional control, disease-free survival, and overall survival were determined using the Kaplan-Meier method. RESULTS 33 patients were identified. Prescribed VB dose was 21 Gy in three fractions (n = 15 [45%]) or 24 Gy in six fractions (n = 18 [55%]). Eighteen patients (55%) received chemotherapy. Median followup was 2.0 years. Twenty-seven patients (82%) underwent pelvic lymphadenectomy, 5 (15%) had nodal sampling, and 1 (3%) had no lymph node assessment. Relapse occurred in 11 patients (33%), all of whom had lymph node evaluation. Locoregional relapse was a component of failure in 6 patients (18%), of whom 3 (9%) failed in the pelvis alone. Three patients (9%) had simultaneous distant and locoregional relapse (two vaginal, one pelvic). Five additional patients (15%) had distant relapse. Six of the 11 patients (55%) with disease recurrence received chemotherapy. Two-year vaginal control and pelvic control were 94% and 87%. Two-year locoregional control, disease-free survival, and overall survival were 81%, 66%, and 79%. CONCLUSIONS Despite having early-stage disease and treatment with VB, patients in this series had relatively high rates of local and distant relapse. Patients who undergo lymphadenectomy and VB remain at risk for relapse. Novel treatment strategies are needed.

Pseudoprogression after Stereotactic Body Radiotherapy

Journal of Thoracic Oncology ® • Volume 9, Number 4, April 2014 Stereotactic body radiotherapy (SBRT) is a highly conformal treatment modality that uses image guidance to allow precise delivery of ablative doses of radiation to a target, resulting in excellent local control with minimal toxicity. SBRT is increasingly used as an alternative to surgical resection for patients with early-stage non–small cell lung cancer who are considered medically inoperable or refuse surgery. In addition, there is interest in incorporating SBRT into the treatment of locally advanced non–small cell lung cancer, most commonly as a boost to residual disease after conventional radiotherapy. As the use of SBRT increases, determination of proper follow-up of patients is paramount. Acute and late imaging changes are common after SBRT, and differentiation between residual/recurrent disease and post-SBRT change can be challenging. Positron emission tomography/computed tomography (PET/CT) is a valuable tool in surveillance, as post-SBRT change typically does not exhibit fluorodeoxyglucose-avidity with standardized uptake values more than 5. However, even with the aid of PET imaging, misinterpretation of abnormalities is possible. Herein, we report such a case.

Head and Neck Soft Tissue Sarcomas Treated with Radiation Therapy

Head and neck soft tissue sarcomas (HNSTSs) are rare and heterogeneous cancers in which radiation therapy (RT) has an important role in local tumor control (LC). The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.