Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor.

Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages.

Assessment of long-term rectal function in patients who received pelvic radiotherapy: a pooled North Central Cancer Treatment Group trial analysis, N09C1.

PURPOSE: Pelvic radiotherapy (PRT) is known to adversely affect bowel function (BF) and patient well-being. This study characterized long-term BF and evaluated quality of life (QOL) in patients receiving PRT. METHODS: Data from 252 patients were compiled from two North Central Cancer Treatment Group prospective studies, which included assessment of BF and QOL by the BF questionnaire (BFQ) and Uniscale QOL at baseline and 12 and 24 months after completion of radiotherapy. BFQ scores (sum of symptoms), Uniscale results, adverse-event incidence, and baseline demographic data were compared via t test, χ (2), Fisher exact, Wilcoxon, and correlation methodologies. RESULTS: The total BFQ score was higher than baseline at 12 and 24 months (P < 0.001). More patients had five or more symptoms at 12 months (13 %) and 24 months (10 %) than at baseline (2 %). Symptoms occurring in greater than 20 % of patients at 12 and 24 months were clustering, stool-gas confusion, and urgency. Factors associated with worse BF were female sex, rectal or gynecologic primary tumors, prior anterior resection of the rectum, and 5-fluorouracil chemotherapy. Patients experiencing grade 2 or higher acute toxicity had worse 24-month BF (P values, <.001-.02). Uniscale QOL was not significantly different from baseline at 12 or 24 months, despite worse BFQ scores. CONCLUSIONS: PRT was associated with worse long-term BF. Worse BFQ score was not associated with poorer QOL. Further research to characterize the subset of patients at risk of significant decline in BF is warranted.

Delineation of Internal Mammary Nodal Target Volumes in Breast Cancer Radiation Therapy.

PURPOSE: The optimal clinical target volume for internal mammary (IM) node irradiation is uncertain in an era of increasingly conformal volume-based treatment planning for breast cancer. We mapped the location of gross internal mammary lymph node (IMN) metastases to identify areas at highest risk of harboring occult disease. METHODS AND MATERIALS: Patients with axial imaging of IMN disease were identified from a breast cancer registry. The IMN location was transferred onto the corresponding anatomic position on representative axial computed tomography images of a patient in the treatment position and compared with consensus group guidelines of IMN target delineation. RESULTS: The IMN location in 67 patients with 130 IMN metastases was mapped. The location was in the first 3 intercostal spaces in 102 of 130 nodal metastases (78%), whereas 18 of 130 IMNs (14%) were located caudal to the third intercostal space and 10 of 130 IMNs (8%) were located cranial to the first intercostal space. Of the 102 nodal metastases within the first 3 intercostal spaces, 54 (53%) were located within the Radiation Therapy Oncology Group consensus volume. Relative to the IM vessels, 19 nodal metastases (19%) were located medially with a mean distance of 2.2 mm (SD, 2.9 mm) whereas 29 (28%) were located laterally with a mean distance of 3.6 mm (SD, 2.5 mm). Ninety percent of lymph nodes within the first 3 intercostal spaces would have been encompassed within a 4-mm medial and lateral expansion on the IM vessels. CONCLUSIONS: In women with indications for elective IMN irradiation, a 4-mm medial and lateral expansion on the IM vessels may be appropriate. In women with known IMN involvement, cranial extension to the confluence of the IM vein with the brachiocephalic vein with or without caudal extension to the fourth or fifth interspace may be considered provided that normal tissue constraints are met.

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.

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.

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.

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.

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.

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 physician's 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 physician's 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 physician's manual match, and were independent of volumetric tumor changes.