ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia.

Expression of ZAP-70 in a subset of patients with chronic lymphocytic leukemia (CLL) positively correlates with the absence of immunoglobulin heavy-chain gene (IGHV) mutations and is indicative of a more active disease and shorter treatment-free survival. We recently demonstrated that ZAP-70 regulates the constitutive expression of CCL3 and CCL4, activation of AKT, and expression of MYC in the absence of an overt B-cell receptor (BCR) signal, bona fide functions of BCR activation. We, here, provide evidence that these features relate to the presence of a constitutive tonic BCR signal, exclusively found in IGHV-unmutated CLL and dependent on the ZAP-70-mediated activation of AKT and its downstream target GSK-3β.

ZAP-70 constitutively regulates gene expression and protein synthesis in chronic lymphocytic leukemia.

The expression of ZAP-70 in a subset of chronic lymphocytic leukemia (CLL) patients strongly correlates with a more aggressive clinical course, although the exact underlying mechanisms remain elusive. The ability of ZAP-70 to enhance B-cell receptor (BCR) signaling, independently of its kinase function, is considered to contribute. We used RNA-sequencing and proteomic analyses of primary cells differing only in their expression of ZAP-70 to further define how ZAP-70 increases the aggressiveness of CLL.

Practice patterns and recommendations for pediatric image-guided radiotherapy: A Children's Oncology Group report.

This report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy.

Clinical implementation, logistics and workflow guide for MRI image based interstitial HDR brachytherapy for gynecological cancers.

Interstitial brachytherapy (IBT) is often utilized to treat women with bulky endometrial or cervical cancers not amendable to intracavitary treatments. A modern trend in IBT is the utilization of magnetic resonance imaging (MRI) with a high dose rate (HDR) afterloader for conformal 3D image-based treatments. The challenging part of this procedure is to properly complete many sequenced and co-related physics preparations.

Higher Reported Lung Dose Received During Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukemia Is Associated With Inferior Survival: A Report from the Children's Oncology Group.

Purpose: To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia on the Children's Oncology Group trial.

Methods And Materials: TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens, allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques.

Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups.

In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case.

A feasibility study of using advanced external beam techniques to create a vaginal cuff brachytherapy-like endometrial boost plan.

The purpose of this study was to explore the feasibility of using advanced external beam radiation therapy (EBRT) planning techniques for creating plans that could be used as a possible alternative for high-dose rate (HDR) vaginal cuff brachytherapy (VCBT) boost in treating endometrial cancer. The computed tomography (CT) images of a total of 4 female patients who had endometrial cancer treated with HDR-VCBT were selected for this study. A typical HDR-VCBT target volume, 0.

Gamma Knife Stereotactic Radiosurgery for Grade 2 Meningiomas.

 This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas.  In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014.  A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study.

Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1 animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness.

Dosimetric impact of cylinder size in high-dose rate vaginal cuff brachytherapy (VCBT) for primary endometrial cancer.

The purpose of this study was to evaluate the dosimetric impact of cylinder size in high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT). Sample plans of HDR VCBT in a list of cylinders ranging from 2.5 to 4 cm in diameter at 0.

A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma.

Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined.

Contouring Guidelines for the Axillary Lymph Nodes for the Delivery of Radiation Therapy in Breast Cancer: Evaluation of the RTOG Breast Cancer Atlas.

Purpose: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning.

Methods And Materials: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed.

Brachial plexus dose tolerance in head and neck cancer patients treated with sequential intensity modulated radiation therapy.

Purpose: We aimed to study the radiation induced brachial plexopathy in patients with head and neck squamous cell carcinoma (HNSCC) treated with Sequential Intensity Modulated Radiation Therapy (S-IMRT).

Methods And Materials: This IRB approved study included 68 patients with HNSCC treated consecutively. Detailed dose volume histogram data was generated for ipsilateral and contralateral brachial plexus (BP) volumes receiving a specified dose (Vds) i.

Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer.

Introduction: This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer.

Patients And Methods: Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.

Age most significant predictor of requiring enteral feeding in head-and-neck cancer patients.

Background: A significant number of patients treated for head and neck squamous cell cancer (HNSCC) undergo enteral tube feeding. Data suggest that avoiding enteral feeding can prevent long-term tube dependence and disuse of the swallowing mechanism which has been linked to complications such as prolonged dysphagia and esophageal constriction. We examined detailed dosimetric and clinical parameters to better identify those at risk of requiring enteral feeding.

Thyroid V50 Highly Predictive of Hypothyroidism in Head-and-Neck Cancer Patients Treated With Intensity-modulated Radiotherapy (IMRT).

Objectives: Radiation-induced hypothyroidism affects a significant number of patients with head-and-neck squamous cell cancer (HNSCC). We examined detailed dosimetric and clinical parameters to better determine the risk of hypothyroidism in euthyroid HNSCC patients treated with intensity-modulated radiation therapy (IMRT).

Materials And Methods: From 2006 to 2010, 75 clinically euthyroid patients with HNSCC were treated with sequential IMRT.

Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol.

Prognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype.

Multisector dosimetry in the immediate post-implant period: significant under dosage of the prostate base.

Purpose: While there are several reports of prostate multisector dosimetry data obtained from CT or MRI scans performed at intervals ranging from 14-70 days after prostate brachytherapy (PB), there are no reports on multisector dosimetry performed in the immediate post-implant period. This study was undertaken to determine the results of prostate multisector dosimetry performed in the immediate post-implant period on day 1 post-implant dosimetry after (125)I PB.

Material And Methods: The day 1 post-implant CT-based V100 and D90 were determined for the prostate base (PGB) and compared to doses to the entire gland (PG), mid-gland (PMG), and apex (PA) in 75 patients who underwent (125)I PB to a dose of 144 Gy.

Low-Dose-Rate Brachytherapy Boosting Concurrent Chemoradiation as a Definitive Treatment Modality for Cervical Cancer: Long-term Clinical Results of Outcomes and Associated Toxicity.

Purpose: To review and report the long-term treatment-induced adverse events (AEs) and outcomes of concomitant chemoradiotherapy boosted by low-dose-rate (LDR) conventional brachytherapy (BT) planning in patients with locoregionally advanced cervical cancer.

Patients And Methods: After obtaining institutional review board approval, we reviewed the records of patients with stage IB1 to IVA, intact cervical cancer who were treated at our institution between 1983 and 2009. Eligible patients underwent definitive radiotherapy with external-beam radiation concomitant with cisplatin-based chemotherapy and boosted by LDR BT.

A comprehensive quality assurance program for personnel and procedures in radiation oncology: value of voluntary error reporting and checklists.

Purpose: This report describes the value of a voluntary error reporting system and the impact of a series of quality assurance (QA) measures including checklists and timeouts on reported error rates in patients receiving radiation therapy.

Methods And Materials: A voluntary error reporting system was instituted with the goal of recording errors, analyzing their clinical impact, and guiding the implementation of targeted QA measures. In response to errors committed in relation to treatment of the wrong patient, wrong treatment site, and wrong dose, a novel initiative involving the use of checklists and timeouts for all staff was implemented.

Cardiac-sparing whole lung IMRT in children with lung metastasis.

Purpose: To demonstrate the dosimetric advantages of cardiac-sparing (CS) intensity modulated radiation therapy (IMRT) in children undergoing whole lung irradiation (WLI).

Methods And Materials: Chest CT scans of 22 children who underwent simulation with 3-dimensional (n=10) or 4-dimensional (n=12) techniques were used for this study. Treatment planning was performed using standard anteroposterior-posteroanterior (S-RT) technique and CS-IMRT.

SU-E-T-570: Improvement to the Histogram Analysis in Radiation Therapy (HART): An Open Source Software System for the Multi-Dimensional Dose- Volume Histogram Analysis in Digital Image Communication in Medicine - Radiation Therapy (DICOM-RT) Treatment Plans.

Purpose: Histogram Analysis in Radiation Therapy (HART) is an efficient and accurate dose-volume histogram (DVH) computational tool in radiotherapy research. Several applications of the program have been presented previously (J Appl Clin Med Phys 11(1): 3013, 2010; Med Phys 38(6), p.3678, 2011) for the Radiation Therapy Oncology Group (RTOG) users.

Intra-operative pubic arch interference during prostate seed brachytherapy in patients with CT-based pubic arch interference of < or =1cm.

Purpose: There are only a few reports on the frequency of intra-operative pubic arch interference (I-PAI) during prostate seed brachytherapy (PB).

Materials And Methods: Two hundred and forty-three patients with a CT-based pubic arch interference (PAI) of < or =1 cm and a prostate volume of < or =50-60 cc underwent PB. Those patients requiring needle repositioning by > or =0.