Improved Tumor Responses with Sequential Targeted α-Particles Followed by Interleukin 2 Immunocytokine Therapies in Treatment of CEA-Positive Breast and Colon Tumors in CEA Transgenic Mice.

Targeted α-therapy (TAT) delivers high-linear-transfer-energy α-particles to tumors with the potential to generate tumor immune responses that may be augmented by antigen-targeted immunotherapy. This concept was evaluated in immunocompetent carcinoembryonic antigen (CEA) transgenic mice bearing CEA-positive mammary or colon tumors. Tumors were targeted with humanized anti-CEA antibody M5A labeled with Ac for its 10-d half-life and emission of 4 α-particles, as well as being targeted with the immunocytokine M5A-interleukin 2.

Genetically-encoded discovery of proteolytically stable bicyclic inhibitors for morphogen NODAL.

In this manuscript, we developed a two-fold symmetric linchpin () that converts readily available phage-displayed peptides libraries made of 20 common amino acids to genetically-encoded libraries of bicyclic peptides displayed on phage. combines an aldehyde-reactive group and two thiol-reactive groups; it bridges two side chains of cysteine [C] with an N-terminal aldehyde group derived from the N-terminal serine [S], yielding a novel bicyclic topology that lacks a free N-terminus. Phage display libraries of SXCXXXXXXC sequences, where X is any amino acid but Cys, were converted to a library of bicyclic -[S]X[C]XXXXXX[C] peptides in 45 ± 15% yield.

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

Purpose: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.

Methods: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m once every 3 weeks for three cycles before RT and 20 mg/m once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.

Surgery Versus Radiation Treatment for High-Grade Neuroendocrine Cancer of Uterine Cervix: A Surveillance Epidemiology and End Results Database Analysis.

Objectives: The objective of this study was to assess treatment and other factors impacting survival in cervical high-grade neuroendocrine carcinoma (HGNEC).

Methods/materials: We identified patients with cervical HGNECs diagnosed during 1988 to 2012 in the Surveillance Epidemiology and End Results database. We determined overall survival by International Federation of Gynecology and Obstetrics stages and by local treatment modalities, that is, radical surgery versus external beam radiation treatment (EBRT) plus brachytherapy using Kaplan-Meier analysis with log-rank test.

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

Background: Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision.

Focal therapy using magnetic resonance image-guided focused ultrasound in patients with localized prostate cancer.

Background: The purpose of this study is to evaluate and report the feasibility, safety, and initial outcomes of patients with limited localized prostate cancer treated using a trans-rectal magnetic resonance image-guided focused ultrasound (MRGFUS) device. Attempts to focally treat only the index lesion for prostate cancer have been explored to reduce side effects while maintaining oncologic control. MRGFUS allows for precise targeting of thermal ablative therapy with real-time thermometry.

Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer.

Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy.

The impact of increasing dose on overall survival in prostate cancer.

Purpose: To assess the impact of increasing dose on overall survival (OS) for prostate cancer patients.

Methods: Treatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028).

Impact of Total Lymph Node Count on Staging and Survival After Neoadjuvant Chemoradiation Therapy for Rectal Cancer.

Purpose: Current guidelines recommend that a minimum of 12 lymph nodes (LNs) be dissected to accurately stage rectal cancer patients. Neoadjuvant chemoradiation therapy (CRT) decreases the number of LNs retrieved at surgery. The purpose of this study was to assess the impact of the number of LNs dissected on overall survival (OS) for localized rectal cancer patients treated with neoadjuvant CRT.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer.

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed.

Dose response for radiation cataractogenesis: a meta-regression of hematopoietic stem cell transplantation regimens.

Purpose/objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI).

Methods And Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence.

Extramedullary relapse following total marrow and lymphoid irradiation in patients undergoing allogeneic hematopoietic cell transplantation.

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution.

Treatment outcomes for patients with chloroma receiving radiation therapy.

Introduction: This study aims to analyse treatment outcomes, disease control and toxicity in patients with chloromas referred for radiation therapy (RT).

Methods: Medical records were retrospectively reviewed for 41 patients with chloromas treated with RT at our institution.

Results: Twenty-five patients were treated with palliative intent, whereas sixteen received RT as a component of curative intent therapy in addition to systemic chemotherapy with or without haematopoietic stem cell transplant (HSCT).

Suberoylanilide hydroxamic acid induces hypersensitivity to radiation therapy in acute myelogenous leukemia cells expressing constitutively active FLT3 mutants.

Histone deacetylase inhibitors (HDIs) have shown promise as candidate radiosensitizer for many types of cancers. However, the mechanisms of action are not well understood, and whether they could have clinical impact on radiotherapy for leukemia is unclear. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) can increase radiosensitivity of acute myeloid leukemia (AML) cells through posttranslational modification of Rad51 protein responses and selective inhibition of the homology-directed repair (HDR) pathway.

Suberoylanilide hydroxamic acid as a radiosensitizer through modulation of RAD51 protein and inhibition of homology-directed repair in multiple myeloma.

Histone deacetylase inhibitors (HDI) have shown promise as candidate radiosensitizers for many types of cancers. However, the mechanisms of action are not well understood, and whether they could sensitize multiple myeloma (MM) to radiation therapy is unclear. In this study, we show that suberoylanilide hydroxamic acid (SAHA) at low concentrations has minimal cytotoxic effects, yet can significantly increase radiosensitivity of MM cells.

Dose escalation of total marrow irradiation with concurrent chemotherapy in patients with advanced acute leukemia undergoing allogeneic hematopoietic cell transplantation.

Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens.

Methods And Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg).

Setup variations in radiotherapy of anal cancer: advantages of target volume reduction using image-guided radiation treatment.

Purpose: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects.

Methods And Materials: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans.

Residual setup errors and dose variations with less-than-daily image guided patient setup in external beam radiotherapy for esophageal cancer.

Background And Purpose: To evaluate residual patient setup errors and daily dose variations of different less-than-daily image guidance (IG) strategies in the delivery of external beam radiotherapy for esophageal cancer.

Material And Methods: Daily image-guided setup data for 25 consecutive esophageal cancer patients treated with helical tomotherapy were evaluated. Seven less-than-daily IG strategies with different imaging frequencies were simulated.

Dosimetric study of volumetric modulated arc therapy fields for total marrow irradiation.

Background And Purpose: Normal organ toxicity is the leading factor that limits dose escalation in total body irradiation for bone marrow transplant (BMT) patients. In recent years, total marrow irradiation (TMI) using the helical tomotherapy (HT) system is being used as a more targeted form of TBI to treat BMT patients. In this study, we evaluated the feasibility of using volumetric modulated arc therapy (VMAT) to deliver TMI treatment.

ACR-ASTRO practice guideline for the performance of therapy with unsealed radiopharmaceutical sources.

This guideline is intended to guide appropriately trained and licensed physicians performing therapy with unsealed radiopharmaceutical sources. Adherence to this guideline should help to maximize the efficacious use of these procedures, maintain safe conditions, and ensure compliance with applicable regulations. The topics dealt with in this guideline include indications for the use of iodine-131, both for the treatment of hyperthyroidism and thyroid carcinoma.

Low-dose valproic acid enhances radiosensitivity of prostate cancer through acetylated p53-dependent modulation of mitochondrial membrane potential and apoptosis.

Histone deacetylase inhibitors (HDI) have shown promise as candidate radiosensitizers for many types of cancers, including prostate cancer. However, the mechanisms of action are not well understood. In this study, we show in prostate cancer cells that valproic acid (VPA) at low concentrations has minimal cytotoxic effects yet can significantly increase radiation-induced apoptosis.

Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma.

Purpose: To establish feasibility, maximum tolerated dose (MTD), and potential efficacy of ablative dose total marrow irradiation (TMI) delivered by helical tomotherapy in patients with multiple myeloma (MM).

Experimental Design: Patients with responding or stable MM received tandem autologous stem cell transplants, first with melphalan 200 mg/m(2), and 60 days or later with TMI. TMI doses were to be escalated from 1,000 cGy by increments of 200 cGy.

Preoperative versus postoperative radiotherapy in soft-tissue sarcoma: multi-institutional analysis of 821 patients.

Purpose: To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS).

Methods And Materials: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included.

A pretherapy biodistribution and dosimetry study of indium-111-radiolabeled trastuzumab in patients with human epidermal growth factor receptor 2-overexpressing breast cancer.

Purpose: The purposes of this study were to evaluate the organ biodistribution, pharmacokinetics, immunogenicity, and tumor uptake of (111)Indium ((111)In)-MxDTPA-trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers and to determine whether (90)Y-MxDTPA-trastuzumab should be evaluated in subsequent clinical therapy trials.

Experimental Design: Patients with HER2-overexpressing breast cancers who were to undergo planned trastuzumab therapy first received unlabeled trastuzumab (4-8 mg/kg IV), followed 4 hours later by 5 mCi (111)In-MxDTPA-trastuzumab (10 mg antibody). Serial blood samples, 24-hour urine collections, and nuclear scans were performed at defined time points for 7 days.

Radiotherapy and extent of surgical resection in retroperitoneal soft-tissue sarcoma: multi-institutional analysis of 261 patients.

Background And Objective: To examine the impact of adjuvant radiotherapy (RT) and surgical technique on survival in retroperitoneal soft-tissue sarcoma.

Methods: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC(R) Medical Systems (Sunnyvale, CA). Patients who received definitive surgery with negative or microscopic-positive margins were included.