A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.

Purpose: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737.

Patients And Methods: Patients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16, and 17, and intravenous gemcitabine on days 1, 8, and 15.

Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study.

An exploratory end point from a recent trial in patients with newly diagnosed multiple myeloma showed that median progression-free survival (PFS) was increased by 10.7 months with denosumab vs zoledronic acid. We performed additional analyses to identify factors that may have contributed to the favorable PFS with denosumab.

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial.

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD).

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance.

First clinical real-time motion-including tumor dose reconstruction during radiotherapy delivery.

Purpose: To clinically implement and characterize real-time motion-including tumor dose reconstruction during radiotherapy delivery.

Methods: Seven patients with 2-3 fiducial markers implanted near liver tumors received stereotactic body radiotherapy on a conventional linear accelerator. The 3D marker motion during a setup CBCT scan was determined online from the CBCT projections and used to generate a correlation model between tumor and external marker block motion.

Spect perfusion imaging versus CT for predicting radiation injury to normal lung in lung cancer patients.

Objectives: In non-small cell lung cancer (NSCLC) patients, to establish whether the fractional volumes of irradiated anatomic or perfused lung differed between those with and without deteriorating lung function or radiation associated lung injury (RALI).

Methods: 48 patients undergoing radical radiotherapy for NSCLC had a radiotherapy-planning CT scan and single photon emission CT lung perfusion imaging (Tc-labelled macroaggregate albumin). CT defined the anatomic and the single photon emission CT scan (co-registered with CT) identified the perfused (threshold 20 % of maximum) lung volumes.

MRI commissioning of 1.5T MR-linac systems - a multi-institutional study.

Background: Magnetic Resonance linear accelerator (MR-linac) systems represent a new type of technology that allows for online MR-guidance for high precision radiotherapy (RT). Currently, the first MR-linac installations are being introduced clinically. Since the imaging performance of these integrated MR-linac systems is critical for their application, a thorough commissioning of the MRI performance is essential.

Nipple-sparing mastectomy in women at high risk of developing breast cancer.

Nipple-sparing mastectomy is a valuable addition to the options available for women at high risk of developing breast cancer. In this review, we summarize current knowledge about the high-risk genes, , and and the associated guidelines with regard to risk-reducing surgery. We consider other genetic risks and high-risk lesions.

Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy.

Objective: The aim of this study was to calculate the range of absorbed doses that could potentially be delivered by a variety of radiopharmaceuticals and typical fixed administered activities used for bone pain palliation in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented.

Methods: Sequential single photon emission CT images from 22 patients treated with 5 GBq of Re-HEDP were used to extrapolate the time-activity curves for various radiopharmaceuticals.

Magnetic resonance imaging in precision radiation therapy for lung cancer.

Radiotherapy remains the cornerstone of curative treatment for inoperable locally advanced lung cancer, given concomitantly with platinum-based chemotherapy. With poor overall survival, research efforts continue to explore whether integration of advanced radiation techniques will assist safe treatment intensification with the potential for improving outcomes. One advance is the integration of magnetic resonance imaging (MRI) in the treatment pathway, providing anatomical and functional information with excellent soft tissue contrast without exposure of the patient to radiation.

The Role of Hypofractionated Radiotherapy in Prostate Cancer.

Purpose Of Review: It is now accepted that prostate cancer has a low alpha/beta ratio, establishing a strong basis for hypofractionation of prostate radiotherapy. This review focuses on the rationale for hypofractionation and presents the evidence base for establishing moderate hypofractionation for localised disease as the new standard of care. The emerging evidence for extreme hypofractionation in managing localized and oligometastatic prostate cancer is reviewed.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer.

Pre-clinical quantitative imaging and mouse-specific dosimetry for In-labelled radiotracers.

Background: Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of In-labelled radiotracers. Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes.

Phase I/II trials of Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.

Purpose: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit.

Methods: Clinical data from 57 patients who received 2.5-5.