Consensus Statement on Proton Therapy for Prostate Cancer.

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery.

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial.

Background: We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR) prostate cancer (PCa) patients.

Patients And Methods: Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b. For the phase I portion of the study patients in cohorts of 15 received 45, 47.

Whole Pelvis Versus Prostate-Only Radiotherapy With or Without Short-Course Androgen Deprivation Therapy and Mortality Risk.

Background: The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT).

Patients And Methods: A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006.

Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer.

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury.

Methods And Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer.

Cardiovascular comorbidity and mortality in men with prostate cancer treated with brachytherapy-based radiation with or without hormonal therapy.

Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC).

Methods And Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors.

Neoadjuvant hormonal therapy use and the risk of death in men with prostate cancer treated with brachytherapy who have no or at least a single risk factor for coronary artery disease.

Background: Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown.

Objective: To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD.

EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks.

The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR) sensitizes non-small cell lung cancer (NSCLC) cells to ionizing radiation remain poorly understood. We set out to characterize the radiosensitizing effects of the tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to pronounced cellular senescence but not apoptosis of irradiated cells, both in vitro and in vivo.

Predictors of prostate cancer-specific mortality in elderly men with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy.

Purpose: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy.

Methods And Materials: The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk of PCSM.

Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction.

Context: Hormonal therapy (HT) when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity. However, it is unknown which comorbid conditions eliminate this survival benefit.

Objective: To assess whether neoadjuvant HT use affects the risk of all-cause mortality in men with prostate cancer and coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI), CAD risk factors, or no comorbidity.

Total androgen blockade versus a luteinizing hormone-releasing hormone agonist alone in men with high-risk prostate cancer treated with radiotherapy.

Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy.

Methods And Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >or=8, or clinical category >or=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.

Gleason Pattern 5 prostate cancer: further stratification of patients with high-risk disease and implications for future randomized trials.

Purpose: To compare prostate-specific antigen (PSA) outcomes in a cohort of men with high-risk prostate cancer based on the presence or absence of any Gleason Grade 5 component (primary, secondary, or tertiary).

Methods And Materials: Our study cohort consisted of 312 men with T1c-T3N0M0 prostate cancer with Gleason Scores of 7 with tertiary Grade 5, 8, or 9-10 who underwent radical prostatectomy or external beam radiotherapy with or without androgen suppression therapy. Cox regression multivariable analysis was used to assess whether a difference existed in risk of PSA recurrence in men with Gleason Score of 9-10 compared with those with Gleason Score of 8 and 7 with tertiary Grade 5, adjusting for treatment, age, and known prostate cancer prognostic factors.

Unusual tumor response and toxicity from radiation and concurrent erlotinib for non-small-cell lung cancer.

We report a case of a never-smoker female with non-small-cell lung cancer (NSCLC) who experienced a striking tumor response to combined low-dose radiation and the epidermal growth factor receptor inhibitor erlotinib, even though erlotinib alone was not effective in preventing tumor progression. Furthermore, the patient developed symptomatic pneumonitis, which is unusual for the small volume of lung that was exposed to a significant dose of radiation. This case demonstrates that combination therapy with radiation and erlotinib has the potential to significantly benefit a subset of patients with NSCLC in addition to those approximately 10% who have tumors which respond to erlotinib alone.

Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumors.

Tumor endothelial marker 1 (Tem1; endosialin) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of Tem1, we disrupted the Tem1 gene in mice by targeted homologous recombination. Tem1(-/-) mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.

Identification of a binding partner for the endothelial cell surface proteins TEM7 and TEM7R.

Tumor endothelial marker 7 (TEM7) was recently identified as an mRNA transcript overexpressed in the blood vessels of human solid tumors. Here, we identify several new variants of TEM7, derived by alternative splicing, that are predicted to be intracellular (TEM7-I), secreted (TEM7-S), or on the cell surface membrane (TEM7-M) of tumor endothelium. Using new antibodies against the TEM7 protein, we confirmed the predicted expression of TEM7 on the cell surface and demonstrated that TEM7-M protein, like its mRNA, is overexpressed on the endothelium of various tumor types.

TEM8 interacts with the cleaved C5 domain of collagen alpha 3(VI).

Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner.

Tumor endothelial markers: new targets for cancer therapy.

Purpose Of Review: Targeting the endothelial cells that line tumor infiltrating blood vessels is a new anticancer strategy that has gained widespread support from biologists and clinicians. Here we highlight different approaches currently being used to target tumor endothelium and discuss new avenues for intervention that have been opened through the recent identification of tumor endothelial markers (TEMs).

Recent Findings: The ability of Avastin to prolong survival in a Phase III clinical trial of human colorectal cancer has established the validity of the anti-angiogenic approach.