The Impact of 18F-DCFPyL PET-CT Imaging on Initial Staging, Radiation, and Systemic Therapy Treatment Recommendations for Veterans With Aggressive Prostate Cancer.

PURPOSE: Our purpose was to study the effect of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) positron emission tomography (PET)-computed tomography (CT) on staging/treatment recommendations of previously untreated prostate cancer. We report here results of a prospective single center single arm imaging trial within Veterans Affairs (Greater Los Angeles): the frequency of patients upstaged to M1 disease (primary endpoint) and the frequency of patients with change in treatment recommendations (secondary endpoint). This is the first report of prostate-specific membrane antigen PET-CT exclusive to U.S. veterans. METHODS AND MATERIALS: Veterans with Gleason ≥4 + 3, clinical stage ≥T2c, or prostate-specific antigen >10 ng/mL were eligible. Patients underwent conventional imaging (99mTc-methyl diphosphonate bone scan or 18F-NaF PET-CT; and pelvic CT or pelvic magnetic resonance imaging) in addition to 18F-DCFPyL PET-CT. The effect of 18F-DCFPyL PET-CT on treatment change was determined by applying prespecified treatment recommendations based on National Comprehensive Cancer Network guidelines and modern clinical practice. RESULTS: One hundred patients underwent 18F-DCFPyL PET-CT. Nineteen out of 84 (23%) patients initially thought to be nonmetastatic were upstaged to M1; 8/16 (50%) patients initially thought to have M1 disease were downstaged to M0. In total, 39/100 (39%) had a change in prespecified treatment recommendations, including change of radiation therapy volume/dose in 39/100 (39%) and starting abiraterone in 22/100 (22%). CONCLUSIONS: Incorporation of 18F-DCFPyL PET-CT into the initial conventional imaging workup for prostate cancer can substantially affect staging/treatment recommendations.

Predictors of prolongation in radiation treatment time in a veteran population treated with chemoradiation for oropharyngeal cancer.

BACKGROUND: Prolonged radiation treatment time (RTT) is associated with worse tumor control. Here we identify and determine the implications of factors that predict treatment prolongation in Veterans Affairs (VA) patients undergoing chemoradiation. METHODS: Chart review from July 2000 to October 2013. 81 patients with advanced stage oropharyngeal cancer treated with chemoradiation. RESULTS: Twenty-nine patients (35.8%) had RTT prolonged by ≥10 days. Prolongation mainly resulted from acute treatment toxicity (n = 22, 76%). There was no significant difference in RTT for patients treated with concurrent cisplatin versus cetuximab, or in patients treated with or without induction chemotherapy. One-/three-year locoregional control and overall survival rates of 83.4%/76.3% and 83.5%/63.6% for patients without prolonged RTT versus 61.8%/61.8% and 82.8%/73.8% for those with prolongation (p >.05). CONCLUSIONS: Prolonged RTT is a significant predictor of worse locoregional control and predominantly resulted from treatment side effects. More aggressive regimens with induction and concurrent chemotherapy did not predispose to prolonged RTT.

A swallow preservation protocol improves function for veterans receiving chemoradiation for head and neck cancer.

OBJECTIVE: Determine the efficacy of a swallow preservation protocol (SPP) on maintaining swallow function in patients undergoing chemoradiation (CRT) or radiation therapy alone (RT) for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective case series. SETTING: Veterans Affairs medical center. SUBJECTS AND METHODS: Patients treated with CRT or RT for HNSCC between February 2006 and November 2013 were studied. Those enrolled in the SPP participated in swallowing, jaw, and tongue exercises during cancer therapy. The comparator group received no swallowing intervention during CRT. A previously described functional outcome swallowing scale (FOSS; 0 = no symptoms and 5 = nonoral feeding for all nutrition) was used to quantify dysphagia prior to and at the completion of cancer therapy, and an analysis was performed to compare swallowing function. RESULTS: Forty-one (all male; mean age, 66 years) and 66 patients (all male; mean age, 61 years) were included in the SPP and comparator groups, respectively. In the SPP group, mean pre- and posttreatment FOSS scores were 2.2 and 2.2, respectively, while the corresponding scores in the comparator group were 1.8 and 2.7, respectively, with posttreatment FOSS scores being significantly worse than pretreatment FOSS scores in the comparator group only. CONCLUSION: Patients enrolled in the SPP demonstrated preserved swallowing function over the course of cancer treatment compared with a comparator group. This confirms the importance of early evaluation and intervention for dysphagia prior to and during CRT or RT alone.

Modeling transmural heterogeneity of K(ATP) current in rabbit ventricular myocytes.

To investigate the mechanisms regulating excitation-metabolic coupling in rabbit epicardial, midmyocardial, and endocardial ventricular myocytes we extended the LabHEART model (Puglisi JL and Bers DM. Am J Physiol Cell Physiol 281: C2049-C2060, 2001). We incorporated equations for Ca(2+) and Mg(2+) buffering by ATP and ADP, equations for nucleotide regulation of ATP-sensitive K(+) channel and L-type Ca(2+) channel, Na(+)-K(+)-ATPase, and sarcolemmal and sarcoplasmic Ca(2+)-ATPases, and equations describing the basic pathways (creatine and adenylate kinase reactions) known to communicate the flux changes generated by intracellular ATPases. Under normal conditions and during 20 min of ischemia, the three regions were characterized by different I(Na), I(to), I(Kr), I(Ks), and I(Kp) channel properties. The results indicate that the ATP-sensitive K(+) channel is activated by the smallest reduction in ATP in epicardial cells and largest in endocardial cells when cytosolic ADP, AMP, PCr, Cr, P(i), total Mg(2+), Na(+), K(+), Ca(2+), and pH diastolic levels are normal. The model predicts that only K(ATP) ionophore (Kir6.2 subunit) and not the regulatory subunit (SUR2A) might differ from endocardium to epicardium. The analysis suggests that during ischemia, the inhomogeneous accumulation of the metabolites in the tissue sublayers may alter in a very irregular manner the K(ATP) channel opening through metabolic interactions with the endogenous PI cascade (PIP(2), PIP) that in turn may cause differential action potential shortening among the ventricular myocyte subtypes. The model predictions are in qualitative agreement with experimental data measured under normal and ischemic conditions in rabbit ventricular myocytes.