A retrospective study evaluating the pretreatment tumor volume (PTV) in non-small cell lung cancer (NSCLC) as a predictor of response to program death-1 (PD-1) inhibitors.

INTRODUCTION OF HYPOTHESIS: Little information is available regarding the imaging characteristics that assist in differentiating responders from non-responders. We hypothesized that patients with higher pretreatment tumor volume (PTV) would have lower response rates and shorter overall survival (OS). METHODS: Data from patients who received at least one dose of program death-1 (PD-1) inhibitors before August 31, 2016 were captured from our institution's pharmacy database. The primary objective was to determine the association of PTV with best response, evaluated utilizing RECIST v1.1 criteria. Secondary objectives were estimation of progression-free survival (PFS) and OS. PTV was measured using the Philips Intellispace Multi-Modality Tumor Tracking application. RESULTS: 116 non-small cell lung cancer (NSCLC) patients were evaluated. 66% patients had adenocarcinoma, 28% had squamous cell carcinoma and 5% had poorly differentiated NSCLC. Median PTV was 53.7 cm3 (95% CI: 13.3-107.9). Only one individual had no metastases and the remainder had M1 disease; 38% M1a, 10% M1b, 51% M1c. Most (79%) were previously treated. There were no complete responses; among those followed for at least 6 weeks, 26% had a partial response, 39% stable disease and 34% PD; 4% had no recorded response. There were no strong associations of PTV with any of the demographic or clinical characteristics. There was no association between PTV and OS (HR 1.2, P=0.26) or PFS (HR 1.1, P=0.47). Liver metastasis was associated with shorter survival (HR=2.8, P=0.05). CONCLUSION: PTV in NSCLC did not prove to be a predictor of response to PD-1 inhibitors but having liver metastasis was associated with significantly shorter survival.

Respiration induced heart motion and indications of gated delivery for left-sided breast irradiation.

PURPOSE: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. METHODS AND MATERIALS: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D(LAD) (the distance from left ascending aorta to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. RESULTS: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D(LAD) and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V(25.2) for the heart. MHD and D(LAD) were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D(LAD) or MHD variations. CONCLUSION: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D(LAD) can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment.

Does brachytherapy improve survival in addition to external beam radiation therapy in patients with high risk stage I and II endometrial carcinoma?

INTRODUCTION: The benefit of adjuvant external beam radiation therapy (EBRT) in combination with intravaginal brachytherapy (BT) in stage I and II endometrial adenocarcinoma remains controversial. We evaluated the effect of adjuvant EBRT and combined EBRT + BT on overall survival and relative survival within a large US population database. METHODS: We performed an analysis of retrospective data from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute from January 1, 1998 to December 31, 2005. A total of 3395 patients with stages IB, IC, and II node-negative endometrial adenocarcinoma comprised the population. Overall survival (OS) and relative survival (RS) curves were constructed via the Kaplan-Meier method and subgroups were compared via stratified log-rank test within T stage/grade combinations. Cox proportional hazards modeling was performed to evaluate the effect of multiple variables. RESULTS: EBRT alone was used in 2128 patients (62.7%) and 1267 patients (37.3%) received a combination of EBRT + BT. Higher grade, black race, older age at diagnosis, and later year of diagnosis are associated with worse overall survival, while lymphadenectomy is associated statistically with improved survival. The addition of BT revealed no statistically significant effect on OS. CONCLUSIONS: This large population-based study revealed no improvement in OS or RS with the addition of BT to EBRT in high risk stage I and stage II endometrial cancer. Although specific patient cohorts may benefit from combined EBRT and BT, additional analysis is warranted to further elucidate optimal treatment strategies for adjuvant radiotherapy based on specific clinical and pathologic features.

Multiple giant coronary artery aneurysms.

Coronary artery aneurysms are rare, and giant coronary artery aneurysms are even rarer. We describe a patient who had giant coronary aneurysms of the right, left circumflex, and left anterior descending coronary arteries. The aneurysms were successfully treated with surgical intervention. To the best of our knowledge, ours is the 1st report of giant aneurysms involving all 3 major coronary arteries.

Methamphetamine-induced dopaminergic deficits and refractoriness to subsequent treatment.

Repeated high-dose methamphetamine administrations can cause persistent dopaminergic deficits. As individuals abusing methamphetamine are often exposed to recurrent high-dose administration, the impact of its repeated exposure merits investigation. Accordingly, rats were pretreated with repeated high-dose injections of methamphetamine, and subsequently "challenged" with the same neurotoxic regimen 7 or 30 days later. Results revealed that the initial methamphetamine treatment caused persistent deficits in striatal dopamine levels, dopamine transporter function, and vesicular monoamine transporter-2 function. The subsequent methamphetamine challenge treatment was without further persistent effects on these parameters, as assessed 7 days after the challenge, regardless of the interval (7 or 30 days) between the initial and challenge drug exposures. Similarly, a methamphetamine challenge treatment administered 7 days after the initial drug treatment was without further acute effect on dopamine transporter or VMAT-2 function, as assessed 1 h later. Thus, this study describes a model of resistance, possibly explained by: 1) the existence of dopaminergic neurons that are a priori refractory to deficits caused by methamphetamine; 2) the existence of dopaminergic neurons made persistently resistant consequent to a neurotoxic methamphetamine exposure; and/or 3) altered activation of post-synaptic basal ganglia systems necessary for the elaboration of methamphetamine-induced dopamine neurotoxicity.