Hybrid tandem and ovoids brachytherapy in locally advanced cervical cancer: impact of dose and tumor volume metrics on outcomes.

PURPOSE: To report the impact of dose and tumor volume metrics at brachytherapy on outcomes for locally advanced cervical cancer treated with tandem and ovoids intracavitary/interstitial brachytherapy. MATERIAL AND METHODS: FIGO stage IB1-IIIB locally advanced cervical cancer treated with intracavitary/interstitial brachytherapy via a tandem and ovoids hybrid applicator were analyzed. Median high-risk clinical target volume (HR-CTV), rate of tumor volume reduction, EQD2 D90, organ at risk doses, and outcomes were recorded. Univariable and multivariable Cox regression was applied for survival analysis, and logistic regression was used for toxicity analysis. RESULTS: Seventy-one patients were identified. Median follow-up was 24.9 months, with a 2-year local control of 83.6%, loco-regional control of 72.0%, and overall survival of 88.6%. Median HR-CTV D90 was 87.4 Gy (IQR = 85.7-90.2). Median HR-CTV D90 > 90 Gy10 showed a trend toward improved local control (LC) (p = 0.19). Median HR-CTV was 37.9 cm3, and median V100 was 86.5%. A median HR-CTV of ≥ 40 cm3 demonstrated worse loco-regional control (LRC) (p = 0.018) and progression-free survival (p = 0.021). Two-year LC and LRC for stage IIB patients with a median HR-CTV < 40 cm3 were significantly improved as compared to ≥ 40 cm3 at 100% and 71.8%, respectively (p = 0.019) and 100% and 56.5%, respectively (p = 0.001). However, this trend was not statistically significant for stage IIIB patients. Higher percent per day reduction in HR-CTV during brachytherapy showed improved LRC (p = 0.045). Four percent of patients experienced acute grade 3 genitourinary toxicity, 1% late grade 3 genitourinary and 1% late grade 3 gastrointestinal toxicity. CONCLUSIONS: Tandem and ovoids intracavitary/interstitial brachytherapy provides satisfactory outcomes with modest toxicity. Higher HR-CTV D90 coverage demonstrated a trend toward improved tumor control. Tumor volume based on median HR-CTV ≥ 40 cm3 at brachytherapy was prognostic for poor outcomes, even within initial FIGO stage groups warranting caution.

Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate.

In the prostate, stem and progenitor cell regenerative capacities have been ascribed to both basal and luminal epithelial cells. Here, we show that a rare subset of mesenchymal cells in the prostate are epithelial-primed Nestin-expressing cells (EPNECs) that can generate self-renewing prostate organoids with bipotential capacity. Upon transplantation, these EPNECs can form prostate gland tissue grafts at the clonal level. Lineage-tracing analyses show that cells marked by Nestin or NG2 transgenic mice contribute to prostate epithelium during organogenesis. In the adult, modest contributions in repeated rounds of regression and regeneration are observed, whereas prostate epithelial cells derived from Nestin/NG2-marked cells are dramatically increased after severe irradiation-induced organ damage. These results indicate that Nestin/NG2 expression marks a novel radioresistant prostate stem cell that is active during development and displays reserve stem cell activity for tissue maintenance.

In Vitro Photoirradiation System for Simultaneous Irradiation with Different Light Doses at a Fixed Temperature.

OBJECTIVE: In this work an irradiance and temperature controlled in-vitro system for conducting investigations in PDT and phototherapy is presented. BACKGROUND DATA: The development of new light sources has caused a considerable increase in research and application of several photodynamic (PDT) therapeutic methods, as well as other light-based therapeutic techniques. However, further work is needed to fully understand and elucidate the mechanisms as well as to increase the effectiveness of PDT. Nowadays, there are no commercial systems to perform automated light exposure experiments with cultured cells. Also, there are very few reports of similar photoirradiation systems. MATERIALS AND METHODS: The system is composed of 24 independent light-emitting diodes that can be used to irradiate separate wells in a microwell plate. The system includes a module to measure changes in temperature within each irradiated well without contact. The light sources are placed on a plate that can easily be changed in order to irradiate at different wavelengths. The performance of the system is fully controlled with a computer, and all the experimental data are properly recorded. RESULTS: The design, construction, operation, and a full characterization of the system are presented. CONCLUSIONS: A novel fully automated photoirradiation system has been developed. The system allows the design of the experiments in this area with precise dosimetry, temperature, and irradiation regime controls reducing manipulation of the samples and saving time.

A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center.

BACKGROUND: Pediatric cancer patients requiring radiation therapy (RT) have been routinely assessed and referred to proton therapy (PT) at an external institution. The benefit of the delivered PT compared to the state-of-the-art intensity modulated x-ray RT (XT) at the home institution was evaluated. PROCEDURE: Twenty-four consecutive children referred for PT during 2010-2013 for craniospinal (CSI, n = 10), localized intracranial (IC, n = 7), head/neck (HN, n = 4) or parameningeal (PM, n = 3) lesions were included. The median age was 8 years (2-16 years). XT plans were generated for each patient, blinded to the PT delivered. Dosimetry, estimated growth hormone deficiency (GHD), and neurocognitive dysfunction (NCD) risks were compared for PT and XT (Wilcoxon). RESULTS: PT started (median) 5 weeks (± 1.3 weeks, 95% CI) after referral. For CSI patients, PT was clearly superior to XT plans with median dose reductions for the heart, lungs and thyroid of 17, 2.5 and 18 Gy, respectively (P = 0.005). The median estimated NCD and GHD risks were 1-3 (max 16) and 2 (max 61) percentage points, respectively, lower for PT compared to XT. The median of the mean doses to the brain, cochleae and pituitary gland was lower with PT than XT for the IC, H/N and PM patients (P < 0.039). For a single IC patient, the dose to hippocampi and optic chiasm was higher for PT compared to XT. CONCLUSIONS: PT clearly benefitted the patients studied, except for IC disease where differences between PT and XT were modest, and comparative PT and XT treatment planning is warranted prior to referral.