Impact of Treatment Modality on Quality of Life Among Uterine Cancer Survivors.

AIMS: Our understanding of the impact of adjuvant therapy on longitudinal quality of life (QoL) following surgery for patients with uterine cancer is limited. The purpose of this study was to compare QoL in patients who have undergone surgery with or without radiation therapy for uterine cancer. MATERIALS AND METHODS: This was a cross-sectional cohort study that examined women treated for uterine cancer at MD Anderson Cancer Center from 2006 to 2017. Participants included those who underwent hysterectomy/bilateral salphingo-oophorectomy alone, with brachytherapy or external beam radiation therapy (EBRT). A non-cancer cohort of women who underwent a hysterectomy/bilateral salphingo-oophorectomy for benign indications was also identified (non-CA). To compare QoL we used the Functional Assessment of Cancer Therapy - Endometrial survey (FACT-En), a validated survey used to assess QoL. The survey has five subscales: physical, social, emotional, functional and an endometrial cancer-specific subscale. Cohorts were compared using ANOVA tests. RESULTS: In total, 309 women responded to the questionnaire (hysterectomy/bilateral salphingo-oophorectomy 64, brachytherapy 77, EBRT 96, non-CA 72). The median time from surgery to survey completion was 6.7 years. The mean total FACT-En score for the entire cohort was 144 [standard deviation 22]. Overall QoL was different between cohorts, with the EBRT cohort reporting the lowest QoL (mean 139.4 [21.6]) and the brachytherapy cohort the highest (150.6 [18.2], P = 0.006). Among patients who had undergone cancer treatment, the EBRT cohort reported the worst endometrial-specific QoL (53.5 [8.6]), while again the brachytherapy group reported the highest score (57.5 [6.1], P = 0.007). CONCLUSIONS: QoL differences in women who have undergone different treatments for uterine cancer may persist years after treatment. In women with endometrial cancer who require adjuvant therapy, brachytherapy does not appear to have any long-term detriments on QoL.

Deformable image registration for dose mapping between external beam radiotherapy and brachytherapy images of cervical cancer.

For locally advanced cervical cancer (LACC), anatomy correspondence with and without BT applicator needs to be quantified to merge the delivered doses of external beam radiation therapy (EBRT) and brachytherapy (BT). This study proposed and evaluated different deformable image registration (DIR) methods for this application. Twenty patients who underwent EBRT and BT for LACC were retrospectively analyzed. Each patient had a pre-BT CT at EBRT boost (without applicator) and a CT and MRI at BT (with applicator). The evaluated DIR methods were the diffeomorphic Demons, commercial intensity and hybrid methods, and three different biomechanical models. The biomechanical models considered different boundary conditions (BCs). The impact of the BT devices insertion on the anatomy was quantified. DIR method performances were quantified using geometric criteria between the original and deformed contours. The BT dose was deformed toward the pre-CT BT by each DIR method. The impact of boundary conditions to drive the biomechanical model was evaluated based on the deformation vector field and dose differences. The GEC-ESTRO guideline dose indices were reported. Large organ displacements, deformations, and volume variations were observed between the pre-BT and BT anatomies. Rigid registration and intensity-based DIR resulted in poor geometric accuracy with mean Dice similarity coefficient (DSC) inferior to 0.57, 0.63, 0.42, 0.32, and 0.43 for the rectum, bladder, vagina, cervix and uterus, respectively. Biomechanical models provided a mean DSC of 0.96 for all the organs. By considering the cervix-uterus as one single structure, biomechanical models provided a mean DSC of 0.88 and 0.94 for the cervix and uterus, respectively. The deformed doses were represented for each DIR method. Caution should be used when performing DIR for this application as standard techniques may have unacceptable results. The biomechanical model with the cervix-uterus as one structure provided the most realistic deformations to propagate the BT dose toward the EBRT boost anatomy.

Primary vaginal cancer: role of MRI in diagnosis, staging and treatment.

Primary carcinoma of the vagina is rare, accounting for 1-3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications.

SU-E-T-425: Impact of Model Based Dose Calculation Algorithm for Ir-192 Intracavitary Brachytherapy with Shielded Applicator.

PURPOSE: To determine the impact of a grid based Boltzmann solver (GBBS) on a cohort of cervical cancer patients treated with Ir-192 intracavitary brachytherapy with shielded applicators. METHODS: Retrospective plans were generated using BrachyVision v8.8 (TPS) with GBBS Acuros v1.3.1. The study includes 24 patients that had CT planning images acquired with CT/MR compatible applicators. Using the TPS applicator library, shielded colpostats and tandem (#AL13122005) were virtually positioned to replace the applicators seen on CT. Dwell weights were based on TG43 delivering 6 Gy to point A. Four GBBS calculations were performed to assess differences from the standard of practice TG43. The different GBBS calculations were: 1) no applicator modeled, body= 1 g/cc muscle, 2) applicator modeled, body=1g/cc muscle, 3) applicator modeled, CT-to-material mapping with contrast (vaginal packing, rectal, Foley balloon) = 1g/cc muscle, and 4) applicator model, CT-to-material mapping without material overrides. The multiple GBBS calculations allow differences from TG43 to be attributed to factors representing the modeling of source and patient boundaries (scatter conditions), tissue heterogeneities, and applicators. RESULTS: Differences between GBBS4 and TG43 at clinical dosimetric points were as follows: [mean ± standard (min, max)], Point A: - 2.5% ± 0.5% (-3.8%, -1.2%), Point B: -1.5% ± 1.0% (-3.2%, 1.1%), ICRU rectum: -8.4% ± 2.5% (-14.0%, -4.1%), D2cc rectum: -6.2% ± 2.6% (- 11.9%, -0.8%), ICRU bladder: -7.2% ± 3.6% (-15.7%, -2.1%); D2cc bladder: -3.4% ± 1.8% (-7.2%, -1.1%). Bar plots comparing the modeling factors previously listed show that applicator modeling is the largest contributor to differences from TG43. CONCLUSIONS: Clinically significant dose differences (>5%) relative to TG43 exist when using a model-based dose calculation algorithm such as the GBBS with shielded applicators. Differences were largely due to applicator modeling, not tissue heterogeneities, source modeling, or patient boundary modeling.

The (in) auspicious role of mesenchymal stromal cells in cancer: be it friend or foe.

Recent progress in the research of mesenchymal stromal cells/multipotent stromal cells (MSC) has revealed numerous beneficial innate characteristics, suggesting potential value in an array of cellular therapies. MSC are easily isolated from bone marrow (BM), fat and other tissues, and are readily propagated in vitro. Transplanted/injected MSC have been shown to migrate to a variety of organs and tissues; however, sites of inflammation and pathology elicit enhanced MSC homing for tissue remodeling and repair. Tumors utilize many of the same inflammatory mediators uncovered in wound healing and likewise provide a site for preferential MSC homing. Although incorporation into the tumor microenvironment is apparent, the role of recruited MSC in the tumor microenvironment remains unclear. Some published studies have shown enhancement of tumor growth and development, perhaps through immunomodulatory and pro-angiogenic properties, while others have shown no apparent effect or have demonstrated inhibition of tumor growth and extended survival. This controversy remains at the forefront as clinical applications of MSC commence in anti-tumor therapies as well as as adjuncts to stem cell transplantation and in ameliorating graft-versus-host disease. Careful analysis of past studies and thoughtful design of future experiments will help to resolve the discrepancies in the field and lead to clinical utility of MSC in disease treatment. This review highlights the current theories of the role of MSC in tumors and explores current controversies.

Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells.

Mesenchymal stem cells (MSC) exhibit tropism for sites of tissue damage as well as the tumor microenvironment. Many of the same inflammatory mediators that are secreted by wounds are found in the tumor microenvironment and are thought to be involved in attracting MSC to these sites. Cell migration is dependent on a multitude of signals ranging from growth factors to chemokines secreted by injured cells and/or respondent immune cells. MSC are likely to have chemotactic properties similar to other immune cells that respond to injury and sites of inflammation. Thus, the well-described model of leukocyte migration can serve as a reasonable example to facilitate the identification of factors involved in MSC migration. Understanding the factors involved in regulating MSC migration to tumors is essential to ultimately develop novel clinical strategies aimed at using MSC as vehicles to deliver antitumor proteins or suppress MSC migration to reduce tumor growth. For example, radiation enhances inflammatory signaling in the tumor microenvironment and may be used to potentiate site-specific MSC migration. Alternatively, restricting the migration of the MSC to the tumor microenvironment may prevent competent tumor-stroma formation, thereby hindering the growth of the tumor. In this review, we will discuss the role of inflammatory signaling in attracting MSC to tumors.

Improving certified nurse aide retention. A long-term care management challenge.

In the long-term care industry, the turnover rate among nurse aides is extremely high. This adversely affects resident satisfaction, resident care, morale, and finances. It presents a challenge to long-term care administration. Refusing to accept high turnover as an impossible situation allows changes to be made. The authors describe how the staff at one intermediate care facility identified its problems, assessed the causes, and implemented corrective action.

Analgesic potency of alpha adrenergic agents after systemic administration in amphibians.

The analgesic and behavioral effects produced by systemic adrenergic agonists dexmedetomidine (0.1-3 nmol/g), clonidine (100-1000 nmol/g), epinephrine (1-30 nmol/g) and norepinephrine (10-300 nmol/g) were determined in Rana pipiens using the acetic acid test. Each agonist produced a dose-dependent analgesic effect that was sustained for at least 4 hr with all agonists. The analgesic effect of epinephrine and dexmedetomidine was observed 15 min after agonist administration and continued for more than 8 hr. Dexmedetomidine was the most potent agonist followed by epinephrine, norepinephrine and clonidine, and the relative potencies compared to epinephrine = 1.0 were 0.01 (clonidine), 0.02 (norepinephrine) and 4.83 (dexmedetomidine). Pretreatment with selective alpha-2 receptor antagonists, yohimbine and atipamezole, significantly decreased the analgesic effect of dexmedetomidine (80 and 87%) and clonidine (66 and 60%), whereas the selective alpha-1 receptor antagonist, prazosin, had no effect on dexmedetomidine but augmented clonidine analgesia. All animals treated with alpha adrenergic agonists retained corneal, righting and hind limb withdrawal reflexes and exhibited normal behavior. These studies demonstrate that systemic adrenergic agonists produce analgesia in amphibians, with a similar order of potency as reported in mammalian studies, and suggest that this analgesia is mediated by adrenergic alpha-2 receptors.

Analgesic potency of mu and kappa opioids after systemic administration in amphibians.

The relative analgesic potency of 11 opioid agents was assessed by using the acetic acid test in amphibians. Systemic administration of the mu agonists, fentanyl, levorphanol, methadone, morphine, meperidine and codeine; the partial mu agonist, buprenorphine; and the kappa agonists nalorphine, bremazocine, U50488 and CI-977 was made by s.c. injection into the dorsal lymph sac of the Northern grass frog, Rana pipiens. All agents produced a dose-dependent and long-lasting analgesia which persisted for at least 4 hr. The analgesic effects of single doses of each agent were significantly blocked or reduced by pretreatment with naltrexone. Systemic opioids produced log dose-response curves which yielded ED50 values ranging from 1.4 nmol/g for fentanyl to 320.9 nmol/g for nalorphine. Comparison of ED50 values gave a rank order of analgesic potency = fentanyl > CI-977 > levorphanol > U50488 > methadone > bremazocine > morphine > buprenorphine > meperidine > codeine > nalorphine. The relative analgesic potency of mu opioids in amphibians was significantly correlated with relative analgesic potency of these same agents obtained on the mouse writhing and hot plate tests. These data suggest that the amphibian model may serve as an adjunct or alternative model for the testing of opioid agents. Furthermore, given the inactivity of kappa opioids on rodent hot plate and tail-flick tests, the acetic acid test in amphibians may be especially well-suited for the assessment of opioid analgesia after administration of kappa-selective opioids.

Transport of esterified retinol in fasting human blood.

The transport of retinyl palmitate in postabsorptive human blood has been investigated. For this purpose, lipoproteins were isolated from fasting serum of normal subjects as well as of patients with various diseases. The serum retinyl palmitate values of these individuals ranged from 2.0-30.3 micrograms/100 ml, with a mean value of 7.6 micrograms/100 ml. In the 14 human subjects investigated, 68.1% of the recovered retinyl palmitate was associated with the VLDL fraction and 28.9% with the LDL fraction. Nevertheless, the individual pattern of retinyl palmitate distribution among VLDL and LDL differed considerably within this group. No esterified retinol, however, was detected in the HDL as well as in the nonlipoprotein fraction (d greater than 1.21 g/ml) of human serum. It is concluded that the transport of esterified retinol in fasting blood is not restricted to chylomicron remnants. Nevertheless, in humans the serum transport of retinyl palmitate is preferentially mediated by lipoproteins of the VLDL fraction.

Comparison between three fluorometric micromethods for determination of vitamin A in serum.

Three common micromethods for vitamin A1 determination were applied to blood, and compared with each other. Methods under investigation were: silicic acid column technique described by Pollack et al [16], HPLC procedure published by de Ruyter and de Leenheer [6, 7] and correction formula method according to Thompson et al [20]. The serum levels of vitamin A were measured in 51 fasting individuals. The average overall agreement was 104% and 116% of the HPLC value for the silicic acid column technique and for the correction formula method, respectively. The mean values obtained by the three methods do not differ significantly. Using these techniques simultaneously, however, in some cases serum values for the same sample show wide differences. Although vitamin A is usually present in biological samples both as retinol and as retinyl esters, the simple correction formula method does not distinguish between them. Their separate estimation, however, can be achieved by different chromatographic procedures. The HPLC method therefore used offers several advantages over the described silicic acid column technique. This technique includes fluorescence detection and provides a rapid and simple estimation of retinol and retinyl palmitate levels using only 180 microliter serum. For these reasons, the HPLC assay is suggested for routine determination of vitamin A in blood.