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Background and purpose Radiation-induced myelopathy, an irreversible complication occurring after a long symptom-free latency time, is preceded by a fixed sequence of magnetic resonance- (MR-) visible morphological alterations. Vascular degradation is assumed the main reason for radiation-induced myelopathy. We used dynamic contrast-enhanced (DCE-) MRI to identify different vascular changes after photon and carbon ion irradiation, which precede or coincide with morphological changes. Materials and methods The cervical spinal cord of rats was irradiated with iso-effective photon or carbon (12C-)ion doses. Afterwards, animals underwent frequent DCE-MR imaging until they developed symptomatic radiation-induced myelopathy (paresis II). Measurements were performed at certain time points: 1 month, 2 months, 3 months, 4 months, and 6 months after irradiation, and when animals showed morphological (such as edema/syrinx/contrast agent (CA) accumulation) or neurological alterations (such as, paresis I, and paresis II). DCE-MRI data was analyzed using the extended Toft’s model. Results Fit quality improved with gradual disintegration of the blood spinal cord barrier (BSCB) towards paresis II. Vascular permeability increased three months after photon irradiation, and rapidly escalated after animals showed MR-visible morphological changes until paresis II. After 12C-ion irradiation, vascular permeability increased when animals showed morphological alterations and increased further until animals had paresis II. The volume transfer constant and the plasma volume showed no significant changes. Conclusion Only after photon irradiation, DCE-MRI provides a temporal advantage in detecting early physiological signs in radiation-induced myelopathy compared to morphological MRI. As a generally lower level of vascular permeability after 12C-ions led to an earlier development of paresis as compared to photons, we conclude that other mechanisms dominate the development of paresis II.

Background Radiation-induced myelopathy is a severe and irreversible complication that occurs after a long symptom-free latency time if the spinal cord was exposed to a significant irradiation dose during tumor treatment. As carbon ions are increasingly investigated for tumor treatment in clinical trials, their effect on normal tissue needs further investigation to assure safety of patient treatments. Magnetic resonance imaging (MRI)-visible morphological alterations could serve as predictive markers for medicinal interventions to avoid severe side effects. Thus, MRI-visible morphological alterations in the rat spinal cord after high dose photon and carbon ion irradiation and their latency times were investigated. Methods Rats whose spinal cords were irradiated with iso-effective high photon (n = 8) or carbon ion (n = 8) doses as well as sham-treated control animals (n = 6) underwent frequent MRI measurements until they developed radiation-induced myelopathy (paresis II). MR images were analyzed for morphological alterations and animals were regularly tested for neurological deficits. In addition, histological analysis was performed of animals suffering from paresis II compared to controls. Results For both beam modalities, first morphological alterations occurred outside the spinal cord (bone marrow conversion, contrast agent accumulation in the musculature ventral and dorsal to the spinal cord) followed by morphological alterations inside the spinal cord (edema, syrinx, contrast agent accumulation) and eventually neurological alterations (paresis I and II). Latency times were significantly shorter after carbon ions as compared to photon irradiation. Conclusions Irradiation of the rat spinal cord with photon or carbon ion doses that lead to 100% myelopathy induced a comparable fixed sequence of MRI-visible morphological alterations and neurological distortions. However, at least in the animal model used in this study, the observed MRI-visible morphological alterations in the spinal cord are not suited as predictive markers to identify animals that will develop myelopathy as the time between MRI-visible alterations and the occurrence of myelopathy is too short to intervene with protective or mitigative drugs.

Carbon- (12C-) ion radiotherapy exhibits enhanced biological effectiveness compared to photon radiotherapy, however, the contribution of its interaction with the vasculature remains debatable. The effect of high-dose 12C-ion and photon irradiation on vascular permeability in moderately differentiated rat prostate tumors was compared using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Syngeneic R3327-HI rat prostate tumors were irradiated with a single dose of either 18 or 37 Gy 12C ions, or 37 or 75 Gy 6-MV photons (sub-curative and curative dose levels, respectively). DCE-MRI was performed one day prior to and 3, 7, 14 and 21 days postirradiation. Voxel-based tumor concentration-time curves were clustered based on their curve shape and treatment response was assessed as the longitudinal changes in the relative abundance per cluster. Radiation-induced vascular damage and increased permeability occurred at day 7 postirradiation for all treatment groups except for the 75 Gy photon-irradiated group, where the onset of vascular damage was delayed until day 14. No differences between irradiation modalities were found. Therefore, early vascular damage cannot explain the higher effectiveness of 12C ions relative to photons in terms of local tumor control for this moderately differentiated prostate tumor and the applied single high doses.

Background: Cancer patients (pts) are burdened by symptoms related to the disease itself or to the toxicities of treatment. A recent meta-analysis has shown that anxiety is the most common mental health issue among cancer survivors [Mitchell AJ, 2013]. The ASCO clinical oncology guideline adaptation recommends all health care providers routinely screen for the presence of emotional distress and symptoms of anxiety from the point of diagnosis onward [Andersen BL, 2014]. Consensus-based recommendations have been published to help cancer centers meet the American College of Surgeons Commission on Cancer's accreditation requirement to screen for distress [Pirl, 2014] At our comprehensive community cancer center we perform distress screening using the M.D. Anderson Symptom Inventory (MDASI), composed of 27 questions. Pts who report moderate and severe levels of distress (≥5) on the MDASI are identified and referred for therapeutic interventions offered by the facility's integrative oncology services. Materials and Methods: The MDASI is an assessment tool that captures pts' perceived symptom burden for real-time clinical intervention, taken at the point of no intervention (baseline) and every 21 days or greater. The 27-question MDASI is comprised of the M.D. Anderson Symptom Inventory (MDASI), a validated 19-item assessment instrument, with a Symptom Inventory Tool (SIT) added by our center of 8 questions and a free-text box. Symptoms are rated “at the worst” on an 11-point numeric scale ranging from 0 (“none present”) to 10 (“as bad as you can imagine”), as experienced by the patient in the past 24 hours. Results: Over a ten-month period (9/1/2014 to 6/30/2015), 247 breast cancer (BC) pts completed the MDASI at intake and again ≥ 21 days after. Analysis of their initial surveys identified 69 pts (27.9%) who rated their distress as ≥ 5 (1st MDASI mean = 6.83), scores which would have initiated a support system response with referrals to integrative medicine services for intervention. Second MDASI results from these 69 BC pts revealed an average 2.29 distress score reduction (2nd MDASI mean = 4.48), with 51 pts (73.9%) reporting a decrease in distress, 7 pts (10.1%) having no change, and 11 pts (15.9%) reporting increased distress. More specifically, the group with decreased distress levels documented a mean distress score of 3 on their 2nd MDASI, averaging a significant 4-point diminution of distress for three-fourths of the BC pts heavily burdened by this symptom. The integrative services most utilized by these pts were Nutrition Therapy (100%), Spiritual Care (96.1%), Mind-Body Counseling (82.4%), Rehabilitation Therapy (41.2%), Acupuncture (35.3%), and Massage Therapy (35.3%). Conclusions: Distress is a relevant symptom reported by cancer pts. This study demonstrates that early intervention in BC pts using integrative oncology approaches reduced distress in 74% of cases. Citation Format: Daneker SR, Bendinger GM, Thomas JW, Smith E, Kendrick D, Hartman S, Gordon C, Barber K, Langlois C, Pabbathi H, McKnight JE, Johnson AT, Lammersfeld C, Denny D, Markman M, Alvarez RH. Efficacy of screening and treatment of breast cancer patients reporting high level of distress [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-19-05.

BACKGROUND: Problems related to sexual function are known to affect quality of life in female breast cancer survivors (BCS). A leading symptom of sexual dysfunction reported by BCS is dyspareunia, defined as moderate to severe penetrative pain with intercourse that results in reduced frequency of intercourse or abstinence. Dyspareunia in females is most commonly caused by vaginal dryness and primarily treated with estrogen therapy, a contraindication for many BCS. A recent trial found that estrogen-deficient BCS with dyspareunia who applied topical lidocaine to the vulvar vestibule (VV) prior to penetrative intercourse (PI) reported decreased pain during PI and improvement of sexual distress (Goetsch MF, JCO 2015). Identification of additional non-hormonal therapies to target the VV prior to PI may therefore provide treatment options for the improvement of sexual dysfunction in BCS with dyspareunia. TRIAL DESIGN: This is a double-blind, randomized trial to evaluate the benefits of applying natural lubricant MoistHer (MH) to the VV prior to PI in female BCS with dyspareunia. Subjects must be female ≥18 years BCS without active treatment (except for hormonotherapy), in a stable heterosexual partnership for ≥5 years, and report ≥ 3 months of consistent pain with PI. Patients with a history of pelvic pain, pelvic floor myalgia, vulvar dermatoses, or vaginismus will be excluded. Subjects will be randomized 1:1 to blinded home therapies of either MH or Topical Lidocaine (TL) for application to VV. MH is a commercially available vaginal moisturizer made of emu oil, tocopherol, safflower oil, and aloe extract and will be supplied by manufacturer Dromeo Inc. TL will be a 4% aqueous lidocaine hydrochloride solution prepared by research pharmacist (RP). Both MH and TL will be dispensed by RP in identical unmarked bottles. Subjects will agree to apply study liquid to VV and attempt PI at least twice per week for 4 weeks while maintaining a study diary to record pain scores. Outcomes will be measured via Sexual Function Questionnaire (SFQ), Female Sexual Distress Score-Revised (FSDS-R), and a rating of pain during PI on a scale of zero (no pain) to 10 (worst pain) via Numerical Rating Scale (NRS), to be completed by subjects at baseline, 2 weeks, and 4 weeks. AIMS: Primary endpoint is pain with PI, to be reported as a score on the NRS. Secondary endpoints are improved quality of sexual life and resumption of PI, to be measured by the SFQ and FSDS-R. STATS/TARGET ACCRUAL: A total of 50 patients will be recruited and randomized to receive either MH or TL at a 1:1 ratio (25 per group) using the Pocock-Simon dynamic allocation method. This sample size will achieve 94% power to detect at least 1.5 points NRS mean difference between treatments. NRS change will be compared between the two arms using a two-sample t-test (Pooled Standard error or Satterthwaite approximation as appropriate). Secondary outcomes include the SFQ and FSDS-R for which a longitudinal analysis of subscale scores will be conducted using a generalized linear mixed-effects model with fixed effects for treatment group and time. All statistical analyses will be conducted using SAS 9.3 [SAS Institute Inc., Cary, NC, USA]. Statistical significance will be defined as p < 0.05. Citation Format: Bendinger GM, Baptist S, Alvarez Tapias C, McGuire E, Rados K, Nixon D, Randolph K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Geisler JP, Manahan KJ, Lammersfeld C, Avarez RH. A randomized study comparing MoistHer to topical lidocaine for female breast cancer survivors with dyspareunia [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-04.

BACKGROUND: A review of the literature identifies high levels of anxiety and depression as adverse effects of oncology diagnosis and treatment, even for patients with curable cancers such as early stage breast cancer (ESBC). Studies have reported that music therapy yields remarkable, multi-dimensional benefits on an individual's mood and state of mind. The purpose of this trial is to evaluate the impact of personalized music therapy (PMT) in reducing anxiety and other adverse mental health symptoms experienced by patients receiving chemotherapy treatment for ESBC. ELIGIBILITY: Females ≥ 18 years diagnosed with ESBC (Stage I-III) initiating intravenous chemotherapy as their only oncology treatment modality who report anxiety ≥ 4 on a numerical rating scale of 0-10. TRIAL DESIGN: This is a 4-week, two-arm, randomized (1:1) trial evaluating the anti-anxiety benefits of PMT for women with ESBC initiating intravenous (IV) chemotherapy. The patients randomized to the experimental group will participate in 30-minute PMT sessions conducted by a Licensed Musical Therapist (LMT). Initial PMT will occur within 1 hour of the patient's first chemotherapy infusion (C1D1), then once weekly for the remaining 3 weeks of the trial. Patients randomized to the control group will be referred to the medical oncologist for standard of care (SOC) anxiety treatment. Outcomes will be measured via the Generalized Anxiety Disorder Assessment (GAD-7), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Symptom Inventory Tool-M.D. Anderson Symptom Inventory (SIT-MDASI) to be completed by both cohorts at baseline and regular intervals for the duration of the study. AIMS: The primary endpoint is to determine the impact of PMT during chemotherapy treatment on patient reported anxiety (GAD-7). Secondary endpoints will determine the impact of PMT during chemotherapy treatment on patient reported depression (CES-D), sleep disturbances (PSQI), and quality of life (SIT-MDASI). STATISTICAL METHODS/TARGET ACCRUAL: Patients will be randomized to receive either PMT or SOC using the Pocock-Simon dynamic allocation method to balance tumor stage between the arms. With 30 patients in each arm and approximate target accrual of 60, the study achieves 80.0% power to detect a 0.65 standard deviation unit effect size of the change in scale measure between baseline and 4 weeks at the 0.05 significance level using a one-sided two-sample t-test. GAD-7 change will be compared between the two arms using a two-sample t-test (Pooled Standard error or Satterthwaite approximation as appropriate). The secondary outcomes include CES-D, PSQI, and SIT-MDASI for which a longitudinal analysis of subscale scores will be conducted using a generalized linear mixed-effects model with fixed effects for treatment group and time. All statistical analyses will be conducted using SAS 9.3 [SAS Institute Inc., Cary, NC, USA]. Statistical significance will be defined as p < 0.05. Citation Format: Toole Jr. M, Bendinger GM, Ensor Jr. JE, Alvarez Tapias C, Smith E, McGuire E, Rados K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Lammersfeld C, Alvarez RH. A randomized study of personalized music therapy for patients with early stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-08-01.

BACKGROUND: Observational studies have repeatedly linked obesity to increased cancer incidence, recurrence, and mortality, leading to cancer treatment guidelines that call for maintenance of a healthy body weight, regular physical activity (PA) regardless of body mass index (BMI), and modest weight loss for overweight and obese cancer survivors (CS). Despite these recommendations, newly published reports suggest that more than 70% of CS are overweight or obese, and only 1/3 engage in the recommended levels of PA. Although trials have demonstrated that energy balance (EB) interventions are feasible in CS, it has been concluded that ongoing behavioral support is needed to implement and sustain changes in weight and PA. Through the subsequent Energy Balance Research (EnBaR) the incorporation of a weight management and PA program focused on ongoing behavioral support for breast cancer survivors (BCS) as an effective method for implementation of lifestyle modifications will be investigated. TRIAL DESIGN: This is a single-arm prospective observational study investigating if implementation of an EB Program for BCS is an effective intervention for producing lifestyle behaviors. Eligible subjects must be female BCS ≥18 years with BMI ≥25 who are initiating hormonotherapy (HT) as their only oncology treatment modality. Subjects will consult with a Registered Dietitian (RD) to establish goals based on specified interventions for reducing overall BMI at the time of initiating their prescribed HT. Subjects will subsequently receive telephone calls from the RD at bi-monthly intervals to discuss the established points of intervention, answering questions proposed by the RD from a set intervention measurement scale. Patients will also report for body composition analysis performed by the RD via InBody at Baseline, Day 90, and Day 180. InBody is a validated tool that utilizes direct segmental multi-frequency bioelectrical impedance analysis (DSM-BIA) to provide a highly accurate report of an individual's body composition. AIMS: Determine change in Percent Body Fat (PBF) and BMI during adjuvant hormone treatment for breast cancer patients. STATS/TARGET ACCRUAL: To assess % change in BMI and PBF between baseline and 180 days, one-sample t-tests will be used. Assuming an average (avg) baseline BMI of 33.7 with a standard deviation of 8.5; a sample of 120 patients will yield 89.4% power using a two-sided t-test to detect a 13% reduction in BMI to an avg of 29.32 and 82.8% power to detect a 12% reduction to an avg BMI of 29.656. Similarly, a t-test will have 83.7% power to detect a 12% decrease in % change in PBF assuming an avg baseline PBF of 41.36 with a standard deviation 10.5. The power calculations were accomplished by generating simulations of size 10,000 replications conducted at the 0.025 significance level using the TTEST procedure of SAS 9.4 [SAS Institute Inc., Cary, NC, USA]. The calculations assume a linear correlation of 0.5 between the baseline and Day 180 measurements and are Bonferroni corrected to maintain a familywise error of 0.05 for the primary analysis. All statistical analyses will be conducted using SAS 9.4. Statistical significance will be defined as p < 0.05. Citation Format: Scheuer R, Bendinger GM, Ensor Jr. JE, Nixon D, Randolph K, McGuirec E, Rados K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Langlois C, Lammersfeld C, Alvarez RH. Positive behavior change and weight loss in breast cancer survivors on hormonal adjuvant therapy: An energy balance research in cancer (EnBaR) prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-03.

Background and aims Interventional treatment of chronic pain is widely practiced for a variety of chronic pain presentations. Response to treatment is varied. Better patient selection methods are required to determine which patients are most likely to benefit. This study aims to establish whether the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria has any predicative value for outcomes of interventional treatments for chronic non-cancer pain. Methods IRAS registered (project ID;231514) ethically approved prospective research study. Single center study – tertiary pain clinic in the UK. All English-speaking patients selected for therapeutic interventional pain procedures (excluding spinal cord stimulation) on comprehensive clinical assessment by an interventional pain consultant were eligible for inclusion. Consented patients self-completed the 2010 American College of Rheumatology diagnostic questionnaire. Primary outcome was >50% pain reduction 3 months after interventional procedure. Statistical analysis included comparison of means with t-test and median with Mann-Whitney test. Results 187 patients were recruited, of which 179 remained in the study. Prevalence of fibromyalgia questionnaire positive patients in group A (≥50% pain reduction) was 19.4% vs 23.1% in group B ( Conclusions We conclude that the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria does not have any predictive value in selecting patients for interventional pain treatments, if clinical judgment supports the intervention.

Key points The often complex, multidimensional, and subjective nature of pain makes it very challenging to assess both in terms of intensity and in terms of relief as a response to treatment. It is important for pain assessment in any setting to have scientifically valid tools to determine quality and intensity of pain, aid diagnosis, direct treatment, and evaluate effectiveness after discrete interventions. Valid, reliable, and sensitive tools are required to direct treatment for patient care, and for service provision to evaluate the success of therapy. Pain measurement tools also aid research on mechanisms of pain and outcomes of treatment. A wide variety of validated measures have been conceived and developed over the last 40 yr, and have been instrumental in highlighting the multifaceted complexity of the human pain experience. It is of utmost importance to note that they do not supplant the need to clinically assess pain, but add to the quality of that assessment. Validity is the degree to which a test measures either a quantity or hypothetical construct which it is intended to assess. This includes

The objective was to determine impact factors that would allow Pseudomonas aeruginosa and Legionella pneumophila to survive sanitation measures of household drinking water systems. Therefore, different disinfectant concentrations were tested under different operating conditions in close-to-practice experiments. Particular attention was paid to the viable but non-culturable (VBNC) state of the pathogens. Legionella pneumophila was able to survive disinfection with ClO2 in a culturable state in the biofilm at 37 °C while successful sanitation could be achieved at 11 °C, however non-culturable cells were still present. Culturable P. aeruginosa outlasted disinfection in biofilms of pipes at elevated nutrient concentrations and in built-in parts at 37 °C. Overall, the VBNC state was not the predominant factor for its survival. Additional experiments showed that the lack of an autochthonous biofilm may promote the growth of P. aeruginosa. This emphasizes the importance of localization and elimination of contamination sources in a plumbing system before disinfection is performed and the need for compliance with operating conditions and construction requirements defined by generally recognized standards of good practice in Germany.

Background and Aims The mechanism of action of spinal cord stimulation (SCS) is poorly understood and the success of treatment can depend on factors beyond the technical aspects of implantation. The aim of this retrospective analysis is the identification of preimplantation psychological values that may predict outcome of SCS treatment. Methods The retrospective analysis consisted of data from 83 patients who underwent SCS implantation from 2005 to 2013. Preimplantation evaluation included pain severity, sleep interference and distress each recorded with a numeric rating scale (NRS 0–10), depression and anxiety (Hospital Anxiety and Depression Score—HADS), catastrophizing (Pain Catastrophizing Scale—PCS), and patient's confidence in performing daily activity (Pain Self-Efficacy Questionnaire—PSEQ). Results A fall in pain score of greater than 50% at one year follow up was the criteria applied to divide patients into two groups. Group A consisted of 39 patients whose pain score fell more than 50% and group B consisted of 44 patients whose pain score fell less than 50% at one year follow up. The median preimplantation pain score was comparable between the two groups. However, the preimplantation scores for sleep interference, HADS-depression, PCS and PSEQ, were significantly worse in group B. Receiver operating characteristic (ROC) curve analysis and univariate regression show that HADS-depression >10 and PSEQ ≤18 are risk factors for failure of SCS treatment, but only sleep interference, assessed with NRS >7 out of 10 was found to be an independent predictor of a less optimal outcome in multiple logistic regression. Conclusions Sleep interference appears to be an independent risk factor for unsuccessful SCS therapy.

Introduction Early initiation of reperfusion therapy including primary percutaneous coronary revascularization (PPCI) has been recognized as a crucial factor determining clinical outcomes in the acute phase of myocardial infarction. In unstable patients with type 2 diabetes mellitus (T2D) the clear benefit from PPCI was proven. We aim to evaluate the prognostic value of factors describing glycometabolic state on admission in patients with T2D undergoing PPCI in acute ST-elevation myocardial infarction (STEMI). Material and methods Prospective analysis of clinical and laboratory variables (mean daily short acting exogenous insulin dose (DID), admission blood glucose, glycated hemoglobin (HbA1c), microalbuminuria) was performed in 112 consecutive patients with T2D with STEMI who underwent PPCI. Women comprised 58% of the group. Results Insulin dosing was targeted to obtain a mean daily glucose level < 7.8 mmol/l. During 12-month follow-up 33 (29.5%) major adverse cardiac events (major adverse cardiac events (MACE) consisting of death, reinfarction, and repeated target vessel revascularization) were reported. Microalbuminuria was present in 68 (60.5%) patients. The mean HbA1c level was 7.9%. In the multivariate logistic regression model only DID > 44 IU remained an independent risk factor for MACE (p = 0.02, OR = 5.2). Conclusions In patients with diabetes with STEMI treated with PPCI, simple measurement of DID during hospitalization can add valuable prognostic information about the future risk of MACE.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify perfusion and vascular permeability. In most cases a bolus arrival time (BAT) delay exists between the arterial input function (AIF) and the contrast agent arrival in the tissue of interest which needs to be estimated. Existing methods for BAT estimation are tailored to tissue concentration curves, which have a fast upslope to the peak as frequently observed in patient data. However, they may give poor results for curves that do not have this characteristic shape such as tissue concentration curves of small animals. In this paper, we propose a method for BAT estimation of signals that do not have a fast upslope to their peak. The model is based on splines which are able to adapt to a large variety of concentration curves. Furthermore, the method estimates BATs on a continuous time scale. All relevant model parameters are automatically determined by generalized cross validation. We use simulated concentration curves of small animal and patient settings to assess the accuracy and robustness of our approach. The proposed method outperforms a state-of-the-art method for small animal data and it gives competitive results for patient data. Finally, it is tested on in vivo acquired rat data where accuracy of BAT estimation was also improved upon the state-of-the-art method. The results indicate that the proposed method is suitable for accurate BAT estimation of DCE-MRI data, especially for small animals.

The identification of the disease progression and drug resistance pathways involved in breast cancer led to the development of mammalian target of rapamycin (mTOR) inhibitors. Since their introduction, mTOR inhibitors have improved clinical outcomes in patients with advanced breast cancer. These agents are generally well tolerated, but they have a unique adverse event (AE) profile of which clinicians and nurses should be aware. Although rare, noninfectious pneumonitis (NIP) is one such mTOR-associated AE that is generally mild and manageable, but it can result in severe or potentially life-threatening toxicity. Previous clinical experience with everolimus and temsirolimus in renal cell carcinoma has led to the development of guidelines for the diagnosis and management of mTOR-associated AEs, including NIP. However, specific guidelines in the advanced breast cancer setting are currently lacking. Herein we review the available literature regarding the development of mTOR-associated NIP in patients with advanced breast cancer. In addition, we have developed a set of guidelines that will provide nurses with appropriate management strategies for the treatment of mTOR inhibitor–associated NIP in patients with advanced breast cancer.

A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity.

BACKGROUND: The increase in breast cancer (BC) survival is largely due to the benefits of hormonal therapy, such as tamoxifen and aromatase inhibitors (AIs), for the treatment of hormone-sensitive breast cancer. Recent clinical trials have demonstrated that AIs are more effective than tamoxifen at reducing BC recurrences. However, BC patients receiving AIs have a higher incidence of osteoporosis, bone fractures, and musculoskeletal symptoms, particularly joint pain and stiffness. The incidence of AIIA in the ATAC trial was 27.8% in patients taking anastrozole versus (vs) 21% in patients taking tamoxifen (Baum M, Lancet 2002). The arthralgia associated with AIs can be so debilitating that it contributes to a significant percentage of non-compliance and discontinuation of systemic treatment. Patients with cancer often show interest in complementary and integrative modalities for symptom management (Vickers AJ, Lancet 2001), of which Acupuncture (Ac) is one of the most utilized therapies. ELIGIBILITY: Subjects must be female ≥18 years, have undergone mastectomy or breast-sparing surgery, and must have recovered from all pain-related effects of the surgery and radiotherapy with a minimum washout period of 30 days prior to registration. Patients should have ER and PR positive BC and be actively taking a 3rd-generation AI (Anastrozole, Letrozole, or Exemestane) for at least the 30 days prior to registration and plan to continue for at least one year after registration. ECOG PS 50,000/uL. Patients must not have received topical analgesic with exception of oral NSAIDS drugs ≤14 days to registration. TRIAL DESIGN: This is a 12-week, two arm randomized (1:1) trial evaluating the benefit of Ac in BC patients experiencing AIIA. AIMS: The aim of this study is to investigate the effectiveness of an integrative approach using Ac vs usual care (UC) treatment consisting of NSAIDs for the management of the AIIA.Primary endpoint is to compare the difference of Brief Pain Inventory-Short Form (BPI-SF) score at baseline vs week 8 between Ac and UC groups. Secondary endpoints are a) to compare the difference of BPI-SF score at baseline vs week 12 between Ac and UC groups, b) to compare the difference in AI adherence between Ac and UC groups and c) to compare the difference in patient initiated AI discontinuation between Ac and UC groups. STATS/TARGET ACCRUAL: This is a randomized controlled phase II study with the goal to compare reduction in BPI-SF score for patients treated with Ac vs UC alone. Patients are randomized 1:1 between the two arms. Prior work has indicated a 2-point BPI-SF score reduction as clinically meaningful. A sample size of 56 patients yields a study with 90% power and a one-sided significance level of 0.025 to determine a difference in pain reduction ≥2. These calculations are based on the assumptions of normal distribution of the improvement in BPI-SF score and a standard deviation that is conservatively calculated to be 2.3. An additional 6 patients will be accrued to account for attrition. Citation Format: Frank HS, Bendinger GM, Ensor Jr. JE, Neufeld N, Nixon D, Randolph K, McGuire E, Rados K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Lammersfeld C, Alvarez R. A randomized controlled trial comparing acupuncture versus usual care for the treatment of aromatase inhibitor-induced arthralgia (AIIA) in women with early-stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-02-04.