Surface Passivation by Quantum Exclusion: On the Quantum Efficiency and Stability of Delta-Doped CCDs and CMOS Image Sensors in Space.

Radiation-induced damage and instabilities in back-illuminated silicon detectors have proved to be challenging in multiple NASA and commercial applications. In this paper, we develop a model of detector quantum efficiency (QE) as a function of Si-SiO2 interface and oxide trap densities to analyze the performance of silicon detectors and explore the requirements for stable, radiation-hardened surface passivation. By analyzing QE data acquired before, during, and after, exposure to damaging UV radiation, we explore the physical and chemical mechanisms underlying UV-induced surface damage, variable surface charge, QE, and stability in ion-implanted and delta-doped detectors. Delta-doped CCD and CMOS image sensors are shown to be uniquely hardened against surface damage caused by ionizing radiation, enabling the stability and photometric accuracy required by NASA for exoplanet science and time domain astronomy.

Oncotype Dx Score, HER2 Low Expression, and Clinical Outcomes in Early-Stage Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: The interaction between HER2-low expression, oncotype recurrence score (RS), and their influence on the prognosis of HR+/HER2- breast cancer (BC) is not very well studied. METHODS: We conducted a retrospective cohort study of patients diagnosed with resectable HER2-low and HER2-zero BC from the National Cancer Database. The primary outcome was overall survival (OS), and the association of RS with the clinical outcomes in HR+/HER2- BC was analyzed as an exploratory endpoint. RESULTS: The distribution of RS was comparable between HER2-low and HER2-zero groups; however, the RSs of HER2-low tumors were more likely to be 16-25. Women with HER2-low tumors had longer 5-year OS than women with HER2-zero tumors in the HR-negative (84.3% vs. 83.9%; p < 0.001, HR: 0.87 (0.84-0.90), p < 0.001) but not in the HR-positive group (94.0% vs. 94.0%; p = 0.38, HR: 0.97 (0.95-0.99), p = 0.01). The survival advantage was observed in patients who received adjuvant/neoadjuvant chemotherapy (p-interaction (chemo vs. no chemo) < 0.001). Among those who received adjuvant chemotherapy in the group with higher RSs (26-100), those with HER2-low BC had higher 5-year OS than HER2-zero BC. CONCLUSIONS: Resectable HER2-low BC had a better prognosis than HER2-zero BC. Among those who received adjuvant chemotherapy in the higher oncotype RS group, those with HER2-low tumors had better survival.

Transportation barriers, emergency room use, and mortality risk among US adults by cancer history.

BACKGROUND: Lack of safe, reliable, and affordable transportation is a barrier to medical care, but little is known about its association with clinical outcomes. METHODS: We identified 28 640 adults with and 470 024 adults without a cancer history from a nationally representative cohort (2000-2018 US National Health Interview Survey) and its linked mortality files with vital status through December 31, 2019. Transportation barriers were defined as delays in care because of lack of transportation. Multivariable logistic and Cox proportional hazards models estimated the associations of transportation barriers with emergency room (ER) use and mortality risk, respectively, adjusted for age, sex, race and ethnicity, education, health insurance, comorbidities, functional limitations, and region. RESULTS: Of the adults, 2.8% (n = 988) and 1.7% (n = 9685) with and without a cancer history, respectively, reported transportation barriers; 7324 and 40 793 deaths occurred in adults with and without cancer history, respectively. Adults with a cancer history and transportation barriers, as compared with adults without a cancer history or transportation barriers, had the highest likelihood of ER use (adjusted odds ratio [aOR] = 2.77, 95% confidence interval [CI] = 2.34 to 3.27) and all-cause mortality risk (adjusted hazard ratio [aHR] = 2.28, 95% CI = 1.94 to 2.68), followed by adults without a cancer history with transportation barriers (ER use aOR = 1.98, 95% CI =1.87 to 2.10; all-cause mortality aHR = 1.57, 95% CI = 1.46 to 1.70) and adults with a cancer history but without transportation barriers (ER use aOR = 1.39, 95% CI = 1.34 to 1.44; all-cause mortality aHR = 1.59, 95% CI = 1.54 to 1.65). CONCLUSION: Delayed care because of lack of transportation was associated with increased ER use and mortality risk among adults with and without cancer history. Cancer survivors with transportation barriers had the highest risk.

Phosphate deficiency modifies lipid composition and seed oil production in camelina.

Camelina (Camelina sativa) is an emerging industrial oilseed crop because of its potential for double cropping, fallow year production, growth on marginal lands, and multiple uses of seed oils and meals. To realize the potential for sustainable production of camelina, a better understanding of how camelina seed oil production and composition respond to low input environments is desired. Phosphorus (P) is one of the least available essential macronutrients to plants with finite worldwide supply. This study investigated seed oil production and lipid composition of camelina in field settings and under greenhouse conditions in response to P deficiency. Lipidomic profiling reveals that P deficiency in field settings triggered extensive leaf lipid remodeling that decreased the ratio of phospholipids to non-P-containing galactolipids from 30% to 5% under P sufficient to deficient conditions. P deficiency increased seed oil content per seed weight by approximately 25% and 20% in field and greenhouse settings, respectively. In addition, P deficiency altered seed fatty acid composition, with increases in monounsaturated 18:1 and 20:1 and decreases in polyunsaturated 18:3. Total seed production was decreased by 10- to 15-fold under P deficiency and the decrease resulted from reduced seed numbers without affecting seed weight. The results from field and greenhouse conditions indicate that P deficiency increases seed oil content, alters fatty acid composition, and decreases greatly seed production, suggesting that achieving a high yield and quality of camelina seed oil is positively linked to P status of soil.

Associations of Early Completion of Advance Directives With Key End-of-Life Quality Measures: Analysis of an ASCO Quality Oncology Practice Initiative Patient Cohort.

PURPOSE: Despite the growing calls for early and ubiquitous completion of advance directives (ADs), studies exploring links between AD completion and their impact on outcomes of patients with cancer have mixed conclusions. We used the ASCO Quality Oncology Practice Initiative (QOPI) registry to compare end-of-life (EOL) quality measures and the effect of QOPI certification among patients with and without early AD completion, defined as completion within the first three oncology visits after cancer diagnosis. METHODS: Deidentified patient-level data were analyzed from the QOPI database from 2015 through 2017. Associations were assessed using Chi-square tests between early AD completion and patient enrollment in hospice < 7 days before death, chemotherapy receipt in the last 14 days of life, or with emergency room visits or intensive care unit admissions in the last 30 days of life. RESULTS: Data from 31,558 patients eligible for the AD question were analyzed. Patients treated at QOPI-certified practices had higher rates of early AD completion than patients at non-certified practices. Early AD completion was not associated with differences in hospice enrollment for < 7 days before death, chemotherapy receipt in the last 14 days of life, or emergency room visits or intensive care unit encounters in the last 30 days of life. CONCLUSION: The study found that QOPI certification is associated with higher rates of early AD completion. However, early AD completion was not associated with recognized EOL quality measures. Future research should focus on the timing, frequency, and content of AD conversations to demonstrate the impact on care at the EOL.

Clinical outcomes of de novo metastatic HER2-low breast cancer: a National Cancer Database Analysis.

The development of novel anti-HER2 drugs opens new treatment options for women with breast cancers, including lower expression of HER2. The epidemiology and clinical outcome of metastatic HER2-low breast cancer remain not well described. We designed a retrospective cohort study of the 2010-2017 National Cancer Database (NCDB) was designed to compare the overall survival of HER2-low and HER2-zero de novo metastatic breast cancer with systemic therapy. Multivariable Cox regression models were performed to estimate hazard ratios (HR), adjusting for sociodemographic and clinical factors. A total of 20,636 of 30,929 (66.7%) patients were HER2-low and 10,293 (33.3%) were HER2-zero. When stratified by hormonal receptor status, HER2-low tumors account for 18,066 (69.7%) cases in HR+/HER2- population and 2570 (51.4%) cases in HR-/HER2- population. The prevalence of HER2-low tumors was similar across racial groups with a slightly lower prevalence among the Hispanic population. Women with HER2-low tumors had longer overall survival (OS) than women with Her2-zero tumors in both HR-positive (median OS 39.0 months vs. 37.1 months; adjusted HR: 0.95, 95%CI (0.91-0.98)) and HR-negative groups (median OS 15.8 months vs. 14.1 months; adjusted HR: 0.92 95%CI (0.86-0.98)). The survival advantage was primarily observed in patients who received chemotherapy as their first line of treatment (HR 0.92 95%CI (0.88-0.96) vs. 0.99 95%CI (0.94-1.04), p-interaction = 0.04). In summary, HER2-low tumors, irrespective of hormone receptor status, have better survival than HER2-zero tumors in the de-novo metastatic setting. The survival advantage was primarily observed in patients who received chemotherapy in the first line.

When cancer survivors are also caregivers: well-being of "dual-role" cancer survivors.

PURPOSE: As the life expectancy of cancer survivors continues to improve, cancer survivors start or resume their life roles as caregivers themselves. We aim to assess the associations between caregiving, cancer diagnosis, and self-reported well-being. METHODS: Data were obtained from the Behavioral Risk Factor Surveillance System (BRFSS) 2016, 2018, and 2020. Outcomes included self-reported general health, physical health, mental health, depression, physical inactivity, and poor sleep. Weighted multivariable logistic regression models were used to calculate self-reported well-being's adjusted odds ratio (aOR). RESULTS: Comparable to the proportion of caregivers in the general population, approximately 1 out of 5 cancer survivors were caregivers to others. Individuals with dual roles were significantly more likely to report poor general health (aOR = 2.45; 95%CI: 1.46-4.11), physical health (aOR = 2.17; 95%CI: 1.32-3.56), mental health (aOR = 2.47; 95%CI: 1.31-4.64), depression (aOR = 1.64; 95%CI: 1.15-2.41), physical inactivity (aOR = 1.56; 95%CI: 1.05-2.31), and poor sleep (aOR = 1.48; 95%CI: 1.00-2.19) than the general population. Differential impacts of an additional cancer diagnosis on the well-being of caregivers were observed by sex, race, and time since cancer diagnosis. CONCLUSIONS: Nearly four million cancer survivors in the USA are concomitant caregivers. Individuals with dual roles reported diminished well-being across a variety of measures than caregivers only. IMPLICATIONS FOR CANCER SURVIVORS: Significant unmet health and psychosocial needs exist among individuals with dual roles. Our findings urge for increased awareness of this additional role/responsibility in cancer survivors and provide direct evidence for healthcare providers and policymakers to develop substantial support from the structural level.

Chronic comorbid conditions among adult cancer survivors in the United States: Results from the National Health Interview Survey, 2002-2018.

BACKGROUND: Cancer survivors develop other chronic medical conditions because of shared risk factors and delayed effects of cancer treatment. This study investigated trends in the prevalence of chronic diseases and estimated their population sizes among adult cancer survivors in the United States from 2002 to 2018. METHODS: Using 2002-2018 National Health Interview Survey data, this study calculated the age-sex-race/ethnicity-adjusted prevalences and estimated the population sizes for the following chronic conditions among cancer survivors: hypertension, diabetes, stroke, heart disease, chronic obstructive pulmonary disease (COPD)/asthma, hepatitis, arthritis, liver disease, kidney disease, and morbid obesity. This study also examined multiple chronic conditions (MCC; 3 or more health conditions). MCC trends were further examined by sociodemographic factors to identify high-risk populations. Parallel analyses were performed for participants without a cancer history to provide a reference. RESULTS: Among 30,728 cancers survivors, increasing trends were observed in the prevalence of hypertension, diabetes, kidney disease, liver disease, and morbid obesity, whereas decreasing prevalence trends were observed for ischemic heart disease, COPD, and hepatitis. Cancer survivors with MCC increased from 4.7 million in 2002 to 8.1 million in 2018 (the prevalence increased from 43.7% to 46.6%). The increase was more pronounced among survivors aged 18 to 44 years. Among adults without a cancer history, the MCC prevalence also increased, although more slowly than among survivors. CONCLUSIONS: The number of adult cancer survivors in the United States with comorbid illnesses has increased substantially over the past 2 decades. Optimal management of comorbid conditions and aggressive interventions for risk reduction may benefit the cancer survivor population.

Quality Care in Survivorship: Lessons Learned From the ASCO Quality Oncology Practice Initiative.

PURPOSE: The ASCO Quality Oncology Practice Initiative (QOPI) project was established to evaluate the influence of guideline recommendations on routine clinical practice. METHODS: QOPI provided summary data from 839 unique practices in which data were collected every six months from the Fall of 2015 to the Spring of 2019. From these data, six items were chosen based on their relationship to domains of survivorship. A zero-inflated negative binomial regression model was used to test for trends in QOPI measures adherence rates over time. The models were adjusted for the time period, region, practice-ownership, multispecialty site, fellowship program, and hospital type. RESULTS: Smoking cessation counseling recommended and smoking cessation counseling administered or referred both increased over time, 50%-61% (adjusted incidence rate ratios (IRR), 1.028; 95% CI, 1.016 to 1.040; P < .001) and 34%-49% (adjusted IRR, 1.052; 95% CI, 1.035 to 1.070; P < .001), respectively. Infertility risks discussed before chemotherapy increased from 36% to 53% (adjusted IRR, 1.056; 95% CI, 1.035 to 1.078; P < .001) and fertility options discussed or referred to specialists increased from 23% to 38% (adjusted IRR, 1.074; 95% CI, 1.046 to 1.102; P < .001). Twenty-nine percent documented a positron emission tomography, computed tomography, or bone scan within the first 12 months for women diagnosed with early breast cancer treated for curative intent (adjusted IRR, 1.000; 95% CI, 0.977 to 1.024; P = .971). Tumor marker surveillance within 12 months increased from 78% to 87% (adjusted IRR, 1.018; 95% CI, 1.002 to 1.033; P = .023). CONCLUSION: As scientific evidence to guide cancer survivorship care grows, the role of guideline recommendations permeating clinical practice using quality metrics will become increasingly important.

Bone-modifying Agents (BMAs) in Breast Cancer.

Bone-modifying agents (BMAs) are mainstays in breast cancer and prevent and treat osteoporosis in early-stage disease and reduce skeletal metastases complications in advanced disease. There is some evidence to support that BMA also prevents skeletal metastases and improves overall survival. Bone loss occurs with chemotherapy-induced ovarian failure, gonadotrophin-releasing hormone (GnRH) agonists, and aromatase inhibitors. In some women, the bone loss will be of sufficient magnitude to increase the risks of osteoporosis or fractures. Recommended steps in osteoporosis prevention or treatment include risk factor assessment, taking adequate amounts of calcium and vitamin D3, and periodic evaluations with dual-energy x-ray absorptiometry scanning. If clinically indicated by the T-scores and fracture-risk prediction algorithms treat with oral, IV bisphosphonates or subcutaneous denosumab (DEN). Zoledronic acid (ZA) or DEN reduces skeletal metastases complications, including pathological fracture, spinal cord compression, or the necessity for radiation or surgery to bone. Also, both of these drugs have the side-effect of osteonecrosis at a similar incidence. Monthly administration of ZA or DEN is standard, but several recent randomized trials show noninferiority between ZA monthly and every 3-month ZA. Every 3-month ZA is a new standard of care. Similar trials of the schedule of DEN are ongoing. ZA anticancer effect is only in postmenopausal women or premenopausal women rendered postmenopausal by GnRH agonists or bilateral oopherectomy. High-risk women, either postmenopausal or premenopausal, receiving GnRH/oopherctomy should consider adjuvant ZA. There are insufficient data to support DEN in this setting. Herein, this narrative review covers the mechanism of action of BMA, randomized clinical trials, and adverse events, both common and rare.

Effect of Foliar Micronutrients (B, Mn, Fe, Zn) on Maize Grain Yield, Micronutrient Recovery, Uptake, and Partitioning.

Timing of micronutrient demand and acquisition by maize (Zea mays L.) is nutrient specific and associated with key vegetative and reproductive growth stages. The objective of this study was to determine the fate of foliar-applied B, Fe, Mn, Zn, and Fe/Zn together, evaluate the effect of foliar micronutrients applied at multiple rates and growth stages on maize grain yield, and determine their apparent nutrient recovery efficiency (ANR). Five Randomized Complete Block Design (RCBD) experiments were conducted in 2014 and 2015 at five locations across Nebraska. Total dry matter was collected at 5-6 stages, and separated into leaves, stalk, and reproductive tissue as appropriate to determine micronutrient uptake, partitioning, and translocation. Foliar B, Mn, Zn, and Fe/Zn had no effect on grain yield for most application time by rate levels, though, at the foliar Mn site, there was a 19% yield increase due to a V18 application of 0.73 kg Mn ha-1 which corresponded with reduced Mn uptake in maize grown in control plots. At the foliar Zn site, there was 4.5% decrease in yield due to a split foliar application of 0.84 kg Zn ha-1 total, applied at V11 and V15 stage, which increased leaf Zn concentrations greater than the established toxic level. Only the Fe site had consistent grain yield response and was the only experiment that had visual signs of micronutrient deficiency. Regardless of application time from V6 to R2, there was a 13.5-14.6% increase in grain yield due to 0.22 kg Fe ha-1 foliar application. Most micronutrients had limited or no translocation, however, early season applications of B, prior to V10, had significant mobilization to reproductive tissues at or after VT. Foliar Mn, Zn, and B application had ANR LSmeans of 9.5, 16.9, and 2.5%, respectively, whereas the Fe/Zn mix had negative ANR LSmeans of -9.1% Fe and -1.3% Zn which indicate suppression. These data highlight the importance of confirming a micronutrient deficiency prior to foliar application, guide specific growth stages to target with specific micronutrients, track the fate of foliar-applied micronutrients, and describe the variable effect of foliar-applied micronutrients on grain yield.

A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.

PURPOSE: Given clinical activity of AR-42, an oral histone deacetylase inhibitor, in hematologic malignancies and preclinical activity in solid tumors, this phase 1 trial investigated the safety and tolerability of AR-42 in patients with advanced solid tumors, including neurofibromatosis type 2-associated meningiomas and schwannomas (NF2). The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives included determining pharmacokinetics and clinical activity. METHODS: This phase I trial was an open-label, single-center, dose-escalation study of single-agent AR-42 in primary central nervous system and advanced solid tumors. The study followed a 3 + 3 design with an expansion cohort at the MTD. RESULTS: Seventeen patients were enrolled with NF2 (n = 5), urothelial carcinoma (n = 3), breast cancer (n = 2), non-NF2-related meningioma (n = 2), carcinoma of unknown primary (n = 2), small cell lung cancer (n = 1), Sertoli cell carcinoma (n = 1), and uveal melanoma (n = 1). The recommended phase II dose is 60 mg three times weekly, for 3 weeks of a 28-day cycle. DLTs included grade 3 thrombocytopenia and grade 4 psychosis. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. The best response was stable disease in 53% of patients (95% CI 26.6-78.7). Median progression-free survival (PFS) was 3.6 months (95% CI 1.2-9.1). Among evaluable patients with NF2 or meningioma (n = 5), median PFS was 9.1 months (95% CI 1.9-not reached). CONCLUSION: Single-agent AR-42 is safe and well tolerated. Further studies may consider AR-42 in a larger cohort of patients with NF2 or in combination with other agents in advanced solid tumors. TRIAL REGISTRATION: NCT01129193, registered 5/24/2010.

Osteoporosis: A Long-Term and Late-Effect of Breast Cancer Treatments.

Osteoporosis is both a long-term effect (occurs during treatment and extends after treatment) and a late-effect (occurs after treatment ends) of breast cancer treatments. The worldwide prevalence of osteoporosis is estimated to be some 200 million patients. About one in three postmenopausal women will experience an osteoporotic (or fragility) fracture of the hip, spine, or wrist. breast cancer treatments, including gonadotropin-releasing hormone (GnRH) agonists, chemotherapy-induced ovarian failure (CIOF), and aromatase inhibitors (AIs), cause bone loss and increase the risks of osteoporosis. Also, breast cancer is a disease of aging, and most of the "one in eight" lifetime risks of breast cancer are in women in their sixth, seventh, and eighth decades. The majority of women diagnosed with breast cancers today will be long-term survivors and experience personal cures. It is the coalescence of osteoporosis with breast cancer, two common and age-related conditions that make osteoporosis relevant in women with breast cancer throughout the continuum from diagnosis, treatment, and survivorship. It is critical to remember that women (and men) will lose bone after age thirty years. However, only certain women will lose bone of sufficient magnitude to merit treatment with anti-osteoporosis drugs. The narrative review is intended for medical, surgical, radiation oncologists, and other mid-level providers, and provides an overview of bone loss and the prevention and treatment of osteoporosis.

Optimism and coping: do they influence health outcomes in women with breast cancer? A systemic review and meta-analysis.

BACKGROUND: Optimism, coping, and resilience may be independent predictors of anxiety, distress, depression, or health-related quality of life (HRQOL) in women with breast cancer. METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) searches of PubMed, PsycINFO, and Google Scholar databases from January 1, 1990, to April 30, 2018, for articles (i.e., studies) determining the impact of optimism, coping, or resilience on anxiety, distress, depression, or HRQOL in women with breast cancer. Articles included only those that measured optimism by the life orientation test (LOT) or LOT-revised (R), coping by the COPE, brief (B)-COPE, or religious (R)-COPE, and resilience by the CD-Resilience Scale (CD-RIS). RESULTS: Forty-one out of 52 (79%) studies showed that optimism is a statistically significant predictor of study-specific aspects of anxiety, distress, depression, or HRQOL. In a meta-analysis focused on depression, optimism was a statistically significant predictor of depression. Coping style is a statistically significant predictor for study-specific aspects of anxiety, distress, depression, or HRQOL in 41/43 (95%) studies. The coping studies were too heterogeneous in their outcome variables to perform meta-analyses. There were too few studies (n = 6) on resilience to draw any conclusions. CONCLUSIONS: Despite many limitations of this literature, including the heterogeneity of study designs, differing sample sizes, across different countries, cultures, ethnicities, and races, most studies support that optimism and coping are predictors of anxiety, distress, depression, or HRQOL. Awareness of these psychological constructs and their potential impact on anxiety, depression, and HRQOL are a high priority.

Metastatic breast cancer patient perceptions of somatic tumor genomic testing.

BACKGROUND: To assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing. METHODS: In a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar's test of agreement. RESULTS: There were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04). CONCLUSIONS: This is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention. CLINICAL TRIAL INFORMATION: NCT01987726, registered November 13, 2013.

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA-mutated metastatic breast cancer. Furthermore, the BROCADE studies demonstrated benefit of adding an oral PARPi, veliparib, to carboplatin and paclitaxel in patients with metastatic breast cancer harboring BRCA mutation. Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay. MATERIALS AND METHODS: Patients received escalating doses of veliparib on a 7-, 14-, or 21-day schedule with carboplatin every 3 weeks. Patients underwent [18]fluoro-3'-deoxythymidine (18 FLT) positron emission tomography (PET) imaging. RESULTS: Forty-four patients (39 TNBC, 5 HR positive/HER2 negative with a defective FA pathway) received a median of 5 cycles (range 1-36). Observed dose-limiting toxicities were grade (G) 4 thrombocytopenia (n = 4), G4 neutropenia (n = 1), and G3 akathisia (n = 1). Common grade 3-4 toxicities included thrombocytopenia, lymphopenia, neutropenia, anemia, and fatigue. Of the 43 patients evaluable for response, 18.6% achieved partial response and 48.8% had stable disease. Median progression-free survival was 18.3 weeks. RP2D of veliparib was established at 250 mg twice daily on days 1-21 along with carboplatin at area under the curve 5. Patients with partial response had a significant drop in maximum standard uptake value (SUVmax ) of target lesions between baseline and early in cycle 1 based on 18 FLT-PET (day 7-21; ptrend = .006). CONCLUSION: The combination of continuous dosing of veliparib and every-3-week carboplatin demonstrated activity and an acceptable toxicity profile. Decrease in SUVmax on 18 FLT-PET scan during the first cycle of this therapy can identify patients who are likely to have a response. IMPLICATIONS FOR PRACTICE: The BROCADE studies suggest that breast cancer patients with BRCA mutation benefit from addition of veliparib to carboplatin plus paclitaxel. This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone. With growing interest in imaging-based early response assessment, the authors demonstrate that decrease in [18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) SUVmax during cycle 1 of therapy is associated with response. Collectively, this study established a safety profile of veliparib and carboplatin in advanced breast cancer while also providing additional data on the potential for FLT-PET imaging modality in monitoring therapy response.

Postvasectomy Scrotal Pain and Hematospermia, a Possible Harbinger for Vasectomy Failure and Recanalization: A Case Report.

INTRODUCTION: Vasectomy is the most common and most effective method of achieving permanent male sterility. However, there is a low risk of vasectomy failure. To our knowledge, there is no symptom complex that has been identified and described that is predictive of early recanalization and vasectomy failure. CASE PRESENTATION: A 44-year-old man underwent a routine bilateral vasectomy without complication. Two months after the procedure, the patient experienced an acute onset of scrotal pain and hematospermia. Several semen analyses were performed during the following months, the results of which demonstrated progressively rising numbers of motile sperm and were indicative of vasal recanalization. The patient underwent repeated vasectomy, during which he was found to have right vasal recanalization leading to vasectomy failure. DISCUSSION: Delayed postvasectomy scrotal pain associated with hematospermia may be a sign of vasal recanalization. We propose that this symptom complex should prompt an investigation for vasal recanalization, during which the patient should be instructed to refrain from intercourse without the use of an additional method of contraception.