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Objective Epithelial ovarian carcinoma (EOC) is diagnosed at advanced stage in the majority of women and, despite being initially chemosensitive, eventually recurs and develops resistance to known therapies. SC-003 is a pyrrolobenzodiazepine-based antibody-drug conjugate targeting dipeptidase 3 (DPEP3), a membrane-bound dipeptidase associated with tumor-initiating cells in patient-derived EOC xenograft models. This first-in-human phase 1a/1b study evaluated the safety/tolerability, pharmacokinetics, and preliminary antitumor activity of SC-003 alone or in combination with budigalimab (formerly ABBV-181), an antibody targeting PD-1, in patients with platinum-resistant/refractory EOC ( NCT02539719 ). Methods Patients received SC-003 at 1 of 6 dose levels (0.025–0.4 mg/kg) every 3 weeks (Q3W), utilizing a standard 3 + 3 design (dose-limiting toxicity [DLT] period: 21 days). Patients with DPEP3-positive tumors were enrolled in the dose-expansion phase of the study and treated with SC-003 monotherapy or in combination with budigalimab. Results Seventy-four patients (n = 29, dose escalation; n = 45, dose expansion; n = 3 budigalimab combination) were enrolled and received ≥ 1 dose of study drug. One DLT occurred (grade 3 ileus) but was considered unrelated to study drug. The MTD for the Q3W schedule was 0.3 mg/kg and the SC-003 doses selected for the dose-expansion phase of the study were 0.3 mg/kg and 0.2 mg/kg. The most common treatment-emergent adverse events were fatigue, nausea, decreased appetite, pleural effusion, abdominal pain, and peripheral edema. The overall response rate was low (4%), and responses were not durable. Post-hoc examination of antitumor activity suggested a higher response rate in patients with higher DPEP3 expression. Conclusions SC-003 lacked the requisite safety profile and antitumor activity to warrant further development.

Thermal infrared sensing from space is a well-developed field, but mixed pixels pose a problem for many applications. We present a field study in Dana Meadows, Yosemite National Park, California to scale from point (~2-m resolution) to aerial (~5-m resolution gridded, 1 km × 6 km extent) to satellite (MODIS, ~1000-m resolution, global extent) observations. We demonstrate how multiple thermal bands on MODIS can be used to separate snow and forest temperatures and determine the fractional snow-covered area (fSCA) over a 3 km × 3 km array of 9 MODIS grid cells. During the day, visible, near-infrared, and shortwave-infrared bands provide a first guess of fSCA and help to constrain the solution. This technique, which has estimated errors

Objectives: To demonstrate safety and tolerability of HIPEC in ovarian cancer. Methods: A phase I, single-institution feasibility study was designed to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS) in ovarian cancer patients, followed by optional normothermic intraperitoneal chemotherapy, at City of Hope National Comprehensive Cancer Center (Duarte, CA). Primary endpoint of the trial was to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS). Progression-free survival was a secondary end-point. Exploratory endpoints included the assessment of molecular markers in tumors. Eligibility criteria included epithelial ovarian cancer (stage III or IV), primary or recurrent, ECOG 0-1, and appropriate surgical candidates. 35 patients were enrolled between 2015 and 2019, who underwent optimal CRS (gross residual disease less than 1 cm), and received HIPEC intra-operatively with cisplatin at 75 mg/m2 for 60 minutes immediately following optimal CRS. Patients were stratified as either 1) primary disease (n=19), defined as having received HIPEC at time of interval CRS following neoadjuvant chemotherapy for primary EOC; 2) recurrent disease (n=16), defined as having received HIPEC at time of interval or upfront CRS for recurrent (salvage) EOC. Adjuvant chemotherapy was given at the discretion of the treating oncologist following HIPEC. Results: Median age was 58 years (36-74 years), with a mean BMI of 26. Primary (interval) patients represented 54% of patients, with pretreatment clinical stages III (53%) and IV (47%). Recurrent (salvage) patients represented 45.7%, with platinum-sensitive (75%) and platinum-resistant (25%). The most common histological subtype was high grade serous (69%). All primary (interval) patients underwent neoadjuvant chemotherapy (3-4 cycles) prior to interval CRS and HIPEC. The majority of recurrent patients (81%) did not receive neo-adjuvant chemotherapy. Thirty-three patients underwent closed technique and two underwent laparoscopic technique. Total mean operating time was 8.4 hours (4.6-15.3). Mean length of stay was 10 days (3-30). All patients underwent optimal cytoreduction (69% with complete R0 resection). Peritoneal carcinomatosis index (PCI) ranged 2 to 30 (median of 8). Patients with PCI /= 8 whose PFS was 12.6 (p=0.04). Time to initiation of adjuvant chemotherapy in recurrent patients was 8.4 weeks. 22.9% of the ovarian cancer cohort was gBRCA mutated. Median PFS for primary patients was 12.6 months (95% CI 6.4; NR); with median follow up of 22.1 months (95% CI 12.6, 31.5). Median PFS for recurrent patients was 18.8 months (95% CI 7.2; 28.7), with median follow up of 36.3 months (95% CI 21.1, 51.5). There were no grade 4 or 5 AEs. Anemia was the most common Grade 3 AE (43%), followed by liver dysfunction and electrolyte abnormalities. The most common AE of any grades were abdominal pain (86%), anemia (77%), and nausea (66%). Two patients (6%) had grade 3 acute kidney injury and one patient had grade 3 chronic kidney disease. Sodium thiosulfate was introduced to the trial in January 2018, following which there were no grade 1-4 acute or chronic kidney injuries. Download : Download high-res image (61KB) Download : Download full-size image Conclusions: HIPEC in ovarian cancer was well tolerated, without any grade 4 or 5 AEs. Renal toxicities were mitigated with sodium thiosulfate. Patients with a low PCI ( /= 8.

Snow cover affects a diverse array of physical, ecological, and societal systems. As such, the development of optical remote sensing techniques to measure snow-covered area (SCA) has enabled progress in a wide variety of research domains. However, in many cases, the spatial and temporal resolutions of currently available remotely sensed SCA products are insufficient to capture SCA evolution at spatial and temporal resolutions relevant to the study of fine-scale spatially heterogeneous phenomena. We developed a convolutional neural network-based method to identify snow covered area using the ~3 m, 4-band PlanetScope optical satellite image dataset with ~daily, near-global coverage. By comparing our model performance to snow extent derived from high-resolution airborne lidar differential depth measurements and satellite platforms in two North American sites (Sierra Nevada, CA, USA and Rocky Mountains, CO, USA), we show that these emerging image archives have great potential to accurately observe snow-covered area at high spatial and temporal resolutions despite limited radiometric bandwidth and band placement. We achieve average snow classification F-Scores of 0.73 in our training basin and 0.67 in a climatically-distinct out-of-sample basin, suggesting opportunities for model transferability. We also evaluate the performance of these data in forested regions, suggesting avenues for further research. The unparalleled spatial and temporal coverage of CubeSat imagery offers an excellent opportunity for satellite remote sensing of snow, with real implications for ecological and water resource applications.

Surgical procedures provide the best chance for cure and long-term survival in non-small cell cancer (NSCLC). Persistent symptoms after surgical procedures are common, and they can negatively affect health-related quality of life (HRQOL). The purpose of this study was to examine the long-term effect of an interdisciplinary supportive care intervention to improve HRQOL, psychological distress, and symptoms in lung cancer survivors who were treated surgically.Patients undergoing curative intent resection for NSCLC were enrolled in a prospective sequential design whereby the control group was accrued first, followed by the intervention group. Patients in the intervention group were assessed and presented by nurses at weekly interdisciplinary care meetings before surgical procedures, and received four educational sessions (physical, psychological, social, and spiritual well-being) after surgical procedures. Appropriate symptom management, social work, rehabilitation, and spiritual support interventions were coordinated by the study nurse. In both groups, HRQOL, psychological distress, and symptom severity were assessed at baseline and at 6, 12, 24, 36, and 52 weeks with the use of surveys that included the validated Functional Assessment of Cancer Therapy-Lung (FACT-L), Lung Cancer Subscale (LCS), and Distress Thermometer. Mean survey scores were analyzed with factorial analysis of covariance at 12 months.A total of 71 survivors (control = 33; intervention = 38) were accrued. No difference was found in age, baseline performance status, or stage of disease between groups. Patients in the intervention group had significantly less distress (mean, 1.0 versus 4.0; range, 0 to 10; p0.001) and more favorable mean FACT-L scores (126.1 versus 98.7; range, 0 to 140; p0.001) and LCS scores (29.4 versus 23.6; range, 0 to 32; p0.001) at 12 months. The mean scores of all categories of questions in FACT-L (physical, social/family, emotional, and functional well-being) were considerably more favorable in the intervention group at 12 months.An interdisciplinary supportive care intervention improves psychological distress and HRQOL at 12 months after lung cancer surgical procedures. This study has important implications in improving HRQOL of lung cancer survivors after surgical procedures. Further study is warranted on incorporating the interdisciplinary personalized interventions used in this study into clinical practice for lung cancer survivors.

Purpose To assess the feasibility, acceptability, and preliminary effects of a nurse-led intervention for managing fear of cancer progression in advanced cancer patients. Methods A single group mixed methods study was conducted in patients with stage III or IV gynecologic or lung cancer (n = 31) with dysfunctional levels of fear of progression or distress. The intervention consisted of seven videoconferencing sessions with skills practice. Feasibility measures included enrollment rate, attendance, attrition, and home practice adherence. Acceptability was based on exit interview responses. Content analysis was used to analyze the qualitative data. Participants completed quantitative questionnaires assessing fear of progression and secondary outcomes at baseline, eight, and 12 weeks. Linear mixed model analysis was used to assess changes in outcome measures. Results The average enrollment rate was seven participants/month over 4.5 months. Participants attended a mean of 5.3 of seven sessions. Attrition rate was 30%. The analysis showed improvements over time in fear of progression and exploratory outcomes. Participants reported feeling calmer and more focused. The skills practice helped to manage anxiety and fears. Themes included: Struggling with fears, Refocusing the fears, and Realizing/reaffirming what is important in life. The most beneficial components included the values clarification exercise, detached mindfulness and worry postponement practices. Conclusion The intervention was acceptable; most feasibility criteria were met. Preliminary data suggest that the intervention reduced fear of progression and improved secondary outcomes. The intervention required a significant time commitment by participants, which may have contributed to increased attrition. To decrease burden, we will shorten the intervention.

Air temperature, ground temperature and relative humidity data were collected in a longitudinal transect of the Nooksack watershed at varying elevations from 500 to 1800 m above sea level. Data were collected by anchoring sensors from trees above winter snow levels and shaded from direct solar radiation. Paired sensors were also buried 3 cm under ground near each air temperature sensor to determine snow absence or presence. Select sites included relative humidity sensors to indicate whether precipitation was occurring. Data were collected every 3-4 h from December 2015 to Sept 2018 (with ongoing collection). Code for analysis of daily mean, minimum, maximum, and temperature change with elevation (lapse rates) are available on Github ( https://doi.org/10.5281/zenodo.3239539 ). The sensor download and intermediate data products are available on HydroShare at ( http://www.hydroshare.org/resource/222e832d3df24dea9bae9bbeb6f4219d ) with publicly accessible visualization available from the Nooksack Observatory at data.cuahsi.org. Hydrologic models are generally structured with a single annual average lapse rate parameter which assumes a linear temperature gradient with elevation. The daily data (2016-2018) is used as part of ongoing studies on the non-linear dynamics and temporal variability of temperature with elevation to improve assessments of watershed function and salmon habitat.

Purpose of the research: Pain and fatigue are recognized as critical symptoms that impact QOL for patients with colon cancer. Barriers to optimum pain and fatigue relief include patient-related beliefs and attitudes about the treatment of cancer-related symptoms. The overall objective of this paper was to describe quality of life (QOL) and barriers to pain and fatigue management in patients with colon cancer. Methods and sample: This longitudinal, descriptive study included was conducted in the ambulatory clinic of one NCI-designated comprehensive cancer center. A cohort of 56 patients with colon cancer and a pain and/or fatigue of � 4 (moderate to severe) was recruited. Subjects completed questionnaires to assess subjective ratings of overall QOL, fatigue, barriers to pain and fatigue, and pain and fatigue knowledge. Key results: The majority of subjects (58%) reported having moderate to severe (4e6) fatigue at the time of accrual. Overall QOL score was moderate (M ¼ 5.20, SD ¼ 1.43), and the social well-being subscale had the lowest score (M ¼ 4.57, SD ¼ 1.82). Patient barriers to pain and fatigue existed in attitudes and beliefs regarding addiction, tolerance, and that fatigue is an inevitable part of cancer and its treatments. Patient knowledge of pain and fatigue was high (77%e88% correct), but lack of knowledge persisted in areas such as addiction to pain medications and utilizing physical activity to manage fatigue. Conclusions: Several patient-related attitudes and beliefs may hinder optimum relief of symptoms such as pain and fatigue. Social well-being may be a major determinant of overall QOL for patients with colon cancer.

Previous studies have suggested that BRCA-related epithelial ovarian cancer (EOC) conveys improved survival compared with that of sporadic EOC, but few studies have evaluated differences between BRCA genotypes. We compared characteristics and outcome by genotype in BRCA-associated EOC. Patients with BRCA-associated EOC who were diagnosed between January 30,1981, and December 30, 2008, were retrospectively identified through institutional review board-approved registry studies. We examined clinical characteristics, including event-free survival (EFS) and overall survival (OS), for BRCA1 versus BRCA2 patients. We identified 197 cases (148 BRCA1 cases; 49 BRCA2 cases); the median follow-up period was 63 months. BRCA2 patients were older (55.4 vs. 51.1 y; P0.01) and had fewer poorly differentiated tumors (67% vs. 82%; P0.05). No difference in EFS was observed. OS at 5 years was 75% in BRCA2 patients versus 61% in BRCA1 patients; this was not statistically significant. A non-significant trend toward improved OS was observed in BRCA2 patients with advanced-stage disease (hazard ratio = 0.59; 95% confidence interval 0.32-1.08). Age and grade differed significantly between BRCA1 and BRCA2 carriers in our study population. Whereas no overall differences in EFS or OS were observed, there was a trend toward improved OS in BRCA2 carriers with advanced-stage disease. This may reflect important differences between BRCA genotypes and should be validated in larger studies.

Purpose: Quality of Life (QOL) and symptom concerns are common in lung cancer. This article presents findings from 2 separate pilot studies that utilize an educational model to reduce barriers to pain and fatigue management (“barriers study”) and an interdisciplinary palliative care approach to manage QOL concerns for patients with lung cancer (“QOL pilot”). Patients and Methods: In the barriers study, a total of 46 patients with lung cancer with a self-reported pain and/or fatigue rating of q 4 were accrued, with 18 patients in the usual care group and 28 in the experimental group, using a quasi-experimental design. This study involved a 4-part educational intervention delivered by a nurse to address pain and fatigue. In the QOL study, the pilot intervention included 10 patients with lung cancer. This pilot included use of QOL assessment completed by a nurse followed by an interdisciplinary case conference intended to initiate supportive care to address QOL and symptom concerns. Patient-reported outcomes such as barriers to pain and fatigue management, fatigue intensity, other symptoms, and overall QOL were analyzed through tabulation of standard summary statistics and multivariate analysis methods. All eligible patients were recruited from the ambulatory clinic of one National Cancer Institute–designated Comprehensive Cancer Center. Results: For the barriers study, patients with lung cancer in the experimental group had a statistically significant decrease in patient-related barriers for both pain and fatigue. Findings from the QOL pilot revealed that patients with lung cancer have multiple QOL concerns and that an interdisciplinary palliative care approach was feasible to address these complex, multidimensional patient needs. Conclusion: Attention to barriers of symptom management, early referral to supportive care services, and coordination of interdisciplinary care are essential to supporting the QOL of patients with lung cancer. The next phase of this research will test QOL/symptom interventions for patients with lung cancer.

Introduction La pancreatite aigue n’est pas une complication classique du syndrome de Cushing. Observation Nous rapport le cas d’une femme de 45 ans, evaluee en 2014 dans le Service d’Endocrinologie du CHU Iasi, avec antecedents de diabete de type 2 et HTA, sans notion d’intoxication etanolique ou litiase vesiculaire. L’examen clinique a retrouve les signes d’hypercortisolism (hypotrophie musculaire des membres inferieures, vergetures pourpres d’apparition recente, echimoses multiples), l’obesite morbide avec distribution androide, TA 160/90 mmHg. Le bilan hormonal fait le diagnostic positif d’hypercortisolism et identifie son caractere ACTH dependant : cortisol matinal 39ug/dl (N : 5- 25), ACTH 97 pg/ml (N 0-46), cortisol matinal apres DXM 1 mg 16ug/dl (N Discussion Jusqu’a present, la litterature medicale decrit quelques dizaines de cas d’hypercortisolisme exogene associes a une pancreatite aigue. L’association de celle-ci au Syndrome de Cushing est beaucoup moins frequente. Ce cas clinique ne peut pas etablir une relation cause-effet hypercortisolisme endogene-pancreatite aigue, mais souleve la souspicion d’un role favorisant ou declanchateur.

A 48-year-old-man with a 3-month history of cough was involved in a motorcycle accident complicated by chest trauma and right ankle fracture. The CAT scan of the chest revealed a left-sided pneumothorax, a left hilar mass, mediastinal adenopathy, and renal masses. The transbronchial biopsy showed a poorly differentiated adenocarcinoma. A follow-up CAT scan revealed a rapidly progressing lung mass with obstruction of the entire left lung, and a thrombus versus mass in the left atrium. The 2D echocardiogram confirmed a 2.7-cm left atrial lesion. The transesophageal echocardiogram described a mass within the left atrium (LA), coming out of the pulmonary vein (Figure 1A). The appearance of the mass changed during systole and diastole (Figure 1A, 1B). This was consistent with an arm of the primary lung tumor extending into the left atrium and did not support the diagnosis of thrombus.1–3 The patient received one cycle of chemotherapy, but died shortly thereafter from progression of his lung cancer. In this case, the transesophageal echocardiogram clarified the etiology of the left atrial mass and prevented unnecessary anticoagulation.

surgery. QI #7 & 8: A total of 119/121 (98.3%) patients received prophylactic parenteral antibiotics within 60 min of cytoreduction and these were discontinued in 120/121 (99.2%) cases. Conclusions: These data can help establish benchmark criteria for integrating ovarian indicators into actual practice. The surprisingly low percentage of “completely staged” patients deserves additional exploration as to whether this is a flaw in reporting or a lack of compliance. The study not only identifies areas for improvement but also demonstrates the importance of documentation when medical reasons prevent indicators from being met. Further validation requires prospective evaluation of these indicators and their correlation to patient outcomes, such as survival.

e19610 Background: This National Cancer Institute funded Program Project (P01) is an interdisciplinary research project focused on palliative care, quality of life (QOL), and symptom control in lun...

Background: Cervical cancer (CC) is the second cause of cancer-related mortality in women worldwide. Response to second-line chemotherapy is infrequent and the poor outcome of patients with advanced disease (median survival 9 months) warrants novel therapeutic strategies that exploit abnormal tumor biology. Based on new evidence that host-dependent immunologic status and HPV-induced immune evasion are responsible for persistent HPV infection, the prime causal factor of CC, immunotherapy is an attractive emerging strategy to target this disease. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that acts to downregulate the T cell immune response. Trial design: A 2-step multicenter trial was designed to evaluate ipilimumab IV in metastatic or recurrent HPV-related CC (NCT01693783). Eligible patients require measurable disease progression and at least one previous platinum based line of chemotherapy. A safety phase I cohort was planned with ipilimumab 3 mg/kg every 21 days for four cycles in 6 evaluable patients. After demonstration of safety, a phase II trial was planned with ipilimumab 10 mg/kg at the same schedule; followed by four additional cycles maintenance therapy at the same dose every 12 weeks for patients with radiologic confirmed response or stabilization. The primary objective is to assess the safety and the objective response rate at the end of cycle 4. 18 evaluable patients are scheduled and if at least 1 partial response is seen, additional 14 patients will be enrolled. Immune assessment studies are performed on peripheral blood collected prior to and following ipilimumab therapy and on archived and fresh tumour tissue obtained prior to treatment and within the first week of cycle 2. Current status: This trial was activated in September 2012. The phase I cohort is now completed, and 20 patients have been enrolled in the phase II. The majority of the patients were able to have the pre and post treatment biopsy. Previous presentation ASCO. Disclosure: All authors have declared no conflicts of interest.

Aim: The primary objective was to determine maximum tolerated dose (MTD) and the potential PK advantage of IP nab-paclitaxel (favorable peritoneal cavity ratio of nab-paclitaxel: plasma). Methods: Phase I study of IP nab-paclitaxel, D1, 8, 15; 28-day cycle; 3 + 3 dose-escalation design in patients (pts) with advanced ovarian cancer primarily confined to the peritoneal cavity, unresponsive to previous regimens, or for which no standard regimens exist. Pts had pre-study IP catheters placed, and had plasma and peritoneal pharmacokinetic (PK) studies on C1D1 and C1D15 Results: 25 pts were enrolled; 2 were inevaluable as they did not complete cycle 1 due to port failure, and leucopenia not qualifying as dose limiting toxicity (DLT). Cohort 1 (35mg/m2), 2 (70mg/m2), and 3 (90mg/m2) were completed without DLT. 6 pts were accrued to Cohort 4 (112mg/m2); one had DLT (leukopenia resulting in treatment delay >15 days). Cohort 5 (140mg/m2) at first enrolled 3 pts with no DLT. Cohort 6 (170mg/m2) enrolled 3 pts; one had DLT (grade 3 abdominal pain and grade 4 neutropenia) and one had grade 4 neutropenia and treatment-related asymptomatic drop in the ejection fraction, neither qualifying as DLT. We concluded that dose level 6 was too toxic; no further Cohort 6 pts were enrolled. We expanded Cohort 5 to 5pts with no DLT (MTD). PK data show a ∼150-fold pharmacologic advantage to IP nab-paclitaxel with low inter- and intra-pt variability. Plasma AUCs from IP nab-paclitaxel are ∼50% of plasma AUCs from IV delivery of the same dose; thus patients are exposed to therapeutic systemic drug levels. Conclusions: The MTD of IP nab-paclitaxel is 140 mg/m2. PK data reveal a significant peritoneal advantage, and the tolerable toxicity suggests that nab-paclitaxel is ideal for IP delivery. Further studies of combination therapy are indicated. Study approval/funding - NCCN; Research support - Celgene Corp Disclosure: B. Paz: Speakers Bureau – Genomic Health, Inc. Stock Shareholder – LS Biopath. All other authors have declared no conflicts of interest.

Purpose Patients with lung cancer experience many symptoms necessitating the use of supportive services. Prognosis remains poor despite advances in treatment, and as the disease progresses, symptom burden increases. This study evaluated quality of life (QOL) and symptom concerns in a cohort of 100 patients with lung cancer at a National Cancer Institute (NCI)—designated Comprehensive Cancer Center. The study aims were to describe (1) treatment received by patients with lung cancer consistent with established National Comprehensive Cancer Network (NCCN) guidelines; and (2) symptoms experienced by patients with lung cancer potentially affecting QOL. Patients and Methods The NCCN guidelines for lung cancer and for palliative care were used as a framework for analysis of the care provided to these patients. One hundred patients were selected by the tumor registry from the 150 new patients with lung cancer seen over a 12-month period. A detailed chart audit tool reflecting the aspects of quality care as described by the NCCN was developed, peer reviewed, and tested to establish reliability. The care for each patient was audited for a 6-month period to capture all encounters in the cancer center. Descriptive statistics were used to analyze the data. Results Eighty-five percent of patients had stage III/IV disease, and 82% had comorbidities. Eighty-three percent received chemotherapy, and 43% received radiation therapy. The most common symptoms reported included pain, dyspnea, cough, and weight loss, with most patients having multiple symptoms. Major deficits were identified in care compared with NCCN guidelines as only 30% of patients had advanced directives, and 32% received no supportive care services (eg, pain consult, social work, nutrition services). Uncontrolled symptoms were a common reason for outpatient visits, with pain, dyspnea, and fatigue as the most common symptoms. Symptoms accounted for 38% of hospital readmissions. Implications Study results served to guide the investigators in developing a pilot intervention to study and test the value of structured QOL assessment and interdisciplinary care planning to address the complex multidimensional needs of patients with lung cancer.