tbuckley/cabot-search huggingface dataset:
Needs assessment for sexual health support following cancer diagnosis.
Authors: Lindsay Louise Welton, Saketh R Guntupalli, Dina M Flink
Journal: Journal of Clinical Oncology (2019)

e23071 Background: Women report distress over relationships, body image and sexual function after cancer; those &lt; 50 have a 3-times greater risk of sexual dysfunction following treatment. Survivors desire integrated and multifaceted interventions to maintain optimal sexual health. Methods: We employed a mixed-method (concurrent nested) design to identify women’s need for sexual health support after diagnosis. Women 18-50 years old were recruited at a national conference for young survivors and local breast/gynecologic clinics. Qualitative and quantitative assessments identified sexual health factors and support needs most prevalent. Summary statistics and theme analysis using grounded theory was conducted. Results: Participants included 128 women (mean diagnosis age 35.6) and were: married (71%), breast cancer (46%), mastectomy (40%), hysterectomy (30%), chemotherapy (81%), radiation (51%) and completed treatment (67%). Nearly 1/3 of women reported their relationship worsening, 97% contribute it to less sexual activity; 71% were unsatisfied with their sexual relationship compared to before diagnosis. Women (77%) feel their oncologist should discuss sexual health and 74% prefer information prior to treatment. When asked to identify resources 82% desired helpful products/strategies; other desired resources include: written education (65%), medications/lubricants (68%), personal counseling (37%), sex therapist (41%) and local/web-based support groups (36%). When asked to describe their experience with sexual health women reported the following themes: supportive partners, sexual health status, guilt, stolen identity, loss of desire, isolation, treatment side effects, menopause, vaginal changes, maintaining relationships, coping mechanisms, fertility, self-image, grief, intimacy, and desire for oncologist support. Conclusions: Sexual health support after diagnosis is an unmet need that can be integrated into treatment to greatly improve the quality of life for survivors. Women desire their oncologist to provide information before treatment and through survivorship on products/strategies, education, and medications/lubricants to maintain sexual function. Young women do not desire social support resources.
Analysis of hydration and antiemetics policies in preventing cisplatin-related gastrointestinal and renal toxicities in low-risk human papillomavirus positive-oropharyngeal cancer (HPV+OPC) patients undergoing chemoradiation in De-ESCALaTE trial.
Authors: Anthony Hee Kong, Pankaj Mistry, Mererid Evans, Andrew G. J. Hartley, Tessa Fulton-Lieuw, David Jones, Matthew Dalby, Alastair Gray, Bernadette Foran, Mehmet Sen, Lorcan O'Toole, H Al-Booz, Karen Dyker, Rafael Moleron Mancebo, Stephen Whittaker, Sinead Maire Brennan, Audrey Cook, Matthew Griffin, Janet Dunn, Hisham Mohamed Mehanna
Journal: Journal of Clinical Oncology (2019)

6076 Background: The De-ESCALaTE trial confirmed the superiority of cisplatin over cetuximab in combination with radiotherapy for the treatment of low risk human papillomavirus positive oropharyngeal cancer (HPV+OPC). The most common serious adverse events (SAEs) for cisplatin were due to vomiting and nausea, in contrast with oral mucositis and vomiting for concurrent cetuximab. In this study, we examined the efficacy of different hydration and anti-emetic policies in preventing cisplatin-related gastrointestinal and renal toxicities as well as related SAEs in the cisplatin arm of the De-ESCALaTE trial. Methods: This was a post-hoc pre-specified analysis of data collected within the De-ESCALaTE trial including pre-hydration, diuretics, the amount of intravenous (IV) fluids before, during and after chemotherapy, whether oral fluid hydration was advised and type of antiemetic regimen prescribed, if any, after chemotherapy administration, including if a triple antiemetic regimen with a NK1 receptor antagonist, steroids and a serotonin 5-HT3 antagonist was given before and after chemotherapy. The primary outcome was number of SAEs per patient; secondary outcome was number per patient of cisplatin-induced severe toxicity events of interest: nausea, vomiting, dehydration or renal toxicity. Results: 166 (mean age 57 yrs; 132 m, 34 f) patients received cisplatin. Hydration and anti-emetics policies for cisplatin treatment are significantly correlated with the rate of SAEs and acute severe nausea, vomiting, dehydration or renal toxicities. Using stepwise backwards multivariable ordinal logistic regression in the presence of baseline characteristics, use of a triple anti-emetics regimen (OR 0.41,p = 0.032) and 2.5 to 3L IV fluids given before and during cisplatin chemotherapy (OR 0.161, p = 0.009) as well as oral fluids advised post chemotherapy (OR 0.365, p = 0.03) were associated with a significantly lower incidence of SAEs and severe toxicities of interest. We will also present data on relative cost-effectiveness of the different regimens. Conclusions: Based on our results, we recommend the use of a triple anti-emetic regimen, adequate hydration of 2.5-3L before and during chemotherapy as well as advising patients to take oral fluids advised to reduce cisplatin toxicities related to nausea, vomiting, dehydration and/or renal injury. Clinical trial information: ISRCTN33522080.
Trends in mortality due to hypercalcemia in breast cancer.
Authors: Stuthi Perimbeti, Rishi Shrivastav, Michele Dana Stanchina, Priyadarshini Pathak, Michael Raphael Rainone, Maneesh Rajiv Jain, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2019)

e18252 Background: Hypercalcemia (HC) in metastatic breast cancers results from various mechanisms including increased bone turnover and secretion of Parathyroid hormone-related peptide. The presence of HC has traditionally been associated with poor prognosis but recent advances in the treatment of both HC with bisphosphonates and RANK-L inhibitors, and metastatic breast cancers with chemotherapy and immunotherapy, have improved symptoms and progression free survival. It has yet to be determined whether HC remains a poor prognostic indicator. Methods: Adult admissions ( &gt; 18 years) between 1999 and 2014 with a primary diagnosis of breast cancer (BC) were extracted from the Nationwide Inpatient Sample using ICD-9 code 174.9. They were stratified for the presence of HC (ICD-9 code: 275.42), and further according to the year of admission. Chi-Square test and cox proportional hazard regression were used to determine in-hospital mortality and hazard of death based on the presence of HC. Results: A total of 484,859 (N = 98,631, weighted N = 484,859) admissions with a primary diagnosis of BC were obtained. The prevalence of HC increased from 0.52% in 1999 to 1.32% in 2014, yet inpatient mortality and adjusted Hazard Ratios (HR) of mortality declined over time as shown in Table. Despite this, patients with HC continued to have a significant increase in hospital mortality and HR (p &lt; .001). Conclusions: Due to advances in medical therapy, in hospital mortality for patients with metastatic breast cancer has been declining over the last 15 years, however, the presence of HC continues to carry an independent risk for mortality. More research is needed to elucidate why HC continues to confer worse prognosis despite new calcium-lowering treatment modalities.[Table: see text]
Real time FTIR spectroscopy of tissue smears from gynecologic cancer tissues: A preliminary study.
Authors: Ilan Bruchim, Dov Malonek, Ben Zion Dekel, Renat Reens Carmel, Gabi Groisman, Mordechai Hallak
Journal: Journal of Clinical Oncology (2019)

e17089 Background: Women with suspected Gynecologic cancer undergo surgical procedures during which tissue from suspected areas is excised. Fast histopathology analysis is performed intra-operatively using frozen section (FS) analysis, results of which are available within less than an hour. However, the accuracy of the FS test ranges between 75% and 100% when compared to final histopathology diagnoses. Fourier transform Infrared (FTIR) spectroscopy, utilized for classification of tissue samples into malignant and benign tumors, has shown comparable results to those of FS histopathology analysis. However, the sample preparation time and the effects of tissue preparation on the measured spectra have been a concern for the utilization of this technique in clinical practice. In this study we used attenuated total reflection (ATR) FTIR spectroscopy to examine fresh tissue impression smears as an alternative to the FS technique for rapid classification of tissue samples obtained during surgery. Methods: The study was approved by relevant ethics committees and was conducted in accordance with the Declaration of Helsinki. All patients provided written, informed consent. In total, 23 biopsies (ovarian and uterine) were extracted from suspected tumor sites during surgical procedures and sent to the histopathology laboratory for both pathological and FTIR analyses. Results of the histopathology analysis classified 15 samples as benign and 8 samples as malignant. Prior to the histopathologic analysis, tissue samples from these tumors were lightly pressed against the surface of an ATR crystal, leaving on its' surface impression smears. These smears were air dried for ~5 minutes. Mid-IR absorbance spectra were collected using an ATR-FTIR spectrometer. Machine learning techniques (PCA-LDA and SVM) were utilized to build discrimination models from the absorbance data of the measured smears. Sensitivity and specificity were calculated. Results: IR absorbance spectra of malignant smears were consistently higher from spectra of benign smears in the 850cm-1 to 1450 cm-1 range and they were consistently lower in the 3200cm-1 to 3600cm-1 range. The PCA-LDA discrimination model correctly classified the samples with a sensitivity and specificity of 100%, and the SVM showed a training accuracy of 100% and a cross validation accuracy of 91.3%. Conclusions: These preliminary results suggest that ATR-FTIR spectroscopy of tissue smears may have an important role in the development of next-generation techniques for intra-operative tumor classification.
AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced tumors: Preliminary results from ongoing phase I studies.
Authors: John D. Powderly, Paul L. de Souza, Rodolfo Gutierrez, Lisa Horvath, Lisa Seitz, Devika Ashok, Adam Park, Matthew J. Walters, Joyson Joseph Karakunnel, Wade Berry, Aimee Rieger, Amanda Garofalo, Dominic W. Lai, Arvind Chaudhry
Journal: Journal of Clinical Oncology (2019)

2604 Background: AB928, a selective, small-molecule A 2a R/A 2b R antagonist, potently blocks the immunosuppressive effects of high adenosine concentrations in the tumor microenvironment. Preclinically, combining adenosine receptor inhibition with either chemotherapy or anti-PD-1 resulted in greater tumor control, suggesting AB928 may have additive activity when paired with either of these agents in cancer pts. Methods: Three dose-escalation (3+3 design) studies are assessing the safety, pharmacokinetics (PK), pharmacodynamics, and clinical activity of increasing doses of AB928 (75, 150, 200 mg orally once daily) in combination with: standard pegylated liposomal doxorubicin in triple-negative breast cancer (TNBC) and ovarian cancer (OC); standard mFOLFOX6 in gastroesophageal cancer (GEC) and colorectal cancer (CRC); and AB122 (240 mg every 2 weeks) in various advanced tumors. Following identification of the recommended phase 2 dose of AB928 in combination with chemotherapy or AB122 in dose escalation, the following tumor cohorts may be expanded (15-40 pts/cohort) to further test the combinations: TNBC and OC, GEC and CRC, and renal cell carcinoma. Results: As of 01Feb2019, 9 pts were treated across the 3 studies, and time on treatment ranged from 1-182 days (table). Overall, AB928 combination therapy was well tolerated. Two pts underwent post-baseline disease assessment; both had stable disease. Preliminary data indicate that AB928 PK and adenosine receptor coverage in cancer pts are similar to what was previously assessed in healthy volunteers. AB122 PK and PD-1 coverage are equally unaffected by AB928 co-administration. Updated data, including biomarker data, will be presented at the meeting. Conclusions: Early results showed a favorable safety profile of AB928 combination therapy. All 3 studies are actively recruiting pts. Clinical trial information: NCT03719326; NCT03720678; NCT03629756. [Table: see text]
Delay in receipt of newly prescribed oral anticancer drugs.
Authors: Daniel O'Neil, Melissa Kate Accordino, Jason Dennis Wright, Cynthia Law, Suzuka Nitta, Donna Buono, Maura Abbott, Yelena Ustoyev, Ellen Cole, Jianhua Hu, Alfred I. Neugut, Chin Hur, Khilna Patel, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2019)

6541 Background: Oral anticancer drug (OACD) prescriptions require coordination between clinicians, payers, specialty pharmacies, and financial assistance (FA) groups, which may delay patient receipt of the drug. Factors associated with delay in receipt of OACDs are unknown. Methods: We prospectively collected data on all new OACD prescriptions (RXs) from the medical oncology practice at the Herbert Irving Comprehensive Cancer Center from 1/1/2018 to 12/1/2018. We collected patient demographic, insurance and clinical information; date of prescription; date of drug delivery; and staff interactions with payers and FA groups. Federal Drug Association (FDA) labels and Micromedex were reviewed for initial drug approval dates, approved indications and average wholesale price. We used multivariable linear and logistic regression to determine factors associated with number of days from prescription to receipt of OACD. Results: During the study period 510 OACD RXs were evaluated. Of these, 84 (16%) were never filled. The most common OACDs were capecitabine (90, 18%), abiraterone (45, 9%), palbociclib (35, 7%) and osimertinib (28, 6%). Of 426 filled RXs, the median time from prescription to receipt was 8 days (IQR 5-13), with 193 RXs (46%) received in ≤7 days, 145 (34%) in 8-14 days and 65 (15%) in 14-28 days, and 23 (5%) at &gt; 28 days. Linear regression showed time to receipt of OACD (log transformed) was associated with having commercial primary insurance (p = 0.02), pursing FA (p = &lt; 0.001), RX of a drug approved by the FDA &lt; 2 years earlier (p = 0.008), drugs without an approved indication for the primary tumor (p = 0.03) and estimated drug cost (p = 0.002). The other included covariates, patient age and prior authorization, were not associated with time to receipt. Logistic regression comparing receipt at ≤14 versus &gt; 14 days found association with FA (OR 3.17; 95%CI 1.78-5.65), FDA approval within 2 years (OR 3.52; 95%CI 1.31-9.45) and off-label use (OR 2.30; 95%CI 1.18-4.50). Conclusions: Over 20% of new OACDs were received 14 days or longer from the date of RX. Financial and insurance related factors; and more expensive and recently approved drugs were associated with longer delays in receipt of therapy. Policy changes to improve the timeliness of OACD access are needed.
Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
Authors: Laurence Albiges, Tom Powles, Michael Staehler, Karim Bensalah, Rachel H. Giles, Milan Hora, Markus A. Kuczyk, Thomas B. Lam, Börje Ljungberg, Lorenzo Marconi, Axel S. Merseburger, Alessandro Volpe, Yasmin Abu-Ghanem, Saeed Dabestani, Sergio Fernández-Pello, Fabian Hofmann, Teele Kuusk, Rana Tahbaz, Axel Bex
Journal: European Urology (2019)
Impact of combined MRP1 inhibition and mutant p53-targeting compound APR-246.
Authors: Anna Sophia Ceder, Sofi E. Eriksson, Emarndeena Haji Cheteh, Vladimir J.N. Bykov, Lars Abrahmsen, Klas G. Wiman
Journal: Journal of Clinical Oncology (2019)

e14712 Background: The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. Mutant p53 protein is often expressed at high levels and accompanied with gain-of-function activities that promote tumor development and resistance towards conventional treatment. APR-246 is a mutant p53-reactivating small molecule undergoing a Phase III clinical study in myelodysplastic syndrome (MDS), and several phase II studies. APR-246 is non-enzymatically converted to its active product methylene quinuclidinone (MQ) which binds to cysteine residues in p53. This stimulates proper folding of p53's DNA-binding core domain, leading to cell death. APR-246 also exhibits pro-oxidant activity as the electrophile MQ binds and inactivates important antioxidants such as glutathione and thioredoxin reductase, which both are essential for cellular defense against oxidative and electrophilic stress. Methods: All results are in vitro experiments by LC-MS as well as experiments in cultured cells, including 14 C-APR-246/MQ detection, cell viability measurements, LC-MS analysis, enzyme recycling measurements and Western blotting. Results: We have utilized 14 C-labelled APR-246 to investigate the effect of APR-246 and its active moiety MQ in tumor cell cultures upon inhibition of efflux transporter multidrug resistance protein 1 (MRP1) or cystine-glutamate transporter (xCT). Transient downregulation or small molecule inhibitors (MK-571, reversan, sulfasalazin) targeting MRP1 or xCT increased drug content and shifted intra- and extracellular thiol status. Missense mutant TP53-carrying cells exhibited higher sensitivity to APR-246 and combination therapies. MRP1 inhibition showed strong synergy with APR-246 and increased intracellular levels of MQ conjugated to glutathione (GS-MQ). We found that GS-MQ conjugate formation is reversible, and suggest that the intrinsic reversibility of MQ adduct formation is an important aspect of the mechanism of action of APR-246. This reversibility may also in part account for the benign safety profile reported from clinical studies with APR-246. Conclusions: Sensitivity to APR-246 is affected by MRP1 efflux activity and the redox status, reflected in ratios of cysteine/cystine and reduced/oxidized glutathione (GSH/GSSG).
STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models
Authors: Weiqing Jing, Donna McAllister, Emily P. Vonderhaar, Katie Palen, Matthew J. Riese, Jill Gershan, Bryon D. Johnson, Michael B. Dwinell
Journal: Journal for ImmunoTherapy of Cancer (2019)

Pancreatic cancer is characterized by an immune suppressive stromal reaction that creates a barrier to therapy. A murine transgenic pancreatic cancer cell line that recapitulates human disease was used to test whether a STimulator of Interferon Genes (STING) agonist could reignite immunologically inert pancreatic tumors. STING agonist treatment potently changed the tumor architecture, altered the immune profile, and increased the survival of tumor-bearing mice. Notably, STING agonist increased numbers and activity of cytotoxic T cells within tumors and decreased levels of suppressive regulatory T cells. Further, STING agonist treatment upregulated costimulatory molecule expression on cross-presenting dendritic cells and reprogrammed immune-suppressive macrophages into immune-activating subtypes. STING agonist promoted the coordinated and differential cytokine production by dendritic cells, macrophages, and pancreatic cancer cells. Cumulatively, these data demonstrate that pancreatic cancer progression is potently inhibited by STING agonist, which reignited immunologically cold pancreatic tumors to promote trafficking and activation of tumor-killing T cells.
Integrating salvage hypofractionated radiosurgery plus low-dose adjuvant bevacizumab for locally recurrent brain metastasis with high dose irradiation previously.
Authors: Yun Guan, Huaguang Zhu, Chaozhaung Wang, Jing Li, Wenqian Xu, Lei Sun, Li Pan, Jiazhong Dai, Yang Wang, Enmin Wang, Xin Wang
Journal: Journal of Clinical Oncology (2019)

e13579 Background: Treatment for recurrent brain metastasis remains uncertain. The purpose of this research was to evaluate the efficacy and toxicity of FSRS with adjuvant bevacizumab as a new salvage treatment for locally recurrent brain metastases with high dose irradiation previously. Methods: Patients with locally recurrent intracranial metastasis with irradiation previously were enrolled in this prospective study. Salvage FSRS dose ranged from 9.5 to 29 Gy in two to five sessions with 62–75% isodose line. Adjuvant bevacizumab was prescribed four cycles (5 mg/kg, q3w). Magnetic resonance imaging (MRI), Karnofsky Performance Scale (KPS), adverse events and clinical outcomes were recorded. The primary objective of this study was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (KPS), imaging response (MRI) and adverse events. Results: From December 2009 to October 2016, 24 patients were enrolled. Of these patients, 9 received WBRT followed by SRS, and 15 underwent SRS. The median 1-year overall survival (OS) after salvage SRS was 87.5%. No treatment-related grade 4 adverse events were recorded. Grade 1/2 fatigue was observed in 8 (33%) patients followed by headache, hypertension and nausea. Grade 3 fatigue and headache occurred in 1 patient. No grade 4 toxicity was observed. Conclusions: Salvage FSRS with early use of low dose adjuvant bevacizumab treatment showed favourable clinical and radiologic control with manageable toxicity for locally recurrent brain metastasis patients who underwent high dose irradiation previously. The diagnosis of RN and LR after salvage FSRS merit further study. [Table: see text][Table: see text][Table: see text]