tbuckley/cabot-search huggingface dataset:
Clinicopathologic features of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): A single-center experience.
Authors: Tugba Akin Telli, Ece Esin, Suayib Yalcin
Journal: Journal of Clinical Oncology (2018)

e16168 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are a heterogenous group of neoplasm originating from the neuroendocrine system of the gastrointestinal tract and pancreas. There aren’t many large well-designed studies investigating NETs in Turkey. The aim of this study is to define the clinicopathologic, demographic and survival features of patients with GEPNETs. Methods: In this study, we reviewed hospital records of patients. The data was analyzed retrospectively and we investigated clinical, pathological and survival features and prognosis of patients with GEP-NETs (n = 128) admitted to Hacettepe University Cancer Institute, Medical Oncology Department between 2003 and 2014. Survival curve estimation was performed using the Kaplan-Meier method. Results: The median age of patients was 51.5 (17-81) . Among 128 patients with GEP-NETs 61 (47.7%) were female and 67 (52.3%) were male. The most common site of tumor was stomach (36.7%). There were 91 (71.1%) NET patients originating from foregut, 20 (15.6%) from midgut and 9 (7.0%) from hindgut. Six patients had unknown primary site NET (UPS) with metastasis. The most common stage at diagnosis was stage 4 (40.9%). The most common grade was grade 1 (56.8%). 70.3% of patients had curative surgery. The median follow-up period was 37 months. Three-years overall survival rate was 78%, while 5 years overall survival rate was 69%. The factors that can significantly affect the overall survival rate were stage (p = 0.003), grade (p < 0.001), presence of metastasis (p < 0.001) and Ki-67 proliferation index (p = 0.001) and these factors were asscociated with 3 and 5 years overall survival rate. Conclusions: Overall survival was found to be related to stage, grade, distant metastasis at diagnosis and Ki-67 proliferation index.
What are patients’ biggest concerns? A patient reported outcome case-management system.
Authors: Rahma M. Warsame, Carrie A. Thompson, Joleen Marie Hubbard, Amie L. Fonder, Miriam A. Hobbs, Lisa Hwa, Taxiarchis Kourelis, Wilson I. Gonsalves, Katrina Croghan, Briant Fruth, Angela Dispenzieri, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2017)

6572 Background: Cancer patients (pts) receive complex care that may cause physical, emotional, &amp; financial sequelae. Current practice limits clinician time to address patient concerns. The Patient Reported Outcome Quality Of Life (PROQOL) system was developed as a self-reported electronic questionnaire to assess symptoms, QOL and provide data about bothersome issues. Our aim was to determine if the PROQOL system improves QOL without negatively impacting routine clinic workflow. Methods: Eligible pts had multiple myeloma, amyloidosis, head &amp; neck or gynecologic cancer seen in Hematology/Oncology clinics at Mayo Clinic, and were stratified by stem cell transplant and active treatment status. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a “was it worth it survey” (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Herein we report the planned results of first 6 months. Results: Among the first 118 pts accrued, 55% were female, median age was 63 (32-86), &amp; 93% were on therapy. Median time from diagnosis to PROQOL was 26 months. The PROQOL system took 3.6 minutes to complete. Baseline median QOL (range) was 7 (3-10) for both groups. The most common PROQOL issue selected was “cancer &amp; diagnosis” (36.5%) followed by “physical health” (35.3%). Specific concerns were related to treatment plan, prognosis, fatigue, sleep, and neuropathy. WIWI showed: 71% of pts thought it was worthwhile, 83% would participate again, 80% would recommend it, &amp; 65% used resources provided. 80% of providers reported the PROQOL did not interfere with care &amp; 75% believed the pt wellbeing may improve. Conclusions: Notably treatment plan &amp; prognosis remain pts' greatest concern despite being over 2 year from diagnosis.The PROQOL system demonstrates integrated PRO reporting in clinic is quick &amp; worthwhile to pts &amp; providers.
Abstract 14270: Medin Amyloid, but Not β-amyloid, Induces Pro-Inflammatory Signaling in Endothelial Cells That is Synergistic With Palmitic Acid
Authors: Nina Karamanova, Seth Truran, Jillian Madine, Hannah Davies, Jenna Anderson, Daniel A Franco, Geidy Serrano, Thomas Beach, Raymond Q Migrino
Journal: Circulation (2017)

Medin is the most common human amyloid protein and accumulates in vessels with aging yet little is known about the pathophysiology of medin and its role in vascular aging. We previously showed that...
Unmet need for clinician engagement about financial toxicity after diagnosis of breast cancer.
Authors: Reshma Jagsi, Kevin C. Ward, Paul Abrahamse, Lauren P. Wallner, Allison W. Kurian, Ann S. Hamilton, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2018)

10080 Background: Little is known about whether growing awareness of the financial toxicity of cancer diagnosis and treatment has led to increased clinician engagement nor the status of current patients' needs. Methods: In 2013-15, we surveyed women with early-stage breast cancer, identified through population-based sampling from two SEER regions (Los Angeles and Georgia), and their physicians. We describe responses about experiences with financial toxicity and its management received from 73% of surgeons (n = 370), 61% of medical oncologists (n = 306), 67% of radiation oncologists (n = 169), and 68% of patients (n = 2502). Results: Half (50.9%) of responding medical oncologists reported that someone in their practice often or always discusses the financial burden of cancer with patients, as did 15.6% of surgeons and 43.2% of radiation oncologists. Among patients, 17% spent ≥10% of household income on out-of-pocket medical expenses and 7% spent ≥10% of household income on out-of-pocket nonmedical expenses. Debt from treatment was reported by 27.1% of whites, 58.9% of blacks, 33.5% of Latinas, and 28.8% of Asians. Privations were common: 21.5% of whites and 22.5% of Asians had to cut down spending on food, as did 45.2% of blacks and 35.8% of Latinas. Few whites (1.4%) or Asians (1.0%) lost their home, but 4.7% of blacks and 6.0% of Latinas did. Many patients desired to talk to healthcare providers about the financial impact of breast cancer: 15.2% of whites, 31.1% of blacks, 30.3% of Latinas, and 25.4% of Asians. Unmet patient needs for engagement with doctors about financial concerns were common. Of the 945 women who expressed worrying at least somewhat about finances, 679 (72.8%) indicated that cancer doctors and their staff did not help at least somewhat. Of the 523 women who expressed a desire to talk to healthcare providers about the impact of breast cancer on employment or finances, 283 (55.4%) reported that they had not had a relevant discussion. Conclusions: Improved clinician assessment and communication regarding financial toxicity are necessary. Even physicians who perceive that they are routinely offering necessary services may fail to meet patient needs. Cure at the cost of financial ruin falls short of physicians' duties.
Germline variants of BAP1 in the Australian population.
Authors: Sebastian Walpole, Antonia Pritchard, Jane Palmer, Madeleine Howlie, Judith Symmons, Hayley Hamilton, William Glasson, Sunil Warrier, Olivia Rolfe, Andrew Stark, Matthew D'Mellow, Nicholas Hayward
Journal: Journal of Clinical Oncology (2018)

e13534 Background: Germline mutations in the BRCA1-associated protein (BAP1) gene are linked to a large spectrum of cancers, defined as the BAP1 tumour predisposition syndrome (BAP1-TPDS). The cancers usually occurring in kindreds with BAP1-TPDS are uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, cholangiocarcinoma and meningioma. A 2017 review identified only 87 probands worldwide with germline BAP1 mutations. Methods: To better understand the frequency of BAP1-TPDS, we took a systematic BAP1 sequencing approach of a defined population. We screened Queensland uveal melanoma probands and their families for mutations in BAP1 (n = 64), identified variants from published studies from Australia and liaised with clinical genetics services Australia-wide to ascertain BAP1 germline variants. Only variants with a population frequency of < 0.0005 were considered. Results: We identified 2 truncating, 1 missense, 2 synonymous, 1 intronic and 1 promoter variant in the sequencing screen (7/64). Two truncating variants were referred by the clinical genetics services and finally, 13 published variants in Australian families were identified. The 4 truncating variants occur in kindreds with classical features of BAP1-TPDS and are disease causing. Of the total 11 missense variants, only 1 occurs in a family with BAP1-TPDS phenotype, which has been previously published (p.T173C) and is predicted to impair ubiquitin hydrolase activity. In silico prediction suggests 8/9 unique missense and 1 synonymous variants either alter splicing or damage protein structure, which requires functional confirmation. The intronic variant lies 8bp into intron 13 and is of unknown consequence. Finally, the promoter variant has been reported in an Italian family with the phenotype; however, in the Australian family, incomplete family history for the proband does not allow for a full assessment. Conclusions: The detection of six definite and two likely deleterious variants in this focused assessment of BAP1 in Australia suggests mutations may be more common than indicated by literature review. This study highlights a need for a comprehensive worldwide database of germline BAP1 variants and cancers present in carriers and development of a guide to clinical testing.
Survival associated with cachexia among SEER-Medicare beneficiaries with lung cancer.
Authors: Shweta Shah, Joshua Noone, Christopher Michael Blanchette, Susan T Arthur
Journal: Journal of Clinical Oncology (2017)

e18117 Background: Lung cancer is the leading cause of cancer death in the United States. It is estimated that 60% of lung cancer patients are afflicted with cancer-associated cachexia syndrome (CACS) and approximately 10% of these patients will die due to CACS. We examined the impact of CACS on survival among lung cancer elderly patients. Methods: We conducted a retrospective study using SEER-Medicare data. Patients were included if diagnosed with first primary lung cancer between January 1, 2005 and December 31, 2010, at least 66 years of age, and continuously enrolled in Medicare Parts A and B in the 12 months prior to diagnosis. We identified cachexia in lung cancer patients using ICD-9 codes. Descriptive statistics were used to identify population characteristics. Propensity score (1:1 nearest neighbor) matching was performed between cachectic and non-cachectic lung cancer patients to compare survival. Results: We identified 84,518 lung cancer patients. Of these, 2,536 (3%) developed CACS after lung cancer diagnosis. The most common comorbid conditions among cachectic and non-cachectic groups were chronic obstructive pulmonary disease (50% versus 45.62%), congestive heart failure (8.56% versus 13.38%), diabetes (7.41% versus 14.75%), peripheral vascular disease (3.82% versus 6.85%), and renal disease (3.63% versus 6.14%). Propensity score 1:1 matching for confounding bias and adjustment for immortal time bias resulted in a cohort of 3734 matched patients. Eighty-eight percent of patients in the cachectic group died during the follow-up period compared to 78% in the non-cachectic group. Median survival time among non-cachectic lung cancer patients was significantly longer than cachectic lung cancer patients (log-rank p &lt; 0.0001). Specifically, median survival in non-cachectic patients was 201 days compared to 92 days among cachectic patients. Conclusions: The occurrence of CACS is independently associated with a significant decrease in survival among lung cancer elderly patients. The results of this study may be useful for identifying healthcare burden and planning treatment modalities for this population.
Prevalence of attention-deficit/hyperactivity disorder in pediatric brain tumor survivors.
Authors: Emily Kauvar Shabason, Cole Brodsky, Julie Baran, Wendy Hobbie, Jane E. Minturn, Nathan Blum, Matthew Hocking
Journal: Journal of Clinical Oncology (2017)

10572 Background: Pediatric brain tumor survivors (PBTS) often have neurodevelopmental late effects, including attention and concentration deficits, which may impact cognitive and academic functioning. Such symptoms are also seen in attention-deficit/hyperactivity disorder (ADHD), which affects ~5-8% of children and adolescents. This study examined the prevalence of ADHD diagnosis and ADHD medication use in PBTS and identified higher risk subsets of patients. Methods: A retrospective chart review was completed of PBTS (n = 106), diagnosed from 1999-2013, who were at least 2 years from the end of tumor-directed therapy (surgery, chemotherapy and/or radiation therapy) and without a multi-system genetic disorder or severe developmental delay prior to brain tumor diagnosis. Subjects were already screened for or enrolled in 3 other studies of PBTS late effects. Statistical analysis involved chi-squared analysis. Results: Among the 106 patients, 55.7% were male, with an average age at time of brain tumor diagnosis of 5.9 years (0-12.2 years). The most common tumor types were glioma (51.9% with 47.2% low grade, 4.7% high grade), medulloblastoma (13.2%) and ependymoma (11.3%), with 50% of tumors supratentorial, 46.2% infratentorial and 3.8% either extending or multifocal across the tentorium. Of the patients, 42.5% received radiation therapy, 38.7% chemotherapy and 86.8% surgery. Nineteen patients (17.9%) had ADHD diagnoses, and 20 (18.9%) had been on ADHD medications. Clinical factors associated with an ADHD diagnosis were supratentorial vs. infratentorial tumors (28.3% vs. 6.1%, p = 0.013), no radiation therapy vs. radiation therapy (27.9% vs. 4.4%, p = 0.002) and no chemotherapy vs. chemotherapy (24.6% vs. 7.3%, p = 0.024). ADHD diagnosis was not associated with age of brain tumor diagnosis or surgical treatment. Conclusions: Our study suggests that PBTS have over twice the ADHD prevalence as the general population, most notably in patients with supratentorial tumors or without a history of radiation therapy or chemotherapy. The results suggest that a closer look at this population is warranted and that select patients may benefit from behavioral or pharmacologic ADHD treatments to optimize functioning.
The relationship between pretreatment positron emission tomography (PET) results and demographic, histopathologic parameters in patients with locally advanced breast cancer.
Authors: Mahmut Gumus, Serap Kaya, Hatice Odabas, Aydin Aytekin, Nilgun Yildirim, Teoman Sakalar, Dincer Aydin, Mehmet Bilici, Haci Mehmet Turk, Faysal Dane, Mustafa Benekli
Journal: Journal of Clinical Oncology (2016)

e23135 Background: Neoadjuvant chemotherapy has been accepted as standart treatment in locally advanced breast cancer recently. 18-FDG-PET/CT is frequently used method for the staging of disease before treatment. We aimed to investigate the role of PET/CT in staging and detection of distant metastasis in addition the relationship of PET/CT with demographic and histopathologic characteristics. Methods: In 6 centers of the different cities of our country, the patients scanned with PET/CT before NAC were evaluated. The SUV of the primary tumor and axilla, age, menopausal status, performance status, clinical stage, tumor localization, hormonal receptor status, presence of Her2 expression, and molecular subtypes of the patients were recorded. ″Mean SUV″ was accepted as mean of the SUVmax of the primary tumor and axilla. Mann-Whitney U ve Kruskall-Wallis H tests were used to investigate the relationship between mean SUV and demographic and histopathologic characteristics. Results: In this study 317 patients were evaluated. Median age was 49(20-82). Of the patients 10.4% was below 35 years, 52% was premenopausal, 89% had ECOG PS:0, 84.5% had stage III disease. In 45.1% of the patients tumor localization was on the right breast. Endocrine sensitivity was 80.1%, Her2 positivity was 42.9% and triple negative molcular subtype was 8.2% of the patients. Mean SUV was found to be significantly higher in patients without hormone sensitivity (ER and PR negative)(p = 0.033). There was a statistically trend between clinical stage and molecular subtype with mean SUV (p = 0.098 and 0.063 respectively). Mean SUV was found to be higher in stage III and triple negative patients. There was no significant relationship between Mean SUV and other parameters(p > 0.05). Conclusions: Taking into consideration of the demographic and histopathological characteristics will increase the success of the treatment in breast cancer patients. Furthermore, PET/CT findings and high level of mean SUV may guide the agressiveness of the tumor.
Cost effectiveness of therapeutic clinical trials for the Irish Health Service Executive: A single centre analysis of hospital and state budget cost savings.
Authors: John Patrick Greene, Li Wah Kyaw-Tun, Rozana Rahman, Elly Che Othman, Anees Hassan, Mustasim Mohamed, Mateen Akhtar, Justin Owen, Alexia Bertuzzi, Janice Walshe, Ray McDermott
Journal: Journal of Clinical Oncology (2016)

e18261 Background: Clinical trials are an important tool in improving health outcomes in oncology patients. They also allow access to drugs that may otherwise be unavailable to patients. Increasingly, newer agents are associated with an increasing cost to hospitals, state budgets and insurance companies. Access to drugs through clinical trials may offset some of this cost to a hospital and health service budget. Methods: A prospective review on monthly basis was performed using known values of commercial stocks used during clinical trials in a single hospital centre during 2015. The available trial drugs were pazopanib, cabozantinib, everolimus, regorafanib, eltrombopag, azacitidine, orternerol, paclitaxel, pembrolizumab, nivolumab, ipilimumab, sunitinib, enzalutamide and vinflunine. Results: In total, 51 patients were recruited to therapeutic studies. A grand total of €1,420,501 (US$1,545,086) was saved to the hospital and state budget excluding commercially available stock. If placebo controlled trials were excluded, total savings were €1,149,445 (US$1,251,060). Conclusions: Clinical trials allow patient access to drugs that may otherwise not be available due to cost or access. Clinical trials also significantly offset the cost of these treatments to hospitals, state healthcare providers and insurance companies. Available clinical trials should be discussed with eligible patients when discussing treatment options. 2015 Direct Savings (€) Indirect Savings (€) Indirect Savings (exclu. placebo) (€) Cost of commercial stock supply (€) Grand Total Grand Total excluding placebo Jan 7,718 39,387 17,957 19 (direct savings + indirect savings - commercial stock) [direct savings + indirect savings (exclu. placebo) - commercial stock] Feb 7,718 35,697 15,845 123 Mar 15,570 51,578 33,304 239 Apr 15,503 73,688 51,427 353 May 40,258 59,057 36,795 186 Jun 42,242 66,704 44,443 333 Jul 103,103 71,410 26,870 596 Aug 74,340 71,410 49,149 943 Sep 104,999 88,206 68,728 943 Oct 91,788 71,803 52,325 313 Nov 87,288 101,063 67,672 1,166 Dec 52,472 53,467 47,902 762 Total 2015 €643,006 €783,475 €512,419 €5,980 €1,420,501 €1,149,445
Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer.
Authors: Yuji Takayama, Koichi Suzuki, Taro Fukui, Kosuke Ichida, Fumiaki Watanabe, Nao Kakizawa, Rina Kikugawa, Fumi Hasegawa, Shingo Tsujinaka, Yasuyuki Miyakura, Fumio Konishi, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2018)

e15630 Background: KRAS mutated circulating tumor DNA (MctDNA) can be monitored in the blood of patients with metastatic colorectal cancer (mCRC), but dynamic changes have not been determined. Methods: Four hundred and fifty-seven plasma samples were collected prospectively from 85 mCRC patients who underwent chemotherapy. MctDNA in plasma was detected by droplet digital PCR, and the percentage of MctDNA in total circulating cell-free DNA was calculated. Results: KRAS assessment in tumor tissues showed 29 patients with the mutant-type (MT) and 56 patients with the wild-type (WT). Twenty-three of 29 MT patients (79.3%) and 28 of 56 WT patients (50.0%) showed MctDNA. Emergence of MctDNA was recognized during treatments with various drugs. Regardless of KRAS status in tumor tissues, patients with MctDNA in blood showed poor progression-free survival with first-line treatment. Median percentage of MctDNA accounted for 10.10% in MT patients and 0.22% in WT patients. These differences between MT and WT likely affected patterns of changes in MctDNA. KRAS monitoring identified dynamic changes in MctDNA, such as continuous, intermittent, and transient changes (quick elevation and disappearance). Emergence of MctDNA involved drug resistance, except for transient changes, which were seen in WT patients and likely corresponded with the drug response. Transient changes could be involved in recovery of sensitivity to anti-EGFR antibody in WT patients. Conclusions: Monitoring MctDNA during various treatments showed dynamic changes in KRAS status and could provide useful information for determining treatments for patients with mCRC. Table. Detail of emergence during each regimen in WT patients. Number of Patients (n) Emergence of MctDNA (n) Percentage of patients with emergence of MctDNA (%)* CT 4 1 25.0 anti-VEGF + CT 33 13 39.4 anti-EGFR 25 9 36.0 Regorafenib 10 3 30.0 TAS-102 10 7 70.0 * Emergence of MctDNA / Number of Patients *100
Architectural Effects of Star‐Shaped “Structurally Nanoengineered Antimicrobial Peptide Polymers” (SNAPPs) on Their Biological Activity
Authors: Steven J. Shirbin, Ignacio Insua, James A. Holden, Jason C. Lenzo, Eric C. Reynolds, Neil M. O'Brien‐Simpson, Greg G. Qiao
Journal: Advanced Healthcare Materials (2018)

Abstract In this work, the effect of two key structural parameters, number of arms and arm length, of star‐shaped “structurally nanoengineered antimicrobial peptide polymers” (SNAPPs) on their antimicrobial activity and biocompatibility, is investigated. A library of star‐shaped SNAPPs is prepared, containing varying arm numbers and arm lengths. Antimicrobial assays are then performed to assess the capacity of the SNAPPs to disrupt the membrane, inhibit the growth, and kill pathogenic bacteria. A major finding of the study is that increasing arm number and length of SNAPPs enhanced antimicrobial activity, which can be respectively attributed to the higher local concentrations of polypeptide arms and increased α‐helical content. SNAPP architecture is shown to affect the bacteria membrane state and therefore mechanism of killing. Two more potent structures with up to twice the antimicrobial activity of the previously reported SNAPP are discovered in this process. Toxicities of the SNAPPs also increase with arm number and arm length, however therapeutic index calculations identified a 16‐arm SNAPP and an easier to prepare 4‐arm SNAPP as the best therapeutic agents. The biocompatibility of the SNAPP with the best biological activity is also evaluated in vivo, showing no markers of systemic damage in mice.