bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple heterochronic gastrointestinal stromal tumors in the stomach detected 6 years after resection: a case report
Authors: Yasuda Tadahito , Eto Kojiro , Yoshida Naoya , Iwagami Shiro , Hiyoshi Yukiharu , Nagai Youhei , Iwatsuki Masaaki , Ishimoto Takatsugu , Baba Yoshifumi , Miyamoto Yuji , Shiota Takuya , Mikami Yoshiki , Baba Hideo 
Published: March 2020

Abstract
Background
To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported.

Case presentation
A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins.

Conclusion
We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.
Relationships among weight stigma, eating behaviors and stress in adolescents in Wuhan, China
Authors: Wang Zhanxia , Wang Bowen , Hu Yiluan , Cheng Lei , Zhang Siqi , Chen Yanan , Li Rui 
Published: March 2020

Abstract
Background
The purpose of this study was to examine the relationships among weight stigma, eating behaviors, and stress, as well as to analyze the effect of stress in mediating the association between weight stigma and eating behaviors.

Methods
The study involved 1818 adolescents between 14 to 19 years of age and was conducted in Wuhan, China in 2019. Weight stigma, eating behaviors (cognitive restraint, uncontrolled eating, and emotional eating), and stress were assessed by self-report questionnaires. Hierarchical linear regression analyses were used to examine the predictors of cognitive restraint, uncontrolled eating, and emotional eating; the serial mediation models analyses were conducted to analyze the effect of stress in mediating the association between weight stigma and eating behaviors for the whole non-overweight (normal and underweight) and overweight or obese participants, respectively.

Results
Hierarchical linear regression analyses showed that experiences of weight stigma significantly predicted uncontrolled eating and emotional eating regardless of body mass index (BMI) (non-overweight adolescents: uncontrolled eating: β [SE] = 0.161 [0.017]; emotional eating: β [SE] = 0.199 [0.008], p < 0.05; overweight or obese adolescents: uncontrolled eating: β [SE] = 0.286 [0.030]; emotional eating: β [SE] = 0.267 [0.014], p < 0.05); experiences of weight stigma significantly predicted cognitive restraint among non-overweight adolescents (β [SE] = 0.204 [0.013], p < 0.05). Mediation analyses showed that stress mediated the associations between weight stigma and uncontrolled eating and emotional eating among non-overweight adolescents (uncontrolled eating: indirect effect coefficient = 0.0352, 95% CI = 0.0241, 0.0478; emotional eating: indirect effect coefficient = 0.0133, 95% CI = 0.0085, 0.0186).

Conclusions
These findings suggest that non-overweight individuals can still experience weight stigma and its associated negative consequences; the relationship between weight stigma and eating behaviors is modulated by weight status; stress mediated the associations between weight stigma and uncontrolled and emotional eating among non-overweight adolescents.
Antibiotic sensitivity and RAPD-PCR studies on cultivable gut bacteria from Indian Medicinal Leech—Hirudinaria granulosa
Authors: Patel Dhaval , Koriya Khushbu , Patel Pinkal , Solanki Jyoti , Mesara Suresh , Nataraj M. 
Published: March 2020

Abstract
Background
Hirudo granulosa—an Indian cattle leech, is frequently used for the treatment of psoriasis and eczema. During treatment which followed by leech biting, it transfers some amount of gut microbes along with saliva. This may result in bacterial infection at the treatment site. Antibiotics used as post-surgical hirudotherapy is the reason for drug resistance. Drug resistance is the result of the change in the genetic makeup of bacteria. Therefore, it is necessary to study antibiotic sensitivity of gut bacteria and characterized them genetically.

Results
Fourteen bacterial isolates were obtained from unused leech in which five were Gram-negative and the other nine were Gram-positive. Similarly from the used leech, thirteen were isolated in which five were Gram-negative and the other eight were Gram-positive. Biochemical analysis reveals that isolates from unused leech saliva belong to Pseudomonas, Micrococcus, Streptococcus, and Vibrio species, while the used leech salivary bacteria were the member of genus Pseudomonas, Comamonas, Escherichia, Citrobacter, Aeromonas, Providencia, Enterobacter, and Yersinia. Antibiotic sensitivity tests for isolates indicated that chloramphenicol (30 μg) and norfloxacin (10 μg) were effective for unused leech isolates while sparfloxacin (5 μg) and Cefaclor (30 μg) were effective against used leech salivary isolates. Random primer (OPL-14)-based random amplified polymorphic DNA (RAPD) fingerprint showed twenty amplified regions among all tested bacteria. Most of the bacteria contain the tested sequence except U2, T2, T9A, and T10 which showed no amplification indicated the absence of primers sequence.

Conclusion
Chloramphenicol, norfloxacin, sparfloxacin, and Cefaclor antibiotics alone or in combination were possibly used to treat post-therapy infections. Bacteria from treated and untreated leeches were clustered at nearby branch in neighbor end-joining phylogenetic tree, which indicates the similar (but not exact) genetic makeup. Therefore, it can be concluded that these antibiotics were possibly used against most of them.
Phase Ib/II study of INNO-206 (EMCH-doxorubicin) in patients with soft tissue sarcoma.
Authors: Chawla Sant P. , Chua Victoria S , Hendifar Andrew , Quon Doris , Nagre Sandeep , Ganjoo Kristen N. , Sankhala Kamalesh , Wieland Scott , Levitt Daniel 
Published: March 2020

10036 Background: The safety and preliminary tumor response of a doxorubicin conjugate, INNO-206, was evaluated primarily in patients with metastatic STS who progressed on prior chemotherpy. INNO-206 consists of doxorubicin attached to an acid-sensitive linker that binds covalently to cysteine-34 in circulating albumin. Methods: INNO-206 was administered IV at doses of either 230, 350 and 450 mg/m2 (165, 260 and 325 mg/m2 dox. eq.) every 21 days for up to 8 consecutive cycles. Subsequent dose levels were administered if < 2/5 or 4/8 patients experienced a non-hematological dose-limiting toxicity during Cycle 1. Tumor response was monitored every other month and treatment continued until tumor progression or unacceptable toxicity. Standard safety monitoring was performed and cardiac function was followed periodically using MUGA or cardiac ultrasound. Results: As of January 11, 2012, 25 patients were entered in the study. 21/25 patients had STS of various types. Of the 5 patients treated at 230 mg/m2 INNO-206, 1 subject had grade 3 fatigue and acid reflux. Of the initial 5 patients entered at the 350 mg/m2 dose, no individuals experienced a grade 3 or 4 non-hematological toxicity during cycle 1. 2 patients treated at the 450 mg/m2 dose developed grade 3 oral mucositis during cycle 1. No patient exhibited cardiotoxicity as determined by MUGA or cardiac ultrasound. The MTD was determined to be 350 mg/m2 INNO-206 (260 mg/m2 dox.eq.). 15 more patients were entered at this dose (total of 20 patients). Of the 16 patients with STS, 3 objective partial responses (one of whom received prior doxorubicin) are ongoing as well as 10 patients with stable disease (range 2-7 months). 1 patient had progressive disease at the first evaluation. 2 patients died within the first cycle, one due to progressive disease and the other due to sepsis. Conclusions: INNO-206 is an active drug for the treatment of patients with advanced STS who have failed prior chemotherapy. Cumulative doses of 2000 mg/m2 of doxorubicin equivalents have been achieved, which is over 3 1/2 x the peak cumulative dose of standard doxorubicin. Adverse events are primarily hematological and no cardiotoxicity has been observed.
Response to radiation therapy in solitary fibrous tumor/hemangiopericytoma.
Authors: Baldi Giacomo , Libertini Michela , Stacchiotti Silvia , Marrari Andrea , Palassini Elena , Bertulli Rossella , De Troia Beatrice , Gronchi Alessandro , Sangalli Claudia , Casali Paolo Giovanni 
Published: March 2020

10065 Background: To reporton the activity of radiotherapy (RT) in a retrospective series of solitary fibrous tumors (SFT)/hemagiopericytoma (HCP), a rare soft tissue sarcoma subtype whose sensitivity to RT is poorly known. Methods: We retrospectively reviewed all patients with a diagnosis of SFT/HCP whom we saw from 2005 to 2011, focusing on cases treated with RT in neoadjuvant, adjuvant, exclusive, palliative settings. Patients who received concomitant chemotherapy were excluded. We confirmed diagnosis by review in all cases. We evaluated the overall response rate (RR) by RECIST. Results: Nineteen patients were identified (males = 9, females = 10; median age = 61 years, range 39-85; site of primary= 6 meninges, 4 pleura, 3 pelvis, 3 retroperitoneum, 2 limbs, 1 abdominal wall; site of RT= 5 bone and soft tissue, 5 pelvis, 3 soft tissue, 2 meninges, 2 retroperitoneum, 1 abdominal wall, 1 pleura; reason for RT= 3 neoadjuvant, 2 adjuvant, 2 exclusive and 12 palliative setting). Median RT dose was 42 Gy (range 12-60). Seventeen of 19 pts are evaluable for response (2 adjuvant). The RR was: 29% (4 pts) partial response, 65% (12 pts) stable disease (SD), 6% (1 pt) progressive disease (PD). All patients treated with neoadjuvant RT had a RECIST SD as best response to pre-operative treatment with evidence of pathologic response in 2 of 3 cases. Conclusions: Contrary to what is widely thought,this retrospective analysis suggests that SFT/HCP is sensitive to radiation therapy. Prospective studies are needed.
Comparison of BRCA1/2-positive and -negative women diagnosed with metachronous breast and ovarian cancers.
Authors: Brandt Amanda C. , Elsayegh Nisreen , Lin Heather , Gutierrez-Barrera Angelica M. , Lu Karen H. , Arun Banu 
Published: March 2020

1546 Background: After a primary breast cancer (BC) or ovarian cancer (OC) diagnosis, women have a risk to develop a second primary cancer, significantly more so in women with a BRCA gene mutation. The objective was to evaluate characteristics of BRCA positive and negative women diagnosed with metachronous BC and OC. Methods: Women with metachronous BC and OC were identified at the University of Texas MD Anderson Cancer Center. BRCA test results, age at diagnosis of both BC and OC, first degree relatives (FDR) with BC and/or OC, total relatives affected, and histopathologic tumor features were obtained from a prospectively maintained research database. Univariate and logistical regression analyses were performed. Results: A total of 64 women with metachronous primary cancers underwent BRCA genetic testing. Of the 45 BRCA positive women, 36 (80%) were diagnosed with BC (mean 40 years) prior to OC and 9 (20%) were diagnosed with OC first (mean 47 years). Of the 19 BRCA negative women, 10 (53%) were diagnosed with BC first (mean 63 years), and 9 (47%) diagnosed with OC first (mean 48 years). Women diagnosed with BC first were more likely to be BRCA positive than women diagnosed with OC first (p=0.03). Patients with a FDR with BC were more likely BRCA positive than women without family history (p=0.0062). Patients with PR negative BR (p=0.0199) or triple negative (TN) BC (p=0.0139) were more likely to test BRCA positive. High grade ovarian carcinomas approached significance (p=0.053) in BRCA positive when compared to BRCA negative cohort. Ethnicity, total number of affected relatives with BC or OC, ER status, Her2 status, and nuclear grade were not statistically significant between the two groups. Conclusions: Women with OC preceding their BC with lack of family history of BC and OC are significantly less likely to test BRCA positive. BC is often the sentinel cancer in women with a BRCA mutation compared to BRCA negative women with metachronous BC and OC. This should be considered during the risk assessment to more accurately estimate the chance of identifying a BRCA mutation in women with metachronous BC and OC.
Retrospective analysis of glioblastoma patients treated with bevacizumab who presented with multifocal disease at diagnosis.
Authors: Hu Jethro Lisien , Nosova Kristin , Nuno Miriam , Yi Anthony , Elramsisy Adam , Mukherjee Debraj , Rudnick Jeremy , Phuphanich Surasak , Bannykh Serguei I. , Yu John , Black Keith L. , Patil Chirag 
Published: March 2020

2080 Background: Glioblastoma patients who present with multifocal disease have an extremely poor prognosis – a recent analysis at our institution demonstrated a median survival of 6 months, versus 11 months for a cohort of unifocal glioblastoma patients matched for age, extent of resection, and KPS. Bevacizumab is frequently used to treat patients with recurrent or progressive glioblastoma. However, its benefit in the setting of multifocal disease is unproven, particularly in light of the concern that antiangiogenic treatment may promote a more invasive, multifocal, and potentially treatment-resistant phenotype. Methods: Between 2004 to 2010, 368 patients were diagnosed with glioblastoma at our institution. We identified 46 patients with multifocal disease on initial presentation, and retrospectively reviewed their clinical course and treatment history. Kaplan-Meier estimates and Wilcoxon tests were used to assess survival distribution. Results: Of the 46 patients with multifocal disease, 12 were treated with bevacizumab (7 upfront and 5 at first recurrence). All 12 bevacizumab-treated patients received external beam radiation therapy, and 11 received temozolomide. In the bevacizumab-treated cohort, median age at the time of surgery was 59 years, and median KPS was 80. For the 34 patients with multifocal disease who did not receive bevacizumab, median age was 69 years, and median KPS was 75. Median survival for the bevacizumab-treated patients was 12.9 months, with 12-month survival of 58.3%. By comparison, median survival for patients with multifocal disease who did not receive bevacizumab was 5.8 months, with 12-month survival of 20.6%. The difference in survival between the two groups was statistically significant, with p-value of 0.045 by the Wilcoxon test. Conclusions: This single-institution retrospective analysis suggests that bevacizumab treatment is associated with a survival benefit for glioblastoma patients who present with multifocal disease. One can infer that the clinical benefit of bevacizumab in this setting outweighs any potential concerns regarding the ability of bevacizumab to promote an invasive, treatment-resistant tumor phenotype.
Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors.
Authors: Patnaik Amita , Kang Soonmo Peter , Tolcher Anthony W. , Rasco Drew Warren , Papadopoulos Kyriakos P. , Beeram Muralidhar , Drengler Ronald , Chen Cong , Smith Lon , Perez Crystal , Gergich Kevin , Lehnert Manfred 
Published: March 2020

2512 Background: Programmed death-1 (PD-1) is an inhibitory T-cell coreceptor that may lead to suppression of antitumor immunity. MK-3475 is a humanized monoclonal IgG4 antibody against PD-1. Preclinically, MK-3475 has shown antitumor activity in multiple tumor types. This first-in-human phase I trial explored safety, PK, PD, and antitumor activity of MK-3475. Methods: An open-label, dose escalation study was conducted in patients with advanced malignancy refractory to standard therapy. Cohorts of 3-6 patients were enrolled (3+3 design) at escalating IV doses of 1, 3, and 10 mg/kg. Following an initial dose and 28-day Cycle 1, patients were allowed to subsequently receive multiple doses given every 2 wks. Radiographic assessment was conducted every 8 wks using RECIST 1.1 guidelines. Results: Nine patients, 3 at each dose level, completed the dose-limiting toxicity (DLT) period (28 d). Patients had non–small cell lung cancer (NSCLC, n=3), rectal cancer (n=2), melanoma (MEL, n=2), sarcoma (n=1), or carcinoid (n=1). To date, a total of 63 doses were administered (median 7/patient; max 12) without DLT. Drug-related adverse events (AEs) across all doses included Grade 1 fatigue (n=3), nausea (n=2), diarrhea (n=1), dysgeusia (n=1), breast pain (n=1), and pruritus (n=1). One drug-related Grade 2 AE of pruritus was reported. No drug-related AEs ≥ Grade 3 were observed. PK data are shown in the table. Based on RECIST, 1 patient with MEL on therapy >6 mths had a partial response, and preliminary evidence of tumor size reduction (stable disease) was observed in 3 additional patients with advanced cancer. Conclusions: MK-3475 was well-tolerated without DLT across 3 tested dose levels. Evidence of antitumor activity was observed. Enrollment continues to obtain additional safety, PK, and efficacy data; updated data will be presented at the meeting. [Table: see text]
Technetium-99m sulfur colloid (TSC) as a phenotypic probe for predicting pharmacokinetics (PK) and palmar-plantar erythrodysesthesia (PPE) toxicity of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).
Authors: Giovinazzo Hugh , Kumar Parag , Sheikh Arif , Ivanovic Marija , Walsh Mark Doughty , Caron Whitney Paige , Song Gina , Whitlow Ann B. , Newman Suzanne E. , La-Beck Ninh My , Kowalsky Richard J. , Zamboni Beth A. , Clarke-Pearson Daniel L. , Brewster Wendy R. , Van Le Linda , Bae-Jump Victoria Lin , Gehrig Paola A. , Zamboni William 
Published: March 2020

5050 Background: There is significant variability in the PK and PD (efficacy and toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur primarily via uptake by cells of the mononuclear phagocyte system (MPS) mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PPE toxicity in pts (n=9) with EOC. Methods: Prior to administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IVP × 1. Dynamic planar and SPECT/CT images of the liver, spleen and hands were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 3 h. Serial PK samples were obtained from 0h to 672h post PLD dose. Plasma was processed to measure encapsulated and released doxorubicin (dox) using solid phase separation and HPLC. CL of PLD and TSC were calculated by non-compartmental analysis. The grade of PPE toxicity was determined by NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC imaging and eight patients completed TSC blood PK and PLD plasma PK studies. There was a positive linear relationship between TSC CL and encapsulated dox CL (R2 = 0.61, p=0.02). When patients were subdivided, there was a stronger relationship between TSC CL and encapsulated dox CL (R2 = 0.81, p=0.03) in pts receiving PLD monotherapy. A positive relationship using Spearman’s correlation (ρ=0.84, p=0.006) was also found between maximum grade PPE toxicity developed and estimated AUC of encapsulated dox in hands [(TSC AUCBlood)/(TSC AUCHand)*Encapsulated Dox AUCPlasma]. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and PD and may be used to individualize PLD therapy in pts with EOC. In addition, our findings suggest TSC may be able to predict the development of PPE in patients.
The PARADIGM trial: A phase III study comparing sequential therapy (ST) to concurrent chemoradiotherapy (CRT) in locally advanced head and neck cancer (LANHC).
Authors: Haddad Robert I. , Rabinowits Guilherme , Tishler Roy B. , Adkins Douglas , Khuri Fadlo Raja , Clark Joseph , Lorch Jochen H. , Limaye Sewanti Atul , Wirth Lori J. , O'Neill Anne , Riley Sarah , Posner Marshall R. 
Published: March 2020

5501 Background: PARADIGM is a multicenter phase III study comparing TPF (docetaxel, cisplatin, and 5-fluorouracil)-based ST (Arm A) to upfront cisplatin CRT (Arm B) in patients (pts) with LAHNC. Pt accrual was terminated in 12/2008 due to slow enrollment with 145 of 300 planned analyzable patients accrued. Safety data was previously presented at the 2010 ASCO annual meeting showing no unusual pattern of toxicities in either arm. Here we present the survival results. Methods: Pts were randomized to receive arm A-ST (as induction chemotherapy (ICT) with TPF x 3) followed by CRT with either weekly carboplatin and once daily radiotherapy, or weekly docetaxel and accelerated boost radiotherapy based on adequate response to ICT; or arm B - accelerated boost CRT with bolus cisplatin x 2. The primary endpoint was survival. With original accrual target of 300 analyzable patients, this study was powered at 80% to detect an improvement in 3-year survival from 55% (arm B) to 70% (arm A). Results: A total of 145 previously untreated pts were enrolled (Arm A: 70; Arm B: 75), of whom 127 were male and 127 were Caucasian. Median age was 55; patients had PS of 0 (97) or 1 (48). Sites of disease were oropharynx: 80, larynx: 24, hypopharynx: 15, and oral cavity: 26. Disease stages were II (1 pt), III (20 pts) and IV (124 pts). After a median follow-up of 49 months, 41 pts have died (20 in arm A and 21 in arm B). Three-year survival was 73% (arm A) and 78% (arm B) (HR1.09; 95% CI 0.59 to 2.03 p=0.77). Three-year progression-free survival was 67% (arm A) and 73% (arm B) (HR 1.2; 95% CI 0.65 to 2.22; p=0.55). Patterns of failure will be presented at the meeting. Conclusions: Althoughthese results suggest no survival differences between CRT and ST for patients with LAHNC, the study was terminated before the planned accrual could be reached. HPV status for the oropharynx cases which represented the majority of patients was not available for stratification; and excellent survival was seen in both arms.