tbuckley/cabot-search huggingface dataset:
A reduced pazopanib dose with food: Is it more patient-friendly and does it reduce drug costs?
Authors: Floor Lubberman, Hans Gelderblom, Paul Hamberg, Walter Vervenne, Sasja F. Mulder, Frank Jansman, Angela Colbers, Winette T.A. Van Der Graaf, David Burger, Saskia Luelmo, Dirk Jan A.R. Moes, Carla M.L.- Van Herpen, Nielka P. Van Erp
Journal: Journal of Clinical Oncology (2019)

4564 Background: Pazopanib has been licensed for advanced soft tissue sarcoma and metastatic renal cell carcinoma in a fixed oral daily dose of 800mg taken fasted. We hypothesized that ingesting pazopanib with food may improve patients’ comfort and reduce gastro-intestinal adverse events. Moreover, a food intervention, resulting in a better absorption, can lead to a lower dose, which could significantly reduce treatment costs. Methods: Part 1 of the study was performed to determine whether 600mg pazopanib taken with a continental breakfast was bioequivalent to 800mg pazopanib taken fasted. In part 2, differences in GI-toxicity and patient satisfaction were assessed by the cancer-therapy-satisfaction-questionnaire after both intake regimens. Finally, patient’s preference for either intake regimen was asked. Results: 16 patients were included in the bioequivalence study. The geometric mean ratio (fed/fasted) of the area under the plasma concentration time curve was 1.10 (90% CI 1.00-1.19), maximum peak concentration was 1.12 (90% CI 1.02-1.22) and pazopanib trough concentration was 1.10 (90% CI 1.02-1.18). In part 2, 60 patients were included. No differences were seen in the occurrence of GI-toxicities under both intake regimens. Patients seem to be more positive about their feelings about side effects (72.3(95% CI 68.1-76.5) vs 68·2 (62.7-73.6); p=.092) and satisfaction with therapy scores were higher (84.7(95% CI 81.4-87.9) vs 81.9 (78.7-85.2); p= .059) when pazopanib was taken with food. 41 (68%) of the patients preferred the intake with continental breakfast. Conclusions: Intake of 600mg pazopanib with food results in bioequivalent exposure and was preferred over a standard pazopanib dose without food. Moreover, with this simple food intervention a large cost reduction can be realized in patients treated with pazopanib. Clinical trial information: NCT02138526.
EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors.
Authors: Carol Gergis, Deepa Rangachari, Masanori Fujii, Andreas Varkaris, Paul A VanderLaan, Susumu Kobayashi, Daniel Botelho Costa
Journal: Journal of Clinical Oncology (2019)

e20593 Background: The epidermal growth factor receptor (EGFR)-A763_Y764insFQEA mutation is a unique exon 20 insertion mutation (accounting for ~10-20% of all EGFR exon 20 insertions) that more closely resembles EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants (i.e. EGFR-exon 19 deletions and L858R) at the structural and enzymatic level as compared to other non-classical mutations. A limited number of preclinical models and clinical reports have detailed the response of EGFR-A763_Y764insFQEA-driven lung tumors to approved or in-development TKIs. Methods: Multiple preclinical models of EGFR-A763_Y764insFQEA and more typical EGFR exon 20 insertion mutations were used to probe representative 1 st generation (gefitinib, erlotinib), 2 nd generation (afatinib, dacomitinib), 3 rd generation (osimertinib), and in-development EGFR exon 20 specific (poziotinib, others) TKIs. Clinical outcomes and prior reports of EGFR-A763_Y764insFQEA mutated lung adenocarcinomas treated with EGFR TKIs were compiled. Results: Cell lines driven by EGFR-A763_Y764insFQEA were consistently sensitive to 1 st , 2 nd and 3 rd generation EGFR TKIs, while models driven by other EGFR exon 20 insertions (i.e. D770_N771insSVD and H773_V774insH) were only inhibited by in-development EGFR TKIs and at doses below those affecting the wild-type receptor. The majority of patients with lung cancers harboring EGFR-A763_Y764insFQEA responded to clinical doses of 1 st , 2 nd , and 3 rd generation EGFR TKIs; and lung cancers with these mutants are currently enrolled in clinical trials of in-development EGFR exon 20 specific TKIs. Conclusions: This is the largest report to confirm that the EGFR-A763_Y764insFQEA mutation is a unique exon 20 insertion mutation sensitive to 1 st , 2 nd , 3 rd generation and in-development EGFR exon 20 specific TKIs. Mechanisms of acquired resistance of this mutant to different EGFR TKIs remain unreported.
Pancreatic cancer: Assessment of neoadjuvant chemotherapy outcome based on radiomics of pretreatment computed tomography.
Authors: Xiang Li, Tianyu Tang, Xueli Bai, Tingbo Liang
Journal: Journal of Clinical Oncology (2019)

e15767 Background: The objective response rate to neoadjuvant chemotherapy (NAC) was limited to around 35% in pancreatic cancer and as more as 30% patients show no benefit to NAC. In this instance, predicting the response to NAC may play an important role in individual treatment for pancreatic cancer patients. We aim to evaluate contrast enhanced-computed tomography (CE-CT) features in predicting treatment response and survival after neoadjuvant chemotherapy (NAC) for patients with borderline resectable and locally advanced pancreatic cancer. Methods: Sixty-one pancreatic cancer patients receiving NAC were enrolled and underwent abdominal CE-CT before treatment. All patients were divided into groups according to the changes of tumor size after treatment. 396 radiomics features were extracted from three-dimensional ROIs (region of interest) based on pretreatment CE-CT images of each patient. The optimal features were selected and three supervised machine learning classifiers were developed. Finally, univariate and multivariate analyses were performed to evaluate the capability of the selected features in predicting histopathologic response and outcomes. Results: Nine, seven and five radiomics features were selected as optimal features for three experiments respectively. Two features, Haralick Entropy and Histogram Entropy, were found consistent in experiments and were both higher in patients with tumor enlargement. Moreover, lower Histogram Entropy was significantly associated with a better histopathologic response (p = 0.008) and smaller tumor size (p = 0.041) in patients with tumor resection. In univariate Cox regression analysis, lower Histogram Entropy (P = 0.006) and lower Haralick Entropy (P = 0.001) predicted a better prognosis. Meanwhile, lower Haralick Entropy (p = 0.048) was independent predictor for longer survival time in multivariate Cox regression analysis. Conclusions: Radiomics features are strongly correlated with NAC treatment response and prognosis in pancreatic cancer, suggesting the great potential of imaging radiomics to help tailoring the treatment into the era of personalized medicine
Temporal trend of microbiological profiles among patients with bloodstream infections: A comparison between cancer and noncancer patients in a nationwide database.
Authors: Ronan Wenhan Hsieh, Gregory M Schrank, Wan-Ting Hsu, Ke-Ying Su, Chien-Chang Lee
Journal: Journal of Clinical Oncology (2019)

e13078 Background: Bloodstream infection (BSI) is a leading cause of in-hospital mortality for cancer patients. Our goal is to describe the temporal trend of microbiological profiles and inpatient outcomes through a large national database. Methods: National Inpatient Sample is the largest U.S. database of hospitalized patients including 20% of patients from 4,378 hospitals. Hospitalizations of patients with BSI were identified by ICD-9 codes for bacteremia and fungemia from 2006-2014. 21 common microorganisms were identified by ICD-9-CM codes as the cause of BSI. We assessed the trend of incidence and mortality by linear regression and compared the in-hospital mortality between cancer and noncancer BSI patients by propensity score adjusted Cox proportional hazard model. Results: A total of 13,996,374 patients with BSI were identified (cancer 13.6%, noncancer 86.4%). Among cancer patients, gram positive bacteria (GPB) are the leading pathogens (27.38%), followed by gram negative bacteria (GNB) (23.59%), fungus (4.81%) and anaerobe (1.21%). Anaerobe had the fastest annual increase rate of incidence (16.54%), followed by GNB (15.77%), fungus (11.61%) and GPB (7.41%). Cancer patients had a faster increase rate of incidence than noncancer patients. The in-hospital mortality was highest for anaerobe (16.14%), followed by fungus (15.71%), GPB (13.65%) and GNB (12.14%). Except for fungal BSI, the mortality for other types of BSI decreased significantly. GNB had the most annual mortality decrease (-2.51%), followed by GPB (-2.48%) and anaerobe (-1.47%). Cancer patients had higher in-hospital mortality than noncancer patients (PS-matched HR 1.25, 95%CI: 1.24, 1.26), especially in GNB BSI (PS-matched HR 1.29, 95%CI: 1.27, 1.31). Using breast cancer patients as reference, lung cancer BSI patients had the worst relative mortality risk (1.65, 95%CI: 1.60, 1.69). Conclusions: The incidence of BSI increased steadily among cancer patients from 2006-2014, with GNB BSI increasing at the highest rate. Except for fungus, mortality of GNB, GPB and anaerobe decreased continually. Compared with noncancer patients, cancer patients had a larger increase in the incidence of all types of BSI, especially anaerobes, and higher mortality than noncancer patients. BSI in lung cancer patients was associated with the highest mortality rate.
Evaluation of prognostic factors after esophagectomy in which preoperative chemotherapy was successful.
Authors: Takashi Ogata, Yota Shimoda, Shinsuke Nagasawa, Masato Nakazono, Kentaro Hara, Yuta Kumazu, Tsutomu Hayashi, Takanobu Yamada, Takashi Oshima
Journal: Journal of Clinical Oncology (2019)

e15568 Background: Current standard treatment for Stage IB/II/III Japanese squamous cell carcinoma of the esophagus is esophagectomy after two courses preoperative chemotherapy with 5-FU/CDDP. Prognosis of cases in which preoperative chemotherapy was successful is usually good, but some cases were recurrence. On the other hand, some reports showed that the negative survival impact of infectious complications after esophagectomy is canceled out by succeeding preoperative chemotherapy. So we evaluate of prognostic factors after esophagectomy in which preoperative chemotherapy was successful. Methods: Between 2011 and 2015, 122 cases were performed esophagectomy after two courses of preoperative chemotherapy using 5-FU/CDDP for stage IB / II / III esophageal cancer, and 46 cases were achieved Grade 2 histopathological effect(2/3 or more disappearance of tumor). We examined 3-year survival rate and 3-year RFS in this 46 cases and examined what could be a prognostic factor. PS, ASA, sex, operation time, volume of bleeding , postoperative complications(C-D classification≧G2), pT, pN, tumor wall retentivity, preoperative nutritional status(Albumin, CRP, Prealbumin, RBP), nutritional indicators at discharge (weight change rate, fat mass change rate, muscle mass change rate) were evaluated as recurrence prediction factor. Results: 3-year OS of histological Grade2 cases were 84.5%, and 3 -year RFS were 88.8%. In 46 cases, relapse was found in 12 cases, and univariate analysis showed pT, pN as a risk of relapse, and multivariate analysis showed only pT as a risk of relapse. There were 5 cases of recurrence within 1 year after esophagectomy, and there was a significantly poor prognosis compared with recurrent cases later than 1 year after esophagectomy. Conclusions: The risk factor of recurrence in patients with squamous cell carcinoma after preoperative chemotherapy followed by esophagectomy was pathological T factor, and recurrent case within 1 year after esophagectomy was significantly poor prognosis.
Pretreatment obesity prolongs survival in elderly patients (≥65 years) with head and neck cancer (HNC).
Authors: Parth Anil Desai, Sushanth Kakarla, Annapurna Saksena, Byeongyeob Choi, Martin Goros, Frank R. Miller, Anand B. Karnad, Sherri Rauenzahn Cervantez
Journal: Journal of Clinical Oncology (2019)

6052 Background: Pre-treatment Body mass Index (BMI) is an important prognostic factor in HNC with variable survival benefit reported till date. Despite increasing incidence of HNC in geriatric patients there is limited information on prognostic variables in this group. Methods: This is a single center, retrospective cohort study of patients with HNC≥65 years of age at their diagnosis from 2012 to 2016. Patients were stratified by BMI (Class 1- BMI&lt;25 kg/m 2 (underweight &amp; normal), Class 2- BMI≥25-29.9 kg/m 2 (overweight), Class 3- BMI≥30 kg/m 2 (obese) ). Various variables were collected &amp; appropriate statistical analysis was done. Results: 188 elderly HNC patients with non-metastatic disease were stratified into three BMI groups (Table) &amp; found to have evenly distributed co-variates. The Median OS was significantly higher in class 3 patients (53 months) compared to class 1 (21 months) (p =0.02). In multivariate analysis, class 3 was an independent good prognostic indicator (Hazard ratio=0.44;Range-0.21-0.90, p=0.03). Stage, CCI score &amp; gastrostomy tube were adverse prognostic factors in the study. Conclusions: Obese elderly HNC patients have survival benefit over normal/underweight patients. Predictive prognostic models incorporating BMI with other prognostic factors are needed to determine appropriate management in these patients. [Table: see text]
Changes in KRAS mutations in patients with oral mucosa and tongue cancer (OMTC) undergoing medical treatment with cetuximab (Cet).
Authors: Aza A. Lyanova, Oleg I. Kit, Yaroslav S. Enin, Natalya N. Timoshkina, Marina A. Engibaryan, Irina V. Aedinova, Viktoriya L. Volkova, Mamuka V. Bauzhadze, Natalia A. Chertova, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2019)

e17524 Background: Mutations in KRAS are known to be predictors of anti-EGFR therapy efficacy. Besides the mutation status of the treatment-naive tumors the changes in the level of mutant DNA during medical treatment are also of clinical interest for the individualization of the treatment. The purpose of the study was to detect somatic single nucleotide polymorphism (SNP) activating mutations in KRAS exon 2 in patients (pts) with OMTC undergoing chemotherapy (CT)±Cetuximab (Cet). Methods: Extracellular DNA samples were obtained from plasma of pts with OMTC (T3-4No-1Mo) undergoing CT (CDDP+5FU)+Cet (group A) before treatment and in 2 weeks after. Patients undergoing CT (CDDP+5FU, no Cet) were included in Group B. 7 activating mutations in KRAS exon 2 were detected by Droplet Digital PCR method (DD PCR) with "KRAS Screening Multiplex Kit" (BioRad, USA). Results: Samples from 28 pts were included. The frequency of SNP activating in KRAS exon 2 before treatment was 25%. In the group A (n = 12) KRAS mutations were not found or the level of mutant DNA did not exceed 1%. No significant changes were found in this group after treatment. The group B (n = 16) had some KRAS variations the majority of which did not change after treatment. However, 2 pts had a sharp increase in mutant DNA: from 0.03% before CT in both cases to 17.04% and 56.38% -after treatment (p &lt; 0.01). Conclusions: Medical treatment, especially CT, could cause the changes in activating mutations in KRAS exon 2 in pts with OMTC. Revealing of these changes is of great importance for the following treatment options. Detection of mutant extracellular DNA by DD PCR could be valuable to monitor their status during the treatment.
A phase III trial-in-progress comparing tislelizumab plus chemotherapy with placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Rui-hua Xu, Hendrik-Tobias Arkenau, Yung-Jue Bang, Crystal S. Denlinger, Ken Kato, Josep Tabernero, Jin Wang, Jiang Li, Henry Castro, Markus Hermann Moehler
Journal: Journal of Clinical Oncology (2019)

TPS2655 Background: In patients (pts) with locally advanced or metastatic G/GEJ cancer, fluoropyrimidine- and platinum (plt)-based combination chemotherapy is first-line standard of care. Despite improvement in chemotherapy regimens, outcomes are poor and survival remains low. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports suggested tislelizumab, as a single agent and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with advanced solid tumors, including G/GEJ cancer. Methods: This global, double-blind, randomized, phase 3 study (NCT03777657) is designed to compare plt/fluoropyrimidine + tislelizumab versus plt/fluoropyrimidine + placebo as first-line therapy for pts with locally advanced or metastatic G/GEJ cancer. Approximately 720 pts from 160 centers will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with chemotherapy. Oxaliplatin (130 mg/m² IV Q3W) plus capecitabine (1000 mg/m 2 orally twice daily for 2 weeks) or cisplatin (80 mg/m² IV Q3W) plus 5-fluorouracil (800 mg/m 2 /day IV on Days 1–5 Q3W) will be used as backbone chemotherapy on an individual basis. Chemotherapy will be administered for up to 6 cycles; capecitabine maintenance therapy is optional for pts who received capecitabine and oxaliplatin. PD-L1 expression will be assessed using the VENTANA PD-L1 (SP263) assay. Progression-free survival and overall survival are primary endpoints in the intent-to-treat and PD-L1-positive analysis sets of the study. Secondary endpoints include overall response rate, duration of response, quality-of-life outcomes, and the safety/tolerability profile of combination therapy. Exploratory endpoints include disease control rate, time to response, and an analysis of potential predictive biomarkers including, but not limited to, PD-L1 expression. Clinical trial information: NCT03777657.
Assessment of a highly curated somatic oncology mutation database to facilitate identification of clinically important variants in NGS results.
Authors: Xiaoju Max Ma, Stephanie J. Yaung, Liu Xi, Christine Ju, John F. Palma, Maximilian Schmid
Journal: Journal of Clinical Oncology (2019)

e18086 Background: The increasing adoption of Next Generation Sequencing (NGS) in molecular profiling of cancer presents a growing need for streamlined interpretation of NGS results in clinical labs. This can be achieved through bioinformatics tools equipped with a highly-curated database on clinically important variants. Methods: We performed an initial assessment of an NGS result interpretation tool called NAVIFY Mutation Profiler (NMP), which enabled us to process a Variant Call Format (VCF) file and generate a report with consensus recommendations of NCCN, ASCO, CAP and ACMG. This annotation tool identifies pathogenic variants and variants of unknown clinical significance (VUS), and groups variants by AMP Tiers. At the time of this assessment, NMP contained curation for ~4,000 variants. In this study, we used NGS results from 38 anonymized clinical cases with known treatment regimens to retrospectively assess NMP as the variant interpretation tool. Our cohort contained lung cancer subjects treated with EGFR tyrosine kinase inhibitor (TKI) (5 cases), as well as subjects relapsed against EGFR TKI (1 case) or ALK TKI crizotinib (22 cases). We also included 10 control cases where standard of care chemo was used because initial diagnostic methods did not reveal any actionable targets. Results: NMP annotated NGS VCF data and generated a report within 10 minutes per case although some cases contained &gt; 100 variants. NMP correctly associated EGFR TKI therapies options with the corresponding 5 cases. As expected, NMP did not recommend targeted therapies for the 10 chemo-treated control cases. For the subject relapsed against EGFR TKI, NMP correctly interpreted the complex EGFR mutation profile containing both activating (L858R) and drug-resistance (T790M) variants. In addition, out of 22 cases relapsed against ALK TKI crizotinib, NMP correctly marked 14 with crizotinib resistance when a known ALK variant conferring crizotinib resistance was detected. There was limited or no published clinical evidence to interpret the remaining 8 cases of ALK TKI resistance. Conclusions: NMP correctly interpreted cases containing EGFR and ALK variants in this study. With a highly-curated knowledge base, this tool simplifies NGS clinical reporting by identifying clinically actionable mutations and associating treatment options qualified by supporting clinical evidence.
Idiopathic Edema
Authors: S. Richardson Hill, W. Guy Hood, T. Albert Farmer, John F. Burnum
Journal: New England Journal of Medicine (1960)

PATIENTS with edema and without evidence of cardiovascular, renal, hepatic or neurologic disease present a frequent diagnostic and therapeutic problem. These cases have been classified in a large and probably heterogeneous group known as "idiopathic edema." The patients are usually females who are under some stress, who tend to be emotionally unstable and who, not infrequently, have a history of renal and peptic-ulcer disease in the past. Their edema may fluctuate with environmental factors, fatigue or emotional reactions, and is frequently associated with headaches. Although a premenstrual exacerbation of symptoms may be noted there is generally no consistent correlation between . . .
Clinicopathological description of a subset of schistosoma mansoni associated colorectal cancer patients in an endemic area in Brazil.
Authors: Gustavo Fernandes Godoy Almeida, Mauricio Assuero Lima de Freitas, Mariana M M Lira, Ana Lucia Coutinho Domingues, Lais Neares, Lauro Vinicius Machado da Silva, Maxwell Moura, Marcelo Maior, Luiz Alberto Reis Mattos
Journal: Journal of Clinical Oncology (2019)

e15154 Background: Schistosoma have been implicated in colorectal carcinogenesis. We aim to describe clinicopathological description of a subset of Schistosoma mansoni-associated colorectal cancer patients in an endemic area in Brazil. Methods: We have performed a survey at cancer registry and identified those colorectal cancer patients who underwent biopsy and/or surgery in our institution in the last 10 years. We performed a comparison between Schistosoma- and non-Schistosoma colorectal cancer patients. T-test were performed to compare clinico-pathological features. Results: 300 hundred patients were identified. From this population, 83 patients had encounters at gastroenterology unit, where schistosoma patients (among those with other diseases) are treated. Among them, 7 patients presented both conditions (colorectal cancer and schistosomiasis), corresponding to 8.4% of these selected population. We identified diferences among Schistosoma- and non-Schistosoma colorectal patients neither in age of cancer diagnosis nor in terms of laterality. We did not find diferences in terms of metastatic disease rate between both populations, however, we have observed a higher incidence of limph node metastasis among Schistosoma colorectal patients. Conclusions: Schistosoma colorectal patients present similarity in terms of age of cancer diagnosis and laterality when compared to non-Schistosoma colorectal patients, however, lymph node metastasis are increased in this population. Next publications from our group will provide information about survival curves and genetic profile.