tbuckley/cabot-search huggingface dataset:
Prevalence of sentinel lymph node evaluation in patients with thick primary cutaneous melanoma.
Authors: Abimbola O Olusanya, Dhruvil R Shah, Anthony D Yang, Emanual Maverakis, Robert J. Canter, Steve R. Martinez
Journal: Journal of Clinical Oncology (2012)

e19013 Background: Sentinel lymph node biopsy (SLNB) was developed for intermediate thickness melanoma. Its use for thick cutaneous melanoma is controversial. We aimed to report on clinical and pathologic factors associated with the overuse of SLNB for thick primary cutaneous melanoma. Methods: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for thick primary cutaneous melanoma (known Breslow thickness &gt; 4.00 mm) from 2004 to 2008. We excluded patients with mucosal melanoma, those without a biopsy-proven diagnosis, those diagnosed at autopsy, patients whose lymph node evaluation was unknown or other than SLNB “yes” or SLNB “no”. We used multivariate logistic regression models to predict use of SLNB. Covariates examined included: age sex, race/ethnicity, Breslow depth, tumor histology, tumor location, and ulceration status. Likelihood of undergoing sentinel lymph node biopsy was reported as odds ratios (OR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. Results: Among 1,981 patients with thick cutaneous melanoma, 1,158 (58.2%) received a SLNB. On multivariate analysis, patients with primary melanomas of the arm (OR 2.07, CI 1.56-2.75; p&lt;0.001), leg (OR 2.40, CI 1.70-3.40; p&lt;0.001) and trunk (OR 1.82, CI 1.38-2.40; p&lt;0.001) had an increased likelihood of receiving a SLNB, as did those with desmoplastic histology (OR 1.47, CI 1.11-1.96; p=0.008). Conclusions: A significant number of patients with thick melanomas receive a SLNB, even though this procedure was not developed for this patient population. We have identified predictors associated with the use of SLNB. These include: arm, leg and trunk primary sites and desmoplastic histology. Further research to assess whether use of SLNB in this population is detrimental or beneficial is needed.
Tumor-related and treatment-related colostomy-free survival (CFS) following chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance 5FU/CisP chemotherapy (CT) in squamous cell carcinoma of the anus (SCCA): Results of ACT II.
Authors: Robert Glynne-Jones, Latha Kadalayil, Helen Meadows, David Cunningham, Leslie M. Samuel, Ian Geh, Charles Lowdell, Roger David James, Sandy Beare, Rubina Begum, Jonathan A. Ledermann, David Sebag-Montefiore
Journal: Journal of Clinical Oncology (2013)

3532 Background: Concurrent CRT is standard treatment for patients (pts) with SCCA. We explore tumor- and treatment-related CFS in a phase III trial (ACT II), which mandated standardised radiation fields and a uniform dose (50.4Gy in 28 daily fractions of 1.8Gy). Methods: The ACT II trial (940 pts) compared both CisP (n=468) versus MMC (n=472) combined with 5-FU/CRT, and 2 cycles of maintenance CT (Maint, n=448) versus none (No-maint, n=446). We investigated the association between CFS and baseline factors (age, sex, T stage, size of tumour, nodal status) and treatment using Cox regression. CFS events included baseline colostomies not reversed at first follow up after treatment and post-treatment colostomies. Results: Median follow-up (all pts) was 5.1 years. Median age: 58 years; tumour site – canal (84%), margin (14%); stage T1-T2 (52%), T3-T4 (46%); N+ (32%), N0 (62%). Of 884 evaluable patients only 20/118 (17%) baseline colostomies were reversed within 8 months, and 37 later. 112 pts had a post-treatment colostomy due to persistent disease (98) or morbidity (14). The 5-year CFS rates by stage were 86% T1, 77% T2, 57% T3 and 47% T4; 72% N0, 60% N+; by treatment arm 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint respectively. The 5-year CFS rates were 72% and 60% for N0 and N+ respectively. The most significant predictors of colostomy in multivariable Cox regression analyses were T stage, sex and baseline haemoglobin (p&lt;0.001 for all). Men were more at risk than women (adjusted HR 1.64; 95% CI: 1.26, 2.14). Age, site of primary or treatment did not impact on CFS. Although significant in univariate analysis, nodal status did not influence CFS when adjusted for other baseline factors. Conclusions: In the largest trial in anal cancer, neither the type of CRT (5FU/CisP vs. 5FU/MMC) nor maintenance chemotherapy improved CFS. 34% (61/177) of all colostomies were baseline fashioned prior to treatment and never reversed after all treatments. The major predictive factors for CFS were T stage, sex and haemoglobin levels. Clinical trial information: NCT00025090.
Graphene Multielectrode Arrays as a Versatile Tool for Extracellular Measurements
Authors: Dmitry Kireev, Silke Seyock, Johannes Lewen, Vanessa Maybeck, Bernhard Wolfrum, Andreas Offenhäusser
Journal: Advanced Healthcare Materials (2017)

Graphene multielectrode arrays (GMEAs) presented in this work are used for cardio and neuronal extracellular recordings. The advantages of the graphene as a part of the multielectrode arrays are numerous: from a general flexibility and biocompatibility to the unique electronic properties of graphene. The devices used for extensive in vitro studies of a cardiac‐like cell line and cortical neuronal networks show excellent ability to extracellularly detect action potentials with signal to noise ratios in the range of 45 ± 22 for HL‐1 cells and 48 ± 26 for spontaneous bursting/spiking neuronal activity. Complex neuronal bursting activity patterns as well as a variety of characteristic shapes of HL‐1 action potentials are recorded with the GMEAs. This paper illustrates that the potential applications of the GMEAs in biological and medical research are still numerous and diverse.
Prevalence of asymptomatic submicroscopic malaria in eastern Indonesia: a cross sectional survey and spatial analysis
Authors: Jontari Hutagalung
Journal: The Lancet Global Health (2017)

BackgroundIn 2013 in Indonesia, 4·8 million people were infected with malaria, and 23 483 malaria-related deaths were reported. Most infections were reported in eastern Indonesia, with two dominant species of malarial parasite: Plasmodium falciparum(62%) and P vivax (33%). Annual parasite incidence was 15·6 per 1000 population. In 2016, the Indonesian Ministry of Health announced that Indonesia would reach the WHO-defined pre-elimination stage for malaria by 2020, and be free of malaria transmission by 2030. Unfortunately, real data on incidence, surveillance, and mapping of malaria cases is scarce. This study will assess whether East Nusa Tenggara Province in eastern Indonesia should proceed with the malaria pre-elimination stage activities.MethodsWe did a survey of 555 people who were systematically selected from five districts in eastern Indonesia. We included healthy participants aged 14 years and older who had a blood haemoglobin concentration ≥100 g/L. We recorded baseline characteristics and risk factors for malaria infection via a standardised questionnaire, and blood samples were taken for analysis. All participants were examined by a local medical doctor. A malaria case was defined as the presence of Plasmodium spp in blood detected with nested PCR (nPCR) or microscopy. Data were collected by standard questionnaire, physical examination and laboratory tests (haemoglobin concentration measurements, microscopic analysis, and nPCR). We mapped nPCR-confirmed cases of malaria using ArcGIS 9.1 spatial and SaTScan analysis. We used univariate and bivariate statistical analysis for statistical analysis.FindingsBetween August, 2013, and September, 2014, we included 555 samples in our survey. 181 (32·6%) samples tested positive for malaria with n-PCR: only nine (1·6%) of these cases were detected by microscopy. P vivax was the most common Plasmodium spp detected (94 cases [51·9%]). Not using bednets was the most important risk factors for malaria in our population (OR 2·34, 95% CI 1·98–4·83); fever, which is the most commonly presented symptom, was noted in only five cases (0·9%). Results of spatial analysis showed three distinct and significant clusters: 13 cases (7·2%, p=0·0041), 54 cases (29·9%, p=0·0025), and 87 cases (48·1%, p=0·001). However, all malaria clusters were in areas of low malaria incidence.InterpretationA malaria pre-elimination programme in eastern Indonesia should be delayed. Routine treatment to stop silent transmission of malaria, and improved laboratory surveillance, are needed.FundingAsia Pacific Malaria Elimination Network (APMEN) Project number 103-02 as part of the APMEN Country Partner Technical Development Program Round-X. Major funding for APMEN is provided by Australian Government Department of Foreign Affair and Trade, alongside funds received from Bill and Melinda Gates Foundation.
Phase II study of oxaliplatin (OXA) and docetaxel (DTX) in recurrent platinum-sensitive ovarian cancer
Authors: G. Ferrandina, M. Ludovisi, G. Dagostino, D. Lorusso, A. Naldini, A. C. Testa, I. Paris, V. Gallotta, C. Pozzo, G. Scambia
Journal: Journal of Clinical Oncology (2004)

5078 Background: We conducted a phase II study in order to evaluate the efficacy and safety of the combination of OXA and DTX in recurrent platinum-sensitive ovarian cancer patients. Methods: Patients received DTX 75 mg/m2 (60-min i.v.) on day 1, followed by OXA 100 mg/ m2 (120-min i.v.) on day 1 every 21 days. Results: Between October 2002 and December 2003, 14 Caucasian patients (median age: 55.5 yrs; range, 39–68) were enrolled. At first diagnosis 1 (7.1%) patient had FIGO stage I ovarian cancer, 12 (85.8%) had FIGO stage III and 1 (7.1%) had FIGO stage IV disease. Sites of relapse were as follows: liver/spleen = 3 cases (21.4%), pelvis = 3 cases (21.4%), lymphnodes = 4 cases (28.6%), peritoneal = 3 cases (21.4%) and multiple sites = 1 case (7.2%). The median platinum-free-interval was 23.5 months (range 13–58). At recurrence the median CA125 was 324.5 U/ml (range 21–5596 U/ml). Of the 13 patients evaluable, 4 (30.8%) had complete response and 3 (23.1%) had partial response to OXA/DTX with an overall response rate of 53.9%. The median time to response was 10 wks (range 5–32) and the median duration of response was 16 wks (range 6–31). Five (38.5%) patients had stable disease (median duration of stabilization: 21 wks, range 12–40). One (7.7%) patient progressed while on treatment. Therefore, an overall clinical benefit was observed in 92.3% of patients. All patients were evaluable for toxicity. A total of 81 courses were given, with a median of 5.5 cycles per patient (range 1–10). Severe toxicities (Grade 3–4 NCI-CTC) included: neutropenia in 33.3% of cycles; severe anemia and thrombocytopenia were not observed. Grade 3–4 neurotoxicity and alopecia were detected in 4.9% and 24.7% of cycles respectively. Allergic reaction was observed only in one case. Doses were reduced by 20% in 13.5% of cycles due to neurological toxicity. Conclusions: In recurrent platinum-sensitive ovarian cancer patients the OXA/DTX combination is highly active with acceptable toxicity, thus making it an attractive regimen which warrants the prosecution of the study. No significant financial relationships to disclose.
Epstein-Barr virus (EBV) associated gastric cancer and its clinical characteristics
Authors: M. A. H. Lee, J. H. Kang, K. S. Lee, Y. S. Hong
Journal: Journal of Clinical Oncology (2004)

4263 Background: Epstein-Barr virus (EBV) is associated with a variety of lymphoproliferative disorders. Recently, many authors reported the association between EBV and gastric cancer, but it is not well known about characteristics of EBV associated gastric cancer. We detected the EBV in gastric cancer by using in situ hybridization(ISH) with tissue microarray and reviewed the patients' chart to determine special characteristics of EBV-associated gastric cancer. Methods: Formalin-fixed and paraffin-embedded blocks from 380 surgically resected gastric specimens were studied by using ISH with tissue microarray. All patients were diagnosed with gastric cancer between January 1998 and March 2003 at kangnam St. Mary's hospital of Korea. Clinical data were obtained from clinical record Results: EBV was detected in 20 of 380 cases (5.3%) with gastric cancer by ISH. In EBV-positive gastric cancer, median age was 58.5 years. Most common symptom was epigastric pain (55%). Most lesions were at upper portion of stomach. Fourteen cases (70%) were located at body, five cases (25%) at antrum, and one case (5%) at cardia. According to histologic grade, 10 patients (50%) had moderate differentiated adenocarcinoma, and 9 patients (45%) had poorly differentiated adenocarcinoma. Most of patients with EBV-positive gastric cancer had early gastric cancer (EGC) by gastrofiberscopic classification (80%). Conclusions: In this study, we tested EBV by using ISH with tissue micoarray in gastric cancer. Although its incidence is very low, EBV associated gastric cancer has tendency to be diagnosed at early stage. We are going to investigate several protein expressions to determine how EBV plays a role in carcinogenesis in gastric cancer. No significant financial relationships to disclose.
Phase I trial of OSI-774 and CPT-11 in patients with advanced solid tumors
Authors: R. D. Rao, J. M. Reid, M. P. Goetz, A. F. Furth, S. J. Mandrekar, A. A. Adjei, M. M. Ames, S. L. Safgren, C. Erlichman, H. C. Pitot
Journal: Journal of Clinical Oncology (2004)

3053 Background: We sought to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLTs) of the combination of OSI-774 (an EGFR inhibitor) and CPT-11 in patients (pts) with advanced solid tumors. Secondary aims included pharmacokinetic evaluation for drug interactions and analysis of relationship between UGT1A1 genotype and toxicity. Methods: Eligibility criteria included presence of tumors known to overexpress EGFR, ECOG performance scores 0–2, adequate hematologic, renal and hepatic function. Therapy was with daily continuous oral OSI-774 and intravenous CPT-11 every 3 weeks (which started on day 7 of OSI-774 therapy in cycle 1). DLTs were defined as grade 4 neutropenia, grade 3 thrombocytopenia or ≥ grade 3 non-hematologic toxicities despite maximal supportive care. The presence of the UGT1A1*28 polymorphism (either 6/7 or 7/7 promoter TA repeats) was ascertained. Results: 19 pts (median age 62) were enrolled. Tumor primaries were colon/rectum (8), lung (7), ovary (2), esophagus (1), and pancreas (1). Median number of previous therapies was 3 (Mean=4.7). 74 cycles were delivered (median 2). Dose de-escalations were necessary (table 1) per protocol. 9 non-dose-limiting, therapy-related ≥ 3 toxic events occurred: hematologic (2), fatigue (5), diarrhea (1), dehydration (1). DLTs occurred in 9 pts: diarrhea (7), nausea (3), melena (1), rash (1), neutropenia (3), and leukopenia (2). Protocol specific gastrointestinal or hematological DLT's were seen in 67% (6 of 9) pts with the *28 polymorphism and in only 20% (2/10) pts without it (2 sided p value= 0.07). No objective tumor responses were seen, however 3 pts had stable disease for >6 months. Pharmacokinetic data analysis is underway. Conclusions: The MTD of this combination has not yet been determined. The DLTs appear related to presence of UGT1A1 polymorphisms. Based on these results, a UGT1A1 genotype-specific dosing schedule is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Stereotactic hypofractionated high-dose irradiation for stage I non-small cell lung carcinoma: Clinical outcomes in 273 cases of a Japanese multi-institutional study
Authors: H. Onishi, Y. Nagata, H. Shirato, K. Gomi, K. Karasawa, T. Arimoto, K. Hayakawa, Y. Takai, T. Kimura, A. Takeda
Journal: Journal of Clinical Oncology (2004)

7003 Background: Stereotactic hypofractionated irradiation (STI) has been actively performed for a radical treatment of stage I non-small cell lung cancer (NSCLC) in Japan. We sought to retrospectively evaluate Japanese multi-institutional results. Methods: From April 1993 to April 2003, 273 patients (age range 35–92, median 76 years) who had stage I (175 T1N0M0 and 98 T2N0M0) primary NSCLC (119 squamous cell, 125 adeno, and 29 others) were treated with hypofractionated high-dose STI in 14 institutions. Of the 273 patients, 169 (61.9%) were medically inoperable due to mainly chronic pulmonary disease or high-age. Tumor size ranged from 7 to 58 mm with a median of 28 mm. The stereotactic three-dimensional treatment was performed using non-coplanar dynamic arcs or multiple static ports. A total dose of 18–75 Gy at the isocenter of tumors in 1–22 fractions was administered. The calculated biologic effective dose (BED, α/β=10) ranged from 57 Gy to 180 Gy with a median of 105. Results: All patients completed the treatment with no complaints. During the follow up of 7–127 (median=24) months, pulmonary complications greater than NCI-CTC criteria grade 2 were noted in only 6 (2.4%) patients. Of 269 patients who were evaluated with CT, we observed CR and PR in 71 (26.4%) and 159 (59.1%) patients, respectively. The local progression occurred in 34 (12.5%) of total patients, and a lower local recurrence rate was observed (8.0% vs. 26.4%, P<0.05) when BED was ≥100 Gy vs. <100 Gy. The intercurrent death was observed in 43 (15.8%), mostly in inoperable patients. The 3-year overall survival rate of medically operable patients was 95.2% vs. 69.4% (P<0.05) when BED was ≥ 100 Gy vs. < 100 Gy. Conclusions: Hypofractionated high-dose STI is a feasible and beneficial method for the curative treatment of patients with stage I NSCLC. Local control and survival rates were better for BED ≥100 Gy than for BED <100 Gy for all treatment methods and schedules. Survival rate for STI in selected patients (medically operable and BED ≥100 Gy) were excellent, potentially equal to those of surgery. No significant financial relationships to disclose.
Incidence of mucositis in patients treated with mTOR inhibitor-based regimens and correlation to treatment response.
Authors: Xiaochun Liu, David S. Hong, Siqing Fu, Sarina Anne Piha-Paul, Lacey McQuinn, Gerald Steven Falchook, Jessica Williams, Daniel D. Karp, Vivek Subbiah, Apostolia Maria Tsimberidou, Filip Janku, Ralph Zinner, Jennifer J. Wheler, Robert A. Wolff, Razelle Kurzrock, Aung Naing
Journal: Journal of Clinical Oncology (2013)

e13575 Background: Mucositis is a well-known side effect of mTOR inhibitor (temsirolimus) treatment of cancer patients, limiting the use of mTOR inhibitors. We investigated whether combination treatment of temsirolimus with another agent that was not known to cause mucositis would result in a higher or lower incidence of mucositis. We further investigated if there was an association between the severity of mucositis and tumor response to the temsirolimus-based combination treatment. Methods: This retrospective data review was approved by IRB and conducted in the department of Investigational Cancer Therapeutics at MD Anderson Cancer Center. We reviewed the electronic medical records of 87 patients who were enrolled in temsirolimus-based combination phase I trials (n=3), including physician notes from the date they enrolled on the study to the date they came off treatments. We first examined the incidence of mucositis during the course of study and its severity. We assessed patient response to the study treatment with severity of the mucositis. Results: The overall incidence of mucositis in the 3 temsirolimus-based combination trials was 46%, similar to the published data for the single agent of 41%. The grades of mucositis were: for grade 1 (n=14), grade 2 (n=17) and grade 3 (n=9). No grade 4 mucositis was observed. Neither gender nor ethnicity altered the incidence of mucositis. The median onset time was 14 days after the start of the studies. Of 87 patients, 20 responded to the study treatments with at least stable disease for longer than 6 months or a partial or complete response. The incidence of the mucositis was not associated with the response to temsirolimus-based treatment. Severity of mucositis did not correlate with response to the temsirolimus-based regimen. (grades 1/2 vs. ≥ grade 3; p=0.512). Conclusions: The incidence of mucositis did not increase significantly in patients who received a temsirolimus-based regimen compared to single-agent temsirolimus. Severity of mucositis did not correlate with tumor response to the temsirolimus-based regimen. Future study is warranted to optimize management for mTOR inhibitor-induced mucositis.
Nucleotide excision repair (NER) gene haplotypes and advanced non-small cell lung cancer (NSCLC) prognosis
Authors: S. Gurubhagavatula, W. Zhou, S. Park, D. S. Neuberg, T. J. Lynch, J. C. Wain, L. Su, G. Liu, D. C. Christiani
Journal: Journal of Clinical Oncology (2004)

3040 Background: ERCC1 and ERCC2,two major components of the NER pathway, are critical to platinum chemotherapy function. We demonstrated previously that DNA repair gene single nucleotide polymorphisms (SNPs) are associated with overall survival (OS) in platinum-treated NSCLC patients. We hypothesized that NER gene haplotypes (i.e., combinations of polymorphic markers on a single chromosome segment) are associated with NSCLC OS. Methods: Four SNPs (ERCC1 C8092Aand C19007T; ERCC2 Asp312Asn and Lys751Gln) were genotyped in 124 stage III (61%) and IV (39%) NSCLC patients treated with platinum chemotherapy. Haplotypes were generated using Partition Ligation-Expectation Maximization algorithms. Results: Median age was 59 (32–77); 48% were female; median follow-up was 64.6 months. Median survival time (MST) was 15.7 months; by stage, MST was 29.6 (IIIA), 17.9 (IIIB), and 10.1 (IV) months. Stage was not associated with any haplotypes. Strong linkage disequilibrium was observed for the two ERCC1polymorphisms, and separately for the ERCC2polymorphisms. ERCC1 haplotype frequencies were: 25% (8092A-19007C), 15% (8092C-19007C), 59% (8092C-19007T), and 1% (8092A-19007T); ERCC2frequencies were: 7% (312Asp-751Gln), 27% (312Asn-751Gln), 62% (312Asp-751Lys), and 4% (312Asn-751Lys). The ERCC1 8092A-19007Cand ERCC2 312Asn-751Glnhaplotypes were associated with significantly decreased OS (p=0.014 and p=0.0004, respectively, logrank test, see table). The combination of high-risk haplotypes from both NER genes was also highly prognostic (p=0.002, logrank test). Conclusions: Specific ERCC1and ERCC2haplotypes confer significantly decreased OS in platinum-treated advanced NSCLC patients. NER gene haplotypes provide prognostic information in NSCLC OS in addition to that previously reported with SNPs. Supported by NIH grants CA092824 and CA074386. No significant financial relationships to disclose.