tbuckley/cabot-search huggingface dataset:
Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma
Authors: E. Simeone, A. Daponte, G. De Feo, V. Montesarchio, V. Chiarion-Sileni, I. De Michele, C. Caracò, G. Palmieri, N. Mozzillo, P. A. Ascierto
Journal: Journal of Clinical Oncology (2009)

e20009 Background: Dacarbazine (DTIC) is the standard treatment for metastatic melanoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Metronomic administration of TMZ might be another way to overcome resistance. Patients and Methods: We reviewed data of metastatic melanoma patients treated at our Institutions with cisplatin (75 mg/m 2 every 28 days) plus TMZ (75 mg/m 2 /die from day 2 for 21 days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC. Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18–74); primary melanoma was ulcerated in 19 cases (58%); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases each and grade 2 in 16 and 9 cases, respectively. Other toxicities included thrombocytopenia (2 case grade 3 and 3 cases grade 2), anemia (1 grade 3 and 4 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 6 patients had a partial response (18.2%; 95% exact CI: 7.0–35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19–57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI:16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr). Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic melanoma are encouraging, in light of the negative prognostic features of treated patients. We are now planning a formal phase II study. [Table: see text]
Chemoradiation-related lymphopenia and its association with survival in patients with anal cancer.
Authors: Grace Lee, Daniel W. Kim, Vinayak Muralidhar, Devarati Mitra, Nora Horick, Christine Elissa Eyler, Theodore S. Hong, Lorraine C. Drapek, Jill N. Allen, Lawrence Scott Blaszkowsky, Bruce J. Giantonio, Aparna Raj Parikh, David P. Ryan, Jeffrey William Clark, Jennifer Yon-Li Wo
Journal: Journal of Clinical Oncology (2020)

3 Background: While treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, little data exists for anal cancer. We evaluated TRL and its association with survival in anal cancer patients treated with chemoradiation (CRT). Methods: A retrospective analysis of 140 patients with non-metastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by G4 TRL ( &lt; 0.2k/μl) two months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. Results: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC ( &gt; 1k/μl). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death (p = 0.013). On log-rank test, the 5-year OS rate was shorter in the cohort with versus without G4 TRL at two months (32% vs. 86%, p &lt; 0.001). Conclusions: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS supports the hypothesis that host immunity plays an important role in survival among patients with anal cancer. These results support ongoing efforts of randomized trials underway to evaluate the potential role of immunotherapy in localized anal cancer.
Phase I, first-in-human study of AbGn-107, a novel antibody-drug conjugate (ADC), in patients with gastric, colorectal, pancreatic or biliary cancers.
Authors: Andrew H. Ko, Andrew L. Coveler, Benjamin L. Schlechter, Tanios S. Bekaii-Saab, Brian M. Wolpin, Jeffrey William Clark, Bruno Bockorny, Li-Yuan Bai, Yi-Lin Cheng, Ting-Ying Cheng, Peter J. Langecker, Shih-Yao Lin
Journal: Journal of Clinical Oncology (2020)

e16771 Background: AbGn-107 is an ADC directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in 24-61% of gastric (G), colorectal (CRC), pancreatic (PDA), and biliary (BIL) cancers. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a Phase Ia trial in patients with the aforementioned GI malignancies. Methods: Standard 3+3 dose escalation was used. Key eligibility included locally advanced or metastatic G, CRC, PDA, or BIL cancer, previously treated, ECOG PS 0-1; positive AG-7 expression was not required. Two dosing intervals were tested: AbGn-107 administered i.v. Q4 weeks (at doses ranging from 0.1-1.2 mg/kg) and Q2 weeks (at doses from 0.8-1.0 mg/kg). Dose limiting toxicities (DLT) were based on grade 3/4 hematologic and non-heme AEs occurring during the initial 4-week rx window. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments Q8 weeks. 1o objectives: safety and MTD; 2o objectives: PK, immunogenicity, and efficacy defined by ORR (RECIST 1.1). Results: 35 patients were enrolled across 6 dose levels (median age 61.5 yo (range 40 – 81); G (0)/CRC (12)/PDA (20)/BIL (3); median # lines of prior rx = 3 (range 1-7). Safety: 5 patients experienced Grade 3 or 4 neutropenia, all at higher dose levels, inc. 1 episode of febrile neutropenia. Other frequent drug-related AEs, mostly grade 1/2, inc. fatigue (29%), nausea (20%), and diarrhea (14%). DLTs included grade 4 CK elevation (n = 1) at 0.8 mg/kg Q4W and grade 3 arthralgias (n = 1) at 1.2 mg/kg Q4W. Based on safety profile and PK data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase. Efficacy: Median duration of treatment = 56 days (range, 8 – 225 days). Six pts have demonstrated a minor response by RECIST (range, -1.3 to -21.1%); 4 pts (all PDA) have had durable dz control &gt; 180 days. Conclusions: Overall, AbGn-107 appears well-tolerated with encouraging prelim signs of efficacy in unselected pts with heavily pre-treated advanced GI cancers. Updated safety and efficacy data will be provided at the time of the meeting for the cohort expansion phase of this study (currently open across multiple sites in U.S. and Taiwan), in which subjects with G, CRC, PDA, and BIL cancers are pre-screened for high levels of AG-7 tumor expression. Clinical trial information: NCT02908451 .
The Deep Genome Project
Authors: K. C. Kent Lloyd, David J. Adams, Gareth Baynam, Arthur L. Beaudet, Fatima Bosch, Kym M. Boycott, Robert E. Braun, Mark Caulfield, Ronald Cohn, Mary E. Dickinson, Michael S. Dobbie, Ann M. Flenniken, Paul Flicek, Sanjeev Galande, Xiang Gao, Anne Grobler, Jason D. Heaney, Yann Herault, Martin Hrabě de Angelis, James R. Lupski, Stanislas Lyonnet, Ann-Marie Mallon, Fabio Mammano, Calum A. MacRae, Roderick McInnes, Colin McKerlie, Terrence F. Meehan, Stephen A. Murray, Lauryl M. J. Nutter, Yuichi Obata, Helen Parkinson, Michael S. Pepper, Radislav Sedlacek, Je Kyung Seong, Toshihiko Shiroishi, Damian Smedley, Glauco Tocchini-Valentini, David Valle, Chi-Kuang Leo Wang, Sara Wells, Jacqueline White, Wolfgang Wurst, Ying Xu, Steve D. M. Brown
Journal: Genome biology (2020)

In vivo research is critical to the functional dissection of multi-organ systems and whole organism physiology, and the laboratory mouse remains a quintessential animal model for studying mammalian, especially human, pathobiology. Enabled by technological innovations in genome sequencing, mutagenesis and genome editing, phenotype analyses, and bioinformatics, in vivo analysis of gene function and dysfunction in the mouse has delivered new understanding of the mechanisms of disease and accelerated medical advances. However, many significant hurdles have limited the elucidation of mechanisms underlying both rare and complex, multifactorial diseases, leaving significant gaps in our scientific knowledge. Future progress in developing a functionally annotated genome map depends upon studies in model organisms, not least the mouse. Further, recent advances in genetic manipulation and in vivo, in vitro, and in silico phenotyping technologies in the mouse make annotation of the vast majority of functional elements within the mammalian genome feasible. The implementation of a Deep Genome Project—to deliver the functional biological annotation of all human orthologous genomic elements in mice—is an essential and executable strategy to transform our understanding of genetic and genomic variation in human health and disease that will catalyze delivery of the promised benefits of genomic medicine to children and adults around the world.
Repeated Assessment of Posttraumatic Stress Disorder Severity and the Risk of Mortality
Authors: Jeffrey F. Scherrer, Joanne Salas, Paula P. Schnurr
Journal: JAMA Network Open (2020)

Ingrid Giesinger, MS; Jiehui Li, MBBS, MS; Erin Takemoto, PhD, MPH; James E. Cone, MD, MPH; Mark R. Farfel, ScD; Robert M. Brackbill, PhD, MPH
Defining the terminology and parameters that should be used in studies into dermoscopy for non‐cancer skin diseases
Authors: E. Errichetti, I. Zalaudek, H. Kittler, Z. Apalla, G. Argenziano, R. Bakos, A. Blum, R. Braun, D. Ioannides, F. Lacarrubba, E. Lazaridou, C. Longo, G. Micali, E. Moscarella, J. Paoli, C. Papageorgiou, T. Russo, A. Scope, G. Stinco, L. Thomas, R.J. Toncic, P. Tschandl, H. Cabo, A. Hallpern, R. Hofmann‐Wellenhof, J. Malvehy, A. Marghoob, S. Menzies, G. Pellacani, S. Puig, H. Rabinovitz, L. Rudnicka, E. Vakirlis, P. Soyer, W. Stolz, M. Tanaka, A. Lallas
Journal: British Journal of Dermatology (2020)

Dermoscopy is a technique using a handheld magnifying device called a dermatoscope that allows doctors to see structures in the skin that are not visible to the naked eye. This helps with the diagnosis of skin diseases and reduces the need for biopsies (removal of a small sample of skin to be examined under a microscope). Its main use is for skin tumours (e.g. skin cancers), but it is increasingly used also in other skin diseases, especially inflammatory and infectious skin diseases. Over the last few years, several articles on dermoscopy of non-tumoural (i.e. not cancer) skin diseases have been published, yet there is poor consistency in the terminology (language) used among the different studies. The present study, involving a total of 37 international experts from all over the world on behalf of the International Dermoscopy Society, aimed to identify uniform terms and basic parameters (what doctors should look for) to adopt/evaluate when using dermoscopy in non-tumoral skin diseases. This aim was achieved by using a standardized agreement procedure (called “modified DELPHI method”). The authors identified five standardized basic parameters. For each of them, possible variables were selected, with a total of 31 different sub-items. Adopting a structured and uniform method to describe dermoscopic findings will help researchers and will allow different studies to be compared. This is particularly relevant for future studies on dermoscopy in general dermatology, which the authors strongly recommend should be designed using the terminology and parameters outlined in this study. This summary relates to the study: Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society
Influence of stamping on the biodegradation behavior of Mg–2Zn-0.5Nd (ZN20) sheet
Authors: Iniobong P. Etim, Wen Zhang, Lili Tan, Ke Yang
Journal: Bioactive Materials (2020)

Stamping processing is commonly used to form medical devices and implant. However, for biodegradable Mg alloy, the stamping will influence the degradation behavior because of the change in microstructure after stamping. So in this study, the As-rolled Mg-2Zn-0.5Nd alloy (ZN20) was processed by stamping. The microstructure, crystallographic orientation and corrosion performance of this processing method was investigated to reveal the influence of the stamping process on the degradation rate of Rolled Mg-2Zn-Nd (ZN20). The degradation rate was measured by immersion of the Mg-2Zn-0.5Nd alloy in simulated body fluid using Electrochemical Impedance Spectroscopy, Potentiodynamic polarization and mass loss. The in vitro degradation result shows that the degradation rate of the Rolled Mg-2Zn-0.5Nd increased from 0.2 mm/year to 0.5 mm/year after stamping processing. The result reveals that the activation of the {101‾2} tension twin during stamping can remarkably weaken the { 0001} basal texture and have a significant influence on the corrosion rate of Stamped Mg-2Zn-0.5Nd sheet. After removing the deformation by annealing, the degradation rate was reduced to 0.15 mm/year. This work is expected to prompt better microstructural design of biomedical Mg in order to control its degradation behavior for biomedical application.
Total skeletal, psoas, and rectus abdominis muscle mass as prognostic factors for patients with advanced hepatocellular carcinoma.
Authors: Yu Yun Shao, Chih-Horng Wu, Po-Chin Liang, Chih-Hung Hsu, Tiffany Ting-Fang Shih
Journal: Journal of Clinical Oncology (2020)

568 Background: We investigated whether low skeletal muscle mass (LSMM) defined according to different muscle groups on computed tomography (CT) scans could predict prognosis of advanced hepatocellular carcinoma (HCC). Methods: We analyzed patients who received first-line sorafenib treatment for advanced HCC in a prospective patient cohort between 2007 and 2012. The muscels areas of total skeletal muscle (TSM), paraspinal muscle (PS), psoas muscle (PM), rectus abdominis (RA), and abdominal wall (AW) were evaluated using a single CT slice at the third lumbar vertebra before treatment. LSMM was determined according to the TSM, PS, PM, RA and AW indices, which was calculated as the parameters divided by the square of the body height. Results: We enrolled 137 patients, with a mean age of 57.5 years; 120 were male and 17 were female. Liver disease etiology was hepatitis B virus in 94 (68.6%) patients and hepatitis C virus in 28 (20.4%) patients. All patients had Child–Pugh class A liver reserve. Women had significantly lower TSM index than men did ( p &lt; .001). Among men, the optimal cut points of the TSM, PM and RA indices for LSMM diagnosis were 39.1, 8.3 and 2.9 cm 2 /m 2 , respectively. Patients with LSMM exhibited poorer overall survival than patients without LSMM, whether LSMM was defined by TSM index (median 5.1 vs. 8.0 months, p = 0.007), PM index (median 5.8 vs. 11.8 months, p &lt; 0.001), or RA index (median 7.2 vs. 8.1 months, p = 0.003). After adjusting for clinical variables including underweight, age, tumor extent, and performance status, LSMM defined by TSM index (hazard ratio [HR]: 2.123, 95% confidence interval [CI]: 1.124-4.010, p = 0.020), PM index (HR: 1.855, 95% CI: 1.163-2.959, p = 0.009), or RA index (HR: 1.650, 95% CI: 1.004-2.710, p = 0.048) remained independent predictors for poor OS. Conclusions: LSMM defined by TSM, PM and RA indices are independent predictors for poor prognosis of advanced HCC, even after adjusted for body weight.
Neoadjuvant mFOLFOXIRI chemotherapy-improved survival benefit comparing with CRT in locally advanced rectal cancer: A propensity score matched analysis from two prospective trials.
Authors: Jianwei Zhang, Jianxia Li, Xiaoyu Xie, Yue Cai, Huabin Hu, Zehua Wu, Jiayu Ling, Yanhong Deng
Journal: Journal of Clinical Oncology (2020)

98 Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, neoadjuvant chemotherapy with mFOLFOXIRI had been investigated. However, no randomized comparison assessing the efficacy of mFOLFOXIRI versus CRT in LARC. Methods: 145 LARC patients received CRT as neoadjuvant treatment in the phase III FOWARC study (NCT01211210) and 103 patients received mFOLFOXIRI alone preoperatively in a phase II study (NCT02217020). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the enhancive chemotherapy regimen as neoadjuvant treatment in terms of survival and activity parameters. Results: In the original cohort, patients in the mFOLFOXIRI group were younger with the median age of 48 versus 56 years old in the CRT group. More patients with tumor length over 5 cm and cT3 or N2 disease in the mFOLFOXIRI group ( P&lt; 0.05). After propensity score adjusted matching, 73 patients were comparable in each groups. The pCR rate was 23.3% in thd mFOLFOXIRI group versus 13.7% in the CRT group, respectively (P = 0.14). The proportion of ypStage 0-I was 45.2% versus 39.7%, respectively (P = 0.5). The local recurrence rate was comparable between the two groups (5.5% vs. 4.1%, P= 0.70). But mFOLFOXIRI decrease the incidence of distant metastasis (8.2% vs. 27.4%, P= 0.002). And the 3 year disease free survival was 86.8% in the mFOLFOXIRI group versus 75.8% in the CRT group, respectively ( P= 0.049). Lower incidence of anastomotic fistula was shown in mFOLFOXIRI alone group than that of CRT group (5.5% vs. 17.8%, P = 0.02). Grade 3/4 neutropenia was more commen in mFOLFOXIRI group (39.7% vs. 8.2%, P &lt; 0.001). Conclusions: Comparing with CRT, preoperative mFOLFOXIRI decreased the incidence of distant metastasis and improved 3 year DFS, and led to less toxicity and fewer postoperative complications. The phase III randomized study comparing FOLFOXIRI with CRT is still ongoing. Clinical trial information: NCT01211210 and NCT02217020.
厳格なカロリーコントロール研究(TICACOS):重症患者における栄養補給の前向きランダム化対照パイロット研究 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Singer Pierre, Anbar Ronit, Cohen Jonathan, Shapiro Haim, Shalita-Chesner Michal, Lev Shaul, Grozovski Elad, Theilla Miryam, Frishman Sigal, Madar Zecharia
Journal: Intensive Care Medicine (2011)
Is mucinous histology a prognostic marker in early and advanced colorectal cancer?
Authors: Rosemary Habib, Val Gebski, Kenneth Micklethwaite, Duncan McLeod, James Toh, Nimalan Pathma-Nathan, Toufic El-Khoury, Grahame Ctercteko, Kavitha Gowrishankar, Nicholas Wilcken, Mark Wong, Adnan Nagrial
Journal: Journal of Clinical Oncology (2020)

253 Background: In early and advanced colorectal cancer (CRC), there is limited data comparing the influence of mucinous (MAC) with non-mucinous adenocarcinoma (NMAC) histology on clinical outcomes. We investigated the association between histological type and outcomes in CRC. Methods: Medical records of patients with stage II, III and IV CRC referred to a tertiary centre in Western Sydney between 2009-2016 were examined and demographic and clinical information extracted. Key prognostic factors were modeled using log rank tests and proportional hazards (PH) regression methods in multivariate analyses. Results: Data on 686 patients was extracted. Median age was 70 years (19 – 94). Median follow up was 38.4 months. 98 patients (12%) had MAC and no differences in stage were observed at presentation between MAC and NMAC (p = 0.16). MAC was associated with increased prevalence of microsatellite instability (36% v 11% p &lt; 0.01), high grade tumours (51% v 18% p &lt; 0.01), female gender (61% v 45% p &lt; 0.01) and right sided primary (65% v 40% p &lt; 0.01). In stage II/III, MAC had comparable relapse free survival (RFS) versus NMAC (median 79 vs 97 months; P = 0.21). However, in the adjuvant chemotherapy group, a poorer RFS was seen for MAC (52 Vs 82 months, HR = 0.52, P = 0.03). In all patients with relapsed disease, MAC was more likely to be associated with peritoneal carcinomatosis (51% vs 26%; P &lt; 0.01), and less likely to be associated with liver metastases (45% Vs 70%, P &lt; 0.01) than NMAC. PH analysis of the MAC cohort revealed poorer RFS for LVI (HR 2.85; p = 0.03), T4 stage (HR 3.15, p = 0.01) and adjuvant chemotherapy (HR 5.49, p &lt; 0.01). On multivariate analysis, T4 remained significant for poorer RFS. No differences were seen in OS in early stage CRC between MAC and NMAC. However, right sided and female gender with stage IV MAC had poorer OS (Right colon: HR 6.6; P = 0.03) (Female: HR 4.90, P = 0.03). Conclusions: MAC is associated with poorer RFS in early stage CRC irrespective of sidedness, and with poorer OS in right sided CRC. Given their poor response to adjuvant chemotherapy, novel adjuvant treatments should be considered for early MAC CRC. In the palliative setting, novel therapies and clinical trials are required for patients with MAC, particularly with right sided primaries.
Offline: 2019-nCoV—“A desperate plea”
Authors: Richard Horton
Journal: The Lancet (2020)

One aspect of the 2019 novel coronavirus (2019-nCoV) outbreak has been surprisingly overlooked. What is life like for those quarantined in Chinese cities? Here is an extract from one correspondent, received on Feb 2, in an email entitled, "A desperate plea from an ordinary citizen in China". I have edited the text only slightly for clarity.