tbuckley/cabot-search huggingface dataset:
Favourable IGCCCG subgroups of stage II NSGCT patients may require less chemotherapy if TNM staging is included
Authors: Y. Haba, M. V. Williams, J. Ong, J. Ostrowski, R. T. D. Oliver
Journal: Journal of Clinical Oncology (2004)

4532 Background: When the IGCCCG prognostic factor analysis was performed there were few stage II cases included in this analysis of chemotherapy cases. Patients were not included from centres which used primary retroperitoneal lymph node dissection followed either by 2 courses of adjuvant chemotherapy or 3 courses at relapse. Primary surgery is the standard of care in North America but not in Europe where primary chemotherapy is used. To investigate this issue the impact of nodal (stage II) versus extra nodal (stage IV) metastases in each of the IGCCCG sub-groups has been examined in an audit of 447 patients treated in centres where chemotherapy rather than RPLND was primary management for stage 2 non-seminoma. Methods: Clinicians from 7 centres (St Barts, Oldchurch, Southend, Colchester, Ipswich, Norwich and Cambridge) have prospectively registered cases in a central data base at St Barts and notes review and follow up has been co-ordinated. Results: Between 1982 and 2002 447 patients were registered and survival analysis performed. Stage II cases comprised 63% of IGCCCG good-risk group (N=298), 42% of intermediate and 10% of poor risk patients. With median FU of 60 months there was no significant difference in survival for good-risk patients 92% of stage II (i.e. N+, n=156); 85% of stage IV (i.e. M+, n=94). In contrast survival was significantly influenced in intermediate and poor risk cases with 79% of stage II (N+, n=29) patients alive compared to 60% of stage IV (M+, n=92) (x2 4.05p = <0.05). There was no difference in survival between patients having 3 or 4 courses of treatment and no relapses in 8 who stopped treatment after two courses because of extenuating circumstances. Conclusions: Extralymphatic spread (stage IV) is prognostically significant within intermediate and poor risk IGCCCG. This influence is not seen in good risk patients and the observation that there may be N+ patients in whom it is possible to reduce treatment to 2 courses should be explored further. No significant financial relationships to disclose.
Estimating the selective effects of heterozygous protein-truncating variants from human exome data
Authors: Christopher A Cassa, Donate Weghorn, Daniel J Balick, Daniel M Jordan, David Nusinow, Kaitlin E Samocha, Anne O'Donnell-Luria, Daniel G MacArthur, Mark J Daly, David R Beier, Shamil R Sunyaev
Journal: Nature Genetics (2017)
Real-world palbociclib dosing patterns and potential wastage associated with dose modifications among post-menopausal women with HR-positive/HER2-negative metastatic breast cancer (mBC).
Authors: Nanxin Li, Ella X. Du, Lihao Chu, Miranda Peeples, Jipan Xie, Victoria E. Barghout, Derek H. Tang
Journal: Journal of Clinical Oncology (2017)

17 Background: CDK4/6 inhibitor palbociclib is recently approved for the treatment of HR+/HER2- mBC and its treatment patterns have not been thoroughly understood. This study described real-world palbociclib dosing patterns in the US. Methods: Postmenopausal women with HR+/HER2- mBC who initiated palbociclib-based therapy (date of initiation was defined as index date) between 02/03/2015 (palbociclib approval date) and 02/29/2016 (end of data) were identified from Symphony Source Lx database. Patients were required to have continuous quarterly medical/pharmacy activity for 1 year prior to and 6 months after the index date. Dose decrease or increase (collectively, dose modification) was defined as a change of daily dose of &gt;=25 mg compared to the last dose. Dose interruption was defined as a treatment gap within 60 days before restarting the treatment as the last dose. Kaplan-Meier analyses were conducted to assess dose decrease rate and dose decrease/interruption rate within one year from the index date. The proportion of patients with and days of overlap in fills during dose modification were assessed. The costs of potential palbociclib wastage related to dose modification were estimated by applying the wholesale acquisition costs (as of Oct 2016) to the number of overlapping days of supply between two adjacent fills. Results: A total of 1,242 patients initiated palbociclib-based therapy in line 1 through 4 for mBC (mean age=62.7 years, median follow-up time=8.7 months). Across line 1 to 4, dose decrease rates were 31.9%-33.7%, and dose decrease/interruption rates were 63.5%-80.9%. A total of 411 (33.1%) patients had dose modification, among whom 203 patients (49.4%) experienced an overlap in prescription fills during dose modification with an average overlap of 12.3 (SD=10.6) days per patient, resulting in costs of potential wastage for $4,556 (SD=$3,920) per patient. Conclusions: This real-world study showed most patients initiating palbociclib-based therapy had dose modification or interruption over a median follow-up of 8.7 months. Half of the patients experiencing dose modifications were associated with potential wastage.
Phase I study of high-dose chemotherapy with peripheral blood stem-cells reinfusion (PBSC) in patients with metastatic or inflammatory breast cancer (MBC)
Authors: M. Fabbro, S. Thezenas, S. Wandzel, A. Kramar, A. Martinez, D. Mir
Journal: Journal of Clinical Oncology (2004)

747 Background. High-dose chemotherapy (HDC) followed by PBSC transplantation in MBC has been reported yet. In an attempt to develop a new active regimen, we carried out a study of dose escalation of Paclitaxel with Ifosfamide and Doxorubicine in chemo-naive patients (pts). Methods. Five dose levels of paclitaxel were investigated (from175 to 300 mg/m2/3 weeks) with Ifosfamide [3 g/m2 d1–4, cycle1–5] and Doxorubine [75 mg/m2 d1, cycle 2–5]. PBSC were collected at first cycle and reinfused on d5 (cycles 3–4-5), followed by filgrastim from d 6–12 at each (cycle. The continuous reassessment method was used to predict the probability of toxicity. DLT's were defined as : toxic death, Gr4 thrombopenia or neutropenia leading to a cycle delay >14d, Gr3 cardiac toxicity, Gr4 mucositis, Gr3 neurological toxicity and any toxicity leading to a cycle delay >14d. Results. Twenty-three pts have been included in this study. Median age was 46 (18 : 61) years. A total of 101 cycles were performed. Non haematological toxicities were as described in the table. Grade III IV asthenia have often been reported. The overall response rate was 77% [95% CI : 55% – 92%], with 18% (4) complete responses and 59% (13) partial responses. Three patients had stable disease and two had progressive disease. Of note, chirurgical treatment has been performed for nine patients. Conclusion. MTD has been reached at a dose of 300 mg/m2 of paclitaxel (accounting for more than 30% of the dose limiting toxicities). We conclude that the recommended dose of paclitaxel is 250 mg/m2 and that high dose regimen of paclitaxel seems to be safe for patients with MBC, particularly regarding cardiotoxicity and also shows promising antitumour activity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Baxter
Imatinib (STI 571) is active in patients (PTS) with high-grade gliomas progressing on standard therapy
Authors: A. Katz, C. H. Barrios, R. Abramoff, S. D. Simon, J. Tabacof, R. C. Gansl
Journal: Journal of Clinical Oncology (2004)

1542 Background: High-grade gliomas (HGG) PTS progressing after surgery, radiation therapy and chemotherapy with Temozolomide have a very short survival. No particular form of therapy has been shown to be effective in this setting. It is also known that the genetic pathways leading to primary and secondary gliomas are markedly different. A significant proportion of younger PTS who develop secondary glioblastomas (GBM) have amplification of the PDGFR alfa, while PTS with de novo GBMs usually do not have this alteration. Molecular targeted therapy need to take these disease characteristics into account in order to be adequately evaluated. Imatinib (Gleevec) have been shown to be active in preclinical models against glioblastoma cell lines and in xenograft models. Methods: We treated 15 PTS with HGG who developed progressive disease after being treated with surgery, radiation therapy and temozolomide. 14/15 PTS were PDGR alfa positive by Immunohistochemistry. All PTS were treated with Imatinib 400 mg/day until progression of disease. Median age was 62, 9/15 PTS were older then 45 years old. Results: Among these older PTS only 1 remained in stable disease for 8+ months, while the others developed progression of disease. Three of the six PTS younger than 45 y.o. responded to the treatment (one to early): 1PR (14+ months), 1 SD (8 months), 1 MR (19 months). Treatment was well tolerated in general and no grade ¾ toxicities were observed. Conclusion: Imatinib seems to be active in a proportion of PTS with progressive HGG. Although these are very small numbers, we speculate that these results may suggest that this drug could be especially active in PTS with secondary HGG, in whom the PDGFR alfa may play an important role in the gliomagenesis process. The trial is still open for accrual and prospective evaluation of gene expression and tissue array were recently incorporated into the study. No significant financial relationships to disclose.
Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma
Authors: Moritz Binder, Megan M. O'Byrne, Matthew J. Maurer, Stephen Ansell, Andrew L. Feldman, James Cerhan, Anne Novak, Luis F. Porrata, Svetomir Markovic, Brian K. Link, Thomas E. Witzig
Journal: American Journal of Hematology (2017)

Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n = 390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r = -0.36), IL-12 (r = -0.17), IP-10 (r = -0.23), and MIG (r = -0.32) concentrations (p < 0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p < 0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p < 0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p < 0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p < 0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p = 0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.
Urine Ammonium Predicts Clinical Outcomes in Hypertensive Kidney Disease
Authors: Kalani L. Raphael, David J. Carroll, Jennifer Murray, Tom Greene, Srinivasan Beddhu
Journal: Journal of the American Society of Nephrology (2017)

Metabolic acidosis is associated with poor outcomes in CKD. Because impaired renal ammonium excretion is important in the pathogenesis of acidosis, urine ammonium excretion might be a better and perhaps earlier acid-base indicator of risk than serum bicarbonate, particularly in patients without acidosis. We evaluated the association between baseline ammonium excretion and clinical outcomes in African American Study of Kidney Disease and Hypertension participants (n=1044). Median daily ammonium excretion was 19.5 (95% confidence interval [95% CI], 6.5 to 43.2) mEq. In Cox regression models (adjusted for demographics, measured GFR, proteinuria, body mass index, net endogenous acid production, and serum potassium and bicarbonate), hazard ratios of the composite outcome of death or dialysis were 1.46 (95% CI, 1.13 to 1.87) in the low tertile and 1.14 (95% CI, 0.89 to 1.46) in the middle tertile of daily ammonium excretion compared with the high tertile. Among participants without acidosis at baseline, the adjusted hazard ratio for those with ammonium excretion <20 mEq/d was 1.36 (95% CI, 1.09 to 1.71) compared with those with ammonium excretion ≥20 mEq/d. Additionally, compared with participants in the high ammonium tertile, those in the low ammonium tertile had higher adjusted odds of incident acidosis at 1 year (adjusted odds ratio, 2.56; 95% CI, 1.04 to 6.27). In conclusion, low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis. Low ammonium excretion could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.
EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis
Authors: Garifallia Sakellariou, Philip G Conaghan, Weiya Zhang, Johannes W J Bijlsma, Pernille Boyesen, Maria Antonietta D'Agostino, Michael Doherty, Daniela Fodor, Margreet Kloppenburg, Falk Miese, Esperanza Naredo, Mark Porcheret, Annamaria Iagnocco
Journal: Annals of the Rheumatic Diseases (2017)

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA.
Gender identity and the management of the transgender patient: a guide for non-specialists
Authors: Albert Joseph, Charlotte Cliffe, Miriam Hillyard, Azeem Majeed
Journal: Journal of the Royal Society of Medicine (2017)

In this review, we introduce the topic of transgender medicine, aimed at the non-specialist clinician working in the UK. Appropriate terminology is provided alongside practical advice on how to appropriately care for transgender people. We offer a brief theoretical discussion on transgenderism and consider how it relates to broader understandings of both gender and disease. In respect to epidemiology, while it is difficult to assess the exact size of the transgender population in the UK, population surveys suggest a prevalence of between 0.2 and 0.6% in adults, with rates of referrals to gender identity clinics in the UK increasing yearly. We outline the legal framework that protects the rights of transgender people, showing that is not legal for physicians to deny transgender people access to services based on their personal beliefs. Being transgender is often, although not always, associated with gender dysphoria, a potentially disabling condition in which the discordance between a person’s natal sex (that assigned to them at birth) and gender identity results in distress, with high associated rates of self-harm, suicidality and functional impairment. We show that gender reassignment can be a safe and effective treatment for gender dysphoria with counselling, exogenous hormones and surgery being the mainstay of treatment. The role of the general practitioner in the management of transgender patients is discussed and we consider whether hormone therapy should be initiated in primary care in the absence of specialist advice, as is suggested by recent General Medical Council guidance.
Relative influence of factors determining a woman’s preference for treatment options in ovarian cancer.
Authors: Laura Jean Havrilesky, Angeles Alvarez Secord, Jessie A Ehrisman, Andrew Berchuck, Fidel A. Valea, Paula S. Lee, Stephanie Gaillard, David Cella, Kevin Weinfurt, Amy Pickar Abernethy, Shelby D. Reed
Journal: Journal of Clinical Oncology (2014)

5544 Background: We examined relative preferences of women with ovarian cancer for symptoms, treatment-related side-effects, and progression-free survival (PFS) when considering a treatment regimen. Methods: Women with advanced or recurrent ovarian cancer were recruited at a single institution to a prospective discrete choice experiment. In each discrete choice, subjects were asked to choose between two treatment scenarios, modeled on the characteristics of standard intravenous (IV) and intraperitoneal/intravenous (IP/IV) treatments for ovarian cancer. Each scenario described 7 attributes with 2-3 levels each: mode of administration (IV versus IP/IV); visit frequency (weekly, twice per 3 weeks, once per 3 weeks); treatment related symptoms (mild to severe nausea and vomiting, abdominal symptoms, neuropathy, and fatigue); and PFS (15, 18, 21, and 24 months). We used a balanced overlap design with 10 versions of the survey. Each subject evaluated 12 random choice scenarios (in which levels of each attribute were varied). We applied mixed logit regression to model participants choices as a function of attribute levels. Results: 95 women completed the survey. Mean age 57; 81% Caucasian. 47% had experienced disease recurrence and 49% were currently receiving chemotherapy. Compared to scenarios with 15 months of PFS, the relative odds that a participant would choose a scenario with 18, 21, and 24 months of PFS were 1.5 (p=0.01), 3.4 (p<0.001) and 7.5 (p<0.001), respectively. However, subjects were willing to give up PFS to avoid severe treatment-related side effects (6.7 months to reduce severe nausea and vomiting during treatment to mild, 5.0 months to reduce severe neuropathy to mild, and 3.7 months to reduce severe IP–related abdominal symptoms to moderate). Findings were similar between women currently receiving chemotherapy and those who were not and between women with disease recurrence and those without. Conclusions: PFS is the predominant driver of patient preferences for chemotherapy. However, women are willing to trade significant PFS time for reductions in treatment-related toxicity. Patient preferences should be considered when interpreting clinical trial results and making treatment decisions.
Measuring quality in cancer care: Utilizing a clinical decision support system to assess pathway adherence.
Authors: Debra A. Patt, Josh Howell, Marcus A. Neubauer, Bo He, Jody S. Garey
Journal: Journal of Clinical Oncology (2017)

172 Background: Quality-based programs depend on clinical data documentation for reporting, treatment planning, and measuring pathways (PW) compliance. Adherence to treatment PW reduces variability and costs of care. Clinical decision support systems (CDSS) are tools embedded in the EHR to capture assessable data: stage, biomarkers, line of therapy, etc. With such data, CDSS can measure and report on clinical quality improvement programs like PW adherence, assessable data and exception reporting. Methods: A retrospective cohort study from Jan 1, 2014 - May 30, 2016 measured the impact of an integrated CDSS assessing compliance to PW and exception reporting across 9 independent oncology practices over a 9 month period. Assessable data, PW adherence, and exception reporting were tracked in 4 month intervals pre and post CDSS intervention by practice and physician. A one month wash out period was included post CDSS implementation. Overall rates of positivity, assessable data, and exception reporting were compared pre and post intervention using the Chi-square test. To account for the effect of time on the intervention, a segmented regression analysis was performed to analyze weekly rates of positivity pre and post intervention. Results: 9 practices, 633 physicians, and 30,666 treatment regimens were included. The weekly adherence rate increased by 7.2% after intervention (p = 0.005) across the group. Assessable data capture significantly improved across the cohort OR 6.79 (5.64-8.16) and individually for most practices. Physicians adherent to PW 75% of the time increased post intervention collectively, OR 1.83 (1.44-2.31), and individually. Exception reporting improved from 29% to 99% (p&lt;0.0001). Conclusions: Across a cohort of community oncology practices rates of assessable data, PW adherence, and exception reporting improved after implementation of an integrated CDSS. Effective CDSSs are a critical component of quality improvement programs and may be used to improve data capture, increase adherence to PW and overall contribute to quality cancer care delivery. [Table: see text]
Quality of life in Irish high-grade non-Hodgkin lymphoma survivors.
Authors: Rebecca Anne Holland, Jo O' Keeffe, Mary Cahill, Kate Murphy, Conleth G. Murphy, Deirdre O'Mahony, Brian Richard Bird
Journal: Journal of Clinical Oncology (2015)

e20597 Background: The incidence and cure rates of aggressive NHL are increasing in Ireland. No data is available on QoL in the lymphoma survivor population who are exposed to multiagent chemotherapy and often radiotherapy. Methods: High grade NHL survivors (known to be disease free) from 2 hospitals were invited to participate in a cross-sectional study by completing the validated Lymphoma specific Functional Assessment of Cancer Therapy (FACT-Lym) questionnaire, and the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) Lymphoma Symptom Index-18 (FLymSI-18). Results: Of 87 questionnaires, 48 were completed and returned by NHL survivors (55.2% response rate). Linear regression analysis showed a mean global FACT-Lym QOL score of 146 (range 0-168). Adjustment of data for time since diagnosis compared QoL across these groups. Linear regression studies found a drop in QOL scores in the 4-5year category, before again increasing in the 5+ year category, which was statistically significant across emotional and functional wellbeing scales as well as global FACT-G and FACT-Lym scores. Higher emotional and physical function was seen compared to a large previously reported US cohort (Smith, S Cancer 2009) Conclusions: Significant differences in QOL exist across time since diagnosis in NHL survivors. Some physical symptoms declined over time. We speculate that anxiety prior to the 5 year
SEGURIDAD Y EFICACIA DE LA TÉCNICA DE MUCUSECTOMÍA ASISTIDA CON BANDAS DE LESIONES EPITELIALES Y SUBEPITELIALES ESÓFAGO-GÁSTRICAS
Authors: B Romero Mosquera, D Martinez Ares, N Quintáns Pinazas, L Cid Gómez, S Vázquez Rodríguez, MI Pérez Lamelas, S Bargiela Vázquez, D González Villar, P Estévez Boullosa, JI Rodríguez Prada
Journal: Endoscopy (2015)

La técnica de mususectomía asistida con bandas facilita la extirpación de lesiones que, mediante una técnica de polipectomía-mucusectomía convencional, dificilmente podrían ser enlazadas con el asa de polipectomía. Resulta útil tanto en la resección de lesiones epiteliales como subepiteliales del tubo digestivo.