tbuckley/cabot-search huggingface dataset:
Inverse Psoriasiform Eruption During Pembrolizumab Therapy for Metastatic Melanoma
Authors: Mariam B. Totonchy, Harib H. Ezaldein, Christine J. Ko, Jennifer N. Choi
Journal: JAMA Dermatology (2015)

At a 12-week follow-up appointment, a dramatic improvement in the appearance of the cutaneous lesions was noted, with near complete resolution of the patches and plaques and small residual foci at the prior larger nodular areas.The patient continued topical nitrogen mustard with continued improvement over 12 additional weeks (Figure 1B).However, the patient subsequently developed ophthalmic symptoms, including vertical and abduction defects, blurred vision, and peripheral vision loss, attributed to ocular involvement of the NXG.The patient then began dexamethasone 20-mg doses twice a week and cyclophosphamide 300-mg/m 2 doses on days 1, 8, and 15 of a 28-day cycle.He has shown clinical and laboratory improvement after 6 months.Discussion | Necrobiotic xanthogranuloma is a chronic granulomatous disorder with the potential to affect multiple organs and is strongly associated with paraproteinemias and lymphoproliferative disease.The typical cutaneous lesions are yellowish-to-orange and erythematous-toviolaceous papules, plaques, and nodules, often with overlying telangiectasias.Scarring and ulceration may also occur in a subset of patients.Ocular lesions are found in the vast majority of patients.For most patients, skin lesions initially start on the trunk or extremities and subsequently involve the periorbital area. 1 Most cases are asymptomatic, although pain, and pruritus may occur. 2 Extracutaneous sites may rarely be involved, including the lung, myocardium, larynx, pharynx, skeletal muscle, kidney, intestine, and ovary. 3ost importantly, approximately 90% of patients with NXG display a paraproteinemia, with IgG-κ monoclonal gammopathy being the most common. 4istopathologically, NXG is characterized by a granulomatous inflammation in the dermis extending into the subcutaneous fat.There are zones of necrobiosis surrounded by granulomas with foreign body-type cells and Touton giant cells. 5Degenerated collagen is common, and cholesterol clefts within the necrobiosis are characteristic of NXG. 5 Treatment approaches depend on whether the physician is treating the cutaneous NXG alone or alongside the paraproteinemia component.Successful treatments with corticosteroids (topical, intralesional, and/or systemic), alkylating agents (chlorambucil and cyclophosphamide), interferon alpha, thalidomide, lenalidomide, intravenous immunoglobulin, phototherapy, and plasmapheresis have been reported. 3Nitrogen mustard is an alkylating antineoplastic agent that has been used to treat cutaneous T-cell lymphoma for over 40 years with a good safety profile. 6 Our patient demonstrated a significant improvement with topical nitrogen mustard, which may be a viable therapeutic option for some cases of NXG.
Human papillomavirus (HPV) transmission from oropharyngeal cancer patients to sexual partners.
Authors: V. Papadimitrakopoulou, M. Guo, C. Etzel, B. Solomon, E. M. Sturgis, S. M. Lippman, W. K. Hong, A. S. Tsao
Journal: Journal of Clinical Oncology (2010)

5527 Background: Human papillomavirus (HPV), especially serotype 16, is implicated in causing a subset of head and neck cancers. Preventing this HPV-related disease and the epidemiology of transmission are important research questions. To define the risk of HPV transmission between patients with HPV-associated head and neck cancer and their respective sexual partners, we performed HPV genotyping on cytology brushings of the oral cavity (OC)/oropharynx (OP). Methods: Patients with confirmed oropharyngeal squamous cell cancer (OPC) and their sexual partners underwent OC/OP swabs/brushings (bilateral buccal mucosa, lateral tongue, tonsillar and base-of-tongue regions, inside upper and lower lips) and answered a questionnaire; swabs and diagnostic biopsies underwent HPV genotyping. Standard PCR assay using consensus primer GP5+\/GP6+ tested for HPV serotypes (including 16, 18 and 31); if positive for HPV, this assay was followed by HPV genotyping via real-time PCR for HPV 16, 18, 31, 33, 35, 45, 52, and 58. Results: We tested 174 patient-partner pairs (n=348 persons); there were 29 HPV-positive OPC patients (17%), of whom 19 partners (66%) had HPV-positive swabs. All 19 HPV-positive partners (100%) were concordant with the OPC patient for at least one HPV type. In 4 of the 29 pairs with an HPV-positive patient, a prior history of HPV-related disease occurred in either the patient (1 rectal cancer) or the partner (3 abnormal Pap smears). Among the 29 HPV-positive patients, smoking status was current in 6 (21%), former in 10 (34%), and never in 13 (45%) and alcohol use was heavy in 4 (14%) and former in 5 (17%). 11 HPV-negative OPC patients (of which 6 were never-smokers) had HPV-positive partners, which will be evaluated further to verify primary-tumor HPV status. Conclusions: We found a high rate of transmission and 100% HPV-genotype concordance between patients and partners. Further analysis and correlation of HPV status with patient-partner characteristics, survey results, treatment outcomes, and HPV genotyping in primary tumor biopsies will be presented. No significant financial relationships to disclose.
Exercise suppresses tumor growth through epinephrine- and IL-6-dependent mobilization and redistribution of NK cells
Authors: Line Pedersen, Manja Idorn, Gitte Olofsson, Intawat Nookaew, Rasmus Hansen, Helle Johannesen, Jürgen C Becker, Britt Lauenborg, Katrine S Pedersen, Christine Dethlefsen, Jens B Nielsen, Julie Gehl, Bente Pedersen, Per thor Straten, Pernille Hojman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed significant exercise related reduction in tumor incidence and
Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo-)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): Safety results of a randomized, phase III trial
Authors: R. Hofheinz, F. Wenz, S. Post, A. Matzdorff, S. Laechelt, L. Mueller, H. Link, M. Moehler, I. Burkholder, A. Hochhaus
Journal: Journal of Clinical Oncology (2009)

4014 Background: 5-FU based CRT is regarded standard perioperative treatment in LARC. Here we report safety data of a non-inferiority phase III trial investigating (neo-)adjuvant CRT with Cape in comparison with 5-FU. Methods: Patients (pts) aged ≥18 years with LARC UICC stages II or III were recruited in this two-arm, two-strata randomized phase-III trial (arm A: Cape, arm B: 5-FU; stratum [S] I: adjuvant, S II: neoadjuvant). Regimens: Arm A: CRT: 50.4 Gy + Cape 1,650 mg/m 2 days 1–38 plus five cycles of Cape 2,500 mg/m 2 d 1–14, rep. d 22 (S I: 2 x Cape, CRT, 3 x Cape; S II: CRT, TME surgery followed by Cape x 5). Arm B: CRT: 50.4 Gy + 5-FU 225 mg/m 2 c.i. daily [S I] or 5-FU 1,000 mg/m 2 c.i. d 1–5 and 29–33 [S II] plus 4 cycles of bolus 5-FU 500mg/m 2 d 1–5, rep. d 29 (S I: 2 x 5-FU, CRT, 2 x 5-FU; S II: CRT, TME surgery followed by 5-FU x 4). Primary endpoint was survival, secondary endpoints comprised safety and disease-free survival. Results: Of 401 randomized pts a total of 392 are evaluable (Arm A n=197, arm B n=195; S I n=231, S II n=161). Both arms were well balanced with respect to age, sex, WHO status, T- and N- stages. Regarding duration of treatment, 78% (Cape) and 80% (5-FU) completed all scheduled treatment cycles in S I, and 46% (Cape) and 40% (5-FU) in neoadjuvant stratum S II. In S II a total of 38% (Cape) and 43% (5-FU) did not continue chemotherapy after tumour resection. Concerning early efficacy endpoints in S II, pts treated with Cape (evaluable thus far n=121) exhibited a higher rate of T-downstaging (defined as ypT0–2; 52 vs 39%; p=0.16) and N0 (71 vs 56%; p=0.09). Regarding overall safety (NCI-CTC), pts receiving Cape experienced significantly less leukopenia (25 vs 35%; p=0.04), but more hand-foot syndrome (31 vs. 2%; p&lt;0.001). Stomatitis/mucositis, diarrhea, nausea/vomiting, and radiodermatitis were not significantly different between both arms. Conclusions: Given the observed safety profile and the trend in improved downstaging in neoadjuvant stratum, Cape exhibits a potential to replace 5-FU as perioperative treatment of LARC. Efficacy results on the primary endpoint are expected for 2010. [Table: see text]
Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer
Authors: Aaron S. Mansfield, Stephen J. Murphy, Tobias Peikert, Eunhee S. Yi, George Vasmatzis, Dennis A. Wigle, Marie Christine Aubry
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (κ = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (κ = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (κ = 0.73). Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis. Clin Cancer Res; 22(9); 2177–82. ©2015 AACR.
Corrected QT interval prolongation in anthracycline-treated survivors of childhood cancer.
Authors: C L Schwartz, W L Hobbie, S Truesdell, L C Constine, E B Clark
Journal: Journal of Clinical Oncology (1993)

PURPOSE Comprehensive cardiac evaluations are currently recommended for all anthracycline-treated patients to detect subclinical cardiac failure. A screening test is needed that would easily and inexpensively identify patients who are at risk for late cardiac decompensation. METHODS We routinely reviewed the ECG and echocardiogram (ECHO) results of 52 of 56 anthracycline-treated long-term survivors of childhood cancer who had received &gt; or = 100 mg/m2 of ANTH (ANTH = 1 mg/m2 of doxorubicin), and who were not in clinical heart failure. Exercise testing was performed in eight patients with a corrected QT interval (QTc) of &gt; or = 0.43. RESULTS Zero of 15 patients (without chest radiation) who received less than 300 mg/m2 of ANTH versus six of 22 who received &gt; or = 300 mg/m2 of ANTH had a QTc &gt; or = 0.43 (P = .03). Three of 15 patients (with chest radiation) who received less than 300 mg/m2 of ANTH versus 12 of 22 who received &gt; or = 300 mg/m2 of ANTH had a QTc &gt; or = 0.43 (P = .03). For all patients (including those with chest radiotherapy), zero of 19 who received less than 300 mg/m2 of ANTH versus eight of 33 who received &gt; or = 300 mg/m2 of ANTH had a QTc of &gt; or = 0.45 (P = .025). Three of 19 who received less than 300 mg/m2 of ANTH versus 19 of 33 who received &gt; or = 300 mg/m2 of ANTH had a QTc of &gt; or = 0.43 (P = .003). One patient had decreased fractional shortening (FS) and QTc prolongation. Cardiac decompensation (with a FS of 24%) occurred with propranolol in a patient with previously normal FS but prolonged QTc. With exercise, the QTc became further prolonged in all four patients with a QTc of 0.44 to 0.46 and in two of four patients with a QTc of 0.43. CONCLUSION Prolongation of the QTc, a measure of myocardial repolarization, may reflect injury to myocardial cells. QTc prolongation may be predictive of an increased risk of late cardiac decompensation. If the utility of the QTc measure is confirmed, screening for evidence of myocardial damage can be easily and inexpensively performed by oncologists and primary caretakers.
Results of 2 phase I studies of intravenous (iv) pelitrexol (AG2037), a glycinamide ribonucleotide formyltransferase (GARFT) inhibitor, in patients (pts) with solid tumors
Authors: F. Robert, C. Garrett, W. R. Dinwoodie, D. M. Sullivan, M. Bishop, M. Amantea, M. Zhang, S. D. Reich
Journal: Journal of Clinical Oncology (2004)

3075 Background: AG2037 is a rationally designed, novel inhibitor of GARFT, which is an essential enzyme in the de novo synthesis of purines, a critical process for cell growth. Methods: The primary objectives of these studies were to determine the maximum-tolerated dose (MTD) and recommended safe dose of AG2037 for Phase II studies (RP2D). AG2037 was given by bolus or slow iv push (every 3 weeks in Study-002 and weekly for 3 consecutive weeks every 4 weeks in Study-003) to pts with advanced solid tumors in cohorts of at least 3 patients at each dose level. The dose for the next cohort was increased by 100% if no drug related Grade 3 or worse toxicity was encountered, and by ∼50% if Grade 2 toxicity was observed. Results: 45 pts in Study-002 were treated at doses ranging from 1 to 576 mg/m2 and 49 were treated in Study-003 at doses ranging from 1 to 760 mg/m2. Study-002 was terminated before MTD was determined since mechanism-based toxicities appeared to correlate to drug exposure and not to peak concentration. For Study-003, at the highest dose (720 mg/m2), Grade 3 anemia, thrombocytopenia, diarrhea, fatigue, mucosal inflammation, dehydration, hyponatremia, confusion, or mental status changes were observed in 1 or 2 of 6 pts. There were no grade 4 toxicities. The MTD was 540 mg/m2/infusion. Grade 3 nausea was the only Grade 3 or 4 related adverse events in the 7 patients treated at MTD. The pharmacokinetics of AG2037 were linear over the studied dose range; plasma concentrations declined in a triexponential manner with a terminal half-life of 85 hours and were inversely proportional to creatinine clearance. RBC polyglutamate increased with dose to a maximum concentration and showed minimal decline between doses. One pt with colorectal cancer had a partial response by RECIST at 6 mg/m2 (Study-003). Conclusions: The RP2D for AG2037 is 540 mg/m2/week for 3 consecutive weeks, every 4 weeks. Expected adverse events on this schedule include mild to moderate myelosuppression, mucositis, diarrhea, anorexia, fatigue, and peripheral neuropathy. Further study in colorectal and other solid tumors is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Inc. Pfizer, Inc. Pfizer, Inc. Pfizer, Inc.
Dose-seeking study of the combination of GM-CSF with pegfilgrastim plus CHOP-rituximab in patients with aggressive non- Hodgkin lymphoma (NHL)
Authors: F. Cabanillas, O. Pavia, E. Rivera, I. Liboy
Journal: Journal of Clinical Oncology (2007)

18501 Background: Therapy for aggressive B cell NHL includes CHOP-rituximab (CHOP-R)q 14 days with G-CSF support. We are now investigating CHOP-R plus pegfilgrastim (Neulasta [N]) and low dose GM-CSF (Leukine). The rationale for low dose GM-CSF is based on its stimulation of ADCC which appears to be the most important mechanism of action of R and upregulation of CD20 on B cells, in addition, to other immunomodulating effects. Some of these are seen at lower levels of GM-CSF and appear to be lost at higher doses. N is given in order to allow delivery of chemotherapy q. 2 weeks. Methods: The goal was to determine the optimal dose of GM-CSF needed to support absolute neutrophil count (ANC) recovery &gt;1,000 by day 14 without inducing marked leucocytosis when combined with N. R is given on day 1, CHOP on day 2 and growth factors start on day 3. We used a single fixed low dose of N 3 mg s.c. on day 3 and an escalating dose of GM-CSF starting at 75 mcg s.c. on day 3. GM-CSF was repeated every Monday, Wednesday and Friday. Results: So far we have delivered 65 evaluable courses to 18 pts (16 evaluable) whose median age was 58 (range 26–87). The plan was to escalate GM-CSF as necessary to support ANC recovery by day 14 without inducing severe leucocytosis. GM-CSF was to be escalated in cohorts of 5 patients at: 75, 125 and 250 mcg. The first cohort of 5 was treated at 75 mcg and all 5 recovered their ANC to &gt;1,000 by day 14 and none exceeded ANC &gt;50,000 before day 14. Therefore the next cohort of 5 received the same dose of 75 and all 5 were able to recover by day 14. Subsequently the next 6 were also treated at the same dose of 75 mcg. During 65 total courses, all but 3 pts recovered ANC to &gt;1,000 before day 14. Chemotherapy doses were not reduced unless severe infection (i.e. septic shock or bilateral pneumonia). Because of prolonged or severe neutropenia, intrapatient dose escalations of GM-CSF were done in 2 pts (to 125 mcg) during the 2nd course and to 250 mcg in 1 pt during the 3rd. Conclusions: GM- CSF 75 mcg on Mondays, Wednesdays and Fridays is adequate and safe to support ANC recovery if combined with 3 mg N. However, in view of encouraging data of McLaughlin et al with 250 mcg of Leukine plus R in indolent NHL, in the next study we will attempt to escalate Leukine to 250 mcg. [Table: see text]
A randomized multicenter Phase Ib/II study to assess the immunological effect of chemoradiation therapy (CRT) in combination with pembrolizumab compared to CRT alone in resectable or borderline resectable pancreatic cancer
Authors: Matthew Katz, Bauer W Todd, Gauri Varadhachary, Nicolas Acquavella, Gina Petroni, Timothy Bullock, Craig L Slingluff, Osama Rahma
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumor-infiltrating lymphocytes (TILs) play a major role in anti-tumor immune responses, and their presence is correlated with survival in a variety of tumors. These TILs do not reach the pancreatic cancer (PC) cells in significant numbers due to the presence of stroma and a
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death—Executive Summary
Authors: Douglas Zipes, A Camm, Martin Borggrefe, Alfred Buxton, Bernard Chaitman, Martin Fromer, Gabriel Gregoratos, George Klein, Arthur Moss, Robert Myerburg, Silvia Priori, Miguel Quinones, Dan Roden, Michael Silka, Cynthia Tracy, Sidney Smith, Alice Jacobs, Cynthia Adams, Elliott Antman, Jeffrey Anderson, Sharon Hunt, Jonathan Halperin, Rick Nishimura, Joseph Ornato, Richard Page, Barbara Riegel, Jean-Jacques Blanc, Andrzej Budaj, ; Poland, Veronica Camm, France Dean, Jaap Deckers, The Netherlands, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith Mcgregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Tamargo, José Zamorano
Journal: Circulation (2006)
Radiological placement of the gastrostomy tube should be the preferred method
Authors: B. L Murphy, P. S Sidhu, R. E Greene
Journal: BMJ (1996)

Percutaneous endoscopic gastrostomy feeding after acute dysphagic strokeStafffind it harder to stop feeding patients with a gastrostomy ED1TOR,-The initial findings of B Norton and colleagues' study comparing percutaneous endoscopic gastrostomy with nasogastric tube feeding after acute dysphagic stroke seem to suggest a better prognosis for patients fed through a gastrostomy.'I welcome the authors' intention to study the effects of this procedure on the long term quality of life and will be interested to learn of their findings.I would ask them to pay particular attention to how we should deal with those patients who do not make a good recovery and who face the prospect of long term feeding through their gastrostomy.Already this is causing problems in continuing care facilities, where decisions may need to be taken on whether to continue such feeding when long term recovery does not occur.Aside from the possible legal aspects of stopping feeding, staff find it harder to stop feeding patients with a gastrostomy than patients with a nasogastric tube.It is technically simple to remove a nasogastric tube, but removing a gastrostomy requires anaesthesia.Surgery for this group of patients is not appropriate at this stage in their care.It may then become difficult for staff to continue caring for these patients while not using the "permanent" gastrostomy tube.If the use of gastrostomy after dysphagic stroke is to become routine we must more openly recognise and deal with the ethical and emotional dilemmas that may arise as a consequence.
Maintaining Outstanding Outcomes Using Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children’s Oncology Group Study ANBL0531
Authors: Clare J. Twist, Mary Lou Schmidt, Arlene Naranjo, Wendy B. London, Sheena C. Tenney, Araz Marachelian, Hiroyuki Shimada, Margaret H. Collins, Natia Esiashvili, E. Stanton Adkins, Peter Mattei, Michael Handler, Howard Katzenstein, Edward Attiyeh, Michael D. Hogarty, Julie Gastier-Foster, Elizabeth Wagner, Katherine K. Matthay, Julie R. Park, John M. Maris, Susan L. Cohn
Journal: Journal of Clinical Oncology (2019)

PURPOSE The primary objective of the Children’s Oncology Group study ANBL0531 (ClinicalTrials.gov identifier: NCT00499616 ) was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival (OS) of 95% or more for the entire cohort. PATIENTS AND METHODS Children younger than age 12 years with intermediate-risk stage 2A/2B or stage 3 tumors with favorable histology; infants younger than age 365 days with stage 3, 4 or 4S disease; and toddlers from 365 to younger than 547 days with favorable histology, hyperdiploid stage 4, or unfavorable histology stage 3 tumors were eligible. Patients with MYCN-amplified tumors were excluded. Patients were assigned to initially receive two (group 2), four (group 3), or eight (group 4) cycles of chemotherapy with or without surgery on the basis of prognostic markers, including allelic status of chromosomes 1p and 11q; ultimate duration of therapy was determined by overall response. RESULTS Between 2007 and 2011, 404 evaluable patients were enrolled. Compared with legacy Children’s Oncology Group studies, subsets of patients had a reduction in treatment. The 3-year event-free survival and OS rates were 83.2% (95% CI, 79.4% to 87.0%) and 94.9% (95% CI, 92.7% to 97.2%), respectively. Infants with stage 4 tumors with favorable biology (n = 61) had superior 3-year event-free survival compared with patients with one or more unfavorable biologic features (n = 47; 86.9% [95% CI, 78.3% to 95.4%] v 66.8% [95% CI, 53.1% to 80.6%]; P = .02), with a trend toward OS advantage (95.0% [95% CI, 89.5% to 100%] v 86.7% [95% CI, 76.6% to 96.7%], respectively; P = .08). OS for patients with localized disease was 100%. CONCLUSION Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.
A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non–Small Cell Carcinoma In Situ or Non–Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study
Authors: Samjot Singh Dhillon, Todd L. Demmy, Sai Yendamuri, Gregory Loewen, Chukwumere Nwogu, Michele Cooper, Barbara W. Henderson
Journal: Journal of Thoracic Oncology (2015)