tbuckley/cabot-search huggingface dataset:
Long-term use of sustained-release cytarabine for symptomatic management and treatment of meningeosis neoplastica.
Authors: Franziska Jahn, Timo Behlendorf, Cordula Globig, Berit Jordan, Hans-Heinrich Wolf, Karin Jordan, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2012)

e19579 Background: Treatment of meningeosis neoplastica remains challenging due to advanced systematic disease and limited treatment options including a high treatment burden. Liposomal Cytarabine (DepoCyte) is a slow-release formulation of cytarabine that maintains cytotoxic concentrations in the Cerebrospinal fluid (CSF) for &gt;14 days following a single injection. This two week interval has potential benefit due to reduced interventions especially in palliative settings. Methods: We reviewed all patients at our institution treated with liposomal cytarabine (LC) between 3/2004 and 9/2011.The data included tumor type, ICF-cell-count, neurologic disorders due to meningeal affection and time interval from intrathecal therapy to progression and to death of the patient.Assessment for meningeosis neoplastica included neurological examination, CSF assessment and brain MR imaging. LC was administered intralumbar at 50 mg every 2-weeks until progression or appearance of severe side effects. Results: To date 51 adult patients eligible for safety evaluation (48 pts. for efficacy evaluation) (median age 61 y [range 23 - 81 y]) were treated with LC. 72.5% of the included patients had lymphoma, 5.9% breast cancer and 21.6% other solid malignancies. Concurrent systemic chemotherapy was given in 82% of the patients. A total of 160 doses were administered (mean 2.9, range 1- 13). The most frequent side effects were mucositis (21.6%), elevated body temperature (15.7%), backpain (9.8%) and nausea/vomiting (7.8/5.9%). In two lymphoma patients with long term use of LC (13/ 4 applications) cauda equina syndroms appeared. In 61.9% of patients a reduction of neurological symptoms could be achieved; 53% of the patients attained a cytological response in CSF. Median overall survival was 20 months. Conclusions: The obtained results are comparable to those previously reported for methotrexate given 3 times a week. Thus our trial indicates that the 14-day dosing interval is on one hand effective to decrease neurological symptoms caused by meningeosis neoplastica with a favourable safety profile and on the other hand is less burdensome for the patients due to reduced manipulation and treatment burden respectively.
A lesson in plasticity: a 74-year-old man with plastic bronchitis
Authors: Anand Shah, Jackie Donovan, Phil Marino, Pallav L Shah, Anand Devaraj, Kshama Wechalekar, Toby M Maher, Michael R Loebinger, Robert Wilson
Journal: Thorax (2017)

AS: A 74-year-old male was transferred to the Royal Brompton hospital from a local hospital with respiratory failure and expectoration of bronchial casts (see figure 1A). The patient recalls recurrent chest infections with occasional haemoptysis in his teens with no prior history of asthma, TB or pertussis. Despite investigation and antibiotic treatment, his symptoms of intermittent, chronic recurrent bronchial cast expectoration continued. A fibreoptic bronchoscopy on the patient, aged 41, revealed erythematous bronchial mucosa in the right middle lobe, with a ventilation/perfusion scan revealing concomitant decreased ventilation. Bronchial washings were unremarkable, and given concern of a pathology originating from the right middle lobe, a right middle lobectomy was performed. Histology showed non-specific inflammatory fibrosis around the lobar bronchus.



Figure 1 
(A) Representative image of an expectorated bronchial cast by the patient. (B and C) CT image demonstrating marked diffuse bronchial wall thickening with mild bilateral patchy ground glass opacities with extensive consolidation in the right upper lobe. Minimal interlobular septal thickening in the lower lobes is also noted. (D) Image following centrifugation of a liquefied bronchial cast expectorated by the patient revealing a turbid fatty layer confirming its chylous nature. (E) Images of lymphangioscintogram (anterior thorax with and without right shoulder and costal margin markers) showing abnormal tracer activity in the right lung (indicated by red arrow) confirming chylous leak. Tracer activity is also seen in the abdominal lymphatic channels and in the liver (indicated by red star) due to systemic circulation of radiotracer on delayed images.



His symptoms, however, did not resolve. Microbiological examination of his casts revealed no growth, and histological examination showed fibrin and mucus with some lymphocytes. Further trials of corticosteroids, nebulised N-acetylcysteine, hypertonic saline, prophylactic azithromycin, systemic antifungals and oral cyclophosphamide were unsuccessful. Extensive immunological and allergic tests were normal.

His symptoms remained stable till age …
Viral reactivations and associated outcomes in the context of immune reconstitution after pediatric hematopoietic cell transplantation
Authors: Rick Admiraal, Coco C.H. de Koning, Caroline A. Lindemans, Marc B. Bierings, Annemarie M.J. Wensing, A. Birgitta Versluys, Tom F.W. Wolfs, Stefan Nierkens, Jaap Jan Boelens
Journal: Journal of Allergy and Clinical Immunology (2017)
Determining needs for nonmedical support during cancer care.
Authors: Michael N. Neuss, Yu Shyr, Anne Washburn, Stephanie L Elliott, Kristin Carson, Kate Carson, Debra L. Friedman
Journal: Journal of Clinical Oncology (2017)

82 Background: The need for supportive care services during cancer treatment appears obvious but ranges from 7 to 100% are reported. (McMurray 2001) (Soothill K, 2001). The Commission on Cancer (CoC) requires programs to assess these needs. We report on the rates of identified needs and our survey methodology. Methods: VICC members developed a 41 element survey to assess financial, emotional, and educational needs. Surveys were made available to patients with instructions, but no facilitators (Method 1). Then the same surveys were personally given to patients by two trained research coordinators who randomly selected, instructed and helped patients to complete the survey (Method 2). We report the responses using the two study methodologies. The difference between the two studies was examined using the two-sided chi-square test. Results: Results are presented in Table below. Conclusions: The rate of self-reported need for supportive and educational services in our study was small, but a meaningful minority of patients require assistance with supportive care. Simple unsupervised surveys led to results which were very similar to those supported by more complex and expensive methodologies. These data will inform the design of future survey methodology as well as intervention targets for patient navigators. [Table: see text]
Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors
Authors: Raja Pramanik, Sandeep Agarwala, Yogendra Kumar Gupta, Sanjay Thulkar, Sreenivas Vishnubhatla, Atul Batra, Deepa Dhawan, Sameer Bakhshi
Journal: JAMA Oncology (2017)

Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence.To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy.A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options.One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression.The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points.A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy.Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit.clinicaltrials.gov Identifier: NCT01858571.
Gemcitabine and oxaliplatine (GEMOX) in gemcitabine-refractory advanced pancreatic cancer: A phase II study
Authors: J.-L. Van Laethem, M. Polus, R. Marechal, A. Demols, F. Gay, M. Marijken, A. Hendlisz, M. Peeters
Journal: Journal of Clinical Oncology (2004)

4119 Background/aims: GEMOX regimen has been shown to be active in first line therapy of advanced pancreatic cancer; this study aims to evaluate the activity and tolerability of GEMOX in patients previously treated by standard administration of gemcitabine. Patients and methods: Thirty patients (M/F : 16/17; median age : 57; locally advanced disease/ metastatic : n=12/21; WHO PS 0/1/2 : n = 12/17/4,mesurable disease) were included. All patients had progressed under or after gemcitabine therapy (gem alone : n = 14, gem + other drug : n = 10; gem + radiotherapy : n = 9) administered as a 30 min IV infusion). The GEMOX regimen consisted of gem 1000 mg/m2 as a 100 min infusion D1 (10 mg/m2/min) and oxaliplatine 100 mg/m2 as a 2h infusion D2, q 2 weeks. Results: All patients received at least one cycle of GEMOX (median : 4; range : 1–21); dose reduction or delay was required in 6 and 8 patients (18 and 24%, respectively). Thirty patients were evaluable for response : PR = 7/30 (23.3%); SD = 8 weeks = 10/30 (30%); SD < 8 weeks = 1/30; PD =11/30 (36%). Median duration of response was 5 months and TTP 4 months (range : 0.5–15 m). Median survival was 4 months. Clinical benefit was observed in 16/31 patients evaluable (51.6%). Grade III/IV toxicities occurred in 7/33 patients (21.2%) and grade I/II/III neurotoxicity was observed in 17(51%)/3 (9%) and 4 (12%)patients,respectively. There was one toxic death due to febrile neutropenia. Conclusions: The GEMOX regimen is active, well-tolerated and may be of benefit in patients who become refractory to standard gemcitabine therapy. No significant financial relationships to disclose.
Serum levels of 9α,11β‐<scp>PGF</scp><sub>2</sub> and apolipoprotein A1 achieve high predictive power as biomarkers of anaphylaxis
Authors: M. Wittenberg, M. Nassiri, W. Francuzik, K. Lehmann, M. Babina, M. Worm
Journal: Allergy (2017)

Abstract Anaphylaxis is a life‐threatening hypersensitivity reaction. To identify biomarkers for the condition, we assessed serum levels of apolipoprotein (Apo)A and ApoE. We found a reduction of both lipoproteins in anaphylactic mice as well as in orally challenged food allergic patients. We then compared patients after acute anaphylaxis with several control groups (nonallergic, history of allergen‐triggered anaphylaxis, acute cardiovascular/febrile reactions). In this unpaired setting, ApoE levels were unaltered, while ApoA1 was reduced in the anaphylactic group. Although unable to discriminate between anaphylaxis and cardiovascular/febrile reactions, ROC curve analysis revealed a reasonably high area under the curve ( AUC ) of 0.91 for ApoA1. Serum 9α,11ß‐ PGF 2 , recently identified as a suitable biomarker for anaphylaxis, outperformed ApoA1 with AUC =0.95. Intriguingly however its power further increased upon combination of both mediators reaching AUC =1 . Our data suggest that ApoA1 combined with 9α,11ß‐ PGF 2 represents a useful composite biomarker of anaphylaxis, achieving superior diagnostic power over either factor alone.
Challenges, barriers, and keys to success for sustainable quality improvement in oncology: A focus group of oncology quality leaders.
Authors: Anne C. Chiang, Katherine Elizabeth Reeder-Hayes, Kristen K. McNiff, Tracey L. Evans, Inga Tolin Lennes, Erica Eaton, Arif Kamal
Journal: Journal of Clinical Oncology (2017)

78 Background: A sustainable, standardized approach for quality assessment and improvement is increasingly expected in oncology. This requires oncology leaders to identify processes and infrastructure to facilitate sustainable initiatives for practice refinement. To date, few summative reports of lessons learned, key success factors, and barriers to regular quality improvement have been reported. Methods: After IRB protocol approval, a focus group of 11 diverse physician oncology leaders was conducted, using a guide developed through multiple discussions by investigators. The physicians represented diverse organizations with community-based, private practice and academic settings. Data analysis of interview transcripts was performed iteratively, with a grounded theory approach with a method called “constant comparisons”, with related open and axial coding techniques. Transcripts were coded independently by two or three coders, and the resulting code lists integrated prior to final analysis. Differences in coding were resolved by consensus. Results: Overall, physician quality leaders discussed needs and barriers in 5 major domains: coordination of care, communication, finances, value, and quality improvement. Two major themes emerged: rapid change cycles in a dynamic landscape of practice--changing business models and care delivery, new expensive drugs, oral chemotherapy--and their respective unintended consequences on quality of care, e.g. financial toxicity for patients, misalignment of financial incentives and a quality agenda. Participants discussed responding to these changes and key factors in harnessing the practice model to deliver quality care. Conclusions: Cancer care delivery is rapidly evolving and undergoing intrinsic cycles of quality improvement. This project helps to inform systemic quality improvement efforts targeted towards oncology practices by identifying areas of concern and highlighting key factors to be addressed to achieve value, alignment and quality of care. Institutional culture and infrastructure including resources and incentives for quality improvement/measurement were identified as critical success factors.
Characteristics and early outcomes of cervical cancer patients at Butaro District Hospital, Rwanda: a retrospective review
Authors: Sonya Davey, Egide Mpanumusingo, Alex Fehr, John Butonzi, Cyprien Shyireambere, Vedaste Hategekimana, Jean Bosco Bigirimana, Ryan Borg, Regis Uwizeye, Neo Tapela, Tom Randall, Lawrence Shulman, Paul Park, Tharcisse Mpunga
Journal: The Lancet Global Health (2017)

BackgroundCancer treatment facilities are scarce in rural areas of low-income and middle-income countries, where the highest burden of cervical cancer exists. The Butaro Cancer Center of Excellence (BCCOE), in rural Rwanda, is a Rwandan Ministry of Health facility supported by Partners In Health and Dana-Farber/Brigham and Women's Cancer Center. The cervical cancer programme includes diagnosis, staging, and treatment. However, because of resource limitations, only 15 patients per month could be referred for radiotherapy to the Uganda Cancer Institute. In this study, we describe cervical cancer treatment at BCCOE and early patient outcomes.MethodsIn July, 2016, we retrospectively reviewed records for patients with cervical cancer enrolled between July 1, 2012, and June 30, 2015, at BCCOE. We extracted data on patients' characteristics, disease stage, treatment, and outcomes.FindingsWe included 438 patients: median age was 52 years (IQR 42–60 years), 35 patients (8%) had laboratory-confirmed HIV, 142 (36%) smoked tobacco, median number of pregnancies was 7 (IQR 5–9), and 41 (10%) had had a hysterectomy before enrolment. 258 patients (60%) had a diagnosis confirmed by pathology, and 391 patients (91%) had a documented disease stage. Of these, 13 (3%) were Stage I, 183 (47%) were Stage II, 154 (39%) were Stage-III, and 41 (11%) were Stage IV. There was a curative, instead of palliative or undecided, intent for 85% of Stage I patients, 91% of Stage II, and, 12% of Stage III. 165 women (38%) were referred for concurrent radiation therapy, chemotherapy, and brachytherapy in Uganda, and 19 (4%) were referred for radical hysterectomy. At their last recorded visit, 77 patients (18%) had no evidence of recurrence, including: 6 (46%) Stage I patients, 66 (37%) Stage II, 5 (3%) Stage III, but no Stage IV patients (p =<0·0001). Overall, 114 patients (27%) were lost to follow-up during or after treatment.InterpretationOur experience shows that a cervical cancer treatment programme is viable in a low-resource, rural setting. However, many challenges exist, especially the severity of disease at intake (about half of patients presented with Stage III or IV disease) and that there are no radiation facilities in Rwanda. Further, a quarter of patients were eventually lost to follow-up during the study. Future implementation interventions will focus on strategies to overcome these challenges.FundingPartners in Health, Dana-Farber Cancer Institute, Rwandan Ministry of Health.
Pharmacokinetics (PK) of the chimeric anti-G<sub>D2</sub> antibody, ch14.18, in children with high-risk neuroblastoma.
Authors: Ami Vijay Desai, Elizabeth Fox, Theresa C. DiSipio, L. Mary Smith, Allison Lim, John M. Maris, Frank M. Balis
Journal: Journal of Clinical Oncology (2012)

9576 Background: The PK of ch14.18, a chimeric monoclonal antibody (cMoAb) that significantly improves survival in high-risk neuroblastoma, was previously reported to be highly variable in children, and its clearance (CL, 130 mL/h · m 2 ) and volume of distribution (Vd ss , 32 L/m 2 ) were &gt;10-fold higher than the CL and Vd ss of other cMoAbs. Characterizing the PK of ch14.18 and the factors responsible for its variability could lead to alternative dosing strategies that reduce toxicity. Methods: Detailed PK sampling was performed prior to, during and for 25 d after 4 daily 10 h infusions of 25 mg/m 2 of ch14.18 administered with sargramostim (ANBL0032) in children enrolled on an IRB-approved institutional correlative protocol supported by United Therapeutics Corp. Ch14.18 concentrations were measured with a validated ELISA with a lower limit of detection of 0.44 mcg/mL. PK parameters were derived using non-compartmental methods and reported as median (range). Results: 5 males and 4 females, median (range) age 3.5 (1-7) yrs, have been enrolled. Six were studied on cycle 1 (C1), 2 on C5 and 1 on C3; 3 of 6 patients studied on C1 were re-studied on C3. Data from 3 patients are not included because pre-treatment plasma samples contained a substance that interfered with the ELISA. The C max after the 4 th daily infusion was 14 (10-24) mcg/mL, and ch14.8 was undetectable at day 25 in 3/6 patients. The half-life was 220 (120-390) h, and the CL was 11 (3.8-16) mL/h · m 2 , which is similar to the average CL of 4 other cMoAbs (11 mL/h · m 2 ). The Vd ss of 2.8 (1.2-3.9) L/m 2 approximated blood volume and was similar to the Vd ss of other cMoAbs (1.7 L/m 2 ) and humanized MoAbs (2.8 L/m 2 ). AUC 0-∞ in 2 patients studied twice were 3440 and 1540 mcg · h/mL on C1 and 2760 and 2690 mcg · h/mL on C3. Conclusions: Ch14.18 CL, Vd ss and half-life in children are similar to those in adults receiving ch14.18 at the same dose and similar to other cMoAbs. Ch14.18 PK in children was less variable than previously reported. The identity of the interfering substance in the plasma of some patients requires further investigation. A limited sampling strategy will be developed from these data for use in larger multi-institutional PK studies of ch14.18.
Adjuvant oral uracil and tegafur (UFT) improves survival after complete mesorectal excision (ME) for pathologic TNM stage III rectal cancer (RC): Results of the National Surgical Adjuvant Study (NSAS)-Colorectal Cancer (CC) 01 randomized trial
Authors: T. Akasu, Y. Moriya, S. Yoshida, K. Shirao, Y. Ohashi, S. Kodaira
Journal: Journal of Clinical Oncology (2004)

3524 Background: Optimal surgery and optimal adjuvant therapy for stage III RC have not been established yet. Although ME and preoperative radiotherapy are becoming standard practices for RC in the Western countries, ME for clinical stage I RC and ME with extended lateral pelvic lymph node dissection (ELPLND) for clinical stage II or III RCs have been standard practices in Japan. Methods: NSAS-CC01 is a randomized trial comparing postoperative adjuvant oral UFT (400 mg/m2/day for 5 days every 7 days for 1 year) after complete ME, versus complete ME alone in terms of relapse-free survival (RFS) and overall survival (OS). The patients who underwent ME or ME plus ELPLND with microscopic negative margins for pathologic stage III RC (PS 0–2, age 20–75 years, no other adjuvant therapy) were eligible for this trial. Extent of resection was determined by preoperative and intraoperative assessments of tumor location and stage according to the guidelines of the Japanese Society for Cancer of the Colon and Rectum. Extent of resection was documented, and pathologic examination was done according to the guidelines. Results: During 1996 to 2001, 276 (140 UFT, 136 surgery alone) patients were allocated from 28 institutions using a randomization center. Pretreatment characteristics were well balanced between the two groups; median age 58 years, male in 60%, the lower RC in 40%, pT3/T4 RC in 80%, ME with ELPLND in 38% of patients. 75% UFT patients completed more than 84% of scheduled doses. Grade 2 and Grade 3 events were observed in 65% and 17% of UFT patients, respectively. Due to them, 18 patients (13%) stopped UFT intake. Planned interim analysis in 2003 (median follow-up: 3 years) revealed significant prolongation of RFS (P=0.001) and OS (P=0.005) in the UFT group. Three-year RFS rate and OS rate were 78% and 91% in the UFT group, and 60% and 81% in surgery-alone group, respectively. Local recurrence rates were low in both groups (UFT 6%, surgery alone 10%). Conclusions: Adjuvant oral UFT improves survival after complete ME for pathologic stage III RC. No significant financial relationships to disclose.