tbuckley/cabot-search huggingface dataset:
Bloodless transplant: Autologous stem cell transplant in Jehovah’s witnesses—An Indian experience.
Authors: Girish V Badarkhe
Journal: Journal of Clinical Oncology (2016)

e19003 Background: Jehovah’s Witnesses are members of a religious group founded in the 1870s in Pennsylvania by Charles Taze Russell. There are an estimated 6 million Jehovah’s Witnesses worldwide. Most Jehovah’s Witnesses will refuse transfusion of any major blood products, which they define as red cells, white cells, plasma, and platelets, on religious grounds, Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of lymphomas and multiple myeloma. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support. Methods: In this study, we treated 5 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF) and plerixafor or G-CSF alone to mobilize stem cells. All patients received pre and post-transplant intravenous iron, erythropoietin along with post transplant G-CSF, eltrombopag and epsilon aminocaproic acid support. Results: There were two major bleeding complications (40%), with one treatment-related deaths (20%). There were three minor bleeding complications (60%). The median nadir in hemoglobin level was 6.5 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median nadir in WBC and platelet count is 50cells/µL and 9x109 / L respectively. The median total number of days with platelet count less than 10x109/L was 6 days; the median days to platelet engraftment was 20 days. Median days to WBC engraftment were 16.5 days. The mean expenditure for the whole transplant was INR 1.34 million($20,000). Conclusions: Autologous stem-cell transplantation can be performed safely without the use of any blood products in developing country like India at a fraction of the cost of transplant at other centers worldwide.
High PEEP Reduces Recruitment/Derecruitment During Neurally Adjusted Ventilatory Assist in Mild Experimental ARDS
Authors: Gaetano Perchiazzi, Mariangela Pellegrini, Hannes Lantz, Göran Hedenstierna, Anders Larsson
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

High PEEP Reduces Recruitment/Derecruitment During Neurally Adjusted Ventilatory Assist in Mild Experimental ARDS
Phase 1 study of entrectinib (RXDX-101), a TRK, ROS1, and ALK inhibitor, in children, adolescents, and young adults with recurrent or refractory solid tumors.
Authors: Ami Vijay Desai, Garrett M. Brodeur, Jennifer Foster, Stacey L. Berg, Ellen M. Basu, Suzanne Shusterman, Amit J. Sabnis, Margaret Macy, Janet Yoon, Karen Gauvain, Vanessa Esquibel, Edna Chow Maneval, Pratik S. Multani, Elizabeth Fox
Journal: Journal of Clinical Oncology (2018)

10536 Background: Entrectinib (RXDX-101) inhibits TRKA/B/C, ROS1, and ALK tyrosine kinases with IC50 < 2 nM. In vivo, entrectinib is active in several fusion-driven solid tumor and TRKB-expressing neuroblastoma (NB) models. Central nervous system (CNS) penetration enables targeting of CNS metastases and primary tumors. Entrectinib has clinical activity in adults with malignancies harboring NTRK1/2/3, ROS1, or ALK gene fusions [Drilon 2017]. Methods: Patients (age 2-21 years) with recurrent or refractory extracranial solid tumors were eligible for this multicenter Phase 1 study. 4 doses levels (250, 400, 550, 750 mg/m2) were evaluated using a 3+3 design to determine the recommended phase 2 dose (RP2D). Entrectinib capsules were administered orally, once daily, on continuous 4-week cycles. Adverse events were graded using CTCAE v4.03; response assessed by RECISTv1.1 and detailed pharmacokinetic sampling was completed. Results: 16 patients enrolled; 15 were evaluable (9 male, 6 female) with median (range) age 10 (4-20) years. Diagnoses included NB (n = 10), inflammatory myofibroblastic tumor (IMT; n = 2), salivary gland adenocarcinoma (n = 1), synovial sarcoma (n = 1), and infantile fibrosarcoma (IFS, n = 1). Somatic target gene fusions were identified in IMTs (DCTN1-ALK, TFG-ROS1) and IFS (ETV6-NTRK3). Dose-limiting toxicities included grade (G) 2 creatinine increase > 7 days in 1/6 patients receiving 550 mg/m2 and 1 patient each with G2 dysgeusia/fatigue > 7 days and G3 pulmonary edema out of 3 patients receiving 750 mg/m2, thus confirming the pediatric RP2D as 550 mg/m2. Overall toxicity profile and drug exposure were comparable to the adult RP2D. 4 patients (2 IMT, 1 IFS, 1 NB) continue protocol therapy. All 3 fusion-positive patients have experienced an objective response. Conclusions: The RP2D of entrectinib in children, adolescents, and young adults with solid tumors is 550 mg/m2 daily. Preliminary antitumor activity has been seen in gene fusion-positive patients. Entrectinib continues to be investigated in expansion cohorts of patients with primary CNS tumors, extracranial solid tumors harboring NTRK, ROS1, or ALK fusions, and patients with NB. Clinical trial information: NCT02650401.
The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy: A case-control study in a Northern Italy Cancer Centre.
Authors: Francesco Iachetta, Candida Bonelli, Alessandra Romagnani, Raffaella Zamponi, Lorenzo Tofani, Enrico Farnetti, Davide Nicoli, Angela Damato, Maria Banzi, Bruno Casali, Carmine Pinto
Journal: Journal of Clinical Oncology (2018)

2573 Background: Deleterious polymorphisms in gene-encoding DPD (DPYD) may result in the severe reduction of DPD enzymatic activity that causes life-threatening toxicities when the standard dose of fluorouracil is used. DPYD*2A (IVS14+1G > A) is the most common single-nucleotide polymorphism (SNP) associated with critical DPD deficiency. To enhance prevention of fluoropyrimidine toxicity, we assessed the potential clinical impact of additional DPYD polymorphisms. Methods: In 2011, we began screening DPYD*2A in patients candidate for fluoropyrimidine based-chemotherapy. We planned a case-control study with all cases of DPYD*2A wild type who developed CTC-NCI-V.3 toxicity ≥ G3 and with a cohort of patients who did not present severe toxicities (ratio 1:1.5). The two groups were matched for tumour site, staging (I-III vs IV) and patient’s age. Then we tested the additional SNPs (c.2846A > T, c.1679T > G, c.2194G > A) using Real Time PCR. Results: From 2011 to 2016 we screened 1,827 patients for DPD deficiency, of those 31 subjects (1.7%) showed DPYD*2A SNP. Complete clinical information was available only for 668 patients and of those, 146 (21.9%) developed severe toxicities (Case group). A control group was instead established with 220 patients who experienced no or mild toxicities. Fifty-three patients carried a variant in one of the additional SNPs: 35 subjects (66%) fell into the Case group and 18 (34%) into the Control group (OR 3.53, 95% IC 1.91-6.53. p < 0.0001). c.2194G > A was the most frequent SNP (12.5%, 46 of 366 pts) and showed a correlation with hematologic toxicity. In particular, neutropenia was observed in 50% of the patients carrying c.2194G > A (23 out of 46) vs 21% of patients c.2194 WT (67 out of 320) (OR = 3.75 95%IC 1.98-7.10; p < 0001). We confirmed that c.2826A > T (1.37%, 5 of 366 pts) was related to various toxicity (p = 0.0097) and c.1679T > G (0.55%, 2 of 366 pts) showed only gastrointestinal toxicity (p = 0.0027). Conclusions: Our data suggested that additional DPYD polymorphisms could enhance prevention of fluoropyrimidine toxicity. c.2194G > A is the most frequent polymorphism and it resulted associated with neutropenia.
TCT-217 Stenting of Coronary Bifurcation Lesions with Bioresorbable Everolimus-Eluting Scaffolds- longterm outcome from Poznan Bifurcation-Absorb Registry
Authors: Magdalena Lanocha, Adrian Wlodarczak, Sylwia Iwanczyk, Pawel Kozak, Aleksander Araszkiewicz, Wlodzimierz Skorupski, Marek Grygier, Stefan Grajek, Maciej Lesiak
Journal: Journal of the American College of Cardiology (2018)
Liver metastasis as an independent predictor for mortality in patients who developed tumor lysis syndrome: Analysis of 132 patients with solid tumors.
Authors: Jonathan Harmon, Sarah Allen, Jill Cassaday, Kirill Ruvinov, Desi Stoyanova, Ramya Tadipatri, Mitchell Ross, Jaya Raj, Jue Wang
Journal: Journal of Clinical Oncology (2018)

e18766 Background: Patients with solid tumors are usually classified as being at low to intermediate risk for developing tumor lysis syndrome (TLS); however, there have been a growing number of case reports describe TLS in patients with solid tumors. Data regarding clinical features, treatment, and survival outcomes in solid tumors are limited. It is unclear whether liver metastasis represents an individual risk factor for TLS. Methods: A pooled analysis of published cases of TLS in solid tumor patients was performed. Descriptive statistics, such as frequency, medians, and ranges, were used to characterize the pooled sample. The survival rate was calculated using log-rank and Kaplan-Meyer analyses. Results: The median age of 132 solid tumor patients who developed TLS was 57 (8-94). Male: female = 1.69. The most common sites were gastrointestinal (29%); genitourinary (17%); lung cancer (16%); melanoma (11%), breast cancer (8.3%). Among the typical biochemical findings of TLS, acute renal insufficiency and hyperuricemia were identified in nearly all patients and increased serum LDH were reported in over 71% of patients. 72% of patients had liver metastatic disease. 23% patients had spontaneous TLS. The rest (77%) of TLS was associated with a variety of treatment regimens, including chemotherapy, immunotherapy, hormonal, radiation therapy, transarterial chemoembolization (TACE) and surgery. The median time from treatment to TLS was 3 days (0.3-21). Seventy-two of 132 (59%) patients died during the acute episode of TLS: 65% patients with liver metastasis and 26% patients without liver metastasis. In a multivariate analysis, older age (HR 2.64; 95% Confidence Interval 1.48-4.70; p = 0.001) and liver metastasis (HR 3.48; 95% CI 1.45-4.71; P = 0.005) were identified as independent predictors for increased mortality. Conclusions: TLS in elderly patients with solid tumors with liver metastases is associated with extremely poor clinical outcome, likely due to late onset after anticancer therapy, under-diagnosis of TLS and missed opportunity for intervention. While TLS in solid tumors is rare, close monitoring and prophylaxis should be considered in these patients.
Passive hyperspectral sensing to identify colorectal cancer in intraoperative colon specimens.
Authors: Robert J. Beaulieu, Seth D Goldstein, Amit Banerjee, Bashar Safar, Nita Ahuja
Journal: Journal of Clinical Oncology (2016)

e15161 Background: Surgical management of colorectal cancer relies on accurate intraoperative identification of tumor and resection to negative margins. Hyperspectral (HS) imaging is a passive, non-ionizing diagnostic method that has garnered increased interest for its ability to detect multiple tumor types and even neoplastic biomarkers. We sought to explore the ability to use HS spectroscopy for transluminal identification of tumor specimens during surgical resection of colorectal cancers. Methods: This study was approved by Johns Hopkins Hospital IRB (IRB00056516). A cohort of patients with confirmed or suspected colorectal cancer who underwent operative resection were enrolled. HS measurements (Labspec 5000, ASD, Inc, Boulder, CO) of resected specimens both intra- and transluminally was performed immediately after resection and again after gross pathologic examination. Spectral results were analyzed with linear discriminant analysis in pairwise comparisons between normal and cancer tissue, and correlated with pathologic evaluation. Results: Eleven patient specimens were successfully analyzed. In 2 patients, histologic evaluation revealed inflammatory disease only. HS spectroscopy accurately predicted an absence of tumor specimen in these samples. For patients with confirmed colorectal cancer, transluminal spectroscopy was able to detect 86% of tumor specimens with a 0% false positive rate (sensitivity 86%, specificity 100%). For intraluminal specimens, spectral tumor detection rate of 100% with no false positives (sensitivity 100%, specificity 100%). Spectral waveforms did not differ significantly before and after gross pathologic examination. Conclusions: HS measurements have high sensitivity (86-100%) and specificity (100%) for the real-time detection of colorectal cancer imaged through the bowel wall and intraluminally. Further, signal fidelity does not appear to degrade within the first 30 minutes following resection. High-resolution optical spectroscopy is a potentially useful tool in the operative management of colorectal cancer. These findings also have implications for the development of advanced diagnostic methods, including endoscopic evaluation.
The genomics of young lung cancer.
Authors: Barbara J. Gitlitz, Deborah Morosini, Alicia L. Sable-Hunt, Bonnie J. Addario, Stacy L. Mach, Mark Byron Jennings, S. Lani Park, Marisa A Bittoni, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2016)

9083 Background: Lung cancer is increasingly understood as a disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize that young age at diagnosis ( < 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration (GA). Our study will prospectively characterize the somatic and germline genomics of young lung cancer. Methods: Accrual opened in July 2014. Patients (pts) are eligible if diagnosed with bronchogenic lung cancer < age 40. The study website, https://www.openmednet.org/site/alcmi-goyl allows for virtual consenting and remote participation from anywhere in the world. We defined 7 GA of interest based on the Lung Cancer Mutation Consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). We aim to show the prevalence of targetable GA in our stage 4 adenocarcinoma (AC) pts will be greater in our population compared to the LCMC, with an increase from 35% to 50%; and an improvement in use of targeted therapy from 22% to 40%. Study subjects without a known genotype undergo genomic profiling with the FoundationOne test. Results: Preliminary results of 63 pts with stage 4 AC show that 83% have either an ALK re-arrangement n = 29 (46%), an EGFR activating mutation n = 16 (25%), a ROS1 fusion n = 4 (6%), a RET fusion n = 2 (3%) or a HER2 mutation n = 2 (3%). Other GA of interest in 22% with AC includes TP53, ATM and BRCA2 mutations. Though numbers are small, analysis of exposures show findings including: ROS1 fusion pts are never smokers, without exposure to secondhand smoke and compared to those with EGFR and ALK mutations, had a higher proportion of family history of lung cancer (60% vs. 25%). Conclusions: The trial is currently accruing (NCT02273336). Thus far in our prospective series our results have far exceeded our statistical expectations, with 83% of our stage 4 AC pts having an actionable mutation. We have defined a genomically enriched subtype of lung cancer and laid the groundwork for further studies of germline and environmental lung cancer risk factors and thus, are planning a large-scale Case Control study of the Epidemiology of YLC. (Final study results of 2 years of accrual will be presented at ASCO 2016 meeting). Clinical trial information: NCT02273336.
Patient-reported outcomes following autologous stem cell transplantation for patients with multiple myeloma.
Authors: Noa Biran, Roxanne Jensen, Arnold L. Potosky, David Samuel DiCapua Siegel, David H. Vesole, Jeanne S. Mandelblatt, Joshua Ryan Richter, Trina McClendon, Charlene Kuo, Claire Coleman, Vasiliki Zotou, Shaw Li, Princess Alintah, Colleen McGuire, Christine Rini
Journal: Journal of Clinical Oncology (2018)

e22069 Background: The management of patients with multiple myeloma (MM) results in a considerable burden to patients, their families, and the system in terms of morbidity, mortality and cost. Autologous stem cell transplantation (ASCT) improves overall survival compared with continued induction/maintenance therapy. However, little is known about the short-term symptoms and functional and cognitive decline in patients after ASCT. We conducted a pilot study to compare patient-reported cognition, symptom severity, and financial distress in patients receiving ASCT. Methods: Patients newly diagnosed with MM (n = 28 to date; 75 target) were enrolled from two centers between October 2016 and December 2017 and assessed prior to transplant and 6-months later. Decline was measured using the Patient Reported Outcomes Measurement Information System (PROMIS), where scores range from 0-100, with higher scores indicating more of the symptoms or better function. The PROMIS cognitive function v2 6a short-form was used to assess cognitive decline. Financial toxicity was assessed with the COmprehensive Score for financial Toxicity (COST) measure. Unadjuuted means are summarized for each outcome. Results: Twenty-two (79%) completed pre and post-ASCT assessments; their median age was 66 (range 51-74). From pre- to 6-months post-ASCT, symptoms improved, with a reduction in anxiety (mean 53.8, SD 11.5 to 44.2, SD 5), depression (mean 50.0, SD 10.5 to 42.5, SD 3.9), fatigue (mean 55.2, SD 10.6 to 46.7, SD 7.3), and pain interference (mean 58.8, SD 12.2 to 44.3, SD 4.6). There were improvements in satisfaction with participation in social roles (mean 48.2, SD 10.3 to 57, SD 9.2) and physical function (mean 40.3, SD 7.4 to 48.2, SD 6.5), reductions in financial toxicity (mean 30.1, SD 5.6 to 23.4, SD 9.4), and increases in cognitive function (mean 51.2, SD 11.4 to 59.4, SD 6.7). These differences are not statistically significant due to small sample size. Conclusions: These preliminary pilot data suggest that ASCT does not have a detrimental short-term effect on symptoms, function, or cognition in older MM patients. The findings will need to be extended in larger samples and compared to non-transplant recipients.
A phase II study of elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.
Authors: Andrew Jenho Yee, Jacob Laubach, Erica Leigh Campagnaro, Brea Lipe, Omar Nadeem, Craig Cole, Elizabeth O'Donnell, Robert L. Schlossman, Giada Bianchi, Andrew Robert Branagan, Samantha J. Shapiro, Cynthia C. Harrington, Jill N. Burke, Marilyn T. Gammon, Kathleen J. Lively, Cassandra Ann Thorburn, Mason L. Mann, Jens Guenter Lohr, Paul G. Richardson, Noopur S. Raje
Journal: Journal of Clinical Oncology (2018)

8012 Background: Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on NK cells and plasma cells that enhances the activity of lenalidomide and bortezomib in multiple myeloma (MM). We studied elotuzumab with pomalidomide, bortezomib, and dexamethasone (elo-PVD) in relapsed and refractory MM. Methods: The primary objective was to determine the overall response rate (ORR). Patients with refractory disease and ≥1 prior lines of treatment (including lenalidomide and a proteasome inhibitor) were eligible to participate. Elotuzumab was weekly for the first 2 cycles and then every other week. Pomalidomide was on days 1-21; bortezomib was on days 1, 8, 15; and dexamethasone was weekly. Each cycle was 28 days. Results: At time of data cutoff, 33 patients (pts) who started treatment were evaluable. The median age was 64 (range 52-79), and the median number of prior regimens was 3 (range 1-9); 27% had high risk FISH. All pts had prior lenalidomide and proteasome inhibitors (bortezomib 94%, 76% carfilzomib) and were refractory to their last line of therapy. Prior therapies also included: auto SCT (45%), pomalidomide (36%), daratumumab (21%), and isatuximab (3%). 31 pts were assessable for response (2 patients did not complete cycle 1 due to rapid disease progression or stroke and were not evaluable). The median length of follow up was 3.3 months (range 0.5-18.2): 23 pts continue on study; 7 pts discontinued for progressive disease and 3 pts discontinued for adverse events (AEs) (sepsis, pneumonia, or stroke). Best ORR was 52% (PR = 11, VGPR = 4, CR = 1); ORR for pts with prior anti-CD38 antibody, 43%; carfilzomib, 43%; pomalidomide, 40%. Median PFS was 9.7 months (95% CI 7.5-Inf). Grade 3-4 hematologic AEs included anemia (7%), neutropenia (34%), and thrombocytopenia (17%). Common non-hematologic AEs all grades included fatigue (38%), upper respiratory infection (38%), constipation (38%), hyperglycemia (38%), and neuropathy (38%, Gr 1-2 only), with 2 possibly related deaths (sepsis, pneumonia). Conclusions: Elo-PVD shows encouraging responses in patients with refractory MM. Treatment was well-tolerated with manageable toxicity and attention to infectious AEs. Clinical trial information: NCT02718833.
Ovarian Sertoli Leydig cell tumors: a single institution series of predominantly postmenopausal women.
Authors: Gregory M. Gressel, Natalia Buza, Lubna Pal
Journal: Journal of Clinical Oncology (2016)

e17052 Background: Sertoli Leydig cell tumors (SLCT) of the ovary are rare, and usually present as progressive virilization in women in their second to third decade of life. Less than 10% of patients are reportedly older than age 50. Methods: A retrospective review was performed of all cases of histologically proven ovarian SLCT diagnosed at a tertiary care institution between 1990 -2014. Results: Of the 16 patients diagnosed with SCLT over a 24-year period, nine patients (56%) were postmenopausal at the time of diagnosis with a median age of 52.5 years (IQR = 39.7 years). These 9 patients had a median interval of 14.7 years (IQR = 15) since the onset of menopause. Hyperandrogenism was a presenting feature in only 5 of 16 (31%) [median age of 49 (IQR = 26.5)] whereas postmenopausal bleeding was noted in 2 of 16 (12%). Only 3 of the patients with hyperandrogenism had preoperative hormonal assays confirming elevated total testosterone. Nine patients (56%), presented with vague symptoms of abdominal pain or bloating and were noted to have pelvic masses that were diagnosed as SLCT at the time of surgical removal. At diagnosis, tumor grade varied from well-differentiated to poorly-differentiated lesions. Nine lesions (56%) were of intermediate differentiation, and 8 patients (15%) received adjuvant chemotherapy. The decision to give adjuvant treatment was made for cases of higher than stage IA cancer, cases where concurrent tumors were identified on the surgical specimen, or in cases of poor tumor differentiation. Disease free survival over a median followup of 31.5 months (IQR = 73.5 months) was 100%. At the time of this study, all patients are alive with no recurrences with the exception of one who died from unrelated causes. Conclusions: Our patient population with SLCT was noticeably older than what has been described in literature, with greater than 50% being postmenopausal. To the best of our knowledge, this is the largest case series of postmenopausal patients with SLCT. Features of androgen excess and abnormal bleeding were evident in only a small sub-group. While the definitive management approach to SLCT remains controversial and varied, prognosis following definitive surgery and risk of recurrence are reassuring.