tbuckley/cabot-search huggingface dataset:
Prevalence of first and subsequent skeletal-related events (SREs) in U.S. elderly patients with metastatic prostate cancer (mPC).
Authors: Arif Hussain, Abdulla M. Abdulhalim, C. Daniel Mullins, Yi Qian, Jorge Arellano, Arun Balakumaran, Ebere Onukwugha
Journal: Journal of Clinical Oncology (2014)

e16006 Background: SREs are common in men with mPC. While some real-world studies have estimated the prevalence of SREs, the majority don’t address the sequential pattern of first and subsequent SREs. We estimated the prevalence of first and subsequent SRE in elderly men with mPC. Methods: We analyzed elderly men diagnosed with mPC between 2000 and 2009 in the SEER-Medicare datasets and followed through 12/31/2010 or until they were lost to follow-up. Post-diagnosis SREs were identified using claims that indicated spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), or radiation (RAD, potentially suggestive of bone palliative radiation). Results: Among 8,997 mPC men with a median follow up time of 18 months, 4,176 (47.7%) experienced at least one SRE post diagnosis. Of the 4,176 men, the proportion of patients (pts) who had RAD, PF, SCC, and SB as their first SRE were 2,095 (50%), 1749 (42%), 287 (7%), and 45 (1%), respectively. Of the 4,176 men who had at least one SRE, 2,619 (62.7%) had a subsequent SRE and 1,442 (35%) had a subsequent SRE of a different type. Among the 1,442 mPC men who had at least 2 types of SRE, the proportion of pts who initially had a RAD, PF, SCC, or SB were 30%, 57%, 11%, or 2%, respectively. Among men who initially had PF, most had a subsequent RAD or SB (Table). Conclusions: In this analysis, half of mPC pts experienced at least one SRE, in whom about two-thirds had a subsequent SRE and a third had a subsequent different type of SRE. PF is the most common first SRE among those with multiple types of SREs, and is most frequently followed by SB or RAD. However, RAD may be an overestimate since a proportion of patients may receive radiation to the prostate instead of the bone. Pts with any SRE type (N=4,176) N (%) Pts with at least 2 SRE types (N=1,442) N (%) SRE pattern RAD first 2,095 426 No 2nd SRE 891 (43) - RAD 963 (46) - PF 194 (9) 343 (80) SCC NR NR SB NR NR PF First 1,749 820 No 2nd SRE 553 (32) - RAD 238 (14) 359 (44) PF 642 (36) - SCC 88 (5) 112 (13) SB 228 (13) 349 (43) SCC First 287 166 No 2nd SRE 98 (34) - RAD 104 (36) 105 (63) PF 40 (14) 41 (25) SCC 26 (9) - SB 19 (7) 20 (12) SB First 45 30 No 2nd SRE 15 (33) - RAD NR NR PF 18 (40) 18 (60) SCC NR NR SB NR - NR: Not reported per NCI DUA agreement.
Administration of BPX-501 Cells Following Aβ T and B-Cell-Depleted HLA Haploidentical HSCT (haplo-HSCT) in Children with Acute Leukemias
Authors: Franco Locatelli, Annalisa Ruggeri, Pietro Merli, Swati Naik, Rajni Agarwal, Victor Aquino, David A. Jacobsohn, Waseem Qasim, Eneida R. Nemecek, Lakshmanan Krishnamurti, Deepa Manwani, Melissa Kuhn, Neena Kapoor
Journal: Blood (2018)
Comprehensive profiling of uveal melanoma.
Authors: David Arguello, Ryan Bender, Takami Sato, Zoran Gatalica
Journal: Journal of Clinical Oncology (2014)

e20036 Background: Although uveal melanoma represents only 5% of all melanomas, it is the most common primary intraocular malignancy of the adult eye. Up to 50% of patients will develop metastases which are resistant to medical interventions. There is a great need for improved therapy as the prognosis is poor for advanced-stage disease. Our study was undertaken to further investigate potential therapeutic targets. Methods: We analyzed 78 uveal melanoma patients (primary n=11, hepatic metastases n=47, non-hepatic metastases n=20) with immunohistochemistry for 24 markers. Tissue permitting, in situhybridization was then performed on 37 of these samples. A smaller cohort underwent mutational analysis by either Sanger sequencing or next-generation sequencing (NGS). Results: Frequency of BCRP (15/19, 78.9%) and MRP1 (22/38, 57.9%) overexpression may explain uveal melanoma’s inherent resistance to traditional chemotherapy, despite biomarkers like TOPO1 (29/56, 51.8%) indicating a potential drug benefit. MGMT overexpression (27/65, 41.5%) may predict those patients who may not derive benefit from DTIC, the current standard of care. Half of patients in this group were PTEN-negative (31/62, 50%), indicating more aggressive disease and potential involvement of AKT pathway activation. High expression of IGF-1R (6/8, 75%), c-Kit (31/42, 73.8%), and cMet (11/25, 44%) might suggest biological importance of these receptors for tumor growth. There are no significant differences in expression patterns of these markers based on biopsy site. All specimens in our smaller cohort analyzed by sequencing methodologies contained mutually-exclusive GNAQ or GNA11 (Q209L) point mutations (14/14, 100%). One patient, specifically, had GNAQ, RB1, and a PTEN mutation by NGS. No other mutations were detected. Conclusions: Metastatic uveal melanoma, in contrast to other malignancies, is a homogenous disease with few mutations. Agents targeting GNA11 and GNAQ, or their downstream MAPK pathways in combination with a blockade of commonly-expressed surface receptors or the AKT pathway, could potentially offer new therapeutic options based on comprehensive analysis. Our findings highlight the importance of multiplatform profiling of uveal melanoma patients.
Predictors of Response in Patients Receiving CD34-Selected Stem Cell Infusions without Conditioning to Correct Graft Failure Following Allogeneic Stem Cell Transplantation
Authors: Maria del Mar Cuadrado, Mark W. Lowdell, Stuart Ings, Michael J. Watts, Richard Szydlo, Chloe Anthias, J. Alejandro Madrigal, Panagiotis Kottaridis, Ben Carpenter, Rachael Hough, Karl Peggs, Kirsty Thomson, Emma Morris, Ronjon Chakraverty
Journal: Blood (2018)
Mutation analysis in colorectal adenocarcinoma specimens to targeted treatment.
Authors: Krzysztof Roszkowski, Bogdan Zurawski, Pawel Basta, Wojciech Jozwicki, Marzena Anna Lewandowska
Journal: Journal of Clinical Oncology (2014)

e14639 Background: This study was conducted to assess whether tumors with mutations in KRAS codon 12 represent a less aggressive subtype compared to those with mutations in KRAS codon 13. Furthermore, we assessed whether the patients with a new diagnosis of colorectal cancer, after the surgical removal of the primary tumor with KRAS mutations in codon 12 or 13, might have a better prognosis regarding overall survival than the patients with wild-type (WT) KRAS. Finally, we sought to determine the differences in the treatment outcome in 100 colorectal cancer patients with WT KRAS and 139 patients with mutations in codon 12 or 13. Methods: Each individual case was evaluated for KRAS mutations in exon 2 (codons 12 and 13) using one of the following methods of mutation analysis: single strand conformation polymorphism (SSCP), Sanger sequencing, polymerase chain reaction (PCR) with a step of hybridization to a strip test containing allele-specific probes (Vienna Lab), Real-Time PCR with allele-specific oligonucleotides (EntroGen, Inc.) or Real-Time PCR with melting-curve analysis (TibMolBiol), and a single sample was tested with TheraScreen real-time. Results: Surprising results from this study were obtained by comparing overall survival of the patients divided into subgroups according to the KRAS mutations in codons 12 or 13 and the administered therapy. As it occurred, in the subgroup of patients carrying a KRAS mutation in codon 13 and treated with Radiotherapy+Surgery (a small group of seven patients), all patients remained alive. Among the patients with KRAS mutated in codon 13 treated with Surgery+Chemotherapy, 30% remained alive. Conclusions: The fact that all patients treated with Radiotherapy+Surgery were alive, again focused our attention on the effect of preoperative radiation therapy on the prognosis for colorectal cancer patients. However, the number of patients in this subgroup is too small to allow any specific explanation of this observation. We should rather point out a problem for further investigation.
HER-FLOT: Trastuzumab in combination with FLOT as perioperative treatment for patients with HER2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the AIO Gastric Cancer Study Group.
Authors: Ralf Hofheinz, Susanna Hegewisch-Becker, Peter C. Thuss-Patience, Volker Kunzmann, Martin Fuchs, Ullrich Graeven, Nils Homann, Volker Heinemann, Michael Pohl, Andrea Tannapfel, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2014)

4073^ Background: Perioperative chemotherapy is a mainstay in the treatment of locally advanced esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in pts with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in pts with locally advanced EGA. Methods: A multicenter phase II study evaluated the efficacy & toxicity of perioperative HER-FLOT (24-h 5-FU 2,600 mg/m², leucovorin 200mg/m², oxaliplatin 85mg/mg², docetaxel 50 mg/m², trastuzumab 6mg/kg then 4 mg/kg d1, repeated d15 for four cycles pre- and postoperatively followed by 9 cycles of trastuzumab monotherapy 6mg/kg 3-weekly) in pts with HER-2 positive EGA (IHC 3+ or IHC 2+/ ISH+). Pts had to have ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally tested pathological complete remissions (pCR). Secondary endpoints comprised disease-free and overall survival, R0 resection rate, toxicity and surgical morbidity. Here we report data of an interim safety analysis conducted in the first n=25 pts as well as surgical and pathological results of the first n=45 pts. Results: n=58 pts with a median age of 62 years were included. n=40 pts had tumors originating from the esophagogastric junction. T stage was: (cT2/3/4/unk) 4/44/9/1. n= 52 pts had cN+ disease. The interim safety analysis of four cycles of preoperative HER-FLOT revealed no unexpected safety findings (adverse events grade 3-4: neutropenia 28%, diarrhea 8%, nausea 8%). Thus far, data on surgery and central pathology of 45 patients are evaluable. R0 resection rate was 93.3%. In five pts anastomotic leakage was diagnosed, and five pts came in need of operative revision. One postoperative death occurred. Regarding the primary endpoint, pCR was found in 10 /45 pts (22.2%) and a further n=11 pts (24.4%) had near complete regression (<10 % residual tumor cells). Conclusions: HER-FLOT was found to be safe and no new or unexpected safety issues were noticed. Preliminary data on centrally assessed pCR rate is very promising with >20% achieving a pCR. Final analysis will be presented at the meeting. Clinical trial information: NCT01472029.
TRY: A phase II study to evaluate safety and efficacy of combined trastuzumab and AUY922 in advanced non-small cell lung cancer (NSCLC) with HER2 overexpression or amplification or mutation.
Authors: Lucia Nogova, Masyar Gardizi, Marc Christiaan Allardt Bos, Matthias Scheffler, Christian Mattonet, Lukas Carl Heukamp, Hans-Ulrich Schildhaus, Uwe Fuhr, Wilfried Eberhardt, Henning Reis, Marcel Wiesweg, Kurt Werner Schmid, Gernot Schoch, Yon-Dschun Ko, Monika Heidi Serke, Martin H. Schuler, Reinhard Buettner, Juergen Wolf
Journal: Journal of Clinical Oncology (2014)

8109 Background: HER2 amplifications and/or mutations are rare genetic alterations in NSCLC accounting for approximately 4%. Preliminary clinical data suggested efficacy of trastuzumab (Herceptin) in patients with HER2 immunochemistry 3+ (IHC3+) status or positive fluorescence in situ hybridization (FISH). The heat shock protein HSP90 is a molecular chaperone modulating stability and/or transport of intracellular client proteins including HER2. In breast cancer HSP90 inhibition showed anticancer activity in HER2-positive patients after trastuzumab failure. Here we are investigating the efficacy of the combination of trastuzumab and the HSP90 inhibitor AUY922 in lung cancer patients with aberrant HER2. Methods: This phase II study recruits metastatic NSCLC patients with HER2 overexpression (IHC DAKO-score 3+) or amplification (FISH positive) or activating mutation after failure of at least one previous standard treatment. In the first part of the study, patients are treated with trastuzumab only (initially 4mg/kg, followed by 2 mg/kg weekly). CT scan is scheduled every 6 weeks during treatment. In case of disease progression, AUY922 (70 mg/m2) is given additionally. Patients are recruited in two German centers: in Cologne and Essen. Results: Within the Network of Genomic Medicine in Cologne, 3,863 NSCLC patients of all stages were screened. Patients with overexpression were tested for amplification and mutation. HER2 amplification was seen in 4% and HER2 mutations in 1.6% of all adenocarcinomas. Patients in Essen are screened separately. The study is ongoing. Five patients with HER2 amplifications were treated in the study. Two patients progressed after 6 and 12 weeks on the combination. One patient showed clinical progression within first 6 weeks on trastuzumab. Two patients are still ongoing on trastuzumab monotherapy. The best CT response was -29.3% in patient on trastuzumab and AUY922 at week 6. Conclusions: HER2 overexpression, amplification or mutation is a rare genetic alteration in NSCLC patients. Data on treatment with HER2 antibody trastuzumab and HSP90 inhibitor AUY922 will be presented Clinical trial information: DRKS00003301.
Dermatological manifestations in cardiofaciocutaneous syndrome
Authors: D. Bessis, F. Morice‐Picard, E. Bourrat, C. Abadie, S. Aouinti, C. Baumann, M. Best, A.‐C. Bursztejn, Y. Capri, C. Chiaverini, C. Coubes, F. Giuliano, S. Hadj‐Rabia, M.‐L. Jacquemont, D. Lacombe, S. Lyonnet, S. Mallet, J. Mazereeuw‐Hautier, J. Miquel, N. Molinari, B. Parfait, C. Pernet, N. Philip, L. Pinson, N. Pouvreau, Y. Vial, P. Sarda, S. Sigaudy, A. Verloes, H. Cavé, D. Geneviéve
Journal: British Journal of Dermatology (2019)

Cardiofaciocutaneous syndrome (CFC) is one of a group of rare genetic disorders called the RASopathies because they are caused by mutations in the genes related to HRAS, KRAS or NRAS. The other RASopathies are Noonan (NS) and Costello (CS) syndromes. These conditions can affect the heart, nervous system, bony skeleton and muscles; there is sometimes an unusual facial appearance and occasionally a tendency to develop tumours. CFC patients often have skin problems but dermatologists have difficulty recognising the syndrome because it is very rare and the skin symptoms are not particularly unusual. Also there is a lot of overlap between the different RASopathies. In this study from France, geneticists and dermatologists reviewed 45 patients with CFC caused by mutations in the genes BRAF, MAP2K1 or MAP2K2 and compared the findings with published data. They noted a lack of precise dermatological descriptions in the RASopathy literature. They observed certain skin conditions more frequently in CFC patients than is reported in the general population. These included common disorders such as prominent follicles (keratosis pilaris), multiple moles, and curly hair, and unusual but rather non-specific features such as lax skin, thickened palms and soles, sparse eyebrows and excessive sweating. The thickened palms and soles responded well to treatment with a drug called acitretin in two patients. As the accompanying commentary points out, most people with these skin features do not have a RASopathy, but that diagnosis is worth considering if the skin condition is unusually marked, is absent in close family members, or associated with other abnormalities.
The National Vaccine Injury Compensation Program
Authors: H. Cody Meissner, Narayan Nair, Stanley A. Plotkin
Journal: JAMA (2019)

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Quantification of Fusion Transcripts Reveals Slower Treatment Kinetics As Compared with Multiparameter Flow Cytometry during Induction Treatment of Acute Myeloid Leukemia in Children
Authors: Lene Karlsson, Charlotte Guldborg Nyvold, Lars Palmqvist, Anne Tierens, Henrik Hasle, Birgitte Lausen, Olafur G. Jonsson, Gitte Wulff Juergensen, Lene Hyldahl Ebbesen, Florian Kuchenbauer, Erik Forestier, Jonas Abrahamsson, Linda Fogelstrand
Journal: Blood (2018)
Correlation between clinical tumor stiffness by elastography and response to neoadjuvant chemotherapy in patients with breast cancer.
Authors: Mitsuhiro Hayashi, Yutaka Yamamoto, Aiko Sueta, Mai Tomiguchi, Saori Fujiwara, Satoko Yamamoto, Touko Inao, Mutsuko Ibusuki, Kei-ichi Murakami, Hirotaka Iwase
Journal: Journal of Clinical Oncology (2014)

1061 Background: Preclinical study has revealed that tumor stiffness can force tumor progression. Tumor stiffness appears to be caused by increased matrix cross-linking and changing in a number of stroma-related genes’ expression, and seems to contribute to high malignant potential of tumor cells or disturb intestinal transportation of anti-tumor drugs in preclinical study. Now ultrasound elastography, can objectively evaluate tumor stiffness, has been clinically applied for differentiation of breast mass, therefore we explored novel clinical significance of tumor stiffness measured by elastography in breast cancer. Methods: We reviewed 432 patients with breast cancer who underwent ultrasound elastography before any treatments, including 79 patients who received neoadjuvant chemotherapy (NAC). We compared pre-NAC tumor stiffness with responses to NAC in patients treated by NAC, and investigated correlations between tumor stiffness and clinicopathological factors in all patients. The tumor stiffness was evaluated by fat lesion ratio (FLR) by strain elastography. Results: We categorized patients into two groups according to tumor stiffness with a cutoff value of FLR 10: 185 patients with high FLR (Hard tumor group) and 247 patients with low FLR (Soft tumor group). In patients treated by NAC, the hard tumor group had significantly lower pathological complete response (pCR) rate than the soft tumor group: 18% (8/44) vs. 63% (22/35), P<0.0001). There were also significant differences of pCR rate when we limited the analysis to triple negative cases (Hard 25% vs. Soft 88%, P=0.03) and HER2-positive cases (Hard 55% vs. Soft 93%, P=0.02). Multivariate analysis indicated that tumor stiffness was an independent predictive factor of pCR (hard tumor: odds ratio 0.04, 95%CI 0.004-0.226, P<0.0001) as well as HER2 status. In all patients, tumor stiffness was significantly correlated with tumor size, lymph node metastasis and fibrotic finding by conventional ultrasound. Conclusions: Pre-treatment tumor stiffness evaluated by ultrasound elastography had a significant relationship with response to NAC in patients with breast cancer.
Patient demand for care: How much does this contribute to inappropriate tests and treatments?
Authors: Keerthi Gogineni, Derek Chinn, Katherine Shuman, Ezekiel J. Emanuel
Journal: Journal of Clinical Oncology (2014)

6530 Background: There are many calls for physicians to provide more cost-effective care. Physicians sometimes claim that patients demand high cost or low value tests and treatments. How frequently do patients demand medical services? Methods: We surveyed oncologists and nurse practioners immediately after patient encounters to determine the frequency of patient requests or demands for tests and treatments, whether the request was appropriate, whether it was granted, and why. Results: Of the 2050 encounters, 73.1% of patients were white with a mean age of 60. Overall 42.0% had Stage IV or refractory disease and 66.3% were undergoing active treatment; 49.5% with palliative intent. Of the 26 clinicians surveyed, 97.0% were white, 54% were female and had a median of 14 years of post-training experience. In the table below, we report the key results of this survey. Providers declined granting a patient’s request 18.1% (32/177) of the time; in 84.4% (27/32) of these cases this was because the test or treatment was felt to be inappropriate or had no evidence for clinical benefit. In less than 1% of encounters (4/2050) did the provider order a test or treatment deemed inappropriate. Conclusions: Inappropriate patient demands for tests or treatments are very uncommon among cancer patients and probably do not drive high utilization of high cost or low value medical services. Survey measure Percentage Patient encounters with requests or demands 8.6% (177/2050) Requests or demands were inappropriate based on clinician judgment 13.6% (24/177) Requests or demands were appropriate based on clinician judgment 79.7% (141/177) Clinician complied with patient request or demand 81.9% (145/177) Clinician ordered an inappropriate test or treatment based on patient demand 0.2% (4/2050)
Low area-level socioeconomic status and breast cancer biologic features in a diverse population-based sample.
Authors: Jennifer J. Griggs, Andrew W. Dick, Ann S. Hamilton, Christina Helen Jagielski, Kendra L. Schwartz, Melony Elizabeth Sorbero
Journal: Journal of Clinical Oncology (2014)

6575 Background: The purpose of this study was to investigate the association between area-level socioeconomic status (SES) and breast cancer biology controlling for demographic factors and comorbid conditions in a diverse population-based sample. Methods: We enrolled women with Stages I – III breast cancer reported to the Los Angeles County and Detroit Tri-County Surveillance, Epidemiology and End Results (SEER) registries between 1998 and 2004. Black women and Latinas were over-sampled. Census block-level SES was assigned using a validated composite of six variables from the 2000 Census and then divided into quartiles. Clinical and pathology data from medical records supplemented SEER registry data. Bivariate and multivariate analyses investigated relationships between SES and tumor grade, hormone receptor status, triple-negative status, and lymphovascular invasion (LVI) controlling for race/ethnicity, obesity status, diabetes, hypertension, and menopausal status. Results: The sample included 1,931 women (988 non-Hispanic whites, 611 blacks, and 332 Hispanics). In bivariate analyses, lower SES was associated with higher grade (p < 0.001), higher rates of LVI (p = 0.007), and hormone receptor-negative disease (p < 0.001). In multivariate analyses, area-level SES was significantly associated with Grade 3 disease (OR 1.86, 95% CI 1.11 – 3.09 for the lowest SES quartile), hormone receptor-negative disease (OR 1.96, 95% CI 1.11 – 3.46 for the lowest quartile, p value for trend 0.02). SES was also significantly associated with triple-negative disease (OR 4.93, 95% CI 1.37 – 17.82 for the lowest quartile, p value for trend 0.01). Black race was not associated with tumor biologic features with the exception of hormone receptor -negative disease (OR 2.11, 95% CI 1.41 – 3.18). Conclusions: In this population-based study, low area-level SES was independently associated with unfavorable tumor biology. Environmental factors, the allostatic load caused by chronic stress, and lifestyle behaviors may contribute to the poorer breast cancer-specific outcomes associated with lower SES.