tbuckley/cabot-search huggingface dataset:
SOPHIA: A phase 3, randomized study of margetuximab (M) plus chemotherapy (CTX) vs trastuzumab (T) plus CTX in the treatment of patients with HER2+ metastatic breast cancer (MBC).
Authors: Hope S. Rugo, Mark D. Pegram, William John Gradishar, Javier Cortes, Giuseppe Curigliano, Jon M. Wigginton, Robert Joseph Lechleider, Fatima Cardoso
Journal: Journal of Clinical Oncology (2016)

TPS630 Background: Despite significant advances in targeted therapy, HER2+ MBC remains incurable. Ideal treatment includes pertuzumab (P) and T in combination with a taxane in the first line setting, followed by ado-trastuzumab emtansine (K) on progression. Optimal treatment regimens in the > third line of therapy are not defined, but continued anti-HER2 therapy is recommended. m is a Fc-modified monoclonal antibody (Mab) to HER2 that recognizes the same epitope on HER2 as does T with similar affinity. m demonstrates increased affinity to the activating CD16A Fc-receptor found on NK cells and macrophages and decreased affinity to the inhibitory CD32B receptor compared to T. In vitro studies showed enhanced antibody dependent cell-mediated cytotoxicity compared to T. In a phase I dose expansion trial, m showed single agent clinical activity against HER2+ tumors in patients previously treated with T and other anti-HER2 agents. Methods: SOPHIA is a randomized, prospective study testing the hypothesis that m plus CTX is more effective than T plus CTX in patients previously treated for HER2+ MBC. Sequential primary endpoints are centrally assessed progression free survival (PFS) and overall survival (OS). The study size of 530 patients is based on a hazard ratio for OS of 0.75 with a power of 80%. Secondary endpoints are investigator assessed PFS and central response rate. Eligibility includes prior treatment with T, P, and K, no more than 3 prior lines of therapy for MBC, prior demonstration of HER2+ status at a local reference laboratory, and absence of active brain metastases. Eligible patients are randomized 1:1 to receive CTX (physician's choice: capecitabine, eribulin, gemcitabine or vinorelbine) plus either m or T until disease progression or toxicity. Antibody may be continued after stopping CTX in patients with responding or stable disease. Progress to date: The trial was initiated July 2015 and is ongoing in the US and Europe with planned expansion to Korea and Israel. ClinicalTrials.gov Identifier NCT02492711; Eudract 2015-000380-13 Clinical trial information: NCT02492711.
Unexpected germline mutations in a pan-cancer analysis including sarcoma, renal, and other cancers.
Authors: Shan Yang, Scott T. Michalski, Jennifer Holle, Tali Ekstein, Erin O'Leary, Carolina Pardo, Nastaran Heidari, Michael Anderson, Karen Ouyang, Robert L. Nussbaum, Stephen E Lincoln, Edward D. Esplin
Journal: Journal of Clinical Oncology (2017)

1584 Background: Multi-gene testing for cancer predisposition is increasingly utilized in clinical care. Although the diagnostic yield and management implications of such testing in breast, ovarian and colorectal cancer are relatively well understood, data for other cancer types are still emerging. In this study we retrospectively examined 39,147 patients referred for hereditary cancer syndrome testing for pathogenic germline variants in 80 cancer risk genes, focusing on those patients with renal, sarcoma, paraganglioma, melanoma, and pancreatic cancers. Methods: Test results and personal/family history were extracted from a sequential series of de-identified clinical test reports. Data for genes not clinically ordered were analyzed under an IRB approved research protocol. Common low penetrance risk alleles were excluded. Results: Overall, 14.3% (5,589) of patients carried germline pathogenic mutations in 80 cancer risk genes. Of the 949 patients with renal cancer 20% (190) were positive, and 44% of these findings were “unexpected”, meaning they appeared in genes that are not commonly requisitioned in renal cancer patients. Of the 423 sarcoma patients, 16% (68) had positive findings, 45% of which were “unexpected”. For both cancer types, greater than 90% of these “unexpected” findings were in genes with published management recommendations. Similar results were observed in melanoma, paraganglioma and pancreatic cancer patients. A second or third pathogenic variant, many of which were also “unexpected”, were found in 3.6% of positive cases. Conclusions: In this series of patients we estimate almost 12% of pathogenic variants across cancer indications are “unexpected”. These data suggest many actionable pathogenic variants are being missed due to adherence to overly restrictive, narrowly constructed tumor-specific panels. Clinicians should expand the scope of their test panels in order to capture variants with the potential to impact patients and their family members by informing implementation of established management guidelines.
NHS and police blamed for killing by psychiatric patient on conditional discharge
Authors: Clare Dyer
Journal: BMJ (2017)

An independent inquiry commissioned by NHS England into the case of a psychiatric patient, previously committed for killing her mother, who killed another woman while on conditional discharge, has identified serious failings by the NHS and the Metropolitan Police.

The patient, Nicola Edgington, 36, was convicted in 2006 of manslaughter on the grounds of diminished responsibility in the death by stabbing of her mother, and she was sectioned as an inpatient at Bracton medium secure centre, run by Oxleas NHS Foundation Trust. In 2009 she was conditionally discharged into supported accommodation in south London, a housing association flat without 24 hour support.

Several reports of threatening behaviour or of behaviours that the team had previously described as potential red flags arose over the next two years but did not trigger readmission. Her behaviour became increasingly erratic in …
Venous vs Arterial Lactate and 30-Day Mortality in Pediatric Sepsis
Authors: Luregn J. Schlapbach, Graeme MacLaren, Lahn Straney
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
HER2-amplification level and tumor-infiltrating lymphocytes in breast cancer patients treated with neoadjuvant trastuzumab.
Authors: Cristina Masini, Giancarlo Bisagni, Moira Ragazzi, Alessandra Bisagni, Katiuscia Dallaglio, Giuseppe Falco, Cristina Bassano, Guglielmo Ferrari, Giorgio Gardini, Alessandra Bologna, Gabriella Moretti, Corrado Boni, Carmine Pinto
Journal: Journal of Clinical Oncology (2016)

596 Background: Trastuzumab-based neoadjuvant treatment (TNT) has shown clinical benefit in terms of both overall response and pathologic complete response (pCR). In particular, TNT is indicated for women with HER2-positive locally advanced breast cancer and allows for breast-conserving surgery. In addition, some evidences show that TIL may play a role in the response to anti-HER2 therapy. This study aims to investigate the possibility that HER2-amplification level and high level of TIL are predictive factors of response to TNT in locally advanced breast cancer. Methods: 75 HER2-positive breast cancer pts treated from 2009 to 2014 with TNT were included in this retrospective study. Preoperative biopsies or cytological samples were collected and analyzed by dual-color fluorescence in situ hybridization (FISH) to determine HER2-amplification. We used the cut-off recommended by ASCO/CAP 2013. TIL were evaluated in both pre- and post-treatment specimen; TIL score was assessed on hematossilin-eosin slides based on Salgado et al. recommendations. Clinical-pathological characteristics were recorded. Statistical analyses were performed using IBM-SPSS (V21.0). A p-value < 0.05 was considered statistically significant. Results: Among the 75 cases, HER2-amplification level was low (LA) in 14 cases (19%), intermediate (IA) in 17 cases (23%) and high (HA = gene copy number > 10 or clusters of signals) in 44 cases (59%). TNT achieved pCR in 19 of 75 tumors and correlated with HER2-amplification level (36% HA vs 6% IA vs 14% LA, p-value = 0.01). TILs levels were evaluated in 58 biopsies and surgical specimens: only 6 pts were classified as lymphocyte-predominant breast cancer (TILs ≥ 50%). The probability of developing pCR increased with TILs levels, although a statistically significant correlation was not achieved. No correlation was found between TIL and HER2-amplification levels. Age, stage, tumor grade and hormone receptor status were not significantly correlated to pCR. Conclusions: We show that while HER2-amplification level correlates positively with pCR to TNT, high level of TIL is not predictive of better response to trastuzumab in locally advanced HER2-positive disease.
Oncological safety of oncoplastic breast conserving surgery-compare with conventional breast conserving surgery and total mastectomy.
Authors: Yumi Kim, Eunshin Lee, Young Joon Kang, Han-Byoel Lee, Jaihong Han, Tae-Kyung Yoo, Hyeong-Gon Moon, Wonshik Han, Dong Young Noh
Journal: Journal of Clinical Oncology (2016)

e12531 Background: In recent decades, the surgical management of breast cancer has steadily and considerably improved. Now oncoplastic technique applies to breast-conserving surgery (BCS) allows large-volume resection without compromising oncological safety. A satisfactory cosmetic result could be difficult to obtain due to high tumor to breast size ratio, unfavorable location, close to the nipple and contralateral ptosis. Oncoplastic techniques allows the performance of wide excision, conserving an excellent breast shape, may be helpful in many cases. This study was aimed to evaluate the oncological safety of oncoplastic surgery for primary breast cancer. Methods: We compared 1320 consecutive patients who underwent surgery between August 2011 and December 2014 for breast cancer at Seoul National University Hospital by one experienced surgeon. Retrospectively medical chart review was done and patients divided into three groups. Among them 42.65% (n = 563) underwent oncoplastic surgery (OPS), 49.70% (n = 656) underwent conventional breast conserving surgery and 7.65% (n = 101) underwent total mastectomy. Among the OPS group, level I technique (round block, Batwing, Nipple reposition) was excluded. Finally 418 patents’ data of OPS group was analysed. Results: 1175 patients’ data were analysed (OPS: n = 418, conventional BCS: n = 656, TM: n = 101). Tumor size (including DCIS, 3.12cm vs 2.75cm), resected area (37.1cm2 vs 28.6cm2) and volume (74.5.0cm³ vs 60.1cm³) in OPS group were significantly bigger than conventional BCS group (p < 0.05). Distance to nipple in OPS group was closer than conventional BCS group (2.42cm vs 4.2cm, P < 0.001). Also margin safety (clear margin ; 80.6% vs 76.1%) in OPS group was better than conventional BCS group (P < 0.001). But operation time and re-excision rate was not significantly difference within two groups. Conclusions: OPS technique allows large-volume resection in more diffuse cancer and closer lesion to nipple with maintenance of oncological safety. Outcomes of OPS are oncologically acceptable with low frequencies of positive margins, while cosmetic results are much improved by OPS. OPS is no longer an option, it is treatment of choice in many patients
CD27 expression and its association with clinical outcome in children and adults with pro-B acute lymphoblastic leukemia
Authors: D Chen, N Gerasimčik, A Camponeschi, Y Tan, Q Wu, S Brynjolfsson, J Zheng, J Abrahamsson, J Nordlund, G Lönnerholm, L Fogelstrand, I-L Mårtensson
Journal: Blood Cancer Journal (2017)

CD27 expression and its association with clinical outcome in children and adults with pro-B acute lymphoblastic leukemia
E7107: Antitumor activity on human SCLC and cervical cancer xenografts in relation to its potential predictive markers of response.
Authors: Masao Iwata, Toshimitsu Uenaka, Yoichi Ozawa, Yoshihiko Kotake, Yoshiharu Mizui, Makoto Asada
Journal: Cancer Research (2007)

5608  E7107 is a semisynthetic derivative of pladienolide B, originally isolated from the fermented broth of Streptomyces platensis Mer-11107. Compared to other anticancer drugs currently in clinical use, Pladienolide B has a unique in vitro antitumor spectrum of activity, suggesting a novel mechanism of action. In addition, while pladienolide B appears to modulate gene expression, additional studies are necessary to determine if E7107 has similar activity. In this presentation, we describe the in vivo activity of E7107 in small cell lung cancer (SCLC) and cervical cancer xenografts in mice as well as early investigations into potential predictive biomarkers. Retrospective analysis of antitumor activities in vivo and the expression of cell-cycle related proteins in vivo indicated that tumors that express a functional loss of pRb, an increased p16INK4a expression and upregulated cyclin E are almost invariably sensitive to E7107. In addition, however, certain other tumors that do not carry these potential biomarkers still respond. E7107 induced significant tumor regression in all four SCLC xenografts (NCI-H69, NCI-H146, NCI-H526, and DMS114) that were included in this analysis and even complete remission in NCI-H69 and NCI-H526 tumors. Of these xenografts tested, 4/4 showed increased expression of p16INK4a, 3/4 (NCI-H69, NCI-H146, and NCI-H526) showed functional loss of pRb, and 2/4 (NCI-H146 and DMS114) showed relatively high expression of cyclin E. Prospective validation of these markers was also performed in cervical xenograft models. Of four cervical xenografts (C-33A, HT-3, HeLa, and HeLa-S3) tested, all showed both increased expression of p16INK4a and functional loss of pRb, and 3/4 (HT-3, HeLa, and HeLa-S3) showed high expression of cyclin E. Expression of these proteins notably predicted in vivo response, with E7107 inducing significant tumor regression in all of the examined cervical xenografts. In conclusion, immunohistochemical staining of p16INK4a and cyclin E in clinical specimens demonstrated higher positive rates for these markers in SCLC and cervical cancer. Currently, studies are underway to elucidate the mechanisms that may link in vivo activity of E7107 and status of these potentially predictive markers.
Minnesota healthcare providers’ breast cancer screening practices at the extremes of age.
Authors: Deanna Gek Koon Teoh, Rachel Isaksson Vogel, Alicia Allen, Anne Hudson Blaes, Susan Mason, Rebekah Nagler, Nancy Raymond, Kristine Talley, Jean Wyman
Journal: Journal of Clinical Oncology (2017)

e13037 Background: Breast cancer screening guidelines disagree on the age to initiate and discontinue screening. We sought to determine the age at which Minnesota providers initiate and discontinue breast cancer screening. Methods: A cross-sectional online survey of Minnesota primary care providers was conducted in 2016. The survey queried providers’ breast screening practices for average-risk women. Data were summarized using descriptive statistics and comparisons by professional characteristics were conducted using Chi-squared tests. Results: There were 805 respondents (8% of 10,392 invitees), of which 456 (56.7%) provided primary care to women and were included in the analysis. 316 (72%) were women, 193 (44%) were physicians, 50 (11%) were physician assistants (PAs), and 197 (45%) were advanced practice nurses (APNs). 85% practiced in a community setting. 38% had practiced &gt; 20 years, and 27% had practiced &lt; 10 years. Among respondents, 67%, 77% and 72% recommended screening mammography for women age 40-44, 45-49 and 70+ years, respectively. Compared to male providers, female providers were more likely to screen women age 40-44 years (73% vs. 49%; p &lt; 0.0001) and 45-49 years (81% vs. 66%; p = 0.002), but there was no difference by gender for patients age 70+ years (72% vs. 74%; p = 0.89). Respondents reporting specialized interest in women’s health were more likely to screen women age 40-44 years (73% vs. 61%; p = 0.006), 45-49 years (83% vs 72%; p = 0.007) and older than age 70 years (77% vs. 69%; p = 0.04). Physicians were less likely to screen women age 40-44 and 45-49 years (57% and 71%, respectively; p = 0.001) than PAs (72%, 78%) and APNs (74%, 83%), but APNs were less likely to screen women age 70+ years (65% vs. physicians 79% vs. PAs 76%; p = 0.006). Number of years in practice was not associated with a difference in age at initiation of screening, however, increasing number of years in practice was associated with screening women age 70+ years (p = 0.02). Conclusions: Although breast cancer screening practices for average risk women vary by healthcare provider characteristics, a majority of Minnesota primary care providers initiate breast cancer screening between ages 40-49 years, and continue screening women age 70 years and older.
A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma
Authors: Anurag K. Singh, Timothy B. Winslow, Mohammad Habiby Kermany, Vincent Goritz, Lilia Heit, Austin Miller, Nicholas C. Hoffend, Leighton C. Stein, Lalith K. Kumaraswamy, Graham W. Warren, Wiam Bshara, Kunle Odunsi, Junko Matsuzaki, Scott I. Abrams, Thomas Schwaab, Jason B. Muhitch
Journal: Clinical Cancer Research (2017)

Purpose: While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation.Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T-cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).Results: RCC cells treated in vitro with radiation had increased TAA expression compared with untreated tumor cells. Fourteen patients received SBRT followed by surgery, and treatment was well-tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ -proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens.Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC. Clin Cancer Res; 23(17); 5055-65. ©2017 AACR.
Elevated FDG Activity in the Nonpneumatized Sphenoid Bone in an Infant
Authors: Yin Jie Chen, Nelleke Tolboom, Lisa J. States, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

A 7-month-old boy with malignant rhabdoid tumor of the right lateral neck, status post resection and chemotherapy, underwent FDG PET/CT for restaging. The images showed diffuse increased activity in the spleen and in the bone marrow of the appendicular bones and the spine, which is related to hematopoietin administered after chemotherapy. The images also revealed intense activity in the region of sphenoid bone, which is not a common region to have elevated FDG activity. The subsequent MRI scan showed that this activity was due to not-yet-converted red marrow in the sphenoid bone in this pediatric patient.
Predicting fitness for chemotherapy in older cancer patients.
Authors: Damien B. Thomson, Alexandra McCarthy, Patsy Yates, Helen Skerman, Euan Thomas Walpole
Journal: Journal of Clinical Oncology (2013)

9516 Background: The Vulnerable Elders Survey-13 (VES-13) is increasingly used to screen for older patients who can proceed to intensive chemotherapy without further comprehensive assessment. This study compared the VES-13 determination of fitness for treatment with the oncologist's assessments of fitness. Methods: Sample: Consecutive series of solid tumour patients ≥65 years (n=175; M=72; range=65-86) from an Australian cancer centre. Patients were screened with the VES-13 before proceeding to usual treatment. Blinded to screening, oncologists concurrently predicted patient fitness for chemotherapy. A sample of 175 can detect, with 90% power, kappa coefficients of agreement between VES-13 &amp; oncologists’ assessments &gt;0.90 ("almost perfect agreement"). Separate backward stepwise logistic regression analyses assessed potential predictors of VES-13 &amp; oncologists’ ratings of fitness. Results: Kappa coefficient for agreement between VES-13 &amp; oncologists’ ratings of fitness was 0.41 (p&lt;0.001). VES-13 &amp; oncologists’ assessments agreed in 71% of ratings. VES-13 sensitivity = 83.3%; specificity = 57%; positive predictive value = 69%; negative predictive value = 75%. Logistic regression modelling indicated that the odds of being vulnerable to chemotherapy (VES-13) increased with increasing depression (OR=1.42; 95% CI: 1.18, 1.71) &amp; decreased with increased functional independence assessed on the Bartel Index (OR=0.82; CI: 0.74, 0.92) &amp; Lawton instrumental activities of daily living (OR=0.44; CI: 0.30, 0.65); RSquare=.65. Similarly, the odds of a patient being vulnerable to chemotherapy, when assessed by physicians, increased with increasing age (OR=1.15; CI: 1.07, 1.23) &amp; depression (OR=1.23; CI: 1.06, 1.43), &amp; decreased with increasing functional independence (OR=0.91; CI: 0.85, 0.98); RSquare=.32. Conclusions: Our data indicate moderate agreement between VES-13 &amp; clinician assessments of patients’ fitness for chemotherapy. Current ‘one-step’ screening processes to determine fitness have limits. Nonetheless, screening tools do have the potential for modification &amp; enhanced predictive properties in cancer care by adding relevant items, thus enabling fit patients to be immediately referred for chemotherapy.