tbuckley/cabot-search huggingface dataset:
Epidermal Nerve Fiber Quantification in Patients With Erythromelalgia
Authors: William G. Mantyh, P. James B. Dyck, Peter J. Dyck, Janean K. Engelstad, William J. Litchy, Paola Sandroni, Mark D. P. Davis
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Erythromelalgia is a clinical diagnosis based on intermittent warmth, erythema, and pain in the distal extremities. One problem facing physicians is how to objectively test for this disease. Given that other painful conditions of the distal extremities (ie, neuropathy related to human immunodeficiency virus, diabetes, or Fabry disease) can be evaluated with a skin biopsy to visualize pathologically decreased densities of the small nerve fibers that innervate the epidermis, one hypothesis is that erythromelalgia could similarly be associated with a loss of epidermal nerve fiber density (ENFD). <h3>Objectives</h3> To examine whether erythromelalgia is associated with a structural loss of small fibers using the ENFD technique and to compare this with functional studies of small nerve fibers. <h3>Design, Setting, and Participants</h3> In a retrospective study of 52 consecutive patients with erythromelalgia who were seen between September 1, 2010, and September 22, 2015, patients were interviewed and examined and their conditions clinically diagnosed by a board-certified dermatologist at a large tertiary referral center, where ENFD testing became a routine part of evaluating erythromelalgia in 2010. Thus, all 52 consecutive patients were included solely based on their clinical diagnosis of erythromelalgia. For quantification of ENFD, observers were masked to all patient information except for name and clinic number. <h3>Main Outcomes and Measures</h3> The hypothesis that patients with erythromelalgia would have decreased ENFD was formulated before data collection. Epidermal nerve fiber density, the primary outcome, is a measurement of the density of small nerve fibers within the epidermis. Secondary measures included functional small fiber evaluation, such as autonomic (heart rate, blood pressure, and sweat testing) and subjective testing of pain. <h3>Results</h3> In this cohort study, 52 consecutively seen patients were identified (female, 42 [80%]; median age, 44 years; age range, 13-82 years). Whereas only 5 of 52 patients (10%) had ENFD at or below the fifth percentile of healthy control individuals, most patients had functional abnormalities of these small fibers; 29 patients (60%) had abnormal sweat test results, 21 (42%) had abnormal pain thresholds, and 20 (38%) had abnormal blood pressure or heart rate control. <h3>Conclusions and Relevance</h3> Unlike other diseases of the small nerve fibers that cause acral pain syndromes, erythromelalgia is not characterized by loss of ENFD. However, most patients have impaired function of these small fibers. Physicians would benefit from performing functional rather than structural small fiber studies when evaluating erythromelalgia.
Prediction of survival in patients with metastatic prostate cancer by single nucleotide polymorphisms of cancer-associated genes.
Authors: Takamitsu Inoue, Norihiko Tsuchiya, Shigeyuki Matsui, Tomomi Kamba, Koji Mitsuzuka, Shingo Hatakeyama, Yohei Horikawa, Chikara Ohyama, Seiichi Saito, Yoichi Arai, Osamu Ogawa, Tomonori Habuchi
Journal: Journal of Clinical Oncology (2012)

177 Background: Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. Methods: A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. A prognostic scoring index using selected SNPs was developed by incorporating the difference in their effect sizes to classify high-risk and low-risk groups and its predictive accuracy was assessed. Results: Fourteen SNPs in six genes, XRCC4, PSM1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20×10 −8 ). The predictive model using the 14 SNPs showed a statistically significant cross-validated accuracy in predicting the groups at high and low risk groups for poor survival (P = 0.0050). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). Conclusions: Using a panel of the SNPs, the prediction of the survival and optimization of the individualized treatment for patients with advanced PCa may be possible.
A matched-pair analysis of dose-escalated adaptive image-guided radiotherapy (IGRT) versus pelvic irradiation with brachytherapy boost for intermediate- and high-risk prostate cancer.
Authors: C. Shah, L. L. Kestin, M. Ghilezan, F. A. Vicini, G. S. Gustafson, D. Brabbins, M. Wallace, K. Marvin, H. Ye, A. Martinez
Journal: Journal of Clinical Oncology (2011)

71 Background: The purpose of this study was to compare clinical outcomes in a cohort of intermediate- and high-risk prostate cancer patients treated with either dose-escalated adaptive IGRT or pelvic external beam RT with high-dose rate brachytherapy boost (EBRT+HDR). Methods: 1,520 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with either CT-based offline adaptive IGRT (n=1,037) or EBRT+HDR, n=438) at William Beaumont Hospital. For IGRT, the CTV included the prostate and proximal seminal vesicles only. Median dose (minimum to cl-PTV) delivered via 3D conformal RT or intensity-modulated RT was 75.6 Gy (range: 73.8-79.2 Gy). For EBRT+HDR, the whole pelvis was treated to 46 Gy + 2 HDR implants with a median of 10.5 Gy (8.75-11.5 Gy) per implant. 208 patients from each group were matched based on criteria of pretreatment PSA ± 4 ng/mL, same Gleason score, T stage ± 2 sublevels, and use of neoadjuvant androgen deprivation therapy (ADT). Results: Mean follow-up was 5.1 years for IGRT vs 7.0 years for EBRT+HDR. Mean pretreatment PSA was 9 for both groups. Mean Gleason was 7 for both groups. EBRT+HDR patients were younger (67 vs 71 years, p&lt;0.01) with a higher percentage of positive biopsy cores (51% vs 39%, p&lt;0.01). Intermediate risk patients comprised 78% and 76% for IGRT and EBRT+HDR, respectively (p=0.56). 42% in each treatment group received neoadjuvant or concurrent ADT. 5-year biochemical control (BC) based on the Phoenix definition was 91% for IGRT vs 87% for EBRT+HDR (p=0.60). For intermediate-risk, 5-year BC was 94% vs 87% (p=0.71) and was 86% vs 86% (p=0.83) for high-risk patients. No significant differences were noted between the 2 groups for local recurrence, distant metastasis, clinical failure, overall survival, and cause-specific survival. Conclusions: In this matched-pair analysis of 416 patients, treatment of intermediate and high-risk prostate cancer with either offline adaptive IGRT or EBRT+HDR yielded excellent clinical outcomes without significant differences. The omission of pelvic radiotherapy in the IGRT patients did not appear to be associated with poorer clinical outcomes with modern high-dose RT. No significant financial relationships to disclose.
Management of early-stage breast cancer: Are we headed in the right direction?
Authors: D. A. Baribeau, U. Zurawska, S. Gandhi, C. Victor, S. Giilck, A. Florescu, S. Verma
Journal: Journal of Clinical Oncology (2011)

e11039 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for the Her 2 positive patients, the outcomes of ER/PR +ve Her 2 negative and Her 2 positive subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+,HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR/HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR positive patients have an excellent outcome. Despite significant improvement in outcomes of HER2 patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2 patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.
High Incidence of HHV-6 Infection Associated with Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) Conditioning Regimen: Results of a Monocentric and Retrospective Study
Authors: Simon Favre, Mathieu Sauvezie, Marie Sarah Dilhuydy, Stéphane Vigouroux, Reza Tabrizi, Gaelle Laboure, Margot Robles, noel-Jean Milpied, Krimo Bouabdallah
Journal: Blood (2016)
A phase II trial of sorafenib (S) and dacarbazine (D) in leiomyosarcoma (LMS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumor (MPNST).
Authors: D. R. D'Adamo, M. L. Keohan, R. D. Carvajal, M. L. Hensley, C. Hirst, L. Qin, C. Antonescu, R. A. Lefkowitz, G. K. Schwartz, R. G. Maki
Journal: Journal of Clinical Oncology (2011)

10025 Background: Sorafenib has a low single agent RR in sarcoma. Other angiogenesis inhibitors are more effective when combined with standard chemotherapy. Sorafenib has been safely combined with dacarbazine for treatment of melanoma. As PRs, MRs and prolonged SD were seen in LMS, SS and MPNST in our single agent S study, we chose to investigate S+D in those histologies. Methods: Patients with LMS, SS or MPNST with up to 2 priors, and adequate hepatic, renal and marrow function receive S at 400 mg BID and D at 1000mg/m2 every 3 weeks. Pts are restaged every 2 cycles. The primary objective of this trial is to determine Clinical Benefit Response rate (CBR=CR+PR + SD x18 weeks) of S+D in these subtypes. A Simon two stage design to distinguish between a CBR rate of 20% and 40% required 4 CBRs out of the first 17 pts to expand to a second cohort, and 11/37 (29.7%) CBRs to be considered positive. Results: From 2/09-12/10, 31 pts have been enrolled: 17 F, 14 M; median age 55, range 27-80; ECOG PS 0 16, 1 14; 20 Previously treated, avg 1.6 prior lines of therapy; Histology - LMS 17, SS 10, MPNST 4. 157 cycles of therapy have been administered. Thus far the CBR is 29% (9/31 – 6 LMS, 3 SS, 0 MPNST). The TTP is 11 weeks. The 3 and 6 month PFR rates are 35% and 26%. The Choi RR (10% decrease in unidimensional disease) is 19% (6/31), whereas the RECIST RR was 10% (3/31). OS is 13.2 months. 15 of the first 25 pts required D dose reductions for hematologic toxicity (platelets and neutrophils). One pt had fatal neutropenic fever, possibly related to treatment. Non- hematological toxicity is similar to what has been reported for S and D. A protocol amendment reduced the dose of D to 850 mg/m2, and none of the subsequent 7 pts have required dose reduction. Conclusions: S+D can stabilize disease in up to 29% of pts with these subtypes, especially SS and LMS. Hematologic toxicity seems greater than D alone but is well tolerated with reduced D dose. CBR appears to be promising.
Double Umbilical Cord Blood Transplantation with Reduced Intensity Conditioning and Sirolimus-Based GVHD Prophylaxis.
Authors: Corey Cutler, Rachel Mitrovich, Grace Kao, Vincent Ho, Edwin Alyea, John Koreth, Philippe Armand, Bimalangshu Dey, Thomas Spitzer, Robert Soiffer, Joseph H. Antin, Karen Ballen
Journal: Blood (2007)
The efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer.
Authors: Osamu Muto, Hitoshi Kotanagi
Journal: Journal of Clinical Oncology (2012)

132 Background: Metastatic gastric adenocarcinoma is an incurable condition. Despite the recently reported benefits of chemotherapies, the prognosis of advanced gastric cancer remains poor. The role of surgical resection is still debatable. Therefore, we investigated the efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer. Methods: We retrospectively evaluated the efficacy of gastrectomy plus chemotherapy for treating stage IV gastric cancer. Among the 753 patients with gastric cancer treated with gastrectomy at our institute between 2003 and 2010, a total of 70 patients classified into stage IV and underwent gastrectomy with perioperative chemotherapy were included in this study. In the analysis, particular attention was paid to the prognostic factors of age, gender, tissue type, metastatic site, pre or postoperative chemotherapy, single agent or combination chemotherapy and the reason for gastrectomy (palliative surgery due to stenosis, bleeding or perforation and reduction surgery). The survival rate was calculated by the Kaplan Meier method and a statistical analysis was performed using the log-rank test. Survival was calculated from the beginning of the treatment until the last follow-up or death from any cause. Results: The median age was 65 years old. Peritoneal, lymph node and liver metastasis were 28, 23, and 13 patients respectively. Fifty-three patients had diffuse type. Gastrectomy followed by chemotherapy and chemotherapy were 53 patients. Single agent chemotherapy were 42 and combination were 28 patients. Thirty-one patients were underwent palliative surgery and 39 patients were reduction surgery. One-year survival rate of all patients was 43% and the median survival time was 19.9 months. In the statistical analysis, only reduction surgery plus chemotherapy demonstrated significant survival benefit. The median survival time was significantly greater in patients undergoing reduction gastrectomy group than in those undergoing palliative gastrectomy (25.3 versus 9.8 months; p=0.005). Conclusions: Long-term survival for patients with stage IV gastric cancer who are managed with reduction surgery and chemotherapy is achievable. Further study with a larger number of patients is warranted.
Validating the woodchuck model for studying antiangiogenic therapies for human hepatocellular carcinoma (HCC).
Authors: Kaunteya Reddy, Edward Ashton, Sandra Buitrago, Alan Hutson, Bud Christopher Tennant, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2012)

239 Background: Anti-angiogenic agents have become the backbone of advanced HCC treatment and provide clinical benefit despite infrequent radiographic response. Animal models that mimic human HCC and treatment response are greatly needed. The laboratory woodchuck (Maramota monax) is a unique animal model that replicates the complex human liver milieu of HCC in the context of chronic hepatitis B viral infection and was selected for this translational study. Methods: Humans: Patients with inoperable HCC were consented and prospectively treated with sunitinib 37.5mg PO qd for one week prior to liver directed therapy(chemoembolization). Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) was done pre-sunitinib and after one week as part of the trial. Woodchucks: Laboratory bred eastern woodchucks were inoculated at birth with known titers of sera from a chronic infectious pool of chronic woodchuck hepatitis virus (WHV), confirmed by ultrasound exam at 12-18 months to have developed HCC. Methods for assessment of woodchuck HCC blood flow using DCE-MRI were optimized. Woodchucks received sunitinib 12mg/kg/day poQD and identical image acquisition and analysis techniques were used for both species and identical parameter sets were obtained for cross comparison done by Dr. Ashton in a blinded fashion. Results: A total of seven patients and eight woodchucks with HCC were included (2 scans per patient/woodchuck, pre and post sunitinib). The “Exact Wilcoxon rank-sum test” was used for statistical analysis. Comparison between median Ktrans, AUCBN(90), necrotic and total volumes of the tumors in both groups revealed all parameters to be similar and only total tumor volume reached statistical significance (P=0.002). Conclusions: Our data indicate similarities between human and woodchucks in the tumor histology, blood flow and baseline and post antiangiogenic therapy functional imaging assessment by DCE-MRI. The current sample size of n=7+8 can detect large differences of roughly 1.5 standard deviation units between humans and woodchucks for our measures at alpha=0.05 and power=0.80. Further studies that explore the translational potential of this unique animal model are warranted.
Assessing the added value of breast tumor markers in breast cancer genetic risk prediction model BRCAPRO.
Authors: B. Arun, S. Biswas, N. Tankhiwale, A. L. Blackford, A. M. Gutierrez-Barrera, J. K. Litton, G. N. Hortobagyi, C. I. Amos, G. Parmigiani
Journal: Journal of Clinical Oncology (2011)

164 Background: BRCAPRO is a widely used genetic risk prediction model for estimating the carrier probabilities of mutations in BRCA1/2 genes. BRCAPRO has been enhanced to utilize information on molecular markers ER, PR, CK5/6, and CK14. However, no independent validation study on the utility of these markers in risk prediction exists to support using these in actual clinical settings. Further, an important predictive and prognostic marker for breast cancer, Her-2/neu (Her2) is not utilized in BRCAPRO. Therefore, the aim of our study was to: 1) incorporate Her2 in BRCAPRO; 2) conduct a validation study of the markers. Methods: Patients with breast cancer at the UT M. D. Anderson Cancer Center’s breast clinic who were referred for genetic evaluation were included. Separate sets of cohort were used for model building with Her2 and validation to avoid bias. This study was approved by the IRB. For the model building, we estimated the joint probabilities of ER and Her2 status for carriers and non-carriers of BRCA1/2 mutations. For the validation, BRCAPRO was run at two settings: 1) no marker data used and 2) ER/PR used. We calculated the Area Under the receiving operator characteristic Curve (AUC) using the probabilities of carrying any of BRCA1 or BRCA2 and conditional probabilities of carrying BRCA1 (CondBRCA1) and BRCA2 (CondBRCA2) given a proband is carrier. Results: The model-building set for Her2 was based on 409 probands and validation set on 796 probands wherein 23% of the probands were carriers. In the model-building step, we found that joint consideration of Her2 and ER/PR is useful in discriminating between carriers and non-carriers in some subgroups, e.g., a proband with ER-, Her2+ is much more likely to be a non-carrier than a carrier. In the validation step, the AUC for CondBRCA1 and CondBRCA2 improved substantially when ER/PR was used. We are in the process of coding Her2 in BRCAPRO and then validating its utility. Conclusions: Breast tumor markers are useful for prediction of BRCA1/2 mutation status in the BRCAPRO model. ER/PR helps discriminate between BRCA1 and BRCA2 mutation carriers. In our ongoing validation study Her2 is expected to improve discrimination between carriers and non-carriers in certain sub-groups.
Campbell replication confirms little or no effect of community deworming
Authors: David Taylor-Robinson, Paul Garner
Journal: The Lancet Global Health (2016)

For many years, international donors, philanthropists, and charities have poured money into deworming programmes for children in low-income and middle-income countries in the belief they will contribute to improved health, school performance, and economic development.1 The Rockefeller Sanitary Commission started funding deworming programmes in 1909 for poor USA communities to eliminate the cause of the "laziness of the poorer classes".2 The idea caught on, research emerged, and enthusiasm increased.
A Biomarker Algorithm Defines Onset Grades of Acute Graft-Vs-Host Disease with Distinct Non-Relapse Mortality
Authors: John E. Levine, Thomas M. Braun, Andrew C. Harris, Ernst Holler, Austin Taylor, Holly K. Miller, John M. Magenau, Daniel J. Weisdorf, Vincent T Ho, Javier Bolaños-Meade, Amin M. Alousi, James L.M. Ferrara
Journal: Blood (2014)
Value of frozen section and primary tumor factors in determining sentinel lymph node metastasis in early breast carcinoma: Indian experience.
Authors: S. P. Somashekhar, R. Jaka, S. S. Zaveri, S. Rai
Journal: Journal of Clinical Oncology (2011)

e11530 Background: The accuracy of intraoperative frozen section examination to evaluate sentinel lymph node (SLN) in detecting metastasis is important as it determines the further management of axilla. Primary tumor characteristics determining the metastasis to the lymph node will help in predicting the probability of spread and to determine the nature of disease. It also helps in refining selection of patients for SLN biopsy. We evaluated all these criteria on Indian patients for the better management. Methods: Between January 2005 and April 2009, 114 consecutive patients of all age group of both sex, with proven carcinoma breast, clinical stage T1/T2 N0 M0 at Manipal Comprehensive Cancer Center, Bangalore were subjected to SLN biopsy and intraoperative frozen examination. First 75 cases had complete axillary clearance for validation irrespective of SLN biopsy result and subsequently, positive cases underwent axillary lymph node dissection (ALND). Results: The association of age with SLN spread is not significant (mean 54.81years, p = 0.265). Frozen section examination had accuracy of 97.37% in determining metastatic sentinel node (sensitivity 96.15%, specificity 100%, p value < 0.001). SLN remained significant indicator of the status of rest of axilla (false negative 1.33%, p < 0.001). Primary tumor characteristics like histological subtypes, grade (81.9% grade III, p = 0.353), ER/PR status (60.2% positive, p = 0.839), Her2-neu status (p =0.296) were not significantly associated with SLN metastasis. Size of the primary tumor (p = 0.002), LVI (p < 0.001), perineural invasion (p = 0.084+) were significant factors determining the SLN metastasis. SLN biopsy evaluation had no false negative values in 13 post-lumpectomy cases. Conclusions: SLN biopsy is a valuable method of determining the axillary nodal metastasis. Intraoperative frozen section examination is highly accurate in detecting nodal metastasis. Primary tumor characteristics like size, LVI and perineural invasion are significant in predicting SLN metastasis. SLN biopsy remains an important method of predicting axillary metastasis even in post-lumpectomy breast carcinomas.