tbuckley/cabot-search huggingface dataset:
Recurrence and survival following preoperative sorafenib for advanced renal cell carcinoma.
Authors: K. Rathmell, C. L. Cowey, G. Grigson, C. Watkins, E. Wallen, M. E. Nielsen, R. Pruthi, P. A. Godley, Y. E. Whang, W. Y. Kim
Journal: Journal of Clinical Oncology (2011)

384 Background: The impact of neoadjuvant or preoperative therapy in the setting of advanced renal cell carcinoma on recurrence-free or survival outcomes is not known. Methods: 28 patients with renal cell carcinoma were treated with preoperative sorafenib in a prospective pilot study (LCCC 0603). Patient files were reviewed a median of 885 days (2.42 years) following nephrectomy. Records were evaluated for 13 patients with nonmetastatic disease for development of recurrence, and for 15 patients with stage IV disease for survival. Results: For the nonmetastatic patients, only 2 patients had developed recurrent disease, one underwent metastectomy and remains in surveillance and the other is on second line systemic targeted therapy. A median recurrence-free survival has not been met after a median 2.5 years. For stage IV disease patients at a median follow up of 2.3 years, a median survival has also not been reached. Four patients are deceased, one patient is lost to follow up, and 10 remain alive. Treatments for metastatic disease included continued sorafenib, high dose interleukin-2, sunitinib, pazopanib, temsirolimus, and everolimus. Some stage IV patients have also enjoyed prolonged treatment-free intervals ranging from six months to over two years, with biopsy confirmed, but indolent disease. Conclusions: Although these data are descriptive, these observations are suggestive that preoperative therapy with sorafenib is unlikely to accelerate the growth of grossly metastatic or micrometastatic disease. Further studies are needed to determine whether preoperative therapy is valuable in improving recurrence-free or overall survival endpoints. [Table: see text]
Bladder preservation with helical tomotherapy-based, image-guided radiotherapy: A clinical study using “plan of the day” adaptive radiotherapy.
Authors: V. Murthy
Journal: Journal of Clinical Oncology (2011)

289 Background: This clinical study assessed the potential of helical tomotherapy-based, image-guided radiotherapy (IGRT) to increase the accuracy of bladder irradiation using a plan of the day adaptive radiotherapy (ART) technique. Methods: Ten patients with stage T 2b -T 4- N 0 M 0 , histologically proven bladder transitional cell carcinoma, who underwent bladder preservation with trimodality therapy in an ongoing trial, are reported. All patients received a dose of 64Gy/32# to the whole bladder. Seven of these also received a simultaneous integrated boost of 68Gy/32 fractions to tumor bed. The ART technique entailed the generation of six planning PTVs and thus six separate IMRT plans for each patient. All patients underwent daily pre and post treatment MVCT imaging to correct for positioning errors, choose the plan of the day, depending on deformation of the bladder, and verify intrafraction filling at the end of treatment. Margins needed to encompass the bladder wall in each direction during radiotherapy was determined in the following three scenarios: (a) centers with availability of daily IGRT and performing ART, (b) centers with IGRT not doing ART, and (c) centers without IGRT using electronic portal imaging for setup. Results: At a median follow-up of 12.2 months, all patients had a complete response in the bladder and one patient had a pelvic nodal recurrence. No patient developed treatment related grade 3 toxicity. Post treatment MVCT scans (n=315) were used to generate margins for centers with varying resources. Overall, the margin needed to encompass the anterior and superior walls 85 to 95% of the time was more than the other walls (Table, margins for six walls in cm). Maximum geographical miss in spite of IGRT was noted for the superior (13.8%) and anterior walls (10.3%). Conclusions: Plan of the day ART is a feasible and promising technique for optimal treatment and dose escalation in bladder cancer. [Table: see text] No significant financial relationships to disclose.
Role of circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer.
Authors: J. B. Aragon-Ching, S. J. Simmens, F. Hendricks, R. Andrawis, H. Frazier, T. Jarrett, S. R. Patierno, R. S. Siegel
Journal: Journal of Clinical Oncology (2011)

60 Background: CTCs have an established role in the prognosis of metastatic prostate cancer. Little data exists regarding the role of CTCs in BR of prostate cancer. The aim of this study was to determine whether there is a correlation between the number of CTCs in men with BR with varying prostate specific antigen (PSA) and PSA doubling time (PSADT) categories. Secondary endpoints looking at correlation of the CTCs with clinical or laboratory factors (Gleason scores, testosterone, hemoglobin, alkaline phosphatase, BMI, imaging results) will also be assessed. Methods: BR was defined as patients (pts) who have undergone primary treatment with prostatectomy or radiation or both, with rise to &gt;/= 0.2 from a prior undetectable level for prior prostatectomy or &gt; 2 mg/dl rise from post-nadir radiotherapy. The study was powered to detect a Pearson correlation of .46 with a sample size of 36. Eleven of planned accrual goal of 36 pts were enrolled from May to September 2010. PSADT was obtained and correlated with the CTC values, categorized as PSADT of &lt; 3 months, 3-14.9 months and &gt; 15 months. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 11 patients was 75 y/o (range: 57-91) with a median PSA of 1.6 ng/mL (range 0.2-6.5) and testosterone levels of 309 ng/dL (range: 31–471). Gleason scores were 8 (n=1), 7 (n=5), 6 (n=2), 5 (n=3). Prostatectomy was the primary treatment in 6 pts, radiotherapy in 5 pts and Cyberknife in 1 pt. Median hemoglobin was 12.43 g/dL, BMI was 26.79 and alkaline phosphatase was 69 IU/L. PSADT varied between 3 to 55 months. All pts accrued had 0 CTC levels. The latter result translates into a 95% confidence interval upper bound of approximately .27 for the proportion of patients in this population who have non-zero CTC levels. Conclusions: Prostate cancer pts with BR have negative blood CTCs and does not appear to correlate with PSA or PSADT. However, the limited number of patients precludes sufficient interpretation at this time and further accrual is ongoing. The absence of CTC levels in this patient population, if supported through further data collection, could emerge as an important unanticipated finding from this study. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute. No significant financial relationships to disclose.
Effect of genitourinary cancer mortality calculated using the potential years of life lost (PYLL): Trends from 1972-2006 based on a report from the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: S. Heshmat, P. C. Moore, M. Kamel, O. Moussa, N. Bissada
Journal: Journal of Clinical Oncology (2011)

350 Background: We aim to illustrate the potential years of life lost (PYLL) and the average years of life lost (AYLL); secondary to genitourinary cancer in US during the period from 1972-2006 utilizing the Surveillance, Epidemiology and End Results (SEER) database, and illustrate the trends in the PYLL over this time period. Methods: PYLL were calculated to assess premature mortality trends in US for ureter, urinary bladder, kidney and renal pelvis, penis, testis, and prostate cancers. AYLL is the average of the differences between the actual ages at death and the expected remaining years of life for each person who died of cancer. Calculations were made based on the SEER cancer mortality data. Results: There were a total of 7,733,235 PYLL in both men and women secondary to urogenital cancer in US in the period from 1972-2006. In both males and females, the greatest PYLL were for kidney and renal pelvis cancer related mortality. In both sexes no improvement in PYLL secondary to ureteral and bladder cancer related mortality was observed. In males the greatest reduction in PYLL was in testicular cancer followed by prostate cancer. Conclusions: PYLL and AYLL are two powerful tools that reflect the impact of cancer related mortality on society. There has been an increasing trend in PYLL related to urogenital cancers over the last 35 years for both males and females. Kidney cancer had the highest increase in PYLL among both genders and more efforts are needed to address its progression. No significant financial relationships to disclose.
Prognostic impact of expression Notch-1 in invasive bladder transitional cell carcinoma.
Authors: Nasser Ghaly Yousif, Abdallah Ali Deb, Majid Al-Matwari, Husham J. Mousa
Journal: Journal of Clinical Oncology (2012)

299 Background: Notch signal pathway plays a fundamental role in mediator of tumorigenesis, either as a tumor promoter or suppressor, depending on cellular context and expression levels; we investigated the prognosis of invasive bladder transitional cell carcinoma patients with over-expression of Notch-1. Methods: Tumor tissue samples from 78 resected patients with invasive bladder transitional cell carcinoma were obtained, and immunohistochemistry was used to evaluate the expression of the molecular markers Notch-1 and Jagged-1. To further confirm the immunohistochemical results tissue samples were subjected to RT-PCR and Western blot analysis, staining evaluation results were analyzed statistically in relation to various clinicopathological characters. Kaplan–Meier and Cox proportional hazards regression methods were used to assess associations of Notch-1 expression with invasive bladder transitional cell carcinoma survival. Results: Survival time in patients with high expression of Notch-1 and Jagged-1 was significantly shorter than that in patients with low expression p=0.009 and more recurrence p=0.01, in multivariate analysis, Notch1 expression was proved to be an independent predictor of prognosis; (hazard ratio Notch-1 was 1.93 (95% CI, 1.02-3.03; P =0.014), expression was not related to patient sex or age. Conclusions: Notch-1 expression is associated with tumor progression, indicating that Notch-1 may be involved in the carcinogenesis and progression of invasive bladder transitional cell carcinoma. These findings also suggest that Notch-1 may be a potential diagnostic marker and therapeutic target in patients.
Use of a novel device to reduce positive margins for ductal carcinoma in situ.
Authors: S. K. Boolbol, C. Cocilovo, L. Tafra
Journal: Journal of Clinical Oncology (2011)

87 Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real-time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decreased re-excision rate in patients with a DCIS component. Methods: 596 patients who were undergoing breast conservation using needle localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation followed by indicated additional cavity resections. Device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy. Results: The improvement in CSR was significant for each diagnosis (p&lt;0.0001). The decrease in candidates for reexcision due to failed CSR was significant for all pathology involving DCIS (p&lt;0.0001). Overall results are presented in the table. Conclusions: Device use delivered significant improvement in CSR and therefore a significant decrease in reexcision rates for patients with DCIS. Further studies need to be conducted evaluating the use of the device on additional margins that the surgeon may resect or in the actual cavity. [Table: see text]
Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method
Authors: Gypsyamber D’Souza, William H. Westra, Steven J. Wang, Annemieke van Zante, Alicia Wentz, Nicole Kluz, Eleni Rettig, William R. Ryan, Patrick K. Ha, Hyunseok Kang, Justin Bishop, Harry Quon, Ana P. Kiess, Jeremy D. Richmon, David W. Eisele, Carole Fakhry
Journal: JAMA Oncology (2016)

Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear.To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC).Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used.Outcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH.Of 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P < .001 for trend), as well as among whites (39% to 86%; P < .001 for trend) and nonwhites (32% to 62%; P = .02 for trend). Similar results were observed for ISH+ OPSCC (P ≤ .01 for all). Among 623 non-OP HNSCCs, a higher proportion were p16+ compared with ISH positive (62 [10%] vs 30 [5%]; P = .001). A high proportion (26 of 62 [42%]) of these p16+ non-OP HNSCCs were found in sites adjacent to the oropharynx. The proportion of p16+ and ISH+ non-OP HNSCCs were similar by sex. Over time, the proportion of non-OP HNSCCs that were p16+ (or ISH+) increased among whites (P = .04 for trend) but not among nonwhites (each P > .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity.During 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.
Pfetin as a risk factor of recurrence in gastrointestinal stromal tumors (GIST).
Authors: H. Orita
Journal: Journal of Clinical Oncology (2011)

e20519 Background: Despite complete resection, gastrointestinal stromal tumors (GIST) may recur or metastasize, depending on tumor grade. As such, a sensitive and specific marker is sought to select patients at high risk for recurrence. Our group reported pfetin as a prognostic biomarker for GIST. In this project, we evaluated the role of pfetin expression by IHC, controlled for clinicopathological data, as a predictor for recurrence. Methods: 45 patients with primary GIST were treated with complete (R0) resection at our institution between 1995 and 2009. Tumors originated in the stomach (38 cases), small intestine (6 cases), and rectum (1 case). Retrospective analysis of the correlation between recurrence controlled clinicopathological data and pfetin expression, by multivariate analysis was performed. Fletcher’s classification and the Japanese cancer center’s classification were used and compared. The reactivity of the monoclonal antibody against pfetin was examined by immunohistochemistry. Pfetin: We have reported pfetin, identified microarray technology and compared between statistically different GISTs for good and poor prognosis, and for prognostic marker. Results: There were 8 recurrences. (1) By univariate analysis, tumor size, mitoses, exposure (to what), and excision (you mean type?) as well as pfetin were significant predictors. (what about pfetin?) According to multivariate analysis using these 5 factors, tumor mitosis and pfetin were the most significant risk (p=0.059). (2)All 8 cases of recurrence were grouped as high risk according to Fletcher’s classification. This demonstrated high accuracy. (3)Pfetin negative cases were significantly related to recurrence (p=0.002). Clinicopathologically, pfetin correlated with mitosis (P=0.024). Conclusions: We determined that tumor mitoses and pfetin under-expression correlate with recurrence. These markers may have utility in selecting patients for adjuvant therapy.
Secretory IgA Deficiency in Individual Small Airways Is Associated with Persistent Inflammation and Remodeling
Authors: Vasiliy V. Polosukhin, Bradley W. Richmond, Rui-Hong Du, Justin M. Cates, Pingsheng Wu, Hui Nian, Pierre P. Massion, Lorraine B. Ware, Jae Woo Lee, Alexey V. Kononov, William E. Lawson, Timothy S. Blackwell
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface with the external environment; however, the role of the mucosal immune system in chronic lung diseases is incompletely understood.
Can we reliably identify patients for radical cystectomy without neoadjuvant chemotherapy?
Authors: R. J. Dickstein, H. B. Grossman, S. M. Pretzsch, J. A. Karam, R. E. Millikan, C. P. Dinney, A. M. Kamat
Journal: Journal of Clinical Oncology (2011)

258 Background: When neoadjuvant chemotherapy is administered prior to radical cystectomy in patients with muscle-invasive urothelial cancer, the patients who benefit most are those with pathologic T3-4 or N+ disease. Thus, some advocate reserving neoadjuvant chemotherapy for patients considered high risk based on presence of the following clinical parameters: lymphovascular invasion, hydroureteronephrosis, presence of a palpable or visible mass on exam under anesthesia or imaging (suggesting cT3 disease), and/or variant histology. The goal of this study was to report the outcome of patients who were classified as “not high risk” (i.e., lacking the above-mentioned criteria) and underwent radical cystectomy without neoadjuvant chemotherapy. Methods: On retrospective review of 858 patients who underwent radical cystectomy from 2000 to 2008, we identified 174 patients with muscle-invasive disease (cT2) who were classified as “not high risk” (i.e., did not have lymphovascular invasion, hydroureteronephrosis, variant histology, and/or palpable or visible mass on imaging studies) and underwent radical cystectomy without neoadjuvant chemotherapy. Endpoints of interest included pathologic upstaging (≥ pT3), pathologic lymph node positivity, need for adjuvant or salvage chemotherapy, disease recurrence, and disease specific survival (DSS). Results: Of the 174 patients, 155 (88.6%) were male and the median age was 67.6 years (range 39-86). At radical cystectomy, 75 patients (42.9%) were upstaged (pT3N0: 45; pT4N0: 6; pTxN+: 24). Thirteen patients (7.4%) received adjuvant chemotherapy for adverse pathology. After a median interval of 27 months, 38 patients (21.7%) developed recurrent disease; isolated pelvic recurrences: 4, distant recurrences: 34, and 2 had both. Eighteen patients with recurrent disease went on to receive salvage chemotherapy. Overall, 25 patients (14.3%) died of disease with a 5-year DSS of 82.3%. Conclusions: Although clinical understaging remains a problem in the management of patients with muscle-invasive urothelial cancer, our criteria for selection of patients for primary radical cystectomy without neoadjuvant chemotherapy results in a cohort with a 5-year DSS of 83%. No significant financial relationships to disclose.
Targeting type I interferon–mediated activation restores immune function in chronic HIV infection
Authors: Anjie Zhen, Valerie Rezek, Cindy Youn, Brianna Lam, Nelson Chang, Jonathan Rick, Mayra Carrillo, Heather Martin, Saro Kasparian, Philip Syed, Nicholas Rice, David G. Brooks, Scott G. Kitchen
Journal: Journal of Clinical Investigation (2016)

Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.
Whole-Exome Sequencing Links CARD11 Inactivation with SCID
Authors: Johann Greil, Tobias Rausch, Thomas Giese, Obul Reddy Bandapalli, Volker Daniel, Isabelle Bekeredjian-Ding, Adrian M Stuetz, Christoph Drees, Susanne Roth, Jürgen Ruland, Jan Korbel, Andreas E Kulozik
Journal: Blood (2012)