tbuckley/cabot-search huggingface dataset:
Surgery for Herniated Lumbar Disk in Individuals 65 Years of Age or Older
Authors: Mattis A. Madsbu, Tore K. Solberg, Øyvind Salvesen, Øystein P. Nygaard, Sasha Gulati
Journal: JAMA Surgery (2017)

This study compares patient-reported outcomes following lumbar microdiskectomy among patients at least 65 years of age vs younger patients.
Evaluation of Cap43/NDRG1/Drg-1 as a molecular target for angiogenesis and prognostic indicator in cervical adenocarcinoma
Authors: S. Nishio, N. Tsuda, K. Kawano, K. Ushijima, H. Tsuda, T. Kasamatsu, Y. Sasajima, M. Kage, M. Kuwano, T. Kamura
Journal: Journal of Clinical Oncology (2008)

16525 Background: Cap43 is a nickel- and calcium-inducible gene that has been found to play a significant role in metastasis and invasion, as well as in the primary tumor growth of malignant tumors, possibly through its ability to induce differentiation. The majority of studies thus far have suggested a negative correlation between Cap43 expression and cancer progression. However, this plausible role of Cap43 in preventing the cancer progression has been shown to depend on tissue of origin and the tumor type. The aim of this study was to investigate associations between Cap43 expression and angiogenesis and other clinicopathological factor in cervical adenocarcinoma. Methods: The records of 100 women who underwent surgery for International Federation of Gynaecology and Obstetrics (FIGO) clinical stage I-II cervical adenocarcinoma were retrospectively reviewed, and microvessel density (MVD) and expression of both Cap43 and vascular endothelial growth factor (VEGF) were evaluated in the surgical specimens by immunohistochemistry. Results: Significant associations were found between the level of Cap43 expression and the level of VEGF expression, MVD, histologic grade, tumor diameter, stromal invasion, lymphovascular space invasion and lymph node metastasis. Kaplan-Meier plots demonstrated a clear influence of Cap43 expression on survival time. The median overall survival time of patients whose tumors showed low levels of Cap43 expression was 54.1 months, as opposed to only 36.4 months for patients whose tumors showed high levels of Cap43 expression (log-rank test; P=0.0018). Conclusions: These results suggest that increased expression of Cap43 may be associated with angiogenesis and may a poor prognostic indicator in cervical adenocarcinoma. No significant financial relationships to disclose.
Defining the optimal PSA range for the maximal predictive efficacy of PSA density to detect prostate cancer on biopsy: Results from a multi-institutional and prospective contemporary cohort.
Authors: Samarpit Rai, Nicola Pavan, Nachiketh Soodana-Prakash, Bruno Nahar, Yan Dong, Ramgopal Satyanarayana, Dipen Parekh, Sanoj Punnen
Journal: Journal of Clinical Oncology (2016)

70 Background: PSA density (PSAD) is an important predictor of prostate cancer (PCa). We assessed whether the predictive accuracy of PSAD varied based on the range of PSA or whether the patient had a previous negative prostate biopsy (PB). Methods: We assessed a prospective cohort of men who were referred for a PB due to suspicion of PCa at 26 different sites across USA. The area under the receiver operating characteristic curve (AUC) was used to assess the added predictive accuracy of PSAD versus PSA across 3 different PSA ranges ( &lt; 4, 4 – 10, &gt; 10 ng/mL) and in men with or without a prior negative PB for the detection of any and significant (Gleason ≥ 7) PCa. Results: Of the 1,290 men, 585 (45%) and 284 (22%) had any and significant PCa, respectively. PSAD was significantly more predictive than PSA for detecting any PCa in the PSA ranges of 4 – 10 (AUC 0.70 vs 0.53, P &lt; 0.00001) and &gt; 10 (AUC 0.84 vs 0.65, P &lt; 0.00001) ng/mL. Similarly, for significant PCa, PSAD was more predictive than PSA in the PSA ranges of 4 – 10 (AUC 0.72 vs 0.57, P &lt; 0.00001) and &gt; 10 (AUC 0.82 vs 0.68, P = 0.0001) ng/mL. Furthermore, PSAD was significantly more predictive than PSA in detecting PCa in men that had a prior negative PB (AUC 0.69 vs 0.56, P = 0.0001 for any PCa and AUC 0.81 vs 0.70, P = 0.0042 for significant PCa), and those that didn’t (AUC 0.72 vs 0.67, P = 0.0001 for any PCa and AUC 0.77 vs 0.73, P = 0.0026 for significant PCa). However the difference between the AUC of PSAD and PSA (ΔAUC) was a lot more pronounced in men that had a prior negative PB (ΔAUC = 0.13 for any PCa and ΔAUC = 0.11 for significant PCa) as opposed to those that didn’t (ΔAUC = 0.05 for any PCa and ΔAUC = 0.04 for significant PCa), suggesting that PSAD is a much better predictor than PSA alone in men who have undergone a previous PB. Conclusions: As PSA increases, the predictive accuracy of PSAD over PSA appears to improve for the detection of any PCa and significant PCa. Additionally, PSAD has a more pronounced predictive value over PSA in detecting any and significant PCa in men who have undergone a prior negativePB. We support the use of PSAD testing to avoid unnecessary biopsies in men who have elevated PSA secondary to an enlarged prostate.
Identification of TNK2 as a critical kinase in rhabdomyosarcoma through a loss of function shRNA screen.
Authors: Fernanda Irene Arnaldez, Choh L Yeung, Carly J Smith, Natasha Caplen, Lee J. Helman
Journal: Journal of Clinical Oncology (2012)

9511 Background: Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. Embryonal rhabdomyosarcomas (ERMS) are characterized by 11p15 LOH while alveolar rhabdomyosarcomas harbor a translocation between PAX3 or PAX7 and FOXO1. Relapsed or metastatic disease has a 5-year survival rate of 25%. Methods: We sought to identify critical genes for rhabdomyosarcoma cell growth and survival. We performed a loss-of-function shRNA screen where a library of 15,000 shRNAs was introduced in RH30 (ARMS) and RD (ERMS) cells engineered to express the bacterial tetracycline repressor in a tet-on system. Relative abundance of cells containing a certain shRNA was determined using specific barcodes. We subtracted “hits” that are common to 4 lymphoma cell-lines to eliminate common survival pathways. Forty genes were associated with rhabdomyosaroma cell growth, of which 15 cause greater suppression in ARMS. We performed a subsequent validation of these 15 genes in multiple ARMS and ERMS cell lines using three different shRNA sequences using lentiviral constructs. In addition, we validated our results in an independent siRNA screen of the protein kinome in RMS cells. Results: TNK2 (tyrosine kinase, non-receptor 2) was identified as tyrosine kinase involved in rhabdomyosarcoma cell growth independently in the inducible shRNA screen and in the non-inducible siRNA platform. This molecule has been involved in downstream signaling from EGFR and integrins. Amplification of the TNK2 gene, located at 3q29, has been described in breast, prostate and lung cancer. More recently, a siRNA screen identified it as a potential therapeutic target in Ewing’s sarcoma. We confirmed TNK2 expression across patient tumor samples in a publically available database; where patients with high TNK2 expression showed lower overall survival. TNK2 knock down resulted in decreased rhabdomyosarcoma cell growth in vitro and in orthotopic xenografts. We confirmed specificity of our findings with a rescue experiment. Conclusions: We identified TNK2 as a potential therapeutic target in rhabdomyosarcoma using a loss-of-function shRNA screen and subsequent validation. Further work is ongoing to fully characterize the molecular mechanisms involved in these findings.
A phase II trial of weekly 1-hour paclitaxel in stage IV melanoma
Authors: F. Collichio, D. Ollila, K. Huck, N. Mullen, H. Shearer, E. Turner, H. Kelly, E. Zeger, M. Socinski, T. Hensing
Journal: Journal of Clinical Oncology (2005)

7565 Background: Stage IV melanoma patients have a median survival of 8 months. Several agents have limited activity with response rates of approximately 20%. Since tumor response to paclitaxel may be schedule dependent, the effect of weekly paclitaxel in patients with metastatic melanoma was studied. Methods: Stage IV melanoma that was surgically unresectable, ECOG performance status (PS) of 0 or 1, measurable disease, age greater than 18, adequate end organ function and hematologic parameters were treated with Paclitaxel at 80mg/m2 intravenously weekly times 6 weeks followed by a 1-week break. Standard paclitaxel premedications were given. Toxicity assessments were done every 2 weeks and tumor measurements were done every 7 weeks. Treatment was given until progression or toxicity. Results: 21 patients (pts) enrolled between 8/99 to 8/04. Pt Characteristics: median age 55, ten males, ECOG PS 0 in 6, and 1 in 15. Sites of measurable disease were lung (9), skin (3), lymph nodes (not regional) (5), liver (3), kidney (3), spleen (1). All but six had prior chemotherapy, biochemotherapy, immune treatment or combinations of these. Number of prior therapies were 1 in 4 pts, 2 in 4 pts, 3 in 5 pts, and 4 in 2 pts. There were a total of 36 cycles administered (median number of 1.8 cycles). There were 18/21 evaluable pts. CR 2(11%), PR 2 (11%), ORR (22%), SD 7(39%), PD (39%). All of the patients with SD, or PR eventually progressed and came off therapy except for one patient with SD who stopped after 4 cycles. The survival at 12 months is 0.299 (CI .080-.517). The median time to disease progression is available for 14 of 17 patients (1 is still on study) and was 13 weeks. No grade (gd) 4 toxicities and only four pts had gd 3 neutropenia, 2 had gd 3 anemia, and one pt had gd 3 ototoxicity. Conclusions: Weekly paclitaxel at 80mg/m2/week X 6 weeks out of 7 is a well tolerated treatment for melanoma that has minimal activity in this heavily pretreated population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Eli Lilly Bristol-Myers Squibb
Malignant ascites as a manifestation of advanced papillary renal cell cancer (pRCC).
Authors: Julia C. Friend, Daniel Su, Rashmi Thimmapuram, James Peterson, Geri Hawks, Martha Ninos, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Journal of Clinical Oncology (2015)

465 Background: Peritoneal carcinomatosis and ascites are frequent and clinically challenging complications associated with several malignancies such as ovarian cancer. Although ascites is rarely reported in patients with advanced renal cell carcinoma (RCC), its true incidence, particularly in non-clear cell variants, remains poorly defined. Here, we describe the incidence of and clinical characteristics associated with ascites in patients with pRCC. Methods: Patients with metastatic renal cell carcinoma (RCC) seen at the NCI Urologic Oncology Branch were identified in a review of our clinical database. The incidence of radiologically and/or cytologically evident ascites, relevant associated clinical characteristics, and survival were evaluated as was the incidence of ascites in a contemporaneous clear cell RCC (ccRCC) cohort. Results: 241 patients with metastatic RCC were seen between 2002 and 2014, including 109 with pRCC and 125 with ccRCC. Seventeen patients with metastatic pRCC (17/109,15.5%) had evidence of malignant ascites, while only 1/125 pts (0.8%) with ccRCC developed this complication. Median age of PRCC patients with ascites was 45.8 years (range: 26.1 to 76.6 years). Ascites was seen in both patients with type 1 (15.6%, 10/64) and those with type 2 pRCC (15.5%, 7/45). Median time to development of ascites from initial diagnosis of metastatic disease was 16 months (95% CI 7-23 months). Median survival from diagnosis of metastatic disease was 25 months (95% CI 13-41months) in patients with ascites, compared to 20 (95% CI 14-31 months) in those without this complication. (p = 0.59). Conclusions: To our knowledge, this is the largest series evaluating the incidence of and outcome associated with ascites in RCC. Although rare in ccRCC, malignant ascites is a fairly common manifestation of metastatic pRCC. In our cohort, patients with ascites appeared to have outcomes comparable to patients with metastatic pRCC without ascites.
Pulmonary Perfusion Changes Following Extracardiac Lateral Fontan and Bilateral Bidirectional Glenn Shunt in Hypoplastic Right Ventricle With Duplicated Superior Vena Cava
Authors: Roberto Andres Salas Fragomeni, Evrim B. Turkbey, Blake C. Jones, Lilja B. Solnes, Steven P. Rowe
Journal: Clinical Nuclear Medicine (2017)

The incidence of congenital heart disease requiring specialized care is 2.5 to 3 per 1000 live births with a prevalence of congenital heart disease of 81.4 per 10,000 live births. Total cavopulmonary or atriopulmonary connection, used for palliation of certain types of congenital heart disease, diverts flow from the vena cava or atrium directly into the pulmonary arteries. Altered anatomy in patients who have undergone this intervention may result in contrast and/or radiotracer localizing preferentially to a single lung leading to interpretation errors and redundant studies. Performing bilateral upper-extremity injections for this patient population may reduce such technical errors and redundant studies.
Trends in resected oesophageal and gastric adenocarcinoma (OGA) outcomes: Royal Marsden (RM) experience 2001-2010.
Authors: Elisa Fontana, Elizabeth Catherine Smyth, David Cunningham, Sheela Rao, David J. Watkins, William H. Allum, Jeremy Thompson, Tom Samuel Waddell, Clare Peckitt, Ian Chau, Naureen Starling
Journal: Journal of Clinical Oncology (2015)

169 Background: OGA is a lethal cancer globally. Overall survival (OS) has improved in the last decade, potentially due to stage migration and changes in management of early stage cancer. To examine this hypothesis we assessed outcomes of resected OGA patients (pts) at RM over 10 years (y), comparing 2 time periods, 2001-2005 (A) and 2006-2010 (B). Methods: Electronic records of all pts who had undergone surgery with radical intent for OGA between 01/2001 and 12/2010 were reviewed. Pt age, sex, ECOG PS, pre-operative staging investigations (CT, EUS, PET-CT), perioperative therapy, pathological stage, dates of death, last follow up and treatment for recurrent disease were recorded. Disease-free (DFS), OS and survival beyond relapse (SBR) were estimated using the Kaplan Meier method; co-variates were compared using the log rank test and Hazard ratios calculated using cox regression within the 2 time periods. Results: 367 pts were identified; 151 (A) and 216 (B). Median age was 67y (A) and 66y (B). Gender distribution, PS, site of primary and pre-intervention lymph node status were comparable. PET-CT use increased from 9% (A) to 37% (B), p&lt;0.001, (84% in 2010). &gt;75% pts in both groups were treated with chemotherapy; use of perioperative therapy increased over time (19% of treated pts in A vs 52% in B). Conversely use of pre-operative therapy alone decreased over time (75% of treated pts A vs. 45% in B). Rates of R0 resection increased from 75% (A) to 89 % (B) (p=0.001). Median number of resected lymph nodes was 20 (A) and 31 (B). ≥T3 tumours (46% vs 33%) and ≥N1 lymph nodes (53% vs 48%) were more common in A. After a median follow-up of 95 (A) and 59 (B) months, relapse occurred in 47% (A) and 38% (B). 5y DFS for A and B was 34% vs. 51% [HR 0.59, (0.45-0.78), p&lt;0.001]. 5y OS for A and B was 40% vs. 55% [HR 0.58, (0.43-0.77), p&lt;0.001]. Median SBR was 7.6 months in both groups (p=0.713). Conclusions: During 2001-2010 survival of pts with resected OGA improved. Relevant factors may include improved preoperative staging by PET, increased numbers of R0 resections and higher lymph node yield. Pattern of chemotherapy usage as a surgical adjunct may also be contributory. However survival for relapsed pts was unchanged.
A novel concept of adoptive immunotherapy with tumor necrosis factor-related, apoptosis-inducing, ligand-expressing natural killer cells for eliciting an anti-breast-cancer response.
Authors: K. Kajitani, H. Ohdan, Y. Tanaka, T. Kataoka
Journal: Journal of Clinical Oncology (2010)

e13048 Background: Previous studies have demonstrated that natural killer (NK) cells can destroy breast cancer cells. In the present study, we have reported that liver NK cells exhibit greater cytotoxic activity against tumor cells than do peripheral blood (PB) NK cells in humans. Methods: We investigated the phenotypic and functional properties of NK cells extracted from liver perfusates of living donors in clinical liver transplantation. Next, the susceptibility of various breast cancer cell lines to the activity of the liver and PB NK cells was tested. Results: Stimulation with IL-2 increased the expression of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on both the PB and liver NK cells. Accordingly, both the liver and PB NK cells exhibited strong cytotoxicity against various breast cancer cell lines (MDA-MB231, MDA-MB453, MDA-MB468, and MCF-7) after in vitro stimulation with IL-2. Further treatment with anti-HER2 monoclonal antibodies (mAbs) remarkably promoted the NK cell-mediated cytotoxicity toward the HER2-expressing breast cancer cell line MDA-MB453. All the breast cancer cell lines expressed remarkable levels of a death-inducing TRAIL receptor—death receptor (DR)4 and 5—which contains cytoplasmic death domains and mediates apoptosis, but they did not express the death-inhibitory receptors (DcRs) 1 and 2. Treatment with anti-TRAIL neutralizing mAbs partially reduced the liver and PB NK cell-mediated cytotoxicity toward breast cancer cells (32% ± 9%, 64% ± 15% reduction respectively at E:T = 5:1); this finding indicated the involvement of TRAIL-induced NK cell-mediated cytotoxicity. The expression of CXC chemokine receptor 3 (CXCR3), which binds to chemokines CXCL9, CXCL10, and CXCL11 secreted by breast cancer cells, was upregulated in the IL-stimulated NK cells. Conclusions: TRAIL+ NK cells kill breast cancer cells via death receptor/ligand interactions. This finding provides the basis for a novel concept, i.e., adoptive transfer of IL-2-stimulated NK cells to breast cancer patients for eliciting an anti-breast-cancer response. No significant financial relationships to disclose.
Clinical impact of the feasibility of epidermal growth factor receptor (EGFR) mutations detection in cytological samples of patients (pt) with non-small cell lung cancer (NSCLC) treated with erlotinib (E) at first line.
Authors: J. Puente, J. L. Gonzalez Larriba, P. Gajate, S. Hernandez, A. Irles, L. Gutierrez, J. Sanz, E. Diaz Rubio
Journal: Journal of Clinical Oncology (2011)

e18051 Background: EGFR mutations have been reported to be a predictor of efficacy of new drugs in NSCLC first line treatment. Recently, two phase III trials have shown the efficacy of gefinitib and erlotinib in this context, but the majority of pt were randomized after large biopsy samples. This study try to evaluate the efficacy and safety of E in untreated pt with advanced NSCLC and mutated EGFR (most of them detected in cytological specimens). Methods: Since 2007 we have screened 270 patients and we have found 40 patients with EGFR mutations (14%). 23 patients were treated with E at 150 mg per day at first line treatment. 13 of 23 pt were identify with cytological samples. Results: Median age was 72 years (33-90). Sex ratio (F/M): 74%/26%. 65% were non-smokers and 91% of them had ECOG 0-1. According with histology, 73.9% adenocarcinomas, 8.7% squamous cell carcinomas, 4.3% bronchioloalveolar carcinomas (13% non-specific). Oncogenic EGFR mutations detected were deletion of exon 19 (52.2%) and mutation of exon 21 (47.8%). Response has been evaluated in 18 p so far: complete response, 1 p; partial response, 11 p; stable disease, 3 p; progressive disease, 3 p; overall response rate, 67%; clinical benefit, 84%. In the cytological subgroup: overall response rate, 64%; clinical benefit, 82%. 11 patients continue under treatment with E. Progression free survival for all pt were 11 months, and 10 months for pt with mutations in EGFR gene detected in cytological specimens. Toxicity profile was predictable (mild to moderate rash, diarrhea and stomatitis). Conclusions: Our results suggest that detection of EGFR mutations in cytological samples is feasible and could have clinical impact when these pt are treated with tirosin-kinase inhibitors. A study comparing histological and cytological samples is on going.
Long-term results of MR-guided laser induced thermotherapy (LITT) of colorectal carcinoma metastases in the liver
Authors: M. G. Mack, K. Eichler, R. Straub, T. Lehnert, S. Zangos, T. J. Vogl
Journal: Journal of Clinical Oncology (2005)

3610 Background: To evaluate MR-guided LITT for the treatment of colorectal liver metastases in a long-term follow-up study. Methods: Percutaneous MR-guided LITT was performed under local anesthesia on an outpatient basis with a Nd:YAG laser (1064 nm) in 805 patients (mean age 61.2 years, range 34–84) with 2397 liver mets of colorectal cancer between 1993 and 2004. 271 patients had recurrent mets after surgery, 288 mets in both liver lobes, 112 refused surgical resection, 30 had general contraindications for surgery and 104 had mets at difficult localization for surgery. 646 patients were treated with the intention to reach a R0 situation (group 1). These patients had not more than 5 liver metastases and no extrahepatic disease. 159 patients had either extrahepatic disease (lung metastases) or >5 mets in the liver. These patients were treated in palliative intention (group 2). Survival rates were calculated using the Kaplan-Meier method. Results: The local hepatic tumor control rate at 6-month follow-up was 2.2% for mets up to 2 cm diameter, 2.9% for mets between 2 and 3 cm diameter, 0.4% for mets between 3 and 4 cm diameter and 2.6% for mets larger than 4 cm in diameter. The mean survival rate for group 1 was 4.0 years (95% CI: 3.7–4.4 years, 1y surv 95%, 2y surv 76%, 3y surv 53%, 5y surv 27%). The mean survival rate for group 2 was 2.8 years (95% CI: 2.4–3.1 years, 1y surv 84%, 2y surv 55%, 3y surv 28%, 5y surv 14%). Patients who refused resection had a mean survival of was 5.5 years, which was statistically significant superior to patients with recurrences after resection, with bilobar metastases and metastases at difficult localization (Tarone Ware p=0.0001, Breslow p=0.0002, Log Rank p=0.0001). Patients with metachronous liver metastases had also superior survival rates compared to patients with synchronous metastases (4.1 years versus 3.5 years (p<0.05). The initial number of liver metastases and the initial lymph node status were also prognostic factors. The primary tumor stage was not a prognostic factor. Conclusions: MR-guided LITT yields high local tumor control and very good survival rates in patients with liver metastases of colorectal carcinoma. LITT appears in selected cases superior to resection. No significant financial relationships to disclose.