tbuckley/cabot-search huggingface dataset:
Prognostic analysis according to the expression of hormone receptors in HER2-positive breast cancer.
Authors: Inmaculada Gallego Jimenez, David Morales Pancorbo, Jose Fuentes Pradera, Javier Salvador, Juan L. Bayo, Reyes Bernabé, Maria Rodriguez de la Borbolla, Eva Fernandez Parra, Amelia Lopez Ladron
Journal: Journal of Clinical Oncology (2012)

e11075 Background: Overexpression HER 2 + + + is a distinct group within the breast cancer with different treatments in both the adjuvant and advanced setting. However, from the clinical point of view, there are significant differences within this group HER2 + + + referred to response to trastuzumab, metastatic sites and survival intervals. Recently reported data guides to a worse prognosis in the subgroup expressing hormone receptors. We propose to study these differences in HER2 + + + between subgroups hormone receptor positive and negative. Methods: Retrospective observational study of all patients diagnosed with HER2 + + + at the Hospital Virgen de Valme between the years 2005-2011. We studied the disease-free interval (DFS) and global survival (OS). We also studied the frequency of brain metastases and cerebral disease-free interval (BDFS). We explore differences between the hormone receptor-negative groups (group A) and positive (group B). All patients have been treated with at least one line of trastuzumab. Results: N = 73 (40 group A and 33 group B). Median age was 58 and 55 respectively. 33 patients had metastases in the course of the disease. 7 patients initially diagnosed with metastatic stage. There is a difference of 5.0 months in group A favorable DFS (p = 0.28). The OS was 52 months in group A versus 48 months in group B (difference of 4 months p = 0.18). The BDFS was 57 months for group A and 15 months for group B (p = 0.1). The incidence of brain metastases was 27% versus 9%. Conclusions: Our data suggests a better prognosis in terms of DFS, OS and BDFS in hormone receptor-negative group. Likewise, the incidence of brain metastases was three times lower. We need well design clinical trials, monitoring and therapeutic strategies for this subgroup of patients.
Survival benefit from bevacizumab in newly diagnosed glioblastoma (GBM) according to transcriptional subclasses.
Authors: Jason T. Huse, Kathryn Beal, Jianan Zhang, Edward R. Kastenhuber, Thomas Joseph Kaley, Lauren E. Abrey, Philip H. Gutin, Cameron W Brennan, Antonio Marcilio Padula Omuro
Journal: Journal of Clinical Oncology (2013)

2057 Background: Genome-wide transcriptional studies (TCGA and others) have identified distinct GBM molecular subtypes, but to date this has not translated into prognostic or therapeutic implications. Bevacizumab has emerged as a new treatment option for GBMs, although a survival benefit has yet to be demonstrated in unselected patients (pts). We analyzed outcomes from a prospective phase II trial in newly diagnosed GBM treated with hypofractionated stereotactic radiotherapy (HFSRT) combined with temozolomide and bevacizumab, and correlated with GBM transcriptional subclasses. Methods: Pts with newly diagnosed GBM with tumor volume &lt; 60cc were eligible. Treatment consisted of HFSRT (6x6 Gy to contrast-enhancing tumor and 6x4 Gy to FLAIR hypersignal with dose painting), concomitant with bevacizumab (10 mg/kg Q2 weeks) and temozolomide (75mg/m 2 daily), followed by standard adjuvant bevacizumab/ temozolomide. Primary endpoint was 1-y overall survival (OS). To establish TCGA transcriptional subclasses, mRNA from formalin-fixed paraffin-embedded tissue blocks was analyzed with a validated, 151-probe Nanostring gene expression assay. Results: A total of 40 evaluable pts were accrued, achieving a 1-y OS of 90% (95% CI 76-96), 2-y OS of 32% (95%CI 19-47) and median OS of 17.4m. The molecular subclass could be defined in 31 pts, as follows: Mesenchymal: 14 (45%) pts, pro-neural: 8 (26%), classical: 7 (23%), neural: 2 (6%). The pro-neural phenotype was associated with reduced overall survival: median OS of 13.5m vs 21.2m for non pro-neural tumors (univariate: p = 0.015; multivariate: p = 0.003). MGMT promoter methylation did not predict survival (p = 0.13). Conclusions: We provide proof-of-principle that GBM transcriptional classification is biologically and therapeutically relevant, identifying non pro-neural GBMs as the best candidates for bevacizumab treatment. Our findings imply that angiogenesis and tumor invasion mechanisms in proneural tumors may be distinct from other subtypes, and we suggest such pts should not be offered bevacizumab treatment upfront. Future randomized trials focusing on non-proneural tumors may finally demonstrate a survival advantage for bevacizumab in GBM. Clinical trial information: NCT01392209.
Next generation sequencing of non-muscle invasive bladder cancer to reveal potential biomarkers and rational therapeutic targets.
Authors: Eugene J. Pietzak, Eugene K. Cha, Aditya Bagrodia, Esther N. Drill, Gopa Iyer, Sumit Isharwal, Qiang Li, Priscilla Baez, Michael F. Berger, Ahmet Zehir, Irina Ostrovnaya, Nikolaus Schultz, Dean F. Bajorin, Jonathan E. Rosenberg, Guido Dalbagni, Hikmat Al-Ahmadie, David B. Solit, Bernard H. Bochner
Journal: Journal of Clinical Oncology (2017)

302 Background: We examined a cohort of index pre-treatment NMIBC tumors using Next Generation Sequencing to identify genetic alterations with potential clinical implications. Methods: 105 patients on a prospective IRB-approved protocol had their pre-treatment index NMIBC tumor and matched germline DNA sequenced with a 341 cancer-associated gene panel in a CLIA-certified clinical laboratory. A genitourinary pathologist reviewed representative H&amp;E slides to confirm grade, stage, and urothelial histology. Restaging TUR was performed in all HGT1 tumors. Results: To characterize the genomic landscape of NMIBC, we analyzed 105 tumors across the disease spectrum including LGTa (n = 23), HGTis (n = 12), HGTa (n = 32) and HGT1 (n = 38). The most frequently altered genes in NMIBC were the TERT promoter (74%), FGFR3 (50%), KDM6A (47%), ARID1A (28%), PIK3CA (27%), KMT2D (24%), STAG2 (21%), and CDKN2A (17%). 81% of tumors had inactivating alterations in a chromatin-modifying gene. Alterations in the RTK/RAS/PIK3 pathway occurred in 83% of tumors, including 58% of high-grade NMIBC having alterations in either ERBB2 or FGFR3. Of the 105 patients, 62 were treated uniformly with a 6-week induction course of BCG without maintenance. We investigated all genes altered on the 341-gene panel in at least 5 patients for their association with recurrence after BCG therapy in this 62 patient cohort. On cox-regression analysis, only truncating mutations in the chromatin-modifying gene ARID1A were associated with recurrence after BCG (HR = 3.14 [95%CI = 1.51, 6.51] p = 0.002). This remained significant when adjusting for multiple comparisons (p = 0.04) and when including ARID1A missense mutations of unknown significance (p = 0.002). Conclusions: Next Generation Sequencing of index pre-treatment NMIBC tumors identified an association between ARID1A mutations and recurrence after BCG therapy. Further investigation is needed to determine whether ARID1A mutations are a potential predictive/prognostic biomarker or therapeutic target. Moreover, most NMIBC tumors had at least one potentially “actionable” alteration that could serve as a target in rationally designed trials of intravesical or systemic therapy.
Pain on movement and pain at rest decrease after zoledronic acid infusion in patients with bone metastases due to breast or prostate cancer
Authors: C. Ripamonti, E. Fagnoni, T. Campa, V. Giardina, C. Brunelli, F. De Conno
Journal: Journal of Clinical Oncology (2006)

18582 Background: There is no study on bisphosphonates assessing separately pain at rest and incident pain. Aim of the study was to evaluate the reduction in pain at rest and incident pain after treatment (up to 6 infusions) with 4 mg zoledronic acid (ZA) I.V. every 28 days in patients with bone metastases. Methods: All consecutive patients with bone metastases from breast or prostate cancer starting ZA treatment (August 2002 - May 2004) at NCI of Milan were enrolled in this observational prospective longitudinal study. Pain at rest and incident pain referred to the prior week were measured by a six level verbal scale (0–5 score) at baseline and on each infusion as well as at follow-up visit (2 weeks after every infusion). The two main endpoints (estimated reduction in pain at rest and incident pain) were defined as the difference between the baseline score and the average of all the post-treatment scores for each patient, and are presented with their respective 95% Confidence Interval. Positive values indicate reduction. Because of the potential confounding effect of analgesics intake, patients without any increase in analgesic consumption while on study were also analyzed as a separate subgroup. Results: 48 patients (mean age 66 years, 33 female), with breast (34) or prostate cancer (14) were enrolled. 30 patients underwent 4 to 6 infusions while 7 dropped out before the first follow-up visit. The analysis was performed on the 41 patients with at least one follow-up evaluation (average number of evaluations = 8.1 range = 1–13). The estimated reduction in pain at rest and incident pain was 0.55 (0.19–0.91) and 0.73 (0.31–1.14) respectively. In the 13 patients who did not report increased analgesic consumption, the estimated reduction was still substantial: 0.61 (0.25–0.97) 1.12 (0.41–1.83) respectively. Conclusions: This is the first study showing that in patients with painful multiple bone metastases, ZA reduces both pain at rest and incident pain in patients with painful bone metastases. [Table: see text]
Diabetes Prevention Program in Youth (Insulin Superheroes Club) Pilot: Improvement in Metabolic Parameters and Physical Fitness After 16 Weeks of Lifestyle Intervention
Authors: Chantis Mantilla, Tamekia Jones, Kristina M. Decker, Andrea M. Jacobo, Sylvia Y. Sontheimer, Margaret R. Mirro, Marion E. Hare, Joan C. Han
Journal: Diabetes Care (2017)

Culturally tailored and comprehensive prevention strategies are vital for addressing the epidemic of obesity and rising rates of type 2 diabetes, particularly among ethnic and racial minority youth (1). The Diabetes Prevention Program (DPP) has demonstrated the efficacy of lifestyle modification in adults (2). However, studies on lifestyle programs for diabetes prevention in youth are limited, and none have reported comprehensive physical fitness outcomes (3–5). We conducted a pilot prospective uncontrolled study (ClinicalTrials.gov identifier NCT03042936) evaluating feasibility and changes in metabolic and physical fitness parameters for the Insulin Superheroes Club (ISC) curriculum, a DPP designed for youth from culturally diverse, minority backgrounds.

Youth aged 7–15 years and a parent with impaired glucose tolerance enrolled in the ISC as a supplement to the Centers for Disease Control and Prevention’s adult DPP. The ISC is a 12-month, multilevel program that includes 16 weekly (phase 1), 3 biweekly (phase 2), and 6 monthly (phase 3) sessions. Participants attended sessions that included 60 min of physical fitness and 30 min of education. The education portion included interactive …
Association between mitotic rate and lymph node metastasis in thin melanoma in the general population..
Authors: Yan Xing, Chung-Yuan Hu, Mee-Young Lee, Virginia Jean Seery, Caroline C Kim, Nicholas E. Tawa, Robert Andrew Frankenthaler, David F. McDermott, Elizabeth Iannotti Buchbinder
Journal: Journal of Clinical Oncology (2014)

e20039 Background: Mitotic rate was incorporated into the AJCC 7th edition staging system for cutaneous melanoma because of its prognostic impact on melanoma-specific survival in patients with thin...
The prognostic significance of maximum standardized uptake value of primary tumor in non-small cell lung cancer patients surgically treated:analysis of 413 cases.
Authors: Billè Andrea, Skanjeti Andrea, Errico Luca, Arena Vincenzo, Gisabella Mara, Lisi Elena, Pelosi Ettore, Ardissone Francesco
Journal: Journal of Thoracic Oncology (2011)
Role of nutritional and inflammatory status in the prognosis of advanced gastric cancer.
Authors: Antía Cousillas, Elena Gallardo, Iria Carou, Ángeles Rodriguez, Víctor Sacristán, Lidia Vázquez, Cristina López-Jato, Francisco Ramon Garcia Arroyo, Cristina Azpitarte, Pedro López-Clemente, Manuel Constenla
Journal: Journal of Clinical Oncology (2017)

35 Background: This study explores the prognosis impact of nutritional and immune status in metastatic gastric cancer (GC). Recently research has been focused on a proinflammatory status and the relevance of inmune system of the patient in GC. Neutrophil-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) has showed prognostic value in local disease. Our study was assesed in metastatic disease. Methods: One hundred and twenty patients with metastatic gastric adenocarcinoma were retrospectively evaluated between 2011 and 2015. 67.2% were metastatic at diagnosis and 32.8% had a recurrence of disease. Clinical, laboratory and histopathological characteristics were selected as risk factors. The optimal cut-off levels were defined as NLR = 3, PNI (10 x albumin concentration +0.005 x total lymphocyte count) = 43.8, albumin = 3.5 g/dL, body mass index (BMI) = 25. Patients with high NLR and hypoalbuminemia were defined as 2, patients who presented only one abnormally were defined as 1 and those with neither abnormality were defined as 0. Lab data levels were related with survival by Kaplan-Meier and compared by long-rank test. Results: Among 120 patients, mean age was 69 years old, 35% female and 72.5% had no comorbidity. NLR &gt; 3 (6.7 vs 12.5months, p = 0.001), low PNI (7.7 vs 13.1months, p = 0.01) and low albumin (6.2 vs 11.2 months, p = 0.002) were correlated with OS. Significantly, patients with an BMI &lt; 25 had a worse prognosis compared with patients with BMI ≥ 25 (7.4 vs 12.4months, p = 0.02). Obesity in metastatic GC was related with good prognosis in our review. In the group of patients with hypoalbuminemia and h-NLR (27.6%) OS was much worse than patients with normal albumin and low-NLR, 33.6% (4.4months vs. 12.8 months, p &lt; 0.001) Conclusions: High NLR ( &gt; 3) and low PNI ( &lt; 43.8), albumin ( &lt; 3.5g/dL) were correlated with worse outcomes. Moreover, the association in a score of NLR plus albumin showed eight months OS diference. As a recent data in other cancer sites, obesity was related with good prognosis in mGC in our review.
Response to Comment on Inzucchi et al. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016;39:1684–1692
Authors: Silvio E. Inzucchi, Catherine M. Viscoli, Lawrence H. Young, Karen L. Furie, Mark Gorman, Anne M. Lovejoy, Samuel Dagogo-Jack, Faramarz Ismail-Beigi, Mary T. Korytkowski, Richard E. Pratley, Gregory G. Schwartz, Walter N. Kernan
Journal: Diabetes Care (2017)

Katsiki and Mikhailidis (1) raise the possibility that reduced uric acid may have been a mechanism of the cardiovascular benefits of pioglitazone in the Insulin Resistance Intervention after Stroke (IRIS) trial. Unfortunately, we did not measure urate levels during the trial, so the question cannot be answered. One small trial suggested modest reductions in hyperuricemia from pioglitazone, on the order of 14% (<1 mg/dL) (2). Data regarding the association between uric acid and cardiovascular disease remain highly controversial, however, and whether lowering urate confers a cardiovascular advantage remains to be demonstrated convincingly.

The issue of effects of pioglitazone on nonalcoholic fatty liver disease is also raised. As Katsiki and Mikhailidis (1) describe, modest decreases in alanine aminotransferase levels were in fact measured in IRIS participants assigned to the pioglitazone group. Because we did not measure liver fat directly, …
Measuring and improving symptom burden in radical cystectomy patients undergoing traditional care compared to enhanced recovery.
Authors: Janet Baack Kukreja, Courtney M Chang, Ting Yu Chen, Qiuling Shi, Xin Shelley Wang, Neema Navai, Ashish M. Kamat, Colin P.N. Dinney, Jay Bakul Shah
Journal: Journal of Clinical Oncology (2017)

340 Background: Bladder cancer is a disease of the elderly associated with high morbidity in those undergoing radical cystectomy (RC). The Optimized Surgical Journey (OSJ) uses enhanced recovery after surgery (ERAS) principles for RC patients to improve postoperative pain and shorten hospital stay. There have been few patient reported outcomes studied in OSJ and ERAS patients. The MD Anderson Symptom Inventory (MDASI) is patient reported outcome measures used for clinical and research purposes related to cancer and its treatment. Our objective was to determine if patient reported outcomes using MDASIs are different in patients following the OSJ compared to a traditional care pathway. Methods: From July 2013 to November 2015, MDASIs were collected from 160 RC patients preoperatively and on postoperative days (POD) 1 through 3. The MDASI consists of 19 core symptom burden related questions and 6 questions analyzing how symptoms have interfered with the patient’s life. Using a 0-10 scale, patient’s rate their symptoms. T-test, Man-Whitney where appropriate and logistic regression were used for multivariable cross sectional analysis. Results: The most bothersome symptoms were abdominal discomfort, disturbed sleep, dry mouth, fatigue, and drowsiness. Nausea, vomiting, bowel pattern, bowel control and appetite were all found to be insignificant. Abdominal discomfort was reported significantly less in OSJ patients on PODs 1 and 2 (p = 0.032 and 0.001, respectively). In multivariable analysis OSJ status was predictive of less abdominal pain (p &lt; 0.001). Dry mouth was also significantly burdensome on PODs 1 and 2 (p = 0.022 and &lt; 0.001, respectively) in non-OSJ patients. Less dry mouth was also predicted by OSJ status in multivariable analysis (p = 0.014). Disturbed sleep, fatigue, and drowsiness were significantly less in patients on the OSJ POD 2. Mood was better in OSJ patients PODs 2 and 3 (p = 0.016). Conclusions: The OSJ can significantly reduce the burden of symptoms in RC patients immediately postoperatively. MDASIs maybe a helpful tool to measure symptom burden. This information can be used in the future to create additional interventions for improvement in RC patient recovery experiences.
Quality control by photograph for evaluation of open (OP) and laparoscopic (LAP) colectomy with D3 resection for stage II/III colorectal cancer: Japan Clinical Oncology Group study JCOG 0404.
Authors: Kentaro Nakajima, Masafumi Inomata, Tomonori Akagi, Tsuyoshi Etoh, Hiroshi Katayama, Masaaki Ito, Shoichi Fujii, Shuji Saito, Fumio Konishi, Yoshihisa Saida, Hirotoshi Hasegawa, Takashi Yamaguchi, Yosuke Fukunaga, Kenichi Sugihara, Masahiko Watanabe, Seiichiro Yamamoto, Yasuhiro Shimada, Yoshihiro Moriya, Seigo Kitano
Journal: Journal of Clinical Oncology (2014)

e14501 Background: The phase lll JCOG0404 (UMIN-C000000105) showed the favorable short term outcome in LAP arms (less blood loss, decreased pain, a shorter hospital stay, and fewer wound-related complications). In JCOG0404 (between Oct 2004 and March 2009, n=1057), for quality control, photographs of resection fields and, resected specimens, and the skin incision were taken in all patients. Methods: These photographs were sent to Study Coordinator and evaluated by the study-specific committee. Patients with distant metastasis and/or severe invasion were excluded in this study. The quality of resection was judged by the following criteria:
Chemo-Immunotherapy with Hyper-CVAD Plus Ritixumab for Adult Burkitt’s and Burkitt’s Type Lymphoma (BL) or Acute Lymphoblastic Leukemia (B-ALL).
Authors: Deborah A. Thomas, Stefan Faderl, Susan O’Brien, Carlos Bueso-Ramos, Jorge Cortes, Guillermo Garcia-Manero, Francis Giles, Srdan Verstovsek, William Wierda, Sherry Pierce, Jiaquin Shan, Mark Brandt, Fredrick Hagemeister, Fernando Cabanillas, Michael J. Keating, Hagop Kantarjian
Journal: Blood (2005)
Overexpression of VEGF-C and -D may predict unfavorable outcome in resected non-small cell lung cancer
Authors: Y. Ko, C. Jung, M. Lee, J. Kang, Y. Hong, K. Lee
Journal: Journal of Clinical Oncology (2007)

21114 Background: Correlation of Vascular endothelial growth factor (VEGF)-C, VEGF-D and/or VEGF receptor 3 (VEGFR-3) with lymphatic spread, tissue invasion and poor clinical outcomes has been observed in various cancers. Nodal metastasis is known to one of poor prognostic factors in non-small cell lung cancer (NSCLC). We investigated the correlation of VEGF-C,-VEGF-D and VEGFR-3 with clinicopathologic parameters and patient survival in NSCLC. Methods: Using immunohistochemial staining, we analyzed the protein expressions of VEGF-C, VEGFD and VEGFR-3 on the tissue array specimens from 180 patients with completely resected NSCLC. A 0 to +1 immunohistochemical staining (IHCS) of the cancer cell was defined as negative, +2 to +3 IHCS was as positive. Results: The expressions of VEGF-C, VEGF-D and VEGFR-3 were observed in 28.9%, 32.8% and 30.6% of cases, respectively. In the Cox regression-based multivariate analysis, it was proved that VEGF-C and D proved to be an independent prognostic factors as well as known prognostic factors, such as tumor size and lymph node metastases (VEGF-C, p=0.001; VEGF-D, p=0.014). VEGF-C expression showed statistically significant correlation with the expression of VEGFR-3 (p=0.02). Conclusion: To be taken, the present study revealed that VEGF-C and D expression may predict poor prognosis in resected NSCLC patients. Therefore, these results seems to be worth developing promising targeting inhibitors on lymphangiogenesis which plays major role in locoregional recurrence for surgically NSCLC patinets. No significant financial relationships to disclose.