tbuckley/cabot-search huggingface dataset:
Effect of serum HER2, TIMP-1, and CAIX on outcome in HER2+ metastatic breast cancer patients treated in first line with lapatinib or trastuzumab combined with taxane: NCIC CTG MA.31.
Authors: Diep Ho, Jessica Huang, Judy-Anne W. Chapman, Kim Leitzel, Suhail M. Ali, Lois E. Shepherd, Wendy R. Parulekar, Catherine Elizabeth Ellis, Rocco J. Crescenzo, Liting Zhu, Shakeel Virk, Dora Nomikos, Samuel Aparicio, Karen A. Gelmon, Walter P. Carney, Allan Lipton
Journal: Journal of Clinical Oncology (2014)

617 Background: The lapatinib-taxane combination led to shorter PFS than trastuzumab-taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum HER2, CA IX, and TIMP-1. Methods: MA.31 accrued 652 patients; 537 (82%) were centrally-confirmed HER2+. Biomarkers were categorized for univariate and multivariate predictive investigations with a median cut-point, ULN cut-points (15 ng/ml for HER2; 506 pg/ml for CAIX; 454 pg/ml for TIMP-1), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariate analysis used continuous and categorical biomarkers for PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown. Results: Serum was banked for 472 (72%) of 652 patients. Higher serum HER2 (>median; >15; >30; or >100 ng/ml; p=0.05-0.002); higher CAIX (>median; >506 pg/ml; p=0.02; p=0.001); and higher TIMP-1 (>median; >454 pg/ml; p=0.001; p=0.02) had worse univariate PFS. In multivariate analysis, higher continuous TIMP-1 was associated with significantly worse PFS: HR=1.001 (95% CI=1.000-1.002; p=0.004). Continuous serum HER2 and CAIX were not significantly associated with PFS. HER2 of 15 ng/ml or higher had shorter PFS (p=0.02); higher categorical CAIX had worse PFS (p=0.01-0.08). The interaction terms of HER2, CAIX, and TIMP-1 with treatment were not significant. Multivariate PFS categorical serum results (Table). Conclusions: Higher levels of serum TIMP-1, CAIX, and HER2 were significant prognostic biomarkers of shorter PFS. No serum biomarker was predictive of differential response to lapatinib vs. trastuzumab. Evaluation of TIMP-1 and CAIX targeted therapy in addition to HER2 targeted therapy is warranted in patients with elevated serum levels of these biomarkers. p-value HR Lower CI Higher CI LTax vs TTax 0.001 1.58 1.20 2.06 Adjuvant anthracyclines 0.011 1.58 1.11 2.25 Adjuvant other therapy 0.043 3.88 1.04 14.41 EGFR (% stain) 0.012 1.01 1.001 1.01 Serum HER2 (>15 vs <15 ng/ml) 0.023 1.51 1.06 2.15 Serum CAIX (>506 vs <506 pg/ml) 0.005 1.54 1.14 2.08 *DH and JH contributed equally.
The prognostic utility of LDH and CRP for survival after melanoma metastasectomy in the urogenital tract.
Authors: Georgios Gakis, Mohamed F Abdelhafez, Tilman Todenhoefer, Markus Renninger, Christian Schwentner, Arnulf Stenzl
Journal: Journal of Clinical Oncology (2012)

e19021 Background: Recent studies suggest that serum lactate dehydrogenase (LDH) and serum C-reactive protein (CRP) are risk factors for survival in patients with metastatic melanoma. However, due to the relatively low tropism of metastatic melanoma lesions in the urogenital tract the clinical benefit of metastasectomy in this highly selective group of patients remains uncertain. The objective of this study was to address the role of LDH and CRP as preoperative serological risk factors for survival in patients with solitary or concomitant metastatic melanoma lesions in the urogenital tract. Methods: All patients who were referred for metastasectomy in the urogenital tract in a tertiary center within 1999-2008 were considered for this analysis. Demographic, disease and survival data were collected. Elevated LDH activity was defined as &gt;250U/l and elevated serum CRP&gt;0.5mg/dl. The primary endpoint was overall survival (OS), calculated using Kaplan-Meier method with log-rank test and multivariate Cox-regression analysis. Results: Of a total of 21 patients,16 (76%) had solitary urogenital metastases and 5 patients (24%) concomittant non-urogenital metastases.Median OS after metastasectomy was 23 months (range: 3-59 months). LDH&gt;250U/l was significantly associated with decreased OS (27.6 vs. 6.0 months; p=0.001), but elevated CRP did not (24.1 vs. 20.7 months; p=0.93). No further significant differences in survival were found for age (p=0.76), gender (p=0.83), number of urogenital metastatic sites (0.97) and preoperative solitary vs. concomitant distant metastases (p=0.48). In multivariate analysis, adjusted for the TNM-stage grouping (M1a-c) and CRP level, elevated LDH maintained significance as negative prognostic factor for overall survival (p=0.0015). Conclusions: To our knowledge, this is the first study addressing the prognostic role of LDH and CRP in patients with melanoma urogenital metastases. If confirmed in large prospective studies, LDH level may be used for preoperative risk stratification in patients scheduled for melanoma metastasectomy in the urogenital tract to identify those patients who profit most from the surgical approach.
Longer Term Efficacy and Safety of Subcutaneous Compared with Intravenous Rituximab: Updated Results of the Phase 3 SABRINA Study
Authors: Andrew J Davies, Biljana Mihaljevic, Santiago Mercadal, Georgi Mihaylov, Sirpa Leppä, Denise Cotting, Klaas Veenstra, Artem Zharkov, Mark Dixon, Martin Barrett, David Macdonald
Journal: Blood (2016)
Congenital and infantile brain tumours: An institutional experience.
Authors: Wen Shen Looi, Mei-Yoke Chan, Ah Moy Tan, Wan Tew Seow, David Chyi Yeu Low, Wen Quan Derrick Lian, Shui Yen Soh
Journal: Journal of Clinical Oncology (2015)

e21026 Background: Whilst brain tumors are the most common solid malignancy in childhood, congenital and infantile brain tumors are rare and present unique management difficulties. The histology differs from those in older children and outcomes are generally poorer. Methods: We performed a retrospective review of congenital and infantile brain tumor patients treated in our institute over a 17-year period (1997 to 2013). We included patients up to 12 months of age. Congenital tumors were defined as those diagnosed antenatally or within 28 days of life. Information on demographics, clinical presentation, management, and outcome was collected. Results: Twenty-one patients were identified: 14 supratentorial and 7 infratentorial. There were 15 male patients and 6 female patients (ratio 2.5:1). The ethnic distribution reflected local population demographics. Five (24%) patients had congenital tumors, of which 3 had abnormalities on antenatal ultrasound. The median age at diagnosis was 4.9 months (range 1 day to 12 months). Common clinical presentations were macrocephaly, tense fontanelles and vomiting. Mass effect was evident, with hydrocephalus in 20/21 (95.2%) patients. Six (28.6%) patients had evidence of hemorrhage on imaging. Of those with histology, astrocytic tumors (5/17, 29%) were the most common. The remainder comprised germ cell tumors, embryonal tumors, choroid plexus tumors, infantile desmoplastic gangliogliomas and ependymomas. Four patients did not have histological diagnoses and were presumptively diagnosed as germ cell tumors, pineal gland tumor, and supratentorial PNET. Tumor excision was undertaken in 16/21 (76.2%) patients, of which 7 (44%) were total and 9 (56%) were subtotal. Eight patients received chemotherapy while 3 patients received radiotherapy after relapse when older. Three patients received best supportive care only. Mortality was 47.6% (10/21) in our series. Five-year overall survival was 50%. Median survival was 52 months. The longest survival recorded was 15 years 4 months. Four of 7 long-term survivors still on follow-up have significant neurological or cognitive impairment. Conclusions: Congenital and infantile brain tumors present unique management challenges and have high morbidity and mortality.
Risk of febrile neutropenia (FN) in cancer patients (pts) receiving myelosuppressive chemotherapy and pegfilgrastim prophylaxis (PEG-P): Does day of administration matter?
Authors: Derek Weycker, Xiaoyan Li, Richard L. Barron, Jacqueline Figueredo, May Hagiwara
Journal: Journal of Clinical Oncology (2015)

e17697 Background: PEG-P is not indicated for administration on the same day as cytotoxic chemotherapy administration because it induces proliferation of chemo-sensitive myeloid progenitor cells. Notwithstanding the indication, some pts receive PEG-P on same day of chemotherapy in clinical practice, and evidence from clinical trials suggests that outcomes may be worse for these pts (Burris, JOP 2010). A large-scale analysis of PEG-P and FN risk in clinical practice was undertaken. Methods: A retrospective cohort design and US private healthcare claims data (2003-2011) were employed. Study population comprised adults who received “intermediate-risk” or “high-risk” chemotherapy regimens for solid tumors and PEG-P in ≥ 1 cycle; PEG-P cycles were pooled for analyses. FN was identified using diagnosis codes for neutropenia, fever, and/or infection; for ambulatory FN, intravenous antimicrobial use also was required. Odds ratios (ORs) for FN during the cycle—adjusted for patient, cancer, and treatment characteristics—were estimated for pts who received PEG-P on last day of chemotherapy administration (“same-day”) versus 1-3 days following chemotherapy completion (“next-day”). Results: Study population included 45,592 pts (75% with breast cancer) who received PEG-P in 179,152 cycles; in 12% of cycles, pts received same-day PEG-P. Odds of FN (adjusted) were higher for same-day pts versus next-day pts in cycle 1 and all cycles collectively (Table); results were robust within tumor/regimen-subgroups (adjusted ORs were 2.9 [cycle 1] and 1.8 [all cycles] in the most common breast cancer regimen, dose-dense AC/AC-T), and with alternative algorithms for defining FN. Conclusions: In this retrospective evaluation, FN incidence was significantly higher among pts who received same-day (vs. next-day) PEG-P in US clinical practice, underscoring the importance of adhering to the indicated administration schedule. FN in Cycle 1 FN in All Cycles No. of Cycles % FN Odds Ratio* 95% CI p-value No. of Cycles % FN Odds Ratio* 95% CI p-value Same-Day Pts 4,336 3.9 1.5 1.3-1.8 <0.001 21,503 2.5 1.4 1.3-1.6 <0.001 Next-Day Pts 32,759 2.8 — — — 157,649 1.9 — — — *Adjusted
Effectiveness of targeting HER2 in heavily pretreated patients with occult HER2-positive (tissue-negative, serum-positive and/or HER2-positive circulating tumor cells) metastatic breast cancer in the clinical routine.
Authors: Christian M. Kurbacher, Annegret Quade, Gerhard Kunstmann, Susanne Herz, Jutta A. Kurbacher, Mathias A. Warm
Journal: Journal of Clinical Oncology (2015)

591 Background: A considerable proportion of patients (pts) with HER2-negative (HER2-) metastatic breast cancer (MBC) present with elevated serum levels of the HER2 extracellular domain (sHER2) and/or HER2-overexpressing circulating tumor cells (CTCs) during their further clinical course. These “occult” HER2-positive (HER2+) pts may be candidates for anti-HER2 therapy (Tx) albeit normally not subjected to such treatment. This retrospective study was undertaken to gain more insights into the feasibility of HER2-directed Tx in occult HER2+ MBC pts in the clinical routine. Methods: From our database, we identified 26 pts with heavily pretreated HER2- MBC (ER+, 21 pts) showing sHER2 values > 15 ng/mL (6 pts), HER2+ CTCs (6 pts), or both (14 pts) having failed 2-16 prior systemic treatments (median: 7) who did not qualify for recruitment onto a prospective clinical trial. All pts received anti-HER2 Tx with trastuzumab (H: 14 pts), lapatinib (L: 4 pts), H+L (2 pts), or H+pertuzumab (H+P: 6 pts). HER2-targeting Tx was given alone (4 pts), or in combination with endocrine agents (4 pts), cytotoxics (16 pts), or other targeted drugs (2 pts). Responses were scored according to RECIST 1.1, OS was calculated from the start of HER2-directed Ctx until death from any reason or loss to follow-up by using Kaplan-Meier statistics. Results: Anti-HER2 Tx was generally well tolerated. Median treatment duration was 16.1 wks (range 1.0-56.1 wks). In 2 pts with L and 1 pt with H+L, Tx was prematurely stopped due to toxicity (diarrhea, fatigue). 10 PR, 10 SD, 5 PD, and 1 non-evaluable (NE) pt accounted for an objective response rate (ORR) of 38.5% and a clinical benefit rate (CBR) of 76.9%. Median OS was 62.9 wks. Conclusions: Our findings indicate that anti-HER2 Tx may be a valid option in pts with heavily pretreated HER2- MBC with pathological sHER2 values and/or HER2+ CTCs in the clinical routine. Thus, results of ongoing randomized trials in this setting are eagerly awaited.
Rebuilding Consensus on Valid Criteria for Disordered Grief
Authors: Holly G. Prigerson, Paul K. Maciejewski
Journal: JAMA Psychiatry (2017)

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Prognostic and predictive significance of PAM50 intrinsic subtypes in the NCIC CTG MA.21 phase III chemotherapy trial.
Authors: Karen A. Gelmon, Judy-Anne W. Chapman, Shuzhen Liu, Margot J. Burnell, Mark Norman Levine, Kathleen I. Pritchard, Timothy Joseph Whelan, Hope S. Rugo, Kathy S. Albain, Edith A. Perez, Shakeel Virk, Patti O'Brien, Lois E. Shepherd, Torsten O. Nielsen
Journal: Journal of Clinical Oncology (2014)

11019 Background: Breast cancer intrinsic subtypes defined by the 50-gene PAM50 test were reported to be prognostic and predictive in endocrine therapy trials. MA21 randomized 2,104 patients to receive dose intense cyclophosphamide, epirubicin and flurouracil (CEF); dose dense, dose intense epirubicin, cyclophosphamide and paclitaxel (EC/T); or 3-weekly doxorubicin, cyclophosphamide and paclitaxel (AC/T). We previously reported that AC/T had reduced relapse free survival (RFS) compared to both CEF and EC/T. Here, we investigated the prognostic and predictive (taxane versus not) significance of PAM50 in MA.21. Methods: Patients were ≤60 years old with node-positive or high-risk node-negative breast cancer. Median follow-up was 8 years. Intrinsic subtypes (luminal A, luminal B, basal-like, HER2E) were determined with FFPE extracted total RNA by Nanostring PAM50. Univariate assessment was with a stratified log-rank test. Effects of intrinsic subtypes and baseline patient characteristics on relapse-free survival (RFS) were investigated with stratified step-wise Cox multivariate regression, adding a factor if p<0.05. Results: The 1,094 cases completing PAM50 intrinsic subtyping were not significantly (p<0.05) different compared to those who did not in terms of treatment and stratification factors. 27% were classified as luminal A; 23% luminal B; 32% basal-like; and 18% HER2E. Intrinsic subtypes had a significant (p<0.001) univariate association with RFS. In multivariate analyses, intrinsic subtype had a significant prognostic effect on RFS (p= 0.001). Compared with luminal A, the hazard ratios (HR) were: luminal B =1.47 (95% CI = 0.93-2.30, p=0.10); basal-like= 1.95 (CI = 1.10-3.47, p=0.02); and HER2E = 2.66 (95% CI = 1.63-4.34, p<0.001). The interaction term between intrinsic subtype and treatment was not significant (p>0.05). Conclusions: Intrinsic subtype defined by the Nanostring PAM50 test had a significant prognostic effect on RFS for breast cancer patients treated with CEF, EC/T and AC/T. Subtype was not predictive of outcome amongst these chemotherapy regimens. Clinical trial information: NCT00014222.
ATLAS study: A randomized double-blind phase 3 study of adjuvant axitinib versus placebo in subjects at high risk of recurrent renal cell carcinoma (RCC).
Authors: Tae Gyun Kwon, Seo Seong, Seok-Soo Byun, Hideaki Miyake, Takeshi Ueda, Dingwei Ye, Jesús García-Donas, Marine Gross-Goupil, Thomas E. Hutson, Robert DeBenedetto, Subramanian Hariharan, Min Young Lee, Rolf Gerhard Linke, Fumito Tsuji, David I. Quinn
Journal: Journal of Clinical Oncology (2014)

TPS4595^ Background: Kidney cancer is diagnosed in approximately 270,000 people each year worldwide, and results in 120,000 deaths, with RCC as the most common form. Up to 30% of patients treated by nephrectomy for localized disease will relapse. 5-year survival rates for TNM stage II, III and IV are 65-80%, 40-60% and 0-20%, respectively. RCC is a high VEGF- and PDGF-expressing tumor. Axitinib, an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3, is approved for the treatment of advanced RCC after failure of one prior systemic therapy. Preclinical data indicate higher potency and selectivity against the VEGFR family for axitinib compared to some other antiangiogenic agents. This phase 3 study tests the hypothesis that prevention of micro-metastases and tumor growth by anti-VEGF treatment with axitinib can prolong disease free interval after nephrectomy for patients with high risk of recurrent RCC. Methods: 692 patients, ECOG PS 0-1, with histologically confirmed preponderant clear cell RCC; treatment naïve and no residual or metastatic disease after nephrectomy will be randomized 1:1 to axitinib or placebo, 5mg PO BID for up to 3 years in a global, randomized, double blind placebo controlled trial. Patient will be stratified according their country and their stage of disease (any Fuhrman grade allowed): 1) pT2, pN0 or pNx, M0; 2) pT3, pN0 or pNx, M0; 3) pT4, pN0 or pNx, M0; or 4) any pT, pN1, M0; and ECOG PS 0-1. Primary objective is disease free survival as assessed by independent review committee. Key secondary objectives are overall survival as well as safety and tolerability of treatment. Efficacy analysis will be performed on the intention-to-treat population. This is a global, multi-center study with sites in Asia, US and Europe. As of January 2014, 167 subjects have been randomized and last patient enrollment is expected at the end of 2014. Clinical trial information: NCT01599754.
Materials, Devices and Systems of Soft Bioelectronics for Precision Therapy
Authors: Hao Wu, Wei Gao, Zhouping Yin
Journal: Advanced Healthcare Materials (2017)

The potential applications of soft bioelectronics in biomedical research and clinical trials have inspired a great deal of research interest in the past decade. While there has been significant amount of work in the fabrication and characterization of soft and stretchable sensors for monitoring of physical conditions and vital signs of human body, the development of soft bioelectronics based medical treatment and intervention systems has just begun. In addition to health monitoring, active treatments are essential for disease control in the healthcare domain, and medical therapy and surgery realized by sophisticated soft bioelectronic systems are better demonstrations of their utility in healthcare. In this Research News, we summarize recent key research achievements in soft bioelectronics enabled precision therapy, with emphasis on drug delivery, therapeutic and surgical mechanisms and tools enabled by integrated systems. Challenges in technology development and prospects for commercialization are also discussed.
Short and long term outcomes with robotic assisted esophagectomy.
Authors: Kenneth L Meredith, Jamie Huston, Pedro Briceno, Ravi Shridhar
Journal: Journal of Clinical Oncology (2017)

125 Background: Surgical resection remains piviotal in the management of patients with esophageal cancer. Minimally invasive esophagectomy(MIE) has demonstrated superior operative outcomes compared to the open approaches. Robotic assistance has potential to further improve outcomes, however the long-term follow with this technique is lacking. Methods: Utilizing the National Cancer Database we identified patients who underwent esophagectomy and stratified by approach: open (OE), laparoscopic (LE) or robotic (RE). Baseline comparisons were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis as appropriate. Pearson’s Chi-square test was used to compare categorical variables. Survival analysis was performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error &lt; 0.05 was considered significant. Results: We identified 18,869 patients who underwent esophagectomy with a mean age of 65 ± 10 years. There were 10,882 (57.7%) OE, 7,102 (37.6%) LE, and 885 (4.6%) RE. There was no difference in T stage or N stage among groups. Thirty and 90-day mortality was 3.2% and 6.9% and was lower in the MIE groups compared to open 6.2% vs 7.9% p &lt; 0.001. Median length of hospitalization in RE, LE and OE was comparable at 9, 10, and 10 days respectively, p = 0.06. Neoadjuvant therapy was administered in 9,118 (48.3%) patients and was more frequent in the RE 66.0% vs 57.5% OE vs LE 32% p &lt; 0.001. Oncologic quality as indicated by R0 resections and median lymph node harvested were improved in patients undergoing RE: 836 (94.9%) and 16, LE: 5,322 (86.7%) and 4, and OE: 9,631 (91.1%) and 12, p &lt; 0.001. The median and 5-year survival by approach: RE, LE and OE was 54.4 months and 47.7%, 55.6 months and 50.3%, and 47.4 months and 43.7%, p &lt; 0.001. MVA demonstrated that age, location, neoadjuvant therapy, T-stage, N-stage, hospital volume, MIE, and R0 resections were predictive of survival. Conclusions: Short and long-term outcomes with robotic assisted esophagectomy demonstrates low mortality with superior R0 resections and lymph node harvest. Overall survival is benefited in patients undergoing MIE.