tbuckley/cabot-search huggingface dataset:
Association of change in AFP &gt; 15 ng/ml/month with stage at diagnosis and mortality in patients with hepatocellular carcinoma (HCC).
Authors: Ysabel Ilagan-Ying, David Edward Kaplan, Tamar H. Taddei, Basile Njei
Journal: Journal of Clinical Oncology (2017)

255 Background: In a recent study, a change in AFP &gt; 15 ng/ml/month was associated with poor post-transplant HCC survival. We hypothesized that change in AFP is associated with stage of HCC at diagnosis and mortality. Methods: Patients with potential HCC from 2008-2010 were identified by querying the Veterans Administration Corporate Data Warehouse. Diagnostic confirmation and tumor staging was obtained by manual chart abstraction. Dates of death were ascertained and censored from 12/31/2014. Logistic regression analysis was performed to determine the association between change in AFP and stage at diagnosis. Multivariable cox regression analysis adjusting for severity of liver disease was performed to determine the association between change in AFP and all-cause mortality. Results: Of 3,988 HCC cases, change in AFP &gt; 15 ng/ml/month was associated with presentation at BCLC stage B (OR 2.26, CI 1.54-3.33, p &lt; 0.001) and C (OR 3.39, CI 2.25-5.01, p &lt; 0.001). There was no statistically significant association between AFP &gt; 15 ng/ml/month with stage BCLC 0 or A (early HCC), or with BCLC stage D, likely reflecting a greater burden of liver disease severity over tumor burden in Stage D. Change in AFP &gt; 15 ng/ml/month was associated with increased all-cause mortality (HR 1.49, CI 1.37-1.62, p &lt; 0.001). Conclusions: In a large cohort of US Veterans with HCC, change in AFP &gt; 15 ng/ml/month may be a useful prognostic marker for presentation with advanced stage cancer and all-cause mortality.
Retrospective analysis of cardiovascular (CV) events following compassionate use of carfilzomib (CFZ) in patients (Pts) with relapsed and refractory multiple myeloma (RRMM).
Authors: Shebli Atrash, Amanda Tullos, Susan Panozzo, Sarah Waheed, Frits Van Rhee, Alejandro Restrepo, Jameel Muzaffar, Aziz Bakhous, Monica Grazziutti, Zainab Shahid, Senu Apewokin, Al-Ola A. Abdallah, Bart Barlogie, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2013)

8595 Background: Herein, we report CV events observed in late-stage, heavily pretreated pts who received salvage CFZ under a compassionate use protocol. Methods: Pts received IV single-agent CFZ (20-45 mg/m 2 ) over 2-30 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle (C) or CFZ with weekly dexamethasone (4-40 mg) during C1, along with other agents (eg, lenalidomide, thalidomide, cyclophosphamide, doxorubicin, cisplatin, vorinostat) during C2 and beyond. CV events were grouped according to preferred terms. Serious CV events were defined as those that required hospitalization. B-type natriuretic peptide (BNP) values were measured at baseline; peak values were recorded during C1. Results: 143 pts (median age, 61 years old; 70% were male) received treatment. Prior to enrollment, pts received a median of 7 prior lines of therapy (range, 2-15), including doxorubicin (range, 0-360 mg/m 2 ). Most pts (92%) had prior autologous stem cell transplants (ASCT), with 74% receiving ≥2 ASCT (range, 0-5). Pts received CFZ for a median of 2C (range, 1-36). Of pts with available BNP values at baseline and during C1 (n=69; 48.3%), the median peak BNP increase from baseline was 407 pg/ml (P&lt;0.001). 27 pts (18.9%) experienced a serious CV event, 21 (77.7%) of which had preexisting CV risk factors. Of these 27 pts, 11 pts (7.7%) developed CHF or worsening of existing CHF (confirmed by echocardiogram [ECHO] ≤1 month from diagnosis), and 13 (9.1%) required hospitalization for hypotension (n=6), arrhythmia (n=2), hypertension (n=2), pulmonary edema (n=1), pulmonary embolism (n=1), or pulmonary hypertension (n=1). Additionally, 3 pts (2.1%) experienced cardiopulmonary arrest. Of the 11 CHF pts, 10 had a baseline ECHO (recorded ≤6 months before study); left ventricular ejection fraction decreased from a median of 55% (pretreatment) to 33% (posttreatment). Conclusions: Late-line, heavily pretreated pts with RRMM occasionally experienced CV events following administration of CFZ with or without other antimyeloma agents. Given the number of confounding factors and the uncontrolled nature of these data, causality for these CV events could not be definitively determined.
Phase I study of gemcitabine, docetaxel, and imatinib in refractory and relapsed solid tumors
Authors: B. Saraiya, V. Karantza-Wadsworth, M. N. Stein, R. Chugh, J. Mehnert, R. Moss, Y. Lin, E. Poplin
Journal: Journal of Clinical Oncology (2009)

e13538 Background: The combination of the tyrosine kinase inhibitor imatinib with cytotoxic chemotherapy targets multiple pathways of tumor progression. In a previous phase I study, the combination of gemcitabine and imatinib was tolerable and had broad activity. The maximally tolerated dose (MTD) was gemcitabine 1500 mg/m2/150 minute and imatinib 400 mg days 1–5, 8–12, and 15–19. Given the activity seen when combining gemcitabine and docetaxel in some solid tumors, this phase I trial studied the addition of docetaxel to gemcitabine/imatinib. Methods: Twenty patients with relapsed/refractory solid tumors were enrolled in this IRB-approved study at the Cancer Institute of New Jersey and University of Michigan. The mean age was 64, mean ECOG PS 1. Five patients had lung cancer; 5, sarcoma; 3 ampullary-biliary tumors; 2 mesothelioma and bladder, 3, other. Imatinib was administered at 400 mg daily on days 1–5, 8–12 and 15–19. Gemcitabine was started at 600 mg/m2 at the fixed dose infusion of 10 mg/min on days 3 and 10 and docetaxel at 30 mg/m2 on day 10. Results: Because of unexpectedly severe hematological toxicities seen with escalating either gemcitabine or docetaxel, the protocol was amended to eliminate days 15–19 of imatinib. The MTD is gemcitabine 600 mg/m2, on days 3 and 10, docetaxel 30 mg/m2 on day 10, and imatinib 400 mg PO given on days 1–5 and 8–12. The dose limiting toxicities were neutropenic fever, pleural and pericardial effusion after cycle 1 of chemotherapy. The best response achieved was stable disease at 6 cycles in one patient each with mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two other patients with NSCLC had stable disease at 4 cycles. Discussion: An unexpectedly low MTD for this triplet was identified, an outcome different from prior experience with the doublets gemcitabine/imatinib or gemcitabine/docetaxel where much higher dosages are tolerated. Our results suggest possible drug-drug interactions that amplify toxicities with little initial evidence of improved tumor control. Given the unexpectedly high toxicity of the combination of gemcitabine, docetaxel and imatinib at low dosages, further development of this regimen is not indicated. [Table: see text]
Expression of tyrosine kinase AXL receptor in patients with metastatic renal cell carcinoma treated with sunitinib and its association with clinical and pathological outcomes.
Authors: Luis Eduardo Rosa Zucca, Flavio Mavignier Carcano, Cristovam Scapulatempo, Renato Oliveira, Mariana Andozia Morini, Guilherme Ribeiro, Cristiano Ribeiro Viana, Rui Manuel Reis
Journal: Journal of Clinical Oncology (2017)

439 Background: Renal cell carcinoma (RCC) represents 2 to 3% of all cancers of the Western countries. Currently, sunitinib, an anti-receptor tyrosine kinase (RTK), particularly of PDGFR and VEGFR, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, we and others have suggested that the RTK AXL may modify the response to sunitinib. Objective: To study the expression of AXL in a series of mRCC patients treated with sunitinib and to correlate it with patient’s clinico-pathological features and therapeutic response. Methods: Sixty four mRCC patients (51 clear cell carcinomas and 13 non-clear cell carcinomas) were evaluated and AXL expression was assessed by immunohistochemistry in TMAs. Results: AXL positivity was observed in 47% of cases. The multivariate survival analysis showed that AXL expression was a poor prognostic factor in patients with mRCC (HR 2.007, 1.006 - 4.006, p=0.048). In addition to the positivity for AXL, other prognostic factors were absence of nephrectomy, more than one site of metastasis, and bone metastasis. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, KPS, more than one site of metastasis, and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Conclusions: AXL expression was correlated with worse clinical outcome and may be an important prognostic biomarker in sunitinib-treated metastatic renal cell carcinoma patients.
Refill gaps and dose reductions in patients treated with abiraterone acetate plus prednisone (AA+P) or enzalutamide (ENZ).
Authors: Dominic Pilon, Ajay S. Behl, Bruno Emond, Yongling Xiao, Patrick Lefebvre, Christopher J. Kane
Journal: Journal of Clinical Oncology (2017)

e572 Background: Recently available treatmentssuch as AA+P or ENZ have improved survival and quality of life for patients with metastatic castrate resistant prostate cancer (mCRPC). However, drug-drug interactions, intolerance or toxicities can potentially lead to dose reductions or treatment interruption. This study assessed refill gaps and dose reduction events in patients treated with AA+P or ENZ. Methods: The MarketScan databases (03/2012-10/2015) were used to conduct a retrospective analysis. Patients initiated on AA+P or ENZ (index date) after 09/2012 with ≥ 6 months of continuous eligibility prior to index date and ≥ 1 diagnosis for prostate cancer were included. Inverse probability of treatment weighting (IPTW) was used to adjust for observed baseline confounders between groups. Weighted Kaplan-Meier (KM) rates and Cox proportional hazard models were used to compare the occurrence of refill gaps ( ≥ 14, ≥ 30, or ≥ 60 days) or dose reductions (i.e., relative dose intensity [RDI] ≤ 80%, and ≤ 85%) between groups. RDI was calculated as the ratio of the delivered dose intensity (total delivered dose divided by the period over which the total dose was measured) to the standard dose intensity as recommended in the package insert for AA+P or ENZ. Results: A total of 2,540 AA+P and 1,265 ENZ patients were identified. IPTW resulted in balanced baseline demographic, comorbidities, and disease characteristics. At 12 months post-index, patients initiated on ENZ were more likely to have an RDI ≤ 80% or ≤ 85% or to have a refill gap ≥ 30 or ≥ 60 days when compared to patients initiated on AA+P (Table). Conclusions: This study showed that mCRPC patients treated with ENZ were more likely to experience a refill gap and to reduce their treatment dose than patients treated with AA+P. [Table: see text]
Technetium-99m sulfur colloid (TSC) as a phenotypic probe for predicting pharmacokinetics (PK) and palmar-plantar erythrodysesthesia (PPE) toxicity of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).
Authors: Hugh Giovinazzo, Parag Kumar, Arif Sheikh, Marija Ivanovic, Mark Doughty Walsh, Whitney Paige Caron, Gina Song, Ann B. Whitlow, Suzanne E. Newman, Ninh My La-Beck, Richard J. Kowalsky, Beth A. Zamboni, Daniel L. Clarke-Pearson, Wendy R. Brewster, Linda Van Le, Victoria Lin Bae-Jump, Paola A. Gehrig, William Zamboni
Journal: Journal of Clinical Oncology (2012)

5050 Background: There is significant variability in the PK and PD (efficacy and toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur primarily via uptake by cells of the mononuclear phagocyte system (MPS) mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PPE toxicity in pts (n=9) with EOC. Methods: Prior to administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IVP × 1. Dynamic planar and SPECT/CT images of the liver, spleen and hands were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m 2 alone or at 30 mg/m 2 in combination with carboplatin IV over 1 to 3 h. Serial PK samples were obtained from 0h to 672h post PLD dose. Plasma was processed to measure encapsulated and released doxorubicin (dox) using solid phase separation and HPLC. CL of PLD and TSC were calculated by non-compartmental analysis. The grade of PPE toxicity was determined by NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC imaging and eight patients completed TSC blood PK and PLD plasma PK studies. There was a positive linear relationship between TSC CL and encapsulated dox CL (R 2 = 0.61, p=0.02). When patients were subdivided, there was a stronger relationship between TSC CL and encapsulated dox CL (R 2 = 0.81, p=0.03) in pts receiving PLD monotherapy. A positive relationship using Spearman’s correlation (ρ=0.84, p=0.006) was also found between maximum grade PPE toxicity developed and estimated AUC of encapsulated dox in hands [(TSC AUC Blood )/(TSC AUC Hand )*Encapsulated Dox AUC Plasma ]. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and PD and may be used to individualize PLD therapy in pts with EOC. In addition, our findings suggest TSC may be able to predict the development of PPE in patients.
MET amplification occurrence and prediction of unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy.
Authors: Yu-hong Li, Xin An, Fang Wang, Qiong Shao, Feng-Hua Wang, Zhiqiang Wang, Cui Chen, Cong Li, Huiyan Luo, Sheng Dong Zhang, Rui-hua Xu
Journal: Journal of Clinical Oncology (2013)

e15047 Background: Several large studies have reported an extremely low incidence of MET gene amplification (GA) in patients with radically resected gastric cancer. The aim of our study was to evaluate the prevalence and prognostic role of MET GA and protein expression in recurrent/metastatic gastric cancer patients who received chemotherapy. Methods: This retrospective study included 232 recurrent/metastatic gastric cancer patients. MET GA and protein expression were evaluated by fluorescent in-situ hybridization (FISH) and immunohistochemistry (IHC), respectively.Results: MET GA and strong protein expression were observed in 8.3% and 9.6% of patients, respectively. MET IHC 3+ was significantly correlated with GA. Patients with MET GA more frequently had a poor performance status (P &lt; 0.001) and poorly differentiate tumors (P = 0.015) than those without MET GA. Both MET GA and IHC 3+ expression were associated with substantially shorter median progression free survival (PFS) and overall survival (OS). The median OS and PFS for patients with MET GA positive vs. MET GA negative were 5.7 vs. 15.5 months (P &lt; 0.001) and 3.6 vs. 6.9 months (P &lt; 0.001), respectively.The median OS and PFS for patients with MET IHC 3+ vs. IHC (0 to 2+) were 6.3 vs. 15.1 months (P &lt; 0.001) and 3.6 vs. 7.0 months (P &lt; 0.001), respectively. Conclusions: In recurrent/metastatic gastric cancer, MET amplification and strong protein expression are not rare and significantly associated with unfavorable clinical outcomes.
Gastric MALT lymphoma (GML) after helicobacter pylori (Hp) eradication: Prognostic value of histological and molecular findings in 120 patients of a prospective multicenter trial
Authors: T. Wündisch, A. Neubauer, A. Gunther, M. Stolte
Journal: Journal of Clinical Oncology (2007)

8041 Background: Long lasting remissions occur in most patients with localized GML after Hp eradication. Ongoing B-cell clonality and the translocation t(11;18) have been described as factors associated with no response, relapse and histological residual disease (hRD). Systematic evaluation of histological findings associated with the clinical course and molecular data has not been described yet. Methods: Detailed analysis of long term follow up data of a prospective multicenter trial including 120 patients (median follow up &gt; 5 years) with Hp-positive stage I1E GML was performed. Histological and molecular data of biopsies from 1187 endoscopies were analyzed using a large data base. Hp-status, granulocytic-, lymphocytic infiltration and intestinal metaplasia (IM) were histologically graduated according to the Updated Sydney system. The histological findings empty lamina propria (ELP), fibrosis, lymphoid follicles (LF) and lymphoepithelial lesions and lymphoid aggregates (LA) were evaluated. Prospective molecular data concerning B-cell clonality as well as retrospective data concerning the status of the translocation t(11;18) were also collected. Results: LA and LF were more present in patients not responding towards Hp eradication [P &lt; 0.0001]. ELP in high frequency is a positive predictor for reaching complete remission (CR) [P= &lt;0,0001]. Fibrosis was only found in CR patients. In patients reaching a histological CR presence of LA and LF were associated with hRD and relapse [P=0.04]. LA / LF were also more prevalent in t(11;18) positive and patients with ongoing B-cell clonality. An association between ongoing monoclonality and t (11;18) was also demonstrated [p=0,012]. In 66% of patients IM was detected, it does not disappear during long term follow up after successful Hp eradication. Conclusions: Simple histological findings can help to predict the clinical course of GML after Hp eradication and are associated with known molecular data. No significant financial relationships to disclose.
Dermoscopic Features of Circumscribed Palmar Hypokeratosis
Authors: Pedro Tiago Vilas Boas da Silva, Enrique Rodríguez-Lomba, José Antonio Avilés-Izquierdo, Cristina Ciudad-Blanco, Ricardo Suárez-Fernández
Journal: JAMA Dermatology (2017)

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Effect of neoadjuvant IMRT for locally advanced rectal cancer on toxicity and pathologic response.
Authors: John David, Salma Jabbour, Gillian K. Gresham, Mathew Deek, Thomassian Shant, John M. Robertson, Peyman Kabolizadeh, Richard Tuli
Journal: Journal of Clinical Oncology (2017)

693 Background: Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques may reduce dose to normal organs at risk. Our purpose was to compare clinical outcomes and acute toxicities between standard 3D conformal (3D) and intensity modulated radiation therapy (IMRT). Methods: LARC patients (pts) treated at 4 large academic centers in the US between 2007 and 2016 were reviewed. Pts received 5FU-based NeoCRT concurrently with IMRT or 3D. Pathologic response (PR) was used as a surrogate for clinical outcome, and common terminology for adverse events version 4 was used to grade toxicities, summarized on a 1-5 scale. Toxicity rates were compared using chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. Results: 128 pts were analyzed: 60.1% male and 39.8% female, median age 57.7 years (Range 31-85). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3D (48.1%, 23.1% vs 32.2%, 23.7%*), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT was significantly associated with increased odds for complete and partial response (OR: 2.9, 95%CI 1.2-7.2*). Additionally, IMRT was significantly associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, diverting ostomy, and trend toward significance for decreased rates of fatigue (p = 0.07) and erythema (p = 0.06) (see table). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3D after adjusting for confounders (OR: 0.27, 95% CI 0.08-0.87*). Conclusions: Neoadjuvant 5FU-based IMRT for LARC leads to reduced acute toxicities and improved PR compared to 3D. Given the challenges associated with prospective validation of these data, IMRT should be considered standard treatment for LARC.[Table: see text]
Perceptions of benefits and harms of alcohol consumption as predictors of alcohol cessation in adult cancer survivors.
Authors: Geoffrey Liu, Dan Pringle, Osvaldo Espin-Garcia, Chongya Niu, Mary Mahler, Oleksandr Halytskyy, Rebecca Charow, Christine Lam, Ravi M. Shani, Jodie Villeneuve, Kyoko Tiessen, M Catherine Brown, Shabbir M.H. Alibhai, Doris Howell, Jennifer M. Jones, Wei Xu, Peter Selby, Lawson Eng
Journal: Journal of Clinical Oncology (2013)

9595 Background: Survivorship programs are being developed at many cancer centers, addressing secondary prevention and healthy lifestyle issues. We evaluated whether perceptions regarding the harms and benefits of alcohol use influenced alcohol cessation or recidivism in adult cancer survivors. Methods: 531 cancer patients of all subtypes were surveyed at a comprehensive cancer center for their alcohol habits before and after cancer diagnosis and their perception of benefits/harms for continued drinking. Multivariate logistic regression models evaluated the association of each variable with change in alcohol consumption after diagnosis adjusted for significant socio-demographic and clinico-pathological covariates. Results: Among 325 current drinkers at diagnosis, 55% quit or cut down their alcohol consumption 1 year after diagnosis, while 16% of 95 ex-drinkers at diagnosis restarted drinking at 1 year. Negative perceptions of the effects of alcohol on the individual patient were strongly associated with cessation: the adjusted odds ratio (aOR) of quitting were significant for a perceived negative effect on quality of life (aOR=2.2, p=0.006), survival (aOR=3.8, p=1.3E-5), fatigue (aOR=3.1, p=4.6E-5) or an increased chance in self-harm (aOR=2.6, p=0.01). Perceptions of how alcohol affected the average cancer patient had similar associations. While perceptions did not influence alcohol recidivism rates, receiving chemotherapy was the only variable associated with continued abstinence (aOR=5.5, p=0.007). Although only 8% of patients received alcohol cessation information from an oncologist, it had the greatest impact on cessation (aOR=6.6, p=0.006), an association not seen with other information sources or other healthcare providers. Conclusions: Perception to the negative effects of alcohol use on their health in cancer survivors strongly predicted for alcohol cessation. The oncologist had a most significant counselling role for alcohol cessation.