tbuckley/cabot-search huggingface dataset:
Treatment outcomes and prognostic factors for primary mediastinal B-cell lymphoma: The MD Anderson experience.
Authors: Mohamed Amin Ahmed, Ramona Barac, L Jeffrey Medeiros, Long Ma, Luis Fayad, Jorge Enrique Romaguera, Yasuhiro Oki, M.Alma Rodriguez, Chelsea Pinnix, Larry W. Kwak, Fredrick B. Hagemeister, Richard Eric Davis, Jason R. Westin
Journal: Journal of Clinical Oncology (2014)

8564 Background: Primary mediastinal B-cell lymphoma (PMBL) has been treated with different chemotherapy regimens. We reviewed medical records and histopathology to determine predictive factors and outcomes for patients (pts) with PMBL seen at the MD Anderson Cancer Center (MDACC) between 1995 and 2013. Methods: Baseline characteristics complete (CR) and partial (PR) response to initial therapy, and status of disease and survival over time were collected. Event-free survival (EFS) was based on dates of relapse, progression, or death. Radiotherapy data will be presented separately. Results: 274 pts with PMBL were identified, making this the largest single-center retrospective report of PMBL. Median age was 40 years (range, 17-86), and 149 pts (54%) were female. For patients treated with R, the CR rates were higher, and EFS and overall survival (OS) were improved for all pts at the median follow-up (MFU) of 38 months (mo), and for CHOP-treated pts at MFU of 37 mo (Table). As R is now standard with initial therapy, we analyzed results for the 3 main R-containing therapies (Table). By univariate log-rank analysis, therapy choice affected the CR rate, and EFS at MFU of 39 mo. R-HCVAD had superior EFS vs. R-CHOP (p=0.015), even though low-stage pts were more common for R-CHOP. For pts given the 3 main R-containing therapies, higher stage (III/IV vs. I/II) was an adverse univariate predictor for EFS (p=0.036) and OS (p=0.04), and B symptoms were adverse for OS (p = 0.026). Multivariate Cox analysis including stage, B symptoms, and therapy (CHOP vs. EPOCH/HCVAD) found only B symptoms to be predictive of shorter OS (p = 0.032), and only treatment to be predictive of shorter EFS (p=0.029). Conclusions: Response rates and survival outcomes are improved for pts with PMBL by R and its use with intensified therapy (R-HCVAD or R-EPOCH). Longer follow-up is needed to compare R-HCVAD and R-EPOCH. Rituximab (R) No (n=74) Yes (n=200) P value Front line CHOP Triple therapy Other Other R-CHOP R-HCVAD R-EPOCH Patients, # 42 25 7 6 123 41 30 CR, % 58 81 <0.001 EFS, % 37 72 <0.001 OS, % 58 87 <0.001 EFS, % 35 65 <0.001 OS, % 51 86 <0.001 CR, % 76 93 83 0.046 CR+PR, % 90 98 97 NS EFS, % 65 88 79 0.013 OS, % 85 92 100 NS Stage I/II, % 83 61 77 0.014 Abbreviation: NS, not significant.
Perinephric white adipose tissue inflammation in clear cell renal cell carcinoma (ccRCC).
Authors: Helena Furberg, A. Ari Hakimi, Ayca Gucalp, Neil M. Iyengar, Samantha Williams, Stacey Petruzella, Daniel M. Tennenbaum, Marguerite Samson, Nicole Mannino, Dilip D. Giri, Xi K. Zhou, Paul Russo, Andrew J. Dannenberg
Journal: Journal of Clinical Oncology (2017)

507 Background: High body mass index (BMI) is an established risk factor for developing ccRCC but is associated with better survival in clinical studies. The obesity paradox may be influenced by metabolically healthy patients classified as obese, and metabolically unhealthy patients classified as normal weight. We evaluated white adipose tissue inflammation (WATi) in perinephric fat as a new marker of metabolic dysregulation and examined its association with clinicopathological characteristics. Methods: In July 2015, we established a prospective cohort study at Memorial Sloan Kettering Cancer Center to investigate the prognostic significance of perinephric WATi among patients undergoing nephrectomy. Perinephric WAT is collected during surgery and patients are followed for clinical outcomes. WATi is defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) and detected through immunohistochemistry. Clinicopathological data are abstracted from the electronic medical record. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests describe the relationship between CLS status and clinicopathological characteristics on the first 38 ccRCC patients. Results: The study cohort had a median age of 56 years (range 47-64 years) and was predominantly male (71%). CLS were detected in 50% of patients, did not differ by age or sex, and were present in all BMI levels; 59% of obese, 38.5% of overweight, and 33% of normal weight patients (p = 0.47). CLS was significantly associated with advanced disease characteristics including higher stage (p = 0.03) and local invasion (p = 0.02). Median tumor size was larger in patients who were CLS+ (3.5 cm, range 2.65-5.75) than CLS- (2.2 cm, range 1.55-3.00; p = 0.02). Conclusions: Perinephric WATi was found in ccRCC patients of all BMI levels and associated with factors related to poor prognosis. Patients with occult inflammation may be at higher mortality risk, regardless of their BMI. Recruitment of additional cases and analyses to examine how CLS influences ccRCC survival are on-going.
Using <sup>124</sup>I-PU-H71 PET imaging to predict intratumoral concentration in patients on a phase I trial of PU-H71.
Authors: John F. Gerecitano, Shanu Modi, Devika Gajria, Tony Taldone, Mary Alpaugh, Erica Gomes DaGama, Mohammad Uddin, Gabriela Chiosis, Jason Stuart Lewis, Steven M. Larson, Naga Vara Kishore Pillarsetty, Komal L. Jhaveri, Brian Krichevsky, Mei Hsuan Chen, Payal Dixit, Mark Dunphy
Journal: Journal of Clinical Oncology (2013)

11076 Background: PU-H71 is a Heat Shock Protein 90 inhibitor that can be labeled with 124 I without altering its biochemical properties. Intratumoral drug concentration can be calculated based on 124 I-PU-H71 (*PU-H71) region of interest analysis and dilution principle. A microdose pilot study has shown uptake of *PU-H71 in a variety of tumors. *PU-H71 PET is currently being used to estimate intratumoral concentrations in subjects on our phase I study. Methods: Patients with previously treated solid tumors or lymphoma are eligible for this phase 1 trial. PU-H71 is given twice-weekly for 2 weeks each 21 days at escalating dose levels. A mix of *PU-H71 and unlabeled PU-H71 is given during cycle 2 followed by serial PET imaging. Patients on the pilot study are administered a microdose of *PU-H71 alone, followed by serial PET scans. Intratumoral PUH-71 concentration is measured directly in optional pre- and post- treatment core needle tumor biopsies (CNB). Results: To date, 13 patients have received PU-H71 on the phase I trial. Of these, 10 have undergone *PU-H71 PET imaging. 4 imaged patients also volunteered for CNBs, with results reported in the table. Of the 10 patients who underwent *PU-H71 imaging in the phase 1 study, 5 also underwent prior *PU-H71 imaging in the microdose pilot. Intratumoral concentrations as calculated in the pilot and phase I studies were in close concordance. Conclusions: *PU-H71 can be used to visualize PU-H71 uptake in a variety of solid tumors and lymphoma, and *PU-H71 PET scans can be used to estimate intratumoral concentrations of PU-H71. Direct intratumoral measurements of PU-H71 correlate reasonably closely with concentrations calculated from *PU-H71 PET imaging. Further refinement of this imaging tool will allow quantitative assessment of PU-H71 uptake in tumors during the ongoing phase I trial. Clinical trial information: NCT01393509. [Table: see text]
Smoking, Obesity and Overall Survival in Non-Hodgkin Lymphoma (NHL): A Population-Based Study.
Authors: Susan M. Geyer, Lindsay M. Morton, Thomas M. Habermann, Cristine Allmer, Scott Davis, Wendy Cozen, Richard K. Severson, Charles F. Lynch, Sophia Wang, Matthew J. Maurer, Patricia Hartge, James R. Cerhan
Journal: Blood (2006)
Molecular analysis-directed, international, phase III trial in patients with advanced non-small-cell lung cancer.
Authors: Gerold Bepler, Charles C. Williams, Michael J. Schell, Wei Chen, Zhong Zheng, George R. Simon, Shirish M. Gadgeel, Xiuhua Zhao, Fred James Schreiber, Julie R. Brahmer, Alberto Chiappori, Tawee Tanvetyanon, Mary Colleen Pinder, Jhanelle Elaine Gray, Eric B. Haura, Scott J. Antonia, Jurgen R. Fischer
Journal: Journal of Clinical Oncology (2013)

8001 Background: ERCC1 (E1) and RRM1 (R1) are predictive markers for platinum agents and gemcitabine (G) respectively. In a phase II trial that utilized E1 and R1 mRNA expression levels for therapeutic decision-making, a response rate of 44%, PFS of 6.6 m, and OS of 13.3 m was achieved. Methods: Pts with advanced, chemo-naive NSCLC, PS 0-1, measurable disease, and a FFPE histological or cell block tumor specimen were eligible. E1 and R1 were analyzed by AQUA and categorized as high or low. Pts were randomized 2:1 to arm A, which received G and carboplatin (Cb) for R1/E1 low, docetaxel (D) and Cb for R1 high and E1 low, G and D for R1 low and E1 high, and D and vinorelbine (V) for R1/E1 high, or arm B, which received GC. Pts received up to 6 cycles. Efficacy was assessed every 6-8 weeks until 1 year from treatment initiation. The primary goal was to improve the 6-m PFS from 38% in arm B (median PFS 4.3 m) to 50% in arm A (median PFS 6.0 m). Secondary goals were improvements in OS (8.0 to 12.0 m) and RR (25% to 50%). Results: Of 275 eligible pts, 183 randomized to arm A. 56 were assigned to GCb, 26 to DCb, 37 to GD, and 64 to DV, which was not significantly different (p=.2) from the expected assignment (30%, 20%, 20%, 30%). In arm B, all 92 pts received GCb. Protein analysis was successful in 91% of pts. The median time from consent to completed gene analysis was 11 days. A tumor rebiopsy for the specific purpose of gene analysis was required in 17% of pts. The 6-m PFS rate and median PFS were 52.0% and 6.1 m in arm A and 56.5% and 6.9 m in arm B (p = 0.18). PFS was not significantly different among the treatment groups in arm A (p = 0.1). A significant survival advantage was found for pts with low E1 and low R1 in arm B compared to the same group in arm A (p = 0.02) although both received GCb therapy. OS and RR were not significantly different between both groups. A comparison between protein and mRNA levels for both genes revealed no significant correlation. Conclusions: This demonstrates that gene expression analysis for therapeutic decision making is feasible in newly diagnosed advanced-stage NSCLC pts. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% pts. The survival results are false negative based on the internal control included in the trial. Clinical trial information: NCT00499109.
Final results of a phase I study of idelalisib, a selective inhibitor of PI3Kδ, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL).
Authors: Don M. Benson, Brad S. Kahl, Richard R. Furman, Jennifer R. Brown, Nina D. Wagner-Johnston, Steven E. Coutre, Stephen Edward Forbes Spurgeon, John C. Byrd, John Leonard, Sissy Peterman, David Michael Johnson, Yoonjin Cho, Roger D. Dansey, Wayne R. Godfrey, Ian Flinn
Journal: Journal of Clinical Oncology (2013)

8526 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells, plays a role in homing and retention in lymphoid tissues, and is hyperactive in many B-cell malignancies. Idelalisib (GS-1101) is a first-in-class, selective, oral inhibitor of PI3Kδ. Initial response rate of 38% was reported previously in iNHL (Kahl, ICML 2011). Long-term follow-up is now presented. Methods: This phase 1 study evaluated the activity of continuous idelalisib monotherapy in pts with relapsed hematologic malignancies. Doses ranged from 50 to 350 mg QD or BID in 8 cohorts. Response was evaluated based on investigator assessments using standard criteria (Cheson, 2007). Pts who continued to benefit were able to enroll in an ongoing extension study. Results: Study enrolled 64 pts with indolent iNHL. iNHL subtypes included 38 FL, 11 SLL, 9 LPL/WM, and 6 MZL. Pts were 69% male, median age [range] of 64 [32E91] years, 58% with refractory disease and 53% with bulky disease (LN diameter ≥5 cm). The median [range] number of prior therapies was 4 [1E10]. The median [range] duration of treatment was 3.8 [0-41] months, with 19 (30%) pts continuing on treatment extension protocol. ORR across all cohorts were 31/64 (48%), with 1 CR (1.6%). The median duration of response (mDOR) was 18.4 months, and median PFS (mPFS) was 7.6 months. For pts dosed with ≥100 mg BID (N=36); the ORR was 24/36 (67%), the mDOR was 15.4 months, and the mPFS was 16.6 months. The ORR for iNHL subtypes was: FL (45%), SLL (64%), LPL/WM (56%), and MZL (33%). Adverse events included (total%/≥G3%) diarrhea (36/8), fatigue (36/3), rash (27/3), nausea (25/2), pyrexia (20/3), chills (20/0), cough (19/2), pneumonia (17/16), and URI (17/0). Lab abnormalities included (total%/≥G3%) ALT/AST elevations (56/25). 8/64 (12.5%) pts discontinued therapy due to potentially treatment-related adverse events. Conclusions: The oral PI3Kδ inhibitor idelalisib is active in heavily pretreated pts with iNHL, can produce durable responses, and has a favorable safety profile. These data support further clinical development; phase 2 and 3 trials in iNHL are ongoing (NCT01732913, NCT01732926). Clinical trial information: NCT00710528.
Unique pattern of metastasis to the adenexa in ALK rearranged non-small cell lung cancer.
Authors: Allison West, Seiko Diane Yamada, Heber Macmahon, Siraj M. Ali, Phil Stephens, Vincent A. Miller, Ravi Salgia
Journal: Journal of Clinical Oncology (2014)

e19036 Background: NSCLC most commonly metastasizes to the brain, bone, liver and adrenal glands. Recent observation of stage IV ALK rearranged NSCLC metastatic to the adnexa in our clinic led to the current study to estimate the frequency of metastasis to the female reproductive system. Methods: A retrospective chart review of female patients with stage IV ALK rearranged NSCLC was performed. Relevant charts were reviewed for pelvic imaging notable for ovarian, adnexal, or pelvic mass or enlargement. Results: Twenty patients met the requirements for chart review: female, NSCLC, and the presence of an EML4-ALK. Of these 20 cases, 16 included imaging of the pelvis by computed tomography as part of work-up for systemic disease; one patient had prior hysterectomy-oophorectomy and was excluded. 5 of 15 charts with pelvic imaging were notable for ovarian enlargement or mass. 2 of these women underwent therapeutic intervention directed at their ovarian masses. Conclusions: The finding of adnexal abnormalities in one-third of female clinic patients with NSCLC harboring an ALK rearrangement is compelling. Metastases to the adnexa in female patients with ALK positive NSCLC should be a consideration during work-up for systemic disease.
Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study
Authors: Gabriela Armuand, Agneta Skoog-Svanberg, Marie Bladh, Gunilla Sydsjö
Journal: Journal of Clinical Oncology (2017)

Purpose To compare the probability of a first live birth, age at time of birth, and time between diagnosis/referent date and birth between childhood and adolescent cancer survivors and an age-matched comparison group. Materials and Methods A total of 1,206 survivors was included in the study, together with 2,412 age-matched individuals from the general population. A Cox proportional hazards model was used to investigate first live birth after diagnosis/referent date. Data were stratified by sex, age at diagnosis, and diagnostic era (ie, diagnosis before 1988 v in 1988 or later). Results Overall, the probability of having a first live birth (hazard ratio [HR]) was significantly lower; men had lower HRs than women (HR, 0.65 v 0.79). There were no significant differences in the probability of having a first live birth among women diagnosed during adolescence (HR, 0.89), but the HR was lower among women with childhood cancers (HR, 0.47). Among male survivors, the situation was the opposite; men diagnosed during adolescence had lower HRs than survivors of childhood cancer (HR, 0.56 v 0.70). Examination of the data from the two diagnostic eras (before 1988 and 1988 or later) shows that the HR increased among female survivors after 1988 (HR, 0.71 v 0.90) and decreased among male survivors (HR, 0.72 v 0.59). A shorter time had elapsed between diagnosis/referent date and the birth of a first child among both male and female survivors compared with controls. In addition, female survivors were younger at time of birth. Conclusion The study demonstrates reduced probability of having a first live birth among cancer survivors diagnosed during childhood or adolescence; men were particularly vulnerable.
Do elderly patients benefit from enrollment in phase I clinical trials?
Authors: Wai Meng David Tai, Cindy Lim, Aziah Ahmad, Whee Sze Ong, SuPin Choo, Wan-Teck Lim, Eng-Huat Tan, Daniel Shao-Weng Tan
Journal: Journal of Clinical Oncology (2013)

9509 Background: Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. We evaluated the clinical characteristics and outcomes of elderly pts enrolled in phase 1 clinical trials in our centre and evaluate the performance of Royal Marsden Hospital (RMH) prognostic score (albumin, LDH, no of met sites) in this pt population. Methods: 296 consecutive pts who were treated in 20 phase 1 trials from 2005-2012 in our unit were analysed. Clinical characteristics and outcomes between young pts (&lt;65, n=202) and older pts (≥65, n=94) were compared. Results: The median age of the older pts was 69 (65-84), 71% were males. 51% of the pts received chemotherapy based treatment with or w/out biological agents. 61% of the pts had lung cancers and 32% had gastrointestinal cancers. 52% of pts had ≥2 co-morbidities. After median follow up of 7.5 mths (0.36-50.6 mths), the median progression free survival (PFS) and overall survival (OS) were 5.8 and 8.8 mths respectively. Although elderly pts had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 vs 9.9 mths), p=0.68) compared to younger pts. The prognostic factors for OS identified in multivariate analysis were prior lines of chemotherapy (0-2 vs ≥3), baseline sodium levels (≥135 vs &lt;135mmol/L) and platelet levels (≤400 vs &gt;400×10⁹). We developed a risk nomogram based on the factors identified prognostic of OS with concordance(c)-index of 0.65. RMH score (2-3 vs 0-1) predicted for OS with hazard ratio of 2.1, p=0.03 and c- index of 0.63. 26% of elderly pts experienced grade 3/4 toxicities in the first cycle of treatment. Common grade 3/4 toxicities were dermatological (25%), haematological (17%) and gastrointestinal (13%). Both age of pts (p=0.70) and dose levels (p=0.18) did not have any bearing on occurrence of grade 3/4 toxicities. Conclusions: Elderly pts (≥65) enrolled into phase 1 clinical trials had similar survival outcomes and toxicity profiles compared to younger pts. Risk scoring models to aid patient selection need further clarification in this population.
Expression of eIF4E relevant biomarkers detected in circulating tumor cells from metastatic NSCLC and prostate cancer patients using antibody-independent ApoStream technology.
Authors: Weiguo Wu, Jacky Woo, Vladislava O. Melnikova, Margaret Pace, Vishal Gupta, Elena Jouravleva, Kenna Lynn Anderes, Elizabeth J. Ackermann, T. Jesse Kwoh, Darren W. Davis
Journal: Journal of Clinical Oncology (2012)

e13562 Background: Enumeration of circulating tumor cells (CTCs) is used clinically to monitor disease progression and has previously been shown to be an independent biomarker for predicting survival of metastatic breast, prostate, and colorectal cancer patients. Molecular characterization of CTCs is rapidly emerging as a minimally invasive approach to interrogate the genotype and phenotype of cancers. However, the use of EpCAM-based enrichment platforms relies on the expression of EpCAM thus limiting the type of tumor cells that can be recovered. ApoStream, is a novel, antibody-independent, dielectrophoretic field-flow fractionation based technology that recovers CTCs from cancer patient blood samples. Methods: A side-by-side comparison of EpCAM dependent CellSearch and ApoStream was performed for CTC enumeration in NSCLC and prostate cancer patients. A multiplexed immunofluorescent assay was developed for CTC (cytokeratin+/CD45-/DAPI+ cells) enumeration. CTCs recovered by ApoStream were evaluated for the expression of multiple eIF4E pathway biomarkers using quantitative laser scanning cytometry (LSC). Results: ApoStream isolated a significantly greater number of CTCs in both NSCLC and prostate cancer patients (NSCLC: range 9-1037, mean=407 by ApoStream versus a range of 30-340, mean=118 by CellSearch , p&lt;0.05; prostate cancer: range 12-3490, mean=1472 by ApoStream versus a range of 16-2155, mean=502 by CellSearch , p&lt;0.05). The eIF4E protein expression in CTCs was positively correlated with the CTC count. A trend toward correlation between the eIF4E protein expression level and the expression levels of Cyclin D1, Survivin and Bcl-2 was observed. Conclusions: The ApoStream platform recovers higher numbers of CTCs from the blood of metastatic NSCLC and prostate cancer patients compared to the EpCAM-dependent CellSearch platform. CTCs recovered by ApoStream are suitable for downstream molecular analyses paving the way for broader applications in translational cancer research.
A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging to evaluate treatment response after WBRT sorafenib.
Authors: Aki Morikawa, Komal L. Jhaveri, Sujata Patil, Melanie Chen, Edward McDonnell, Deirdre A. Neville, Fung Ming Mak, Bolorsukh Gansukh, Humm L. John, Andrei Holodny, Heiko Schöder, Kathryn Beal, Andrew David Seidman
Journal: Journal of Clinical Oncology (2014)

TPS2103 Background: WBRT is a standard therapy for metastatic breast cancer (MBC) patients with brain metastases (BM). Despite WBRT, disease progression in the brain is common, and survival is poor. One approach to improve outcome is the use of radiosensitizers. Sorafenib, a multi-kinase TKI with anti-VEGF activity, has demonstrated anti-tumor efficacy in MBC and radiosensitizing activity in preclinical studies. Concurrent use of anti-VEGF drug with radiotherapy (RT) has a potential to confound response assessments due to pseudo-progression and pseudo-response using brain magnetic resonance imaging (MRI). FDG PET is not ideal for brain imaging due to high background glucose uptake. Thus, a newer imaging modality is warranted for accurate response assessment. [18F] 3’deoxy-3’-fluorothymidine (FLT) is a new PET tracer which has shown to correlate with cellular proliferation and may be useful in improving response assessment. Methods: We are conducting a phase I trial of sorafenib with WBRT in MBC patients with BM using a 3+3 design. Sorafenib is given orally daily and continuously with the start of WBRT for a total of 21 days. Dose limiting toxicities are assessed weekly for 4 weeks. There are 3 doses levels: 200mg, 400mg, and 600mg daily. The primary endpoints are to determine a maximum tolerated dose (MTD) and to evaluate safety and toxicity. The secondary endpoint is central nervous system progression-free survival. An additional 6 patients will be enrolled as a safety-expansion cohort at the MTD. Key eligibility criteria include MBC with new or progressive ≥ 1cm BM, age≥18 , ECOG PS 0-2, planned WBRT, non-escalating dose of corticosteroid for ≥5 days, and no other concurrent anti-tumor therapy other than trastuzumab.In addition, as an imaging correlative study, we are evaluating FLT-PET to assess radiographic changes after WBRT sorafenib with planned sample size of 20 patients (10 patients in the sorafenib + WBRT cohort and 10 patients in the WBRT only cohort). A total of 3 FLT scans are done: baseline, 7-10 days and 10-12 weeks after the WBRT. Accrual is currently ongoing. Clinical trial information: NCT01724606 and NCT01621906.