tbuckley/cabot-search huggingface dataset:
Patterns of nonhematologic malignancies in a population of African American veterans with monoclonal gammopathy of unknown significance (MGUS).
Authors: Hady Ghanem, Swathi Namburi, Gabriel Rivera, Richard Amdur, Geraldine P. Schechter
Journal: Journal of Clinical Oncology (2012)

8103 Background: Monoclonal Gammopathy of Unknown Significance (MGUS) is characterized by the presence of a monoclonal immunoglobulin in the serum or the urine with no evidence of hematologic malignancy. A possible relationship between MGUS and increased incidence of NHM has been suggested in Caucasian populations. However, data in African Americans with MGUS are lacking. Methods: Non-MGUS controls were selected randomly from patients who did not have a paraprotein detected on electrophoresis (NMGUS) and were matched 2-to-1 to MGUS cases. Descriptive statistics and comparisons are presented to compare MGUS and NMGUS groups. Results: 492 male patients with MGUS patients were matched with 984 male NMGUS patients. 451 patients had abnormal serum protein studies (91.6%) and 40 had light chain disease (8.4%). Median age at diagnosis of MGUS was 68 years (28-81). 144 MGUS patients (29.2%) and 296 NMGUS patients (30%) had 1 or more NHM. The median age of diagnosis of 1st NHM was 70 (25-94) in the MGUS group and 68.4 in the NMGUS group (34.5-94.4). 19 MGUS patients (3.8%) and 27 NMGUS patients had 2 different types of NHM (2.7%). 1 MGUS patient (0.2%) and 3 NMGUS patients (0.3%) had 3 NHM. 57 patients had MGUS before NHM (11.5%) and 69 patients were diagnosed with MGUS after the diagnosis of NHM (14%), and median differences between diagnosis of MGUS and 1st NHM were 4 years (1-12 years) and 5 years (1-38 years) respectively. Types of NHM were comparable, and prostate cancer was the most prevalent NHM in both groups (15% of MGUS patients and 17% of NMGUS patients). Median time of follow up was 49.3 months for MGUS patients and 35.2 months for NMGUS patients 140 of the MGUS patients (28.4%) and 214 non-MGUS patients (21.75%) had died at data cut-off. Conclusions: Based on these observational data, prevalence and types of NHM appear to be comparable in MGUS and NMGUS African American patients. All cause mortality appears to be higher for NHM patients if they had MGUS. This pattern will need to be verified prospectively in a larger group of patients.
Defining a standard set of patient-centered outcomes for patients with lung cancer.
Authors: Jan P. Van Meerbeeck, Kimberley S. Mak, Annelotte van Bommel, Caleb Stowell, Michael Peake
Journal: Journal of Clinical Oncology (2015)

e17685 Background: Value-based healthcare improves outcomes while controlling costs. Registries and clinical trials frequently capture survival outcomes for lung cancer, but a unifying set of outcomes that matter to patients is lacking. Our objective was to define a Standard Set of multi-dimensional patient-centered health outcomes for measuring, comparing, and improving lung cancer treatment quality. This Set applies to all patients with newly diagnosed lung cancer, including non-small cell and small-cell lung cancer, treated with either curative or palliative intent. Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international, multi-disciplinary working group of medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts, patient representatives, and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus Set of important outcomes and case-mix variables for risk adjustment to enable meaningful benchmarking. Results: The outcome variables included in the Standard Set are overall survival, disease-specific mortality, cause of death, and treatment-related mortality. We recommend that complications during or within six months of treatment be collected. Patient reported outcomes should be tracked regularly using the EORTC QLQ-C30 core quality of life questionnaire and lung-cancer specific module (EORTC QLQ-LC13). Baseline demographic, clinical, and tumor information is also included in the Standard Set to improve interpretability of comparisons. Conclusions: We defined a Standard Set of outcomes that we believe should be measured in all patients with lung cancer. The Set provides a universal rubric for outcome comparisons, with the ultimate goal of improving the value of care.
Preliminary analysis of the mutational landscape of non-rhabdomyosarcoma soft tissue sarcoma: A Children's Oncology Group study.
Authors: Raphael Asher Wilson, James Robert Anderson, Julie M Gastier-Foster, Douglas S. Hawkins, Sheri L. Spunt, Stephen Skapek
Journal: Journal of Clinical Oncology (2014)

10510 Background: Pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) represent a histologically diverse group of more than 20 tumor subtypes, including synovial sarcoma, liposarcoma, and malignant peripheral nerve sheath tumors. Unlike children with rhabdomyosarcoma, systemic chemotherapy has failed to improve survival for those with NRSTS. Of the nearly 50% with intermediate or high-risk disease, only 50% and 15%, respectively, are expected to survive. Methods: To determine more effective, targeted therapies, we analyzed 55 archived formalin-fixed paraffin-embedded (FFPE) cases of NRSTS using Sequenom’s MassARRAY system to interrogate 296 unique “actionable” mutations (mutations that can be targeted by currently available drugs) in 33 oncogenes and tumor suppressor genes. We also analyzed 15 of the samples for copy-number variation and 74 additional “actionable” mutations in 9 cancer-associated genes using the Affymetrix OncoScan platform. Results: Using MassARRAY, we found 11 mutations in 8 NRSTS subtypes. Interestingly, about half of these mutations are in genes involved in the Ras signaling pathway. We found an additional 33 potential mutations in 15 NRSTS subtypes, 28 of which are involved in Ras signaling; these mutations were detected at around 10% of the alleles present in a sample, the detection limit for MassARRAY, so they cannot be distinguished from background with certainty. Using OncoScan, we found that 67% and 73% of the samples contained mutations in EGFR and TP53, respectively, and 53% contained mutations in NRAS. 6 of the 15 samples contained between 1 and 5 large chromosomal gains or losses, while 2 of the samples had more than 10 large gains or losses. 3 recurrent gains were found in several of the samples, while 10 of the samples contained gains or losses in at least one gene. Conclusions: The rarity of the individual NRSTS subtypes has made it nearly impossible to determine the mutational profiles and optimal treatment for this group of tumors. With the ability to extract information from FFPE material using new genomic platforms, we have successfully grouped tumor subtypes and have identified actionable mutations guiding future directions.
Cutaneous complications in hematopoietic cell transplant recipients: Impact of biopsy on patient management.
Authors: Oana Valeria Paun, Tycel Jovelle Phillips, PingFu Fu, Robert Novoa, Kord Honda, Kurt Quoc Lu, Hillard M. Lazarus
Journal: Journal of Clinical Oncology (2013)

7036 Background: Although skin biopsies are recommended for diagnostic purposes in hematopoietic cell transplant (HCT) recipients, their utility in directing management of post transplant cutaneous eruptions remains uncertain. Little evidence was found in support of this procedure either from a diagnostic or prognostic perspective. Methods: We retrospectively evaluated 351 consecutive HCT recipients transplanted at our institution between January 2005 and December 2011; 156 patients underwent 388 cutaneous biopsies. Results: The group that underwent cutaneous biopsy after transplantation and the group that was spared the procedure were homogenous with regards to age and gender. The pre-biopsy diagnosis and final diagnosis differed in 213 episodes (55%) as determined by histologic evaluation. Biopsy results led to a change in therapy in 61 of 388 (16%) biopsied rashes. With regards to therapy changes, 24 of 61 (39%) occurred in response to a clinical diagnosis of GVHD. In this situation the most frequently noted change was augmentation or addition of systemic immuno-suppression (19 of 24). Changes in systemic therapy occurred with similar frequencies with respect to concordance or discordance between clinical and histopathologic diagnosis (p = 0.12). We used classification and regression tree analysis to develop an algorithm to predict the biopsy yield as expressed by change of management. This is a non-parametric decision tree learning technique that produces a classification tree based on a categorical dependent variable, formed by a collection of rules based on variables in the modeling data set. Conclusions: Cutaneous biopsy findings often changed the clinical dermatologic diagnoses of HCT recipients; however, the impact of biopsy results on treatment decisions was less profound; altered diagnoses in patients who underwent biopsy often did not lead to therapy changes. Skin biopsies of post-transplant patients may not be mandatory for either diagnostic or therapeutic reasons, but in carefully chosen circumstances can yield extremely important data. A prospective study should be undertaken in order to evaluate current practice data and to validate our decision making analysis tree.
Prostate cancer specific mortality and overall survival outcomes for salvage radiation therapy after radical prostatectomy.
Authors: Shree Agrawal, Jason A. Efstathiou, Jeff M. Michalski, Thomas Michael Pisansky, Bridget F. Koontz, Stanley L. Liauw, Matthew Abramowitz, Alan Pollack, Mitchell Steven Anscher, Drew Moghanaki, Robert B. Den, Anthony L. Zietman, W. Robert Lee, Kevin L. Stephans, Jason W.D. Hearn, Daniel Eidelberg Spratt, Tianming Gao, Michael W. Kattan, Andrew J. Stephenson, Rahul D. Tendulkar
Journal: Journal of Clinical Oncology (2017)

9 Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT. [Table: see text]
A prospective longitudinal study of cancer-related fatigue in patients undergoing breast-conserving surgery and radiation with or without chemotherapy for breast cancer.
Authors: Mylin Ann Torres, Thaddeus Pace, Jennifer Felger, Tian Liu, Karen D. Godette, Liza Jane Stapleford, Donna Mister, Andrew H. Miller
Journal: Journal of Clinical Oncology (2012)

9122 Background: We prospectively evaluated risk factors for persistent cancer-related fatigue in women with breast cancer undergoing lumpectomy with or without chemotherapy (CTX) prior to whole breast radiotherapy (XRT). We assessed the potential role of inflammatory mediators, demographic characteristics, and treatment history including CTX. Methods: Following lumpectomy, 60 women received a definitive course of whole breast XRT (50 Gy plus a 10 Gy boost). Prior to XRT, at week 6 of XRT, and 6 weeks post XRT, subjects completed the Multidimensional Fatigue Inventory (MFI) and underwent blood draws for inflammatory mediators (protein and mRNA). Results: Independent multivariate analyses of clinical and demographic factors revealed that CTX (p&lt;.001) , given neoadjuvantly or adjuvantly, and age &lt;50 (p=.03) were significant predictors of higher fatigue scores post XRT. Mean MFI scores in patients treated with CTX (n=24) were 20 points higher than patients not treated with CTX (p&lt;.001) with a clinically meaningful difference in scores being 10 points on the MFI. Gene ontology analysis of differentially expressed genes indicated increased activation of genes involved in immune and inflammatory responses in fatigued vs. non-fatigued patients (p&lt;.001). Of the inflammatory mediators, plasma IL-6 prior to XRT was the strongest predictor of post XRT fatigue (p=.02). Moreover, plasma IL-6 concentrations prior to XRT were significantly higher in patients who received CTX (mean 4.96 vs. 2.53, p=.01). Patients who received CTX also had significantly higher levels of NF Kappa B DNA binding 6 weeks post XRT (p&lt;.001), and transcription factor binding analysis revealed a greater representation of genes with the NF Kappa B DNA binding motif in fatigued vs. non-fatigued patients (p =.05). Conclusions: Collectively, these data suggest an interaction between CTX and XRT leading to inflammation and fatigue several weeks post XRT. This relationship was independent of whether CTX was given pre or post-operatively. Treatments targeting inflammation before XRT may reduce fatigue post therapy, particularly in patients previously treated with CTX.
An internally and externally validated nomogram to predict severe neutropenia in Japanese patients (pts) with advanced colorectal cancer (aCRC) treated with irinotecan (IRI)-based regimens.
Authors: Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Ken-ichi Fujita, Toshikazu Moriwaki, Masato Nakamura, Takehiro Takahashi, Akihito Tsuji, Katsunori Shinozaki, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

3543 Background: Irinotecan (IRI)-based regimens are one of the standard treatments for advanced colorectal cancer (aCRC). In Asians, UGT1A1*6 and UGT1A1*28 are associated with IRI-related severe neutropenia. We conducted a prospective observational study to examine the correlation between UGT1A1genotypes and the clinical outcome of IRI-based regimens in Japanese patients (pts) with aCRC (NCT 01039506). We presented the data of the interim safety analysis at the 2013 ASCO annual meeting (Abstract No. 3535) and the European Control Conference (ECC) 2013 (Abstract No. 2364). We developed a final nomogram that predicts severe neutropenia, based on the data from 1,312 pts enrolled into the study, and externally validated it using independent data from 350 pts. Methods: From October 2009 to March 2012, pts with histologically confirmed aCRC treated with IRI-based regimens were enrolled into the study. UGT1A1 genotypes were categorized into three groups: wild (*1/*1), hetero (*1/*6, *1/*28), and homo (*6/*6, *6/*28, *28/*28). Detailed toxicities in the first three months of treatment were prospectively recorded. A nomogram for predicting severe neutropenia was developed using multiple logistic regression that included UGT1A1genotypes and non-genetic factors. The nomogram was internally validated using bootstrap resampling, and externally validated using independent cohorts from six sites. Results: The final nomogram was developed using the safety data from 1,312 of the 1,376 enrolled pts. The frequencies of UGT1A1 polymorphisms were 48%, 41%, and 11% for the wild, hetero, and homo groups, respectively. Severe neutropenia was observed in 31% of all pts: 25%, 34%, and 49% for the three groups, respectively. The nomogram integrates important factors such as regimen, initial doses of IRI, age, sex, performance status, UGT1A1 genotype, pre-treatment neutrophil count, and total bilirubin. The concordance index (c-index) was 0.693, which was higher than that of 0.593 for a model that used just the UGT1A1genotype. The nomogram was externally validated with a c-index of 0.702, using independent data from 350 pts. Conclusions: This nomogram can be used to accurately predict IRI-related severe neutropenia in Japanese pts with aCRC.
Determinants for no definitive therapy for early-stage non-small cell lung cancer in U.S. population.
Authors: Yu-Wei Chen, Angela Y. Chang, Chen-Hao Chen, Yu-Han Chiu, Yen-Chen Feng, Sheng-Hsuan Lin, Yi-Han Sheu, Yen-Fen Lin
Journal: Journal of Clinical Oncology (2015)

1590 Background: Surgery or radiation therapy (RT) remains the definitive treatment for early-stage (Stage I/II) non-small cell lung cancer (NSCLC). Early-stage NSCLC should be treated appropriately since survival decreases progressively with advanced stages. Our study aims to identify the factors associated with receiving no definitive therapy among US patients. Methods: Patients ≥ 18 years and diagnosed with stage I/II NSCLC from 2004-2011 in Surveillance, Epidemiology and End Results Program (SEER) were identified. Definitive therapy was defined as receiving surgery and/or RT. Socio-economic characteristics (income, educational status and residence type) were collected at county-level. Predictors for no definitive therapy were estimated with a multivariable logistic regression model. Results: A total of 32,401 patients were identified. 4,997 patients (15%) had no definitive therapy and among them only 456 (9%) did not receive surgery due to contraindications/patient refusal. Independent predictors for no definitive therapy include individual characteristics, such as older age, male, African Americans, not-married status, histology types other than adenocarcinoma, as well as county-level characteristics include living in a county with lower median household income, higher percentage of population with education level < high school, and a non-metropolitan setting. Conclusions: A significant proportion of patients diagnosed with early-stage NSCLC in the US did not receive definitive therapy. Socio-economic characteristics should be explored further to explain this phenomenon. Independent Predictors Adjusted OR 95% CI Age (every 10 years increase) 1.86 (1.80-1.92) Median house Income (every 10,000 USD increase) 0.86 (0.81-0.91) %Education < high school level (every 20% increase) 1.39 (1.23-1.56) Sex Male vs Female 1.32 (1.02-2.10) Race Black vs White 1.67 (1.51-1.85) Other vs White 1.14 (0.99-1.31) Marital status Married/Domestic partners Ref Single/Divorced/Separated/Widowed 1.96 (1.83-2.10) Residence Non-Metropolitan vs Metropolitan 1.12 (1.02-1.24) Histology type Squamous cell carcinoma vs Adenocarcinoma 1.13 (1.04-1.23) Others vs Adenocarcinoma 2.37 (2.20-2.56)
A single-arm phase II study of afatinib treatment for advanced EGFR-mutant non-small cell lung cancer (mNSCLC) patients (pts) with EGFR-tyrosine kinase inhibitor (TKI) resistance.
Authors: Jair Bar, Dana Botser, Rossie Navon, Nir Peled, Haim Biran, Einav Nili Gal-Yam, Sayeh Ben-Arieh, Stephen Raskin, Amir Onn
Journal: Journal of Clinical Oncology (2015)

e19031 Background: mNSCLC pts benefit from EGFR TKI treatment. However, resistance inevitably occurs and is difficult to treat. We wanted to evaluate the efficacy of an ErbB-family inhibitor, afatinib, for patients with EGFR TKI resistance. Methods: Advanced mNSCLC pts or NSCLC pts with 6 months or longer benefit from EGFR TKI that failed on EGFR TKI as well as on chemotherapy were eligible. Afatinib was started at a dose determined by patients’ performance status, body mass index (BMI) and estimated glomerular filtration rate (eGFR). Primary endpoint was progression free survival (PFS), secondary endpoint was overall survival (OS). Data was analyzed for potential prognostic factors. Results: A total of 41 patients were recruited to this study since January 2013 till closure of recruitment at the end of June 2014. 29% were with performance status (PS) of 3-4, 68% with eGFR ≤ 80 cc/h, 15% with BMI of ≤ 20 kg/m2, 76% with prior treatment lines ≥ 2. At a median follow up of 7.9 months, median PFS was 2.9 months (95% CI 1.7-4.4), median OS was 6.2 months (95% CI 4.3-7.4). Response rate was 26%. 12% stopped treatment due to toxicity or patient’s decision. Four SAEs in 3 (7.7%) patients were considered treatment-related (diarrhea (2), nausea/vomiting (1), fall (1)). There were no treatment-related deaths or pneumonitis. PS and BMI were found to be significant predictors of OS on multivariate analysis. Interestingly, of the 3 patients with OS > 12 months were two patients with EGFR exon 20 insertions. Conclusions: Afatinib may be considered as a therapeutic option for mutant EGFR advanced NSCLC with acquired resistance to EGFR TKIs. Clinical trial information: NCT01932229.
Association of the canonical NF-κB pathway with clinical outcome measures in ER-negative breast cancer.
Authors: Julie C Doughty, Lindsay Bennett, Elizabeth A Mallon, Paul G. Horgan, Joanne Edwards
Journal: Journal of Clinical Oncology (2013)

588 Background: Although breast cancer morality rates have fallen, resistance to treatment remains a major problem. The NF-κB pathway regulates transcription of a wide range of genes involved in inflammation, proliferation and apoptosis and are hypothesized to play a role in tumor progression. Methods: Immunohistochemistry was employed to assess expression of members of the NF-κB pathway in a cohort of 544 breast cancer specimens with full clinical follow-up. Antibodies for the p65 subunit, phosphorylated p65 at the serine 536 residue (p-p65 S536), nuclear localization signal of p65 (p65 NLS), IKKα and IKKb had specificity confirmed by both a single band of appropriate size on a western blot and appropriate expression patterns in cell pellets treated with TNFα. Results: When the full cohort was considered patients with tumors that expressed high levels of cytoplasmic IKKα had significantly shorter disease free survival compared to those with low expression (P=0.015). Increased expression of nuclear p-p65 S536 was also associated with shorter disease free survival (P=0.005). By western blot analysis we observed that expression levels of p-p65 S536 were higher in MD-MBA-231 cells which are ER negative compared to MCF-7 cells that are ER positive, suggesting that NF-κB may have a prominent role in ER negative disease. However when the cohort was subdivided, by ER status the association observed for IKKα expression and shorter disease free survival was attenuated in ER positive tumors (p=0.008). In addition this attenuation with the ER positive cohort was also observed for nuclear p-p65 S536 (P=0.002). Other members of the pathway investigated (p65, p65 NLS and IKKb) were not associated with disease free survival. Conclusions: These results suggest that in the clinical setting the NF-kB canonical pathway is associated with poor prognosis in ER positive tumors and not with ER negative tumors as the cell line work would suggest. These results require validation in an independent cohort, but highlight the need to consider subtypes of breast cancer as individual diseases with increasingly different therapeutic targets.