tbuckley/cabot-search huggingface dataset:
Cetuximab concurrent with postoperative radiation (Cet-XRT) in poor risk patients with resected squamous cell carcinomas of the head and neck (SCCHN).
Authors: Daisuke Araki, Mary Weber Redman, Renato Martins, Keith D. Eaton, Christina S. Baik, Laura Quan Man Chow, Bernardo Goulart, Sylvia Mina Lee, Rafael Santana-Davila, Jay Justin Liao, Upendra Parvathaneni, Neal Futran, Eduardo Mendez, Cristina P. Rodriguez
Journal: Journal of Clinical Oncology (2015)

e17037 Background: Postoperative cisplatin (cis)-XRT is the standard of care for high-risk SCCHN. We have used Cet-XRT in the postoperative setting for patients (pts) deemed poor candidates for cis. Methods: We retrospectively identified pts who received Cet-XRT after curative resection for locoregionally advanced SCCHN. Demographics, Charlson Comorbidity Index (CCI), ECOG performance status (PS), tumor and treatment data were collected. Outcomes were estimated using the Kaplan Meier method, multivariable analysis (MVA) was used to identify predictors for outcomes. Results: From 1/2006 and 12/2013 40 pts received Cet-XRT (450/200 mg/m2 weekly during XRT). The median age was 65 (21-78): 31 (77.5%) pts were male, and 35 (87.5%) Caucasian. Pts smoked a median 20 pack-years (0-120). Median CCI was 3 (2-6): median ECOG PS 1 (0-3). Pathologic stage was III in 5 (12.5%) and IV in 35 (87.5%). Primary sites were: oral cavity in 18 (45%), larynx in 6 (15%), oropharynx in 4 (10%), paranasal sinus in 3 (7.5%), skin in 6 (17.5%), unknown in 2 (5%) pts. Tumor differentiation was: poor in 18 (45%), moderate in 18 (45%), well in 2 (5%) and unspecified in 2 (5%). 3 (7.5%) pts had p16+ oropharynx cancer. High risk features included: extranodal spread in 20 (50%) pts, positive margins in 21 (52.5%), perineural involvement in 15 (37.5%), and lymphovascular invasion in 12 (30%). The median number of Cet doses given was 6 (2-9): median radiation dose 6300 cGy (400-7200). PEG tubes were insterted in 22 (55%) pts, and tracheostomy in 6 (15%). A rash was observed in 16 (72.7%) pts. 8 (36.4%) pts had 1 ER visit, and 2 (9%) had 2 ER visits during Cet-XRT. 10 (45%) required 1 inpatient admission, and 1 (4.5%) required 2. With a median follow-up of 24 months, the 2 year KM estimates were: overall survival (OS) 41%, recurrence free survival (RFS) 34%, locoregional control (LRC) 63%, and distant metastatic control 59%. On MVA, only PS > 0 predicted for inferior OS HR = 5.43 p = 0.003, RFS HR = 4.07 p = 0.007, and LRC HR = 4.92 p = 0.04. Conclusions: LRC was encouraging using Cet-XRT. Aggressive inpatient supportive care was needed in some pts. Further study of the efficacy and cost compared to XRT alone is needed prior to adoption as a standard.
Genome-wide methylation profiling to identify potential epigenetic biomarkers associated with response to sunitinib in metastatic renal cell cancer (mRCC) patients (pts).
Authors: Jenny J. Kim, Mariette Labots, Luigi Marchionni, Shahnaz Begum, Gerrit A. Meijer, Henk M.W. Verheul, Michael Anthony Carducci, Hans J. Hammers, Mohammad Allaf, George J. Netto, Mohammad Hoque
Journal: Journal of Clinical Oncology (2013)

4566 Background: There exists a significant heterogeneity in the clinical response to sunitinib among pts treated for mRCC and, thus, a biomarker which would predict pts’ response up front would be an invaluable tool in the clinical management of these pts. In this regard, whole genome methylation array was performed between 2 extreme groups: sunitinib responders (RES) and non-responders (NRES) to identify differentially methylated genes between these subsets of pts. Methods: mRCC pts who received sunitinib therapy with available frozen nephrectomy tissues (stored at -80°C) and clinical data were identified. RES were identified as pts with progression free survival (PFS) of &gt; or =11 months (mos) and NRES as those with PFS &lt; or = 3 mos. After DNA extraction and quality assurance according to standard protocol, whole genome methylation array was performed using Infinium Humanmethylation450 BeadChip Kit - Illumina. Data normalization was achieved by subset-quantile within array normalization (PMID: 22703947). Differentially methylated regions were identified using logit transformed Beta values, using an F-test after shrinking variance via empirical Bayes (PMID: 21118553). Results: Total of 13 pts who received sunitinib therapy with available frozen nephrectomy tissues were identified. Of the 13, 5 pts qualified for each RES and NRES cohort as described in methods section. All pts in RES group had clear cell subtype. Two pts of the NRES group were of non-clear cell subtype. The QC plots showed that all arrays were successful. For RES vs. NRES, one genomic location, DENND2D, was significantly hypermethylated in the RES group with a false discovery rate (FDR) of &lt;10%. DENND2D has been identified as a tumor suppressor-like gene in non-small cell lung cancer and melanoma cell lines in the recent past. Conclusions: In this study, DENND2D was significantly hypermethylated in sunitinib RES compared to NRES among mRCC pts. Data analysis with a less stringent FDR is also being pursued. Technical validation as well as clinical validation of DENND2D utilizing a larger pt cohort are ongoing.
Racial disparities in financial outcome among older adults with cancer: Analysis of the Health and Retirement Study.
Authors: Emily Castellanos
Journal: Journal of Clinical Oncology (2017)

3 Background: Financial hardship from cancer is often attributed to high costs of care, but the relationship of out-of-pocket (OOP) medical burden to racial disparities seen in financially distressed cancer patients is underexplored. Using the Health and Retirement Study, a national longitudinal survey of U.S. households from 1992-2012, we examined the effect of a cancer diagnosis on financial hardship and OOP medical spending among black and white adults age-eligible for Medicare insurance. Methods: Analyses were restricted to adults 65 years or older to reduce heterogeneity in employment and insurance. Financial hardship was defined as new financial insolvency, &gt; 50% decline in net worth, acquisition of debt, or high medical burden (OOP medical spending &gt; 20% of income). The proportions of black and white cancer patients reporting financial hardship, as well as OOP medical spending, household debt, income, net worth, and insurance status by racial group were determined. Statistical comparisons using a t-test for proportions or Wilcoxon rank-sum testing were performed. Results: A total of 2158 white and 322 black cancer patients were identified. Black cancer patients were more likely than white cancer patients to report new financial insolvency (6.8% vs 1.6%; p &lt; 0.0001), loss of &gt; 50% of net worth (26.7% vs 15.3%; p &lt; 0.0001), or new debt (27.6% vs 14.9%); p &lt; 0.0001). OOP medical spending, median household income, and net worth were significantly lower in black vs white cancer patients. The rate of high medical burden was similar between black vs white patients (22.1% vs 21.6%, respectively). Dual Medicare/Medicaid enrollment was higher among black vs white cancer patients, at 23.1% and 7.4%. Conclusions: Significant racial disparities in the prevalence of financial hardship were seen among older adult cancer patients, despite lower OOP medical spending and increased dual Medicare/Medicaid enrollment by black vs white cancer patients. Interventions aimed at alleviating disparities in financial outcome among cancer patients should account for pre-existing differences in socioeconomic status in addition to direct medical costs.
Next-generation sequencing (NGS) in advanced lung cancer in the community: A molecular profiling program of the Sarah Cannon Research Institute (SCRI).
Authors: Zeqiang Ma, Todd Michael Bauer, Pranil Chandra, Debbie Haynes, James Prescott, Dawn Michelle Stults, Suzanne Fields Jones, John D. Hainsworth, Jeffrey R. Infante, Howard A. Burris, David R. Spigel
Journal: Journal of Clinical Oncology (2014)

e19022 Background: A NGS program was launched in 10/2012 at a single community practice in middle Tennessee. This program was designed to discover molecular alterations with proven/potential therapeutic significance for patients (pts) with advanced cancers. We report the lung cancer cohort findings. Methods: Pts with advanced lung cancer who were candidates for systemic treatment (ECOG ≤ 2) were consented for molecular profiling. Tissue specimens were tested by NGS with 1,000X coverage in a CLIA/CAP-certified lab. Oncogenic hotspot mutations in 35 genes were tested. Results were reported to the treating M.D. <12 days of tissue procurement. Results were stored in a database to enable correlation with clinical outcomes. Results: From 10/2012-12/2013, 1,040 tumor samples were profiled across tumor types; 238 (23%) were from pts with lung cancer (all histologies). 18% (43/238) of the lung samples were inadequate for testing. Of the 195 samples with sufficient tissue, 80 (41%) had >1 mutation: 55 (28%) with single mutations and 25 (13%) with multiple mutations. The mutation frequency by histology was: adenocarcinoma 59% (54/91 pts), squamous 22% (10/45 pts), large cell 67% (4/6 pts), and small-cell 18% (5/28 pts). The most frequent mutations were KRAS and EGFR (16% and 12%, respectively). Other alterations identified included: STK11 5%, MET 4%, BRAF 3%, RUNX1 2%, FGFR3 2%, MEK1 2%, PIK3CA 2%, and KIT 2%. 24% (47/195) of profiled pts were enrolled to clinical trials after receiving NGS results (25 without discoverable mutations, 22 with mutations.) Conclusions: NGS in lung cancer is feasible in the community. 41% of pts with lung cancer had a mutation, and a third of these pts had multiple alterations. As NGS panels expand and tissue procurement improves, genomic profiling in the community could potentially broaden treatment and clinical trial options for patients with lung cancer. KRAS and EGFR Mutations. Gene Codons tested Mutated codons # of mutations % of detected mutations KRAS 12, 13, 61, 146 12 29 91% 13 1 3% 61 2 6% EGFR 709-719, exon 19 deletion, 768-790, exon 20 insertion, 833, 858-861 727 1 4% 768 1 4% 769 2 8% 790 1 4% 796 1 4% 833 1 4% 834 1 4% 852 1 4% 858 5 19% Deletion/insertion 12 46%
A phase II trial of MEK inhibitor BAY 86-9766 in combination with sorafenib as first-line systemic treatment for patients with unresectable hepatocellular carcinoma (HCC).
Authors: Ho Yeong Lim, Chia-Jui Yen, Won-Young Tak, Jeong Heo, Hye Jin Choi, Cheng-Yao Lin, Jung-Hwan Yoon, Chiun Hsu, Kun-Ming Rau, Ronnie Tung Ping Poon, Winnie Yeo, Joong-Won Park, Miah Hiang Tay, Wen Son Hsieh, Christian Kappeler, Prabhu Rajagopalan, Heiko Krissel
Journal: Journal of Clinical Oncology (2012)

4103 Background: Sorafenib (S) is the only approved systemic treatment for unresectable HCC. Nevertheless, there remains an unmet medical need for more effective treatment options for this disease. BAY 86-9766 (B) is an oral, allosteric inhibitor of MEK, a key component of the MAP kinase pathway. This study evaluated the efficacy and safety of a combination therapy with B plus S in patients (pts) with HCC. Methods: This is a single arm, open-label, phase 2 study. Eligible were pts with unresectable HCC, Child-Pugh Class A, performance status (PS) 0-1, and no prior systemic anticancer therapy for HCC. Pts started Cycle 1 (21 days) with B 50 mg bid orally plus S 600 mg daily (200 mg AM, 400 mg PM) orally. If there was no hand-foot skin reaction, fatigue, or gastrointestinal toxicity ≥ grade 2, S was escalated to 400 mg bid from Cycle 2 on. Treatment continued until progression or withdrawal criteria were met. Tumor assessment was performed every 6 weeks during treatment. Safety was evaluated every week for the first 6 weeks and every 3 weeks thereafter. Results: Seventy pts from Asia started study treatment. Pts were predominantly male (86%); median age was 56 years; 54% had PS of 0 and 46% PS of 1. The vast majority had liver cirrhosis (83%) and infection with HBV (76%) or HCV (17%). Sixty-five were evaluable for efficacy per protocol. Three pts (5%) had confirmed partial response and 25 pts (38%) had prolonged stable disease (≥10 weeks), with a disease control rate of 43%. Median time-to-progression was 4.1 months. Survival data are not mature, yet. The most frequent drug-related adverse events (AEs) were rash (60%), diarrhea (59%), AST elevation (43%), vomiting (30%), nausea (29%), ALT elevation (26%), and anorexia (26%). There were 4 Grade 5 related AEs (hepatic failure, sepsis/hepatic encephalopathy, tumor lysis syndrome, and unknown cause, respectively). Dose modifications due to AEs were necessary in almost all pts. The median daily dose was 64.2 mg for B and 443.3 mg for S, respectively. Conclusions: B in combination with S showed antitumor activity in pts with HCC. However, frequent dose modifications due to AEs might have limited the treatment effect of this combination.
Bisphosphonates in the adjuvant setting of breast cancer therapy: Effect on survival—A systematic review and meta-analysis.
Authors: Liath Vidal, Irit Ben-Aharon, Shulamith Rizel, Rinat Yerushalmi, Aaron Sulkes, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2012)

548 Background: The role of bisphosphonates (BP) in the adjuvant setting in breast cancer has been evaluated in several studies, yielding inconsistent evidence. We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluate the effects of BP treatment on survival in patients with early breast cancer in the adjuvant setting. Methods: RCTs that compared BP therapy in addition to the standard adjuvant therapy (cytotoxic or hormonal) with standard adjuvant therapy only were identified by searching the Cochrane Library, LILACS, MEDLINE databases and conference proceedings (12.2011). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and relative risks of adverse events were estimated and pooled. All statistical tests were two-sided. Results: Thirteen trials met the inclusion criteria., among which are the two recently published abstracts of large scale RCTs (NSABP-B34, GAIN) evaluating a total of 15,762 patients. Ten trials reported the OS outcome. Meta-analysis revealed no statistically significant benefit for BP (HR 0.89, 95% CI = 0.79 to 1.01). Nine trials reported the DFS outcome. Meta-analysis revealed no statistically significant better DFS for the intervention (HR 0.95 (0.80-1.11)). Six trials reported DFS stratified upon menopausal status. Postmenopausal patients who were treated with BP therapy had statistically significant better DFS than the control group (HR 0.81(0.69-0.95)). In meta-regression, chemotherapy was negatively associated with HR of OS (coefficient, -0.23; standard error, 0.144). BP therapy resulted in less fractures in the intervention arm, but higher incidence of osteonecrosis of the jaw and pyrexia. Conclusions: Our meta-analysis indicates a positive effect for adjuvant BP on survival outcomes only in postmenopausal patients with breast cancer. Meta-regression appraised the effect of confounders such as chemotherapy, showed a negative association between chemotherapy use and the effect of bisphosphonates on survival. Further large scale RCTs are warranted to unravel the specific subgroups and adjuvant treatments that would benefit from the addition of BP in the adjuvant setting.
Comprehensive genetic characterization of 12 AML cell lines using a novel AML targeted sequencing strategy.
Authors: Andrew R. Carson, Bradley A. Patay, Suzanne M. Graham, Ross Cubbon, Jeffrey E. Miller
Journal: Journal of Clinical Oncology (2014)

7103 Background: Next generation sequencing (NGS) has revealed much of the common genomic architecture of Acute Myeloid Leukemia (AML). However, the high cost of NGS and its interpretation limits specificity and coverage in most sequencing strategies. This prevents broad clinical adoption of NGS for characterizing AML samples and cell lines. Instead, investigators use limited diagnostic assays that fail to fully characterize complex variants such as internal tandem duplications in FLT3. Full characterization of variants in AML cell lines is essential, as these cells may be used to model cancer pathogenesis, develop therapeutics, and standardize diagnostic performance. Furthermore, discerning clonal architecture may prove crucial for personalized therapies. To illustrate the increased capacity and resolution of NGS for the comprehensive characterization of AML samples, we sequenced the
Sex steroids, sex-binding globulin, and prolactin in tissues of adenocarcinoma and esophageal squamous cell carcinoma.
Authors: Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Valeria Bandovkina, Evgeniy N. Kolesnikov, Roman E. Myagkov, Vladimir Trifanov, Lyudmila Dmitriyevna Tkalya, Natalya Chugunova, Irina Stasio Tavaryan
Journal: Journal of Clinical Oncology (2017)

79 Background: Some researchers suggest that squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus (ACE) are characterized by different pathogenesis, epidemiology and tumor biology, and therefore require different therapeutic strategies. The purpose of the study was to analyze local hormonal status in malignant esophageal tumors and surrounding tissues depending on the histogenesis. Methods: Levels of sex steroids – free testosterone (fT), estrone (E1), estriol (E3), prolactin (PRL) and sex steroid-binding globulin (SSBG) were studied by the standard ELISA methods in tumor tissue, perifocal zone and resection line of 39 patients aged 58-74 years: 27 SCC, 12 ACE, stage II, G2, pT1-2N1M0. Results: Differences were found in local hormonal content in all studied samples dependint on the tumor histotype. Levels of SSBG, PRL and E1 in ACE were higher than in SCC by 1.3, 3.3 and 1.4 times, respectively, while fT concentration was 2.4 times lower. Levels of PRL, E1 and E3 in perifocal zone of ACE compared to SCC were higher by 2.8, 3.3 and 3.1 times, and fT was 1.3 times lower. Resection line of ACE differed from that of SCC by higher tissue concentrations of SSBG – by 1.3 times, PRL – by 1.5 times, E1 – by 1.3 times, E3 – by 1.7 times and a lower level of fT – by 1.5 times. As a result, fT/E1 ratios in ACE and surrounding tissues were on average 3 times lower than in corresponding SCC samples. Conclusions: Levels of hormones in esophageal tumors and surrounding tissues depend on the histogenesis. ACE was characterized by hyperestrogenism in esophageal tissues along with a high prolactin concentration, while SCC – by hyperandrogenism with a low PRL level. Different pathogenesis of SCC and ACE was demonstrated by the fact that hormonal profile in both tumor and resection line depended on the tumor histology.
Impact of CEA alone or as part of a high intensity surveillance strategy in detecting curative colorectal cancer recurrence: A systematic review and meta-analysis.
Authors: Marck Mercado, Rachel Hart, Adena Scheer, Andrea Tricco, Jemila Hamid, Christine Brezden-Masley
Journal: Journal of Clinical Oncology (2017)

566 Background: Consensus is lacking regarding an effective surveillance strategy for the detection of colorectal cancer (CRC) recurrence at a curative stage. This study aims to evaluate the effect of carcinoembryonic antigen (CEA) measurement alone vs. CEA as part of an intensive surveillance strategy for the detection of curative CRC recurrence. Methods: A systematic review was performed using MEDLINE and EMBASE from January 2000 to April 2016 to identify randomized controlled trials (RCTs), cohort studies, quasi-experimental design studies, and case control studies including stage II/III CRC patients with curative resection and surveillance with repeated CEA measurements. Data screening, abstraction, and risk of bias assessment was independently performed by two reviewers. Risks of recurrence amenable to surgical resection, local and distant recurrence, disease-specific mortality and overall mortality were pooled using random effects meta-analysis. Results: Two RCTs and 9 cohort studies were included. A meta-analysis of 861 patients in RCTs demonstrated a non-significant reduction in the detection of curative recurrence using CEA measurement alone vs. intensive surveillance strategies with CEA (RR 0.76; 95% CI 0.41-1.41). There were no significant differences observed in the risk of locoregional or distant recurrence. Patients with CEA alone had a non-significant higher risk of disease specific and overall mortality ([RR 1.19; 95% CI 0.89-1.60], [RR 1.21; 95% CI 0.84-1.76], respectively). The heterogeneity of the cohort studies inhibited a quantitative meta-analysis. Among 2783 patients in 9 cohort studies using intensive surveillance strategies with CEA measurement, the rate of curative recurrence ranged from 21.3% to 56.8%. Conclusions: Limited data exists to guide the optimal surveillance strategy post-curative CRC resection. This study highlights the potential benefit of intensive surveillance strategies with CEA measurement as compared to CEA measurement alone in detecting curative CRC recurrence. However, further research to determine optimal CRC surveillance strategies is warranted.
Correlate effects of local therapy for the primary tumor in metastatic breast cancer at diagnosis with molecular subtypes.
Authors: Fatima Zahra Hijri, Samia Arifi, Sami Aziz Brahmi, Nezar Bouyahia, Zineb Benbrahim, Khaoula Daoudi, Adil Najdi, Mohamed Amine Berreho, Chakib Nejjari, Affaf Amarti, Mellas Nawfel, Omar El Mesbahi
Journal: Journal of Clinical Oncology (2012)

e11502 Background: Few studies demonstrated that surgical resection of the primary tumor in patients with metastatic breast cancer at diagnosis is associated with significant improvement of survival. The aim of this study is to evaluate the correlation impact of local surgery in metastatic breast cancer at diagnosis with molecular subtypes. Methods: A retrospective study was conducted from 2007 to 2011 in our institution, of all stage IV breast cancer patients; who undergo breast surgery. Clinical , tumor characteristics, molecular subtypes, prognostic factors, therapeutic results data were analyzed. Results: We selected 59 cases. The mean age was 36 years (range: 22-44). 55 % women presented with locally advanced breast cancer with 13% T4 d . All patients underwent mastectomy except 4 who underwent conservative surgery .41 patients had axillary lymph node dissection. 63% were luminal A, 17% were luminal B, 7% were Her2-positive and 13% were basal-like . All patients received anthracycline based regimen and only 33% received taxanes. Loco regional radiotherapy (RT) was given to 6 women. Average follow-up was 13 months: - 20 patients represented partial response : 15 patients in luminal A , 3 patients in luminal B ,1 patients in basal-like and 1 patient in HER2-positive. - 11 patients (19%) were stable : 9 patients in luminal A and 2 patient in luminal B . -24 patients represented a progressive disease including 11 patients presented locoregional recurrence : 75 % in HER-positive, 40 % in basal-like, 50% in luminal B and 30% in luminal A (p=0.4). - 4 patients died in basal-like. The median local recurrence-free survival was 19 months and the median progression-free survival was 20 months. The local relapse is less observed in patients who: have a small tumor size (p = 0.003), had axillary lymph node dissection (p = 0.02) and loco regional radiotherapy (p = 0.03). The metastatic progression is less observed in patients with small tumor size (p = 0.01). Conclusions: Local Therapy of the primary tumor improves local control of disease, particularly in women with Small tumors. However, no significant correlation between impact of locale therapy and Molecular Subtypes was observed.