tbuckley/cabot-search huggingface dataset:
The well-being of long-term cancer survivors.
Authors: Jeffrey Sullivan, Julia Thornton Snider, Emma van Eijndhoven, Katharine Batt, Tony Okoro, Manan Shah, Thomas DeLeire
Journal: Journal of Clinical Oncology (2016)

30 Background: While numerous studies have examined the outcomes of individuals recently diagnosed with cancer, less is known about the well-being of long-term (LT) cancer survivors. Methods: Using the Health and Retirement Study (HRS), a nationally representative survey of US residents over age 50, we defined four cohorts: US residents over age 50, individuals recently diagnosed with cancer (≤4 years from diagnosis), LT cancer survivors (&gt;4 years from diagnosis) and individuals with a chronic condition (diabetes, heart disease, hypertension, lung disease or prior stroke). We compared well-being measures across cohorts. We imputed total medical spending using the Medical Expenditure Panel Survey and the Medicare Current Beneficiary Survey. Results: We identified 22,034 US residents over age 50; 754 individuals recently diagnosed with cancer; 1,764 LT survivors; and 12,874 individuals with chronic illness. Over the biannual survey waves from 2004-2012, this amounted to 22,034; 3,880; 8,480; and 57,363 person-years, respectively. (The 50+ cohort was analyzed in 2010, the most recent year in which the HRS was nationally representative.) Given the large samples, most differences between LT survivors and other cohorts were statistically significant (p&lt;0.05). However, LT survivors’ outcomes were often closer to those of individuals with chronic illness than to the recently diagnosed. Earnings if employed of the recently diagnosed and self-reported health of the chronically ill were not significantly different from LT survivors. Conclusions: Although cancer has a negative impact on well-being in the short term, over time cancer survivors’ well-being improves, becoming more similar to that of individuals with a chronic condition. [Table: see text]
External validation of preoperative AST/ALT (De-Ritis) ratio as a prognostic indicator in localized and metastatic renal cell carcinoma.
Authors: Dattatraya H Patil, Rishi Robert Sekar, Jeff Pearl, Yoram Baum, Mehrdad Alemozaffar, Christopher Paul Filson, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2016)

589 Background: Recently, the De-Ritis ratio, defined as the ratio of preoperative aspartate aminotransferase (AST) to alanine aminotransferase (ALT), was shown to be an independent predictor of overall and recurrence-free survival in a European cohort with localized renal cell carcinoma (RCC). In this study, we perform an external validation of the De-Ritis ratio as a prognostic indicator in a distinct cohort of patients with localized and metastatic RCC. Methods: Patients that underwent nephrectomy for localized and metastatic RCC between 2001 and 2014 with available laboratory values within one week of surgery were queried from the Emory Nephrectomy Database. De-Ritis ratio of 1.2 was used to divide subjects into high and low subgroups. Using clinical follow-up data, prognostic value of the De-Ritis ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. Results: In a cohort of 451 patients, an elevated De-Ritis ratio (AST/ALT ≥ 1.2) was associated with significantly decreased overall survival (log-rank, p=0.0023) and recurrence-free survival (Log-rank, p=0.0395). On multivariate analysis, De-Ritis ratio was shown to be an independent and significant predictor of overall survival (HR=0.52, p=0.002) and recurrence-free survival (HR=0.47, p=0.014) as seen in Table. Conclusions: Elevated De-Ritis ratio (AST/ALT ≥ 1.2) is an independent and significant predictor of overall and recurrence-free survival and is capable of differentiating high-risk disease in patients with localized and metastatic RCC. These findings are consistent with a previous study investigating the prognostic value of the De-Ritis ratio in a European cohort, and further validates its prognostic ability in a geographically distinct cohort including patients who presented with metastatic disease [Table: see text]
Tumor marker CA 11-19 as a new serum blood test for monitoring colorectal cancer.
Authors: John J. Costanzi, Tommye Ann Jordan, Lisa Jensen-long
Journal: Journal of Clinical Oncology (2016)

536 Background: Colorectal cancer remains the third most frequent cause of cancer deaths globally. The FOBT (fecal occult blood test) and FIT (fecal immunochemical test) as well as CEA are increasingly being used to screen or monitor patients at increased risk for colorectal cancer (CRC), however none has optimal performance in terms of both sensitivity and specificity. Data was recently published* on the new serum blood test colorectal tumor marker CA11-19. This data showed a sensitivity of 98% (95% CI, 93.1%-99.5%) and specificity of 84% (95% CI, 80.0%-87.9%) at a cut-off value of 6.5 U/mL with a high sensitivity for detection of early stage CRC as opposed to CEA whose values are reported ~40% and ~30–80%** respectively for sensitivity and specificity. This study will look at case studies that show an array of long-term monitoring outcomes which suggest possible use of CA 11-19 instead of CEA. Methods: Using a sandwich ELISA assay, a new colon cancer antigen, CA 11-19, (100 kDa glycoprotein) was measured in samples of 7 patients with a variety of conditions in normal, benign GI diseases, polyps and colon cancer. This long-term follow up is recorded from 8 to 20 years. Results: Serum samples previously frozen were used to measure the CA11-19 antigen. An average follow up time of 15 years (range 8 to 20 years) was recorded. Elevated levels of CA11-19 were detected in patients with polyps and CRC prior to treatment and decreased levels were measured after the removal of the polyps or cancer. Importantly, rising rates of CA11-19 were seen in patients with cancer recurrences of colorectal cancers. Conclusions: CA 11-19 is a serologic tumor marker for colorectal cancer with a published sensitivity of 97.7% and a specificity of 84.4%*. Preliminary reports from 7 cases show long-term data which could be more helpful in monitoring and or follow-up of high risk patients for CRC than the current CEA testing method. Additional studies are needed to further validate the use of CA 11-19 in these patient groups.
An interim analysis of a phase II study using an epigenetic biomarker (CHFR methylation status) to personalize chemotherapy in patients with operable esophageal cancer.
Authors: Ronan Joseph Kelly, John Wrangle, Russell K. Hales, Daniela Molena, Stephen C. Yang, Kristen Rodgers, Margaret Lang, Jeffrey Reynolds, Tammy Beckman, Amanda Choflet, Malcolm Brock, James Gordon Herman
Journal: Journal of Clinical Oncology (2014)

76 Background: Preoperative chemoradiotherapy using a platinum plus either a taxane or 5FU results in a pathological complete response rate (pCR) of approximately 25% to 30% in patients with operable esophageal cancer. A predictive biomarker to personalize chemotherapy in an effort to increase pCR would be a significant advance. Checkpoint with forkhead and ring finger domains (CHFR) is an E3 ligase which plays a role in response to mitotic stress. In our retrospective data, hypermethylation and silencing of CHFR, correlates with improved response and prolonged survival following therapy with taxanes. The primary endpoint of this study is to determine if there is a higher pCR rate when CHFR methylation status (MS) is used to decide if patients receive a taxane or 5FU. Methods: All patients presenting to Johns Hopkins with operable T2-T4/N0-N3 esophageal cancer are eligibile. A methylation-specific PCR which demonstrates CHFR MS has been developed by our lab. Methylated (M) patients receive weekly cisplatin (30mg/m 2 )/paclitaxel (50mg/m 2 ) and unmethylated (U) patients receive previously described regimens of folfox or cisplatin/5FU. All patients receive concurrent radiation. Results: From July 2011 to September 2013, 35 patients have been assessed, 18 U (51%), 14 M (40%) and 3 unknown (9%). Twenty-four patients (22 males and 2 females) have been treated on study (age 48 – 74 years old, median 63.8) with 14 tumors U (58%) and 10 tumors M (42%) respectively. To date, 2/13 U patients (15%) have had a pCR and 3/8 M patients (38%) have had a pCR (p=0.32). Toxicities of each regimen are consistent with previous reports. Conclusions: Trimodality therapy is standard of care for operable esophageal cancer in the United States. Different chemotherapies have been combined with radiation prior to surgery to improve pCR rates but no biomarkers to personalize chemotherapy exist at present. Epigenetic biomarkers such as CHFR MS potentially may be used to decide which patients are more sensitive to taxane based regimens. Accrual to this study is ongoing. Clinical trial information: NCT01372202.
A phase 1b, open-label, non-randomized multicenter study of birinapant in combination with conatumumab in subjects with relapsed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
Authors: Erika Paige Hamilton, Michael J. Birrer, Brian Anthony DiCarlo, Stephanie Gaillard, Lainie P. Martin, John J. Nemunaitis, Raymond P. Perez, Russell J. Schilder, Christina M. Annunziata, Colin G. Begley, Steven Jeffrey Hager
Journal: Journal of Clinical Oncology (2015)

5571 Background: Treating patients (pts) with relapsed ovarian cancer remains challenging. Birinapant is a bivalent SMAC mimetic in clinical development for solid and hematological malignancies. In vitro there is synergy with birinapant and Amgen's DR-5 agonist antibody, conatumumab. Birinapant alone was not active in relapsed ovarian cancer, but the combination with conatumumab is thought promising. This study sought to determine the safety and tolerability of birinapant with conatumumab in relapsed ovarian cancer. Methods: Pts with relapsed epithelial ovarian, primary peritoneal or fallopian tube cancer were enrolled to 1 of 2 cohorts. Birinapant was dosed intravenously (IV) at 13 mg/m2 2x weekly, 3 weeks of 4 (Days 1, 4, 8, 11, 15, and 18; Cohort 1); and 13 mg/m22x weekly, 4 weeks of 4 (Days 1, 4, 8, 11, 15, 18, 22 and 25; Cohort 2), with conatumumab at a fixed dose of 10 mg/kg IV, on Day 1 and Day 15 for each 28-day cycle. Assessments for dose limiting toxicities (DLTs), as well as safety, clinical response, pharmacokinetics (PK) and pharmacodynamics were performed. Results: To date 18 pts have been enrolled; 6 to Cohort 1 and 12 to Cohort 2. DLTs were seen in 1 pt in Cohort 1 (Grade 3 amylase and lipase elevation) and 1 pt in Cohort 2 (Grade 3 cranial nerve palsy). The most common ( ≥ 3 pts) reported adverse events (AE) were fatigue; nausea; vomiting; abdominal pain; headache; hypomagnesemia; pruritis; chills; constipation; depression; diarrhea; dizziness; pyrexia; mucositis; urinary tract infection. The only serious adverse event seen in > 1 pt was bowel obstruction (2 pts). An additional pt in Cohort 2 developed Grade 2 cranial nerve palsy. The PK of birinapant and conatumumab were unchanged from that reported previously for either agent. Pharmacodynamic evaluation is ongoing. Best response was PR seen in 1 pt; an additional 4 pts demonstrated best response of SD. Median time on study is 1.9 months (0.1-5.9 months). Conclusions: The combination of birinapant plus conatumumab in relapsed ovarian cancer is tolerable. Dose expansion (Cohort 3) is continuing at a dose of birinapant 11 mg/m2 2x weekly, 3 weeks of 4. Clinical trial information: NCT01940172.
External beam radiation therapy (EBRT) use and safety with radium-223 dichloride (Ra-223) in patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) from the ALSYMPCA trial.
Authors: Steven E. Finkelstein, Jeff M. Michalski, Joe M. O'Sullivan, Chris Parker, Jose E. Garcia-Vargas, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

182 Background: In ALSYMPCA, Ra-223, a first-in-class α-emitter, improved overall survival and delayed time to first symptomatic skeletal event vs placebo (pbo). This post hoc analysis evaluated safety and efficacy of Ra-223 plus EBRT. Methods: Pts had symptomatic (recent EBRT for bone pain or any regular analgesic use) CRPC with ≥ 2 bone and no visceral mets; best standard of care; and prior docetaxel (pD) or were unfit for or declined docetaxel (no pD). Pts were stratified by pD use (yes/no), baseline total alkaline phosphatase level (tALP; &lt; 220 U/L or ≥ 220 U/L), and current bisphosphonate (bp) use (yes/no) and randomized 2:1 to 6 Ra-223 injections (50 kBq/kg IV q 4 wk) or pbo. EBRT for bone pain was permitted within 12 weeks prior to randomization and during study. Baseline pain by prior EBRT, time to first on-study EBRT use for bone pain, and adverse events (AEs) by concomitant EBRT (cEBRT) were analyzed. Results: Pts with no prior EBRT had less pain at baseline; a WHO pain score ≤ 1 (no opioid use) was present in 46% (355/724) of pts with no prior EBRT vs 36% (53/147) of pts with prior EBRT. Ra-223 vs pbo significantly reduced EBRT use in the overall population (HR = 0.67, P = 0.001) and in pts with ≤ 20 bone mets (HR = 0.49, P &lt; 0.001), current bp use (HR = 0.47, P = 0.004), tALP &lt; 220 U/L (HR = 0.66, P = 0.008), and no pD (HR = 0.65, P = 0.038). At 6 months, the percentage of Ra-223 pts requiring EBRT was similar for prior and no prior EBRT subgroups (24% vs 20%), increasing at 12 months (38% vs 29%). cEBRT did not affect Ra-223 safety, and myelosuppression was low (Table). Conclusions: cEBRT did not adversely affect Ra-223 hematologic safety. Ra-223 significantly reduced risk of EBRT use. In Ra-223 pts, prior EBRT did not appear to affect later EBRT use. Clinical trial information: NCT00699751. [Table: see text]
Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia
Authors: Zachary R. Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J. Castillo, Steven P. Treon
Journal: Journal of Clinical Oncology (2017)

Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88. Deletions involving chromosome 6q are common and include genes that modulate nuclear factor-κB, BCL2, BTK, apoptosis, differentiation, and ARID1B. Non-chromosome 6q genes are also frequently deleted and include LYN, a regulator of B-cell receptor signaling. MYD88 and CXCR4 mutations affect WM disease presentation and treatment outcome. Patients with wild-type MYD88 show lower bone marrow disease burden and serum immunoglobulin M levels but show an increased risk of death. Patients with CXCR4 mutations have higher bone marrow disease burden, and those with nonsense CXCR4 mutations have higher serum immunoglobulin M levels and incidence of symptomatic hyperviscosity. Mutated MYD88 triggers BTK, IRAK1/IRAK4, and HCK growth and survival signaling, whereas CXCR4 mutations promote AKT and extracellular regulated kinase-1/2 signaling and drug resistance in the presence of its ligand CXCL12. Ibrutinib is active in patients with WM and is affected by MYD88 and CXCR4 mutation status. Patients with mutated MYD88 and wild-type CXCR4 mutation status exhibit best responses to ibrutinib. Lower response rates and delayed responses to ibrutinib are associated with mutated CXCR4 in patients with WM. MYD88 and CXCR4 mutation status may be helpful in treatment selection for symptomatic patients. Novel therapeutic approaches under investigation include therapeutics targeting MYD88, CXCR4, and BCL2 signaling.
Gemcitabine, oxaliplatin, and bevacizumab (GEMOX-B): A promising regimen for the treatment of advanced biliary tract cancers.
Authors: A. Mahipal, E. Rosato, S. J. Littman, H. Hargrove, A. R. Bapat, C. Doria, E. P. Mitchell
Journal: Journal of Clinical Oncology (2011)

355 Background: Biliary-tract cancers (BTCs) arise from the epithelium of the gallbladder and bile ducts and are relatively rare, affecting 9-12,000 people in the United States annually. Peak incidence is in the seventh decade of life. Prognosis of advanced BTCs is poor with median overall survival of approximately 10 months. There has been no standard treatment regimen because of lack of randomized clinical trials data. Phase II trials have demonstrated the efficacy of the combination of gemcitabine and oxaliplatin with the response rate of ∼50%. In a recently published phase II trial, the addition of bevacizumab to this regimen (GEMOX-B) resulted in 63% progression-free survival (PFS) at 6 months. In this retrospective study, we evaluated the efficacy of GEMOX-B in patients with advanced biliary tract cancers treated at Thomas Jefferson University. Methods: All patients received treatment on day 1 and 15 of 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m 2 and oxaliplatin 85 mg/m 2 . All patients were administered diphenhydramine, dexamethasone, and ondansetron prior to chemotherapy. Response was assessed using the RECIST criteria. PFS was measured from start of chemotherapy to disease progression or death. Results: A total of 6 patients with BTCs were treated with GEMOX-B. One patient was male and 5 were female. The median age was 45 years (40-64 years). All patient had ECOG performance score 0-1. Three patients had progressed on prior therapy. A total of 65 cycles were administered with the median being 9 (range: 7-21) cycles. Two patients (33%) had partial response and 4 patients (66%) had stable disease. One patient progressed after 6.4 months of therapy. One patient died due to pneumonia but had stable disease at time of death. One patient developed encephalopathy, likely due to bevacizumab. Two patients are still receiving treatment. The median PFS has not been reached (range: 6-42 months). Conclusions: This retrospective study further suggests that GEMOX-B is an active regimen in BTCs. Additional studies are needed to further evaluate the toxicity and efficacy of this regimen and understand molecular pathways governing sensitivity to chemotherapy. No significant financial relationships to disclose.
Intensity-modulated radiation therapy for postoperative oral cavity cancer: experience and feasibility
Authors: S. Liu, T. Yen, Y. Chang, Y. Chen
Journal: Journal of Clinical Oncology (2008)

17026 Background: Intensity-modulated radiation therapy (IMRT) has been widely accepted for treatment of head and neck malignancies. However, for oral cavity cancer, the most common and validated use of IMRT was focused on disease with gross and measurable tumor. This study examined the feasibility of postoperative IMRT with or without concurrent chemotherapy (CCRT) for oral cavity cancer (OCC). Methods: Between Sep 2006 and Sep 2007, 20 OCC patients were treated with composite tumor resection and/or lymph node dissection as indicated. Postoperative IMRT with or without concurrent chemotherapy, which contained cisplatin and 5-fluorouracil (5-FU), was applied as adjuvant treatment. Target delineation, area coverage and dose specification followed our institutional guideline (Table 1). The loco-regional control, pattern of failure and radiation morbidity was assessed. Results: The median follow-up time was 4.9 months (1-11 months). One patient died of CCRT-related complication (sepsis and upper gastrointestinal bleeding). Two patients developed loco-regional recurrence: one within clinical target volume 1 (CTV1) for primary tumor site and one within CTV3 for contralateral level Ib lymphatics. The median time from completion of treatment to loco-regional failure was 4.5 months. In 5 patients received IMRT alone, no grade 3/4 radiation dermatitis was noted and only one patient (20%) developed grade 3 mucositis. By contrast, grade 3/4 dermatitis and grade 3 mucositis developed in 80% and 100% of 15 patients received CCRT, respectively. Conclusions: Postoperative IMRT for OCC might be effective for loco-regional control. Loco-regional failure was limited within radiation field. The acute skin and mucosa reaction of IMRT alone was acceptable, whereas that of 5-FU-containing CCRT may need modification. Further clinical trials to validate these preliminary results are warranted. Target delineation, area coverage and dose specification of postoperative IMRT for OCC Target delineation and area coverage Dose specification High risk Intermediate risk CTV1 Entire surgical bed/anatomic defect + 1-cm margin or preoperative gross tumor + 2-cm margin Entire nodal level around involved LN 66 Gy 60 Gy CTV2 Level Ib, II, III and Va in LN (+) side; add level Ia for anterior tongue/FOM lesion 59.1 Gy 54 Gy CTV3 LN (+) site: level IV, Vb, SCF LN(−) site: Level Ib-IV, SCF Contralateral elective nodal irradiation in T3/4, N+, or oral tongue/FOM lesion 56.1 Gy 51–54 Gy Abbreviations: FOM, flour of mouth; SCF, supraclavicular fossa; LN, lymph node No significant financial relationships to disclose.
Prevalence of unsuspected venous thromboembolism (VTE) on routine computed tomography (CT) scans in cancer patients.
Authors: K. Olejeme, M. Suarez-Almazor, G. W. Gladish, X. Lei, C. P. Escalante
Journal: Journal of Clinical Oncology (2010)

e19513 Background: Cancer patients have a 4-6 fold increased risk of venous thromboembolism (VTE) compared with the general population. Retrospective studies show a 1.5 to 6% prevalence of unsuspected VTE on routine imaging in cancer patients. The aim of this study was to prospectively determine the prevalence of unsuspected VTE in cancer patients undergoing routine staging CT and to evaluate factors predicting its occurrence. Methods: We administered questionnaires to 500 cancer patients who were scheduled for staging CT scans of the chest, abdomen and/or pelvis. Inclusion criteria were no history of PE or DVT or concurrent treatment with anticoagulants. Questionnaires ascertained demographics, medication history and concomitant symptoms. Two radiologists evaluated all CT scans independently and confirmed the diagnosis of VTE in consensus. Physicians were notified of their patient's diagnosis of unsuspected VTE. Fisher's exact test was used to examine differences between cases and controls. Results: Of the 500 patients evaluated, 6 did not meet the inclusion criteria and 13 did not complete the questionnaire; 481 were analyzed; 48.8% were female; mean age was 57.9 years. Twelve patients were diagnosed with unsuspected VTE: 2.4% (95%CI 1.0; 3.8); 9 had PE and 3 had iliac/femoral thrombi; 8 were women, mean age was 57.2 years. All VTE patients had a stage 3 or 4 solid tumor; 4 had colon cancer; 2 lung cancer. Four patients received treatment with bevacizumab, 3 with cisplatin and 2 with carboplatin. Comparing cases (unsuspected VTE) with controls, no differences were observed in age. Significant differences were observed with any chemotherapy (83.3% vs 26.5%, p<0.0001), bevacizumab (37.5% vs 6.4%, p<0.02), catheter use (50% vs 13.5%, p<0.003), abdominal pain (41.7% vs 11.8%, p<0.01). Following the diagnosis of unsuspected VTE, 6 patients received treatment (5 anticoagulation, 1 aspirin). Conclusions: Our study confirms the presence of unsuspected VTE in cancer patients undergoing staging CT. Concomitant treatment, catheter use and abdominal pain were related to unsuspected VTE. Not all patients were treated for their VTE, possibly reflecting the lack of clear guidelines to manage these patients. No significant financial relationships to disclose.