tbuckley/cabot-search huggingface dataset:
Phase 2 trial of Symptom screening with Targeted Early Palliative care (STEP) for patients with advanced cancer.
Authors: Camilla Zimmermann, Breffni Hannon, Monika K. Krzyzanowska, Madeline Li, Gary Rodin, Ashley Pope, Nadia Swami, Mohana Giruparajah, Doris Howell, Amit M. Oza, David Warr, Jennifer J. Knox, Natasha B. Leighl, Srikala S. Sridhar, Rebecca M. Prince, Stephanie Lheureux, Aaron Richard Hansen, Christopher M. Booth, Deborah Jane Dudgeon, Lisa W Le
Journal: Journal of Clinical Oncology (2019)

11604 Background: Routine early palliative care (EPC) by specialized teams improves quality of life for patients with advanced cancer, but may not be scalable. To plan for a larger randomized controlled trial, we conducted a phase 2 trial of STEP, a novel intervention of targeted EPC based on symptom screening. Methods: Participants with advanced cancer, ECOG 0-2, and clinical prognosis ≥6 months were recruited from lung, gastrointestinal, genitourinary, breast and gynecology outpatient clinics. Symptoms were screened at every outpatient visit using the Edmonton Symptom Assessment System-revised (ESAS-r). Moderate to severe symptom scores (≥4/10 for pain, nausea, dyspnea, depression, anxiety; ≥7/10 for fatigue, appetite, drowsiness, well-being) triggered an e-mail to a nurse, who called the patient, offering an EPC visit. Participants completed outcome measures at baseline, 2, 4 and 6 months (primary endpoint). Trial feasibility criteria were: i) ≥100 patients accrued in 12 months; ii) ≥70% complete screening for ≥70% of visits; iii) ≥60% of those for whom a call is triggered meet at least once with the EPC team; iv) ≥60% complete measures at each endpoint. Results: From 11/2016-1/2018, 116 patients were enrolled; 89/116 (77%) completed screening for ≥70% of visits and 59% (69/116) received a call triggered by symptoms. Of those receiving a call, 62% (43/69) received EPC; 3 further patients were referred by their oncologist. Measure completion was 79% (81/116) at 2, 61% (71/116) at 4, and 57% (66/116) at 6 months. By trial end (6 months), patients who received a call and accepted EPC involvement had better symptom control (ESAS-r-CS mean change in those receiving vs. deferring EPC: -0.07±16.9 vs 11.8±13.7, p = 0.02) and less deterioration in mood (PHQ-9: -0.4±3.4 vs 2.6±2.3, p = 0.003). There was no difference between those receiving versus deferring EPC in quality of life (FACIT-Sp: -4.7±13.6 vs -3.2±15.4, p = 0.75; QUAL-E: -2.6±8.4 vs -1.5±11.0, p = 0.62), or satisfaction with care (FAMCARE-P-16: -3.2±7.9 vs -3.5±6.1, p = 0.79). Conclusions: STEP is feasible in patients with advanced cancer. More than half of patients have moderate to severe symptoms, and acceptance of the triggered EPC visit should be encouraged.
Gallbladder perforation related to bevacizumab in a patient with lung adenocarcinoma.
Authors: Basak Oyan, Mehmet Akif Ozturk, Murat Kalayci
Journal: Journal of Clinical Oncology (2013)

e20723 Background: Gastrointestinal perforation is one of the most important complications of bevacizumab. In patients with metastatic non-small cell lung cancer, gastrointestinal perforation has been reported with an incidence of less than 1%. Gallbladder perforation in patients receiving bevacizumab is a very rare complication. Methods: A 66-year-old male patient with stage IV lung cancer (adenocarcinoma) admitted to emergency room with the complaints of right upper quadrant abdominal pain, fever, emesis and no bowel movements, seven days after the 3 rd cycle of pemetrexed-cisplatin and bevacizumab chemotherapy. CT scan of abdomen showed air images adjacent to the gallbladder suggesting a perforation and an abscess formation of 3.5x3 cm in diameter. The patient underwent surgery. There was a defect of 2 cm in gallbladder wall and there were 4 gallstones inside the gallbladder. Cholecystectomy was performed and the abscess localized between the gallbladder and liver was drained. The pathological examination showed bleeding areas and atrophy in mucosa. No tumor involvement and no microthrombi in microvessels were seen. After recovery, bevacizumab was permanently discontinued. Results: Based on reports from FDA, there are 15 cases of bevacizumab-induced gallbladder perforation, excluding the described case. When the characteristics of the patients are analyzed, it was seen that 75% of gallbladder perforations occurred within the first 6 months of therapy. Most cases were under treatment for gastrointestinal malignancies. Our case is the fifth case with the diagnosis of lung cancer. Although the coexistence of cholelithiasis in other cases is unknown, chronic inflammation in addition to the disruption of vascular regeneration by bevacizumab may increase the risk of gallbladder perforation. Conclusions: Chronic inflammation related to cholelithiasis can be a predisposing factor of bevacizumab-induced gallbladder perforation. Therefore, caution should be exercised when treating these patients with bevacizumab.
Tackling Epilepsy With High-definition Precision Medicine
Authors: Hugh Kearney, Susan Byrne, Gianpiero L. Cavalleri, Norman Delanty
Journal: JAMA Neurology (2019)

Various types of epilepsy are a leading cause of neurological disability worldwide; they have in common a propensity to recurrent unprovoked seizures. There is increasing interest in the concept of precision medicine for therapy. While treatment aimed at the level of an ion channel or single pathway has provided benefits for a small number of individuals with genetically mediated cases, a high-definition approach extending beyond genes to a broader array of personalized factors may improve outcomes.Advances in sequencing technologies have driven genetic discovery in epilepsy. This has provided targets for precision medicine in monogenic types of epilepsy. However, these typically represent a small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure reduction. Such a unifocal view may overlook neurodevelopmental and neuropsychiatric comorbidities, which can be more challenging than the seizures themselves. Therefore, a panoramic approach to treatment encompassing both molecular diagnostic techniques and amelioration of network function by addressing factors beyond seizure reduction may be considered as part of a high-definition approach to tackling epilepsy.High-definition medicine will require the development of analytical techniques, including artificial intelligence, that use and combine behavioral, environmental, molecular genomic, chronotype, and microbiomic data to offer the best individualized therapeutic options for disease management in each person with epilepsy. While an accurate molecular diagnosis remains the first step of the iterative process to the development of a precision medicine for an epilepsy, treatment targeted at a single molecular pathway may reduce seizure frequency but are not likely to address the multiple comorbidities associated with involved aberrant neural networks. To provide an improvement in precision medicine for epilepsy, a high-definition approach may be required that encompasses a panoramic view of factors that can be manipulated either directly or indirectly, now and in the future.
Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer
Authors: Xianyu Zhang, Weiwei Zhao, Wei Wei, Zilong You, Xiaohua Ou, Mingming Sun, Yanling Yin, Xiaoyan Tang, Zhen Zhao, Changming Hu, Feifei Liu, Junhao Deng, Linlin Mao, Danyan Zhou, Yuxia Ren, Xiaoxia Li, Shangfei Zhang, Chang Liu, Jingshu Geng, Guodong Yao, Bingbing Song, Yupeng Liu, Dalin Li, Yongdong Jiang, Yanbo Chen, Yashuang Zhao, Shihui Yu, Da Pang
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer. Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. Results: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. Conclusions: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.
The utility of HCC screening among cirrhotics
Authors: P. Niravath, T. Hayes, S. Hilsenbeck
Journal: Journal of Clinical Oncology (2007)

15108 Background: Screening known cirrhotics for hepatocellular cancer (HCC) has long been a contentious topic. Studies to date have failed to conclusively prove or disprove the validity of AFP and hepatic ultrasound as screening mechanisms for HCC among cirrhotics, particularly in the American population. It is not clear whether these screening mechanisms provide any benefit in terms of reduced morbidity and mortality. Methods: The study examined all cirrhotics who developed HCC at the Houston Veterans Affairs Medical Center between 1999 and 2005. Those who were screened with AFP and/or imaging (either ultrasound, triphasic liver protocol CT, or MRI) were compared to those patients who were not screened at all. The screened and unscreened patients were compared in terms of Barcelona Clinic Liver Cancer Stage (BCLC) at the time of diagnosis. Results: Statistical analysis revealed a significant difference between the screened and unscreened groups in terms of BCLC stage at diagnosis, with the unscreened group being diagnosed at later stages than the screened group. Of the 155 patients observed, 26 were appropriately screened, and 129 were not. The BCLC stages at diagnosis for the two groups are shown in the table . The different trend in the two groups was found to be statistically significant with a p-value of 0.004. Furthermore, among the screened group, no particular method of screening (AFP vs. imaging vs. combination) was shown to be superior to another. Conclusions: Screening for HCC among cirrhotics using AFP and/or imaging every 6 months does correlate with HCC diagnosis at an earlier BCLC stage, thus portending better treatment options and improved prognosis. Therefore, screening all known cirrhotics for HCC may lead to decreased mortality. [Table: see text] No significant financial relationships to disclose.
Active immunotherapy in patients with progressive disease (PD) after first-line therapy: Racotumomab experience.
Authors: Roberto E Gomez, Saily Alfonso, Eduardo Rafael Santiesteban, Elia Neninger, Maria Laura Ardigo, Ana Maria Vazquez, Tania Crombet, Rolando Perez, Agustin Lage, Amparo Macias
Journal: Journal of Clinical Oncology (2013)

3086 Background: Racotumomab is a therapeutic vaccine that induces a cellular and humoral immune response against NeuGc-containing gangliosides expressed in several tumors but not in normal human tissues. A previous randomized, double blinded, placebo-controlled trial has demonstrated low toxicity of racotumomab and a statistically significant benefit in overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) who had achieved partial or complete response or disease stabilization after first line therapy. Methods: An open, non-randomized study was performed to evaluate if racotumomab could also be beneficial in patients with progressive disease. Patients with recurrent and advanced stages (IIIB/IV) of NSCLC, in progression after completion of first-line onco-specific treatment as per the NCCN Oncology Therapeutic Guidelines (surgery, chemotherapy and/or radiotherapy) were included in the study. Most of them had received 4 to 6 cycles of cisplatin/vinblastin. Vaccination consisted of 5 intradermic doses of racotumomab (1 every 14 days), followed by 1 dose every 28 days until patient refusal or worsening of ECOG status. The patients did not receive second-line therapy. Results: 180 patients were included in an intent to treat (ITT) survival analysis (Kaplan Meier estimate), after at least 10 months of follow-up. Median survival was 8.06 months. OS rate (%) at 24 months was 21%. A control group of 85 consecutive patients treated at the same institution by the same investigators, who did not receive second-line therapy or racotumomab showed a median survival of 6.26 months (log rank test p= 0.011). OS rate (%) at 24 months was only 7%. A per protocol survival analysis including only the 124 patients (68.8%) who received ≥ 5 doses of racotumomab showed a median survival of 12 months. OS rate (%) at 24 months was 30%. Conclusions: Patients with PD after first-line treatment show favorable results in survival when vaccinated with racotumomab. This result is similar to previous clinical trials where racotumomab was administered to patients with objective response (partial or complete) or stable disease after first line therapy.
Pain assessment behavioral scale in agonic cancer patients: Experience in total care—An end-of-life care home service.
Authors: Maricarmen Alfaro, Raquel Baldeos, Beatriz Rosales, Maria Berenguel, Alfredo Aguilar
Journal: Journal of Clinical Oncology (2012)

e19636 Background: Assessing pain in nonverbal, especially agonic cancer patients is a great challenge. In the absence of self-report, measurement of pain could be difficult and patient`s behavior could be useful. The aim of this work was to evaluate the Pain Assessment Behavioral Scale (PABS) in cancer agonic patients. Methods: PABS scale was used to evaluate 118 cancer patients enter in agony. Pain levels was categorized according to PABS score in Mild Pain (score 1-3), Moderate Pain (score 4-5), Severe Pain (score&gt;6). We correlated levels of pain with age, sex, cancer metastatic site or active tumor localization with the ANOVA, Chi square or Fisher tests when were appropriated. A P&lt;0.05 was considered significant. Results: Fifty two patients (44.1%) were male and 66 female (55.9%). The median age was 74 (Standar Deviation [SD]:13.1; Range: 30-94). Most frequent primary tumors were colorectal (16%), lung (11%), Pancreas (9.3%), Breast (8.5%), lymphomas (6.8%), prostate (6.8%) and gastric (5.6%) cancer. Involvement of primary active tumor or active metastases was present in lung (22%), Central Nervous System (CNS) (13.6%), liver (22%), and bone (7.6%). The median of PABS score was 5 (SD=1.25; range: 2 – 8). Seven cases had mild pain (5.9%), 105 moderate pain (89%) and 6 severe pain (5.1%). There was no correlation of pain levels with age (P=0.420), sex (P=0.098), active tumor or metastatic involvement of lung (P=0.321), CNS (P=0.972), Liver (P=0.575) or bone (P=0.529). Conclusions: In our experience, PABS scale is a useful tool to evaluate pain in agony cancer patients. We found no correlation between active tumor or metastatic localization with the intensity of pain.
Association of interleukin-1 gene polymorphisms with gastric cancer: A meta-analysis
Authors: B. Vincenzi, D. Santini, G. Patti, F. Pantano, O. Venditti, L. Rocci, A. Frezza, R. Coppola, F. Graziano, G. Tonini
Journal: Journal of Clinical Oncology (2007)

21142 Introduction: Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the original studies. Materials and Methods: We searched the MEDLINE, CENTRAL, and PubMed databases (last research performed on July 2005) and reviewed cited references to identify relevant studies. Search key words were: gastric cancer (OR stomach cancer OR gastric adenocarcinoma OR stomach adenocarcinoma) and IL-1 (OR IL1). The literature review identified 23 titles that met the search criteria. Data from 15 articles that investigated the association between any of IL-1B-511 and IL-1B-31 polymorphisms and gastric cancer met the inclusion criteria, and they were included in the meta-analysis. Eight studies evaluated the role of IL-1B-511, four the role of IL- 1B-31 and three investigated both IL-1B-511 and IL-1B-31. Results: By pooling all the studies identified, our study shows that individuals IL-1B-31T carrier have got an increased risk developing gastric cancer (OR of 1.25; 95% CI 1.06–1.47) in particular in Caucasian sub-group (OR of 1.41; 95% CI 0.97–2.05). IL-1B-31CC genotype confers a decreased risk (OR of 0.80; 95% CI 0.68–0.95) especially in Caucasian population (OR of 0.71; 95% CI 0.49–1.03) compared to Asians (OR of 0.83; 95% CI 0.69–0.99). This association might be explained with the well-known near complete linkage disequilibrium between IL1B-511T and IL1B-31C polymorphism. Furthermore our results suggest a strong association between IL1B-511T polymorphism and gastric cancer risk only in Caucasians and not in Asians. Conclusions: In conclusion, although affected by the common bias of each epidemiologic studies, this pooled analysis suggests that IL1B-511T polymorphism is associated with an increased risk of developing gastric cancer in Caucasian population. No significant financial relationships to disclose.
Long-term survival of women with breast cancer with ≥10 lymph nodes at diagnosis.
Authors: Ludimila Cavalcante, Simon B. Zeichner, Gabriel P Suciu, Ana L. Ruiz, Alicia Hirzel, Almos Trif, Elisa Krill-Jackson
Journal: Journal of Clinical Oncology (2013)

e11575 Background: Axillary lymph node status is one of the most important prognostic factors in patients with breast cancer, and those with more than ten metastatic lymph nodes at diagnosis have a decreased overall survival. The purpose of this study is to better characterize the clinical course of this high-risk, poorly described patient population and determine the factors associated with long-term survival. Methods: A retrospective cohort analysis of all breast cancer patients with greater than ten metastatic lymph nodes diagnosed at Mt. Sinai Medical Center from January 1990 to December 2007 (n= 175). Descriptive frequencies, overall median survival (OMS), 5- and 10-year survival were calculated for standard prognostic factors and treatment variables. Univariate statistical analysis was performed, followed by a multivariate prognostic analysis for time-to-event data, using the Cox and extended Cox regression model. Results: The majority of patients were non-Hispanic white females between the ages of 56-70, diagnosed between 1990-1999, with tumors between 2-5 cm and 10-15 metastatic lymph nodes. Most were ER/PR positive, HER2 negative, and treated with surgery, chemotherapy, radiation and hormonal therapy. The OMS was 94 months (CI = 69-114) with 5- and 10-year survival rates of 64.3 and 41.6%, respectively. Ages between 21-45 years (OMS of 187 months, p = 0.03), tumors less than 2 cm (146 months (95% CI = 85-198), p = 0.02), ER positivity (131 months (95% CI = 94-157) vs. 39 months (95% CI = 27-59), p = 0.0003) and treatment received between 2000-2003 (98 months (95% CI = 55-133), p = 0.02) were all associated with significantly improved survival. Conclusions: Over the past decade there were significant gains in the long-term survival of breast cancer patients with greater than ten positive nodes at diagnosis, possibly due to improvements in multimodality therapy, such as the introduction of taxanes, although stage migration may be another contributing factor. Our study further showed an encouraging survival for ER positive patients and a dismal one for ER negative patients, highlighting the need for new targeted therapies directed towards ER negative tumors.
Neurological morbidity in survivors of childhood acute lymphoblastic leukemia (ALL)
Authors: B. Morris, R. Khan, D. Ledet, C. Howell, C. Pui, M. Hudson, K. Ness
Journal: Journal of Clinical Oncology (2009)

9529 Background: The majority of children diagnosed with ALL over the past two decades have achieved long-term survival. This remarkable success is attributed in part to intensive central nervous system (CNS)-directed therapy that effectively prevents CNS relapse. Because treatment-related neurological morbidity is recognized but poorly characterized, the objective of this cross-sectional study was to estimate the prevalence of neurological symptoms and signs in long-term survivors of childhood ALL. Methods: After obtaining IRB approval, all long-term ALL survivors (≥ 5 years since diagnosis) aged 6–28 years who remained active patients at our institution were identified. All participants completed a questionnaire consisting of independent (and when possible validated) instruments designed to identify various neurological symptoms, as well as, a comprehensive and standardized neurologic examination by a board-certified neurologist. Results: Of the 433 potentially eligible subjects, 162 (37.4%) were enrolled. Participant demographic information and previous treatment exposure were similar to those not enrolled in the study. The rates of endorsed neurological symptoms were: neuropathy (40.1%), dizziness (33%), back pain (22.8%), fatigue (19.1%), falls (15.4%), headache (14.8%), seizures (10.5%), urinary incontinence (8.6%), and stroke (1.2%). Neurological examination confirmed an underlying sensory neuropathy in 44 patients (27.3%). Otherwise, signs of chronic cranial nerve dysfunction (1.9%) and motor weakness (5.6%) were rare. Conclusions: Symptoms and signs of a chronic sensory neuropathy, presumably from previous vincristine exposure, were evident in many patients. Complaints of fatigue, dizziness, and chronic back pain were also relatively common. The number of patients who routinely fall is of concern. Whether these falls are associated with symptoms/signs of neuropathy, weakness, and/or dizziness will require further analysis. Although headache was a common complaint, its prevalence may not differ significantly from a normal age-matched population. No significant financial relationships to disclose.
Leptomeningeal Metastasis in Carotid Body Paraganglioma
Authors: Sarthak Tripathy, Nishikant Avinash Damle, Priyanka Naranje, Shamim Ahmed Shamim, Madhavi Tripathi, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2019)

Abstract Carotid body paragangliomas are mostly benign tumors with very rare propensity to metastasize to lymph nodes, bones, liver, and lungs. Leptomeningeal metastasis from a carotid body paraganglioma is a very rare phenomenon. We describe 68 Ga-DOTANOC PET-CT findings of a 33-year-old man, a known case of metastatic paraganglioma who underwent scan for response assessment to everolimus therapy.