tbuckley/cabot-search huggingface dataset:
Challenges in management of advanced neuroblastoma: Experience at Tata Memorial Hospital, Mumbai, India
Authors: G. Biswas, P. Kurkure, S. Banavali, S. Achrekar, P. Kulkarni, R. Bhagwat, L. Sharma
Journal: Journal of Clinical Oncology (2004)

8562 Background: Poor therapeutic response in advanced neuroblastoma prompted us to implement St. Jude's Protocol [NB - 84, TMH NB-2] since 1987 and Ifosfamide based chemotherapy [ICE, TMH NB-3] since 1996 with the aim to improve survival rate with manageable toxicities.Methods: 128 cases of neuroblastoma from 1987 to 2000 were analysed. In infants (n = 29) median age at presentation 9 months, duration of symptoms 60 days, M: F:: 1.6: 1. An asymptomatic abdominal mass (62%) as a commonest presenting symptom & primary site (62.1%). Stage III(17), IV(1) received 6 # of adriamycin & cyclophosphamide or 1 -2 # of adriamycin, cyclophosphamide, Cisplatin & Etoposide. Surgery considered after 3/6 # or 1/2# of chemotherapy respectively. In children > l year (n=99) median age at presentation 48 months, duration of symptoms 60 days, M: F:: 1.3: 1. Commonest presenting symptom as fever (51%) & primary site as abdomen (66.7%). Stage IIB(3),III(30), IV(60) received 1cycle of TMH NB-2 as induction followed by either 2# of TMH NB-2 or 4 # TMH NB-3 as consolidation. In StageIII surgery offered after induction, whereas in stageIV at the end of consolidation. Radiotherapy or 131I MIBG treatment was given where surgery not feasible or in R1 resection. ABMT was offered for gross residual disease when economically feasible & 13 Cis Retinoic acid for minimal residual disease in stage IV. Results: Infantile group 62% constituted intermediate risk (stage III, IV). Overall response (CR+VGPR+PR) to therapy was 97%. OS is 75.06%. 58% are alive & disease free at a median follow-up of 42.9 months. In children>1year 94% constituted high risk (IIB, III, IV).74% showed response to therapy. OS is 54.31%. 18.6 % are alive & disease free at a median follow up of 14.9 months. Conclusions: High risk patients remains an area of concern in our setting. Proper risk stratification has not been possible at our center & remains the main constraint in tailoring therapy. Innovative & aggressive treatment strategies to improve survival & response rates now remains a need of time. No significant financial relationships to disclose.
A double-blind, placebo-controlled study of once-weekly epoetin alfa in children with cancer undergoing myelosuppressive chemotherapy
Authors: B. I. Razzouk, M. Hockenberry, P. S. Hinds, W. Rackoff, J. D. Hord
Journal: Journal of Clinical Oncology (2004)

8527 Background: This study was designed to assess the effect of epoetin alfa (EPO) on hemoglobin (Hb) and quality of life (QOL) in children with cancer receiving myelosuppressive chemotherapy (CT). Methods: This was a double-blind, placebo (PBO)-controlled study of pts aged 5–18 y with malignant solid tumors (ST), Hodgkin's lymphoma (HL), acute lymphocytic leukemia (ALL), or non-Hodgkin's lymphoma (NHL) and Hb <12 g/dL. Pts were stratified by tumor type (ST/HL or ALL/NHL) and randomized 1:1 to receive IV EPO 600 U/kg or PBO weekly for 16 wks. Primary end point was pt-reported Peds Quality of Life Inventory (PedQL-I™) Total Score; secondary endpoints included parent-reported PedsQL-I and pt- and parent-reported PedsQL Cancer Module (PedsQL-CM: Cognitive Problems, Communication, Nausea, Pain and Hurt, Physical Appearance, Procedural Anxiety, Treatment Anxiety, Worry), Hb, and transfusions. QOL was assessed using age-specific (5–7 y, 8–12 y, 13–18 y) versions of each tool. Results: 222 pts (111 EPO, 111 PBO) were included in the intent-to-treat analysis: 27 HL, 98 ST, 75 ALL, and 22 NHL. Neither the pt- nor parent-reported PedsQL-I Total Score was significantly different between groups at last value. A significant improvement was seen in the pt-reported PedsQL-I Total Score in pts 5–7 y (EPO, n = 13; PBO, n = 32) receiving EPO vs PBO (P =.043). Pt- and parent-reported Cognitive Problems scores were improved in ALL/NHL pts receiving EPO vs PBO (P=.026 and P=.014, respectively), but no other PedsQL-CM domain. Mean Hb change at last value was not significantly different between groups. Repeated-measures analysis of Hb showed an improvement favoring EPO (P =.012). More pts treated with EPO vs PBO were transfusion free (36% vs 23%; P=.038). Death, serious adverse event, and discontinuation rates were similar in both groups. Conclusions: IV EPO was well tolerated in pediatric cancer pts. Although few differences between QOL scores were detected, there was significant improvement in QOL in pts aged 5–7 y and improved Cognitive scores in ALL/NHL pts. EPO pts had greater increases in Hb and a significant reduction in transfusions vs PBO. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson ILEX Oncology, Inc.; Johnson & Johnson; Ortho Biotech Products, L.P. Johnson & Johnson Ortho Biotech Products, L.P. Ortho Biotech Products, LP
The KRAS-variant and treatment response in BATTLE-1.
Authors: Joanne B. Weidhaas, Edward S. Kim, Roy S. Herbst, Jun Yu, Frank Slack, George R. Blumenschein, Anne S. Tsao, Ignacio Ivan Wistuba, J. Jack Lee, Vassiliki Papadimitrakopoulou, Waun Ki Hong, John Heymach, Hai T. Tran
Journal: Journal of Clinical Oncology (2014)

8135 Background: The program, “BATTLE: Biomarker-integrated Approaches of Targeted Therapy of Lung Cancer Elimination” was initiated to establish individualized targeted therapy for NSCLC patients for whom standard therapy had failed. This trial prospectively examined patient tumor biomarker profiles, and assigned them to corresponding targeted therapies (erlotinib, vandetanib, bexarotene+erlotinib, and sorafenib). The primary end-point was 8-week disease control (DC) rate, with a secondary endpoint of overall survival (OS). The KRAS-variant is a germ-line mutation that predicts increased NSCLC risk, as well as tumor biology across numerous cancer types. Methods: 161 patients from the BATTLE-1 clinical study with sufficient DNA available were tested for the KRAS-variant. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Log-rank test was used to test the difference in survival distributions among groups. Results: Overall, 16 BATTLE patients had the KRAS-variant, 10.2% (11/107) without tumor acquired EGFR or KRAS mutations (WT), 4.3% (1/23) with tumor acquired EGFR mutations, and 9.7% (3/31) with tumor acquired KRAS mutations. For the primary objective of the study of 8-week DC, KRAS-variant patients faired worse (48.5% non-variant vs 28.6% KRAS-variant patients). For WT patients, the KRAS-variant predicted borderline worse OS (p=0.072) and significantly worse PFS (p=0.01). The impact of the KRAS-variant on outcome depended significantly on treatment type. KRAS-variant patients treated with Erlotinib had significantly worse PFS (p=0.001). KRAS-variants patients treated with Vandetanib had significantly worse OS (p=0.029). However, KRAS-variant patients treated with Sorafenib had borderline improved OS (p=0.056). For Sorafenib treated patients with tumor acquired KRAS mutations, those with the KRAS-variant had significantly improved PFS (p=0.045) vs non-variant patients. Conclusions: The KRAS-variant appears to be a predictive biomarker in NSCLC, regardless of tumor acquired KRAS and EGFR mutations. These findings will be further investigated in the BATTLE2 trial as well as RTOG 0617 to confirm the potential of the KRAS-variant to be employed to direct treatment for NSCLC patients. Clinical trial information: NCT00409968.
Patients survival after radical and palliative surgical treatment of gastrointestinal melanoma metastases.
Authors: Gianfranco Gallino, Roberto Patuzzo, Andrea Maurichi, Roberta Ruggeri, Ilaria Mattavelli, Gabriella Nicolò, Annabella Di Florio, Giulia Elisa Bonarini, Adele Di Fazio, Giampiero Castelli, Stefano Signoroni, Mario Santinami
Journal: Journal of Clinical Oncology (2015)

e20104 Background: Malignant melanoma represents one of the most common malignancies metastasizing to gastrointestinal tract. The aim of this study was to investigate the outcome of patients undergone therapeutic or palliative surgery for melanoma metastases to gastrointestinal tract. Methods: The clinicopathological data of 90 stage IV melanoma patients undergone surgical resection for gastrointestinal metastases at the National Cancer Institute of Milan from 1985 to 2014 were evaluated. The performed surgical procedures were radical or palliative resections. Results: The intent of surgery was palliative in 60 patients (66.7%) and curative in 30 (33.3%). The 5-year survival for the whole patients who received complete and incomplete resections were 28% and 4% respectively (p < 0,001). A radical surgery performed in the gastrointestinal tract resulted to be related to a better survival irrespectively to the presence of melanoma metastases in other districts. Also a palliative surgical treatment was related to higher survival rates nevertheless this procedure was conducted with the evidence of melanoma relapse in other organs. Conclusions: Radical and palliative surgery of gastrointestinal melanoma metastases was related to an improve of survival for melanoma patients, even in presence of synchronous metastases to other organs. These findings could be of further relevance in order to candidate selected patients to targeted therapies.
Oncologist preferences in advanced soft tissue sarcoma: A discrete choice experiment.
Authors: Lisa M. Hess, Jasmina I Ivanova, Viviana Garcia Horton, Sophia Graham, Olivia Liu, Yajun Zhu, Maria Lorenzo, Steven J. Nicol
Journal: Journal of Clinical Oncology (2017)

147 Background: Soft-tissue sarcomas (STS), a rare heterogeneous group of cancers originating in the muscle, fat, blood vessels or other fibrous/connective tissues, account for 1% of all cancers diagnosed annually in the US. The National Comprehensive Cancer Center guidelines include a wide range of regimens that lack supporting randomized trial evidence, and there are few treatment pathways to guide treatment decision making. A discrete choice experiment (DCE) was conducted to quantify the relative value of overall survival (OS), progression-free survival (PFS), tumor response rate (RR), risk of hospitalization due to side effects, and convenience of therapy (days per month to administer treatment) among oncologists. Methods: An online DCE survey was administered to oncologists recruited from an online panel, who were licensed to practice in the US at the time of the survey and prescribed chemotherapy to patients with STS. Oncologists were asked to choose between pairs of hypothetical treatments characterized by a common set of attributes: OS (14, 20 or 26 months), PFS (3, 5 or 7 months), RR (12, 18, or 26%), risk of hospitalization due to side effects (12, 30 or 46%), and days/month to administer treatment (1, 2 or 4 days). A hierarchical Bayes model was used to analyze preferences, the relative importance of treatment attributes (from 0-100%), and trade-offs between attributes. Results: 160 eligible oncologists completed the survey: 74% male; 41% private practice; and 64% affiliated with an academic teaching hospital. OS had the highest relative importance (44.6%, standard deviation, SD, 16.0%), followed by the risk of hospitalization (18.4%, SD 8.3%). PFS, RR, and days to administer treatment had lower relative importance (16.5%, 10.6%, and 9.9%, respectively). For a 1-month increase in OS, oncologists were willing to trade off 8.9 percentage points increase in hospitalization risk, a 2.1 month reduction in PFS, 13.1 percentage points decrease in RR, and an additional 4.6 days/month to administer treatment. Conclusions: Oncologists in the US value maximizing the life of patients with STS while avoiding hospitalizations. Patient preference interviews are ongoing with patients with STS, which will be presented at the meeting.
Inpatient 100% mortality review at a NCI Comprehensive Cancer Center Hospital.
Authors: Angela Jain, Delinda Pendleton, Jamie Doyle, Stefan K. Barta, Mark A Hallman, Dwight D. Kloth, Kenneth Patrick, John A. Ridge
Journal: Journal of Clinical Oncology (2017)

88 Background: Fox Chase Cancer Center set about to identify opportunities to improve care (OIC) for cancer patients dying in the hospital. The team developed and tested a mortality review decision tree and paradigm that helped to identify OICs. Volunteer members of hospital staff representing most domains of patient care comprised the committee. Monthly meetings defined the review process, developed the form, initiated the program and refined the process as experience accumulated. Methods: Forms incorporated information from Temple University Hospital, Comprehensive Cancer Center Consortium for Quality Improvement(C4QI), and measures to be monitored by CMS. Deaths were considered “anticipated” or “unanticipated,” and with or without OIC. Issues in cases with OIC were recorded for each death. Level 1 review was completed by a research student or a member of the risk management team to organize clinical data. A level 2 review was then performed by a member of the committee and deaths were categorized. Level 3 review was undertaken at monthly meetings and action items determined. Results: From March 2014 to December 2015, 246 cases were reviewed. The elements were chosen for the level 1 &amp; 2 review and collating objective data. Whether the patient was treated with curative intent, procedures were definitive or palliative, if chemotherapy, radiation or surgery were delivered, or if there was a complication within the last 2 weeks of life were recorded. Hospitalization features such as institution of palliative care, appropriate advanced directives, code status on admission and at death, and ICU admission were noted. Issues often arose when deaths were expected and predicted at admission. Increased need for inpatient palliative care teams and hospice support have been recognized. Better communication between patients, families, and oncologists should reduce hospitalization for patients whose death is imminent. Conclusions: Submitting 100% of inpatient deaths to formal mortality review discloses opportunities to improve care and allows focus on problems that occurred even when the patient’s death was expected.
Utilizing patient navigators to enhance oral chemotherapy education and safety for at-risk patients.
Authors: Mingqian Lin, Douglas W Hackenyos, Daqin Mao, Feng Qing Wang, John Kalil Erban, Susan K. Parsons
Journal: Journal of Clinical Oncology (2017)

43 Background: Oral anticancer drugs are increasingly being used as standard therapy. At Tufts Medical Center Cancer Center, 10% of patients on active cancer treatment are receiving oral chemotherapy. To address barriers to medication education and timely management of treatment effects, we began an initiative involving our pharmacy specialist who reviews newly-started oral chemotherapy treatments for safety concerns, dose appropriateness, and drug interactions. In response to the cultural-linguistic needs of our Chinese patients (20% of our patients, largest minority group) and unique challenges of our patients of lower SES (40% of our patients), we are also leveraging patient navigators (PN) to improve timely care and understanding of and adherence to oral cancer medications for our most vulnerable patients. Methods: PN regularly interact with patients and work closely with the care team to address patients’ concerns. Formal PN visits with patients in clinic are documented in the EMR. To assess the scope of issues related to oral chemotherapy and/or supportive care drugs (e.g. anti-nausea, anti-constipation) and the potential impact in using PN, we reviewed PN encounter notes from the first 6 months of 2016 to identify patient-reported issues. Results: In reviewing 492 PN encounter notes from the first 6 months of 2016 (111 patients were navigated), 138 (28%) of all patient encounters involved assistance related to oral chemotherapy, supportive care drugs, and/or comorbidities medications. Examples of patient-reported issues include confusion about purpose and/or type of drug, dosing scheduling, side effects management, and logistical challenges (e.g. refills, copays, specialty pharmacy orders). Conclusions: From the PN encounter notes, we identified a need for more formalized patient-centered interventions to enhance education, monitoring, and patient-provider communication about oral chemotherapy to proactively resolve medication-related issues. We are piloting an evidence-based approach involving pharmacist-PN-patient teaching sessions, tailored patient education tools, and scheduled check-ins between PN and patients adapted from the MASCC Oral Agent Teaching Tool model.
Doxycycline Used As Post Transplant Antibacterial Prophylaxis Improves Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Stem Cell Transplantation.
Authors: Shaji K. Kumar, Angela Dispenzieri, Martha Q Lacy, Suzanne R Hayman, Francis K Buadi, David Dingli, Steven R Zeldenrust, Marina Ramirez-Alvarado, Prashant Kapoor, William Hogan, S. Vincent Rajkumar, Morie A Gertz
Journal: Blood (2012)
Abstract 53: PP1, a Derivative of Salubrinal, Ameliorate Ventricular Function After Myocardial Infarction in Rats
Authors: Chunlei Liu, Yunyun He, Kunlun He
Journal: Circulation Research (2015)

Objective: salubrinal, an inhibitor of ER-stress, has potent effect on cell injury. In this study, we investigated the effect of salubrinal and its derivative-PP1 on chronic heart failure induced by myocardial infarction ( MI). Methods: Male wistar rats were randomly divided into 5 groups:i) sham-operated; ii) vehicle (MI+ DMSO); iii) MI + salubrinal; iv) MI + PP1; v) MI + kaptopril. After 6 weeks treatment, transthoracic echocardiographic and hemodynamic parameters were evaluated. The cardiac tissue sections were subjected to TUNEL to assess the level of apoptosis. The expression of mRNA and protein involved in apoptosis, autophagy, ER stress was analyzed using real-time reverse transcription-polymerase chain reaction and western blotting, respectively. Results: The VW/BW and LVW/BW were reduced by salubrial and PP1.The LVEDD, LVESD were significantly decreased while the EF and FS were greatest increased by salubrinal and PP1. The hemodynamic parameters including CO, SV, LVEDV, LVESV, LVEDP, LVESP, +dp/dtmax, -dp/dtmax, +dv/dtmax, -dv/dtmax, Ea, Tau were ameliorated. By calculating the apoptotic index, we found that salubrinal and PP1 have a great anti-apoptotic effect. The mechanism analysis demonsted that salubrinal and PP1 have a cell protection effect through downregualtion of PERK, GRP78, chop, caspase12 and upregulation of p62 , LC3II, ATF4 as detected by real-time PCR and western blotting. Conclusions: The current study suggested that salubrinal and PP1 have a cell protection effect involed in ER stress related autophay and apoptosis.This may implicate that salubrinal and PP1 may be a potent compound for the treatment of chronic heart failure.
Referral to infertility counseling in cancer patients undergoing chemotherapy.
Authors: Amanda Redden Hathaway, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2017)

220 Background: Reproductive concerns in survivorship are associated with distress, depression and anxiety. Patients who receive pretreatment fertility counseling report a better quality of life after treatment. Despite this, only about 50% of patients in studies recall discussion of fertility issues prior to chemotherapy. Methods: A retrospective review was conducted to evaluate discussion of fertility in patients ages 19-35 seen at the University of Alabama at Birmingham Hematology/Oncology clinic from 1/1/15-12/31/15. Patients who never received therapy that could alter their childbearing potential were excluded. Patients’ sex, age at diagnosis, type of cancer, documented discussion of fertility implications prior to therapy, and referral to Reproductive Endocrinology (REI) were documented. Rates of discussion of fertility risks and rate of referral were determined. Results: Fifty-four patients met inclusion criteria for the study. 46.3% were female. 30 patients (55.6%) had a hematologic malignancy and 24 patients (44.4%) had a solid tumor malignancy. Documentation of fertility risk was seen in 33.3% of patients with 29.2% referred to REI. Seven (24.1%) patients had hematologic malignancies and eight (33.3%) had solid tumors were referred to REI. Of the 25 female patients, only five (16.7%) were referred to REI, whereas another five patients could have been deemed not suitable for referral due to previous surgery or metastatic disease making the appropriate referral rate of 25%. Of the 29 male patients, nine were referred to REI, one had semen analysis without REI referral, and one refused REI evaluation making overall referral rate 34.5%. 35 of the 54 patients received their initial chemotherapy at our facility, and of those 34.3% were referred to REI. Conclusions: Despite guidelines recommending discussion of fertility risks with all patients of child-bearing age prior to chemotherapy, less than half of patients at our institution are referred to REI. [Table: see text]
Re-engineering the Pancreas Tumor Microenvironment: A "Regenerative Program" Hacked
Authors: Gerard I. Evan, Nasun Hah, Trevor D. Littlewood, Nicole M. Sodir, Tania Campos, Michael Downes, Ronald M. Evans
Journal: Clinical Cancer Research (2017)

Abstract The “hallmarks” of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks. Defined as genomic regions containing clusters of multiple enhancers, super enhancers play pivotal roles in cell/tissue specification, identity, and maintenance. Hence, interfering with such super enhancer–driven repair networks should exert a disproportionately disruptive effect on tumor versus normal pancreatic tissue. Novel drugs that directly or indirectly inhibit processes regulating epigenetic status and integrity, including those driven by histone deacetylases, histone methyltransferase and hydroxylases, DNA methyltransferases, various metabolic enzymes, and bromodomain and extraterminal motif proteins, have shown the feasibility of disrupting super enhancer–dependent transcription in treating multiple tumor types, including PDAC. The idea that pancreatic adenocarcinomas rely on embedded super enhancer transcriptional mechanisms suggests a vulnerability that can be potentially targeted as novel therapies for this intractable disease. Clin Cancer Res; 23(7); 1647–55. ©2017 AACR. See all articles in this CCR Focus section, “Pancreatic Cancer: Challenge and Inspiration.”