tbuckley/cabot-search huggingface dataset:
Concurrent temozolomide and radiation as the initial treatment for anaplastic glioma.
Authors: C. K. Tham, S. See, S. H. Tan, W. H. Ng, K. H. C. Lim, J. Thomas, E. T. Chua
Journal: Journal of Clinical Oncology (2011)

2051 Background: Concurrent temozolomide (TMZ) and radiation (RT) is often used as initial treatment for anaplastic gliomas based on the positive findings of phase III trials in glioblastoma multiforme. However, there is no prospective randomized data currently to prove the efficacy of the combined modalities for anaplastic glioma. We aim to investigate if the addition of TMZ to RT is better than RT alone for the initial treatment of anaplastic glioma. Methods: Patients with anaplastic astrocytoma or oligoastrocytomas treated at our centres between year 2000 to 2010 were reviewed. Only patients who received upfront RT or concurrent TMZ and RT (TMZ-RT) were included. Results: Sixty-two patients were included. Majority of the patients (n=55; 88.7%) were 65 years old or younger. Thirty-six (58.1%) patients had tumour resection while the remaining had biopsy only. Twenty-one patients (33.9%) had oligodendroglial component in the tumour histology. Patient demographics were comparable between the two groups except that the patients who had TMZ-RT had higher Karnofsky performance status score (KPS) compared to those who received RT alone. Median progression-free survival (PFS) was 16.7 months (95% CI: 9.40, 34.83 months) for patients who had RT alone and 14.8 months (95% CI: 8.64, 28.58 months) for those who had TMZ-RT; the difference is not statistically significant. Univariable Cox regression analysis showed that surgical type (resection versus biopsy) was associated with PFS. After adjusting for surgical type and age, there is no statistically PFS difference between the two treatment arms. Median overall survival (OS) was 27.4 months (95% CI: 10.64, NE months) for patients who had RT alone and 34.1 months (95% CI: 19.81, 42.09 months) for those who had TMZ-RT; the difference is not statistically significant. Age, KPS and oligodendroglial were associated with OS in the univariable analysis. After adjusting for these factors, there is no statistically OS difference between the two treatment arms. Conclusions: Our data did not reveal any significant benefit of TMZ-RT compared to RT alone as the initial treatment of anaplastic glioma. Prospective randomized trials are needed to evaluate the optimal treatment for this disease.
Would women with breast cancer prefer to receive an antidepressant for anxiety or depression from their oncologist?
Authors: Daniel Curtis McFarland, Megan Johnson Shen, Kirk Harris, Amy Tiersten, John Mandeli, Jimmie Holland
Journal: Journal of Clinical Oncology (2015)

219 Background: Patient treatment preferences for the management of anxiety and depression influence adherence and treatment outcomes, yet breast cancer patient preferences for provider-specific pharmacologic management of anxiety and depression is unknown. This study examined breast cancer patients’ antidepressant prescriber preferences and their preferences for treatment by a mental health professional. Methods: Breast cancer patients (Stage 0-IV) were asked two questions: 1) “Would you be willing to have your oncologist treat your depression or anxiety with an antidepressant medication if you were to become depressed or anxious at any point during your treatment?”; and 2) “Would you prefer to be treated by a psychiatrist or mental health professional for problems with either anxiety or depression?” Additionally, the Distress Thermometer and Problem List, Hospital Anxiety and Depression Scale, Risky Families Questionnaire, and demographic information were assessed. Results: One hundred twenty-five participants completed the study. 60.4% were willing to accept an antidepressant from an oncologist and 26.3% preferred treatment by a mental health professional. 77.3% who were willing to receive an antidepressant from their oncologist reported either no preference or that treatment by a mental health professional didn’t matter (p = 0.01). Participants taking antidepressants (p = 0.02) or reporting high chronic stress (p = 0.03) preferred a mental health professional. Conclusions: The majority of patients accepted antidepressant prescribing by their oncologist; only a minority preferred treatment by a mental health professional. These findings suggest the benefit for promoting education of oncologists to assess psychological symptoms and manage anxiety and depression as a routine part of an outpatient visit.
Pre-clinical rationale for combination PI3K and BRD4 inhibition in advanced prostate cancer.
Authors: Paul Toren, Amina Zoubeidi, Jared Allman
Journal: Journal of Clinical Oncology (2016)

234 Background: The PI3K/Akt pathway is frequently activated in aggressive and resistant prostate cancer. Here we detail our pre-clinical evaluation of AZD8186, a novel β and δ selective PI3K small molecule inhibitor. Further, we investigate how increased transcription of the myc oncogene may represent a mechanism of resistance to monotherapy PI3K/Akt inhibition. Therefore, we further evaluated co-targeting strategies against both the PI3K/Akt pathway and the epigenetic reader protein BRD4. Methods: Human prostate cancer cell lines LNCaP and 22RV1 were tested for sensitivity to AZD8186 in vitro. Caspase-3 activity and flow cytometry were used to assess apoptosis. Western blotting and RT-qPCR were used to measure AR and myc pathway genes and protein expression. Castrate resistant LNCaP xenografts were treated with 10mg/kg and 25mg/kg doses of AZD8186 given orally 4 days on, 3 off. Results: In vitro results demonstrated sensitivity to AZD8186 with decreases in cell proliferation and increases in apoptosis. In vivo results demonstrated a dose-dependent decrease in tumor growth velocity with AZD8186 with on-target decreases in pAkt was observed in xenograft tumour samples. Further, increases in myc protein and mRNA levels were seen in xenograft samples treated with AZD8186 compared to control. Downstream increases in EGFR and IGF-IR mRNA transcripts induced by AZD8186 were also seen in vitro and in vivo. Increases in myc, EGFR and IGF-IR was also seen in cells and tumours treated with an Akt inhibitor. Addition of the BDR4 inhibitor JQ1 decreased the increase of myc induced by AZD8186 and also partially abrogated the increases in EGFR, IGFR. Greater suppression of PSA expression was seen with the combination of AZD8186 and JQ1 compared to AZD8186 and enzalutamide. Similar results were seen in the 22RV1 cell line. Conclusions: Inhibition of PI3K with AZD8186 inhibits growth of PTEN-negative LNCaP cells. However, feedback activation of myc and AR pathways occurs. We demonstrate BRD4 inhibition using JQ1 which co-targets both myc and AR feedback pathways as a rationale combination strategy with PI3K inhibition. This strategy warrants further investigation in prostate cancers with an activated PI3K/Akt pathway.
Enhanced recovery after surgery protocols as a management strategy following major pancreatic surgery.
Authors: Lavanniya Kumar Palani Velu, Vishnuvardhan Chandrabalan, Ross Carter, Colin McKay, Nigel B Jamieson, Euan Dickson
Journal: Journal of Clinical Oncology (2015)

396 Background: Enhanced Recovery After Surgery (ERAS) protocols have been shown to have positive effects on lengths of stay (LOHS) and resource utilisation without a rise in readmission and post-operative morbidity rates in colorectal, hepatic and oesophago-gastric surgery. This study aimed to investigate the effects of an ERAS protocol on postoperative morbidity and readmission rates following pancreatic surgery in a tertiary referral centre. Methods: The perioperative care of patients undergoing pancreatic surgery was guided by a locally developed ERAS protocol incorporating pre-operative counselling and carbohydrate loading. Intra-thecal opiate and Patient Controlled Analgesia devices were utilised for postoperative analgesia. Supplemental intravenous fluid prescription was protocolised. Oral intake was restarted from post-operative day (PoD) 1 and escalated on an on-demand basis. Patients were mobilised from PoD 1 and escalated daily. Drain removal and step down care decisions were guided by serum markers and clinical progress. Results: 212 consecutive patients from 2010 to 2014 were included (conventional, N = 108, ERAS protocol, N = 104). 134 (63.2%) patients underwent pancreaticoduodenectomy, 41 (19.3%) patients underwent distal pancreatectomy, 11 (5.2%) patients underwent total pancreatectomy and the rest underwent palliative bypass or other procedures. There was a statistically significant reduction in the volume of supplemental intravenous fluids received with no significant renal impairment noted. Median LOHS was reduced to 10 days (Inter-quartile range [IQR] 7 – 19) from 16 days (IQR 12 – 26) (P &lt; 0.001). Median critical care stay was reduced from 7 days (IQR 5 – 10) to 6 (IQR 4 -7) (P = 0.020). There was a statistically significant reduction in clinically significant wound complications (P = 0.019). There were no statistically significant increases in readmission rates, pancreas-specific or other generic post-operative morbidity rates. Conclusions: ERAS protocols are a viable peri-operative management strategy after major pancreatic surgery, and data suggests that LOHS can be reduced without an associated increase in readmission or post-operative morbidity rates.
Implementation of the Needs Assessment Tool for patients with interstitial lung disease (NAT:ILD): facilitators and barriers
Authors: C Reigada, A Papadopoulos, J W Boland, J Yorke, J Ross, D C Currow, S Hart, S Bajwah, G Grande, A Wells, M J Johnson
Journal: Thorax (2017)

A Needs Assessment Tool (NAT) was developed previously to help clinicians identify the supportive/palliative needs of people with interstitial lung disease (ILD) (NAT:ILD). This letter presents barriers and facilitators to clinical implementation. Data from (1) a focus group of respiratory clinicians and (2) an expert consensus group (respiratory and palliative clinicians, academics, patients, carers) were analysed using Framework Analysis. Barriers related to resources and service reconfiguration, and facilitators to clinical need, structure, objectiveness, flexibility and benefits of an 'aide-memoire'. Identified training needs included communication skills and local service knowledge. The NAT:ILD was seen as useful, necessary and practical in everyday practice.
Pharicin B, a Novel Diterpenoid, Stabilizes Retinoic Acid Receptor-α Protein and Induces Differentiation of AML Cells in the Presence of Physiological Doses of ATRA.
Authors: Guo-Qiang Chen, Zhi-Min Gu, Mei-Yi Zhou, Ying-Li Wu, Ying Huang
Journal: Blood (2008)
Quantitative RT-PCR (qRT) based analysis of sentinel lymph nodes (SLNs) from malignant melanoma (MM) patients: Prognostic significance of multimarker molecular assay
Authors: M. G. Cao, C. Badenas, J. A. Puig, J. Malvehy, S. Vidal, R. Rull, C. Carrera, S. Puig
Journal: Journal of Clinical Oncology (2005)

7514 Background: Detection of micro metastases in SLNs in MM pts is an important prognostic factor. When SLNs are involved survival is reduced in 40%, nevertheless, prediction of outcome is imprecise with conventional techniques. Polymerase chain reaction (PCR) can detect a single metastatic cell in 10(6) to 10(7) normal cells. Some previous reports have suggested that detection of tumor-specific mRNA by RT-PCR analysis of SLN may identify patients with increased risk of recurrence and death, but most of these studies had been done including few patients, short follow-up, paraffin-embedded sentinel lymph nodes and non quantitative RT-PCR techniques. We hypothesized that using a quantitative real time retranscriptase polymerase chain reaction (qRT) assay with multiple mRNA markers could improve prognostic prediction. Methods: 157 patients (pts) with cutaneous melanoma >0.75mm Breslow thickness underwent SLN biopsy. A portion of each SLN was stored frozen at -80C and assessed by qRT for mRNA of three genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family) and tyrosinasa. Results: Twenty-five (15.9%) pts had histologically positive (HISTOL+) SLN by hematoxylin and eosin and/or immunohistochemestry. Marker expression for Tyrosinasa, MART-1 and MAGE-A3 in HISTOL+ and HISTOL- pts were as follows: 92%, 72%, 36% and 77.3%, 34.8%, 10.6%. At 60 months DFS in pts with zero, one, two or three positive tumor markers was: 92.5%, 79.3%, 52.6% and 0%, respectively. Sixty-six (42%) pts were positive at least for two markers, at 60 months disease free survival for them was 43.5% versus 89.6% for patients with one or none molecular markers (p=.001), this prognostic value was confirmed as an independent factor by multivariate analysis (HR=2.37, p=0.036). In a subset analysis of HISTOL+ pts, MART-1 was the stronger prognostic factor for disease free survival (p=0.003). Conclusions: Multimarker qRT is an useful molecular staging test that may more precisely identify the pts’s outcome. The unexpected independent prognostic value of MART-1 in HISTOL+, suggests a correlation of this gene with aggressiveness of melanoma. No significant financial relationships to disclose.
Economic burden of common adverse events (AEs) associated with metastatic colorectal cancer (mCRC) treatment in the United States (US).
Authors: Dominick Latremouille-Viau, Jane Chang, Annie Guerin, Sherry Shi, Ed Wang, Justin Yu, Christopher Ngai
Journal: Journal of Clinical Oncology (2016)

21 Background: Treatments for mCRC have distinct safety and tolerability profiles. Common AEs associated with mCRC treatments may compromise the course of treatment, worsen quality of life, and increase healthcare resource utilization and costs. This study assessed the costs of common AEs in mCRC patients (pts) in the US. Methods: Adult mCRC pts treated with chemotherapy (chemo) or targeted therapies were identified from the Truven MarketScan databases (2009 - 2014). Up to the first 3 mCRC treatment episodes were considered. mCRC treatment episodes were categorized as with or without (w/o) AEs based on the occurrence of AEs, listed in product labels, during the episode. Total healthcare costs (medical and pharmacy; 2014 USD) were measured by mCRC treatment episode and reported per-patient-per-month (PPPM). mCRC treatment episodes with AEs were matched by type of treatment (monotherapy/combination, chemo, anti-VEGF, and anti-EGFR) and line of therapy to those w/o AEs. Adjusted total cost differences were estimated by comparing costs during mCRC treatment episodes with vs w/o AEs using multivariate two-part models, adjusting for potential confounding factors; 95% confidence intervals (CIs) and p-values were estimated with bootstrap. Results: A total of 4,158 mCRC pts with ≥ 1 mCRC treatment episode were included (mean age= 59 years; 58% male; 2261 [54%] with a 2nd and 1115 [27%] with a 3rdepisode). The most prevalent metastatic sites were liver (60%) and lung (14%). On average, 2 mCRC treatment episodes were observed per patient with an average length of 166 days per episode. Most mCRC treatments included chemo (96%) and were combination regimens (81%). Conclusions: The most costly AEs were hematologic, followed by respiratory, CNS, cardiovascular, and endocrine/metabolic AEs in mCRC pts. Adjusted total cost difference, with AEs vs. w/o AEs, PPPM; 95% CIs; *p<0.05 Hematologic 1,574 (814 ; 2,334)* Respiratory 1,213 (415 ; 2,011)* Central nervous system (CNS) 1,053 (213 ; 1,893)* Cardiovascular 1,002 (121 ; 1,883)* Endocrine/Metabolic 997 (249 ; 1,744)* Dermatologic 726 (-458 ; 1,911) Hemorrhagic 631 (-321 ; 1,582) Hepatobiliary/Pancreas 332 (-480 ; 1,143) Gastrointestinal 171 (-640 ; 982)
Stage I and II endometrial carcinoma treated with surgery and vaginal brachytherapy alone: A community experience.
Authors: A. S. DeNittis, B. S. Wojciechowski, A. M. Wojciechowski, A. Shevade, D. Holtz, C. J. Dunton
Journal: Journal of Clinical Oncology (2011)

e15593 Background: To report a community experience for women diagnosed with intermediate risk (Stage I and II) endometrial carcinoma treated with surgery followed by vaginal cylinder brachytherapy. Methods: From January 2003 to February 2011, 51 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IC and IIA endometrial carcinoma were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection followed by adjuvant high-dose rate (HDR) vaginal brachytherapy alone. The average age of the patients was 71 years. All patients were completely surgically staged and the average number of lymph nodes removed was 11. Brachytherapy was given 4-8 weeks postoperatively. All patients received 30 Gy in six 5-Gy fractions administered two fractions per week for three weeks. The prescription depth was 0.5 cm for an apical length of 4 cm. Results: After a median follow-up of 34 months (range: 1 to 96), 94% of patients were alive and 98% were free of vaginal cuff recurrence based on Kaplan-Meier analysis. One vaginal cuff recurrence (1.9%), two pelvic recurrences (3.8%) and two distant metastases (3.8%) were observed. 7 of 51 patients (14%) experienced grade one toxicities which included 4 with vaginal telangiectasias and mild friability, two with vaginal dryness and two with vaginal atrophy. No Grade two toxicities were reported. Conclusions: Our results confirm that adjuvant HDR vaginal brachytherapy alone in the community setting for stage I and II intermediate risk endometrial carcinoma provides the patient with long-term local control and overall survival and is well-tolerated. This data is consistent with the results of recent published randomized controlled trials.
IPSS Independent Prognostic Value of Plasma CXCL10, IL-7 and IL-6 Levels in De Novo Myelodysplastic Syndromes,
Authors: Animesh Pardanani, Christy Finke, Terra L Lasho, Aref Al-Kali, Kebede Begna, Curtis A. Hanson, Ayalew Tefferi
Journal: Blood (2011)
Octreotide use in patients with metastatic pancreatic neuroendocrine tumors.
Authors: A. Cheema, J. Weber, L. K. Kvols, J. R. Strosberg
Journal: Journal of Clinical Oncology (2011)

e14579 Background: Octreotide LAR was recently proven to significantly prolong progression-free survival in patients with metastatic midgut carcinoid tumors. Its antiproliferative effects in patients with pancreatic neuroendocrine tumors (pNETs) has not been determined. Methods: Patients with metastatic pNETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were analyzed retrospectively for overall survival (from time of initial diagnosis), histologic grade, hormone secretion and somatostatin-analog use. Kaplan Meier analysis with log-rank testing was used to compare patients who received octreotide LAR versus those who did not. Results: 267 patients with metastatic (stage IV) pNETs were identified. 180 patients had low-grade, 27 had intermediate-grade and 27 had high-grade tumors. 70 patients had functional tumors (hormone secreting) and 197 had nonfunctional tumors. 150 patients (59%) received octreotide LAR during their course of disease and 104 (41%) did not. Among patients with nonfunctional tumors, 53% received octreotide for its antiproliferative effect. The 5-year survival rate among patients who received octreotide LAR was 63% versus 46% among patients who did not receive octreotide LAR. Multivariate analysis of risk factors (including tumor grade) will be presented. Conclusions: A retrospective analysis of a large institutional cohort of patients with metastatic pNETs suggests that octreotide LAR use may be associated with prolongation of overall survival. However, randomized prospective trials are needed to confirm this finding.
Pre-immature dendritic cells pulsed with human papillomavirus 16 E7 peptide vaccine in advanced cervical cancer
Authors: M. S. Achtar, R. Ibrahim, V. E. Herrin, B. Gause, S. Steinberg, F. Grollman, O. Rahma, S. Bernstein, C. Maruffi, J. Berzofsky, S. N. Khleif
Journal: Journal of Clinical Oncology (2005)

2522 Background: Cervical cancer remains the second leading cause of death from cancer in women. Despite the high cure rate in the early disease, patients have more than 50% chance of dying from advanced disease. Approximately 99% of cervical cancers are associated with Human Papilloma Virus (HPV). The protein products of the early genes E6 and E7 in high-risk HPV types (eg, HPV types 16 & 18) have been implicated in the oncogenic capability of these viruses. The continued expression of these proteins in cervical cells appears to be a critical event in the progression and maintenance of cervical cancer, hence; an attractive vaccine therapy target. Methods: Fifteen patients with advanced cervical cancer (HPV16 E7 positive) were treated on this phase II/pilot trial with E7 peptide-pulsed PBMC’s. The vaccine was given intravenously and repeated at week 3, then every 4 weeks for a maximum of 15 vaccinations or until disease progression. Results: Cr release assay demonstrated evidence of E7 specific CTLs in 6/14 tested patients (42.8%). ELISPOT assay confirmed the above Results: The median survival was 12.9 months for all patients, 8.6 for those patients without response and 20.3 for patients with immunologic response. The median Progression Free Survival was 4.1 months for all patients, 3.5 for those patients without response and 6.5 for patients with immunologic response. No grade IV toxicities occurred. Grade III toxicity occurred only in two patients (anemia and thrombocytopenia) which most likely is due to the disease. Four patients received less than 4 vaccinations because of disease progression. One patient started the study NED and remained NED. Conclusions: Our vaccine demonstrated safety and specific immunity induction. Despite the advanced disease, clinical responses have been seen and warrant further investigation. We believe that this treatment may form a potentially promising approach in combination with other therapeutic modalities in advanced cervical cancer. No significant financial relationships to disclose.