bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).
Authors: Sandler Howard M. , Hu Chen , Rosenthal Seth A. , Sartor Oliver , Gomella Leonard G. , Amin Mahul , Purdy James , Michalski Jeff M. , Garzotto Mark , Pervez Nadeem , Balogh Alexander G. , Rodrigues George , Souhami Luis , Reaume M. Neil , Williams Scott G. , Hannan Raquibul , Horwitz Eric M. , Raben Adam , Paulus Rebecca , Shipley William U. 
Published: February 2017

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.
Expression patterns of gpNMB in breast cancer (BC): Retrospective evaluation of tumor tissue from the phase II EMERGE study.
Authors: Yardley Denise A. , Melisko Michelle E. , Forero Andres , Bagley Rebecca G. , Zhang Joshua , Vahdat Linda T. ,   The EMERGE Study Group
Published: February 2017

129 Background: Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in ~20% of BC. gpNMB promoted BC metastases in a murine model and is a poor prognostic marker in BC patients (pts) (Rose 2010). Glembatumumab vedotin (GV, CDX-011) is a novel antibody-drug conjugate targeting gpNMB+ cancer cells with the potent cytotoxin monomethyl auristatin E. In a Phase I/II and in the Phase II EMERGE study, GV was well-tolerated (treatment-related toxicity included rash, neutropenia, and neuropathy) with promising activity in gpNMB+ BC tumors including TNBC. In EMERGE, GV vs. investigator’s choice chemotherapy, demonstrated an objective response rate of 30% (7/23) vs. 9% (1/11) in pts with tumor gpNMB overexpression (gpNMB in > 25% of tumor cells); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC. Improvements in progression-free survival (hazard ratio (HR) = 0.11) and overall survival (HR = 0.14) in gpNMB-overexpressing TNBC were noted. Methods: This retrospective analysis of the EMERGE study examined frequency of gpNMB overexpression by various baseline and disease characteristics. Tumors were centrally assessed by immunohistochemistry (IHC) and included data for 328 pts. Results: Tumor gpNMB overexpression was present in 21% (69/328) of screened and 40% (38/96) of TNBC pts. gpNMB overexpression was consistent in progesterone, estrogen, or HER2+ expressing tumors at rates of 12-15%. gpNMB overexpression was not observed among 17 lobular tumors, but was present in 21% (57/270) of ductal tumors. gpNMB overexpression was seen across organ sites, including lung (43%, 3/7), lymph node (31%, 12/39), chest wall (23%, 3/13), breast (21%, 44/209), bone (13%, 1/8), and liver (13%, 3/24). There were no apparent differences in gpNMB overexpression by age, race or disease setting (early vs. advanced) at tissue collection. Analysis is ongoing to determine if prior treatments may upregulate gpNMB expression. Conclusions: gpNMB overexpression in BC, especially in TNBC, appears consistent in archival primary and/or metastatic BC, regardless of age. A randomized multicenter study of GV in gpNMB overexpressing metastatic TNBC (METRIC) is ongoing. Clinical trial information: NCT01156753.
Association of PIK3CA mutation with response (ExRx) to cetuximab (C) in metastatic (met) triple-negative breast cancer (TNBC).
Authors: O'Shaughnessy Joyce , Ramos Corinne , Stephens Phil , Hoke Nicholas N , Palma Norma Alonzo , Levin Maren K. , Horiates Marina , Horak Christine E. , Wang Kai 
Published: February 2017

151 Background: 10 to 17% of TNBCs harbor PIK3CA mutations (TCGA Nature 490:61, 2012; Khambata-Ford S. ASCO 2010, abst 1056). Here we report clinical history and molecular findings for a TNBC patient with loss of mutant PIK3CA in a C-refractory metastasis that was present in her primary BC, who has had an ExRx to C. Methods: Following IRB-approved informed consent, targeted NGS was performed on the pt’s FFPE primary TNBC and on a C-refractory recurrent lung metastasis at a CLIA-certified laboratory (Foundation Medicine) to characterize all classes of genomic alterations across 287 cancer-related genes. RPPA was performed at a CLIA-certified laboratory (Theranostics Health) where immunostaining with 24 antibodies was directed against HER1/2/3 pathway proteins and AR. Results: 37 yo woman presented in 2006 with grade 3 primary TNBC, infraclavicular LNs and lung metastases at 33 weeks gestation. There was no response to preop doxorubicin/cyclophosphamide and following delivery of a healthy baby, she was treated with irinotecan, carboplatin, and C (#NCT00248287) and had near complete response (CR) in her lungs and pathologic CR in breast. In 2008, after 20 mos on C, chest CT showed a new lung met which was resected and she remains disease-free on C alone. NGS: Primary BC: PIK3CA C420R, TP53 mutations, MCL1 amplification (amp), and RAD51D germline mutation; C-refractory lung met: TP53, MLL2 mutations, MCL1, MYC, KDM5A, CCNE1 amp and RAD51D germline mutation (loss of PIK3CAmutation confirmed). RPPA: Primary BC: p-AR S650 (3+); p-ERK (2+), and HER1, p-HER1, p-HER3, p-AKT, p-S6, p-4EBP1 (1+); C-refractory lung met: loss of p-ERK; p-HER1, p-4EBP1 (2+), and p-AR, p-AKT, p-mTOR (1+). PTEN: Primary BC: 60% cells positive by IHC MAb 6H2.1 (Cascade Biosciences). Conclusions: The pt’s ExRx to C was dependent on presence of PIK3CA mutation which was lost in the C-refractory lung met. Loss of RAD51D function may also have contributed (Liping L. Ca Res 68:9141, 2008). High p-AR expression did not preclude response to C. Activating PIK3CA mutations induce an EGFR/ERK paracrine signaling axis in TNBCs (Young CD. Mol Cell Proteomics 2015). A prospective trial of EGFR inhibition in PIK3CA-mutant TNBC is warranted.
Distance to nearest radiation facility and treatment choice in early stage breast cancer.
Authors: Acharya Sahaja , Michalski Jeff M. , Perkins Stephanie Mabry 
Published: February 2017

73 Background: Breast conserving surgery followed by breast radiation (RT), collectively termed breast conserving therapy (BCT), is a recommended alternative to mastectomy (MT) for early stage breast cancer. Limited access to RT may result in more extensive surgical treatment. The purpose of this study is to assess the association between distance to nearest RT facility and MT use in a modern cohort of BCT eligible women. Methods: Women with Stage 0 – II breast cancer eligible for BCT diagnosed from 2004 – 2010 were identified from a US state registry. Distance from patient census tract to nearest RT facility census tract was calculated. Multivariate logistic regression was used to identify explanatory variables that significantly influenced MT use, adjusting for age, poverty, insurance, race, Hispanic ethnicity, marital status, diagnosis year, distance to nearest RT facility, T stage, N stage, ER/PR status and grade. Results: Of the 24,994 eligible women, 25.4% (n = 6,346) underwent MT and 74.6% (n = 18,648) underwent a breast conserving surgery. 32% of patients lived in a census tract that was > 5 miles from a RT facility. MT use increased with increasing distance to RT facility (24.5% at ≤ 5 miles, 26.5% at > 5 to < 15 miles, 29.5% at 15 to < 40 miles and 43% at ≥ 40 miles, p < 0.001). The likelihood of MT was independently associated with increasing distance to RT facility (Odds Ratio [OR]: 1.02 for every mile increase, 95% Confidence Interval [CI]: 1.01 – 1.02, p < 0.001). Compared to patients living ≤ 5 miles away from a RT facility, patients living 15 - < 40 miles away were 1.3 times more likely to be treated with MT (OR: 1.31, 95% CI: 1.15 – 1.51, p < 0.001), and those living ≥ 40 miles away were more than twice as likely to be treated with MT (OR: 2.29, 95% CI: 1.51 – 3.45, p < 0.001). When restricting the sample to women with T1 disease (n = 16,656), distance to RT facility remained a significant explanatory variable for MT use on multivariate analysis (p < 0.001). Conclusions: MT use in a modern cohort of women eligible for BCT is independently associated with increasing distance to RT facility. Measures to improve RT access should be explored to ensure universal opportunity for BCT.
Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC): Alliance A221301, a randomized, double-blind, placebo-controlled trial.
Authors: Navari Rudolph M. , Qin Rui , Ruddy Kathryn Jean , Liu Heshan , Powell Steven Francis , Bajaj Madhuri , Dietrich Leah L. , Lafky Jacqueline M. , Loprinzi Charles L. 
Published: February 2017

176 Background: The purpose of the study was to determine the effectiveness of olanzapine (OLN) for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC). Methods: A randomized, double-blind, phase III trial was performed in chemotherapy-naïve patients receiving cisplatin, > 70 mg/m2, or cyclophosphamide-anthracycline-based chemotherapy, comparing OLN to placebo in combination with aprepitant (APR), a 5-HT3 receptor antagonist (5-HT3), and dexamethasone (DEX). The OLN regimen was 10 mg of oral OLN, 125 mg APR, a 5-HT3, and oral DEX 12 mg pre-chemotherapy, day 1, and 10 mg/day of oral OLN and 8 mg DEX on days 2-4 post-chemotherapy plus 80 mg APR on days 2, 3 post-chemotherapy. The placebo (PLA) regimen was oral placebo, pre-chemotherapy, day 1, and on days 2-4 post-chemotherapy; the APR, 5-HT3, and DEX pre- and post-chemotherapy were identical to that used in the OLN regimen. Fosaprepitant (150 mg IV), day 1 was allowed for substitution for the oral aprepitant. Palonosetron, ondansetron, or granisetron were the permitted 5-HT3 options. Nausea was measured on a 0-10 visual analogue scale, with 0 being “no nausea at all” and 10 being “nausea as bad as it can be”. No nausea was the primary endpoint and, complete response (no emesis and no use of rescue medications) was a secondary endpoint. Results: 401 patients (202 OLN, 199 PLA) were enrolled in the study. The proportion of patients who had no nausea was significantly greater for the OLN regimen compared to the PLA regimen for the acute period (24h post-chemotherapy) (74% vs. 45%, p < 0.0006), for the delayed period ( 24-120 h post-chemotherapy) (43% vs. 26%, p < 0.0006), and for the overall period (0-120 h) (39% vs. 22%, p < 0.0006). Complete response was significantly improved for the OLN patients compared to PLA patients for the acute (85% vs. 65%, p < 0.0001), the delayed (67% vs. 53%, p < 0.0078), and the overall periods (64% vs. 41%, p < 0.0001). There were no grade 3 or 4 toxicities. Conclusions: No nausea, the primary endpoint, and complete response, a secondary endpoint, were significantly improved with OLN, compared to PLA. Clinical trial information: NCT02116530.
Hematology and oncology fellows' attitude and knowledge in cancer pain management.
Authors: Mahmoud Fade A. , Arnaoutakis Konstantinos , Motwani Pooja , Schafer Liudmila N. , Mehta Paulette , Makhoul Issam 
Published: February 2017

178 Background: The American Society of Clinical Oncology considers palliative care an integral part of cancer therapy. Our Hematology and Oncology fellowship at the University of Arkansas for Medical Sciences (UAMS) began a year-long palliative care curriculum to improve symptom management education. In this pilot study we evaluate fellows’ attitude and knowledge in cancer pain management before and after implementing a pain management curriculum. Methods: Hematology and Oncology Fellows were divided into three groups. Each group delivered a one hour lecture in pain management for a total of 3 didactic lectures. We adopted “Evidence based Practice of Palliative Medicine by Goldstein and Morrison” as the main textbook. Fellows answered a 30 item questionnaire to address attitudes and knowledge in pain management. Answers were scored using a 5 point Likert scale (1 = strongly disagree and 5 = strongly agree). Results: 11 fellows participated; six males, five females, median age 34 (R 28-40), one US graduate, and ten foreign graduates. More fellows felt comfortable managing acute (M = 4.3, SD = 0.48) compared to chronic (M = 3.8, SD 0.78) cancer related pain. Most believe that if they were taught the principle of pain management they would feel more comfortable managing pain (M = 4.6, SD = 0.51). Post pain management module, there was a statistically significant improvement in fellow’s knowledge in pain management in the setting of renal failure (P = 0.02) and bone pain (P = 0.006), and a trend towards statistically significant in both opioid rotation and conversion (P = 0.06). Fellows did poorly on opioid-drugs interaction and management of neuropathic pain. Fellows valued palliative medicine service as a great resource for their patients but most believe that they should not refer all their patients to palliative medicine for pain management. Conclusions: Pain management skills are eroding among Oncology fellows and efforts should be made to enhance symptom and pain management education in oncology training programs. This curriculum improved knowledge and self-efficacy in pain management and revealed areas for further improvement. More research is needed to address whether fellows use and apply pain management skills in the clinical setting.
Characteristics and outcomes of advanced cancer patients admitted to an acute palliative care unit (PCU) with severe dyspnea receiving high flow oxygen (HFO).
Authors: Delgado-Guay Marvin Omar , Rodriguez-Nunez Alfredo , Adegboyega Oluwatobi O , Newton Amy , Hernandez-Azmitia Maria Gabriela , Park Minjeong , Hui David , Bruera Eduardo 
Published: February 2017

247 Background: Dyspnea is very complex and distressing symptom in patients with advanced cancer. The therapeutic goal of its symptomatic management is to relieve the patient’s breathlessness sensation. Limited literature has addressed the characteristics and clinical outcomes of advanced cancer patients with severe dyspnea receiving HFO admitted to PCU. Methods: We reviewed the records of 101 advanced cancer patients with dyspnea receiving HFO and 110 matched PCU inpatients with dyspnea receiving regular O2 flow (NoHFO) between January 1 to December 31, 2012. Demographics, frequency and intensity of symptoms at PCU admission and follow-up, and outcomes were recorded. Results: Median age: 60 years, range (51, 69). 56% were Male. White(71%), Hispanic(13%), African American(10%), Asian (4%). Primary cancer: Lung (27%), Gastrointestinal (19%), Hematological (18%), Breast (13%), Gynecological (6%). Dyspnea was present in all cases and it was related mainly to: lung involvement by cancer (53%), pneumonia (40%), Congestive Heart Failure (6%), COPD (8%). ECOG: 4. No significant difference in age, ethnicity and type of cancer, ECOG, and possible cause of dyspnea among both groups. HFO and NoHFO were started the same day of admission. Median ESAS symptoms (Interquartile range: IQR) for HFO was Pain 4.5 (2, 7) vs. 5 (3, 7) for NoHFO, p = 0.1423; fatigue [7(5, 8) vs. 7 (5, 8), p = 0.450]; depression [3 (1, 5) vs. 3.5 (2, 5), p = 0.81]; anxiety 7 (4, 9) vs. 6 (3, 8), p = 0.01; dyspnea [7.5( 6, 9) vs. 5 (3, 8), p < 0.0001]. Memorial Delirium Scale 5 (2, 15) vs. 7(2, 15), p = 0.77). Morphine Equivalent Daily Dose: 48 (36, 120) vs. 55 (30, 120), p = 0.72. The median difference among first and follow up ESAS was Pain 0 (-3, 1) vs. -1(-2, 1), p = 0.62; fatigue[(-2, 1) vs. 0 (-2, 0), p = 0.63]; depression [0 (-1, 1) vs. 0 (-1, 2), p = 0.93]; anxiety [0 (-2, 2) vs. 0 (-2, 2), p = 0.94; dyspnea [0( -1, 1) vs. -1 (-2, 1), p = 0.18]. Memorial Delirium Scale 0 (-1.5, 5.5) vs. 0 (-2, 3), p = 0.21).The median time (IQR) from HFO started to discharge was 10 days (6, 15) vs. 8.5 (5, 14) days for NoHFO, p = 0.07). The median time(IQR) from HFO started to Death was 10.5 (7, 19) vs. 13.5 (7, 26) days for NoHFO, p = 0.18. 77/101(76%) HFO patients vs. 56/110 (51%) NoHFO died at the hospital, p = 0.002. 24/101(23%) HFO patients were discharged alive weaned off HFO. The Odd ratio for hospital death in patients with HFO vs. NoHFO was 4.83 (95% CI: 1.72 – 13.59), p = 0.003. Conclusions: Severe dyspnea is significant at the end of life of advanced cancer patients. Patients with HFO require similar MEDD than NoHFO patients. Inpatient mortality is higher in patients with HFO. More research is needed.
Stress biomarkers in advanced cancer patients experiencing the pain, fatigue, sleep disturbance symptom cluster.
Authors: Kwekkeboom Kristine L , Costanzo Erin S. , Campbell Toby Christopher 
Published: February 2017

5 Background: Cancer symptom clusters such as co-occurring pain, fatigue, and sleep disturbance, are common and debilitating for patients with advanced disease. Stress-related neuorendocrine system alterations are thought to play a significant role in symptom co-occurrence. While studies have documented relationships between stress biomarkers and symptoms in persons with cancer, few have done so in the context of a specific symptom cluster or among persons receiving treatment for advanced disease. Objectives: This preliminary analysis describes biomarkers of neuroendocrine stress systems – salivary cortisol and salivary alpha amylase (sAA) – and their relationship with the pain, fatigue, sleep disturbance symptom cluster in cancer. Methods: We analyzed baseline data from 14 participants of a RCT of a cognitive-behavioral symptom cluster intervention. Participants were receiving chemotherapy for recurrent or metastatic cancer. The sample was largely female (93%), aged 50-74 years old (M=63.57), with lung (57%), breast (14%), GYN (22%) or prostate (7%) cancer. Participants reported symptom cluster severity and collected saliva over two days prior to a new chemotherapy cycle. Cortisol concentrations were determined by luminescence immunoassay and salivary alpha-amylase by enzyme kinetic reaction assay using standardized kits (Salimetrics, State College, PA). Results: Mean (SD) cortisol and sAA levels were within normal range and followed typical diurnal patterns (Table 1); although evening levels of cortisol appeared higher in this sample compared to those of healthy adults. Low to moderate observed correlations between symptom cluster severity and stress biomarkers (evening cortisol r = -.204; evening sAA r = .326) were not significant in this small sample. Conclusions: Elevated evening cortisol levels may suggest dysregulation of the stress response in this population. The ongoing study will further evaluate if alterations in neuroendocrine function contribute to the symptom cluster experience. Clinical trial information: NCT01954420. [Table: see text]
Feasibility of a pilot study of an intervention to Enhance Communication during Hospice care with Oncology (ECHO).
Authors: Bauman Jessica Ruth , Schleicher Stephen , Nipp Ryan David , El-Jawahri Areej , Pirl William F. , Greer Joseph A. , Temel Jennifer S. 
Published: February 2017

51 Background: When patients with cancer transition to hospice, the role of oncology clinicians can be unclear. During this time, patients and families often feel abandoned by their oncology team. We assessed the feasibility of a novel intervention to enhance continuity of care between the oncology team and patients and their families after they enroll in hospice. Methods: Family caregivers (FCs) of patients with cancer (lung, head and neck, sarcoma, melanoma, and gynecological) who enrolled in home hospice from 3/2014-6/2015 were eligible to participate in the study. The ECHO intervention consisted of check-in phone calls from the oncology team to the FC (weekly x 4 weeks, biweekly x 4 weeks, then monthly), an optional in-person clinic visit, and a bereavement call. FC questionnaires assessing satisfaction, perceived stress, quality of EOL care, and regret were completed at enrollment, weeks 1 and 2, and then every 4 weeks, as well as at a phone interview post- death. The primary outcome was feasibility, which we defined as > 70% of the FCs receiving > 50% of the phone calls and > 70% of the FCs completing > 50% of the questionnaires. Results: Of 37 eligible FCs, 24 (80%) enrolled, 7 were not reached, and 6 declined. At the time of analysis, 19 were evaluable as 2 patients died before the intervention began, 1 FC withdrew, and 2 interventions were ongoing. Median time from hospice referral to study enrollment was 3 days (range 1-7) and from study enrollment to patient death was 34 days (range, 3-135). Clinicians completed 156 of the expected 172 calls (90.7%) to FCs. FCs completed 75 of the expected 91 (82.4%) questionnaires. 100% of the FCs received > 50% of scheduled phone calls and 79% of the FCs completed > 50% of the questionnaires. In qualitative interviews post-death, FCs indicated that the phone calls were appreciated and helpful. Conclusions: This intervention enhancing communication with the oncology team throughout hospice was well received by FCs. Additionally, the intervention proved feasible, as the majority of phone calls and questionnaires were completed. A randomized study is warranted of the impact of ECHO on the quality of EOL care and FC outcomes including satisfaction, bereavement adjustment, and mood. Clinical trial information: NCT02069769.