tbuckley/cabot-search huggingface dataset:
Evaluation of health care resource utilization (HRU) in real-world patients treated for chronic lymphocytic leukemia (CLL).
Authors: Bruce A. Feinberg, Brad Schenkel, Ali McBride, Lorie Ellis, Janna Radtchenko
Journal: Journal of Clinical Oncology (2014)

302 Background: Elucidating healthcare resource utilization (HRU) in real-world clinical practice is essential in understanding the economic burden of a disease. The objective of this study was to evaluate HRU in treated CLL patients. Methods: Using proprietary MORE Registry Research Edition claims, patients treated with antineoplastics for CLL identified by ICD-9 codes during a 48-month period (August 2009-2013) were selected. Patients who were pregnant or &lt;18 years of age, or were treated for secondary malignancies were excluded. Descriptive statistics were used to analyze HRU primarily focused on hospitalizations, office visits, and emergency room (ER) visits. Chi-square tests were used to compare HRU rates by age group (&lt;65 and ≥65); t-tests were used to compare means. Results: Of 2,013 CLL patients, median age was 72 years, 78% were ≥65 years of age, 61% were male, 67% Medicare, and 34% were treated in the relapsed setting. The mean comorbidity index was significantly higher in the ≥65 age group compared to the &lt;65 age group (2.2 vs. 1.3, p&lt;0.001). Overall, 97% of patients had an office visit, 31% had a hospitalization, and 34% had an ER visit. There were no statistically significant differences in HRU between age groups, although rates trended higher in the older group: office visits 97% vs. 96%, hospitalizations 32% vs. 29%, and ER visits 34% vs. 32%. Mean hospital length of stay (LOS) was 5.7 days and trended higher in the ≥65 age group (5.8 vs. 5.4 days), but the difference was not statistically significant. Conclusions: Healthcare resource utilization was considerable among patients treated for chronic lymphocytic leukemia. Approximately one-third of patients were hospitalized, and one-third experienced an emergency room visit. Despite a higher mean comorbidity index in the ≥65 age group, HRU was not significantly higher in the older group. Further evaluation of HRU among CLL patients by line of therapy, age, comorbidity index, and payer type is warranted.
The relationship between quality of life (QoL) and tumor response in patients (pts) with metastatic colorectal cancer (mCRC) receiving panitumumab (pmab) plus FOLFIRI as first-line therapy: An analysis of study 314.
Authors: M. Karthaus, J. Thaler, R. Hofheinz, L. Mineur, H. Letocha, R. Greil, E. Fernebro, E. Gamelin, A. Baños, C. Kohne
Journal: Journal of Clinical Oncology (2011)

3634 Background: Study 314 was a phase II, single-arm, multicenter study designed to assess the efficacy/safety by KRAS tumor status of first-line pmab plus FOLFIRI in pts with mCRC. Here, we investigate the relationship between QoL and tumor response. Methods: Pmab (6mg/kg) and FOLFIRI were administered every 14 days until disease progression, consent withdrawal, or unacceptable toxicity. EUROQOL EQ-5D Index scores were recorded at screening, every 8 wks until wk 32, every 3 months thereafter until disease progression, and 56 days after stopping study treatment (safety follow up visit). EQ-5D scores range from –0.594 to 1 (1=perfect health). A change of ≥0.08 may be considered clinically meaningful. Data were analyzed descriptively by tumor KRAS status (wild type [WT] or mutant [MT]) and by best overall response. Results: A trend for better tumor response in pts with higher baseline EQ-5D scores was observed. In pts who achieved CR/PR, the difference in EQ-5D score between the WT group and the MT group exceeded the clinically meaningful threshold at wks 8 and 24. Conclusions: Patients with WT KRAS mCRC who respond to panitumumab appear to maintain their EQ-5D score over time. The relationship between QoL and tumor response in this treatment setting should be evaluated in a larger patient population. Change in EQ-5D score from baseline. CR or PR SD PD WT MT WT MT WT MT Mean (SE) baseline score n 45 22 25 26 4 3 0.812 (0.034) 0.817 (0.052) 0.833 (0.039) 0.790 (0.034) 0.720 (0.178) 0.588 (0.205) Mean (SE) change from baseline Wk 8 n 43 21 23 23 3 2 +0.049 (0.032) –0.036 (0.052) –0.023 (0.044) +0.015 (0.030) +0.047 (0.047) –0.087 (0.122) Wk 16 n 39 22 20 19 1 1 +0.067 (0.031) +0.018 (0.045) +0.024 (0.039) –0.007 (0.073) –0.240 (–) –0.327 (–) Wk 24 n 33 19 10 9 1 0 +0.053 (0.028) –0.027 (0.033) +0.014 (0.073) +0.111 (0.046) 0.000 – Wk 32 n 15 8 3 5 1 0 +0.019 (0.037) –0.015 (0.080) +0.195 (0.195) +0.172 (0.081) –0.311 (–) – Safety follow-up visit n 19 14 13 15 2 1 +0.048 (0.042) –0.019 (0.038) –0.040 (0.060) –0.034 (0.085) –0.087 (0.343) +0.000 (–) Abbreviations: CR, complete response; PD, disease progression; PR, partial response; SD, stable disease; SE, standard error.
Treatment of urinary bladder cancers by growth hormone-releasing hormone antagonists: A preclinical report.
Authors: Ferenc G. Rick, Petra Popovics, Norman L. Block, Jinlin He, Xian Yang Zhang, Irving Vidaurre, Karoly Szepeshazi, Andrew V. Schally
Journal: Journal of Clinical Oncology (2016)

433 Background: Urinary bladder cancer is the fifth most frequent cancer diagnosed and among the most expensive cancers to treat in the United States. The management of muscle-invasive tumors presents a clinical challenge because of the toxicity and limitations in efficacy and durability of current therapeutic modalities. Novel therapeutic strategies for this disease are of paramount importance. Growth hormone-releasing hormone (GHRH) receptors and its splice variant were detected in a series of urothelial malignancies and GHRH has been shown to influence the growth of these tumors. Herein we evaluated the effect of GHRH antagonists on the growth of various experimental human urinary bladder cancers in vitro and in vivo in nude mice. Methods: We investigated the effects of several GHRH antagonists MIA 602, MIA 606 and MIA 690 on growth of urothelial HT-1376, J82, and RT-4 tumors xenografted into nude mice. The presence of GHRH receptors was validated by Western blotting. Results: The receptors for GHRH and their main splice variant, SV1, were detected in tumor samples of all 3 human bladder cancer models. In the HT-1376 tumors, the GHRH antagonists caused a 30-60% reduction in volume and 52-70% decrease in tumor weights (p &lt; 0.05). All three antagonists strongly inhibited growth of J82 cancers as shown by a 62-75% reduction in tumor volume and 54-66% decrease in tumor weights (p &lt; 0.05). Treatment with MIA-602 and MIA-606 resulted in a similar marked inhibition of growth of RT-4 cancers; tumor volume and weights were reduced by about 51-71% in the treated groups (p &lt; 0.05). The mice tolerated this therapy well; body and organ weights were not significantly changed by the treatments. No toxicity from the GHRH antagonists was noted. Conclusions: We demonstrated the efficacy of potent GHRH antagonists and their lack of toxicity in inhibiting the growth of experimental models of bladder cancer in vivo. The expression of GHRH receptors was detected in all 3 models of human primary urothelial bladder carcinomas. Our findings warrant further development of GHRH antagonists for clinical therapy of bladder cancer alone or in combination with current chemotherapeutic agents and Exploration of their mechanism of action.
Prognostic role of programmed cell death protein 1 expression in surgically treated patients with upper tract urothelial carcinoma.
Authors: Nozomi Hayakawa, Eiji Kikuchi, Ryuichi Mizuno, Keishiro Fukumoto, Takeo Kosaka, Shuji Mikami, Akira Miyajima, Mototsugu Oya
Journal: Journal of Clinical Oncology (2016)

402 Background: Programmed cell death protein (PD-1) expressed on active T cells, and its ligand PD-L1 expressed on the surface of cancer cells, complementarily down-regulate T cell activation and are related to immune tolerance. A close association between PD-1 expression and poor prognosis has been reported in several cancers, however, in upper tract urothelial carcinoma (UTUC) the role of PD-1 expression on clinical outcome has not been investigated. Methods: The protein expression of PD-1 was evaluated by immunohistochemistry and the relationship with clinicopathological features was investigated in surgical specimens obtained from 100 patients who had been surgically treated for UTUC. At a magnification of 200x, PD-1 protein expression was estimated and the positive cells were graded as no (negative), moderate (1-10 cells), and strong ( &gt; 10 cells). Results: Twenty-four patients (24.0%) had strong PD-1 staining, 32 patients (32.0%) had moderate PD-1 staining, and 44 patients (44.0%) had no PD-1 staining. PD-1 staining was associated with pathological T stage (p = 0.023), tumor grade (p = 0.005), and lymphovascular invasion (p = 0.033). Lymphovascular invasion (p &lt; 0.001) and PD-1 staining (p = 0.02) were independent factors for predicting disease metastasis. The 5-year matastatic free survival rate in patients with strong PD-1 staining was 57.3 %, which was significantly lower than that with no PD-1 staining (87.3%, p=0.001) and that with moderate PD-1 staining (74.3%, p = 0.05). In a sub-group analysis of patients with ≥pT2 (N = 59), a significant difference in disease metastasis was observed between patients with strong PD-1 staining and no PD-1 staining (p = 0.018), but was not observed between strong and moderate PD-1 staining (p = 0.146). Conclusions: PD-1 expression may be a useful indicator for a worse prognosis in UTUC patients who undergo radical nephroureterectomy. Targeting therapy against PD-1 might be a promising therapeutic modality for UTUC.
Lymphopenia as a prognostic factor in renal cell carcinoma.
Authors: Mohammad Mozayen, Anteneh Tesfaye, Khalil Katato
Journal: Journal of Clinical Oncology (2012)

470 Background: Lymphopenia is known to be a negative prognostic marker for NHL and hematological malignancies, recent observational studies evaluated the presence of lymphopenia and its impact in solid tumor like colon, lung and pancreatic cancer. We aim to assess the effect of Lymphopenia at the renal cell carcinoma (RCC) survival. Methods: A retrospective review of 207 patients diagnosed with RCC between 1995 and 2008 in a community hospital setting was done. Patients with additional malignancies, lymphoma of the kidneys, with no follow up data or no preoperative complete blood count test were excluded. Demographics, preoperative complete blood count, pathology, disease stage, operative note, and subsequent follow up data were reviewed. Lymphopenia was defined as absolute lymphocytic count &lt; 1200/µl. Last follow up date was used to calculate the 3 year overall survival. The primary outcome was 3 year overall survival. Results: A total of 207 patients were included in the study. Caucasians were 176(85.9%), African Americans were 13.7% and Asians were 1(0.5%). Males (M) were 127 (62.3%) and females (F) were 77(37.7%). The median age of the study population was 65 (22-91. Clear cell histology was seen in 79%. Stage I was seen in 53.9%, II in 23.5%, III in 13.7% and IV in 8.8% of the study population. Lymphopenia was seen in 81 (40%) patients (95 CI 34-48). Lymphopenia was seen in 31.8% of stage I; 50% of stage II, 41.4% of stage III, and 65% of stage IV patients (p=0.017). Lymphopenia was seen in 28.6% of African Americans and 42.7% of Caucasians (p=0.11). Lymphopenia was seen in 32.1% of females and 45.7% of males (p=0.03). The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3-year overall survival for patients with lymphopenia was 60.5%, compared to 73.6% in non-lymphopenic patients (p=0.04). Conclusions: Lymphopenia was seen to be higher among males and Caucasians, more frequently at advanced stage at diagnosis. Patients with lymphopenia were observed to have significantly worse survival when compared to patients with normal lymphocytic count in RCC. We conclude that lymphopenia is considered as a negative prognostic factor for RCC, and needed to be studied in the correlation of other known prognostic factors.
Astrocyte elevated gene 1 (AEG-1) mRNA expression in non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations.
Authors: S. Viteri, R. Rosell, C. Costa, M. Taron, J. J. Sanchez, S. Benlloch, T. Moran, B. Massuti, C. Camps, M. Majem, E. Carcereny, F. Cardenal, A. Gasco, N. Mederos, I. Magri, C. D. Rolfo, M. R. Garcia-Campelo, A. Gimenez Capitan, I. de Aguirre, C. Queralt
Journal: Journal of Clinical Oncology (2011)

10541 Background: NSCLC p with EGFR mutations respond to the oral EGFR tyrosine kinase inhibitors erlotinib and gefitinib, although the duration of response in individual p is unpredictable. In our previous study, we found that erlotinib-treated p with low BRCA1 mRNA levels had a progression-free survival (PFS) of 27 months (m) vs 10 m for p with high levels (P=0.02). AEG-1 is a multifunctional oncogene that plays a role in several carcinogenic processes. Through PI3K/Akt, AEG-1 activates IKK, leading to phosphorylation and destabilization of the NF-kB inhibitor NFKBIA, which is a gatekeeper for EGFR signaling. Methods: Tumor mRNA expression levels of BRCA1 and AEG-1 were assessed by quantitative PCR in 77 erlotinib-treated p with EGFR mutations. Expression levels were dichotomized at the median. Results: PFS was longer in p with low AEG-1 expression (27 vs 12 m; P=0.003). Median survival (MS) was not reached for p with low AEG-1 levels and was 24 m for p with high levels (P=0.08). Based on these results, we generated an AEG-1/BRCA1 risk model: p with high levels of both genes were considered high-risk, p with low levels of both genes were low-risk, and p with high levels of one and low levels of the other gene were intermediate-risk. PFS was not reached in the low-risk group, while it was 18 m for the intermediate-risk group and 8 m for the high-risk group (P=0.00006) (HR for high- vs low-risk groups, 6.6; 95%CI, 2-4-18; P<0.00001). MS was not reached in the low-risk group, while it was 31 m for the intermediate-risk group and 18 m for the high-risk group (P=0.05). In the multivariate analysis for PFS, the only independent prognostic variables were bone metastases (HR, 2.7; 95%CI, 1.1-6.5; P=0.03) and the AEG-1/BRCA1 risk groups (HR for high-risk group, 7.7 (95%CI, 2.8-21.3; P<0.00001). Conclusions: The two-gene risk model based on AEG-1 and BRCA1 mRNA expression was strongly associated with clinical outcome, with significantly shorter PFS and MS in the high-risk group. This model can be useful for the proper individualized management of p with EGFR mutations.
Do the preferences of patients with terminal cancer or their family caregivers and end-of-life care discussions influence utilization of hospice-palliative care?
Authors: A. R. An, Y. H. Yun, W. J. Lee, K. H. Jung, Y. R. Do, S. Kim, D. S. Heo, J. S. Choi, S. Park, H. S. Jeong, J. H. Kang, S. Kim, J. Ro, S. R. Park
Journal: Journal of Clinical Oncology (2011)

9041 Background: We aimed to determine whether utilization of hospice-palliative care (HPC) was associated with end-of-life (EOL) care discussions and the stated preferences of patients and their family caregivers, a topic dealt with in few studies. Methods: As part of the Study to Understand Risks, Priority, and Issues at End-of-Life (SURPRISE), a prospective multicenter cohort study, we administered similar questionnaires to 619 patients and their family caregivers at the time of the terminal diagnosis and a follow-up questionnaire to 363 caregivers 3 months after the patient died. The baseline questionnaire covered demographic characteristics, religion, EOL care preference (HPC, intensive care, and cardiopulmonary resuscitation [CPR]), and EOL care discussions held with physicians concerning outpatients or inpatient visits, utilization of HPC, home care services, the intensive care unit (ICU), CPR, or social services. The follow-up questionnaire determined actual utilization of HPC. Results: A total of 257 (70.8%) family caregivers completed the second questionnaire and 104 (40.5%) of their patients utilized HPC. The multivariate model showed that the family caregivers’ preference for HPC was associated with its actual utilization (adjusted odds ratio [aOR], 2.07; 95% confidential interval [CI], 1.14 to 3.75), whereas the patients’ preference was not. Patients were more likely to utilize HPC if family caregivers had discussed with physicians either HPC (aOR, 2.34; 95% CI, 1.29 to 4.24) or ICU admission (aOR, 2.41; 95% CI, 1.05 to 5.55). Another factor associated with HPC utilization was the religion of the family caregiver (Catholic or Protestant vs. Buddhist or none, aOR, 1.97; 95% CI, 1.13 to 3.44). No patient or demographic-clinical factor was related to HPC utilization. Conclusions: HPC utilization appears to be influenced by family caregiver (rather than patient) preferences and by EOL care discussions between physicians and family caregivers.
Final results of a multicenter phase II trial assessing sorafenib (S) in combination with irinotecan (i) as second- or later-line treatment in metastatic colorectal cancer (mCRC) patients (pts) with KRAS-mutated tumors (mt; NEXIRI).
Authors: M. Ychou, O. Bouche, S. Thézenas, E. Francois, A. Adenis, J. Bennouna, J. Taïeb, F. Desseigne, J. Seitz, T. Conroy, M. Galais, E. Crapez, S. Poujol, F. Bibeau, P. Laurent-Puig, E. Samalin
Journal: Journal of Clinical Oncology (2011)

e14002 Background: The raf kinase inhibitor S is the lead compound in a series of raf signalling pathway inhibitors that could inhibit cell growth and proliferation of pts in KRAS mt pts. The aim of this phase II trial was to evaluate the disease control rate (DCR) of i combined with S as second- or later line treatment (tt) in mCRC pts with KRAS mt. Methods: In the previous phase I, the recommended dose of Iwas 180 mg/m2 in a bi-weekly regimen with a fixed dose of S (400 mg twice daily) (1 cycle= 2 courses of I). In the phase II, pts received this combination until progression or toxicity. Eligibility criteria included: measurable and unresectable mCRC, age > 18 years, PS ≤ 2, progression after I-based chemotherapy, one or more previous lines and centralized confirmation of KRAS mt in codons 12 or 13 in the primary tumour (PT) or metastases. Primary endpoint was DCR according to RECIST criteria with independent review of CT-scan. Secondary were toxicity, PFS and OS. Tt regimen was considered promising if at least 14 out of 54 pts had DC in a two-stage Simon design. Pharmacokinetic, pharmacogenetic and pathologic studies were also undertaken. Results: Fifty-four pts were included between 06/09 and 12/09 from 10 centers. Median age was 60 yrs (range: 43-80), 59% were males, 46% PS 0, 63% PT in colon. Previous tts were 5FU 100%, I 100%, oxaliplatin 100%, bevacizumab 89%. The median number of cycles was 4 (1-8) and 13 pts (24%) completed at least 6 cycles. No toxic death was seen. Gr 3 toxicities were: hand-foot syndrome 15%, diarrhea 39%, neutropenia 19% and 16% showed Gr 4 neutropenia. In 46 pts (85%) S dose was reduced to 400 mg daily after two courses due to toxicity, then increased again to 800 mg in 55% of pts. The DCR was 64.9% [IC95%, 51-77] in intention to treat (52 evaluable pts). Median PFS and OS were 3.5 [IC95%, 2.0-3.7] and 7.7 months [IC95%, 4.8-9.7], respectively. Conclusions: NEXIRI regimen as second- or later-line tt for mCRC pts with KRAS mt shows promising activity in this heavily pre-treated KRAS mt population. These data justify conducting a randomized phase II/III trial to confirm the efficacy of this combination.
Use of an automated notification tool to drive real-time patient symptom intervention.
Authors: Scott Hartman, Brandon Bosch, Diane Denny, Maurie Markman
Journal: Journal of Clinical Oncology (2016)

160 Background: Cancer Treatment Centers of America, Inc. (CTCA) is a national network of hospitals that specialize in the treatment of patients fighting complex or advanced-stage cancer. The Symptom Inventory Tool (SIT) is an assessment tool that captures the patients’ perceived symptom burden for real-time clinical intervention, from baseline and every 21 days thereafter. The SIT is comprised of questions utilizing the M.D. Anderson Symptom Inventory tool, a validated assessment instrument with questions added and a free text box by CTCA. Methods: An e-mail notification system associated with the SIT was established to allow efficient communication with specialists and support team members who would not traditionally see the patient without such a trigger signifying a need. While the SIT report is housed within the EHR, an automated e-mail profile may be established for each clinician and or team, tailored to the clinical specialty, based on symptom(s) of interest. Patients completing the SIT and scoring a particular symptom(s) at or above a threshold will “trigger” notification of that their score along with information allowing follow-up. Notifications can be set at 15 minute intervals, hourly, daily, etc. Results: 31 users/groups, representing a wide variety of disciplines and multiple care teams, currently utilize the SIT e-mail functionality including: Pain, Distress, Mind Body Medicine, Survivorship, Physical Therapy, and Sleep. The content of the e-mail consists of the patient name, medical record number, and (self-defined) symptom scores of interest. These same patients triggering a notification may be readily tracked for follow-up by the support team throughout their course of treatment or seen only once depending upon patient preference and identified need. Conclusions: The e-mail notification process has promoted communication with specialists and other support team members outside of the core team, cognizant of their different communication needs. Moreover, it allows for effective alignment of resources based on clinician expertise.