tbuckley/cabot-search huggingface dataset:
Psychosocial oncology quality indicators prioritization exercise.
Authors: Tory Cadotte, Zahra Ismail, Lesley Moody, Maria Rugg
Journal: Journal of Clinical Oncology (2016)

277 Background: One of Cancer Care Ontario’s (CCO) roles is to monitor and report on cancer system performance to support quality improvement. CCO’s Psychosocial Oncology (PSO) program developed a measurement plan with potential indicators to evaluate patient access to and the effectiveness of PSO services across the province. The objective of this study was to conduct a modified Delphi process to build consensus and prioritize PSO indicators based on their relevance to provincial goals, ability to measure regional and provincial performance and result in tangible actions. Methods: Through consultations and literature reviews, 16 measurement concepts were identified as quality indicators for the PSO Program. Members of the PSO Provincial Committee (n = 32) evaluated each indicator based on set criteria: relevance, outcome-focused, directional, and actionable. Two rounds of input was gathered through a structured worksheet with a minimum response rate of 60%. Round one was based on a simple ‘Yes or No’ response to the indicators’ ability to meet the defined criteria. Participants were encouraged to comment on each indicator and suggest new indicators. Indicators not meeting at least half of the evaluation criteria, on average, were removed from the list. Net new indicators suggested by at least 10% of respondents were included in round two. In round two, members rated each indicator on a scale of 1-5, indicating to what degree the indicator met the evaluation criteria. Results: After round one, the original list was narrowed from sixteen to nine indicators. Four new indicators were also added. After round two, three indicators were identified as meeting the evaluation criteria: 1) wait times to specialized PSO services, 2) access to registered dietitian services by the head and neck cancer population, and 3) documented follow-up with patients with anxiety and/or depression. Prioritized indicators were reviewed with the PSO Committee and CCO senior leadership to confirm direction. Conclusions: The prioritization exercise provided consensus across divergent perspectives and identified top priorities. Work is underway to further develop/refine these indicators for provincial reporting.
Phase II trial of everolimus with sorafenib for patients with differentiated thyroid cancer (DTC) who progress on sorafenib alone.
Authors: M. S. Brose, A. B. Troxel, R. Mamtani
Journal: Journal of Clinical Oncology (2010)

TPS263 Background: Several trials have shown the activity of multikinase inhibitors in the treatment of iodine-refractory differentiated thyroid cancer. Phase II trials at our institution and others demonstrated that sorafenib has significant clinical activity. Radiographically, resistance often occurs in a subset of sites. Using immunohistochemistry (IHC) on progressing nodules we have observed subregions of tumor cells that express higher levels of p-AKT and p-S6 (downstream of mTOR). Finally, discontinuation of sorafenib can lead to an increase in the progression rate due to the resumption of growth of previously responsive nodules. Taken together, these data argue for the continuation of sorafenib while adding additional therapeutic agents to target the progressing clone of cells. This use of “intelligent design” has led us to open a phase II trial in which we add everolimus, which targets mTOR activity, to sorafenib in patients at the time of progression on sorafenib alone. Methods: Thirty-five patients with iodine-resistant DTC that have progressed on sorafenib will be treated with everolimus + sorafenib. Patients will start at 200 mg PO BID of sorafenib and 5 mg QD of everolimus. We will escalate the dose of everolimus and sorafenib as toxicity allows to a maximum of 400 mg BID of sorafenib and 10 mg QD of everolimus using a fixed dosing schedule to obtain MTD in each patient. A two-stage single-arm phase II design will be employed. The primary endpoint is an estimated doubling of PFS, where the expected PFS without treatment is 4 months (based on phase II data). Secondary endpoints include response rate and overall survival. Archival pre-treatment tissue and on treatment tissue where available will be studied using IHC. Using laser capture micro-dissection, regions of heterogeneity will be subjected to separate genomic analysis for a panel of 250 known somatic mutations using sequenome technology. This study builds on our prior experience with sorafenib in this population and our in vivo preclinical data. We use a novel approach to addresses the issue of tissue heterogeneity, which is a growing problem for the many patients that now have progression in a subset of metastatic sites. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer
Peripheral Blood Stem Cell Mobilization with Single Agent Plerixafor Induces FoxP3 Expression in Donor T Cells and Enables Durable Long Term Hematopoietic Engraftment Across Mismatched Major Histocompatibility Complex Barriers
Authors: Brian Kornblit, Billanna Hwang, Barry Storer, Monica S Thakar, Erlinda B Santos, Richard A. Nash, Brenda M. Sandmaier
Journal: Blood (2011)
Relationship between financial toxicity and health-related quality of life in patients with advanced solid tumors.
Authors: Jonas A. De Souza, Bonnie J. Yap
Journal: Journal of Clinical Oncology (2014)

31 Background: Financial toxicity is an important Patient-Reported Outcome (PRO). Its relationship with health-related quality of life (HRQOL) has not been previously described. Therefore, we report the relationship between financial toxicity and health-related quality of life (HRQOL) in patients with advanced cancers. Methods: The global HRQOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G) and its subscales Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB). Financial toxicity was assessed by the COST (COmprehensive Score for financial Toxicity), a PRO measure previously developed in 155 patients with advanced cancers. Correlations were calculated using Spearman's correlation. Subject data on tumor type, age, gender, race, income, insurance type and educational level were collected. Results: Fifty patients were assessed. All participants were diagnosed with advanced cancers, were receiving treatment at the time of participation, and had received treatment for at least 3 months. The median COST was 22 (range 0-44), and mean 22.51 (s.d. ±10.80). A negative correlation existed between the COST and HRQOL as measured by the FACT-G (r = -0.47, P &lt;.001), and its subscales: PWB (r=-0.35, p &lt; 0.05), SWB (r=-0.33, p &lt; 0.05), EWB (r=-0.32, p &lt; 0.05) and FWB (r=-0.41, p &lt; 0.01). In this small sample, there were no correlations between the COST and sociodemographic characteristics. Conclusions: Results demonstrate an inverse relationship between patient-reported HRQOL and financial toxicity, suggesting that higher financial toxicity is associated with worse HRQOL. A larger study is in progress to identify cancer patients at higher risk of financial toxicity.
The effect of bevacizumab on primary progressive cancers.
Authors: V. Ranpura, X. Su, S. Wu
Journal: Journal of Clinical Oncology (2011)

e13075 Background: Effective treatment has not been identified for primary progressive cancers, which are characterized by rapid progression within 3 months. We hypothesized that angiogenesis may play an important role in the development of primary progression. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of the angiogenesis inhibitor bevacizumab on primary progressive tumors. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until December 1st, 2010 were searched to identify relevant studies. Primary progressive cancer was defined as progressive disease to systematic anti-neoplastic therapy as the best response by RECIST criteria. Eligible studies included prospective RCTs in which the combination of bevacizumab and chemotherapy or biological therapy was compared to chemotherapy or biological therapy alone in cancer patients. Summary incidence of primary progressive cancer, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 2,981 patients with a variety of advanced tumors from 6 studies were included for analysis. The overall incidence of primary progressive cancer with chemotherapy or biological therapy was 33.2% (95% CI: 20.7-48.6%). When compared to the systematic therapy alone, the addition of bevacizumab significantly reduced the overall risk of primary progression (27.8% versus 33.2%; RR 0.86, 95% CI: 0.78-0.96, p<0.006). However, the effect varied significantly with tumor types (p=0.001), with the highest reduction seen in patients with renal cell cancer (RR 0.61; 95% CI: 0.46-0.80) and the lowest in malignant mesothelioma (RR 1.34, 95% CI: 1.03-1.74). The risk reduction did not vary significantly with bevacizumab doses (p=0.91) and chemotherapy regimens (p=0.13). The risk reduction was significantly correlated with an increase in response rate (p=0.003). Conclusions: The addition of bevacizumab to chemotherapy or biological therapy may be effective in the treatment of primary progressive cancers.
Gemcitabine and cisplatin (GC) for metastatic breast cancer (BC)
Authors: R. Gerson, H. Fuentes, A. Serrano, A. Villalobos
Journal: Journal of Clinical Oncology (2005)

871 Background: Metastasic BC has a poor prognosis, chemotherapy is the main treatment; anthracyclines and taxanes are considered as first line of treatment. New antitumor agents and combinations are explored. GC has shown to be effective in metastasic BC. Objectives: To evaluate efficacy and safety of GC in metastasic BC pts. Patients and Methods: > 20 yrs old with confirmed diagnosis of metastasic BC, Karnofsky scale > 60, medullar, hepatic and renal normal function. G 1250 mg/m2 d1,8 and C 35 mg/m2 d1,8 or 70 mg/mg d1. Age, previous therapy, number and sites of metastasis, cycles, therapeutic response and duration, as well as hematologic and non-hematologic toxicity were analized. Results: 19 women, mean age 51.4 +/- 10.6 yrs old, range 37 - 71. All in metastasic phase, metastasis to liver in 10 pts, lung 12, bone 9, cervical lymph nodes 4, brain 2, skin 3 pt. GC as first line in 2 pt, as second in 6, as third in 9, as fourth and fifth in 1pt. Seventeen pts had received anthracyclines and taxanes. Mean cycles of GC 5.2, range 1 to 9. CR 2 pt, PR 6, SD 8, Progression in 2 and one non evaluable; OR: 44.4% and clinical benefit 84.2%. Mean duration response 6.8 +/- 3.7 mos, range 2 to 15. Mean TTPd 7.9 +/- 4.0 mos, range: 2 - 20. Twelve deaths has been registered (63.1%). Mean survival: 9.7 +/- 4.2 mos, range 2 - 20. Hematologic toxicity: anemia GI 75%; leucopenia GI 37.5%, GII 6.25%; neutropenia GI 12.5%, GII 25%; thrombocytopenia GI 56.2%. Non hematologic toxicity: nausea GII 25%, asthenia GI 6.2%, vomiting GI 6.2%. Conclusions: GC is very active in pretreated metastasic BC, it is associated to toxicity of low intensity. New designs for trials in phase III for evaluating GC as first line treatment are required. No significant financial relationships to disclose.
Non-myeloablative HSCT in elderly AML/MDS patients in 1st CR
Authors: R. Tibes, M. de Lima, E. Estey, M. Shahjahan, R. Champlin
Journal: Journal of Clinical Oncology (2005)

6655 Background: Reduced intensity allogeneic transplant (“minitransplant ”) may extend the age limit beyond which patients with AML in first CR can receive a transplant. However, until now, the feasibility of minitranplant has not been explored. Methods: From 2001–2003, all pts age >50 admitted to the Leukemia Service with AML or high-risk MDS (10- 29% blasts) and cytogenetic abnormalities other than inv (16), t(8;21) or t(15;17) were to receive a transplant consult with the intent of performing a minitransplant in 1st CR if a sibling or unrelated donor could be found. Herein we describe the effectiveness of this program, focusing on 99 pts who entered CR (CR rate 39%). Results: 62 of the 99 pts received a transplant consult. 68% of the remaining 37 pts were felt to be poor candidates for transplant and were not referred for consult, 16% refused, and in 16% logistical factors (e.g. insurance approval) prevented consultation. Donors were identified for 25 of the 62 consulted pts (20 siblings, 5 unrelated). 18 pts were transplanted (14 in 1st CR; 4 in 1st relapse). Time from CR to transplant ranged from 1 to 32 weeks (median 11). We divided the 99 pts into 4 groups: Pts who received a consult were younger than those who did not (p = .01); among consulted pts, those with a donor were younger than those without (p = .03). Transplanted pts were younger than non-transplanted pts (p= .01) and less likely to have unfavorable (-5, -7) cytogenetics (p = .02); among pts without unfavorable cytogenetics, similar proportions of transplanted (67%) and non-transplanted pts (58%) had an antecedent hematologic disorder or 2ndary AML/MDS. Relapse-free survival was significantly longer in the transplant group (P=0.03). Discussion: The superior RFS in transplanted pts may be due to their younger age, better cytogenetics, or unknown selection factors, as well as to the efficacy of the transplant. Even with a systematic plan in place, the procedure is available in 1st CR to only 14% of older pts with cytogenetic abnormalities. No significant financial relationships to disclose.
Survival rates of older lung cancer patients: Analysis from the SEER database.
Authors: M. Prabhakar, B. Kanapuru, A. Jemal, W. B. Ershler, J. W. Yates
Journal: Journal of Clinical Oncology (2011)

e19683 Background: Non-small-cell lung cancer (NSCLC) is a common malignancy in the elderly and its incidence is increasing among women. In general, responses to therapy, other than surgery for local disease, has been disappointing and survival rates remain low. Methods: Data from nine SEER sites were examined for relative survival for patients registered during three successive decades: ’77-’86, ’87-’96 and ’97-’06. Survival for three age groups (65-74, 75-84 and 85+) for males and females were analyzed. Relative survival at 1, 5, and 9 years post diagnosis was compared. Results: Modest improvement in categorical survival occurred over the three decades for each of the categories studied. Women consistently demonstrated better survival than men for each of the time periods and in each of the age groups. Conclusions: The successful management of regional and distant NSCLC continues to be disappointing in spite of improvements in the delivery of radiation and chemotherapy. Promising early detection of local disease and surgical intervention following spiral CT scanning in high risk populations provides hope for improved outcomes in the near future. Explanations for the improved survival in women remain to be elucidated. Relative survival rates for lung cancer. Time since diagnosis (years) Age group (years) Calendar period 1977 to 1986 survival % (SE) 1987 to 1996 Survival % (SE) 1997 to 2006 Survival % (SE) Male Female Male Female Male Female 1 65-74 35.4 +/- .6 41.6 +/- 1.0 38.7 +/- .6 44.7 +/- .8 40.3 +/- .6 47.5 +/- .8 75-84 28.1 +/- .8 33.0 +/- 1.4 31.8 +/- .8 35.6 +/- 1.0 33.9 +/- .8 38.6 +/- .8 85+ 22.6 +/- 2.0 22.5 +/- 2.8 24.6 +/- 1.8 26.5 +/- 2.0 22.9 +/- 1.6 27.8 +/- 1.6 5 65-74 10.7 +/- .4 14.7 +/- .8 12.7 +/- .4 16.2 +/- .6 13.4 +/- .6 18.8 +/- .8 75-84 6.8 +/- .6 10.8 +/- 1.0 8.3 +/- .6 11.3 +/- .8 10.8 +/- .8 13.7 +/- .8 85+ 4.8 +/- 1.4# 7.1 +/- 2.4# 3.8 +/- 1.2 6.3 +/- 1.4# 5.5 +/- 1.6 8.3 +/- 1.6 9 65-74 1.6 +/- 1.6 10.6 +/- .8 2.2 +/- 1.2# 11.3 +/- .6 1.6 +/- 3.0 13.6 +/- 1.0 75-84 4.4 +/- .6 7.3 +/- 1.0 5.5 +/- .6 7.8 +/- .8 6.1 +/- 1.2 8.5 +/- 1.2 85+ 1.6 +/- 1.6# 1.4 +/- 1.6# 2.2 +/- 1.2# 4.4 +/- 2.0 1.6 +/- 3.0# 6.6 +/- 3.0# Abbreviations: SE, standard error to estimate 95% confidence interval.# Relative survival increased from a prior interval and has been adjusted.
Effect of changes in the glycolytic metabolism on tumor progression and dissemination in gastric cancer.
Authors: D. Zieker, I. Koenigsrainer, S. Beckert, J. Glatzle, M. Loeffler, R. S. Taichman, A. Koenigsrainer
Journal: Journal of Clinical Oncology (2011)

47 Background: Metastases are a frequent finding in gastric cancer patients and are associated with a poor prognosis. Recent data indicate that there might be a link between metabolic changes in the glycolytic system and dissemination in gastric cancer. The enhanced expression of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) and its signalling targets CXCR4 and CXCL12 seem to play a crucial role in enabling gastric tumours to develop dissemination. Methods: Microarray analysis was conducted investigating human specimens from consecutive gastric cancer patients with dissemination versus gastric cancer patients without dissemination. Subsequently siRNA-knock- down concerning PGK1 and CXCR4 and transfection (overexpression) of PGK1 was performed. Further, our thesis was investigated in a metastatic nude mouse model simulating human gastric cancer behavior by orthotopic tumour implantation. Tumour growth was detected by PET-MR-imaging and section of the animals. Results: Microarray analysis revealed a significant overexpression of PGK1, CXCR4 and CXCL12 in gastric cancer specimens with dissemination. Further siRNA-knock-down of PGK1 and CXCR4 showed a significant co-regulation on expression and protein level in vitro. The transfection (overexpression) of PGK1 also revealed a significant upregulation of its signalling targets CXCR4 and CXCL12 on expression and protein level. In addition the transfected cells showed a 50-fold distinctive property in the invasion assay compared to cancer cells without PGK1 overexpression. The in-vivo results obtained in the mouse model showed that elevated PGK1 expression increased invasive and metastatic behavior of implanted gastric tumours significantly and PET-MR-imaging and section correlated very well comparing tumour growth and metastasis. Conclusions: The overexpression of the glycolytic enzyme PGK1 and its signalling targets in gastric cancer might be a promising regulation-pathway promoting dissemination. This data may provide new prognostic markers and/or potential therapeutic targets to prevent migration of gastric carcinoma cells and has intriguing connection to an old hypothesis advocated by Otto Warburg for tumour metabolism. No significant financial relationships to disclose.
Outcomes of minimally invasive versus open esophagectomy for esophageal cancer: A single-center case-control study.
Authors: Hugo Miguel Teixeira Ferraz Dos Santos Sousa, Márcio Mesquita, Marisa Aral, José Costa-Maia
Journal: Journal of Clinical Oncology (2016)

171 Background: Esophagectomy is a major surgery associated with significant morbidity and mortality. There is growing evidence in literature that the minimally invasive approach in esophagectomy (MIE) may decrease morbidity. The aim of this study was the comparative analysis of the outcomes between MIE and open esophagectomy (OE) for esophageal cancer. Methods: Analysis (case-control study) of a prospective database with esophageal cancer cases submitted to curative intent surgery, between May 2006 and October 2014, in an Upper GI Surgery Unit. For this analysis, cases of non-resectional surgery were excluded. Results: From the initial population (n = 79), 65 cases (Group A: 24 MIE - 13 totally MIE and 11 hybrid MIE; Group B: 41 OE, including 5 cases of conversion from MIE) were included. Both groups were matched for gender, age, comorbidities, BMI, tumor location and histology, staging (cT and cN), neoadjuvant therapy and type of surgery. The presence of postoperative morbidity was 37,5% in MIE vs 61% in OE (p = 0,058), with a rate of respiratory complications of 16,7% and 22%, respectively (p = ns). Statistically significant differences were seen in Clavien classification of postoperative morbidity (p = 0,018) and in postoperative mortality (MIE 0% vs OE 22%, p = 0,021). Conclusions: The results of this case-control study provide further evidence for the feasibility and possible improvements in the postoperative morbidity and mortality of MIE, when performed in differentiated centers.
Cancer detection between peripheral zone and transitional zone targeted biopsies: Preliminary results from a prospective cohort of men undergoing MRI-US fusion biopsy.
Authors: Bruno Nahar, Nachiketh Soodana-Prakash, Nicola Pavan, Samarpit Rai, Felipe Munera, Rosa P Castillo, Raymond R Balise, Murugesan Manoharan, Bruce Kava, Ramgopal Satyanarayana, Mark L. Gonzalgo, Chad Ritch, Dipen Parekh, Sanoj Punnen
Journal: Journal of Clinical Oncology (2016)

56 Background: Multiparametric MRI has emerged as a popular imaging modality to localize prostate cancer. Nevertheless, interpretation of MRI is subjective, with concerns for false positives, particularly in the transitional zone (TZ), where hyperplastic changes may be confused for suspicion of cancer. We analyzed a prospective cohort of men undergoing MRI-US fusion biopsy and compared cancer detection rate between lesions seen in the peripheral zone (PZ) and the TZ. Methods: 133 men with elevated PSA or positive DRE underwent MRI-US fusion biopsy with average of 2 cores taken per target for the detection of prostate cancer between October 2014 and July 2015. Each targeted lesion in the PZ and TZ was previously classified by radiologists according to the MRI PI-RADS score and grouped according to their level of suspicion as probably benign (1-2), indeterminate (3) or probably malignant (4-5). Histopathology from targeted cores were categorized as no cancer, non-significant cancer (Gleason 6) and significant cancer (Gleason ≥ 7). We compared the cancer detection rates between lesions in PZ and TZ lesions, based on PI-RADS score. Results: We identified 143 lesions in the PZ and 82 lesions in the TZ. Among lesions found in the TZ, 57.3% were reported as probably malignant, compared to 44.7% of lesions seen in the PZ. Cancer was diagnosed in 23% of the lesions in the PZ, compared to only in 9.7% in the TZ (p&lt;0.01). With respect to significant cancer there was a trend towards higher detection of significant cancer in the PZ (13.29% vs. 6.10% p=0.12) compared to TZ. Furthermore, lesions in the PZ with a PI-RADS score &gt; 4 were associated with a three-fold increase in the odds of detecting cancer compared to lesions with PI-RADS &lt; 4 (OR 3.08; CI 95% 1.29 – 7.31, p&lt;0.011), whereas in the TZ there was no increased risk of cancer with higher PI-RADS scores (OR 1.0 CI 95% 0.20 – 4.84, p&lt;1.0). Conclusions: To our knowledge this is the first study to address a concern regarding an increased likelihood of false positives when reporting the presence and aggressiveness of cancer in the TZ versus the PZ. This may lead to unnecessary biopsies in men undergoing MRI of the prostate.