tbuckley/cabot-search huggingface dataset:
Unmet psychosocial needs among cancer patients at the National Cancer Centre Singapore (NCCS).
Authors: R. C. Ng, H. Verkooijen, L. L. Ooi, W. Koh
Journal: Journal of Clinical Oncology (2010)

6057 Background: Studies in U.S. and Australia have shown a high degree of unmet needs in cancer patients. Aim: To define the prevalence of unmet needs in cancer patients at NCCS and factors associated with high unmet needs. Methods: Questionnaire study conducted among breast, gynecologic, and colorectal cancer patients using a modified version of CaSUN (Cancer Survivors' Unmet Needs measure) looking at disease information, physical, social support, financial and psychological needs. Total score was divided into 1) No unmet need vs. any unmet need and 2) High (top 25%) vs. low (lower 75%) unmet needs. Logistic multivariate analysis was used to identify impact of individual factors adjusted for confounders. Results: Response rate was 75.7% with 535 participants. The mean age was 58.5 years and 20% were males. 83% were Chinese, 11% Malay and 6% Indians. Majority had breast cancer followed by colorectal and gynecological cancer at 61%, 32% and 7% respectively. Cancer stages were evenly distributed. Only 36% of participants were employed and 74% were diagnosed <1 year ago. Prevalence of any unmet need was 75.2%. Disease information needs was highest (61.5%) followed by financial (40.2%), social support (39.7%), psychological (27.3%) and physical (26.1%). Factors independently associated with high unmet needs were age<60, Malay, stage 3 cancer and <1 year from diagnosis (Table). Gender, education, employment, marital status and cancer type were not. Conclusions: Prevalence of unmet needs was 75.2%, with disease information needs the highest followed by financial needs in our copayment health system. This study identifies important areas for cancer workers to focus upon. Adjusted odds ratio of factors associated with high needs Variable Adjusted OR (95% CI) Age 60 and above 1.00 <60 2.95 (1.77–4.92) Race Chinese 1.00 Malay 2.10 (1.15–3.84) Indian 2.11 (0.93–4.81) Current stage Stage 1 1.00 Stage 2 1.11 (0.61–2.02) Stage 3 2.11 (1.14–3.89) Stage 4 1.19 (0.61–2.33) Period of diagnosis 1 year or more 1.00 < 1 year 1.94 (1.23–3.07) No significant financial relationships to disclose.
Cancer incidence among first-degree relatives in families with Nijmegen breakage syndrome
Authors: N. I. Kitsera, H. Akopyan, R. Polishchuk, L. Kostyuchenko, N. Markevych
Journal: Journal of Clinical Oncology (2008)

22052 Background: Increased occurrence of malignant tumors in families of Nijmegen breakage syndrome (NBS) patients has been described. The aim of this work was to perform clinical and genealogical investigations in NBS families from West Ukraine, particular among first-degree relatives. Methods: Clinical and genealogical analysis was conducted in 19 families with NBS. Clinical diagnosis of NBS was confirmed by cytogenetic and molecular genetic analyses. 21 children with NBS (11 boys and 10 girls) were examined at the age from 3 months to 12 years. All the children were homozygous carriers of mutation 657del5. Combined immunodeficiency was found in each case. Results: Oncohematological complications were developed in 7 (33,3%) probands at the age of 5–12, among them lymphoma in 5 patients (2 girls and 3 boys), lymphohystiocytosis (1 boy) and undifferencial cancer of nose cavity (1 girl). The siblings in 4 (21,1%) NBS families had the same diagnosis. One of these families was a consanguineous couple (marriage between third cousins) and two their childs had the developed NBS. The elder sister with NBS died from measles aged 1,5. The younger brother was diagnosed NBS and non-Hodgkin's lymphoma at the age 8. Now he is 18 years old. In family P. the elder sister with NBS died at the age of 3 suffering Hodgkin's lymphoma, the other sister was diagnosed NBS aged 7 months. Gastric and duodenum cancer were noted in these families. In family S. the elder brother, suffering Hodgkin's lymphoma, died at the age of 5. He wasn't diagnosed NBS. Two other brothers were diagnosed NBS at the age of 7 and 1,5. In family L. NBS was diagnosed in two brothers at the age of 4,5 and 2,5 at the same time. The younger brother died from non-Hodgkin's lymphoma aged 5. The third pregnancy of his mother was stopped by spontaneous abortion (male fetus was diagnosed to have 657del5/657del5 mutation of NBS1 gene). Fourth present pregnancy is female fetus of heterozygous state. There was no cancer incidence noted in these families. There was no case of cancer among the parents' of NBS children. Conclusions: Every third proband with NBS was diagnosed cancer at the age of 5–12. Two NBS incidences were occurred in siblings in four families (21,1%) from 19. A genealogical analysis seems to be very informative in NBS families. No significant financial relationships to disclose.
Primary sarcoma and sarcomatoid carcinoma of the urinary bladder: Comparison of clinical features, treatment, and survival.
Authors: Jue Wang
Journal: Journal of Clinical Oncology (2016)

381 Background: Sarcomatoid carcinoma (SaC), sarcoma (SC) and of the urinary bladder are rare entity. As a result, the natural history of these unusual tumors and the optimal management are uncertain. In addition, no previous studies have directly compared the cancer specific survival of patients with SC and SaC to patients with urothelial carcinoma (UC) of the urinary bladder. Methods: Patients with diagnosis of SC, SaC and high grade UC of urinary bladder were identified in the Surveillance, Epidemiology and End Results program (SEER) (1973 to 2012). Demographic of patients and clinical characteristics at diagnosis were compared. Differences in cancer specific survival were compared using univariate and multivariate analysis. Results: A total of 470 patients with SC, 361 with SaC and 58, 835 patients with high grade UC were identified. Patients with SC were younger (p &lt; 0.001), more commonly in female (p &lt; 0.001); black (p &lt; 0.001), and advanced stage disease (p &lt; 0.001), in comparison with patients with high grade UC. On another hand, Patients with SaC were generally older than those with SC and UC. The 5-year cancer specific survival rate was 51.8 % for patients with high grade UC and 36.4% for SC; 32% for SaC. On multivariate analysis there was an increased mortality risk in patients with SaC vs high grade UC. Conclusions: Even after adjusting for demographic, and treatment characteristics, SaC has worst survival than SC and UC. The current finding support bladder cancer is a heterogeneous group of tumors with distinct clinical behavior, distinct prognostic implications, and should receive tailored treatment.
Activity of pomalidomide plus dexamethasone (Pom/dex) in dual lenalidomide/bortezomib refractory multiple myeloma (MM).
Authors: M. Lacy, M. A. Gertz, S. R. Hayman, A. Dispenzieri, S. Kumar, J. Mikhael, A. K. Stewart, J. Allred, S. J. Mandrekar, S. V. Rajkumar
Journal: Journal of Clinical Oncology (2010)

8002 Background: Patients with MM who have progressed after multiple novel agents have limited treatment options. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent. Pom/dex has demonstrated response rates (≥PR) of 63% in relapsed MM (JCO 2009, 27:5008-5014) and 32% in a lenalidomide-refractory cohort (ASH 2009). The efficacy of pomalidomide in patients who have failed both lenalidomide and bortezomib is unknown and this study was designed to study this question. Methods: Patients refractory to both lenalidomide and bortezomib therapy; defined as relapsing on or within 60 days of stopping each regimen, were enrolled. Pomalidomide was given orally 2 mg daily on days 1–28 of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis. Results: 35 patients resistant/refractory to lenalidomide and bortezomib were enrolled. The median age was 62 years (range, 39-77). The median time from diagnosis to enrollment was 63 months (range 27-249). 14 patients had high risk molecular markers including loss of 17p (N=5), t(4;14) (N=4) and plasma cell labeling index ≥3% (N=8) The median number of prior regimens was 6 ( 3-9) including 81% with ≥5 prior regimens. Toxicity consisted primarily of myelosuppression: grade 3/4 neutropenia (29%); grade 3/4 thrombocytopenia (3%); and grade 3/4 anemia (9.6%). Grade 3/4 non-hematologic toxicities occurred in 16%: pneumonitis (3%), hyperglycemia (3%), renal failure (3%), fatigue(3%) thrombosis (3%). Grade 1 or 2 neuropathy occurred in 6% (3% grade 1; 3% grade 2). Best responses consist of VGPR 3 pts (9%), PR 8 pts (23%), and MR 5 pts (14%) (ORR 46%). With a median follow-up of 2.7 months, 77% remain progression free, and 94% remain alive. Conclusions: Pom/dex is active and well tolerated in this heavily pre-treated population of dual bortezomib/lenalidomide-refractory MM patients. The majority of patients have not progressed and objective responses are seen in 49%. This study confirms therapeutic benefit for Pom/dex in patients relapsing after other novel therapies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Melanoma pigmentation affects melanoma-specific survival and provides a potential target for radiopharmaceutical-based imaging and therapy.
Authors: D. Kee, W. Liu, B. A. Devitt, R. Wolfe, R. Ware, R. Salemi, A. Dobrovic, S. Brglevska, J. Kelly, J. Callahan, A. Katsifis, P. Roselt, O. C. Neels, T. Bourdier, R. J. Hicks, G. A. McArthur
Journal: Journal of Clinical Oncology (2011)

8563 Background: The significance of melanoma pigmentation is poorly studied despite being fundamental to melanocyte biology. We examined its pathological and clinical associations in primary melanoma; and as a diagnostic target for the novel melanin binding PET tracer [18F]MEL050 in advanced melanoma. Methods: Data collected prospectively from 253 patients with primary cutaneous melanoma. Standard histological features, BRAF (exon 15) and NRAS (exon 2) mutation status, and clinical outcome results were correlated against pigmentation assessed macroscopically by a pathologist. Second, in 5 patients with stage III/IV melanoma planned for resection, we performed a pilot study of [18F]MEL050-PET in patients with positive FDG-PET imaging. Results: Pathological and outcome data obtained for 253 and 216 patients respectively with a median follow-up of 47 months. Lack of melanin was present in 46 of 253 (18.2%) of tumors and was associated with increased thickness, nonsuperficial spreading histotype, presence of ulceration and BRAF WT. On Cox proportional hazards analysis, amelanosis was an independent predictor of worse melanoma specific survival (MSS) and relapse free survival (RFS) but not overall survival (OS) (Table). [18F]MEL050 uptake was demonstrated in 3 of 3 patients with melanotic tumors with 60 min standardized uptake values (SUV) of 7, 10.4, 10.6. No significant tumor [18F]MEL050 signal in 2 of 2 patients with amelanotic tumors, or in 1 FDG-positive mediastinal node, presumed inflammatory. Conclusions: Loss of melanin synthesis occurs occasionally in primary melanomas and more frequently in metastases, and in our patient cohort was associated with a more aggressive phenotype and worse outcomes. [18F]MEL050 may thus allow noninvasive characterization of this apparently important prognostic factor. Cox proportional hazards analysis of outcomes. OS MSS RFS HR P value HR P value HR P value Age >60 2.6 0.008 2.0 0.11 1.4 0.35 Thickness per mm 1.3 <0.001 1.3 <0.001 1.3 <0.001 Ulceration 2.2 0.03 2.7 0.02 1.5 0.28 Amelanosis 2.0 0.06 2.5 0.03 2.3 0.03
Next Generation Sequencing Identifies Novel Oncogene Alterations In CRLF2-rearranged Precursor B-Cell Acute Lymphoblastic Leukemia
Authors: Akinori Yoda, Terry Haley, Oliver B. Weigert, Jeffery Kutok, Adalis Maisonet, Maura Salois, Edward Fox, David M Weinstock
Journal: Blood (2010)
Oncologists' dispositional affect and likelihood of end-of-life discussions.
Authors: William F. Pirl, Jennifer Lerner, Lara Traeger, Joseph A. Greer, Areej El-Jawahri, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2016)

9 Background: Oncologist-patient end-of-life (EOL) discussions are associated with less aggressive care at EOL. Prior research on EOL discussions has not explored the role of oncologists’ dispositional affect, trait patterns of emotional responses. Affect could possibly facilitate or hinder broaching difficult EOL topics. We examined associations between oncologists’ disposition for experiencing positive and negative affect and likelihood of EOL discussions reported by their patients with advanced cancers. Methods: 350 patients with incurable lung and GI cancers were enrolled in a randomized trial of early palliative care within 8 weeks of diagnosis. Oncologists providing care for participants completed a measure of dispositional affect, Positive and Negative Affect Schedule (PANAS). Positive and negative affect scales were analyzed dichotomously (above/below sample median). At 24 weeks in the trial, patients reported if they had ever discussed with their oncologist the care they would want to receive if they were dying (yes/no). Associations between oncologists’ affect and patient-reported EOL discussions were tested with multilevel models clustered by oncologist, adjusting for patient age, cancer type, and randomization. Results: At 24 weeks, 57/242 (23.6%) patients reported having had EOL discussions. The PANAS was completed by 17/19 (89%) oncologists with patients in the trial. Patients treated by oncologists with higher negative affect reported more EOL conversations, but this did not reach statistical significance: OR = 1.76 [.81, 3.83], p = .15. Patients treated by oncologists with higher positive affect also reported more EOL conversations, but this did not reach statistical significance: OR = 1.66 [.83, 3.35], p = .15. However, patients treated by oncologists with both higher positive and higher negative affect were over 3 times as likely to report having had EOL discussions: OR = 3.22 [1.02, 10.23], p = .046. Conclusions: Patients treated by oncologists with greater propensity to experience both positive and negative affect were more likely to report EOL discussions compared to those treated by oncologists who experience lower levels of affect. More research is needed to better understand these relationships.
A phase II trial to assess the activity and safety of the hypoxia-activated prodrug evofosfamide (TH-302) in combination with sunitinib in patients with disseminated grade 1 and 2 pancreatic neuroendocrine tumors (pNET) as a first-line approach: The GETNE-1408 trial.
Authors: Enrique Grande, Daniel E. Castellano, Ana B. Custodio, Rocio Garcia-Carbonero, Encarnación González, Carlos López-López, Javier Munarriz, Isabel Sevilla, Alexandre Teule, Marta Benavent Viñuales, Teresa Alonso, Pablo Gajate Borau, José Palacios, Jaume Capdevila
Journal: Journal of Clinical Oncology (2016)

TPS479 Background: Pancreatic-NETs are highly vascular tumors. The anti-angiogenetic sunitinib was approved in advanced pNETs based on prolongation of progression-free survival. Upregulation of several proangiogenic factors that reflects intratumor hypoxia conditions might drive resistance to sunitinib in pNETs. Evofosfamide is a prodrug that under hypoxic conditions preferentially releases a brominated version of isophosphoramide mustard and has shown activity in cell lines from neural crest derived tumors such as melanoma and glioblastoma/astrocytoma. We hypothesize that evofosfamide may have activity in the pathologic hypoxic conditions present in the tumor environment of neuroendocrine tumors inducing responses that may be consolidated and prolonged with sunitinib in patients with advanced pNETs that are naïve for systemic treatment. Methods: This is a prospective, non randomized, open-label, phase II study that is being conducted in 10 university sites belonging to the Spanish Task Force Group for NETs (GETNE) in Spain. Patients with histologically proven diagnosis of progressive unresectable or metastatic pNET with Ki67 &lt; 20% and grade 1 or 2 will receive sunitinib orally at 37.5 mg PO daily on days 1 to 28 of a 28-day cycle (4 weeks) plus evofosfamide administered at 340 mg/m2 by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 28-day cycle (4 weeks). Hypoxia-related tumor markers, single nucleotide polymorphisms related to activity and metabolism of antiangiogenic agents (VEGFR2, VEGFR3, PDGFR-α, VEGF-A, IL8, CYP3A4, CYP3A5, ABCB1-2) will be correlated with clinical outcome. In this study it is planned to include 43 patientsbased on a two-stage Simon’s phase II design (α = 0.05, β = 80%). If the trial shows 8 responses or more among 43 patients, the treatment will be considered for further investigation. EudraCT number: 2014-004072-30 Clinical trial information: NCT02402062.
Development of quality indicators for treatment of ductal carcinoma in situ (DCIS) of the breast using a multidisciplinary Delphi process.
Authors: May Lynn Quan, William Ghali, Peter S. Craighead, Heather E. Bryant
Journal: Journal of Clinical Oncology (2012)

248 Background: Ductal carcinoma in situ (DCIS) of the breast accounts for ~30% of new breast cancer diagnoses. Measuring quality of DCIS treatment is problematic due to its distinctively different clinical behaviour from invasive breast carcinoma, where standard outcomes such as mortality are not relevant. Therefore, we sought to develop clinically relevant quality indicators to evaluate treatment of DCIS. Methods: A Delphi consensus process was undertaken using a multidisciplinary panel of nine clinical and methodologic experts from Ontario, Alberta, and British Columbia. Panel members were nominated based on membership in provincial breast tumour site groups. Four criteria for a good quality indicator were used; the indicator measures a treatment that benefits the patient, there is support from scientific literature or professional consensus for benefit; the indicator is under control of the health care provider, the indicator is extractable from the medical record. Candidate indicators were identified from published clinical practice guidelines in North America. Three iterations of ratings using Likert scale rankings were utilized to identify final quality indicators, which were then prioritized. Results: A total of 10 candidate indicators were identified from four clinical practice guidelines encompassing the diagnosis, surgery and adjuvant treatment components of DCIS. A total of eight indicators were identified and prioritized (Table). Conclusions: We successfully developed practical quality indicators for evaluating the treatment of DCIS, which can be used in any jurisdiction to measure key performance benchmarks and identify variations in care warranting intervention or improvement. [Table: see text]
Timely access to care for colorectal cancer (CRC): A description and analysis of associated factors
Authors: G. A. Porter, K. M. Inglis, J. L. Murdoch, P. J. Veugelers
Journal: Journal of Clinical Oncology (2006)

6028 Background: There are multiple points in the presentation, diagnosis and treatment of CRC where access to physicians and/or medical services may affect the timeliness of appropriate care. A single interval, such as time from diagnosis to surgery, may incompletely reflect the timeliness of care in CRC. We describe the various components of access to care for resectable CRC, and identify factors associated with variation in such components. Methods: From 02/15/2002 to 02/15/2004, all patients undergoing surgery for primary CRC within a single health district were enrolled in a prospective consecutive cohort study. A comprehensive, standardized method of ascertaining specific time intervals, including a patient interview, was used to quantify the timeliness of presentation, diagnosis and surgery. Differences in these time intervals according to demographic and clinical factors were examined using multivariate linear regression. Results: Among the 455 patients in the study cohort, the median time intervals (interquartile range) for the various components of access to care were as follows: symptoms to first physician visit - 36 days (12–79); first physician visit to diagnosis - 51 days (15–127); diagnosis to surgery - 23 days (10–39). On multivariate analysis, the interval from initial symptoms to first physician visit was 96% longer for patients &lt; 50 years (p = 0.02) and 144% longer for rectal lesions (p &lt; 0.001). The interval from first physician visit to diagnosis was 190% longer for patients &lt; 50 years (p &lt; 0.001), and was positively correlated with gross household income (p = 0.02). The interval from diagnosis to surgery was 33% longer in females (p = 0.003) and 70% longer for rectal lesions (p &lt; 0.001). None of these intervals were found to vary significantly according to geographic residence, education level, body mass index, number of years with family doctor, smoking history, or previous use of CRC screening. Conclusions: The timeliness of access to care for CRC involves several defined components; the longest interval is from initial physician visit to diagnosis. Although associated factors vary somewhat according to the specific interval, interventions aimed at improving the timeliness of access to care in CRC should address younger patients and those with rectal cancer. No significant financial relationships to disclose.
Inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) to increase radiosensitivity of human pancreatic cancer (PAC) cell lines proficient in homology-directed repair (HDR).
Authors: Maeve A. Lowery, Fabio Vanoli, Kenneth H. Yu, Maria Jasin, Eileen Mary O'Reilly, Mary Ellen Moynahan
Journal: Journal of Clinical Oncology (2012)

204 Background: Radiation-induced single strand DNA breaks (SSBs) are primarily repaired by base excision repair, of which PARP1 is a key component. Unrepaired SSBs may cause collapse of stalled replication forks during DNA replication generating DNA double-strand breaks (DSBs). PARP inhibition has been shown to potentiate the effect of radiotherapy (RT) in a variety of human cancers in vitro and in vivo. We investigated the ability of the PARP inhibitor olaparib to radiosensitize BRCA1/2 wild-type human PAC cell lines and quantified repair capability of an induced DSB by HDR using the I-SceI-induced DSB DR-GFP assay. Methods: MiaPaCa -2 and ASPC-1 human PAC cells lines were exposed to RT administered in a single fraction by 157-gammacell irradiator at doses of 2, 4, 6 and 8 Gy in the presence or absence of olaparib at a dose of 500nM (4 hours pre and 20 hours post RT). Plates were incubated at 37C for 10-14 days and stained with Giemsa. Clonogenic survival assays following olaparib continuous exposure at concentrations up to 10 µM for 10-14 days were also performed. HDR of an induced DNA DSB was assessed in ASPC1 and MiaPaCa cell lines by co-transfection with an I-SceI expression vector and the DR-GFP reporter plasmid(Pierce et al., 1999), and in BRCA2 deficient CAPAN-1 cells harboring a stably integrated chromosomal DR-GFP gene (Moynahan et al. 2001). Results: Linear quadratic models were fitted to the data sets to generate survival curves. The half maximal inhibitory concentration (IC 50) of RT was 2Gy for both cell lines. The sensitivity enhancement ratio (SER) at 25% survival was 1.44 and 1.53 for MiaPaCa-2 and ASPC-1 cell lines respectively. Both cell lines were resistant to treatment with single agent olaparib to dose of 10µM and were proficient in HDR of DNA DSBs when compared to the BRCA2-deficient Capan-1 cell line. Conclusions: Inhibition of PARP increases radiosensitivity in human PAC cell lines proficient in HDR of DNA DSBs and resistant to treatment with single agent PARP inhibitor. Therapeutic strategies incorporating PARP inhibition and RT offer potential to improve clinical outcomes for patients presenting with localized sporadic and BRCA mutated PAC.