tbuckley/cabot-search huggingface dataset:
Late anorectal complications and psychosocial impact: A report from the Childhood Cancer Survivor Study.
Authors: Arin L Madenci, Bryan V Dieffenbach, Daisuke Yoneoka, Jamie Knell, Brent Weil, Andrew J Murphy, Todd M. Gibson, Yutaka Yasui, Wendy Leisenring, Rebecca M. Howell, Lisa Diller, Kevin R. Krull, Gregory T. Armstrong, Kevin C. Oeffinger, Christopher Bertero Weldon
Journal: Journal of Clinical Oncology (2018)

e22512 Background: We sought to evaluate late anorectal complications (LAC) and psychosocial impact among childhood cancer survivors. Methods: We identified survivors of childhood cancer diagnosed in 1970-1999 who self-reported LAC, defined as anorectal fistula, stricture, or pathology-confirmed subsequent malignant neoplasm (SMN) > 5 years from diagnosis. We evaluated incidence and risk factors for LAC and associations between LAC and psychosocial morbidity, defined by the Brief Symptom Inventory-18 (BSI-18) and 36-Item Short Form Health Survey (SF-36), compared to age-adjusted normative data. Results: Among 24,304 survivors (mean±standard deviation age = 29.9±8.8, follow-up time = 16.6±6.6 years), the 35-year cumulative incidence of LAC (fistula, n = 173; stricture, n = 75; anorectal SMN, n = 14) was 0.017% (95% confidence interval [CI] = 0.014-0.020); median age at occurrence was 24 years (range 5-52). Compared to siblings, survivors were not at significantly increased risk of LAC (hazard ratio [HR] = 1.29, 95% CI = 0.95-1.75), adjusting for age, sex, race, and body mass index. Among survivors, risk factors for LAC included pelvic radiotherapy ≥50 Gy (ref. none, HR = 4.44, 95% CI = 2.90-9.32), and > 2 abdominal/pelvic surgeries (ref. no surgeries, HR = 2.62, 95% CI = 1.68-4.09), adjusting for age, sex, tobacco use, and decade of diagnosis. LAC was independently associated with psychosocial impairment (Table). Conclusions: Late anorectal complications are uncommon among childhood cancer survivors. However, in survivors who experience them, there is substantial psychosocial morbidity, warranting conscientious efforts to reduce symptoms. Table. Associations between LAC and psychosocial morbidity Measure ORa 95% CI SF-36 physical component Physical health 2.68 1.02-7.03 Bodily pain 3.11 1.11-8.76 General health 3.92 1.57-9.78 SF-36 mental component Emotional role 4.15 1.90-9.10 Social function 7.93 3.49-19.03 Mental health 3.53 1.49-8.39 Summary 4.26 1.92-9.43 BSI-18 Depression 2.52 1.61-3.96 Anxiety 2.52 1.67-3.80 Somatization 1.72 1.06-2.77 Global 2.14 1.39-3.30 aAdjusted for age, sex, race, education, income, body mass index, cranial or pelvic radiotherapy, and number of surgeries
Propensity score-matched analysis of systemic chemotherapy versus hysterectomy for patients with residual cervical disease after definitive radiotherapy/concurrent chemoradiotherapy.
Authors: Munetaka Takekuma, Fumiaki Takahashi, Seiji Mabuchi, Wataru Kudaka, Koji Horie, Mariko Ikeda, Ayumi Shikama, Akira Mitsuhashi, Shoji Nagao, Shiro Suzuki, Mika Mizuno, Shin Nishio, Hideki Tokunaga, Yukinobu Ota, Takahiro Kasamatsu, Ryo Kitagawa, Takafumi Toita, Hiroaki Kobayashi, Mitsuya Ishikawa, Nobuo Yaegashi
Journal: Journal of Clinical Oncology (2018)

5527 Background: Patients with persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy (RT/CCRT) have a poor prognosis. Salvage hysterectomy (HT) is considered curative treatment; however, very little data exists showing the survival advantage of HT over standard therapy. Methods: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005–2014 were reviewed retrospectively. Those who underwent a HT for residual cervical disease after definitive RT/CCRT were matched (histology, FIGO stage at initial treatment, brachytherapy application, age and performance status at diagnosis of residual tumor, diameter and parametrial invasion by residual tumor, and the number of lymph node tumors at diagnosis, etc.) with propensity scores for patients who underwent systemic chemotherapy (CT). Oncologic outcomes between the two groups using a propensity score matched–cohort analysis were compared. Results: A total of 142 patients with residual cervical disease after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). A difference in all background factors between HT and CT groups was not observed. At a median follow-up of 4.6 years, 33 (46.5%) and 47 deaths (66.2%) occurred in HT and CT groups, respectively. Median overall survival was 3.8 and 1.5 years in HT and CT groups, respectively (p= 0.0019, hazards ratio [HR] 2.438, 95% confidence interval [CI] 1.362–4.361), and median progression-free survival was 2.7 and 0.7 years, respectively (p= 0.0046, HR 2.235, 95% CI 1.262–3.960). Increasing tumor size was significantly associated with a high incomplete resection rate (p= 0.0385, Odds Ratio 0.941, 95% CI 0.888–0.997). The cut-off value for the residual tumor diameter regarding complete resection after receiver operating characteristic (ROC) analysis was 11 mm (sensitivity 70%, specificity 86.9%). Conclusions: Salvage HT may be considered curative treatment for patients with residual cervical disease after definitive RT/CCRT. The diameter of residual tumor is important in selecting appropriate candidates for HT.
Systematizing precision oncology clinical trial participation through the integration of electronic medical record (EMR) data and routine tumor profiling.
Authors: Eddy Shih-Hsin Yang, Robert D Johnson, Kat Kwiatkowski, Justin Brown, Betty Prescott, Desiree Mitchell, Dan R Rhodes
Journal: Journal of Clinical Oncology (2018)

e18578 Background: Inadequate recruitment of patients represents a major impediment to successful completion of precision oncology clinical trials. Rapid and efficient identification of all potentially eligible patients across a healthcare system, along with broad access to tumor profiling, is a vital component to trial accrual. Integrating EMR data and routine tumor profiling may overcome this clinical challenge. Methods: IRB approval was obtained to retrospectively prescreen patients via the EMR as part of a recruitment strategy for next-generation tumor sequencing (NGS). Patients in the UAB Comprehensive Cancer Center EMR with cancer were included. The EMR was queried for patient demographics, treatment codes, diagnosis codes, pathology codes, and patient encounters. Resulting data tables were de-identified and linked in a HIPAA-compliant process. An informatics platform developed at Strata Oncology (“Strata POINT”) generated a list of patients with prostate cancer potentially eligible for the TRITON 2 and TRITON 3 clinical trials. Prioritized patient lists were returned to authorized hospital study staff to re-identify eligible patients for tumor profiling utilizing the StrataNGS test. Results: A total of 11,111 cancer patients were identified. Of these, 790 were documented to have prostate cancer. Using treatment codes and filtering for second generation anti-androgens and taxane-based chemotherapies, we found 38 patients potentially eligible for TRITON 2 and 51 patients potentially eligible for TRITON 3. Of the 89 patients, 23 had clinic visits within the week following the date that query results were available. 40 patients have since received tumor profiling, and 5 patients had alterations in BRCA2 (n = 3) or ATM (n = 2). Conclusions: We demonstrate a novel methodology for rapidly identifying patients for precision oncology clinical trials by integrating EMR data and routine tumor profiling. This approach offers a powerful tool for increasing patient access to precision medicine across a large healthcare system.
Essential Role of<i>BRCA2</i>in Ovarian Development and Function
Authors: Ariella Weinberg-Shukron, Mariana Rachmiel, Paul Renbaum, Suleyman Gulsuner, Tom Walsh, Orit Lobel, Amatzia Dreifuss, Avital Ben-Moshe, Sharon Zeligson, Reeval Segel, Tikva Shore, Rachel Kalifa, Michal Goldberg, Mary-Claire King, Offer Gerlitz, Ephrat Levy-Lahad, David Zangen
Journal: New England Journal of Medicine (2018)

The causes of ovarian dysgenesis remain incompletely understood. Two sisters with XX ovarian dysgenesis carried compound heterozygous truncating mutations in the BRCA2 gene that led to reduced BRCA2 protein levels and an impaired response to DNA damage, which resulted in chromosomal breakage and the failure of RAD51 to be recruited to double-stranded DNA breaks. The sisters also had microcephaly, and one sister was in long-term remission from leukemia, which had been diagnosed when she was 5 years old. Drosophila mutants that were null for an orthologue of BRCA2 were sterile, and gonadal dysgenesis was present in both sexes. These results revealed a new role for BRCA2 and highlight the importance to ovarian development of genes that are critical for recombination during meiosis. (Funded by the Israel Science Foundation and others.).
Health-related quality of life (HRQoL) deterioration and pain progression in men with non-metastatic castration-resistant prostate cancer (M0 CRPC): Results from the PROSPER study.
Authors: Gerhardt Attard, Fred Saad, Bertrand F. TOMBAL, Maha Hussain, Cora N. Sternberg, De Phung, Shevani Naidoo, Katharina Modelska, Arlene Reisman, Cristina Ivanescu, David F. Penson
Journal: Journal of Clinical Oncology (2018)

5010 Background: The Phase 3 PROSPER trial (NCT02003924) showed a statistically significant improvement in metastasis-free survival (MFS) with enzalutamide (ENZA; n = 933) vs. placebo (PBO; n = 468) in asymptomatic men with M0 CRPC and prostate-specific antigen doubling time ≤10 months. We report the results of the HRQoL and pain evaluations. Methods: Functional Assessment of Cancer Therapy–Prostate (FACT-P) and Brief Pain Inventory, Short Form, were used to assess HRQoL and pain at baseline (BL) and every 16 weeks during treatment. Pain progression was defined as ≥2 points in pain severity items and mean scores increase from BL; HRQoL improvement/deterioration as an increase/decrease from BL using pre-established thresholds for clinically meaningful difference. Time to first confirmed (at two consecutive visits) and unconfirmed HRQoL deterioration/pain progression were assessed using Kaplan-Meier estimates and Cox proportional hazards models under censoring not at random assumption. Results: BL characteristics and scores were similar between arms with low pain (median 0) and high HRQoL (median FACT-P total score, 121). Decrease in attrition rate was greater in PBO vs. ENZA mainly due to disease progression (53% vs. 68% at week 49, respectively). Most patients reported no change or improvement in HRQoL. Proportion of patients with pain progression at week 49 was similar between ENZA (11–20%) and PBO (14–21%). Lower risk of pain progression was observed with ENZA vs. PBO in the confirmed analysis (hazard ratio [HR] 0.78–0.93; p > 0.05). Nominal statistically significant lower risk of deterioration was observed with ENZA for FACT-P total, FACT Advanced Prostate Symptom Index, prostate cancer subscale (PCS), and emotional well-being (EWB) in the confirmed (HR 0.75, 0.77, 0.77, 0.69, respectively; p < 0.05) and for PCS and EWB in the unconfirmed (HR 0.82, 0.80, respectively; p < 0.05) analyses. Conclusions: In PROSPER, ENZA significantly delayed MFS vs. PBO without worsening HRQoL and significantly reduced the risk of clinically meaningful HRQoL deterioration in several FACT-P domains. Pain progression was similarly low in both arms. Clinical trial information: NCT02003924.
TCT-453 Appropriateness of Transcatheter Aortic Valve Replacement: Insight from the OCEAN-TAVI Registry
Authors: Taku Inohara, Sreekanth Vemulapalli, Shun Kohsaka, Yusuke Watanabe, Shinichi Shirai, Norio Tada, Motoharu Araki, Toru Naganuma, Futoshi Yamanaka, Hiroshi Ueno, Minoru Tabata, Kazuki Mizutani, Akihiro Higashimori, Kensuke Takagi, Masanori Yamamoto, Kentaro Hayashida
Journal: Journal of the American College of Cardiology (2018)
Burden of illness in patients with acute myeloid leukemia aged ò65 years ineligible for intensive chemotherapy.
Authors: Marie-Helene Lafeuille, Murali Sundaram, Patrick Lefebvre, Bruno Emond, Hela Romdhani, Mekre Senbetta
Journal: Journal of Clinical Oncology (2017)

e18529 Background: Management of older patients with acute myeloid leukemia (AML) is challenging due to a higher comorbidity burden, poorer performance status and less favorable biology. This study assessed treatment patterns and healthcare resource utilization (HRU) in the US in patients diagnosed with AML aged ≥65 years who did not receive intensive chemotherapy. Methods: Patients aged ≥65 years with ≥2 diagnoses for AML were identified from the Truven Health MarketScan Analytics Databases (01/01/2011-07/31/2016). Patients had ≥1 bone marrow diagnosis procedure (BX; first AML diagnosis following BX defined as the index date), ≥12 months of continuous eligibility pre-index, no treatment with intensive chemotherapy at any time, no diagnosis for AML relapse or remission or stem cell transplant before BX, and &lt;2 diagnoses for other blood cancers pre-index. Post-index treatment patterns and HRU were reported. Results: 1,492 patients with AML were identified (mean [standard deviation] age: 76.8 [7.0] years; 61% males). Mean post-index follow-up was 212 (255) days and 43% were treated with antineoplastic agents (AA). Most common first-line treatments were azacitidine (35%), decitabine (32%) and hydroxyurea (16%). 4% received low-dose cytarabine. Patients with ≥1 blood transfusion (61%) received 8.9 (9.5) transfusions per month during 177 (244) days on average. A total of 3% received stem cell transplant. Patients had a mean of 3.7 (5.3; pre-index: 0.4 [0.7]) days of hospitalization, 0.2 (1.4; pre-index: 0.0 [0.2]) days of hospice care, and 5.2 (4.5; pre-index: 2.6 [2.4]) office visits per month post-index. Compared to treated patients, untreated patients (32%; i.e., patients with no AA, blood transfusion or stem cell transplant) had fewer days of post-index follow-up (106 vs. 263), more days of hospitalization (4.8 vs. 3.2), and of hospice care (0.4 vs. 0.1), and fewer office visits (3.8 vs. 5.8) per month (all P&lt;0.01). Conclusions: Patients ≥65 years diagnosed with AML not receiving intensive chemotherapy incurred more HRU after AML diagnosis. About a third was untreated and had higher HRU than treated patients. This suggests major unmet needs for well-tolerated treatment options for these patients.
P01.001 Bevacizumab use in adult pilocytic astrocytoma, a single center experience
Authors: M Ruff, D Carabenciov, J Uhm
Journal: Neuro-Oncology (2018)

BACKGROUND: Temozolomide (TMZ) administered daily with radiation therapy for six weeks, followed by adjuvant TMZ for six months is standard therapy for patients (pts) with newly diagnosed glioblastoma (GBM).Thrombocytopenia (TBP) usually appears in 10 % of patients and is Downloaded from https://academic.oup.com
Depression in patients with a metastatic cancer: Analysis of 796,072 cases.
Authors: Eric Adjei Boakye, Kahee A. Mohammed, Nosayaba Osazuwa-Peters, Paula Buchnan, Jiajing Chen, Eric S. Armbrecht, Thomas E. Burroughs
Journal: Journal of Clinical Oncology (2016)

6572 Background: Cancer diagnosis often triggers depression among patients, and depression is associated with poor health behavior as well as poorer overall prognosis. The purpose of this study was to examine the predictors of depression among patients with a metastatic tumor. Methods: We conducted a cross-sectional analysis of 796,072 hospital records from 2008 – 2013 National Inpatient Sample for patients with a procedure code for metastatic tumor, per the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Depression was defined using ICD-9-CM for major depressive disorder. Weighted, multivariable logistic regression model was used to examine the association between sociodemographic and clinical factors and depression among patients with a metastatic tumor. Results: The prevalence of major depressive disorder in patients with a metastatic tumor in our study sample was 9.1%. In multivariable analysis, we found an inverse relationship across age groups with the younger age group, 45 years or less (adjusted odds ratio [aOR] = 2.44; 95% CI: 2.32 – 2.57) more likely to be depressed. Compared to men, women were more likely to be depressed (aOR = 1.72; 95% CI: 1.69 – 1.75), as were patients with a higher number of comorbidities (aOR = 1.15 per 1 unit increase in Elixhauser comorbidity score, 95% CI: 1.14 – 1.15). African Americans were less likely to be depressed than Caucasians (aOR = 0.51; 95% CI: 0.49 – 0.52). In addition, patients who had Medicare (aOR = 1.34; 95% CI: 1.31 – 1.37) or Medicaid (aOR = 1.18; 95% CI: 1.15 – 1.22) were more likely to be depressed compared to those with private payer. In comparison to patients admitted to hospitals in the Northeast, the rates of depression were higher in the Midwest (aOR = 1.26; 95% CI = 1.23– 1.29). Finally, compared to patients with lung cancer, lower odds of depression were noted in patients with any type of cancer except for prostate cancer (aOR = 1.16; 95% CI = 1.11– 1.21). Conclusions: Based on these findings, healthcare providers should regularly screen patients with metastatic cancer for depression, particularly those in higher risk categories and can work collaboratively with patients on evidence-based psychological support and pharmacological treatments.
Comprehensive genomic profiling to identify clinically relevant genomic alterations in patients with advanced penile cancers.
Authors: Andre Poisl Fay, Russell Madison, Richard J. Lee, Jose A. Karam, Jeffrey S. Ross, Vincent A. Miller, Phil Stephens, Siraj Mahamed Ali, Sumanta K. Pal, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

4573 Background: Penile cancer (PC) is a rare disease with incidence highest in the developing world. Advanced disease has poor clinical outcome as effective systemic therapies are lacking. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs) that may help to understand the biology underlying PC and to explore targeted therapy opportunities. Methods: DNA was extracted from 40 microns of FFPE sections from 37 patients with penile cancers. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 627X for up to 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies approved/experimental in mechanism-driven clinical trials. Results: All but a single case were squamous cell carcinoma, and were predominantly from western countries. The median age of the PC patients was 62 years (range 25 - 87 years). HPV-16, HPV-6, and HPV-11 were found in 8 (21.6%), 1 (2.7%), and 1 (2.7%) patients, respectively, with the rest being HPV negative. There were 223 total GA (mean 6 GA/specimen) involving 73 individual genes and 91 CRGA were found (mean 2.5 CRGA/ specimen) involving 29 genes (Table 1). EGFR amplifications occurred in 22% of cases with a median copy number of 19, and were mutually exclusive from PIK3CA alterations (8/9 mutations) in 24% of cases. The CCND1/FGF3/4/19 amplicon was found in another 8.1% of cases and FGFR3 and FBXW7 mutations in another 5.4% of cases each, with these cases lacking the other oncogenic drivers listed above. No significant relationship of GA to HPV status was observed. Conclusions: CGP identified CRGAs in 97.3% of PC cases, with EGFR amplifications and PIK3CAalterations occurring in a mutually exclusive fashion, with both potentially able to benefit from targeted therapy. Studies are in progress to assay cases from endemic countries to assess whether the biology is distinct from cases of western origin, particularly in light of HPV status. Gene Short Variants CNA Rearrangement CDKN2A 16 4 1 NOTCH1 9 0 3 PIK3CA 8 1 0 EGFR 0 8 0 CCND1 0 5 0 FBXW7 4 0 0 BRCA2 3 0 0 FGFR3 3 0 0
Pre-chemotherapy functional and body status of patients with advanced gastrointestinal cancer in comparison to breast cancer patiens and healthy women.
Authors: Katrin Stuecher, Claus Bolling, Lutz Vogt, Axel Dignass, Rolf Kleinschmidt, Winfried Banzer
Journal: Journal of Clinical Oncology (2016)

e15005 Background: Many studies report that frailty, cachexia and decreased physical function during chemotherapy (CT) of cancer patients predict a higher mortality risk. Although a high prevalence of these symptoms in gastrointestinal (GI) cancer patients is known, there is almost no data on functional and body status in this population. The aim of the study is to compare muscle status and physical function of patients with advanced GI cancer to breast cancer patients and healthy women. Methods: In a 3-arm cross-sectional study 30 female advanced cancer patients (UICC ≥ III) (breast (n = 15; 63.9 ± 2.3 years; BMI 23.6 ± 3.8 kg/m2); GI (n = 15; 70.1 ± 3.1 years; BMI 23.6 ± 5.3 kg/m2) before first-line CT and 15 healthy age-matched women (69.4 ± 1.4 years; BMI 24.2 ± 3.3 kg/m2) are examined. Body composition was obtained from bioelectrical impedance analysis, daily physical activity from accelerometry (Actigraph), self-selected gait speed by using a capacitive force-measuring platform (Zebris) and maximal isometric voluntary force (MIVF) by a strain gauge force transducer (ASYS). Results: ANOVA with post-hoc test and Bonferroni correction show sign. differences in functional and body status of GI cancer patients compared to breast cancer patients and healthy women. GI cancer patients show lower values in phase angle (4.5 ± 0.8°; 5.4 ± 0.4°; 5.3 ± 0.5 °; p < .01), MIVF (5.5 ± 2.2 ; 9.1 ± 3.3 ;8.4 ± 1.8 N/kg/body weight; p < .01). The moderate to vigorous activity (7.3 ± 11.9; 36.9 ± 28.5 min; p = .001), steps per day (3125 ± 2396; 8703 ± 4104, p < .001) and gait speed (3.5 ± 1.1; 4.9 ± 0.6 km/h; p < .001) are sign. decreased compared to healthy women. Conclusions: This is one of the first studies with detailed information and comparative analysis on the functional and body status of patients with advanced GI cancers before CT. The functional and body status is very limited before CT compared to advanced breast cancer patients and healthy women. Gait speed, phase angle and force are below the cut-off values for low prognosis of survival and may reflect a diminished tolerance of CT. Measures to improve muscle status, physical function and its effects on treatment is warranted in advanced GI cancer patients. Clinical trial information: 129/14.