tbuckley/cabot-search huggingface dataset:
Prospective multicenter trial: Hormonal changes by switching from GnRH agonist to GnRH antagonist in patients with early stage of castration resistant prostate cancer as a second line hormonal therapy.
Authors: Hiroji Uemura, Yumiko Yokomizo, Masahiro Yao, Narihiko Hayashi, Kazuki Kobayashi, Jun-ichi Ohta, Kazuo Kitami, Takeshi Kishida, Akitoshi Takizawa
Journal: Journal of Clinical Oncology (2018)

e17030 Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. However, the hormonal changes by switching from GnRH agonist to GnRH antagonist remains obscure. We investigated whether the switching from GnRH agonist to GnRH antagonist (degalerix) for patients with castration resistant prostate cancer (CRPC) as the 2nd line hormonal therapy was effective, and analyze the hormonal changes of lutenizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T). Methods: 37 patients who were pathologically diagnosed as prostatic adenocarcinoma and developed CRPC after 1st line hormonal therapy with GnRH agonist plus anti-androgens were enrolled. After confirming anti-androgen withdrawal syndrome, they were treated with switching from GnRH agonists to degalerix. The primary endpoint was PSA response (PSA decline or up to 10%). Secondary endpoints were PSA progression free survival (PPFS), the time to treatment failure, cancer specific survival, and safety. Also, the change of LH, FSH and T between at baseline and 12 weeks after switching LHRH agonists were compared. Results: Mean age was 76 years old, super high risk; 20 cases (54.1%), high risk; 11 cases (29.7%), intermediate risk; 5 cases (13.5%), low risk; one case (2.7%). PSA responder rate was 13.5% (5 cases). In responders, the median PSA response time was 5.75 months, the median PPFS was 1.77 months. Regarding safety, 2 cases (5.4%) showed G3 of AE. LH levels showed significantly increase and FSH significantly decreased at baseline compared with 12 weeks. A PSA responder showed T decrease associated with LH increase and FSH decrease. Conclusions: The effectiveness of switching from GnRH agonist to GnRH antagonist showed to be limited. However, PSA response is possibly influenced by the change of LH and FSH. Although no predictive factor of the switching has been recognized, the change of gonadal hormones may be useful. Also, we expect the possibility of switching to GnRH antagonist in the early stage of CRPC. Clinical trial information: 000015300.
Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome
Authors: Gisela Teixido-Tura, Alberto Forteza, Jose Rodríguez-Palomares, Jesús González Mirelis, Laura Gutiérrez, Violeta Sánchez, Borja Ibáñez, David García-Dorado, Artur Evangelista
Journal: Journal of the American College of Cardiology (2018)
RANK expression predicts long term outcome in early luminal breast cancer
Authors: L. Kassem, P. Clézardin, I. Treilleux
Journal: Annals of Oncology (2018)

Background: Drugs targeting the RANK/RANK-ligand pathway may improve the outcome in early breast cancer, mainly due to prevention of bone metastasis. We aimed at exploring the value of RANK expression in primary breast cancer samples and its impact on the incidence of bone and visceral metastases. Methods: RANK expression was assessed in samples of 79 ER-positive/HER2-negative early breast cancer by immunohistochemistry in tissue micro array (TMA) blocks. Correlation between high and low RANK expression was done with the clinicopathological factors using Fisher's exact test and with bone metastasis free survival (BMFS), visceral metastasis free survival (VMFS) and overall survival (OS) using Kaplan Meier and Cox regression tests. Results: Median age at diagnosis was 56 years (42-85 years). RANK was highly expressed in 27 patients (34.2%) while 52 patients (65.8%) had low expression. BMFS in patients with high RANK expression was poorer than those with low expression with an 8y BMFS of 54.9% in patients with high expression versus 83.9% in the RANK low expression group (HR = 2.93, 95%CI: 1.36 to 6.30, p = 0.006). RANK expression was similarly associated with more visceral metastases with 8y VMFS of 54.5% versus 83.8% respectively (HR = 3.20, 95%CI: 1.47 to 6.99, p = 0.004). Moreover, OS was worse in cases with high RANK expression with 8y OS of 70.0% versus 90.2% respectively (HR = 2.79, 95%CI: 1.20 to 6.49, p = 0.017). In the multivariate analysis, high RANK expression was still an independent predictor for bone metastasis (HR = 2.43, 95%CI: 1.10 to 5.37, p = 0.028) and visceral metastasis (HR = 2.69, 95%CI: 1.21 to 6.0, p = 0.016). Conclusions: RANK expression in the primary ER+/HER2- breast cancer samples is associated with more bone and visceral metastasis denoting inherent aggressiveness of this subgroup of patients rather than organ tropism. Further research is still needed to confirm these results. Legal entity responsible for the study: Centre Léon Bérard. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Management and outcomes of 222 CLL patients (pts) treated with venetoclax (VEN) in the real world.
Authors: Chadi Nabhan, Andrew Klink, Jennifer Samp, James Michael Pauff, Jackie Nielsen, Brian Meissner, Holger Keim, Kaitlin Kennard, Anthony R. Mato
Journal: Journal of Clinical Oncology (2018)

7529 Background: VEN is an oral bioavailable BCL-2 inhibitor approved by the FDA in April 2016 for use in CLL. More data are needed to understand real world initiation, management and outcomes of CLL pts treated with VEN. Methods: This was a retrospective cohort study of CLL pts who initiated VEN. Investigators from 25 community centers provided pt-level data from medical records including demographics, clinical characteristics, ramp up management and outcomes. Tumor burden was assessed per FDA label, tumor lysis syndrome (TLS) was defined by Howard criteria and response was based on iwCLL criteria. The primary endpoint was response. Characteristics and outcomes were summarized by descriptive statistics. Results: 222 VEN pts were included, of whom 22% used VEN in combination with ibrutinib (7%) or an anti-CD20 (14%). Median age was 64 years (range 57-71); 82% had TP53 interruption ; 84% had ≥1 prior line of therapy (median 1; range 0-6); 62% had prior kinase inhibitor (KI) use; and 4% had prior use of 2 KIs. At baseline, 11%, 49% and 40% had low, medium and high tumor burden, respectively, and 27% initiated VEN as inpatient. During ramp up, 6% had a dose interruption; no dose modifications were reported due to hematologic abnormalities. TLS events occurred in 6% of pts (n = 13) with 2 pts experiencing clinical TLS, mainly among high risk pts. 34 pts (15%) discontinued VEN, mainly due to relapse (n = 5), refractoriness (n = 9), or in setting of disease response (n = 8). Maximum dose of 400mg was achieved in 53% of pts and 46% (n = 103) were maintained at doses < 400mg following ramp up. With a median follow up of 6.1 months, ORR was 75% (CR: 26%). Median time to best response was 3 months. Responses were not negatively affected by TLS or maintenance doses < 400mg. Among 38 pts assessed for minimal residual disease (MRD) during VEN, 23 (61%) were MRD negative. Resolution of baseline lymphadenopathy, lymphocytosis, or B symptoms were reported among 93%, 95%, and 96%, respectively. Conclusions: In this study, most VEN-treated CLL pts completed the ramp up, few experienced a TLS /hematologic event, and responses were comparable to clinical trials. Inpatient management deviated from the FDA label suggesting opportunity to improve adherence to initiation guidance.
Aberrant CD137 ligand expression induced by GATA6 overexpression promotes tumor progression in cutaneous T-cell lymphoma
Authors: Hiroaki Kamijo, Tomomitsu Miyagaki, Naomi Shishido-Takahashi, Rina Nakajima, Tomonori Oka, Hiraku Suga, Makoto Sugaya, Shinichi Sato
Journal: Blood (2018)
Towards personalised risk assessment and clinical management: A worldwide study of age-, sex-, geographic region-, gene- and cancer-specific risks for Lynch syndrome.
Authors: Aung K. Win, Jeanette C. Reece, Grant Lee, Robert W. Haile, Gabriela Möslein, Finlay A. Macrae, Mark A. Jenkins
Journal: Journal of Clinical Oncology (2018)

1526 Background: Lynch syndrome is a cancer predisposition caused by inherited mutations in mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or EPCAM. Accurate cancer risk estimates are required for mutation carriers and their family members to develop appropriate genetic counselling guidelines and targeted screening and clinical management. Cancer risks for Lynch syndrome may differ not only by age, sex and the gene mutated but also by the genetic variant and geographic region of the carrier. Methods: We analysed pedigree data (age, sex, cancer histories and mutation status of family members) of Lynch syndrome families that were submitted by researchers and clinicians from 23 countries to the International Mismatch Repair Consortium (IMRC) (http://www.sphinx.org.au/imrc). For each cancer, we estimated age-specific cumulative risk (penetrance) and hazard ratios for carriers compared with the general population. We estimated penetrance by: cancer site, sex, the gene mutated, type of mutation, and geographic region. Results: IMRC has already received pedigree data from 6651 families with a mismatch repair gene mutation (2214 MLH1, 2717 MSH2, 1118 MSH6, 558 PMS2, 44 EPCAM) throughout the world (2482 in North America, 101 in South America, 3307 in Europe, 431 in Asia, 330 in Australasia). Preliminary analyses suggest that the risk of colorectal cancer to age 70 is highest for both male and female carriers in Australasia and North America and lowest for carriers in South America and Asia. Conclusions: Preliminary results from this world's largest study on Lynch syndrome penetrance suggest that cancer risks for people with Lynch syndrome differ by geographic region, which is consistent with existence of environmental modifiers for the disease and might justify region-specific screening guidelines. Gene Region Hazard ratio Risk to age 70 males Risk to age 70 females MLH1 Europe 19 (14–26) 50% 32% North America 32 (26–38) 61% 48% Australasia 32 (22–46) 68% 55% South America 6 (1.5–22) 12% 10% Asia 7 (4.5–15) 20% 14% MSH2 Europe 14 (11–16) 39% 24% North America 33 (28–40) 61% 50% Australasia 36 (24–54) 73% 59% South America 70 (10–490) 82% 75% Asia 8 (4.8–17) 21% 15%
Abstract 14666: Treating Aging Model of Werner Syndrome Specific Induced Pluripotent Stem Cells by Crisper/cas9 Systems
Authors: Gakuto Yozu, Shinsuke Yuasa, Hiroyuki Daida, Keiichi Fukuda
Journal: Circulation (2016)

Backgrounds: Werner syndrome (WS) is a rare autosomal recessive disorder characterized by premature onset of several aging-associated diseases, such as atherosclerosis, diabetes, cancer, and early ...
Association of CD8+/FOXP3+ ratio and PD-L1 expression with survival in pT3N0M0 stage esophageal squamous cell cancer.
Authors: Yingming Zhu, Minghuan Li, Jinming Yu
Journal: Journal of Clinical Oncology (2017)

e15517 Background: Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). Methods: The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Results: Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p &lt; 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p &lt; 0.001). Conclusions: Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.
Early palliative care intervention for women with gynecologic malignancies.
Authors: Anne R. Van Arsdale, Merieme Klobocista, Cristian Zanartu, Priya Pinto, Bruce D. Rapkin, Dennis Yi-Shin Kuo, Gary L. Goldberg, Akiva Pesach Novetsky, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2016)

e21508 Background: While there have been reports of the benefit of early end-of-life planning and palliative care for women with gynecologic malignancies, the optimal timing and acceptability for early palliative care have yet to be defined. Methods: After IRB approval all patients defined as having a high risk gynecologic malignancies, less then 30% five year predicted survival, were referred to palliative care consultation within 8 weeks of tumor board registration for primary occurrence or recurrence. Patients were randomized to quality of life assessment by standardized QLQ-30 versus QLQ-30 and idiographic quality of life survey. The primary endpoint was increase in palliative consultation from historical 50% as reported at our tertiary care institution. Secondary endpoints included quality of life measures as well as metrics of aggressive care at the end of life. Results: At the time of interval assessment, 78 patients had been screened for early palliative care referral. Of these 58 patients were eligible for study, and 35 were seen in for palliative care 66%. The most commonly reported problem assessed at consultation were pain, and goals of care planning, including health care proxy. Of those patients not enrolled, reasons for nonparticipation included, refusal of medical oncologist to allow patient recruitment contact, death, enrollment in hospice, and patient refusal. 19% of all eligible and 32% of patients seen for early palliative care enrolled in hospice after consultation. Conclusions: Early palliative care intervention is feasible in the majority of patients diagnosed with high risk gynecologic malignancies within 8 weeks of tumor board registration. Additional cancer care and delivery research is needed to understand the association of early palliative care consultation with quality measures of end of life care and access to hospice care.
Early and late morbidity of radical hysterectomy with lymphadenectomy in early-stage cervical cancer: A prospective multicentric cohort of 232 patients.
Authors: Vincent Balaya, Léa Rossi, Charlotte Ngo, Anne-Sophie Bats, Patrice Mathevet, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2017)

e17007 Background: The aim of this study was to assess the early and late post-operative morbidity of patients who have undergone a radical hysterectomy (RH) for early-stage cervical cancer. Methods: We retrospectively analyzed the data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I &amp; II). Patients underwent a radical hysterectomy for early-stage cervical cancer between January 2005 and March 2012 in 23 French oncologic centers. Results: A total of 412 patients were enrolled and 284 had a radical hysterectomy. Data were complete for 232 patients: 115 by laparoscopic-assisted vaginal way, 80 patients by total laparoscopic way, 9 patients by total vaginal way, 22 patients by laparotomy and 6 patients by robot-assisted way. The median age was 44 years (range = 25-85 years). 89.6 % of patients had a stage IB1 disease. 72.4% were epidermoid carcinoma and 24.6% adenocarcinoma. Eighty-one patients (35%) had only a sentinel lymph node biopsy and 151 patients (65%) had an additional pelvic lymphadenectomy. There were 45 cases of urinary infections (19.4%), 17 cases of dysuria (7.3%), 10 cases of urinary incontinence (4.3%), and 6 cases of ureteral or vesical fistula (2.6%). The genito-femoral nerve was injured in 25 cases (10.7%) and the obturator nerve was injured in 22 cases (9.5%). There were 38 cases of limb lymphedema (16.3%) and 14 cases of pelvic lymphocyst (6%). Conclusions: These complications rates are similar with those found in the current literature. Urinary infections and limb lymphedema are the main complications of RH. The functional outcomes could be improved by applying nerve-sparing techniques. [Table: see text]
Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc).
Authors: Michael J. Overman, Patricia LoRusso, John H. Strickler, Sandip Pravin Patel, Stephen John Clarke, Anne M. Noonan, Thiru Prasanna, Manik A. Amin, John J. Nemunaitis, Jayesh Desai, Kenneth John O'Byrne, Thomas J. George, Judson Englert, Dewei She, Zachary A. Cooper, Yuling Wu, Anis Khan, Rakesh Kumar, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2018)

4123 Background: Oleclumab is a human mAb that binds to CD73 and inhibits production of immunosuppressive adenosine. This is a first-in-human study to investigate the safety, efficacy, and pharmacodynamics of oleclumab alone or in combination with durvalumab in patients (pts) with advanced panc or MSS-CRC. Methods: A 3+3 dose-escalation design was followed in which pts received one of 4 escalating doses of oleclumab IV with or without durvalumab 10 mg/kg IV Q2W until disease progression, followed by study expansion with high dose of oleclumab plus durvalumab 10 mg/kg Q2W. AEs and tumor response (RECIST v1.1) were assessed. Free soluble CD73 and cell surface CD73 on lymphocytes were measured by ELISA and flow cytometry, respectively. Tumoral CD73 was centrally assessed by an in situ enzyme assay and IHC. Results: The initial dose-escalation and PD exploration enrolled 42 monotherapy and 24 combination pts with no reported DLTs. The minimum target serum concentration was exceeded at the top 2 doses. Sustained decrease in free soluble CD73 and CD73 on peripheral T cells was demonstrated across all doses and pts. Decreased CD73 enzymatic activity was observed in all evaluable frozen tumor biopsy samples (n = 4) 20 days after treatment with the top 2 doses of oleclumab. Treatment with oleclumab alone decreased tumoral CD73 expression (5/9) while increasing CD8+ TILs in all 5 samples. Subsequently, durva + oleclumab highest dose was selected for expansion in 2-5L CRC (21 pts) and 2-3L panc (20 pts). The most commonly reported TRAEs in combo expansion were diarrhea (8.7%), pyrexia (8.7%), fatigue (6.5%), and increases in ALT (6.5%), AST (6.5%), and ALP (6.5%). PR was observed for 1/21 CRC (5L) and 2/20 panc (2 and 3L) pts; SD was observed in 2/21 CRC and 3/20 panc pts. Duration of treatment for subjects with disease control was 84-322 days (CRC) and 28-232 days (panc). Treatment is ongoing for 1 CRC (322 days) and 2 panc pts (140 and 182 days). Conclusions: Treatment with oleclumab and durvalumab had a manageable safety profile and PD consistent with mechanism of action. Combination therapy has encouraging clinical activity in panc and potentially in CRC pts. Clinical trial information: 02503774.
A novel circulating tumor cell blood test for early detection of colorectal, prostate, and breast cancers: Results from 709 samples.
Authors: Ashish Nimgaonkar, Oscar Segurado, Wen-Sy Tsai, SEE-TONG Pang, Ming-Feng Hou, Ying Chang, Drew Watson, Ying-Hsu Chang, Po-Hung Lin, Jen-chia Wu, Hung-Jen Shao, Jr-Ming Lai, Feng-Ming Lin, Si-Hong Lu, Shih-En Chang, Ben Hsieh, Mana Javey, Rui Mei
Journal: Journal of Clinical Oncology (2018)

e13549 Background: Early detection is key to reducing cancer deaths. Despite available screening options for many cancers, patients are still diagnosed in advanced stages. A sensitive, affordable blood test could improve testing compliance, and detect cancer at earlier, more treatable stages. Here we present results from prospective, multi-center, IRB-approved studies for colorectal, prostate and breast cancer. Methods: 2 to 4 mL blood were processed through the CMx test platform which includes biomimetic chip, proprietary EpCAM antibody and an air foam release mechanism to increase sensitivity. Released CTCs were confirmed with tissue-specific antibodies CK20, PSMA and mammaglobin. The diagnosis and staging of cancers was confirmed by biopsy. For colorectal and prostate cancer, a scoring system was developed based on an algorithm that incorporated CTCs and age. For breast cancer, a preliminary scoring is being evaluated. Results: In colorectal cancer, 620 subjects were evaluated and the test had a sensitivity of 87% for the detection of cancer and 77% for pre-cancerous lesions. The specificity of the test was 97.3%. In prostate cancer, 43 patients were evaluated prospectively with biopsy when indicated. BPH patients were excluded from analysis. The test detected 100% (25/25) confirmed cases of Stage I-III prostate cancer and correctly identified 100% (20/20) of healthy controls. A test developed for a subset of patients in the PSA gray zone (4-10ng/ml) following a PSA screen detected prostate cancer with a sensitivity of 80% and specificity of > 90%, showing a potential to significantly reduce unnecessary biopsies compared to standard of care tests. In breast cancer, in a training set of 26 patients, the test detected 83% of patients with Stages I to III. Additional samples are being collected to develop and validate a prediction algorithm. Conclusions: This study demonstrates that the CellMax CTC blood test is capable of detecting colorectal, prostate and breast cancers with high concordance to established tests. This blood draw based globally affordable test can be integrated into a patient’s routine physical increasing testing compliance and enabling more cancers to be detected early.
Nationwide in hospital outcomes of allogenic hematopoietic cell transplant (AHCT) in acute myeloid leukemia (AML).
Authors: Meera Yogarajah, Johnn Muthu
Journal: Journal of Clinical Oncology (2017)

e18542 Background: AHCT is the definitive treatment for AML with unfavorable risk however with increased morbidity and mortality limiting its use in adults above 60 years of age. National in patient sample (NIS) database was analyzed to study trends and predictors of mortality in AML patients receiving AHCT. Methods: NIS database includes 20% of all hospitalizations in USA. NIS database from 2010 - 2014 was analyzed. ICD-9 codes were used to extract patients and to analyze demography, comorbidities, complications and outcomes. A multivariable logistic regression was performed to identify predictors of mortality. Results: 1755 patients with AML and AHCT were identified from the database. Males 55.2%, median age 52, age &gt;60 years 35%, Whites 80.6%, Blacks 5.5%, Hispanics 6.7% and others 7.2%. Median length of stay was 26 days. Inpatient mortality showed a decreasing trend from 2010 to 2014 (6.7%, 4.6%, 3.9%, 4.8%, 4.6%) likely due to better supportive care. p (trend) = 0.29. Univariate analysis for age &gt;60 years did not show increase in mortality however multivariate analysis did show increase in mortality (Odds ratio 2.281, p = 0.006). Other predictive factors of increased mortality were presence of complications of AHCT. Infection (OR 8.392, p &lt; 0.001), acute graft versus host disease (GVHD) (OR 2.139, p = 0.033) and pneumonia (OR 3.584, p &lt;0.001) were associated with increased mortality. Independent predictive factors of mortality were renal failure (OR 14.186, p &lt; 0.001) and liver disease (OR 3.228, p &lt; 0.001). Conclusions: Age more than 60 by itself is not associated with increased mortality in the absence of complications and comorbidities. Infection is a major predictor of mortality. [Table: see text]