tbuckley/cabot-search huggingface dataset:
New insights in cisplatin and radiation-induced ototoxicity: A French Childhood Cancer Survivors Study (FCCSS).
Authors: Brice Fresneau, Felicia Santos, Rodrigue Allodji, Chiraz Fayech, Stephanie Bolle, Giao Vu-Bezin, Vincent Souchard, Nadia Haddy, Francois P. Doz, Delphine Berchery, Pierre Lemire, Neige Journy, Cristina Veres, Laurence Brugieres, Dominique Valteau-Couanet, Ibrahima Diallo, Christelle Dufour, Florent De Vathaire
Journal: Journal of Clinical Oncology (2019)

10061 Background: Platinum chemotherapy (CT) and cranial radiotherapy (RT) are risk factors of ototoxicity. Effects of RT dose at inner ear and of other CT were investigated. Methods: Of 7670 5-year childhood cancer survivors from the FCCSS treated before 20 years of age in 1942-2000 for solid cancer or lymphoma, 5243 with ototoxicity long-term follow-up data were included. Severe ototoxicity, defined as the need of hearing aids or Brock grade 3-4 hearing loss, was identified from self-administrated questionnaires, clinical visits and cohort linkage with the French Hospital Database and health insurance information system (SNIIRAM). The mean RT dose at inner ear was estimated using home-made software. Multivariable Cox models adjusted for gender, age at diagnosis, time period and social deprivation index was used to identify risk factors for severe ototoxicity. Results: After a mean follow-up of 30 years, 199 cases of severe ototoxicity were identified. Cumulative incidences at 30 and 50 years of age (30,50y-CumInc) were, 2.8% (95%CI = 2.4-3.3) and 5.5% (4.6-6.5), respectively. Mean RT dose at inner ear (Hazard Ratio HR = 1.6 (95%CI = 1.0-2.5), 4.5 (2.7-7.2), 5.7 (3.0-10.8) and 14.0 (9.2-21.2) for 0- &lt; 5, 5- &lt; 30, 30- &lt; 40 and ≥40 Gy), as well as cisplatin (HR = 2.8, 95%CI = 1.9-4.0), melphalan (HR = 3.3, 95%CI = 1.9-5.7) and busulfan exposure (HR = 2.6, 95%CI = 1.6-4.4) were significantly associated with severe ototoxicity. Concerning melphalan (n = 199/5243 exposed), almost all cases were identified in neuroblostma patients (NBL), who also received cisplatin 200mg/m²/cycle (26/92 NBL, 30y-CumInc = 36.4% (95%CI = 25.9-48.4), vs. 3/107 non-NBL, 30y-CumInc = 1.6% (0.4-5.6)). Concerning busulfan (n = 131/5243 exposed), all cases were identified in NBL (n = 16/63, all treated with melphalan and cisplatin) and brain tumors (n = 13/28, all with RT at inner ear ≥5Gy). The 30y-CumInc in patients with RT at inner ear ≥5Gy was 7.4% (95%CI = 5.7-9.6) and 39.8% (22.5-60.0) respectively with and without busulfan. Conclusions: RT at inner ear has significant deleterious impact on audition, with cumulative incidence still worsening &gt; 30years after RT, and with likely potentiation by busulfan. The deleterious effect of melphalan was related to previous treatment with cisplatin, either by interaction between these drugs, or by the high cisplatin dose by cycle used in NBL.
Prognostic value of tumor parameters measured by MRI in cervical cancer patients receiving CCRT.
Authors: Chang Sun, Shun Lu, Ran Lin Wang, Hanyi Zhang, Mingyu Tan, Jin Yi Lang
Journal: Journal of Clinical Oncology (2019)

e17027 Background: This study aimed to evaluate the response of solid tumors after the completion of external beam radiotherapy (EBRT) and investigate the prognostic value of tumor parameters such as tumor volume and size (TV &amp; TS) and tumor volume reduction rate (TVRR) early during the treatment in local advanced cervical cancer patients. Methods: We retrospectively reviewed 310 Chinese patients with locally advanced cervical cancer. They were all received concurrent chemoradiotherapy (CCRT) during the treatment based on intensity modulated radiotherapy (IMRT). Clinical data at the time of diagnosis, including FIGO stage, TV and TS were measured by pelvic magnetic resonance imaging (MRI) before and after EBRT were available. Information about distant metastasis, relapse and date of death was also collected, with a follow-up until Aug 2018. Youden index was used to identify the optimal cut-off point of continuous tumor parameters and divide patients into subgroups. Prognostic factors (age, FIGO stage, RT dose, pre-RT TS and TV, mid-RT TS and TV, TVRR) were using the log-rank test and Cox regression models to analyze the association between predictors and time-to-event outcomes. Results: The median follow-up time was 50 months. In univariate analysis, the FIGO stage, TVRR, TV and TS were associated with overall survival rate. Interestingly, the group of higher TVRR showed a better OS, PFS and LRFS than the group of lower TVRR ( P &lt;0.05). Moreover, the groups of lower TV and TS showed better OS, PFS and LRFS than the higher groups, respectively. In the OS-related multivariate analysis, the mid-RT TV remained statistically significant after adjustment for age and FIGO stage ( P &lt; 0.05). In the PFS-related multivariate analysis, the tumor volume reduction rate (TVRR) remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P &lt;0.05). In addition, in the LRFS-related multivariate analysis, TVRR also remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P &lt;0.05). Conclusions: Our results confirmed that tumor parameters including TS, TV and TVRR, measured before the completion of CCRT, are valuable prognostic factors in patients with locally advanced cervical cancer.
Safety and activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrent glioblastoma (GBM).
Authors: Roy E. Strowd, Benjamin M. Ellingson, Patrick Y. Wen, Manmeet Singh Ahluwalia, Anna F. Piotrowski, Arati Suvas Desai, Jennifer Leigh Clarke, Frank S. Lieberman, Serena Desideri, Louis B. Nabors, Xiaobu Ye, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2019)

2027 Background: Hypoxia inducible factor 2-alpha (HIF2a) mediates cellular responses to hypoxia and is overexpressed in GBM. PT2385 is an oral HIF2a inhibitor with in vivo activity against GBM. Methods: A two-stage single-arm open-label phase II study of adults with first recurrent GBM following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium. PT2385 was administered at the phase II dose (800 mg b.i.d.). The primary outcome was objective radiographic response (CR+PR); secondary outcomes were safety and survival. Exploratory objectives included PK (day 15 Cmin), PD, and pH-weighted amine-CEST MRI to quantify tumor acidity at baseline and explore associations with drug response. Stage 1 enrolled 24 patients with early stoppage for ≤1 response. Results: Of the 24 patients, mean age was 61±11 years, median KPS 80, MGMT promoter methylated in 46%. PT2385 was well tolerated. Grade ≥3 drug-related AEs were hypoxia (n = 2), anemia (1), hyperglycemia (1), hyponatremia (2) and lymphopenia (2). No objective radiographic responses were observed; median PFS was 1.8 months (95%CI 1.6-3.1). Drug exposure varied widely (Table) and did not differ by corticosteroid use (p = 0.12), antiepileptics (p = 0.09), or sex (p = 0.37). Patients with high systemic exposure had significantly longer PFS (6.7 vs 1.8 months, 0.009). Non-enhancing infiltrative disease with high acidity gave rise to recurrence. Baseline acidity correlated significantly with treatment duration (R 2 = 0.49, p = 0.017). Conclusions: Drug exposure to PT2385 was variable. Signals of activity were observed in GBM patients with high systemic exposure and acidic (e.g. hypoxic) lesions on baseline imaging. A second-generation HIF2a inhibitor is being studied. Clinical trial information: NCT03216499. [Table: see text]
The results of colorectal cancer screening in the Republic of Kazakhstan during the period from 2013 to 2018.
Authors: Dilyara Kaidarova, Alma Zhylkaydarova, Yelena Ukolova, Abay Jumanov
Journal: Journal of Clinical Oncology (2019)

e13074 Background: Colorectal cancer (CRC) remains one of the actual problems in oncology. In 2017, in the structure of oncopathology of the Republic of Kazakhstan (RK), CRC took the 3rd place in terms of incidence - 17.5, and in mortality - 8.2 per 100 thousand people. The population screening of CRC has been introduced in the Republic of Kazakhstan since 2011, among the population aged 50 to 70 years, with a survey interval every 2 years. Fecal immunochemical test (FIT) and total colonoscopy (TC) were introduced in 2013. Methods: For the period 2013 - 2018, 5133602 subjects were examined. The analysis of screening indicators was carried out: the number of positive results of FIT, completion rate of follow-up colonoscopy and CRC detection rate. The analyzed groups were divided into regions with: A - high (26 - 30.7 per 100 thousand people), B - medium (13.2-21.8), C - low (5.9 - 10.8) incidence. Results: The positive FIT for the study period was found on average, in 1.23% (62971) positive results in the Republic of Kazakhstan, in group A it was 1.50% (27675), in group B - 1.26% (17178), and in group C - 0.94% (18118). The number of TC: in group A - 76.1% (21067), in group B - 75.8% (13016), in group C was 66.7% (12080), in total - 46163 cases in the Republic of Kazakhstan, which is 73.3% of indications. During the period of study 2480 patients with colorectal cancer were identified: in group A - 0.07% (1236), in group B - 0.05% (638), in group C - 0.03% (606) people. Conclusions: For regions with different incidence rates is necessary to define performance indicators to improve the quality assurance in CRC screening.
Monitoring of neuroendocrine tumors in elderly patients in the Brittany region.
Authors: Jean-Philippe Metges, Delphine Deniel Lagadec, Marc Pracht, Astrid Lievre, Gilles Robinet, Sandrine Estivin, Romain Corre
Journal: Journal of Clinical Oncology (2019)

e15690 Background: NeuroEndocrine Tumors (NETs) remain a poorly known entity, especially in older patients. The therapeutic management is multidisciplinary combining surgery, interventional radiology, chemotherapy, cancer supportive care and also geriatrics oncology. The aim of this study performed by the OncoGeriatry Coordination Unit (UCOG) of Brittany, in collaboration with the National Reference Network for the management of NET (RENATEN), was to analyze the current management of NETs in older patients (more than 75 years old) and to develop recommandations to optimize the management of elderly patients with NENs. RENATEN’s guidelines mean systematic discussion of the cases in Regional Multidiscplinary Tumor Board (MTB) dedicated to NETs (RENATEN MTB). Methods: This study is a retrospective observational study including patients aged 75 years and over, with a NET that has been diagnosed in an pathological laboratory or whose file has been discussed in a MTB (usual MTB or RENATEN MTB) between 2014 and 2017 in the Brittany area. Results: 51 patients with a median age of 79 years [75-92] have been included up until now, among whom 77% had digestive NET, 12% urological, 8% dermatological (Merkel tumor), 4% pulmonary, 2% gynecological and 2% NETs of unknown origin. Tumor grade was 1, 2, 3 and unkown in 20%, 14%, 37% and 29% respectively. Overall, 33% of the tumors were well differentiated and 63% were metastatic (synchronous metastases :78%). Only 20% of patients benefited from a geriatric oncology consultation to help the clinician in the therapeutic decision. File of 53% of patients has been discussed one time in a specialized RENATEN MTB and 57% in another MTB. No proof of discussion in MTB was found in 12%. The treatment proposed in the RENATEN MTB was effective in 85% of patients (2 patients died immediately after RENATEN MTB, 2 patients did not wish to be treated). Only 14% of patients received initial surgery, 10% radiotherapy and 41% chemotherapy. The overall survival of this cohort is 11.3 months [0.3 -89] (for grade 3, 7.9 months [0.8-21.7]). Conclusions: The rate of multidisciplinary meeting presentation has to be improved, as well as the geriatric oncology management. A cohort of more than 100 patients will be presented at the meeting and treatment response and survival data based on age class, tumor grade, histological subtypes and therapeutic strategy will be shown.
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma
Authors: Thierry Facon, Shaji Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O’Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur Raje, Michel Attal, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Tahamtan Ahmadi, Christopher Chiu, Jianping Wang, Rian Van Rampelbergh, Clarissa M. Uhlar, Rachel Kobos, Ming Qi, Saad Z. Usmani
Journal: New England Journal of Medicine (2019)

Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.
Patient-reported outcomes during hospitalization for patients with late discharge after an open surgery for GYN tumors.
Authors: Xin Shelley Wang, Qiuling Shi, Charles S. Cleeland, Ting-Yu Chen, Araceli Garcia-Gonzalez, Maria Iniesta-Donate, Tsun Hsuan Chen, Donna Griffin, Larissa Meyer
Journal: Journal of Clinical Oncology (2019)

e18078 Background: Using patient-reported outcomes (PRO) in perioperative care is increasingly common in patients undergoing major surgery. Few reports relate the patient’s symptomatic status using validated PROs during hospitalization with other outcomes, such as length of stay (LOS). Methods: Patients with GYN tumors scheduled for open surgery at MD Anderson Cancer Center were recruited prospectively. The MD Anderson Symptom Inventory gynecology perioperative care module (MDASI-PeriOp-GYN) was used to assess symptoms daily during hospitalization. Longitudinal analysis compared patient’s PROs between groups who were discharged within and beyond the median LOS. Results: From Feb 2018–Dec 2018, 83 patients were evaluable. The median LOS was 3 days. 70% of patients were discharged within 3 days, and 30% were hospitalized longer (defined as late discharge group, range 4-10 days). The median LOS for the two groups was 5.64 vs. 2.41 days, P &lt; .0001. Compared to patients who were discharged within 3 days, late discharge patients had longer surgical time (310 min vs. 209 min, P &lt; .0001), and greater operative blood loss (668mL vs. 289 mL, P &lt; .001). Additionally, more patients in the late discharge group had a worse performance status (ECOG PS 2-3: 24% vs. 3.5%, P &lt; .05), and higher comorbidity (Charlson comorbidity Index &gt; 1: 92% vs. 69%, P &lt; .05), and more used opioids within 6 month pre-surgery (16% vs. 1.7%, P &lt; .05). For all patients, the 5 worst symptoms during the first 3 hospital days were pain, fatigue, drowsiness, dry mouth, bloating. Late discharge patients reported significant more severe pain, distress, dry mouth, and interference with walking during the first 3 days post-surgery (all P &lt; .05). Conclusions: Despite all patients undergoing standardized perioperative care on an Enhanced Recovery pathway, this study demonstrates how baseline and intraoperative factors are associated with longer LOS and more severe symptom burden, especially pain and interference with walking.
Performance of Oncotype Dx test in patients with T1bN0, grade 1, hormone receptor-positive, HER2-negative breast cancer.
Authors: Vinay K. Gudena, Lindsey Causey, Dawn Stuart, Keisha Martini
Journal: Journal of Clinical Oncology (2019)

e12043 Background: NCCN (National comprehensive cancer network) recommends to consider Oncotype DX testing for patients diagnosed with T1bN0 stage 1A breast cancers that are hormone receptor positive and HER-2 negative. This study is a retrospective review of these patients diagnosed at Cone Health Cancer Center between 2012 and 2018 who had Oncotype DX testing. Methods: Patients with T1b hormone receptor positive and HER-2 negative breast cancers, who had Oncotype DX testing performed were queried from tumor registry from 2012 to 2018. Registry provided data on the patients ER/PR and Her 2 neu as well as whether they received chemotherapy. Patient charts were reviewed for grade, Ki 67 and their Oncotype Dx scores. Results: A total of 104 patients with T1b N0 (stage IA ) invasive breast cancers that were ER and PR positive and HER-2 negative between 2012 and 2018 had Oncotype DX test performed. Grade 1 tumors comprised 75 patients. Among these, four patients received adjuvant chemotherapy who had Oncotype scores of 22, 27, 29 and 38. Among patients with Ki 67 ≤ 10% and grade 1, only one patient out of 104 required chemotherapy. Conclusions: This retrospective analysis suggests that 97% of patients with T1b, grade 1, ER/PR positive, HER-2 negative breast cancers had Oncotype scores of less than 25. Hence Oncotype testing may be safely omitted for this group. Grade along with Ki 67 can identify a subset of T1bN0 ER/PR positive and Her 2 negative patients who do not need Oncotype testing.[Table: see text]
Sarcoidosis as a paraneoplastic syndrome for breast cancer.
Authors: Pamela Barletta, Mukunthan Murthi, Douglas Salguero, Mehdi Mirsaeidi
Journal: Journal of Clinical Oncology (2019)

e12587 Background: Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The pathogenesis of sarcoidosis is believed to be a result from a cellular immune reaction from exposure to occupational, environmental, or infectious elements that lead to the formation of noncaseating granulomas. Non-caseating granulomas are also present in cancer , and it is well known that the cancer cells carry neo-antigens, leading to a possible association between cancer and sarcoidosis. Several studies have shown an increased risk of breast cancer , in particular, in patients with sarcoidosis, but only a few studies have analyzed the incidence of sarcoidosis following breast cancer diagnosis. The present study aimed to identify patients with sarcoidosis following a diagnosis of breast cancer in our cohort of sarcoidosis. Methods: This is a retrospective case-series study between 2008-2018 of patients with sarcoidosis in the University of Miami Sarcoidosis Program. Sarcoidosis was defined per the World Association for Sarcoidosis and other Granulomatous Disorders guidelines. Breast cancer diagnosis was confirmed through pathology. We collected demographic data of age, gender, ethnicity and the time between diagnosis of breast cancer and sarcoidosis by chart review. Clincial data including clinical manifestations, laboratories, staging, and treatment were also collected. Results: Among 125 patients in our registry, 26 patients had a diagnosis of both cancer and sarcoidosis. In this, 12 (46%) developed sarcoidosis after the diagnosis of breast cancer and are the study population. Among them, 12(100%) were female. The most common ethnic group in the study population was European American with 8(67%) followed by African Americans 2(16.7%) and Hispanic 2(16.7%). Eight (67%) patients were treated with chemotherapy, 7(58%) with radiotherapy, of this, 6 (50%) received both. Mean (SD) age of onset of sarcoidosis was 61.9 ( 10.8) years . The mean time interval between breast cancer diagnosis and the onset of sarcoidosis was 5.58 ( 5.24) years ( (see Figure 1). Nine (75%) had pulmonary sarcoidosis and 3(25%) cardiac sarcoidosis. Among the subjects with pulmonary sarcoidosis 1(11.1%) had Stage 4, 4(44.4%) had Stage 2 and 4(44.4%) had stage 1. Conclusions: Our findings suggest sarcoidosis may be a paraneoplastic characteristic of breast cancer. The mechanism of granuloma development remains unclear. Cancer mediated immune dysregulation could be a potential contributing factor. Further studies are warranted to establish a definitive association.
Abstract 2872: Non-uniform Muscle Contraction Sustains and Facilitates Triggered Arrhythmias in Rat Cardiac Muscle
Authors: Taichi Nishio, Masahito Miura, Taiki Hattori, Naomi Murai, Chiyohiko Shindoh
Journal: Circulation (2009)

Background: Arrhythmias are benign or lethal depending on the sustainability and frequency of the arrhythmia, and lethal arrhythmias are prone to occur in diseased hearts with non-uniform muscle co...
Adequacy of self-reported family history in electronic health record for genetic risk assessment for Lynch syndrome.
Authors: Mala Pande, Connie Okon, Y. Nancy You, Susan K. Peterson, Banu Arun, Patrick M. Lynch
Journal: Journal of Clinical Oncology (2019)

1515 Background: Self-reported family cancer history (FCH) is one of the key indicators of hereditary cancer risk. Studies have shown that accurate FCH documentation by healthcare providers is suboptimal, but data regarding patient-provided FCH are limited. We evaluated the quality of FCH as entered by the patient into the electronic health record (EHR) to determine its adequacy for Lynch syndrome (LS) risk assessment. Methods: At our tertiary referral cancer center, FCH is self-reported via an online questionnaire sent prior to appointment, which is reviewed/updated by clinic nurse during initial visit and then imported into EHR review of systems. Records of all new patients from September 2016 to August 2017 were retrospectively reviewed and analyzed. FCH quality was estimated by calculating rates of reporting of 3 FCH variables required for PREMM5, a risk-prediction model for LS. Parameters required for the model were sex, age, personal history of cancer, and for FCH, degree of kinship (first/second degree), cancer site/type, and age at diagnosis. Results: Of 47,647 unique patients, 47.5% reported FCH for 1 or more relative (46.1% were first degree, 64.8% second degree, 3.0% other, and 2.4% missing). A cancer type/site was specified for 88.8% reporting FCH. Age at diagnosis was listed for 21.7% of the relatives’ cancers. Overall, only 20.9% provided all 3 FCH data elements required for running PREMM5 (9.9% of the total sample, n=4738). Fewer men (9.5%) than women (28.1%) provided all 3 FCH elements. Furthermore, 46.7% of breast cancer patients, 21.9% of gastrointestinal cancer patients, 47.2% and 23.1% of patients seen for cancer prevention screening and endoscopy respectively, reported 3 FCH elements. Lower rates were observed for other cancers. Conclusions: Patient self-reported FCH is suboptimal for estimation of LS risk and genetic counseling referral. Future steps to optimize online patient-facing FCH collection to enable routine automated risk-assessment in an essentially provider-free setting may include, patient education regarding importance of FCH, EHR prompts for FCH completion, and implementation of algorithms in EHRs using FCH to identify patients at risk for hereditary cancer predisposition syndromes.