tbuckley/cabot-search huggingface dataset:
Immunohistochemical identification of <i>SDHA</i>-mutant gastrointestinal stromal tumors (GISTs).
Authors: Andrew J. Wagner, Stephen P. Remillard, Yixiang Zhang, Jason L. Hornick
Journal: Journal of Clinical Oncology (2012)

10029 Background: GISTs are most commonly driven by activating mutations in KIT or PDGFRA. However, 15% of GISTs in adults and &gt;90% in children lack such mutations. A subset of KIT/PDGFRA wild-type GISTs shows distinctive morphologic and clinical features and loss of expression of succinate dehydrogenase (SDH) B. Only a fraction of SDHB-deficient GISTs carry loss-of-function mutations in SDHB or SDHC. Due to the complexity of its locus and the presence of several pseudogenes, SDHA is rarely analyzed. Recently, mutations in SDHA were shown to lead to loss of expression of SDHA and SDHB in paraganglionomas. We sought to determine whether SDHA IHC could identify GISTs with SDHA mutations. Methods: Tumors (n=11) with features of SDH-deficient GIST (gastric origin, epithelioid morphology, multinodular/plexiform architecture) were selected from pathology archives under an IRB-approved protocol. Expression of SDHA and SDHB was determined on tumor sections by IHC. Genomic DNA was isolated from SDHA-negative tumors and amplified using primers specific to introns flanking each of the 15 SDHA exons. Amplicons were bidirectionally sequenced and compared to genomic repository data. Exons with somatic mutations were also examined in DNA from corresponding normal tissue to determine germline status. Results: All tumors (100%) were deficient for SDHB expression by IHC. Four of 11 (36%) SDHB-deficient GISTs also lacked expression of SDHA. SDHA expression was intact in the 7 remaining tumors, including 3 with known SDHB (n=2) or SDHC (n=1) mutations. Nonsense mutations in SDHA were identified in all 4 SDHA-deficient tumors, caused by a single base pair (bp) substitution (n=3) or a single bp deletion (n=1), and heterozygous mutations were also found in DNA from normal tissue of all 4 patients. Somatic loss of the 2 nd allele has thus far been found in 3 of 4 tumors; 2 by loss of heterozygosity and 1 by a 13-bp deletion. Further analysis of the 4 th specimen is ongoing. Conclusions: SDHA mutations are a common cause of SDH-deficient GISTs and result in combined loss of expression of both SDHA and SDHB. Loss of SDHA expression by IHC reliably predicts SDHA mutations and can be used to select cases for SDHA genetic testing.
Efficacy of gemcitabine/irinotecan in female patients ≤ 56 yrs with metastatic pancreatic cancer
Authors: J. A. Posey
Journal: Journal of Clinical Oncology (2006)

14139 Background: Pancreatic cancer remains extremely lethal due to marginally effective systemic therapies. Erlotinib, a tyrosine kinase inhibitor combined with gemzar has recently been approved for use in advanced disease for a modest improvement in survival. Other combinations with gemzar have demonstrated higher response rates in randomized trials, but without survival benefit. Gemzar and irinotecan was an early combination with promise from phase I/II findings; however, results from a randomized trial did not support wide use of the regimen. Methods: Five successive female patients, not on-study, with unresectable pancreatic cancer were treated with gemcitabine(Gem) and irinotecan (CPT-11) from 10/00 to 12/05 following a highly successful outcome in one patient who remains alive and without active disease. Two patients received Gem at 1 gm/m 2 /CPT-11 at 100 mg/m 2 on days 1+8 every 21 days and three patients received fixed-dose rate (FDR) Gem 900 mg/m 2 and CPT-11 at 100 mg/m 2 on days 1 + 15 every 28 days. Ages at presentation were 47, 49, 50, 53, and 56. All patients had metastatic disease with primary tumors involving the head 2, body 2, and neck 1. One patient had recurrent metastatic disease following adjuvant xeloda/ XRT. One pt had a hx of diabetes. Number of courses ranged 4–12. One pt received in addition CI 5-FU/ XRT and 1 pt received 5 doses of FDR Gem prior to progressing and receiving combination treatment. Results: 39 courses of Gem/CPT-11 were administered on D1 + 8 or 15. Treatment delays occurred twice with both schedules due to grade 3 neutropenia. Grade ½ toxicities include nausea, fatigue, and diarrhea. 3 CR, {2 &gt; 4 yrs}, 1SD, 1MR Conclusions: The quality and durability of the observed responses in this subset of pancreatic cancer patients’ has prompted an archival comparative tissue analysis of patients enrolled on PANCAN institutional trials during this period. No significant financial relationships to disclose.
HOW DOES THE ASE ALGORITHM FOR INTEGRATING MULTIPLE PARAMETERS OF MITRAL REGURGITATION SEVERITY COMPARE WITH AN MRI STANDARD?
Authors: Islamiyat Babs Animashaun, Edgar Argulian, Lillian Aldaia, Leo Marcoff, Stephen James Horgan, Konstantinos P. Koulogiannis, Steven Wolff, Linda D. Gillam, Seth Uretsky
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF SOCIOECONOMIC DISPARITIES ON PATIENT OUTCOMES UNDERGOING MITRACLIP
Authors: Medhat Farwati, Anas Saad, Mohamed M. Gad, Keerat Rai Ahuja, Manpreet Kaur, Agam Bansal, Vardhmaan Jain, Essa Hariri, Nicholas Kassis, Amar Krishnaswamy, Samir R. Kapadia
Journal: Journal of the American College of Cardiology (2020)
A comparison between next-generation sequencing and ASO-qPCR for minimal residual disease detection in multiple myeloma.
Authors: Hiroyuki Takamatsu, Ryoichi Murata, Jianbiao Zheng, Martin Moorhead, Yasushi Terasaki, Takashi Yoshida, Malek Faham, Shinji Nakao
Journal: Journal of Clinical Oncology (2013)

8601 Background: Although molecular CR in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual which is laborious and time-consuming. The usage of the LymphoSIGHT method, a next-generation sequencing (NGS)-based platform, may overcome these challenges and increase sensitivity and specificity. We compared the LymphoSIGHT approach with ASO-qPCR for minimal residual disease (MRD) detection in autografts in the autologous peripheral blood stem cell transplantation (ASCT) setting. Methods: Seventeen Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a PR or CR after ASCT. Bone marrow (BM) slides from 13 MM patients and fresh BM cells from 4 MM patients at diagnosis as well as autografts were obtained for DNA extraction. Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. The presence of the myeloma clonotype was then assessed in follow-up samples. Results: MRD in autografts was detected in 6 of 17 (35%) by ASO-qPCR and 13 of 17 (76%) by NGS. When MRD was assessed by NGS, 6 MRD (+) cases received post-ASCT therapy while 4 MRD (-) cases and 7 MRD (+) cases were followed without post-ASCT therapy. The MRD (-) cases tended to show a better PFS than the MRD (+) cases with post-ASCT therapy (P = 0.26) and those without post-ASCT therapy (P = 0.09) although overall survival rates were comparable among the three groups. There was no difference in PFS between MRD (-) and MRD (+) cases when MRD was assessed by ASO-qPCR (P = 0.6). These studies will be extended in 30 additional MM patients, and results will be presented. Conclusions: MRD-negativity in autografts revealed by NGS may be more closely associated with durable remission of MM than that revealed by ASO-qPCR.
Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial
Authors: Gary Middleton, Kristian Brock, Joshua Savage, Rhys Mant, Yvonne Summers, John Connibear, Riyaz Shah, Christian Ottensmeier, Paul Shaw, Siow-Ming Lee, Sanjay Popat, Colin Barrie, Gloria Barone, Lucinda Billingham
Journal: The Lancet Respiratory Medicine (2020)
Psychological study of adolescent and young adult (AYA) cancer patients and their parents throughout and beyond their cancer treatment: A pilot study.
Authors: Helen Hatcher, Carole Lack, Cathy Walsh, Laura Abbas, Jo Fretwell, Wendy Moss, Nicky Dobson, Ian Goodyer, Salma Alam
Journal: Journal of Clinical Oncology (2012)

9589 Background: The cancer journey for an AYA is often complicated by diagnostic delays, poor prognosis and negative physical and psycho-social consequences. Distress of young patients and survivors is often overlooked and the real incidence of psychopathology remaining hidden. We aimed to understand the psychological impact and identify which factors most affect the patient experience. Methods: 172 patients on the Cambridge AYA register were invited to take part. Patients were asked to complete 2 questionnaires, SCL90 and RSQ, measuring psychological symptoms and response styles respectively, and to take part in a semi-structured interview. Parents were asked to complete the York Survey and be interviewed. Results: 33 patients and 45 parents/others were recruited. Questionnaires completed: 33 SCL90 and RSQ; 42 York Survey. Interview data from: 23 patients, 26 parents, 3 others. Patient sample: 16 male, 17 female; mean age (recruitment) = 20.76 (16-26); age (diagnosis) = 17.26 (12-24). Diagnoses evenly distributed across solid and haematological malignancies. All patients had experienced significant levels of psychological distress at some point in their cancer journey. 51% reached caseness on the SCL90 (showed a symptom profile consistent with a high risk of a disorder). Caseness increased with age and was correlated with higher rumination scores. Positive influences included family, friend and peer support, good communication and support from the AYA service and specialist nurses. Negative influences included delayed diagnosis, poor communication styles, anxiety about long term effects and lack of appropriate psychological support. Conclusions: We have shown evidence of elevated psychological symptoms in this population. Patients and their families have prioritized clear needs; early diagnosis, high quality of information and communication, access to psychological help at each stage and post treatment help in gaining independence and planning for a positive future. We should work towards meeting these needs for this vulnerable group.
DIFFERENTIAL PATTERNS OF MEAN AORTIC VALVE GRADIENT RISE IN PATIENTS WITH BIOPROSTHETIC VALVE DEGENERATION AFTER SURGICAL AORTIC VALVE REPLACEMENT
Authors: Phoebe Erickson, Alexander Camacho, WEI HE, Ayman Shaqdan, Judy Hung, Sammy Elmariah
Journal: Journal of the American College of Cardiology (2020)
Which treatment options impact outcomes in elderly chronic lymphocytic leukemia patients with high prevalence of comorbidity?
Authors: Sacha Satram-Hoang, Carolina M. Reyes, Khang Hoang, Fayez Momin, Sridhar Guduru, Sandra L. Skettino
Journal: Journal of Clinical Oncology (2013)

7016 Background: Therapy selection in chronic lymphocytic leukemia (CLL) patients is based on disease severity as well as patient characteristics such as age and comorbidity. While treatment outcomes are mostly available from clinical trial data in younger patients, less is known about the effect of comorbidities on outcomes in elderly CLL patients in the real-world setting. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was utilized in this retrospective cohort analysis of 3,366 first primary CLL patients. Patients were diagnosed between 1/1/1998-12/31/2007, were &gt;66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received first-line treatment with any oral or infused therapy. CLB is covered by Medicare Part D and data for its use were only available from 2007-2009 in the dataset. Cox regression with backward elimination and propensity score weighted Cox regression estimated the relative risk of death. Date of last follow-up was 12/31/2009. Results: There were 153 CLB, 606 R-mono, 702 R+IV Chemo, and 1,905 IV Chemo-only patients. CLB and R-mono patients were older at diagnosis with mean age of 77 compared to R+IV Chemo (73 years) and IV Chemo-only (76 years; p&lt;.0001). Patients administered R-mono had a higher comorbidity burden and more advanced disease compared with other treatment groups. In the survival analysis we compared CLB to R-mono during the time period 2007-2009 and R+IV Chemo to IV Chemo-only during the time period 1998-2009. The adjusted multivariate survival analysis revealed a significant mortality risk reduction with R+IV Chemo compared with IV Chemo-only patients (HR, 0.72; 95% CI, 0.62-0.84) while a non-significant mortality risk reduction was noted with R-mono compared to CLB patients (HR, 0.47; 95% CI, 0.21-1.05). Older age and increasing comorbidity score were significantly associated with higher mortality. Conclusions: These findings suggest that chemo-immunotherapy is more effective than chemotherapy in an elderly population with a high prevalence of comorbidity. This extends the conclusions from clinical trials in younger, medically fit patients.
THE PROGNOSTIC VALUE OF [15O]H2O POSITRON EMISSION TOMOGRAPHY DERIVED MYOCARDIAL ISCHEMIC BURDEN
Authors: Pepijn Van Diemen, Jan-Thijs Wijmenga, Roel Driessen, Michiel Bom, Stefan Schumacher, Wynand Stuijfzand, Pieter Raijmakers, Henk Everaars, Ruben De Winter, Peter van de Ven, Albert van Rossum, Ibrahim Danad, Paul Knaapen
Journal: Journal of the American College of Cardiology (2020)
INFECTIVE ENDOCARDITIS OF UNICOMMISURAL AORTIC VALVE COMPLICATED BY MITRAL-AORTIC INTERVALVULAR FIBROSA PSEUDOANEURYSM
Authors: Salima Bhimani, Jared Klein, Hani K. Najm, Robert Stewart, Patel Chandrakant, Rukmini Komarlu
Journal: Journal of the American College of Cardiology (2020)
Salvage chemotherapy with paclitaxel, ifosphamide and nedaplatin for cisplatin refractory germ cell tumors
Authors: T. Miki, Y. Mizutani, T. Nomoto, T. Nakamura, A. Kawauchi, D. Oka, K. Nishimura, N. Nonomura, A. Okuyama
Journal: Journal of Clinical Oncology (2006)

4587 Background: Only 20–30 % of patients with cisplatin (CDDP) refractory germ cell tumor (GST) will remain continuously disease free with salvage chemotherapy. The present study investigated the chemotherapy with paclitaxel (TXL) in combination with ifosphamide (IFM) and nedaplatin (NDP), which is a derivative of CDDP, as salvage chemotherapy for CDDP refractory GCT. Methods: Between 2000 and 2005, 33 patients with CDDP refractory GCT were enrolled. All patients were male, with median age 30 (range: 17–45). Median number of previous regimens was 2 (range: 1–4). The combination chemotherapy consisted of TXL: 200 mg/m 2 on day 1, NDP: 100 mg/m 2 on day 2 and IFM: 1.2 g/m 2 on day 2–6 every three weeks. Results: A median of 5 cycles was administered to 33 patients. Grade 3/4 toxicity were reported as follows: neutropenia: 90%, thrombocytopenia: 70%, anemia: 70%, nausea/vomiting: 90%, diarrhea: 6%, alopecia: 97%. No treatment related death was observed. Response rate was 82% (CR: 9%, PR m− : 67%, PR m+ : 6%, NC: 6%, PD: 6 %). Nineteen (58%) patients achieved a no evidence of disease status with a median duration of follow-up of 18 months (7–60 months). Six patients (18%) remain alive with disease. However, 8 patients (24%) died of the disease. Conclusions: This study demonstrates that the chemotherapy with TXL in combination with IFM and NDP showed a significant anticancer activity for patients with CDDP refractory GCT. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for CDDP refractory GCT. No significant financial relationships to disclose.
Neuroendocrine tumors of uterine cervix in Mexican women.
Authors: Lucia Edith Flores, Dan Green, Daniela Morales-Espinosa, Lucely Cetina
Journal: Journal of Clinical Oncology (2012)

e15569 Background: Neuroendocrine tumors of the uterine cervix are rare, aggressive, and carry a poor prognosis. Most are small cell (SCNEC) and large cell (LCNEC). The limited knowledge of this neoplasm is based on small series due to the rarity of the diagnosis.There is a lack of information about NEC in Latin America. We describe both demographic and clinical characteristic of Mexican patients; and their multidisciplinary management in a reference center. Methods: We studied retrospectively clinical and histopathological variables of 33 women treated at the National Cancer Institute of Mexico from 1991 to 2010 with NEC. Patients were allocated into groups according to staging (Group 1 FIGO stages IB1 and IB2; Group 2 IIA-IVA, and Group 3 IVB). Results: Mean age at diagnosis was 50 y.o.; mean tumour size was 4.9 cm. There were 59.4% SCNEC and 40.6% LCNEC. Stage at diagnosis: IB1 15% (n=5), IB2 3% (n=1), IIA 18.2% (n=6), IIB 27.3% (n=9), IIIA 6% (n=2), IVB 27.3% (n=9). Common sites of metastases were lung and liver. The most common presenting symptom was transvaginal bleeding. In Group 1, 6/7 patients received multimodal management with surgery, chemoradiotherapy and induction or adjuvant chemotherapy. In Group 2, 12/17 patients received three modalities, 3/17 received only 2, due to comorbidty. In Group 3, 8/9 received 2 modalities. Patients with one treatment modality were those with disease progression. Cisplatin was used concurrently with radiotherapy; paclitaxel and carboplatin or etoposide and cisplatin were used for either induction or adjuvant settings. Disease free survival in months was: 50.3 (group 1); 23.1 (group 2), and 3.5 (group 3). Overall survival was: 68.5, 46.3, and 17.2 months, respectively. Main sites of recurrence were pelvis, mediastinum, lung, liver, central nervous system, pancreas, adrenal gland, bone and soft tissue. Conclusions: TheNational Cancer Institute of Mexico offers multidisciplinary treatment emphasizing local control after systemic therapy in both early and locally advanced disease; providing the most favourable disease-free survival and overall survival described. To our knowledge, this is the first report of NEC in the Mexican population, where carcinoma of uterine cervix represents yet an important public health issue.
Oral cavity squamous cell carcinoma in the elderly: A retrospective study in 129 patients over 11 years (2000-2010).
Authors: Laetitia Gambotti, Emilie Schwob, Patrick Goudot, Chloë Bertolus
Journal: Journal of Clinical Oncology (2013)

e17023 Background: There is no consensus for the management of elderly patients with oral cavity squamous cell carcinomas (OC SCC). Surgeons have to estimate for each patient the benefit or the risk of aggressive treatments in this population. We report the experience of one French university hospital center in the treatment of OC SCC in patients aged &gt; = 70 years. Methods: One hundred and twenty nine patients aged &gt; = 70 years with a primary OC SCC diagnosed between 2000 and 2010 were included retrospectively. Independent risk factors of post-operative complication were identified using a logistic regression. Overall survival (OS) was estimated with Kaplan Meier method. Independent factors of survival were calculated using a Cox model. Results: Mean age was 78 (+/-6), sex ratio was 1.2. Women presented significantly more precancerous lesions (36% vs 21%, p=0.04), less alcohol intoxication (13% vs 59%, p&lt;0.001) and less tobacco consumption (41% vs 81%, p&lt;0.001). Half of the sample was stage T4 of TNM classification. Eighty eight percent of the patients received a curative treatment, including surgery for 101 patients. Among them, the surgical treatment was considered as “standard” (vs “substandard”) for 70%. Thirty percent of the surgical patients presented a post-operative complication. Independent risk factors of complications were T3/T4 stage (OR 4.5 [1.3-15.1]) N+ (vs N0 of TNM classification) (OR 7.3 [2.2-24.0]) and alcohol intoxication (OR 3.6 [1.1-11.4]). The median OS was 13.6 months (43.8 months for T1). There was no significant difference of OS between standard or substandard treatment groups. The independent negative prognostic factors for OS were age &gt; 79 years (HR 1.8 [1.2-2.7]), N+ (HR 1.9 [1.3-2.9]) and ASA score 3/4 (HR 1.8 [1.1-2.9]). Conclusions: In our experience, surgeons probably made the good choice between standard or substandard treatment according to the patient profile but this choice must be oriented by professional guidelines.
DULAGLUTIDE REDUCES HBA1C IRRESPECTIVE OF ANTIHYPERGLYCEMIC AGENTS, DURATION OF DIABETES, BMI AND WEIGHT LOSS: A POST HOC ANALYSIS FROM THE REWIND TRIAL
Authors: Anita Kwan, Hertzel Gerstein, Denis Xavier, Jan Basile, Juan Maldonado, Sohini Raha, Manige Konig
Journal: Journal of the American College of Cardiology (2020)
Access to medical treatments in relation to the social status of the cancer patient cured at the Veneto Oncology Institute of Padua (IOV).
Authors: Silvia Imbevaro, Alberto Bortolami, Magdalena Mazurek, Paola Rescigno, Antonio Jirillo, Maria Giacobbo
Journal: Journal of Clinical Oncology (2013)

e12028 Background: The NHS in Italy is a public system of universal nature that guarantees health care to all citizens. Few Italian studies relate the therapy received by a cancer patients with their socio-economic status, so we decided to analyze the situation of the IOV. Methods: It is an observational monoinstitutional study conducted on 886 patients (pts) treated at the IOV from May 2006 to December 2011. They were selected from the Onco-AIFA registry which is a national tool used to monitor anticancer high-cost therapies. The socio-demographic data were obtained from medical records.We verified if there are differences in access to treatments (number of diagnostic tests, chemotherapy treatments, specialist and follow visits) in association with the socioeconomic determinants. We analyzed the survival differences in connection with demographic and clinical characteristics.The statistical analysis was performed using the Kruskal-Wallis test and the Cox model. Results: There are 520 pts evaluable of the 886 pts selected: 42% suffering from colorectal cancer, 28% lung cancer and 30% breast cancer. The median age is 63 years (41% male). With regard to the profession the sample is divided as follows: 34% traders/artisans/workers, 25% technical professions/office workers, 14% highly specialized occupations, 25% retired/housewives. The statistical analysis shows no significant differences in the number of exams and medical services in relation to the profession, except one that regards the mean number of chemotherapy infusions (25 manual professions vs. 20 other professions, p = 0.007). The socioeconomic variables do not affect survival, unlike the age (hazard ratio [HR], 1.42, p &lt;.001) and the type of cancer (HR, 0.72, p &lt;.001). The average cost of benefits per pt is about 4.600,00 euro/year, there is a major expense for traders/artisans /workers compared to other professions (+19%). Conclusions: The analysis of the sample of cancer pts did not reveal significant differences if it comes to access to care, so the system does not seem discriminatory. Probably these differences are homogenized by the state of economic well-being enjoyed so far by pts of the IOV.