tbuckley/cabot-search huggingface dataset:
105 cases of renal tumors in patients age 15 to 35: A specific entity? Experience of the Gustave Roussy Institute.
Authors: Charles Dariane, Claudia Pasqualini, Nathalie Gaspar, Laurence Brugieres, Catherine Patte, Jean Jacques Patard, Herve Baumert, Yohann Loriot, Christophe Massard, Karim Fizazi, Zahira Merabet, Mario Di Palma, Bernard J. Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2014)

4575 Background: To describe the specific features of malignant renal tumors occurring in young adults. Methods: Medical charts of all 15-35 yo pts diagnosed with a primary renal malignant tumor from1990 to date and treated at Gustave Roussy were retrieved. Results: Overall, 105 pts were analyzed with a median follow up of 21.1 months (IQR 5.53-47.2). First pathological entity was Renal Cell Carcinoma (RCC) (n= 89) and second one was nephroblastoma (n=9). Median age at diagnosis was 28.7(24-32) : 31.1 (27.8-33.6) for RCC and 23.6 (22.2-25.8) for nephroblastoma. Only 24% pts underwent a tumor biopsy as first procedure while others had nephrectomy or tumorectomy front line. Among nephroblastoma, only 2 had first biopsy and received neo-adjuvant chemotherapy. Four had synchronous metastasis, 3 remained localized and received adjuvant chemotherapy and 2 developed peritoneal immediate recurrence after surgery requiring additional chemotherapy and radiation therapy. Regarding ccRCC (37pts), 87% of pts presented with symptoms; 76% presented metastasis at diagnosis or during follow up. Prognosis groups of mRCC (83pts), according to IMDC, were good/intermediate and poor in 44/34/5 respectively. One out of 9 pts with nephroblastoma has died. Conclusions: We report a large cohort of 15-35 yo patients with malignant renal tumors, highlighting (i) the issue of highly aggressive RCC disease in young adults and (ii) the challenge of differential diagnosis of nephroblastoma. Interestingly, nephroblastoma were diagnosed in pts aged up to 31 and diagnosis procedure did not comply with required pediatric guidelines. This report suggests the need of standardized guidelines in young adult renal tumors management. Age [15-20] [20-25] [25-30] [30-35] 1/ Histology Nb of pts Total =105 13 19 28 45 RCC - ccRCC - translocation - pRCC - other RCC Nephroblastoma Miscellaneous 89 37 20 17 15 9 7 10 2 3 2 3 1 2 11 4 3 1 3 4 4 25 10 9 2 4 2 1 43 21 5 12 5 2 0 2/Survival mRCC (n=83) OS (mos) PFS first-line (mos) ccRCC 21.5 (4.6-44.4) 3.2 (1.8-7) translocation 11.1 (5.4-23.4) 3.6 (2.6-6.5) pRCC 19.1 (11-50.6) 2.9 (2.3-9.2)
Effects of concomitant therapies on γδ T-cell responses to zoledronate in patients with advanced prostate cancer.
Authors: Deborah Enting, Maria Luisa Iannitto, Hardev S. Pandha, Matthias Eberl, Simon Chowdhury, Adrian C Hayday
Journal: Journal of Clinical Oncology (2014)

11081 Background: γδ T cells have attracted interest as a biological tool for cancer therapy owing to demonstrated tumour cytocidal potential in vitro, and their correlation with improved outcome in patients with malignancies. They are also not MHC-restricted, offering opportunities beyond individual-specific therapies. Indeed, clinical trials with bisphosphonate-activated γδ T-cell-based immunotherapy are ongoing. However any clinical adoption of γδ immunotherapy will need to be in the context of other therapies ('standard-of-care'). The influence of concomitant therapies such as chemotherapy on the effector function of γδ T cells remains largely unexplored. Methods: We developed an immunomonitoring protocol to determine the γδ T cell response to zoledronate (ZOL) in the context of hormonal therapy with or without docetaxel chemotherapy in patients with advanced prostate cancer. Blood samples were collected prior to ZOL and chemotherapy and 6 days later, with a second collection cycle after 4 weeks. Phenotypic and functional analyses were performed on purified peripheral blood mononuclear cells from each of the four successive collection points. Results: Many patients receiving ZOL show a markedly low percentage of γδ T cells. Moreover, the percentage of NKG2D+ γδ T cells is significantly reduced in both treatment groups, although the majority of patients experienced a conspicuous boost in this compartment after ZOL treatment. However, this 'bounce-back' effect was lost in patients who have received ZOL long term. Conclusions: Thus, ZOL modulates γδ T cell phenotypes in vivo but repeated long term ZOL treatment could lead to exhaustion of this immune compartment. This observation could have important clinical implications with regards to the duration of bisphosphonate treatment, which currently is undetermined. Furthermore, in the form of an interventional clinical trial, we are now assessing whether adjuvant IL-2 therapy can prolong the activation potential of γδ T cells in the context of ZOL, offering a simple immune-enhancement potential that might usefully be adopted for particular cohorts of patients.
Current Status of mCRC in East Europe and Middle East.
Authors: Ozan Yazici, Gokhan Ucar, Vamvakopoulou Vasileia, Serdar Nazim Turhal, Birol Yildiz, Michalis Karamouzis, Sinan Yavuz, Nuri Karadurmus, Nurullah Zengin, Huseyin Abali, Ravit Geva
Journal: Journal of Clinical Oncology (2018)

853 Background: Results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients (pts) in real life.This multinational registry study aimed to evaluate the real life data effecting survival of pts with mCRC. Methods: Multinational, retrospective registry study.Those mCRC pts with at least 3 year follow up data OR died before 3 year time period:diagnosis in between 2005 – 2012. Results: Totally 208 (57%) male,156 female (43%) mCRC pts were included.Median age was 62 years (min:23 max:85).Primary locations; right (n = 71, 19.5%), transvers (n = 13, 3.6%), left colon (n = 276,75%). Sites of metastasis: liver 69.7%, lung:27.4%, local relapse %12.6, peritoneum 12%, distant lymph node 10%, CNS: 1.6%. Metastasectomy (mtc) was done in 38.5%, mtc regions: liver (22.3%), lung (4.7%), other (%11.5 ). K-N RAS and BRAF wild pts were 37.4%, 16.5% and 14.3%. Aflibercept was available for %57 of pts. MSI rate was 1.6%. Most common first line chemotherapy (FLC); Oxaliplatin (O) based combination (C) 29.9%, irinotecan (İ) C with bevacizumab (bev) 16.5%, O with bev. 16.5%. Responses to FLC; CR: 8%, PR: 30.5% stable: 28.3%, progres: 24.7%. Median OS of FLC; combination with bev: 35 months (m) (95%CI, 29.1 – 40.8), anti-EGFR:38 m (95%CI, 30.1–45.8 ),only chemotherapy: 32 m (95%CI 26.3 - 37.6), p &gt; 0.05. Second mtc was done 10.2%.Second LC was given to %66.7 of pts. İ combination with bev (24.5%) was most common SLC. Responses to SLC; CR:4.9%, PR: 15.1% , stable:13.2% progres:29.1%. Total %31.3 and 22% of pts had third and fourth LC, most common one was single agent 5-FU. Median PFS1: 10 m (95%CI 8.3 – 11.6 ), PFS2: 7 m (95%CI 6.2 –7.7 ), PFS3: 6 m (95% CI 4.6 – 7.3 ). Median OS of all pts were 35 m (95%CI 30.7 – 39.2 ). In pts with metastasectomy compared with others median OS was; 43 m (95%CI 34.4 – 51.5) vs 29 m (95% CI 25.8 vs 32.1), respectively , p: &lt; 0.001. Median OS in right, transvers and left colon was; 25 m (95%CI, 16.6 – 33.3), 33 m (95%CI, 8.7 – 52.7), 37 m (95%CI 32.4 – 41.5), (p = 0.25). In K-N Ras wild group median PFS; anti-EGFR:13 m (95 % CI, 9.3 - 16.6) bev:13 m (95 %CI, 4.4 - 21.5), chemo:9 m (95 % CI, 6.3 - 11.6), (p: 0.3). Conclusions: The current study demonstrated median OS and prognosis of left-transvers-right colon was consistent with the phase trials.
Blood tests in malignant pleural mesothelioma (MPM).
Authors: Kazue Yoneda, Fumihiro Tanaka, Nobuyuki Kondo, Masaki Hashimoto, Teruhisa Takuwa, Seiji Matsumoto, Yoshitomo Okumura, Noriaki Tsubota, Ayuko Sato, Tohru Tsujimura, Chiharu Tabata, Takashi Nakano, Seiki Hasegawa
Journal: Journal of Clinical Oncology (2014)

7582 Background: Serum mesothelin is the best available blood test for diagnosing MPM, but provides a poor sensitivity (J Clin Oncol 2012). We previously showed that two blood tests, a test for circulating tumor cell (CTC) and a test for endothelial cell (CEC), provided significant diagnostic and prognostic performance (ASCO 2011 and 2012), and we compared these blood tests in the present study. Methods: A total of 140 patients, who present at Hyogo College of Medicine Hospital with suspicion of MPM, were enrolled; the final pathological diagnosis was MPM in 107 patients and non-malignant diseases in 33 patients. CTC-count in 7.5mL of peripheral blood and CEC-count in 4.0ml of peripheral blood were quantitatively evaluated with the “CellSearch” system. The MESOMARK ELISA kit was sued for measurement of serum soluble mesothelin-related peptides (SMRP). Results: A receiver-operating characteristic (ROC) curve analysis showed each test provided a significant diagnostic performance; at the cut-off value of 1/7.5mL (for CTC-test), 70/4.0mL (for CEC-test), and 2nmol/L (for SMRP-test), each test provided a high specificity (over 90%) but a poor sensitivity (28%-44%) (Table). When these tests were combined and a patient with positive result in any test (CTC≥1, or CEC≥70, or SMRP≥2) was judged to have MPM, the diagnostic performance improved with the sensitivity of 79% (specificity, 76%). In addition, patients with positive-CTC (CTC≥1) or higher-CEC (CEC≥70) showed a significantly poor prognosis (median survival time, 11 months vs 23months; p<0.001). Conclusions: Novel blood tests (CTC-test and CEC-test) improved a diagnostic performance of SMRP-test, and provided a significant prognostic value in MPM. Diagnostic performance of blood tests. CTC CEC SMRP AUC-ROC 0.619 0.725 0.703 P-value 0.039 <0.001 0.009 Cut-off 1cell/7.5mL 70cells/4.0mL 2 nmol/L Sensitivity 28% 44% 33% Specificity 95% 91% 91%
Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT
Authors: Michaël Chopin, Aaron T. Lun, Yifan Zhan, Jaring Schreuder, Hannah Coughlan, Angela D’Amico, Lisa A. Mielke, Francisca F. Almeida, Andrew J. Kueh, Ross A. Dickins, Gabrielle T. Belz, Shalin H. Naik, Andrew M. Lew, Phillipe Bouillet, Marco J. Herold, Gordon K. Smyth, Lynn M. Corcoran, Stephen L. Nutt
Journal: Immunity (2019)
Human Papillomavirus Vaccination
Authors: Megan A Moreno
Journal: JAMA Pediatrics (2018)

Human Papillomavirus VaccinationThe human papillomavirus (HPV) vaccine is a vaccination for cancer prevention.The HPV vaccine prevents cervical cancer, as well as other cancers including cancer of the oropharynx (back of the throat), anal cancer, penile cancer in men, and vaginal and vulvar cancer in women.In addition to cancer prevention, the HPV vaccine also prevents infection with HPV types that cause genital warts in both women and men.Physicians can screen for cervical cancer in women.There are no recommended cancer screening tests for the other types of cancers caused by HPV infections.These cancers may not be detected until they have already caused health problems.
Hematological Cancer Consortium: Multi-Center Acute Myeloid Leukemia Registry Data from India
Authors: Rajan Kapoor, Hasmukh Jain, Anu Korula, Dinesh Bhurani, Venkatraman Radhakrishnan, Chepsy C Philip, Jina Bhattacharyya, Maitreyee Bhattacharyya, Smita Kayal, Pankaj Malhotra, Govind Babu, Lalit Kumar, Om Prakash, Ambily Nadaraj, Jeyaseelan Lakshmanan, Biju George, Poonkuzhali Balasubramanian, Bhausaheb Bagal, Satyaranjan Das, Rayaz Ahmed, Prasanth Ganesan, Gaurav Prakash, Nikita Mehra, Manju Sengar, Vikram Mathews
Journal: Blood (2018)
Monitoring changes in circulating tumor DNA in gastrointestinal malignancies using a novel next-generation sequencing method.
Authors: Edward Samuel James, Azeet Narayan, Nicholas J. Carriero, Bryan William Chang, Jill Lacy, Stacey Stein, Howard S. Hochster, Abhijit Patel
Journal: Journal of Clinical Oncology (2014)

3645 Background: Circulating tumor DNA (ctDNA) is showing promise as a highly-specific cancer biomarker. We have developed an ultrasensitive ctDNA assay that can evaluate recurrent cancer-associated point mutations and insertions/deletions simultaneously in multiple genes without prior knowledge of the tumor’s mutation profile. Here we report on use of this assay for non-invasively assessing tumor mutation status and for monitoring treatment response or disease progression in patients with gastrointestinal malignancies. Methods: Plasma samples were collected at multiple time points in a cohort of patients (pts) with colorectal, pancreatic, or bile duct malignancies in the locally advanced, metastatic and adjuvant settings. Mutation-prone regions of genes known to be commonly mutated in GI tumors were amplified by multiplexed PCR, and the resultant amplicons were subjected to next-generation ultra-deep sequencing. Application of novel techniques to suppress sequencer and PCR errors allowed mutations to be identified and quantified with a sensitivity of approximately 1 variant in 5,000 molecules. Results: 75 plasma samples from 17 pts were analyzed for the presence of tumor-derived mutations. We found plasma DNA mutations in the following genes: KRAS (7 pts), TP-53 (2 pts), and PIK3CA (1 pt). Among the 8 pts whose tumors were profiled by an independent clinical lab, our plasma results showed perfect concordance of mutation status and type. Testing of serial samples revealed that ctDNA levels changed appropriately with therapy or with disease progression. Examples include one case that showed a dramatic decrease in ctDNA after initiation of first-line chemotherapy, a second case that had rising levels upon development of liver metastases, and a third case that showed reversal of a rising trend upon switching to a different chemotherapeutic regimen. Conclusions: We present here a novel NGS-based method for identifying and measuring mutant ctDNA. Results from this cohort of patients with GI malignancies indicate that this approach may find clinical utility for non-invasive assessment of tumor mutation status and for monitoring of recurrence, progression, or therapeutic response.
Impact of new oncolytic herpes simplex virus vector armed with interleukine-12 for cervical cancer therapy.
Authors: Masahiro Kagabu, Yuki Miura, Tatsunori Saito, Ryosuke Takeshita, Naoto Yoshino, Toru Sugiyama
Journal: Journal of Clinical Oncology (2014)

3102 Background: Cervical cancer is the third most common cancer in women, and the seventh overall, the incidence and mortality of cervical cancer in the world was approximately 530,000 and 275,000 respectively according to a database of the Agency for Research on Cancer (IARC) in 2008. Requirement of new treatments it is mandatory to improve the outcome of the pathology. Replication-selective oncolytic herpes simplex viruses (oHSV) have emerged as a new platform for cancer therapy. Accumulating evidence indicates that, aside from the extent of replication capability within the tumor, the efficacy of an oncolytic HSV-1 depends on the extent of induction of host antitumor immune responses. We analyzed therapeutic potential of third-generation of oncolytic HSV-1 termed T-01 and Replication-competent HSV-1 vectors expressing IL-12 (T-mfIL12) for cervical cancer in mouse model. Methods: (1) In vitro, we investigated cytotoxicity reaction of human and mouse cervical cancer cell lines (TC-1, SKG-IIIa, CaSki, HeLa). (2) In vivo, we analyzed TC-1 cell lines in immune-competent models. Animals were challenged with a lethal dose of TC-1, 17 days after the first intratumoral (i.t.) administration of T-01 or T-mfIL12 was performed. Intratumoral administration of T-01 or T-mfIL12 were performed 4-5 days interval total 6 times. Results: T-01 and T-mfIL12 has great cytotoxicity for human and mouse cervical cancer cell lines. In addition, our results indicate that administration of T-01 and T-mfIL12 produced greatest antitumor effects in cervical cancer models. Furthermore, in immune-competent models, we found an increase of the number of cancer specific CD8+ T-cell in spleen of mice treated with T-01 in comparison with the control treated mice. Conclusions: Our data suggest that administration of T-01 and T-mfIL12 is an effective treatment against cervical cancer model. It may potentially be translated into the clinical area.
Percutaneous irreversible electroporation (IRE) in the management of pancreatic cancer.
Authors: Govindarajan Narayanan, Peter Joel Hosein, Caio Max S. Rocha Lima, Rekha Suthar, Jaime R. Merchan, Maria Restrepo, Ana Echenique, Tatiana Froud, Shivank Bhatia, Katuska J Barbery, Jose M Yrizarry
Journal: Journal of Clinical Oncology (2014)

e15249 Background: IRE is a new non-thermal ablative technology that uses high voltage direct current to create permanent pores in the cell membrane leading to cell death. A retrospective review of patients with pancreatic adenocarcinoma who underwent percutaneous IRE at our institution was performed. Overall survival and safety outcomes were evaluated. Inclusion criteria included unresectability of primary tumor and intolerance of standard therapy. Methods: IRE is a new non-thermal ablative technology that uses high voltage direct current to create permanent pores in the cell membrane leading to cell death. A retrospective review of patients with pancreatic adenocarcinoma who underwent percutaneous IRE at our institution was performed. Overall survival and safety outcomes were evaluated. Inclusion criteria included unresectability of primary tumor and intolerance of standard therapy. Results: Overall survival for the entire cohort from the date of IRE was 14.5 months (95% CI: 10.4-18.6 months). Separating into two groups based on stage, the overall survival for LAPC patients was 16.2 months (95% CI: 10.1-22.3 months) versus 8.6 months (95% CI: 3.1-14.1months) for MPC patients. Two patients underwent surgery 4 and 5 months after IRE, respectively. Both had margin negative (R0) resections; one of the two had biopsy proven recurrence 34 months post IRE and the second remains disease-free at 34.5 months. Complications included pancreatitis (n=7), abdominal pain (n=10), hematoma (n=7), spontaneous pneumothorax (n=1), duodenal stent (n=1); sepsis 48 hours post IRE (n=1) and main portal vein thrombus at one month follow up CT scan (n=1). Twenty patients have expired, and no deaths were directly related to the procedure. Conclusions: This is the largest series of patients using percutaneous IRE for the treatment of pancreatic cancer and demonstrates promise in prolonging survival in patients with localized or metastatic pancreatic adenocarcinoma compared to historical controls. Further trials are required to define the role IRE in the management algorithm of pancreatic cancer.
Daratumamab in High Risk Relapse/Refractory Myeloma Patients Effect of 1q21 Gain and GEP70 Status
Authors: Meera Mohan, Niels Weinhold, Frits van Rhee, Carolina D. Schinke, Sharmilan Thanendrarajan, Leo Rasche, Jeffery R. Sawyer, Erming Tian, Faith E. Davies, Gareth J. Morgan, Maurizio Zangari
Journal: Blood (2017)
Hormonal status of the tissue of skin melanoma and its perifocal area.
Authors: Valeriya Bandovkina, Elena Frantsiyants, Victoriya Pozdnyakova, Ekaterina Komarova, Yulia Pogorelova
Journal: Journal of Clinical Oncology (2014)

e20009 Background: We have not found any works related to determining the level of sex hormones directly in the tissue of malignant skin melanoma; their role in pathogenesis of the disease has not been identified so far. Methods: Levels of prolactin (Prl), progesterone (P4), total and free testosterone (T and free T), estrone (E1) and estriol (E3) in 40 samples of skin melanoma tissue (17 samples of pT1-2N0M0 and 23 pT3-4N0-'M0 ones) and perifocal area tissue (PA, n=40 – skin samples 1 cm away from the visible edge of the tumor) were studied by the IFA method. For the control, intact skin of patients having no oncopathology was used. Results: In case of pT1-2N0M0, local androgen imbalance was marked: the level of T went down in 1.8 times, while free T was 1.5 times higher. Saturation of the tumor with E1 increased 1.6 times and the concentration of E3 was reduced in 2.5 times. Parameters of other hormones studied remained within the limits for intact tissue. In case of pT3-4N0-'M0, the level of all hormones under study in the melanoma tissue was changed: Prl saturation was 3.9 times higher, free T – 1.6 times, E1 – 5.7 times, the level of P4 went down in 2 times, that of
Melanoma mortality trends in Brazil, an age-period-cohort analysis.
Authors: Gelcio Luiz Quintella Mendes, Rosalina Jorge Koifman, Sergio Koifman
Journal: Journal of Clinical Oncology (2014)

e20043 Background: Melanoma mortality rate (mR) increased in many countries during the last 50 years, and incidence patterns have changed during this period. In the last years there is a trend towards increase in the incidence of thin lesions and stability in thicker tumors. The objective of this study is to evaluate the temporal trend on of mortality according to an age-period-cohort modeling. Methods: Deaths related to cutaneous melanoma in the period of 1980 to 2009 by geographic region and sex were ascertained from the Mortality Information System of the Public Health System´s Department of Informatics (DATASUS), and population features, from the Brazilian Institute of Geography and Statistics (IBGE). Data were arranged in the Lexis diagram and rate plots were performed. A formal age-period-cohort analysis was carried out. Since the full models had better adjustment and the cohort component was evident, we fit the age-cohort-period model. Results: In this period there were 24,375 registries of deaths from melanoma. In the analysis of the rate plots it was verified that the mR increased for age groups over 50 years old and a reduction of mR for groups younger than 35 years. With relation to cohort effect, there was an increase in mortality rate ratio (mRR) until the 1960´es birth cohort, then the mRR tended to plateau and this trend decreased in the cohorts born in the late 1980s, suggesting a decrease in mR of younger generations. When the geographic regions were analyzed individually, it was seen in most regions a plateau in mRR after the 1960s and 1970s birth cohorts. There was no different in the mRR according to sex. Conclusions: The increase in melanoma mortality during the last decades of the 20th century may be largely a function of a cohort effect encompassing the generations born up to 1960s, and the leveling off of incidence of thicker lesions as well as data presented in this study suggest that the mortality will not grow up in the next years. It is possible that these younger cohorts have a less aggressive disease.