tbuckley/cabot-search huggingface dataset:
Palliative external-beam radiotherapy in recurrent ovarian carcinoma.
Authors: David Gareth Fackrell, Muhammad Suhail Anwar, Indrajit Nalinika Fernando, Yvonne Doyle, Ahmed El-Modir
Journal: Journal of Clinical Oncology (2012)

e15534 Background: Up to 80% of patients with advanced ovarian cancer will recur following first-line platinum based chemotherapy. Palliation of focal lesions is often needed to alleviate symptoms. Response rate to second and third-line chemotherapy remain disappointing. The study aim was to characterise the patient population referred for palliative radiotherapy for advanced and recurrent ovarian carcinoma and to assess the effectiveness of radiotherapy in this population. Methods: We retrospectively reviewed the medical records of 94 patients with advanced recurrent ovarian carcinoma referred for palliative radiotherapy between March 1994 and July 2011. The median age of the patients was 62 years (range 33 to 85). One to 16 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 7 cycles). The indications for palliative treatment were: pain (n = 41), mass (n = 32), brain metastases (n = 19), vaginal bleeding (n = 9), rectal bleeding (n = 4), shortness of breath (n = 3), tenesmus (n = 2), skin ulceration (n = 2) and jaundice (n = 1). Some patients received treatment for more than one indication. Sites irradiated included the pelvis (n = 44), brain (n = 19), abdomen (n = 10), bone (n = 5), supraclavicular fossae (n = 4), groins (n = 3), chest (n = 3) and other (n = 6). The median radiotherapy dose was 20 Gy (range: 6 – 50 Gy). The median fraction size was 4 Gy (range: 1.8 – 8 Gy). Results: The overall response rate was 61.7%. Complete palliative response was achieved in 17% of the patients. 27.6% of patients suffered progressive disease during treatment. 10.7% had stable disease. The median duration of palliation was 6 months and closely approximated their survival. The treatment was very well tolerated. Grade 1 or 2 diarrhoea and nausea were the main side effects. Conclusions: External-beam radiotherapy can provide effective and durable palliation of symptoms in patients with recurrent platinum-resistant ovarian carcinoma. The results from palliative radiotherapy are comparable to the published series using second and third-line chemotherapy in the treatment of recurrent focally symptomatic ovarian cancer.
Abstract 1736: Targeting Hsp90-Cdc37 complex overcomes drug resistance in glioma cells harboring FGFR3-TACC3 fusion gene
Authors: Tao Li, Farideh Mehraein-Ghomi, Sanjeev V. Namjoshi, Lynette M. Phillips, Elizabeth A. Ballard, Mary E. Forbes, ping-Chieh Chou, Xuejun Yang, Wei Zhang
Journal: Cancer Research (2019)

Abstract Glioblastoma is one of the most lethal malignancies with the poorest prognosis among tumors of the central nervous system. Fusion genes are common chromosomal aberrations in many cancers that may give rise to an in-frame fusion protein with oncogenic function. These fusion genes can be used as prognostic markers as well as drug targets in clinical practice. The FGFR3-TACC3 (F3T3) fusion gene was discovered in glioblastoma, with an occurrence rate of up to 8.3% and leading to uncontrolled proliferation and chromosomal instability. Our studies have shown that glioblastoma cells harboring the F3T3 are resistant to the frontline glioblastoma drug Temozolomide (TMZ). Using the Comet assay, we show that TMZ-mediated DNA damage is repaired more rapidly in cells harboring the F3T3 compared to control. Our studies on the mechanism of this drug resistance show that the F3T3 confers an aberrant activation of FGFR and ERK pathways when treated with TMZ. To further explore druggable target(s) to overcome resistance caused by F3T3, we immunoprecipitated (IP) the proteins that interact with F3T3 in U251 glioblastoma cells overexpressing the F3T3 or wildtype FGFR3, followed by LC-MS/MS analyses. Our quantitative proteomic analysis revealed interactions of the F3T3 fusion protein with Hsp90α and Cdc37 proteins. These interactions were further validated by reciprocal IPs followed by Western blotting. Activation of many kinases, such as FGFRs, depends on their interaction with the Hsp90 molecular chaperone system. Hsp90 recruitment is mediated by the co-chaperone adaptor protein Cdc37, which simultaneously binds to both the kinase and Hsp90. To test inhibition of F3T3 association with the Hsp90-Cdc37 complex, we treated U251 cells constitutively expressing F3T3 with the Hsp90 inhibitor Onalespib. We show that Onalespib treatment at 26 nM significantly suppresses the proliferation of F3T3 expressing U251 cells in comparison to micromolar levels of the pan-FGFR inhibitor BGJ398 and PD173074. Our results provide evidence that the F3T3 fusion gene contributes to drug resistance via multiple chemo-resistance pathways. Importantly, our findings establish that F3T3 is an Hsp90 client that shows strong addiction to the Hsp90-Cdc37 complex for cell growth and suggests a novel strategy for targeting F3T3 fusion gene in glioma. Citation Format: Tao Li, Farideh Mehraein-Ghomi, Sanjeev V. Namjoshi, Lynette M. Phillips, Elizabeth A. Ballard, Mary E. Forbes, ping-Chieh Chou, Xuejun Yang, Wei Zhang. Targeting Hsp90-Cdc37 complex overcomes drug resistance in glioma cells harboring FGFR3-TACC3 fusion gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1736.
Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study
Authors: Gary Duclos, Xavier Bobbia, Thibaut Markarian, Laurent Muller, Camille Cheyssac, Sarah Castillon, Noémie Resseguier, Alain Boussuges, Giovanni Volpicelli, Marc Leone, Laurent Zieleskiewicz
Journal: Intensive Care Medicine (2019)
Minimal Residual Disease (MRD) Assessment after Induction Chemotherapy in Children and Adults with Acute Lymphoblastic Leukemia (ALL): A Valuable Strategy in Resource Constraint Settings in the Indian Subcontinent
Authors: Karuna kUMAR, Swasti Sinha, Vellaichamy Annapandian, Nataraj Ks, Shoba Badiger, Sunil Bhat, Sharat Damodar
Journal: Blood (2017)
Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell–mediated tumor regression
Authors: Anders Etzerodt, Kyriaki Tsalkitzi, Maciej Maniecki, William Damsky, Marcello Delfini, Elodie Baudoin, Morgane Moulin, Marcus Bosenberg, Jonas Heilskov Graversen, Nathalie Auphan-Anezin, Søren Kragh Moestrup, Toby Lawrence
Journal: The Journal of Experimental Medicine (2019)

Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint therapy. Specific depletion of the CD163+ macrophages results in a massive infiltration of activated T cells and tumor regression. Importantly, the infiltration of cytotoxic T cells was accompanied by the mobilization of inflammatory monocytes that significantly contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates the tumor immune microenvironment and promotes both myeloid and T cell-mediated antitumor immunity, illustrating the importance of selective targeting of tumor-associated myeloid cells in a therapeutic context.
Differential Organ-Specific Tumor Response to Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Authors: Li-Chun Lu, Chiun Hsu, Yu-Yun Shao, Yee Chao, Chia-Jui Yen, I-Lun Shih, Yi-Ping Hung, Chun-Jung Chang, Ying-Chun Shen, Jhe-Cyuan Guo, Tsung-Hao Liu, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Liver Cancer (2019)

Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs.We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites.Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005).The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.
Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia
Authors: Tait D. Shanafelt, Xin V. Wang, Neil E. Kay, Curtis A. Hanson, Susan O’Brien, Jacqueline Barrientos, Diane F. Jelinek, Esteban Braggio, Jose F. Leis, Cong C. Zhang, Steven E. Coutre, Paul M. Barr, Amanda F. Cashen, Anthony R. Mato, Avina K. Singh, Michael P. Mullane, Richard F. Little, Harry Erba, Richard M. Stone, Mark Litzow, Martin Tallman
Journal: New England Journal of Medicine (2019)

Data regarding the efficacy of treatment with ibrutinib–rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.
Pemetrexed in combination with paclitaxel: A phase I clinical and pharmacokinetic trial in patients with solid tumors
Authors: T. Graefe, C. Bolling, C. Lubbing, J. Latz, J. Blatter, A. Hanauske
Journal: Journal of Clinical Oncology (2006)

2051 Background: Pemetrexed (Alimta [AL]) and paclitaxel (P) are clinically active in a variety of tumors. The primary objective of this trial was to determine the maximum tolerated dose (MTD) of the ALP combination; secondary objectives were: determination of dose-limiting toxicities (DLTs), definition of a recommended phase II dose, pharmacokinetic (PK) characterization and the anecdotal collection of antitumor activity. Methods: Escalating doses of P (3h infusion, d1 and d8) and AL (10 min infusion, d8 prior to P) were given in a 21d cycle. Results: 59 patients (pts) were enrolled. DLTs occurred at the following ALP (mg/m 2 ) doses: 400/30 [G3 bilirubin (b), G3 and G4 thrombocytopenia (plts)]; 500/30 (G4 plts); 500/40 (G3 b); 500/75 (G4 ANC); 500/100 (G4 leukopenia, G4 ANC). With G4 leukopenia and G4 ANC in 4/6 pts and febrile neutropenia in 1 pt, the MTD was reached at the ALP (mg/m 2 ) dose of 500/120. To confirm safety at the recommended dose-level, another 6 patients were treated at the ALP (mg/m 2 ) dose of 500/100. 18 pts [mesothelioma (3), esophagus (2), lung (1), liver (1), renal (1), stomach (1), thyroid (9)] showed stable disease as best response. 4/14 (29%) pts with thyroid carcinoma showed long lasting partial responses [duration (months) 29+, 22, 18, 15]. One additional PR (2) was observed in a pt with penile carcinoma. AL PK when administered with P were consistent with those for AL administered as a single-agent. Conclusions: The ALP combination is safe and shows broad clinical activity. 500/100 mg/m 2 is the recommended dose for further studies. Promising antitumor activity was observed in thyroid cancer. A phase II trial in thyroid carcinoma will be conducted. [Table: see text]
Testicular microlithiasis in Japanese male infertility patients: Clinical implications for predicting future testicular malignancy.
Authors: Gaku Arai, Hiroshi Okada, Yuko Sadaoka, Shigeyuki Ohta, Koujiro Nishio, Ryo Sato, Makoto Kawaguchi, Yoshitomo Kobori, Yshio Ashizawa, Hiroshi Yagi, Shigehiro Soh
Journal: Journal of Clinical Oncology (2013)

e15579 Background: Testicular microlithiasis (TM) is commonly diagnosed by scrotal ultrasonography (US) in which it appears as multiple, small, uniform, echogenic foci without shadowing, scattered randomly throughout the testicular parenchyma. It is also prevalent in several urologic diseases including subfertility and testicular germ cell tumor. TM has been reported to be associated with carcinoma in situ (CIS) and the development of second testicular germ cell tumor (TGCT) after contralateral orchiectomy treatment for primary TGCT; however, no prospective studies have investigated the relationship between the detection of TM in patients without TGCT and future development of TGCT. In the present study, therefore, we investigated the prevalence of TM in the testes of male infertility patients and unilateral TGCT patients to determine if TM could be a predictor of future germ cell tumor in such patients. Methods: A total of 1,139 subfertile patients (296 with nonobstructive azoospermia, 58 with obstructive azoospermia, and 785 with oligozoospermia) and 22 unilateral testicular germ cell tumor patients were enrolled in the study. Prevalence of testicular microlithiasis according to testicular ultrasonography was compared between patients, and development of testicular germ cell tumors was monitored for at least 3 years. All patients were fully informed about the study, and their prior consent was obtained according to the recommendation of the institutional ethics committee. Results: The prevalence of TM was significantly higher in unilateral TGCT patients (40.9%) than in subfertile men (8.6%). No infertile patients without TM developed TGCT but one infertile patient with TM developed TGCT (seminoma) during follow up. One seminoma patient with TM in his remaining testis went on to developed testicular seminoma 3years after primary surgery. Conclusions: Testicular microlithiasis is more common in testicular germ cell tumor patients than in subfertile men. Since TM could be a surrogate marker for future TGCT in both patient populations, TM patients are recommended to perform careful self-checking of the testes and periodical testicular ultrasonography.
Most deaths related to non-cardiac surgery occur outside operating room, finds study
Authors: Barbara Kermode-Scott
Journal: BMJ (2019)

Most deaths related to non-cardiac surgery occur in the recovery period (after surgery and after discharge from hospital), not during surgery, a large multicentre, international, prospective cohort study has found.

The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study found that 0.7% of deaths of adult patients who underwent non-cardiac surgery occurred in the operating room and 99.3% occurred after the procedure, with 29% occurring after discharge from hospital. The findings were reported in the Canadian Medical Association Journal .1

Death after surgery is …
Total lesion glycolysis (TLG) at baseline FDG-PET/CT compared with maximum standard uptake value (SUV<sub>max</sub>) to predict survival in non-small cell lung cancer (NSCLC).
Authors: Ling Li, Feng-Ming (Spring) Kong, Nan Bi, Jingbo Wang, Pawinee Mahasittiwat, Paul Stanton, Timothy Ritter
Journal: Journal of Clinical Oncology (2013)

7579 Background: SUV max at baseline FDG-PET has been reported as a significant prognostic factor while recent studies suggest that metabolic tumor volume (MTV) may be more important factor in patients with NSCLC. We hypothesized that TLG is a better prognostic factor than either SUV max or MTV alone for overall survival (OS) and progression free survival (PFS) in NSCLC because it integrates both volumetric and biologic activity. Methods: The study population included a prospectively recruited cohort of stage I-III NSCLC patients treated with chemoradiation. FDG PET/CT scans were performed within 2 weeks from treatment start. The SUV in the tumor was normalized to that of the background level in the middle of ascending aorta to minimize the confounding effect from inter-scan variation in SUV measurement. MTV was delineated by auto-threshold at 1.5 times background level in the aorta followed by knowledge based manual editing. Mean and maximum SUV normalized to the background level were computed. TLG was calculated as the product of lesion SUV mean and MTV. Results: A total of 96 patients with minimum follow-up of 1 year were eligible. The median follow-up among survivors was 30 months. Univariate analysis demonstrated that MTV and TLG were significant factors for both OS and PFS (all P&lt;0.05). There was a significant correlation between SUV mean and PFS (P=0.013), but there was no significant association between SUV mean and OS. SUV max was not a significant factor for either OS or PFS (all P&gt;0.05). Under multivariate Cox regression analysis, MTV (HR= 2.62, P= 0.003) and NSUV mean (HR=0.351, P=0.003) were significantly associated with PFS; but only TLG was significantly associated with OS (HR=2.14, P=0.006)adjusted by of TNM stage and other clinical factors. Conclusions: These results support our hypothesis that metabolic tumor volume and biologic average glucose metabolic activity of this volume are more important prognostic factors for overall prognosis than SUV max in NSCLC patients treated with chemoradiation. Should this be validated by independent studies, future clinical trial should take this into consideration for individualized care.
The dramatic rise of ultra-processed foods
Authors: Agnes Ayton, Ali Ibrahim
Journal: BMJ (2019)

We agree with Astrup and colleagues that the World Health Organization should reconsider its dietary recommendations and prioritise a food based approach in future dietary guidelines.1 People consume foods and not individual nutrients. Reduced intake of saturated fats and their replacement with vegetable oils was first recommended in US dietary guidelines in 1977.2 Vegetable oils have been promoted as healthier alternatives to …
Retrospective analysis of clinico-pathological features and outcomes of 2,686 hormone receptors-positive breast cancer (HR+) patients in a consecutive mono-institutional series
Authors: A. Ferro, R. Triolo, O. Caffo, M. Barbareschi, E. Leonardi, M. Frisinghelli, A. Caldara, G. Ambrosini, A. Lucenti, E. Galligioni
Journal: Journal of Clinical Oncology (2007)

11036 Background: Clinico-pathological patterns, management and outcomes of HR+ vs HR- have been evaluated in a retrospective study. Methods: A series of 2686 BC patients (pts), treated at our institution from 1988 to 2000 with known immunohistochemical receptor status was investigated. Correlation between HR status and tumour size (T), nodal status (N), grading (G), mib-1, HER-2 and p53 and was evaluated by χ square test. Statistical analysis was performed to test the interaction between HR status and Disease Free Survival (DFS) and with specific and overall survival, using the log-rank test. Results: Among 2686 patients, 467 HR- (17%) and 2219 (83%) HR+ (364 pre and 1855 postmenopausal) were observed, with 1586 ER+PgR+, 555 ER+PgR-, 78 ER-PgR+. Pts with positive HR status showed a statistically significant correlation with lower T, G, mib-1, HER-2 and p53 expression.Chemotherapy was administered to 681 HR+BC (31% ) and to 301 HR-BC (65%), according to stage, age, and G. Tamoxifen based endocrine therapy was administered to 1167 HR+BC (53%) (associated to chemotherapy in 428 and alone in 739 pts). At a median follow up of 108 months, 499 relapses occurred in HR+ (22%) , and 141 in HR- pts (30%), with a 5,10, 15y DFS of 83%,72%, 62% in HR+ and 72%,66%, 57% respectively in HR- pts. More frequent sites of relapse were soft tissue (46%) and bone (35%) in HR+ and soft tissue (50%) and visceral (30%) in HR- pts. Seven hundred sixty pts have died: 576 HR+ (26%) and 184 HR- (39%), with a 5, 10, 15y specific survival of 90%, 84%, 75% which was significantly superior to the 78%, 73%, 69% respectively of HR-. However, considering that 230 HR+ and 44 HR- pts died without relapse, the 5,10,15y overall survival was 90%, 75% 61% for HR+ and 78%, 67%, 60% respectively for HR-. It appears therefore that the specific survival advantage in early years in favour of HR+ is progressively reduced by non specific mortality in late years which results in similar 15 y OS rates among HR+ and HR- pts. Conclusions: Our series appear to confirm the relationship between HR+ status and other more favourable clinical-pathological features, although long term OS is not apparently affected. No significant financial relationships to disclose.
The choice of first-line therapy in advanced Hodgkin lymphoma: Retrospective comparison of ABVD and escalated BEACOPP regimen
Authors: W. Jurczak, D. Krochmalczyk, A. Giza, J. Węgrzyn, M. Sobocinski, J. Gawelko, B. Malkowski, J. Czyz, J. Pawlega, A. B. Skotnicki
Journal: Journal of Clinical Oncology (2007)

8063 Background: HD patients with high risk have a relatively poor prognosis with less than 50% 5-year overall survival (OS) if treated with ABVD regimen. Methods: Therapy results of all 105 patients with advanced HL (CS IIBX -IV) treated from diagnosis at our Department in the last decade, are presented. The choice of initial 3 cycles between ABVD and escalated BEACOPP was done at the patients preferal and physician's adivice. Further 3 chemotherapy cycles depended on initial response assessment: poorly responding ABVD treated patients were offered therapy escalation. Patients with a good response (over 80% regression) after the first 3 cycles were later treated with ABVD. EFS and OS were primary endpoints of the study. Results: We divided patients into 2 treatment groups, depending on the first 3 cycles (escalated BEACOPP n = 57 or ABVD n = 48). Poor response resulting in therapy intensification was not considered as an event defined only as a relapse or progression during therapy. There was a statistically insignificant imbalance between the risk factor distribution with less favorable prognosis in patients treated with esc BEACOPP: 38 % of pts in IV th clinical stage (as compared to 31% in ABVD group), 3,08 EORTC risk factors (as compared to 2,64 in ABVD group) and 2,19 according to German Hodgkin Study Group (1.93 respectively). Increased toxicity of esc BEACOPP regimen was due to grade 3/4 cytopaenia (present in all patients) resulting in more infection episodes (according to WHO scale stage 3 - 16 pts , stage 4 - 8 pts; in ABVD group, 2 and 1 pt respectively). There were no treatment related mortalities. In esc BEACOPP projected 5 y OS was 96% and EFS 89% , which is comparable to GHSG results. 5 y OS and EFS in ABVD group are 87% and 66% respectively. The difference in EFS is statistically significant (p&lt; 0.05). Conclusions: In our study we checked the feasibility of esc BEACOPP regimen in high risk HD pts. The results show the importance of the intensity of the first line approach. In the poor responders after the initial 3 cycles, even early treatment intensification, didn’t improve the outcome. De-escalation of therapy after the first 3 cycles, in good responders, didn’t make OS and EFS inferior to GHSG results in which they recommend 6 cycles of esc BEACOPP therapy. No significant financial relationships to disclose.