tbuckley/cabot-search huggingface dataset:
Outcome of patients (pts) with relapsed, advanced upper gastrointestinal (GI) carcinoma treated in a specialist oncology phase I unit.
Authors: Khurum Hayat Khan, Joo Ern Ang, Naureen Starling, Krunal Jitendrakumar Shah, L. Rhoda Molife, Udai Banerji, Johann Sebastian De Bono, David Cunningham, Stanley B. Kaye
Journal: Journal of Clinical Oncology (2013)

45 Background: Conventional chemotherapy in advanced upper GI cancer after progression on first line therapy yields low response rates and no clear survival benefit. In this context, some pts are offered experimental treatments, including participation in Phase I clinical trials. Methods: Baseline pt and tumour characteristics, toxicity, response and outcome data of pts with upper GI cancers consecutively treated within the Drug Development Unit, Royal Marsden Hospital, from 2005 to 2009, were documented. Results: Ninety-six pts (median age 59 years [range 24-77]; male/female ratio 3.6, median of 2 [range 0-4] prior lines of chemotherapy) with oesophageal (42%), gastric (14.5%), pancreatic (26%) and oesphagogastric junction (7%) carcinomas were treated in 30 Phase I trials; of these, 36% participated in studies containing conventional cytotoxic chemotherapies. The overall response rate by RECIST was 11% with a disease control rate of 49%. The overall clinical benefit rate (i.e. no disease progression at 6 months) was 14%, respectively. In all pts, the median progression free survival (PFS) and overall survival (OS) were 7.0 weeks (95% CI: 5.6-8.4) and 19 weeks (95% CI: 17-21), respectively; these were not superior in pts who received chemotherapy-containing regimens (p=0.364, p=0.897). Pts with CBR ≥6 months a median OS of 55 weeks (95% CI: 46-64); 59% of them were treated with single-agent molecular targeting agents. Grade 3 or 4 toxicities were observed in 37 pts (39%) and led to trial discontinuation in nine (9%); no toxicity-related death occurred in these pts. In the multivariate analysis of baseline factors, serum albumin (&lt;35 g/dl, HR 2.0 [95%CI: 1.3-3.2] p=0.002) and serum lactate dehydrogenase (LDH) (&gt;192 umol/l, HR 1.7 [95% CI: 1.1-2.6], p=0.016) were prognostic of OS. Conclusions: Phase I clinical trials should be considered a valid option in pts with advanced upper GI cancers with disease relapse after first-line chemotherapy In our experience the risk of toxicity is low/moderate and there is the potential for clinical benefit.
Effect of all-trans retinoic acid on proliferation of human rhabdomyosarcoma and remission in an in vivo mouse xenograft model.
Authors: R. H. Saab
Journal: Journal of Clinical Oncology (2010)

9569 Background: Rhabdomyosarcoma (RMS) is the third most common soft tissue cancer in children. 30% of treated children will experience relapse, with poor outcome. New approaches are needed to improve cure rate and prevent relapse. Retinoic acid is a differentiation agent that is known to induce differentiation of normal myoblasts, among other cell types. When used in the setting of minimal residual disease, All-trans retinoic acid (ATRA) improves outcome of children with metastatic neuroblastoma, another childhood primitive tumor. Few in-vitro studies have been done to test the efficacy of retinoic acid in RMS. Methods: We used embryonal and alveolar rhabdomyosarcoma cell lines to evaluate the effect of ATRA on cultured RMS cells. We analyzed treated RMS cells (versus vehicle-treated controls) for effects on cell proliferation, apoptois, differentiation, and senescence. In addition, we used human RMS xenografts in immunosuppressed (NOG-SCID) mice, to evaluate the effect of ATRA therapy in-vivo. We treated mice carrying RMS xenografts with chemotherapy until tumors clinically resolved, then commenced “maintenance therapy” of presumed minimal residual disease with either ATRA or vehicle control for a period of four weeks. The time to tumor re-growth was subsequently monitored. Results: We found that ATRA had a significant effect on preventing RMS cell accumulation in culture. In addition to an inhibitory effect on cellular proliferation, we found that ATRA induced differentiation and formation of myotubes in embryonal, and to lesser extent alveolar, RMS cell lines. Using RMS cell lines as mouse xenografts, we found that using ATRA as maintenance therapy after remission induction by chemotherapy had a modest effect on delaying time to tumor relapse. Conclusions: Our results suggest that ATRA may be useful as maintenance therapy of minimal residual disease to prevent relapse of childhood rhabdomyosarcoma. Studies are underway to evaluate primary human RMS samples (biopsies) for expression of retinoic acid receptor elements, to identify the proportion of patients that may benefit from such therapy if incorporated into future clinical trials. No significant financial relationships to disclose.
Evaluation of Splenic Function in Infants with Sickle Cell Anemia in the BABY HUG Trial.
Authors: Zora R. Rogers, Renee R. Rees, Winfred C. Wang, Daner Li, Rathi V. Iyer, Sohail Rana, Julio C. Barredo, James F. Casella, Catherine Driscoll, Stuart Toledano, Scott T. Miller, Sherri A. Zimmerman, John H. Miller, Eglal Shalaby-Rana, Steve Dertinger, Bruce Thompson, Russell E. Ware
Journal: Blood (2004)
Cancer registry-survey data linkages to measure patient-centered quality of care: SEER-MHOS and SEER-CAHPS.
Authors: Erin E. Kent, Michelle Mollica, Sarah Gaillot, Michael T. Halpern, Ron D. Hays, Lisa M Lines, Marie A. Topor, Gigi Yuan, Nicola C. Schussler, Edgardo Ramirez, Ashley Wilder Smith
Journal: Journal of Clinical Oncology (2016)

303 Background: Limited opportunities exist to conduct population-based surveillance of cancer patient-reported outcomes. Data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program has recently been linked with data from two Centers for Medicare &amp; Medicaid Services quality improvement surveys: the Medicare Health Outcomes Survey (MHOS) and the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. We provide an overview of the data available, recent findings, and priority areas for future research. Methods: Since 1998, the MHOS has conducted 2-wave/biennial surveys of individuals ages 65+ and individuals with disabilities enrolled in Medicare Advantage (MA) health plans on aspects of health-related quality of life, functional status, comorbidities, and symptoms. Fourteen cohorts are available, representing over 126K patients with cancer and over 1.9 million MA enrollees without a history of cancer. The SEER-MHOS publicly available data resource has produced over 40 data use agreements and 19 publications. SEER-CAHPS links cancer registry data with cross-sectional survey data of Medicare beneficiaries (both fee-for-service and MA) that contain information on patient experiences with care, including access to needed and timely care, doctor communication, health plan customer service, and care coordination. The current linkage contains survey data from 1998 to 2010 and includes over 150K and 570K respondents with and without a history of cancer, respectively. Plans to launch the publicly available resource are underway. Results: Recent findings include the impact of diagnosis and treatment on health-related quality of life in older cancer survivors, physical health impairments and variation of treatment received, the impact of cancer on activities of daily living, and variations in care ratings between participants with and without cancer across the cancer control continuum. Conclusions: The SEER-MHOS and SEER-CAHPS linked data resources provide population-based surveillance data on cancer patient-reported outcomes which allow unprecedented opportunities to evaluate national quality improvement activities.
PSMA, EpCAM, VEGF, and GRPR as imaging targets in locally recurrent prostate cancer after radiotherapy.
Authors: Hilde Hoving, Hildo J. K. Ananias, Maxim Rybalov, Henk Vanderpoel, Stefano Rosati, Igle De Jong
Journal: Journal of Clinical Oncology (2014)

201 Background: Currently, there is no imaging modality that can accurately discriminate between locally and distant recurrent prostate cancer after treatment with curative intent. Major drawback of the available techniques is that they are not prostate cancer specific. Selecting patients for salvage cryotherapy of the prostate or salvage prostatectomy by excluding distant metastases proves a diagnostic challenge. In this retrospective pilot study expression of prostate-specific membrane antigen (PSMA), epithelial cell adhesion molecule (EpCAM), vascular endothelial growth factor (VEGF) and gastrin-releasing peptide receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or external beam radiotherapy (EBRT) was investigated and their adequacy for targeted imaging was analyzed. Methods: Prostate cancer specimens were collected of 17 patients who underwent salvage prostatectomy because of locally recurrent prostate cancer after brachytherapy or EBRT. Local recurrence was based on rises in PSA and prostate biopsies. Immunohistochemistry was performed on the radical prostatectomy specimens. A pathologist blinded to clinical and pathological data scored the immunoreactivity on a four point scale in prostate cancer and in stroma. Results: Staining for PSMA was seen in 100% (17 out of 17), EpCAM in 82.3% (14 out of 17), VEGF in 82.3% (14 out of 17) and GRPR in 100% (17 out of 17) of prostate cancer specimens. Staining for PSMA, EpCAM, and VEGF was seen in 0% (0 out of 17) and for GRPR in 100% (17 out of 17) of specimens’ stromal compartments. In 11.8% (2 out of 17) of cases GRPR staining intensity of prostate cancer was higher than that of stroma, while in the remaining 88.2% (15 out of 17) of cases GRPR staining in cancer and stroma was equal. Conclusions: Based on the absence of stromal staining PSMA, EpCAM, and VEGF had a high tumor distinctiveness. GRPR had a low tumor distinctiveness as a result of the high stromal expression. Therefore, PSMA, EpCAM, and VEGF can be used for targeted imaging of locally recurrent prostate cancer after radiotherapy.
Induction chemotherapy with cisplatin and gemcitabine followed by re-irradiation for locally recurrent nasopharyngeal carcinoma
Authors: D. T. T. Chua, J. Sham, G. Au
Journal: Journal of Clinical Oncology (2005)

5535 Background: Patients with advanced local recurrence of nasopharyngeal carcinoma (NPC) have a poor prognosis. Retreatment by radiotherapy alone has a relatively poor chance of control and outcome. Induction chemotherapy may shrink the tumor and thereby facilitates subsequent re-irradiation. We conducted a phase II study to evaluate the efficacy and safety of cisplatin and gemcitabine as induction chemotherapy followed by re-irradiation for locally recurrent NPC. Methods: Twenty patients with locally recurrent NPC not amenable to brachytherapy or surgery were enrolled between Sept. 2001 and Oct. 2003. The recurrent T stage was rT2 in one, rT3 in six, and rT4 in thirteen. One patient also had unilateral nodal recurrence. Induction chemotherapy consisted of cisplatin 40 mg/m2 and gemcitabine 1.25 G/m2 on days 1 & 8 every 21-day for three cycles followed by re-irradiation using intensity-modulated radiotherapy. Results: A total of 58 chemotherapy cycles were administered to patients and most (85%) received 3 cycles. Hematological toxicity was moderate with grade 3 and 4 neutropenia occurred in 55% and 5% of patients, respectively. Severe thrombocytopenia was uncommon with only 5% grade 3 toxicity. The most common non-hematological toxicity was rash which occurred in 60% of patients. After induction chemotherapy, fifteen patients achieved partial response (75%) and five had static disease (25%). Seventeen patients received re-irradiation and one had radiosurgery after chemotherapy. No significant acute toxicity was observed during radiotherapy. After re-irradiation or radiosurgery, eleven patients had complete response (61%) and 4 had partial response (22%). After a median follow-up of 14.5 months, 45% of patients had no progression of loco-regional disease and 55% are still alive. The one-year loco-regional control rate and survival rate were 63% and 80%, respectively. Conclusions: The combination cisplatin and gemcitabine was well tolerated and effective in recurrent NPC. The current approach of using induction chemotherapy prior to re-irradiation may improve the outcome of patients with advanced local recurrence of NPC and merits further investigation. No significant financial relationships to disclose.
The effect of 4SC-207, a novel antimitotic agent, on multidrug-resistant cell lines.
Authors: R. Baumgartner, R. Krauss, S. Hamm, R. Doblhofer, B. Hentsch
Journal: Journal of Clinical Oncology (2011)

e14090 Background: 4SC-207 is a novel small molecule with strong anti-mitotic activity. In this study the potency on in vitro cell proliferation, including chemotherapeutically resistant P-gp-expressing cells, was investigated. These observations were confirmed in in vivo xenograft tumor models. Methods: In vitro proliferation assay: 4SC-207 was tested on a panel of 50 ATCC cell lines. After a 24 h pre-growth period cells were incubated with 4SC-207 at different concentrations for 72 hours. After treatment cells were precipitated and stained with 0.4% wt/v sulforhodamine B solution in 1% acetic acid. Measurement of optical density was performed at 520 nm. Proliferation inhibition was determined as growth inhibition of 50% (GI50). In vivo xenograft model: 4SC-207 was tested both i.v. and p.o. in a xenograft NMRI mouse model using human colon adenocarcinoma cell line RKOp27. In the i.v. study 4SC-207 was administered at a dose of 40 mg/kg BID on days 1-7 and SID on days 8 and 11-14. In the p.o. study 4SC-207 was administered at a dose of 80 mg/kg SID on days 1, 2, 6, 7, 11, and 12. Endpoints consisted of tumor volume and body weight and hematologic parameters. Results: In vitro proliferation assay: 4SC-207 effectively inhibited the proliferation of most tested tumor cell lines with average GI50 values between 4 nM and 12 nM. 4SC-207 was also active on cell lines such as human colon cell lines HCT-15 and DLD-1 which display P-gp up-regulation and are known to be resistant to a large set of conventional anti-cancer agents (e.g. taxanes). In vivo xenograft model: 4SC-207 displayed a strong anti-tumor activity. Treatment with 4SC-207 induced complete tumor stasis (i.v.: Treated/Control = 0.09; p.o.: T/C = 0.1). Effects on body weight were mild and other signs of overt toxicity were not observed. Conclusions: 4SC-207 is a highly potent, novel anti-mitotic compound with strong in vitro and in vivo anti-tumor activity. 4SC-207 is also active on P-gp expressing tumor cells and offers the opportunity for treatment of hematological and solid tumor types which are resistant to standard anti-cancer agents.
Changes in body composition after androgen deprivation therapy (ADT) in prostate cancer patients. Relationship with disease outcome
Authors: A. Berruti, F. Vana, M. Tucci, A. Mosca, L. Russo, G. Gorzegno, A. Saini, P. Perotti, M. Tampellini, L. Dogliotti
Journal: Journal of Clinical Oncology (2008)

16007 Background: ADT increases fat body mass (FBM), decreases lean body mass (LBM); and decreases bone mineral density (BMD) in men with prostate carcinoma. No data are actually available regarding the relationship between treatment-related changes in body composition and patient outcome. Methods: Using dual energy x-ray absorptiometry (DEXA) we determined BMD, FBM and LBM at baseline and after 1 and 2 years in 50 consecutive patients with high risk non metastatic prostate cancer submitted to luteinizing hormone relasing hormone analogues (LHRH-A), recruited between 1997 and 2000. Results: patient median age (range) was 71 yrs (44–83). Nineteen patients had AUA stage B disease, 27 patients stage C and 4 patients stage D1. BMD (gm/cm2) at lumbar spine [mean, 95% Confidence Interval (CI)] was 0.943 (0.874–1.013) at baseline, 0.933 (0.866–1.00) after 1 year, and 0.927 (0.863–0.991) after 2 years (p<0.03); the corresponding LBM data (gm) were 50216 (48068–52364), 49553 (47314–51791), and 49377 (47247–51507), respectively (p<0.03); while FBM data (gm) were 19463 (17143–21783), 21028 (18964–23093), and 21680 (19427–23932), respectively (p=0.000). After a median follow-up of 76 months 11 patients (22.0%) underwent adverse skeletal related events (SREs), 20 (40.0%) had PSA progression, and 22 (44.0%) died. Changes in BMD after 1 year failed to show any relationship with time to SRE onset (TTSRE), PSA recurrence and death. LBM decrease below the median change after 1 year did not correlate with either TTSRE or survival while was predictive for lower risk of PSA recurrence just failing to attain the statistical significance [Hazard Ratio (HR) 0.40, 95% CI 0.15–1.08, p=0.07]. FBM increase above the median change after 1 year was a significant predictor of higher risk of SREs [HR 5.40, 95% CI: 1.09–26.8, p<0.04], higher risk of death [HR 3.45, 95% CI: 1.29–9.23, p<0.02] and lower (not significant) risk of PSA progression [HR 2.07, 95% CI: 0.80–5.40, p=0.13]. Conclusions: this explorative analysis suggest that changes in body composition, FBM in particular, assessed by DEXA, may provide predictive information of outcome in prostate cancer patients given ADT. More mature data will be provided at the meeting. No significant financial relationships to disclose.
Urologists’ experiences with treatment of castration-resistant prostate cancer.
Authors: Daniel M. Geynisman, Jaime Doyle, Alexander Kutikov, Robert G. Uzzo, Yu-Ning Wong, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2016)

315 Background: Urologists are at the forefront of treating prostate cancer. Since 2010 four non-chemotherapy drugs have been approved for castration-resistant prostate cancer (CRPC). We aimed to ascertain Society of Urologic Oncology (SUO) members’ practices, training, and barriers as they relate to the treatment of CRPC. Methods: An IRB approved nine item REDCap survey was emailed to 697 SUO members (440 US urologists) without a financial incentive. Urologists were asked whether they should and/or have treated men with CRPC, what barriers they experience and how these barriers may be overcome. Results: Eighty-four surveys were completed. 86% definitely or somewhat agreed that it was within the purview of urologists to prescribe therapy for CRPC. Abiraterone, enzalutamide, sipuleucel-T, or Radium-223 were prescribed by 51% and out of those, 44% personally prescribed them to &gt; 50% of their CRPC patients; 52% were aware of other urologists who prescribed these drugs. Education on the use of these drugs was most commonly via self-study (19%), national meetings (19%), pharmaceutical representatives (17%), and informal discussions with colleagues (16%). Although some did not see barriers (27%), side-effects management (23%), the time it takes to counsel patients on these therapies (14%), and their practice’s time and energy costs (14%) were the greatest obstacles to using these medications. 34% felt that more educational sessions at national meetings or greater support by professional organizations would help them increase drug administration. 53% see the recent changes in the management of CRPC as increasing the collaboration between urologists and medical oncologists and 30% believe there are increasing opportunities for urologists to strengthen their relationship with their CRPC patients. Conclusions: The majority of SUO respondents agreed that it is within the scope and practice of urologists to prescribe therapy for CRPC. Half have prescribed these therapies themselves and/or were aware of other urologists who had done the same. Some would be encouraged to increase their use of therapies for CRPC via greater support by professional organizations and education at national meetings.
Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation
Authors: Mahban Rahimifard, Faheem Maqbool, Shermineh Moeini-Nodeh, Kamal Niaz, Mohammad Abdollahi, Nady Braidy, Seyed Mohammad Nabavi, Seyed Fazel Nabavi
Journal: Ageing Research Reviews (2017)
Aprepitant as salvage therapy in patients (pts) with chemotherapy (ctx)- induced nausea and emesis (n/v) refractory to prophylaxis with 5-HT3-antagonists and dexamethasone (dexa)
Authors: C. Bokemeyer, K. Oechsle, M. R. Mueller, J. T. Hartmann, L. Kanz
Journal: Journal of Clinical Oncology (2005)

8166 Background: Despite prophylaxis with 5-HT3-antagonists and dexa n/v are among the most common ctx-induced toxicities. The NK1-antagonist aprepitant has shown efficacy in the prevention of acute and delayed emesis in phase III trials in pts receiving cisplatin-based ctx. The aim of this trial was to evaluate the efficacy of adding aprepitant in pts refractory to prophylaxis with 5-HT3-antagonists and dexa. These pts received aprepitant in addition to the same regimen of 5-HT3-antagonist and dexa as in the previous cycle of ctx. Patients and Methods: Between 09/03 - 10/04 29 pts, median age 51 years (23 - 77), with different malignancies (e.g. lymphoma n=11, gastric cancer n=5, lung n=3) received in total 73 cycles of ctx with aprepitant. Aprepitant was applied at 125 mg p.o day (d) 1 and 80 mg d 2+3. All pts were refractory to antiemetic therapy with 3 mg granisetrone and 8 mg dexa i.v. d 1 and 4 mg dexa d 2–3 during cisplatin- (n=10), other platin- (n=5) or non-platin-based (n=14) ctx. Currently 26 pts are evaluable for efficacy. Results: All pts with aprepitant considered their nausea to be below 30° on a visual analogue scale from 0 to 100 and reported a significant subjective improvement. Due to the addition of aprepitant the number of pts with nausea > 4 d decreased from 20 (77%) to 3 (12%) and with emesis >2 d from 22 (85%) to 0 (0%) (p< 0.001). The number of pts with nausea at 0–1 day increased from 0 (0%) to 16 (62%) (p<0.001) and without any emesis from 2 (8%) to 20 (77%) (p< 0.001). Until now 11 pts have received aprepitant for more then one cycle (2 - 8). The efficacy of aprepitant was consistant during all consecutive cycles of ctx. No toxicity possibly related to aprepitant was seen. Conclusion: Aprepitant has demonstrated significant activity as salvage therapy in pts with n/v refractory to prophylaxis with 5-HT3-antagonists and dexa following platinum- and nonplatinum-based ctx. This effect appears to be consistant over multiple cycles of ctx. No significant financial relationships to disclose.