tbuckley/cabot-search huggingface dataset:
Shingles vaccine coverage for 70 year olds is falling
Authors: Susan Mayor
Journal: BMJ (2016)

The number of elderly people being vaccinated against shingles is decreasing, latest figures from the vaccination programme in England have shown.1

Public Health England reports that the proportion of people aged 70 receiving shingles vaccine as part of the routine national programme fell from 61.8% in 2013-14 to 54.9% in 2015-16, representing a 6.9% decrease since the programme started in September 2013.

The number of 78 year olds having the shingles vaccine in the …
A Novel Treatment Protocol Successfully Prevented Graft Rejection and Improved Disease-Free Survival in Class 3 Children with Thalassemia
Authors: Javid Gaziev, Pietro Sodani, Antonella Isgrò, Marco Marziali, Maria Domenico Simone, Fabio Torelli, Marco Andreani, Manuela Testi, Katia Paciaroni, Cristiano Gallucci, Andrea Roveda, Gioia De Angelis, Cecilia Alfieri, Guido Lucarelli
Journal: Blood (2011)
Influence of imatinib interruption and imatinib rechallenge on the residual tumor volume in patients with advanced GIST: Results of the BFR14 prospective French Sarcoma Group randomized phase III trial.
Authors: J. Domont, J. Blay, I. L. Ray-Coquard, B. Bui Nguyen, A. Adenis, M. Rios, F. Bertucci, F. Duffaud, D. Cupissol, C. Chevreau, E. Bompas, V. Bourne-Branchu, S. Chabaud, A. Le Cesne
Journal: Journal of Clinical Oncology (2011)

10054 Background: We previously demonstrated that imatinib mesylate (IM) must not be interrupted after 1, 3 and 5 years in responding patients (pts). The impact of treatment interruption on the emergence of resistance to IM or on overall survival (OS) can not be established in this study. However, the tumor volume of residual lesions at the time of IM interruption and at the time of the best response when IM was reintroduced could influence the long term OS. Methods: This prospective multicenter BFR14 study was initiated in June 2002 and closed for inclusion in July 2009. Seventy one non progressing patients were randomized in the interruption arm (I arm) after 1 (32 pts), 3 (25 pts) and 5 years (14 pts) of IM 400 mg/day. IM was reintroduced in case of progressive disease (PD) (same dose). Tumor volume at the time of randomization, at relapse and after IM rechallenge (best response) were analyzed and compared. Results: As of January 2011, 54/71 patients restarted IM, 51 at PD and 3 without documented PD. The analysis was performed on the 51 PD pts where tumor assessments were available at the time of randomization, at PD and after IM reintroduction. At the time of randomization, 17 pts (33.3%) were in CR, 25 (49%) in PR and 9 pts (17.6%) had a disease stabilization according to RECIST. Among the 51 PD pts after IM interruption, 25 pts (49%) exhibited a PD of the previous known target lesions while 26 pts (51%) had new lesions (with concomitant PD of known lesions in 12 pts). Only 41.2% (7 pts) of CR and 56% (14 pts) of PR observed at the time of randomization achieved a new CR and PR respectively as best response when IM was restarted. If we considered exclusively the cohort of pts without new lesions at PD (progression on preexisting target lesions), only 16.7% of CR at the time of randomization experienced a new CR. Conclusions: IM interruption in responding pts with advanced GIST results in tumor progression in the majority of pts even in pts considered in CR before randomization. Further tumor control was obtained in all but 2 pts following IM reintroduction but the tumor status according to RECIST at best response was not similar to those observed at randomization.
Changes in body fat and lipid metabolism in testicular cancer patients undergoing curative chemotherapy.
Authors: Peter-Paul Michiel Willemse, Rutger W. van der Meer, Saskia van Elderen, Jacobus Burggraaf, Hildo J Lamb, Albert de Roos, Susanne Osanto
Journal: Journal of Clinical Oncology (2012)

337 Background: Testicular cancer (TC) survivors are at increased risk to develop metabolic syndrome and cardiovascular disease. We assessed the utility of proton magnetic resonance spectroscopy (H1-MRS) and aortic Pulse Wave Velocity (aoPWV) with MRI to detect the early effects of chemotherapy-induced changes in lipid metabolism on liver fat storage and vascular function in testicular cancer patients undergoing curative treatment. Methods: Nineteen 19 chemo-naïve TC patients (age 20–54 years) were studied before, shortly after (&lt;3 months), and 9 months after the start of three or four cycles of cisplatin-based chemotherapy. At each visit, fasting blood samples for serum glucose, insulin, HbA1c, and lipids were collected, and abdominal subcutaneous (scFat) and visceral fat (visFat) volume, hepatic triglyceride content (HTgC), and aoPWV were assessed by MRI. All measurements were performed using validated methodology. Data were analysed using RM-ANOVA. Results: Shorty after cessation of chemotherapy there was an increase in fasting serum insulin (5.7±4.4 vs. 9.6±6.3; p=0.05), HOMA-index (1.3± 0.3 vs. 2.3± 0.4; p=0.006), HbA1c (5.2±0.3 vs. 5.3±0.6; p=0.03), total cholesterol (4.88±1.31 vs. 5.61±1.50; p=0.002) and LDL-cholesterol (3.31±1.16 vs. 3.73±1.41; p=0.02). This coincided with relative volume increases of scFAT (6.9%; 95%CI 0.4–13.4%) and visFAT (18.7%; 95%CI 2.4–35.1%), a unsignificant increase in HTgC (47.4%; 95%CI −5.4–129.5%). AoPWV did not change (0.2%; 95%CI −0.5–0.8%). All parameters that were increased at 3 months returned to baseline at 9 months, but the increases in scFAT and visFAT remained. Conclusions: Cisplatinum-based chemotherapy in TC patients is associated with disturbances of glucose and lipid metabolism shortly after therapy but returns to baseline later. These changes did not translate into significant increases in HTgC and aoPWV, suggesting that these measures are of limited value to detect early chemotherapy-induced changes. Interestingly, scFAT and visFAT showed sustained increases, and this may explain the observed higher incidence in metabolic syndrome and (ensuing) cardiovascular disease in chemotherapy-treated TC patients.
Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer (DRPC).
Authors: C. W. Reuter, M. A. Morgan, V. Gruenwald, M. Fenner, P. Ivanyi, A. Ganser
Journal: Journal of Clinical Oncology (2011)

172 Background: Cabacitaxel has recently been approved by the FDA as second-line chemotherapy for patients progressing during or after first-line docetaxel chemotherapy. However, cabacitaxel treatment is hampered by high costs and toxicity. Carboplatin in combination with docetaxel may also be effective in DRPC. Platinum(II)-complexes have been shown to lower testosterone levels by inhibiting 3β-hydroxysteroid dehydrogenase and 17α hydroxylase (Schertl et al. J Cancer Res Clin Oncol. 2007;133:153-67). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 55 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m 2 iv for one hour on days 1, 8, (15) plus prednisone 2×5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before and during carboplatin/docetaxel chemotherapy (n=25). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 28/55 (50.9%) patients. At the time of the current analysis the median follow-up time was 11.9 months and 32/55 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.7, 9.3) and median overall survival (OS) was 17.1 months (CI 95% 10.3, 23.9). In PSAR, PFS was 13.6 (CI 95% 7.8, 19.4) months versus 4.3 (CI 95% 2.9, 5.7) months in PSANR (p&lt;0.001; hazard ratio HR 0.159) and OS was 24.4 months (CI 95% 18.1, 30.8) versus 8.1 (CI 95% 3.4, 12.8) months (p&lt;0.001; HR 0.208). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (44.2/40.4%). Median free testosterone levels were 1.05 pg/ml before and 0.26 pg/ml during carboplatin/docetaxel treatment (p&lt;0.01). Conclusions: Our data suggest that carboplatin/docetaxel may be an important therapeutic second-line treatment option for DRPC patients by inferfering with the testosterone synthesis. No significant financial relationships to disclose.
Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study
Authors: Georges Reniers, Sylvia Blom, Clara Calvert, Alexandra Martin-Onraet, Abraham J Herbst, Jeffrey W Eaton, Jacob Bor, Emma Slaymaker, Zehang R Li, Samuel J Clark, Till Bärnighausen, Basia Zaba, Victoria Hosegood
Journal: The Lancet HIV (2016)
Bevacizumab (BEV) plus second-line taxane (TAX) or other chemotherapy (CT) for triple-negative breast cancer (TNBC): Subgroup analysis of RIBBON-2.
Authors: A. Brufsky, V. Valero, B. Tiangco, S. R. Dakhil, A. Brize, A. A. Duenne, N. Bousfoul, H. S. Rugo, D. A. Yardley
Journal: Journal of Clinical Oncology (2011)

290 Background: In three randomized trials in the first-line metastatic breast cancer (MBC) setting, combining BEV with CT significantly improved progression-free survival (PFS; primary endpoint) and objective response rate (ORR) vs. CT alone. BEV also showed a significant PFS benefit in the second-line MBC setting (RIBBON-2) when combined with TAX or other CT. We analyzed data from the subgroup of patients (pts) with TNBC in RIBBON-2. Methods: Eligible pts had MBC that had progressed on first-line CT without BEV. Second-line CT (TAX, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or placebo (PLA). All pts could receive BEV at progression. The primary endpoint was PFS. Results: RIBBON-2 included 684 pts; 159 (23%) had TNBC and of these, 67 (42%) received TAX with BEV/PLA. Baseline characteristics were broadly similar in the two treatment arms. In an exploratory analysis of pts with TNBC, BEV + CT led to significantly improved PFS and ORR vs. CT alone, and a trend toward improved overall survival (OS). The magnitude of the effect was particularly pronounced in pts receiving TAX CT. Conclusions: Pts with TNBC derive significant ORR and PFS benefit from BEV combined with second-line CT. Despite the small sample size, there was a trend (HR 0.624; p = 0.0534) toward OS benefit in pts treated with BEV, especially with TAX CT. [Table: see text]
Lymphocyte Recovery Predicts Outcomes In Cord Blood and T-Cell Depleted Haploidentical Stem Cell Transplantation
Authors: Stefan O. Ciurea, Victor E. Mulanovich, Ying Jiang, Roland Bassett, Gabriela Rondon, John McMannis, Marcos de Lima, Elizabeth J. Shpall, Richard E. Champlin
Journal: Blood (2010)
Bone Marrow Cellularity Is a Single Most Important Independent Prognostic Factor In AML Patients with t(8;21)
Authors: Ho-Jin Shin, Jooseop Chung, Hyeoung Joon Kim, Sang Kyun Sohn, Yoo-Hong Min, Jong-Ho Won, Sung Hwa Bae, Inho Kim, Je-Hwan Lee, Seong-Jun Choi, Jung-Hee Lee, Hwi-Joong Yoon, Jae Hoon Lee, Seok Jin Kim, Deog Yeon Jo, Young Don Joo, Dae Sik Hong, Dae Young Zang, Chul W. Jung, Jin Seok Ahn, Sun-Hee Kim, Junglim Lee, Soo-Mee Bang, Kyoo Hyung Lee
Journal: Blood (2010)
Factors associated with a delay in diagnosis of recurrent prostate cancer after radical prostatectomy.
Authors: K. E. Hoffman, M. Chen, P. L. Nguyen, C. L. Bennett, A. O. Sartor, K. Stein, D. A. Kuban, A. V. D'Amico
Journal: Journal of Clinical Oncology (2011)

208 Background: Salvage radiation therapy has an improved chance of increasing prostate cancer survival if it is administered at the earliest sign of recurrence, when prostate-specific antigen (PSA) is low. We identified factors associated with delay in diagnosis of recurrent prostate cancer after prostatectomy. Methods: We analyzed 375 men with PSA recurrence after prostatectomy enrolled in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry. Delay in diagnosis was defined as the time, in months, between recorded PSA greater than or equal to 0.2 ng/ml and enrollment in the registry. Multivariable regression analysis was used to identify sociodemographic and clinical factors associated with diagnosis delay. Diagnosis delay was dichotomized at the median (10 months) for the analysis. Results: At enrollment the median age was 70 years, median time since prostatectomy was 71 months, and median PSA was 0.7 ng/ml. On multivariable analysis, older men (p=0.043), men with greater length of time since surgery (p&lt;0.001), and men who contemplated delaying their PSA test (p=0.004) were more likely to have a delay in diagnosis of PSA recurrence. Men with Gleason 8 or higher disease at initial cancer diagnosis were less likely to have a delay (p=0.028). Conclusions: Older men, men with greater time interval since prostatectomy, and men who contemplate delaying their PSA test are more likely to have a delay in diagnosis of recurrent prostate cancer. Since early salvage radiation therapy may be curative, physicians should encourage PSA vigilance and early referral if a rising PSA is noted among men with these characteristics. [Table: see text]
Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Is Able to Distinguish Diffuse from Normal MRI Pattern of Marrow Involvement in Patients with Multiple Myeloma
Authors: Evangelos Terpos, Vassilis Koutoulidis, Sofia Fontara, Flora Zagouri, Dimitris Matsaridis, Dimitrios Christoulas, Andreas Koureas, Efstathios Kastritis, Meletios A. Dimopoulos, Lia A. Moulopoulos
Journal: Blood (2014)
Hematologic toxicities in cancer patients treated with the multityrosine kinase sorafenib: A meta-analysis of clinical trials.
Authors: F. A. Schutz, Y. Je, T. K. Choueiri
Journal: Journal of Clinical Oncology (2011)

352 Background: Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. Methods: The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). Results: A total of 3,221 patients were included. The incidence of sorafenib-associated all- grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR=0.62; 95% CI 0.39-0.98), an increased risk of all-grade (RR=1.69; 95% CI 1.33-2.17) and high-grade (RR=1.61; 95% CI 1.02-2.57) neutropenia, all-grade (RR=2.56; 95% CI 1.37-4.80) and high-grade (RR=3.63; 95% CI 1.98-6.66) thrombocytopenia, and high-grade lymphopenia (RR=1.84; 95% CI 1.22-2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. Conclusions: Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia. [Table: see text]
Sequential High Dose Immuno-Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation for Patients with Untreated Primary Central Nervous System Lymphoma - a Multicentre Study by the Collaborative PCNSL Study Group Freiburg
Authors: Gerald Illerhaus, Kristina Fritsch, Gerlinde Egerer, Monika Lamprecht, Nikolas von Bubnoff, Hans-Heinrich Wolf, Gottfried Dölken, Stephan Stilgenbauer, Jens Panse, Stefan Balabanov, Peter Hau, Norbert Frickhofen, Martin Bentz, Alexander Roeth, Robert Möhle, Tobias Birnbaum, Michael Pfreundschuh, Claudia Hader, Gabriele Ihorst, Martina Deckert, Marco Prinz, Elisabeth Schorb, Heidi Fricker, Benjamin Kasenda, Jürgen Finke
Journal: Blood (2012)
Effect of routine ipsilateral adrenalectomy on cancer-specific survival and risk of adrenal insufficiency for patients with pT3/4 renal cell carcinoma.
Authors: C. J. Weight, S. P. Kim, R. H. Thompson, S. A. Boorjian, B. C. Leibovich
Journal: Journal of Clinical Oncology (2011)

324 Background: The indications for the removal of the ipsilateral adrenal gland in patients with renal cell cancer (RCC) have not been well defined. Most continue to advocate ipsilateral adrenalectomy in patients with risky features such as a tumor thrombus, large, locally advanced tumors, and/or upper pole tumors. We evaluated the oncologic outcomes of concurrent adrenalectomy with either partial (PN) or radical nephrectomy (RN) in a large single institution cohort. Methods: From 1970–2006, 4,019 consecutive patients with RCC treated by RN (n=3,107) or PN (n=912) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer specific survival (CS) were also compared between those who underwent concomitant adrenalectomy (n=1,464) and those who did not (n=2,555) using multivariate cox models. Results: Median postoperative follow-up was 6 years. Synchronous ipsilateral adrenal involvement was rare even for those with large (&gt;7cm) tumors (2.5%), upper pole (1.3%), and locally advanced (pT3/4) tumors (3.5%). The development of asynchronous adrenal metastasis occurred in 109 patients (2.7%) at a median of 3.7 years after initial surgery. The risk of developing an ipsilateral (1.4% 95% CI 0.8, 2.0) vs. contralateral (1.8% 95% CI 1.0, 2.6) asynchronous adrenal metastasis was equivalent at 10 years, in those who did not undergo adrenalectomy at initial surgery. At 10 years, 7.3% (99% CI: 4.4, 10.2) of patients with higher stage tumors (pT3/4) are predicted to develop a contralateral adrenal metastasis. On multivariate analysis, routine adrenalectomy was associated with a decreased risk of subsequent adrenal metastasis (HR 0.88: 99% CI 0.81, 0.95), but did not significantly impact CS (HR 1.15: 99% CI 0.99, 1.34). Conclusions: Asynchronous metastasis can usually be salvaged without apparent effect on CS. Ipsilateral adrenal involvement from RCC was uncommon even in large, locally advanced, and/or upper pole tumors. Routine adrenalectomy in these high risk patients may lead to an unacceptably high rate of adrenal insufficiency when a significant subset develops a contralateral adrenal metastasis. No significant financial relationships to disclose.
An experimental model of FOLFOX-induced sinusoidal obstruction syndrome.
Authors: Stuart M. Robinson, Jelena Mann, Derek M Manas, Alastair D Burt, Derek A Mann, Steve A White
Journal: Journal of Clinical Oncology (2012)

222 Background: Sinusoidal obstruction syndrome (SOS) following oxaliplatin based chemotherapy is a cause for major concern when undertaking liver resection for colorectal liver metastases. To date no relevant experimental models of oxaliplatin induced SOS have been described limiting our ability to understand the pathogenesis of this condition. Methods: C57Bl/6 mice were treated with intra-peritoneal FOLFOX (n=10), or vehicle (n=10), weekly for five weeks and culled one week following final treatment. Organs were harvested for subsequent histological and biochemical analysis. Results: Mice treated with FOLFOX developed peri-venular sinusoidal dilatation and hepatocyte atrophy in keeping with features of SOS seen in patients treated with this regimen. In addition we noted up-regulation of genes within the liver associated with matrix remodelling such as MMP2 (p&lt;0.001), pro-collagen I (p&lt;0.001) and TGFβ (p&lt;0.001). We also demonstrated up-regulation of pro-thrombotic genes PAI-1 (p&lt;0.001) and vWF (p&lt;0.001) and genes involved in angiogenesis e.g. VEGFA (p&lt;0.01). Conclusions: We have provided the first direct evidence that FOLFOX directly results in the development of SOS in an experimental model. This system will enable us to gain a detailed understanding of the pathogenesis of this condition and provide a means to explore various strategies to prevent its development making major liver resection much safer after down-staging chemotherapy.
Prospective clinical trial of the merits of retroperitoneal lymph node dissection at the time of nephroureterectomy for upper tract urothelial carcinoma.
Authors: S. R. Rao, J. J. Correa, W. J. Sexton, J. M. Pow-Sang, P. E. Spiess
Journal: Journal of Clinical Oncology (2011)

293 Background: The role of retroperitoneal lymph node dissection (RPLND) in patients with upper urinary tract urothelial carcinoma (UUT-UC) remains controversial. The purpose of this prospective study was to assess the safety and feasibility of RPLND at the time of nephroureterectomy (NU) and to determine the incidence of lymph node metastasis and hence the clinical merit of this procedure at the time of NU. Methods: From March 2009 to October 2010, sixteen patients with UUT-UC underwent open (8), laparoscopic (4) or robotic (4) NU with modified RPLND. Each patient received the appropriate modified template dissection depending on the site of the UC. Demographic data, clinical and pathologic stage, histologic nodal status, perioperative complications and recurrence data were documented. Results: On final pathology, 11 (69%) patients had pTa disease, 1 (6%) had pT1, 3(19%) had pT3 disease and 1 (6%) had a benign angioma. The average lymph node count was 8 (range 3–27). No patient had positive lymph node metastasis. The median operative time was 252 minutes (range 146–371). Average EBL was 342 ml (range 100–950). Median hospital stay was 7 days (4–18). Median follow up was 5 months (range 0–16). There were four bladder tumor recurrences and one recurrence in the opposite renal pelvis and ureter. Two patients with pT3 disease as well as the patient with recurrence in the opposite UUT received chemotherapy. Four patients (25%) were given blood transfusions (median 1.2, range 1–2), one patient (6%) developed a chylous leak which resolved in four weeks, one patient (6%) developed postoperative ileus and one patient (6%) had a bowel injury during lysis of adhesions necessitating resection and anastomosis of small bowel. There was no injury to major vessels or other solid organs. Conclusions: Our preliminary results indicate that RPLND during NU for UUT-UC is a safe procedure with minimal morbidity. A larger prospective clinical trial as a multicenter study is required to adequately assess the pathological and treatment related outcomes. No significant financial relationships to disclose.