tbuckley/cabot-search huggingface dataset:
Narrow band-ultraviolet B plus acyclovir in the treatment of herpes zoster in elders: clinical observation of 128 cases
Authors: Hai-gang Lu, Jian-she Chen
Journal: BMJ (2013)

A total of 258 cases of elderly patients with herpes zoster were divided into treatment group (n=128) and control group (n=130). The treatment group received a once daily dose of narrow-band ultraviolet irradiation plus oral acyclovir 0.8 g, 5 times a day. However, the control group received a once daily dose of infrared therapy plus the same oral acyclovir. At Day 9, the effective rates of treatment and control groups were 91.7% (117/128) vs. 74.6% (97/130) (P<0.05). Also, in terms of pain relief time (2.56±1.51) vs. (5.44±4.06) days, crusting time (4.51±0.48) vs. (6.11±1.81) days and healing time (5.65±0.56) vs. (9.28±0.21) days, the treatment group was better than those of the control group (P<0.01).


Key words: 
Herpes, zoster; Ultraviolet
甲状腺功能亢进合并脑梗死一例
Authors: 王晓玲, 张旋, 曹秉振
Journal: BMJ (2012)

患者男,27岁,因左侧肢体无力25 d,加重伴意识模糊15 d于2010年5月12日入院.患者25 d前无明显诱因出现左手活动不灵,15 d前左半身无力明显,在当地医院就诊过程中突发言语不能、烦躁、意识模糊,测体温40℃,查TSH＜0.01 mU/L,游离T4 65.9 pmol/L,游离T314.3 pmol/L,诊断为甲状腺功能亢进(甲亢)危象前期,给予甲泼尼龙、他巴唑、丙硫氧嘧啶等治疗6d,体温逐渐下降,但出现明显的左侧肢体偏瘫伴有育语不能、意识模糊.头颅MRI检查显示右侧颞叶、基底节及左侧额叶多发病灶,性质不明. 关键词：脑血管意外
Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.
Authors: Christopher Nutting, Keith Rooney, Bernadette Foran, Laura Pettit, Matthew Beasley, Laura Finneran, Justin Roe, Justine Tyler, Tom Roques, Audrey Cook, Imran Petkar, Shree Bhide, Devraj Srinivasan, Cheng Boon, Emma De Winton, Robert Frogley, Kathrin Mertens, Marie Emson, Emma Hall
Journal: Journal of Clinical Oncology (2020)

6508 Background: Most newly diagnosed oro- &amp; hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary &amp; nodal tumour; 54Gy/30f to remaining pharyngeal subsite &amp; nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior &amp; middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site &amp; AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Results: 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&amp;4 disease; 86% had concomitant chemotherapy only, 4% induction &amp; concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3–37.4), p &lt; 0.0001; superior &amp; middle PCM dose was S-IMRT 57.2Gy (56.3–58.3) vs. Do-IMRT 49.7Gy (49.4–49.9), p &lt; 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusions: Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC. Clinical trial information: 25458988 .
Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors.
Authors: Jia Wei, Qin Liu, Huizi Sha, Hanqing Qian, Jie Shao, Lijing Zhu, Lifeng Wang, Rutian Li, Baorui Liu
Journal: Journal of Clinical Oncology (2020)

3134 Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Nanotechnology has been reported to enhance immune responses of vaccines. Moreover, immunizing patients against such neoantigens, in combination with checkpoint inhibitor (CPI) and/or antiangiogenic drugs may elicit greater anti-tumor responses. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) is an amphiphiles nanovaccine loaded with personalized vaccine encoding multiple neoantigens designed to induce neoantigen specific T cells responses. Patients will receive PVAC in combination with PD-1 monoclonal antibody and/or antiangiogenic drugs. Primary end points include safety and tolerability. Results: 13 microsatellite stability (MSS) patients, which had relapsed from standard treatments, are enrolled in this study. 5 patients (1 gastric cancer, 1 liver cancer, 1 cervical carcinoma, 1 soft tissue sarcoma, 1 renal carcinoma) received PVAC in combination with PD-1 mAb, and another 8 patients (3 gastric cancer, 2 colon cancer, 1 NSCLC, 1 renal carcinoma) received PVAC in combination with PD-1 mAb and antiangiogenic therapy. No DLTs were reported. Five patients developed grade 1 and one patients developed grade 2 subcutaneous indurations in the injection sites, which collected with nanovaccine. One patient had grade 2 rash caused by antiangiogenic drug. No drug related SAEs have been observed. There are 1 CR, 6 PR, 4 SD and 2 PD. Neoantigen specific T cell responses have been detected by IFN-γ ELISpot from PBMCs. Conclusions: PVAC is safe and well tolerated. Clinical responses have been observed in combination with PD-1 mAb and antiangiogenic drugs and neoantigen-specific T cell response have been observed after vaccination. Clinical trial information: ChiCTR1900022986 .
Clinical characteristics and prognosis of children aged five or above with stage 3/4 neuroblastoma
Authors: Yi Zhang, Weiling Zhang, Dongsheng Huang, Tao Han, Tian Zhi, Jing Li, You Yi, Yuan Wen, Fan Li, Yanyan Mei
Journal: BMJ (2017)

Objective
To study the clinical characteristics and prognosis of children aged 5 or above with stage 3/4 neuroblastoma (NB).


Method
Among 180 children with NB admitted from March 2007 to June 2015, 54 were aged 5 or above with stage 3 or 4. The clinical characteristics, therapeutic efficacy and prognosis of above 54 cases were analyzed.


Results
There were 36 boys and 18 girls with a male to female ratio of 2∶1. The most common of primary site was retroperitoneum (41/54, 75.5%), followed by mediastinum (10/54, 18.5%), spine and pelvic cavity (3/545, 6%). After treated by average 9 cycles of chemotherapy, 34 cases (63%) achieved complete remission (CR), 13(24.1%) achieved partial remission (PR), 5 (9.3%) presented disease progression (DP), and 2 died (3.7%). Patients were followed up for median 30 months (8-99 months), 24 cases died and 30 survived with a overall survival (OS) rate of 55.6%. In 30 survival cases, there were 23 cases (76.7%) of event-free survival (EFS) , and 6 cases (20.0%) of PR and 1 case (3.3%) of DP. There were significant differences in prognosis among patients with different responses to first therapy (χ2=8.963, P=0.003). Among 20 children with stage 4 NB treated by autologous peripheral blood stem cell transplantation (APBSCT), 13 cases died and 7 survived with an average survival time of(73.55±8.89)months. Among 29 cases without APBSCT, 11 cases died and 18 survived with an average survival time of(40.19±5.52)months. There was no significant difference in survival between APBSCT and no-APBSCT.


Conclusion
Children aged 5 or above with NB tend to have advanced stage, relapse and long treatment cycle, but the survival still can be improved with the appropriate treatment.


Key words: 
Neuroblastoma; Child; Treatment outcome; Prognosis
Art in Endoscopy: “Oil painting”
Authors: Tanya Bisseling
Journal: Endoscopy (2020)

This detailed image shows a colonic tubular adenoma with low grade dysplasia. In the normal course of events it would simply be characterized as a polyp, Kudo IIIL, Paris Is, and Hiroshima B-type. However the original image resembled a 17th-century oil painting, prompting the idea to also photo-edit it in a baroque style. Thus we see here a tubular adenoma as Rembrandt van Rijn might have painted it!
Randomized phase II trial of MIBG versus MIBG/vincristine/irinotecan versus MIBG/vorinostat for relapsed/refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy Consortium.
Authors: Steven G. DuBois, Meaghan Granger, Susan G. Groshen, Denice Tsao-Wei, Anasheh Shamirian, Scarlett Czarnecki, Fariba Goodarzian, Rachel Berkovich, Hiroyuki Shimada, Yael P. Mosse, Suzanne Shusterman, Susan Lerner Cohn, Kelly C. Goldsmith, Brian D. Weiss, Gregory A. Yanik, Clare Twist, Meredith Irwin, Julie R. Park, Araz Marachelian, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2020)

10500 Background: 131 I-metaiodobenzylguanidine (MIBG) remains one of the most active agents for neuroblastoma. It is not clear if putative radiation sensitizers improve upon this activity. The primary aim of this trial was to identify the MIBG treatment regimen with highest response rate among: MIBG monotherapy (Arm A); MIBG/Vincristine/Irinotecan (Arm B); MIBG/Vorinostat (Arm C). The secondary aim was to compare toxicity across arms. Methods: We conducted a multicenter, randomized phase II trial. Patients 1-30 years with relapsed/refractory high-risk neuroblastoma were eligible with at least one MIBG-avid site and adequate autologous stem cells (ASCs). All patients received MIBG 18 mCi/kg on Day 1 and ASC on day 15. Patients on Arm A received only MIBG; patients on Arm B also received vincristine (2 mg/m 2 ) IV on Day 0 and irinotecan (50 mg/m 2 ) IV daily on Days 0-4; patients on Arm C also received vorinostat (180 mg/m 2 ) orally once daily on days -1 to 12. The primary endpoint was response after one course according to NANT response criteria. The trial was designed as a pick-the-winner study with a maximum of 105 eligible and evaluable patients to ensure an 80% chance that the arm with highest response rate is selected, if that response rate is at least 15% higher than the other arms. Results: 114 patients enrolled. Three patients were ineligible and 6 eligible patients never received MIBG, leaving 105 eligible and evaluable patients (36 Arm A; 35 Arm B; and 34 Arm C; 55 boys; median age 6.5 years). 9 patients had received prior MIBG monotherapy, 65 prior irinotecan, and 7 prior vorinostat. After one course, the response rates (Partial Response or better) on Arms A, B, and C were 17% (95% CI 7-33%), 14% (5-31%), and 32% (18-51%). An additional 4, 4, and 7 patients met NANT Minor Response criteria [partial response in one disease category (e.g., bone marrow) and stable disease in other categories] on Arms A, B, and C, respectively. On Arms A, B, and C, rates of any grade 3+ non-hematologic toxicity were 19%, 49% and 32%; rates of grade 3+ diarrhea were 0%, 11%, 0%; and rates of grade 3+ febrile neutropenia were 6%, 11%, and 0%. Conclusions: The combination of vorinostat/MIBG had the highest response rate, with manageable toxicity. Vincristine and irinotecan do not improve the response rate to MIBG and are associated with increased toxicity. These data provide response rates for MIBG monotherapy in a contemporary patient population assessed with current response criteria. Clinical trial information: NCT02035137.
Trends in Sex and Racial/Ethnic Diversity in Applicants to Surgery Residency and Fellowship Programs
Authors: Krystina Choinski, Evan Lipsitz, Jeffrey Indes, John Phair, Qi Gao, John Denesopolis, Issam Koleilat
Journal: JAMA Surgery (2020)

This study uses the Electronic Residency Application Service database and Association of American Medical Colleges records to investigate trends in sex and racial/ethnic diversity of the applicant pool to US surgical residency and fellowship programs.
SBT6050, a HER2-directed TLR8 therapeutic, as a systemically administered, tumor-targeted human myeloid cell agonist.
Authors: Heather Metz, Monica Childs, Jamie Brevik, Damion Winship, Ty Brender, Michael Comeau, Kara Moyes, Jenny Chang, Jeffrey Adamo, Ben Setter, Hengyu Xu, Li-Qun Fan, Sean Smith, Phil Tan, Robert DuBose, Yvette Latchman, Peter Baum, Valerie Odegard
Journal: Journal of Clinical Oncology (2020)

3110 Background: Solid tumors are replete with myeloid cells which, when activated, drive potent anti-tumor responses. Clinical development of systemically administered myeloid cell agonists, however, has been hindered by acute toxicities due to peripheral activation of the targeted cell types. Intratumoral administration, the route of delivery typically used for innate immune/myeloid cell agonists, is limited by tumor accessibility and a dependence on abscopal responses. A systemically delivered myeloid cell agonist with tumor-localized activity has the potential to overcome challenges encountered with other innate immune/myeloid cell agonists in clinical development. Methods: SBT6050 is a novel therapeutic comprised of a potent toll-like receptor (TLR) 8 agonist payload conjugated to a HER2-directed monoclonal antibody. Delivery of the payload into the endosome of human myeloid cells, where TLR8 resides, requires the co-engagement of HER2 on tumor cells and Fc gamma receptor on human myeloid cells. Thus, SBT6050 is designed for systemic delivery and tumor-targeted activation of human myeloid cells. Results: Studies with human immune cells show that SBT6050 potently induces, in a HER2-dependent manner, multiple anti-tumor immune activities due to its direct activation of myeloid cells and the subsequent induction of T and NK cell cytolytic activity. SBT6050 is designed to activate human myeloid cells only in the presence of HER2-positive tumor cells with moderate (2+ by IHC) or high (3+ by IHC) expression levels. Tumor-localized activity has been demonstrated in mouse models using a SBT6050 mouse surrogate. Systemic delivery results in robust single agent efficacy in multiple mouse tumor models, even those engineered to lack T cells, without accompanying peripheral cytokine production. Trastuzumab and SBT6050 bind to distinct epitopes on HER2 and enhanced activity is observed when the two agents are combined. Conclusions: SBT6050 is a systemically administered, tumor-targeted myeloid cell agonist that demonstrates single agent efficacy in multiple mouse tumor models without peripheral cytokine production. A first-in-human study with SBT6050 is expected to begin this year for patients with HER2-expressing solid tumors.
HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist, versus leuprolide acetate for advanced prostate cancer.
Authors: Neal D. Shore, Daniel J. George, Fred Saad, Michael Cookson, Daniel R. Saltzstein, Ronald F. Tutrone, Hideyuki Akaza, Alberto Bossi, David van Veenhuyzen, Bryan Selby, Xiaolin Fan, Vicky Kang, Jacqueline M. Walling, Bertrand F. Tombal
Journal: Journal of Clinical Oncology (2020)

5602 Background: LHRH agonists are the mainstay for medical castration in advanced prostate cancer; however, they cause an initial testosterone (T) surge with a delayed onset of castration and require depot injection. Relugolix is the first oral GnRH receptor antagonist, which was previously shown to rapidly suppress T levels. The HERO trial compared the safety and efficacy of relugolix with leuprolide acetate in advanced prostate cancer patients. Methods: HERO is a 48-week, global, pivotal phase III trial that randomized 934 patients with androgen-sensitive advanced prostate cancer in a 2:1 ratio to receive relugolix 120 mg orally QD after a single l or leuprolide acetate 3-month depot injection. The primary endpoint was to achieve and maintain serum T suppression to castrate levels (&lt; 50 ng/dL) through 48 weeks. Key secondary endpoints included castration rates at Day 4, profound castration (&lt; 20 ng/dL) rates at Days 4 and 15, PSA response rate at Day 15 and FSH levels at Week 25. Testosterone recovery was evaluated in a subset of 184 patients. Results: A total of 96.7% (95% CI: 94.9%, 97.9%) of men on relugolix achieved and maintained castration through 48 weeks compared to 88.8% on leuprolide. The difference of 7.9% (95% CI: 4.1%, 11.8%) demonstrated non-inferiority (margin -10%) and superiority (P &lt; 0.0001) of relugolix to leuprolide. All key secondary efficacy endpoints tested demonstrated superiority over leuprolide (P &lt; 0.0001) (Table). In the testosterone recovery subset, median T levels were 270.76 ng/dL in the relugolix compared to 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy. In a prespecified analysis, the incidence of major adverse cardiovascular events (MACE) was lower in the relugolix group than in the leuprolide group (2.9% vs. 6.2%, respectively); otherwise the safety and tolerability profiles were generally similar. Conclusion: Relugolix achieved castration as early as Day 4 and demonstrated superiority over leuprolide in sustained T suppression through 48 weeks, faster T recovery after discontinuation and a 50% reduction in MACE. Relugolix has the potential to become a new standard for T suppression for patients with advanced prostate cancer. Clinical trial information: NCT03085095 . [Table: see text]
Phase II randomized controlled trial (RCT) of medical intensive nutrition therapy (MINT) to improve chemotherapy (CT) tolerability in malnourished patients with solid tumor malignancies.
Authors: Michael Shusterman, Gagandeep Brar, Kelsey Klute, Victoria Cooley, Alexandra Rosenstock, Eun Kyeong Hwang, Dina Elmonshed, Joseph T. Ruggiero, Allyson J. Ocean, Elizabeta C. Popa, Scott T. Tagawa, Ana M. Molina, David M. Nanus, Ronald J. Scheff, Ashish Saxena, Marcus D. Goncalves, Paul J. Christos, Manish A. Shah
Journal: Journal of Clinical Oncology (2020)

12090 Background: Malnutrition is an underrecognized predictor of inferior cancer related outcomes. Subjective global assessment (SGA), a brief validated survey for malnutrition, may predict increased CT toxicity. This phase II RCT was performed to validate SGA as a predictive tool for malnutrition and to evaluate the impact of MINT on CT associated toxicity. Methods: CT naive pts screened by SGA were assigned to well-nourished (SGA A) or malnourished (SGA B/C) cohorts. Both cohorts were followed for CT delivery, toxicity, quality of life (QOL) by FACT-G, biomarkers, radiology, and survival. SGA B/C pts, stratified by regimen/disease, were randomized 1:1 to MINT vs. usual care. The MINT cohort received weekly registered dietician counseling and symptom assessment over the 8-week study period. Percent standard and planned CT doses were calculated. Wilcoxon rank sum tests were used for differences between groups, log-rank tests for survival, and multivariable linear regression for adjusted comparisons. Results: 186 eligible pts were enrolled (94 SGA A, 92 SGA B/C). SGA A were younger (median age [range]; 63 [22, 89] vs. 70 [22, 91], p = 0.011) and more fit (ECOG 0-1; 96.8% vs. 72.8%, p &lt; 0.001). Baseline QOL was higher for SGA A (median [range], 87 [34, 115]) vs SGA B/C (70 [31, 101], p &lt; 0.001). SGA A was associated with higher CT delivery: median proportion of planned CT (1 [Q1 0.87, Q3 1] vs 0.94 [0.70, 1], p = 0.022) and standard CT (0.91 [0.72, 1] vs. 0.74 [0.57, 0.95] p &lt; 0.001). Adjusted for age/ECOG, SGA A remained associated with &gt; 80% of planned (OR 2.32, p = 0.05) and standard (OR 2.33, p = 0.04) CT. SGA B/C pts (n = 92) were randomized to MINT vs usual care: median nutrition encounters MINT 5.5 vs. usual care 0.5; we observed no differences in CT delivery: median proportion of planned CT (0.91 [0.69, 1] vs. 0.94 [0.74, 1], p = 0.84) and standard CT (0.75 [0.58, 0.96] vs 0.71 [0.52, 0.99], p = 0.59). SGA A was associated with a longer 12-month survival (77.8% [95% CI 69.6%, 86.9%]) vs. B/C (53.3% [42.8%, 66.4%], p &lt; 0.0001; 12-month survival was similar for MINT (52.3% [38.1%, 71.9%]) vs usual care (54.4% [40.2%, 73.6%], p = 0.58). Conclusions: SGA is a validated tool to characterize malnutrition in pts receiving CT. Malnourished pts received significantly less CT, experienced worse baseline QOL, and had worse 12-month survival. Intensive medical nutrition therapy was not associated with differences in CT associated toxicity. Novel nutritional interventions are still needed to improve pt outcomes.
Effects of community-based supervised exercise in the quality of life, physical fitness, and functioning of breast cancer survivors.
Authors: Alberto Alves, Sofia Viamonte, Anabela Amarelo, Catarina Garcia, Pedro Antunes, Barbara Duarte, Micael Vieira, Madalena Teixeira, Ana Tavares, Ricardo Lopes, Patricia Mendanha, Maria Martins, Inês Isabel Leão, Joana Catarina Lima Marinho, Luisa Helguero, Andreia Capela, Ana Joaquim
Journal: Journal of Clinical Oncology (2020)

e24035 Background: Physical exercise is recommended to cancer patients. We aim to evaluate the efficacy of a low-cost community-based supervised exercise program in early breast cancer survivors after primary treatment. Methods: A single-arm clinical trial, controled by a run-in period, of a 16-weeks intervention consisting of 3 weekly sessions of combined aerobic and strength exercise at moderate to vigorous intensity in group classes of no more than 20 participants. Participants were evaluated at weeks 1, 8 and 16 (M1, M2 and M3) of the run-in period and 8 and 16 of the experimental phase (M4 and M5) for quality of life (QoL) (EORTC QLQ-C30), handgrip strength, sit-to-stand (STS) test and maximal aerobic capacity. Results: Of the 82 participants, 25 completed the program and evaluations. Median age was 58 years (39-73), 64% underwent mastectomy, 48% had axillary lymph node dissection, 80% was treated with radiotherapy, 80% with chemotherapy and 84% with hormonotherapy. Median time from surgery was 13 months (4-107). Physical functioning domain of QoL improved significantly following 8 (p = 0.04) and 16 weeks (p = 0.03) of exercise training. Handgrip strength in surgical and non-surgical limbs increased after 8 weeks and maintained after 16 weeks of control phase, further increasing after 8 weeks (p = 0.01) and 16 weeks of exercise (p = 0.00). Lower-limb strength also increased after 16 weeks of exercise (p = 0.01), and maintained during control (p = 0.09). Additionally, maximal aerobic capacity tended to further increase after exercise training (p = 0.06), after increasing during control phase (p = 0.02). Conclusions: A low-cost community-based supervised exercise program improves physical fitness and functioning in breast cancer survivors after primary treatment. Clinical trial information: NCT04024280 . [Table: see text]