tbuckley/cabot-search huggingface dataset:
Can polymetastatic disease be arrested using SABR? A dosimetric analysis to inform development of a phase I trial.
Authors: Mark Thomas Corkum, Hatim Fakir, David A. Palma, Timothy K. Nguyen, Glenn Bauman
Journal: Journal of Clinical Oncology (2020)

e21567 Background: Phase II randomized trials suggest that stereotactic ablative radiotherapy (SABR) improves progression-free and overall survival in patients with oligometastatic cancer, with phase III trials currently testing SABR in up to 10 metastases. Whether SABR could provide similar benefits in polymetastatic disease ( &gt; 10 metastases) is unknown. A critical first step is to determine the feasibility of planning SABR for a large number of metastases throughout the body while maintaining acceptable organ at risk (OAR) doses. Therefore, we sought to evaluate the dosimetric feasibility of using SABR in polymetastatic disease ( &gt; 10 sites) while adhering to OAR constraints to be used in a phase I trial (ARREST). Methods: Five craniospinal CT simulations were utilized to retrospectively contour 24 (n = 2), 30 (n = 2) and 50 (n = 1) tumour targets not present on the initial scan. Standard PTV margins were added based on institutional immobilization practices. OAR constraints from published clinical trial protocols were used. Radiotherapy plans for the highest dose level in our planned phase I trial (30Gy in 5 fractions) were created utilizing a minimum number of isocentres. Plans were created using Raystation (RaySearch Laboratories, Stockholm, Sweden) for delivery on linear accelerators using volumetric modulated arc therapy. Results: The gross tumour volumes (GTVs) ranged from 134.8– 184.2cm 3 in our five test cases. The first two cases with 24 GTVs have been planned and were deemed to be clinically acceptable. PTV volumes were 483.0cm 3 and 417.4cm 3 , utilizing five and six isocentres for treatment respectively. Median PTV D95 was 29.7Gy and 29.0Gy, whole body V10 was 21.2% and 17.4%, and V5 was 41.8% and 44.8%. All OAR goals were met, though low-dose conformality was less than traditional SABR treatment plans (R100 of 1.04 and 0.93; R50 of 9.90 and 6.98, respectively). The remainder of the test cases will be presented. Conclusions: In our test cases, planning SABR in polymetastatic disease appears dosimetrically feasible. Our phase I clinical trial (ARREST) is under development, which will evaluate the feasibility and toxicity of delivering SABR in polymetastatic disease in a 3+3 dose escalation study. The starting dose level will be 12Gy in 2 weekly fractions, escalating the dose by adding 6Gy weekly until our target dose of 30Gy in 5 weekly fractions. Our study population will include &gt; 10 sites of disease, all tumour types, and patients must have exhausted standard lines of systemic therapy.
Prospective evaluation of patients for stereotactic radiosurgery/radiotherapy (SRS/SRT) by an experienced SRS/SRT radiation oncologist at a hospital-based cancer center lacking SRS/SRT capability.
Authors: Don Stacy, Christopher Rucker, Kimberly Cottongame, Lester Combs, Chad Jones, Hobie Cornett, Jessica Ivey
Journal: Journal of Clinical Oncology (2020)

e14043 Background: To prospectively determine the need for SRS/SRT at a hospital-based cancer center lacking SRS/SRT capability. Methods: An experienced SRS/SRT radiation oncologist prospectively evaluated new and established patients for radiation treatment at a hospital-based cancer center from July 30, 2018 through September 20, 2019. All radiation treatment options (per the NCCN Practice Guidelines in Oncology) were explained in detail to each patient. The radiation oncologist’s specific treatment recommendation to each patient was based on the radiation oncologist’s expertise. Cases for which the radiation oncologist recommended SRS/SRT were recorded. Results: From August 06, 2018 through September 25, 2019 an experienced SRS/SRT radiation oncologist evaluated 177 new or established patients for radiation treatment and recommended SRS/SRT for 23 patients (6 lung, 2 adrenal, 9 brain, 3 spine, 1 pituitary, 1 bone, and 1 prostate). Conclusions: To provide comprehensive radiation oncology patient services, SRS/SRT capability is required at a hospital-based cancer center evaluated by an experienced SRS/SRT radiation oncologist in this report, as SRS/SRT was recommended for twenty-three of one hundred seventy-seven (13%) patients evaluated for radiation treatment in a fourteen-month period.
Muscle impairment during follow-up as an independent prognostic factor for poor overall survival in pancreatic cancer.
Authors: Aurélien Lambert, Julia Salleron, Céline Gavoille, Auréline Viard, Ahmet Ayav, Thierry Conroy, Valérie Laurent
Journal: Journal of Clinical Oncology (2020)

e16726 Background: We aimed to assess that muscle impairment during follow-up is as an independent prognostic factor for poor overall survival in pancreatic cancer (PC) and is more accurate than a single muscle mass evaluation. Methods: Data from all patients with pancreatic adenocarcinoma at our center from 2009 to 2015 were retrieved (N = 114). A retrospective review of the total psoas area (TPA) was performed using manual segmentation on a single cross-sectional image through the third lumbar vertebrae for each available scan (N = 713, median number of scans per patient was 6 [3; 8]). For each patient, when at least two CT scans were available, the decrease in the TPA from baseline (Muscle Impairment) was expressed by a percentage. Results: In the univariate analysis, a TPA level under 420 mm 2 /m 2 during the follow-up, with a HR = 3.419 ([2.168; 5.394]; 95% CI; p &lt; 0.0001) and a TPA decrease of more than 20% from the baseline with a HR = 7.169 ([4.526; 11.353]; 95% CI; p &lt; 0.0001) were prognostic factors for death. The multivariate analysis confirmed the results with a HR = 5.799 ([3.418; 9.839]; 95% CI; p &lt; 0.0001) in the non-surgery group and a HR = 8.089 ([2.157; 30.339]; 95% CI; p = 0.0019) in the surgery group for a decrease in the TPA of more than 20% from the baseline. Conclusions: Muscle impairment during follow-up is a strong and independent prognostic factor for poor overall survival in patients with PC. It is in favor of a higher risk of death.
Outcomes of daratumumab, pomalidomide, and dexamethasone (DPd) followed by high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) in patients with relapsed/refractory myeloma RRMM.
Authors: Al-Ola A. Abdallah, Ajoy Dias, Hameem I Kawsar, Ghulam Rehman Mohyuddin, Monia Sigle, Zahra Mahmoudjafari, Leyla Osman Shune, Joseph McGuirk, Siddhartha Ganguly
Journal: Journal of Clinical Oncology (2020)

e20508 Background: The number of therapeutic options for patients with RRMM has increased significantly. Our institute treated a series of patients with induction therapy consisting of DPd followed by HDCT/ASCT. We present the early outcomes of these patients. Methods: We treated 16 patients with RRMM at the University of Kansas Health System between May 2016 and October 2019, with DPd as induction therapy followed by HDCT/ASCT. DPd was administered as Daratumumab 16 mg/kg weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks; pomalidomide was dosed at 4 mg orally on days 1-21 of a 28-day cycle; and dexamethasone 20 or 40 mg weekly. Responses were evaluated using the 2016 International Myeloma Working Group (IMWG) criteria. Results: Patients had received a median of two prior regimens. Out of the 16 patients: 81% received ASCT prior to this treatment. In addition, 75%,81% and 68% were refractory to proteasome inhibitors (PI), immunomodulatory agents (IMiDs), and double refractory to IMiDs and PI, respectively. Median time from diagnosis to treatment was 12 months. Median number of DPd cycles received was 4 cycles. A median follow-up of 27 (9-39) months, the overall response rate (ORR) after induction treatment with DPd was 100%. ORR on day 100 post ASCT was 100%, 65% achieved ≥CR, and 81% achieved ≥VGPR. There was no treatment related mortality on day 100. Median progression free survival was 34 months (95%, CI = NA), median overall survival was not reached. The most common grade ≥ 3 adverse events were thrombocytopenia 53%, anemia 40%, neutropenia 53%. Conclusions: DPd as induction therapy followed by HDCT/ASCT demonstrated deep, durable, and clinically meaningful responses with manageable safety profile in patients with RRMM. [Table: see text]
Brigatinib in Japanese ALK positive NSCLC patients previously treated with ALK tyrosine kinase inhibitors: J-ALTA.
Authors: Tatsuya Yoshida, Makoto Nishio, Toru Kumagai, Toyoaki Hida, Ryo Toyozawa, Tadasuke Shimokawaji, Koichi Goto, Kazuhiko Nakagawa, Yuichiro Ohe, Nobuyuki Yamamoto, Kentarou Kudou, Takayuki Asato, Pingkuan Zhang, Takashi Seto
Journal: Journal of Clinical Oncology (2020)

9537 Background: Brigatinib is an ALK inhibitor with demonstrated activity against ALK resistance mutations. To evaluate efficacy and safety in Japanese patients with ALK-positive non-small cell lung cancer (NSCLC), a prospective, single-arm, phase 2 study was conducted. We report the efficacy and safety of brigatinib in patients who have progressed on alectinib with or without prior crizotinib and of those who previously received up to two ALK tyrosine kinase inhibitors (TKIs) with or without prior chemotherapy. Methods: A safety evaluation lead-in was followed by an expansion stage of an ALK TKI-naïve and two ALK TKI-refractory cohorts. The refractory cohorts included patients with stage IIIB, IIIC, or IV NSCLC with ALK rearrangements. This report describes efficacy results from the post-alectinib patients in the expansion cohort and safety results from all refractory patients. The primary endpoint was confirmed objective response rate (ORR) assessed by IRC, secondary endpoints included duration of response (DoR), progression-free survival (PFS), disease control rate (DCR), and intracranial ORR (iORR). Brigatinib was administered at 180 mg QD with 90 mg QD lead-in for the first 7 days, and efficacy was evaluated every 8 weeks. Results: A total of 72 patients were enrolled in 28 sites, including a cohort of 47 patients with prior alectinib, with/without crizotinib between January 2018 and September 2019. The primary analysis of brigatinib in this cohort (data cut-off date 26 September 2019) demonstrated an IRC-assessed, confirmed ORR of 30% and a median DoR of 6.1 months. The median PFS was 7.3 months. Clinically meaningful intracranial efficacy was also observed (see table). Grade ≥3 TEAEs included blood creatine phosphokinase increase (18.1%), lipase increase (13.9%), hypertension (11.1%), amylase increase (4.2%), and pneumonitis (1.4%). Brigatinib also showed anti-tumor activity in patients with refractory secondary mutations in the ALK kinase domain, including G1202R, I1171N, V1180L, and L1196M. Conclusions: Brigatinib showed clinically meaningful efficacy in Japanese patients refractory to prior alectinib (first line or post crizotinib), regardless of prior chemotherapy. The safety profile of brigatinib was consistent with prior studies and no new safety findings were identified. Clinical trial information: NCT03410108 . [Table: see text]
丹红注射液在急性冠状动脉综合征防治中的作用
Authors: 赵步长, 赵涛, 赵明中
Journal: BMJ (2012)

急性冠状动脉综合征( ACS)具有发病急、病情变化快、死亡率高的特点,是临床上常见的心血管病之一.近年来,随着基础与临床研究的不断深入,ACS的防治指南不断更新,治疗效果显著提升.作为世界民族医药的重要组成部分——中医药在心血管疾病防治方面也做了广泛研究,积累了许多经验.针对ACS发病特点推出的丹红注射液,在ACS防治中发挥了重要作用,对此做一概述。
Delayed adjuvant radiotherapy in early-stage cervical cancer with intermediate-risk features has a detrimental effect on survival that cannot be corrected by adjuvant chemotherapy.
Authors: Joyson Kodiyan, Adel Guirguis, Hani Ashmalla
Journal: Journal of Clinical Oncology (2020)

6037 Background: GOG-0263 is currently investigating the role of adjuvant chemotherapy (CT) concurrently with radiotherapy (RT) in patients with early stage cervical cancer that underwent radical hysterectomy and pelvic lymphadenectomy harboring intermediate risk features. We used a retrospective database to investigate whether adjuvant chemotherapy significantly influenced overall survival (OS), and whether its effectiveness is influenced by delays in radiotherapy. Methods: All data was obtained from the NCDB (National Cancer Database) and initially contained 115,747 cases of cervical cancer diagnosed between 2004 and 2015. Analyzed patients had early stage disease, received radical hysterectomy with pathologic stage I to IIA, and had intermediate risk features including size greater than 4 cm or lymphovascular invasion. All patients received adjuvant RT with or without CT. Cases with positive margin or nodes, with parametrial extension, or metastasis were excluded. Cases were weighted by inverse probability of treatment (CT) using clinical and socioeconomic variables, and analyzed for OS using multivariate models. Predictors of receiving CT were determined using multivariate logistic regression. Results: The final cohort was 557 patients with median follow-up of 43 months (range, 1.54-143.7). Median survival without CT (n = 244) versus with CT (n = 313) was 42.2 versus 43.9 months (HR 0.81, 95%CI 0.661-0.995, p = 0.045). Median time from diagnosis to RT was 91 days (range, 21-691), and predicted for inferior OS (p = 0.007). No significant interaction existed between RT delay and receipt of CT (p = 0.997). Cases with squamous histology were less likely to receive CT than adenocarcinoma histology (OR 0.345, 95%CI 0.159-0.725, p = 0.006). Conclusions: Poor survival outcomes are observed in patients with early stage cervical cancer harboring intermediate risk features when adjuvant radiotherapy is delayed. This outcome was not corrected by addition of chemotherapy.
Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors
Authors: Phonphimon Wongthida, Matthew R Schuelke, Christopher B Driscoll, Timothy Kottke, Jill M Thompson, Jason Tonne, Cathy Stone, Amanda L Huff, Cynthia Wetmore, James A Davies, Alan L Parker, Laura Evgin, Richard G Vile
Journal: Neuro-Oncology (2020)

Diffuse midline glioma, formerly DIPG (diffuse intrinsic pontine glioma), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated (i) whether direct delivery of adenovirus-expressing cluster of differentiation (CD)40 ligand (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and (ii) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.
Efficacies and safety of traditional Chinese medicine plus bifonazole cream for tinea pedis patients
Authors: Jianping Zhang, Qiuyan Yang, Jiayuan Hu, Qi Shao
Journal: BMJ (2014)

To evaluate the efficacy and safety of traditional Chinese medicine plus bifonazole 1% cream in the treatment of tinea pedis. A total of 375 patients with tinea pedis were randomly assigned to receive traditional Chinese medicine plus bifonazole 1% cream (treatment group, n=196) or bifonazole 1% cream alone (control group, n=179). Efficacy was estimated in terms of mycological care, total clinical sign and symptom scores. And adverse reactions were also recorded. The results showed that, at Week 2 post-treatment, the cure rate was 45.41% (89/196) and effective rate 77.04% (151/196) in combination group versus 34.08% (61/179) and 61.45% (110/179) in control group. There was significant inter-group difference (P 0.05).


Key words: 
Tinea, foot; Treatment outcome
Cost-effectiveness analysis of stereotactic ablative radiotherapy in patients with oligometastatic cancer.
Authors: Abhishek Kumar, Christopher Andrew Straka, Lucas Vitzthum, Daniel R Cherry, Patrick T Courtney, Paul Riviere, James Don Murphy
Journal: Journal of Clinical Oncology (2020)

7085 Background: The SABR-COMET randomized clinical trial found that stereotactic ablative radiotherapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of SABR compared to standard therapy among cancer patients with oligometastatic disease. Methods: We constructed a Markov model to simulate treatment with stereotactic ablative radiotherapy or standard therapy among patients with oligometastatic cancers. The model derived transition probabilities from clinical trial data to estimate risks of toxicity, disease progression and survival. Healthcare costs and health utilities were estimated from the literature. Cost-effectiveness was estimated with an incremental cost-effectiveness ratio (ICER) defined as dollars per quality-adjusted life year (QALY), with an ICER less than $100,000/QALY considered cost-effective. One-way and probabilistic sensitivity analyses were used to examine model uncertainty. Results: The addition of SABR increased total costs by $54,279 and improved effectiveness by 1.20 QALYs compared with standard therapy, leading to an ICER of $45,162/QALY. The model was sensitive to assumptions about tumor progression, though the model was not sensitive to assumptions about survival or cost of treatment. The cost of SABR would need to increase approximately six-fold from $12,241 to $78,151 before SABR becomes cost-ineffective. Probabilistic sensitivity analyses demonstrated that SABR was the cost-effective treatment option 97.2% of the time. Conclusions: The addition of SABR increased costs and improved quality adjusted survival, overall leading to a cost-effective treatment strategy for patients with oligometastatic cancer.
Risk factors for herpes zoster in multiple myeloma patients
Authors: Lina Xiang, Ying He, Qiang Zhuang, Yongyong Ma, Songfu Jiang
Journal: BMJ (2018)

Clinical data of 153 patients with multiple myeloma admitted from January 2005 to December 2015 were retrospectively reviewed, including 56 cases complicated with herpes zoster (case group) and 97 cases without herpes zoster (control group). The risk factors for herpes zoster in multiple myeloma patients were analyzed by univariate and multivariate logistic regression.Univariate analysis showed that herpes zoster significantly associated with albumin/globulin ratio (A/G) <0.5 (χ2=10.989, P<0.05), unremitted myeloma(χ2=12.310, P<0.05), neutropenia (χ2=8.100, P<0.05)and treatment with bortezomib(χ2=9.465, P<0.05). Multivariate logistic regression analysis showed that herpes zoster was positively correlated with A/G <0.5(OR=6.344, 95%CI: 1.511-26.645, P<0.05), neutropenia(OR=6.402, 95%CI: 1.420-28.869, P<0.05), treatment with bortezomib(OR=7.335, 95%CI: 1.587-33.911, P<0.05); and negatively correlated with remitted myeloma (OR=0.064, 95%CI: 0.017-0.237, P<0.05). It is necessary to take corresponding countermeasures targeting the risk factors to prevent herpes zoster in multiple myeloma patients.


Key words: 
Multiple myeloma; Herpes zoster; Risk factors
服用萘普生诱发急性胰腺炎一例
Authors: 陈炎, 陈亚蓓, 陶荣芳
Journal: BMJ (2007)

患者女,46岁,因两侧腕、掌指、指间、踝、膝及趾关节对称性疼痛,肿胀伴晨僵3年于2005年12月11日来院就诊.发病后曾于当地乡村医院予针刺、服中药及草药药酒等治疗,无效.查体:体温36.4℃,脉搏74次/min,呼吸22次/min,血压110/78 mm Hg(14.6/10.4 kPa);慢性病容,贫血貌,心、肺、腹部等无异常;两侧腕、掌指、指间、踝、膝及趾关节肿胀,畸形,压痛,两侧掌指关节半脱位,受侵关节伸屈受限,四肢肌肉及双侧大小鱼际肌萎缩;神经系统查体无阳性。
老年人单纯收缩性高血压的治疗
Authors: 吴海云
Journal: BMJ (2012)

老年高血压患者,多数表现为单纯收缩性高血压.对于老年人,收缩压升高是发生心脑血管事件的重要危险因素.单纯收缩性高血压的老年患者,甚至80岁以上者,同样可以从降压治疗中获益；在降压药物治疗时,需要特别注意防止体位性低血压的发生,一般可采用常规剂量的1/3作为起始量,缓慢、谨慎地调整,直至血压达标。
Clinical research on second electric transurethral resection for noninvasive bladder cancer
Authors: Ying Liu, Jian Jin, Qi-zhong Fu, Hui Chi
Journal: BMJ (2009)

Objective To explore clinical significance in the second electric transurethral resection for noninvasive bladder cancer (TURBt). Methods Ninety-four patients with diagnosed noninvasive bladder cancer in the observed group were undergone the second TURBt after primary one to observe the existence of tumor residue and its location, and changes in its pathological stage and grade, with forty-two noninvasive bladder cancer patients by single TURBt and partial cystectomy or radical total cystectomy as controls. Different treatment plans were instituted according to their outcomes of the second TURBt. Results Tumor residues were found in 49 patients (52%) with the second TURBt and pathological stage and grade were found increased in 15 patients. Treatment plans were changed for 15 patients according to their outcomes of the second TURBt. Tumor recurred in five patients in the observed group and nine in the control group after follow-up for 18 to 36 months (24 months in average). Conclusions The second TURBt is an only effective method to treat for patients with noninvasive bladder cancer to reveal their actual situation, evaluate their stages and examine residue of the tumor, especially more importance for those patients with later stages, larger size and multiple occurrence of the tumor, which can decline its recurrence and postpone its progression.

Key words: 
Urinary bladder neoplasms;  Cystectomy;  Second-look surgery;  Treatment outcome
Immunohistochemical determination of PD-L1 expression with three different antibody clones and determination of SOX10 expression in triple negative breast cancer.
Authors: Margit Maria Guhl, R.M. Bohle, Martin Ertz, Mariz Kasoha, Mohammed Eid Hammadeh, Ingolf Juhasz-Boess, Erich-Franz Solomayer
Journal: Journal of Clinical Oncology (2020)

e15237 Background: In triple negative breast cancer (TBNC), checkpoint inhibitors directed against PD-L1/PD-1 show an improvement of therapy. For the immunohistochemical diagnosis of the predictive biomarker PD-L1, there are various antibodies and kits available. We examined the expression of PD-L1 in TNBC with different antibody clones to compare these results with regard to the staining of tumor cell membranes, staining of immune cells and cytoplasmic staining in order to find out whether the different clones or methods can be exchanged. It was also checked whether PD-L1 or SOX10 expression correlates with the existing clinical parameters. Methods: Breast cancer tissue of 60 patients with TNBC were examined for the expression of PD-L1 and SOX10 by immunohistochemistry. The detection kit used, was the ultraView universal alkaline phosphatase red detection kit for the antibodies anti-human PD-L1 clone 22C3 from Dako, the clone 28-8 from abcam and the SOX10 antibody clone SP267 from Cell Marque. The anti-PD-L1 antibody clone SP142 was detected with OptiView DAB. The cut-offs for the expression of PD-L1 at the tumor cell membrane were &lt; 1%, &gt; 1 to &lt; 50% and &gt; 50%. In the evaluation of SP142 the staining of the immune cells was evaluated with the score: percentage of PD-L1 positive immune cells to the tumor cells that were present. For SOX10, the nuclear staining was evaluated with the score: &lt; 1, &gt; 1 to 50, &gt; 50 to &gt; 100 and 100. The relationship between PD-L1 expression (TC and IC) and SOX10 expression was evaluated with the clinical parameters of the patients from the time of diagnosis until the end of data collection. Results: The antibodies clone 22C3 and clone 28-8 lead to the same results (22,0 % PD-L1 (TC) positive). Clone SP142 showed significantly (p &lt; 0,001) more PD-L1 positive cases(40,7%). For the additional evaluation of the cytoplasmic staining with clone 22C3 and clone 28-8 it could be shown that the PD-L1 Expression is equivalent (40,7%) to the immune cell staining with clone SP142. With exception of Ki67 we were unable to demonstrate any correlation between PD-L1 (membrane and cytoplasmic), SOX10 and other clinical parameters in TBNC. Conclusions: The antibodies clone 22C3 and 28-8 can be used equivalently for PD-L1 determination in TBNC. Clone SP142 showed different results. The cytoplasmatic staining with 22C3 and 28-8 could gain importance in the future because the results were equivalent to the immune cell staining with clone SP142. There is no correlation between PD-L1 and SOX10 in TNBC.