tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of nivolumab +/- ipilimumab for patients with metastatic sarcoma (Alliance A091401): Results of expansion cohorts.
Authors: James Lin Chen, Michelle R. Mahoney, Suzanne George, Cristina R. Antonescu, David A. Liebner, Brian Andrew Van Tine, Mohammed M. Milhem, William D. Tap, Howard Streicher, Gary K. Schwartz, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2020)

11511 Background: In the open-label multicenter phase II study, A091401, nivolumab (N) and nivolumab+ipilimumab (N+I) demonstrated a confirmed response rate (RR) of 5% and 16%, respectively in patients (pts) with advanced sarcoma (D’Angelo SP et al Lancet Oncology 2018). Responses occurred in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, leiomyosarcoma, sarcoma not otherwise specified and alveolar soft part sarcoma. Here, we report efficacy of N and N+I, in each of 3 expansion cohorts [gastrointestinal stromal tumor (GIST), UPS and dedifferentiated liposarcoma (DDLS)]. Methods: Pts refractory to ≥ 1 regimen(s) were randomized (non-comparative) to receive either N [N (3 mg/kg q2W)] or N+I [N (3 mg/kg Q3W x4, then Q2W) plus I (3 mg/kg q3W x4)]. The primary endpoint was 6 month confirmed RR (RECIST v1.1). For UPS and DDLS, 2 confirmed responses in the 1st 12 evaluable pts was needed (85% power, 1-sided alpha=0.15, 5 v 25% RR). For GIST, a confirmed response in the 1st 9 evaluable pts expanded enrollment to 24 (80% power, 1-sided alpha=0.10, 5 v 20% RR). Other endpoints: adverse events (AEs, TRAEs), progression-free and overall survival (PFS, OS), and correlatives. Results: See table. Clinical trial information: NCT02500797 . Conclusions: Neither N or N+I lead to confirmed responses in GIST. In DDLS and UPS, the primary response endpoint was met with N+I but not with N alone (RR 14% for N+I vs. 7% and 8% for N alone). For the GIST cohort TRAE was higher with N+I, holding enrollment as required per protocol. There remains a pressing need to determine genomic and clinical biomarkers of response, resistance and toxicity. Correlative analyses (whole exome sequencing, multiplex IHC and RNAseq) are in progress. Support: U10CA180821, U10CA180882; ClinicalTrials.gov Identifier: NCT02500797. [Table: see text]
Curative effect of community-home hospice care for terminal cancer patients
Authors: Xu-hai Sun, Qi Lu, Lin Jin, Yan Zhang, Yun Cui
Journal: BMJ (2013)

A total of 48 terminal cancer patients of Desheng Community were selected for developing life care, psychological support, pain relief and observations. As a result, the main symptoms of terminal cancer patients were alleviated. The average pain scores decreased from 5.6±2.7 to 3.0±2.4, average anxiety scores 14.2±6.8 to 6.3±3.0 and average depression scores 15.2±8.2 to 8.4±5.0. There were significant differences according to t-test (P<0.01).


Key words: 
Hospice care; Community health services
Does sinonasal cancer survival differ based on human papillomavirus status?
Authors: Shreya Pusapadi Ramkumar, Aleksandr R Bukatko, Matthew C Simpson, Eric Adjei Boakye, Gregory M Ward, Jastin L Antisdel, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2020)

6565 Background: The sinonasal tract is a lesser known “hot spot” for the human papillomavirus (HPV), compared with the oropharynx. Additionally, unlike the oropharynx, the role of HPV tumor status in the survival and overall prognosis of the sinonasal tract and other non-oropharyngeal head and neck cancer sites remains inconclusive. Understanding differences in survival based on HPV status could be useful clinically, as it has been for HPV-positive oropharyngeal disease. This study examined whether there are survival differences in sinonasal cancer based on HPV status. Methods: This study included adult sinonasal cancer cases diagnosed between 2010 and 2015 in the National Cancer Database. A multivariable Cox proportional hazards model estimated the association between sinonasal cancer HPV status (HPV-positive, HPV-negative) and all-cause mortality while controlling for covariates (sex, age, race/ethnicity, insurance status, urban/rural, county-level household income, county-level percentage without high school diploma, comorbidity score, stage, histology, facility type, and treatment). A second multivariable proportional hazards model stratified HPV-positive tumor status by high-risk HPV (16, 18, 26, 31, 33, 35, 36, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, and 85) vs. low-risk HPV (6, 11, 32, 34, 40, 42, 44, 54, 61, 62, 64, 71, 72, 74, 81, 83, 84, 87, and 89) and compared their all-cause mortality to HPV-negative patients. Results: There were 1,750 sinonasal cancer patients included in this study, and 484 (27.7%) had HPV-positive disease. Among patients with HPV-positive disease, 75.6% had high-risk types. Mortality risk among all HPV-positive patients combined was 23% lower than HPV-negative patients (aHR = 0.77; 95% CI 0.64, 0.93). After stratifying by high-risk vs. low-risk HPV, high-risk HPV positive patients had 30% lower mortality risk than HPV-negative patients (aHR = 0.70; 95% CI 0.57, 0.88) while risk of mortality did not significantly differ between low-risk HPV-positive patients and HPV-negative sinonasal cancer patients. Conclusions: Sinonasal cancer shows differential survival based on HPV status, and sinonasal cancer patients positive for high-risk HPV had a significantly greater survival advantage than low-risk strains and those with HPV negative disease. HPV status might yet play a role in prognostication of sinonasal cancer, if future studies confirm these findings.
Comparison of proximal femoral locking plate and proximal femoral intramedullary nail-spiral blade in minimally invasive internal fixation for elderly patients with intertrochanteric fracture
Authors: Lai Chen, Lin Liu, Lingchao Ye, Huaxing Hong
Journal: BMJ (2014)

Objective
To compare the proximal femoral locking plate (LPFP) and proximal femoral intramedullary nail-spiral blade (PFNA) in minimally invasive internal fixation for elderly patients with intertrochanteric fractures.


Methods
One hundred and thirty patients aged over 60 years with intertrochanteric fractures were treated with minimally invasive internal fixation from January 2010 to June 2013, among them LPFP was applied in 69 cases and PFNA in 61 cases. The operation time, the numbers of intraoperative X-ray fluoroscopy, intraoperative blood loss, postoperative flow and decreased postoperative hemoglobin, postoperative complications, medical expenses, fracture healing time, postoperative hip Hariss function score were documented and compared between two groups.


Results
There were no significant differences in intraoperative blood loss [(132±95) and (110±79) ml], postoperative draining [(44±16) and (41±17) ml], decreased postoperative hemoglobin, fracture healing time [(10.5±1.0) and (10.4±1.5) weeks] and postoperative hip Hariss function score (87±10 and 90±8) between two groups. In LPFP group the number of intraoperative X-ray fluoroscopy (8.1±0.8 and 8.6±0.9), hospitalization expenses, postoperative complications (7/69 and 16/61) were less than those in PFNA group (P<0.05 or 0.01), however, the operation time was longer (P<0.01).


Conclusion
LPFP may be a better choice in internal fixation for elderly patients with intertrochanteric fractures.


Key words: 
Femoral fractures; Internal fixators; Locking compression plate; Fracture fixation, intramedullary
Evaluation of the occurrence and management of PARP inhibitor toxicities.
Authors: Rachel Hatch, Sweta Patel, Christine Cambareri, Tanya Uritsky, Lainie P. Martin
Journal: Journal of Clinical Oncology (2020)

e18073 Background: Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a major cornerstone of therapy in the management of patients with ovarian cancer and other cancer types. The most common adverse events with PARPi therapy include bone marrow suppression, gastrointestinal (GI) toxicity, and fatigue. Currently, information is scarce regarding the management of some of these adverse events. Methods: A retrospective, descriptive observational study of adult patients with gynecologic malignancy, who received at least 2 weeks of PARPi therapy, was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019, from initiation of therapy through one-year post-initiation or last follow-up. The primary endpoint was the status of PARPi therapy at the end of the study period. Secondary endpoints included time to toxicity, progression free survival (PFS), and overall survival (OS). Descriptive statistics were used to analyze all endpoints. Results: Of the 85 patients included in the study, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on PARPi therapy, 16 (19%) discontinued the due toxicity, and 40 (47%) discontinued due to progression. Of 147 unique toxicities, 67 (46%) were GI-related, 48 (33%) were hematologic, and 32 (22%) were other toxicities, including fatigue, elevated serum creatinine, hypertension, and rash. Twenty-three percent of all toxicities were categorized as grade 3 or 4 per the Common Terminology Criteria for Adverse Events v5.0. The median number of management strategies required for GI toxicities was 1 (range 1-7), hematologic toxicities was 2 (1-8), and fatigue was 1.5 (1-4). Primary management strategies included pharmacologic therapy (96%) for GI toxicities; transfusion support (65%), holding PARPi therapy (67%), and dose reduction (52%) for hematologic toxicities; and dose reduction (78%) for fatigue. Hospital admission due to PARPi toxicity occurred in 12% of patients. The median time to toxicity was 29 days (1-330) and the median time to discontinuation due to toxicity was 72.5 days (9-353). Fifty-four patients (64%) had progression of disease and 18 (21%) died within one-year of initiation. Median PFS was 181 days and median OS was 338 days, censored for time to last follow-up. Conclusions: This observational study outlines the incidence of PARPi toxicity and some of the management strategies within an academic health system, further guiding practitioners in an area with limited information.
创伤性膈肌破裂28例
Authors: 卢敏, 胡永校
Journal: BMJ (2005)

据文献报道[1],创伤性膈肌破裂,特别是无膈疝症状时,诊断困难,伤势严重,临床上对该病认识不足,延误诊断率高达50%.我院自1998至2003年共收治创伤性膈肌破裂患者28例,现报告如下。
Factors of angiogenesis (VEGF and CD34) in primary and recurrent soft tissue sarcomas.
Authors: Evgeniya M. Nepomnyashchaya, Elena P. Ulianova, Aleksandr B. Sagakyants, Inna A. Novikova, Larisa N. Vashchenko, Tatiana V. Ausheva, Oksana G. Shulgina, Irina R. Dashkova, Liubov Yu Vladimirova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e23545 Background: The tumor ability to induce and maintain angiogenesis is one of the main stages of its development. Studies of molecular mechanisms of angiogenesis showed that the dynamic balance that ensures the formation and development of new vessels inside the tumor depends on pro- and anti-angiogenic factors. VEGF and the CD34 endothelial cell marker are considered among the main activators of angiogenesis. Our purpose was to study characteristics of angiogenesis in primary and recurrent soft tissue sarcomas. Methods: The study included 30 patients with primary sarcomas (group 1) and 26 patients with recurrent sarcomas (group 2). Sections of tissues embedded in paraffin blocks were studied by immunohistochemistry using the Thermo Scientific 480S automated stainer. The Reveal Polyvalent HRP-DAB Detection System was used for the visualization. The density of blood vessels stained with antibodies against VEGF and CD34 was determined. The statistical analysis of results was performed in the STATISTICA 10.0 program (StatSoftInc., USA). Results: The numbers of blood vessels ranged: CD34 in group 1 – 7-16 blood vessels in one field of view; in group 2 – 2-18 vessels. VEGF in group 1 – 2-20 vessels, with up to 40 vessels in 3 cases (11.5%) only; in group 2 – 5-11 vessels, with up to 20 vessels in 2 cases (7.7%). The average numbers of microcirculatory vessels stained with antibodies against VEGF and CD34 were: CD34 –12.2±1.04 and 8.4±1.4 (p = 0.0247) in groups 1 and 2, respectively; VEGF – 12.8±4.06 and 8.4±11.6 (p = 0.3074) in groups 1 and 2, respectively. Conclusions: The IHC analysis showed the minimal numbers of microcirculatory vessels in one field of view in patients with recurrent soft tissue sarcomas. The value was 1.5 times lower for both CD34 and VEGF, compared to patients with primary tumors. However, only CD34 value was statistically significant (the Mann–Whitney U-test). Probably, a certain decrease in angiogenesis factors in recurrent tumors can be explained by adjuvant chemotherapy suppressing tumor growth.
Breast imaging protocol options and the attention in clinical application
Authors: Jing Li
Journal: BMJ (2018)

乳腺癌是严重危害我国女性生命和健康的疾病，早期诊断、早期治疗是降低乳腺癌死亡率的关键。影像学检查在乳腺癌筛查、早期诊断、治疗前分期、疗效评估、监测复发等方面发挥着重要作用。乳腺影像检查方法很多，常用的方法包括乳腺X线摄影、超声和MRI。知晓各种影像检查方法的优缺点及临床适应证，合理利用综合影像检查方法，能够对乳腺病变进行精准的诊断和评估，指导临床制定规范化的治疗方案。
Incidence of second primary malignancy (SPM) in patients with mucosa-associated lymphoid tissue lymphoma (MALToma).
Authors: Nibash Budhathoki, Sunita Timilsina, Charles Thomas, Aaron Damato, Catherine S. Magid Diefenbach, Marc Justin Braunstein
Journal: Journal of Clinical Oncology (2020)

e20043 Background: MALTomas are extranodal marginal zone lymphomas that arise from B cells in various mucosal lymphoid tissue and are typically indolent. Patients with MALTomas may be at risk for additional cancers due to their long-term survival following treatment, however the incidence of SPM in MALTomas in the U.S. has not been previously described. Methods: Adults with MALT lymphoma were identified using the 2000-2016 SEER-18 database. SPM was defined as tumors diagnosed ≥6 months and up to x months from lymphoma diagnosis. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected cases of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As summarized in the table, 12,500 patients were diagnosed with MALT lymphoma of which 1466 (11.8%) developed 1626 SPMs (O/E rate 1.5, 95%CI 1.4-1.5, P &lt; 0.001, EAR 70.4). Median latency period was 54 months (range 6 - 201). Non-Hodgkin lymphomas at separate tissue sites were the most common SPM, with 299 documented cases (O/E rate 6.2, 95%CI -5.4-6.8, P &lt; 0.001, EAR 33.4). Between 6-24 months from MALToma diagnosis, head and neck, renal cell, liver, and anal cancers were increased, while after 24 months, gastric and small bowel cancers, CLL, ALL, and myeloma were increased compared to the general population of the same age group. Conclusions: There is distinct pattern of SPM among patients with MALT lymphoma in within and after 2 years from diagnosis, with an increased incidence compared to the general population. Consider the median latency, SPM may be due in part to the long-term survival and relatively older age of this population. [Table: see text]
Response to immune checkpoint inhibitor (ICI) rechallenge after high-grade immune related adverse events (irAE) in patients (pts) with metastatic melanoma (MM).
Authors: Payal Shah, Patrick Boland, Anna C. Pavlick
Journal: Journal of Clinical Oncology (2020)

10045 Background: ICIs have transformed MM mortality. Pts receiving ICIs may experience high-grade irAEs that limit continuation of treatment per current guidelines. We aimed to evaluate the safety and response rate of ICI rechallenge. Methods: 551 MM pts treated with ICI were retrospectively reviewed from Jan 2014 to Jan 2020 after IRB approval. The incidence of a recurrent irAE in pts with ICI rechallenge within the same drug class after an initial high-grade (Grade III/IV) irAE was evaluated. Age, gender, irAEs, and outcomes were descriptively analyzed within the rechallenged cohort. Results: 32.7% of pts (180/551) experienced a high-grade irAE. 60.0% of these (108/180) pts were on combination therapy with at least one ICI. 50.6% (91/180) of pts were rechallenged with ICI within the same drug class. The rechallenged cohort had a median age of 63.8 [range: 28-86] years and 48.4% was female. The cohort’s initial irAE occurred at a median of 7.6 weeks from treatment onset with Grade 3/4 severity of 60.0% /40.0% (91). Toxicities included colitis 27.5% (25/91), hepatitis 23.1% (21/91), skin toxicity 22.0% (20/91), adrenal insufficiency 5.5% (5/91) hypophysitis 5.5% (5/91), neurological abnormality 4.4% (4/91), pancreatitis 3.3% (3/91), hematological abnormality 3.3% (3/91), arthralgia 3.3% (3/91), myalgia 3.3% (3/91), pneumonitis 2.2% (2/91), insulin dependent diabetes 1.1% (1/91), fatigue 1.1% (1/91), vasculitis 1.1% (1/91), and hyponatremia 1.1% (1/91). ICI rechallenge occurred at a median of 9.7 weeks from the first Grade 3/4 irAE. 51.8% (29/56) pts initially treated with combo were rechallenged with combo, while 48.2% (27/56) were rechallenged with single agent ICI. Of pts initially treated with single ICI, 60% (21/35) were rechallenged with single agent ICI and 40% (14/35) with combo. With a median follow-up of 21.1 months after rechallenge, irAEs occurred in 75.8% (69/91), with 44.9% of irAEs (31/69) presenting as a different type from the initial event and 31.9% (22/69) as high-grade events. There were no rechallenge irAE-related deaths. Within the rechallenge cohort, 39.6% (36/91) of pts had disease progression. Clinical benefit was achieved in 60.4% (55/91) of pts: 40.7% (37/91) complete response, 11.0% (10/91) partial response and 8.8% (8/91) stable disease. Conclusions: ICI rechallenge can be safely administered in pts with MM after recovery from an initial high-grade irAE. Rechallenge irAE’s did not always reflect initial irAE’s. Close monitoring for any type or grade of IRAE is recommended.
Real-world disease burden for patients (pts) with myelofibrosis (MF) treated with ruxolitinib (RUX).
Authors: Aaron Thomas Gerds, Jonathan Kish, Kejal Parikh, Djibril Liassou, Talia Miller, Ronda Copher
Journal: Journal of Clinical Oncology (2020)

e19539 Background: MF is an aggressive myeloid neoplasm and until recently RUX was the only treatment available. Real-world, long-term outcomes in pts with MF have not been described. Methods: Providers from multiple community oncology clinics in the USA reviewed the charts of consecutive pts with MF (primary or post-polycythemia vera/essential thombocythemia MF) who received RUX at any time from Jan 1, 2015 to Dec 31, 2017; data were collected Nov 15–26, 2019. Pt characteristics, treatment patterns, and outcomes (symptoms, blood counts, disease transformation) were retrospectively abstracted into an electronic case report form (eCRF) at each visit during the first 6 months, at any RUX dose modification; and at 12, 24, and 36 months post-RUX initiation. Pt characteristics, treatment patterns, rationale for dose modification, and treatment duration are described for pts during the first 6 months of therapy. Results: eCRFs were completed for 104 pts with MF treated with RUX. 42 pts received a RUX dose modification and 62 did not. Median follow-up from RUX initiation was 23.5 months. In the first 6 months of therapy, 40.4% of pts had a RUX dose modification (76.2% dose reduced; 23.8% dose increased). The most common reason (70%) for dose increase was titration to therapeutic dose. The most common reason (75%) for dose reduction was hemoglobin 8–10 g/dL or platelet count 50–75 × 10 9 . The starting dose of RUX was higher for no RUX dose modification pts (mean total daily dose 34.9 mg vs 27.0 mg, P &lt; 0.01). RUX dose-modified pts were older vs pts with no RUX dose modification ( P = 0.01); International Prognostic Scoring System (IPSS) risk score ( P = 0.89) and the proportion of pts with primary MF ( P = 0.06) were similar (Table). Overall, 64.4% of RUX treated pts discontinued therapy (RUX dose-modified 78.6%; no RUX dose modification 54.8%, P = 0.01). Median duration of RUX treatment was 11.0 months (RUX dose modified 10.6 months; no RUX dose modification 12.2 months; log rank P = 0.12). Conclusions: In this real-world study, 64.4% of pts discontinued RUX during follow-up. Higher rates of discontinuation and shorter time to discontinuation were noted for pts with a dose modification during the first 6 months of therapy. Given the short duration of therapy observed in this study as compared with published clinical trials, additional MF treatments are needed that offer pt benefit. [Table: see text]
颈部刀刺伤并大出血的院前急救与外科救治
Authors: 陈伦牮, 热沙来提, 戈小虎
Journal: BMJ (2006)

颈部刀刺伤引起大出血常较严重,多有休克或呼吸道受压并危及生命,我院从1999年至2004年,收治10例颈部刀刺伤大出血患者.现报告如下. 1.临床资料:10例中,男性9例、女性1例,受伤至入院时间5 min～2 h,临床特征见表1.其中7例颈总动脉损伤,颈部出血呈喷射状,均在来我院就诊前的处理中在锁骨上方将颈总动脉直接压向颈椎横突上而减少出血;8例于院前均建立通畅快速的输液通道,补充血容量;合并气管、食管裂伤的患者保持呼吸道通畅,行气管插管或气管切开。
Immediate post-thermal ablation biopsy of colorectal liver metastases to predict oncologic outcomes.
Authors: Nikiforos Vasiniotis Kamarinos, Efsevia Vakiani, Mithat Gonen, Nancy E. Kemeny, Anne M. Covey, Karen T. Brown, Lynn A Brody, Amy R Deipolyi, Juan Camacho, F. Edward Boas, Hooman Yarmohammadi, Joseph Erinjeri, Elena N Petre, T. Peter Kingham, Michael Ian D'Angelica, Leonard B. Saltz, Stephen Barnett Solomon, Constantinos T. Sofocleous
Journal: Journal of Clinical Oncology (2020)

4602 Background: Thermal ablation (TA) is used as a local cure for selected colorectal liver metastases (CLM) with minimal risk. A critical limitation of TA has been early local tumor progression (LTP). The goal of this study is to establish the role of ablation zone (AZ) biopsy in predicting LTP. Methods: This institutional review board-approved prospective study included patients with CLM of 5cm or less in maximum diameter, with confined liver disease or stable, limited extrahepatic disease. Both radiofrequency(RF) and microwave(MW) ablation modalities were used. A biopsy of the center and margin of the AZ was performed immediately after ablation. The applicators were also examined for the presence of viable tumor cells. All samples containing morphologically identified tumor cells were further interrogated with immunohistochemistry to determine the proliferative and viability potential of the detected tumor cells. Ablation margin size was evaluated on the first CT scan performed 4–8 weeks after ablation and was confirmed by 3D assessment with Ablation Confirmation Software (Neuwave™). Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results: Between November 2009 and February 2019, 102 patients with 182 CLMs were enrolled. Mean tumor size was 2.0 cm (range, 0.6–4.8 cm). MW was used in 95/182 (52%) tumors and RF in 87/182 (48%). Median follow-up was 19 months. Technical effectiveness was evident in 178/182 (97%) ablated tumors on the first contrast material–enhanced CT at 4–8-weeks post-ablation. The cumulative incidence of LTP at 12 months was 19% (95% confidence interval [CI]: 14, 27). Samples from 64 (35%) of the 178 technically successful cases contained viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. In a multivariate model, margin size of less than 5 mm (P &lt; .001; hazard ratio [HR], 4.3), and positive biopsy results (P = .02; HR, 1.8) remained significant. LTP within 12 months after TA was noted in 3% (95% CI: 1, 6) of tumor-negative biopsy CLMs with margins of at least 5 mm. Conclusions: Biopsy and pathologic examination of the AZ predicts LTP regardless of TA modality used. This can optimize ablation as a potential local cure for patients with limited CLM.