tbuckley/cabot-search huggingface dataset:
Nanoliposomal irinotecan and metronomic temozolomide for patients with recurrent glioblastoma: BrUOG329, a phase IB/IIA Brown University Oncology Research Group (BrUOG) trial.
Authors: Heinrich Elinzano, Jessica B. McMahon, Alex B. Mohler, Jordan B. Robison, Arieana B. Carcieri, Steven A Toms, Deus B. Cielo, Wendy B. Turchetti, John Vatkevich, Roxanne Wood, Amy Webber, Howard Safran
Journal: Journal of Clinical Oncology (2020)

e14548 Background: Nanoliposomal irinotecan (nal-IRI)) is a novel formulation of irinotecan, encapsulating drug molecules within long-circulating liposome-based nanoparticles with resulting favorable pharmacokinetic and biodistribution properties. Nanoliposomes improve the solubility and bioavailability of drugs and potentially increase their ability to cross the blood brain barrier. We performed a phase I study to determine the maximum tolerated dose (MTD) and preliminary efficacy of nal-IRI in combination with metronomic temozolomide (TMZ) in patients with recurrent glioblastoma. Methods: Patients with recurrent glioblastoma who had progressed after at least 1 line of therapy with a KPS of &gt; 60 were eligible. All patients received TMZ 50 mg/m 2 PO daily with nal-IRI IV every 2 weeks until disease progression. Three dose levels of nal-IRI were planned, 50 mg/m 2 , 70 mg/m 2 and 80 mg/m 2 . Dose limiting toxicities (DLTs) were defined as those occurring during the first 2 cycles (28 days) of treatment. Patients were accrued in a 3+3 design. Accrual at the MTD level was to be expanded to 25 patients, unless the study was terminated early if 0-1 responses were observed in the first 13 evaluable patients. Results: Twelve patients were treated over 2 dose levels (nal-IRI 50-70 mg/m 2 ). At dose level 2, nal-IRI 70mg/m 2 , 2 of 3 patients developed DLTs, including one patient who developed grade 4 neutropenia, grade 2 diarrhea and grade 3 anorexia and one patient with grade 3 diarrhea, grade 3 hypokalemia and grade 3 anorexia. Accrual at nal-IRI 50 mg/m 2 , defined as the MTD, was expanded to 9 patients. Treatment-related toxicities at this dose level included grade 3 ALT (N = 1). As there were no responses seen in the initial 12 patients (0/12, 0%), the BrUOG Data Safety Monitoring Board terminated the study. Conclusions: The MTD of nal-IRI was 50 mg/m 2 every 2 weeks with TMZ 50mg/m 2 /day. DLTs were grade 3 diarrhea and anorexia. No antitumor activity was seen in the first 12 patients and the study was terminated. Clinical trial information: NCT03119064.
A closer look at Hispanics with follicular lymphoma in a majority-minority community.
Authors: Michelle Janania Martinez, Tyler William Snedden, Juan Garza, Prathibha Surapaneni, Snegha Ananth, Jeremy Rawlings, Dave Gregorio, Sushanth Kakarla, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque
Journal: Journal of Clinical Oncology (2020)

e20047 Background: Follicular Lymphoma (FL) is the most common type of indolent non-Hodgkin lymphoma. It is most commonly diagnosed in non-Hispanics (NH) and is well characterized in this population. Hispanics (HI) on the other hand have been historically underrepresented in clinical trials and observational studies. Some studies suggest that there are differences in age, clinical presentation, treatment patterns and outcomes in HI. The aim of our study was to determine demographics and clinical characteristics of FL patients and compare outcomes between HI and NH. To our knowledge, this is the largest cohort of FL patients from a single academic institution that serves predominantly HI. Methods: We retrospectively analyzed 123 patients with FL; all received care between 2008-2018. Key variables included age, gender, race/ ethnicity, comorbidities, insurance status, stage, treatment received, outcome at 3 and 5 years and vitality status in 2018. Continuously distributed outcomes were summarized with mean/standard deviation and categorical outcomes with frequencies/percentages. Significance of associations between categorical outcomes was assessed with Pearson’s Chi Square or Fisher’s Exact test. All statistical testing was two-sided with a significance level of 5%. Results: We identified 123 patients with diagnosis of FL, 71 HI (58%), 49 NH (40%), 3 unspecified (2%); 88% Caucasian, 5% African American, 4% Asian, 3% other; 56% females and 44% males. Median age at diagnosis was 56.31 (SD 11.97). Funding source was commercial insurance N = 55 (45%), Medicare N = 40(33%), hospital payment plan N = 20 (16%), unfunded N = 5 (4%) and Medicaid N = 3 (2%). Most prevalent co-morbidities were HTN 40% and diabetes mellitus 20%; 40% had no co-morbidities. At diagnosis ECOG of 0-1 was seen in 116 (94%); 21 were Stage I (17%), 19 Stage II (15%), 40 Stage III (33%), and 43 Stage IV (35%). FLIPI score was 0-1 in 43 patients (35%), 2 in 32 (26%), 3 in 23 (19%), not documented in 25 (20%). Median PFS was 1287.10 days (SD 879.18). At 3 year follow up there was: complete/ partial response in 76% HI vs 84% NH; disease progression in 18% vs 3%; death in 6% vs 3%, respectively (p-value = 0.739). At 5 year follow up: complete/partial response in 76% HI vs 86% NH; disease progression in 14% vs 10%; death 10% vs 3%, respectively (p-value = 0.62). At the end of 2018, 88% HI were alive compared to 95% NH, [p-value = 0.457]. Conclusions: Contrary to existing data, our study found that HI with FL have no difference in outcome when compared to NH. This could be explained by our prevalently HI population, but further studies are needed.
Clinical and molecular characteristics of the patients in the liquid biopsy study in mEGFR-NSCLC in a Spanish population (OPH-1).
Authors: Fernando Franco, Roberto Serna, Alfredo Sanchez, Carlos García Girón, Manuel Domine, Carlos Camps, Jose Miguel Sanchez Torres, Juana Maria Oramas Rodriguez, Luis Enrique Chara Velarde, Ana Laura Ortega, Maria Angeles Sala, Berta Hernandez, Maria Sereno, Joaquim Bosch-Barrera, Airam Padilla, Jose Balsalobre Yago, Remei Blanco, Xabier Mielgo, Atocha Romero, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2020)

e21515 Background: The liquid biopsy (LB) is an important tool in the diagnostic and follow up of the patients with non-small cell lung cancer (NSCLC) and can provide big information about the mutational variability of the disease during of the treatment. Methods: We conducted a multicenter study with 200 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyse the ctDNA by dPCR pre-treatment, at 8 weeks, at 7 months and at the progression of the disease (PD). Results: A total of 200 patients (60% women / 40% men) were included. The median of age was 68-year. The never smokers were 56% and 34% ex-smokers. 92% of the cases were adenocarcinomas. According to the stage of the disease, 52% were stage IVB, 38.5% stage IVA and 9.5% unknown. The first-line treatment was afatinib in 47.5%, erlotinib in 21.5% and gefitinib in 31%. According to the type of sensitivity mutation, 61.5% corresponded to Del19, 32% to L858R, 2.5% to G719X and 2.5% to L861Q. At the time of diagnosis, 63% had pulmonary metastatic involvement and 42.5% liver metastasis. At the time of data analysis, 66% of the patients had some progression of the disease (PD) and 37% died. 68% of the patients with Del19 received afatinib, while 20% of the patients with L858R received afatinib, 54.5% erlotinib and 32% gefitinib (p = 0.02). With a median follow-up of 20 months, progression-free survival was 11.8 months, without any differences according to the treatment (p = 0.93). The groups with worse PFS included: the squamous histology (HR 5.7; 95%CI 2.04-15.91, p = 0.001), the G719X mutation (HR 3.36; 95%CI 1.21-9.25, p = 0.019) and the liver metastasis (HR 1.65; 95%CI 1.01-2.68, p = 0.042). The sensitizing mutation was detected in the 80.8% of the patients in the LB by dPCR and the T790M in 2%. However, in the first control only was detectable in 18.5%. At the time of PD, the percentage of detection of T790M raised to 52.3%, and the sensitizing mutation 79.44%. At that moment, patients who developed T790M were mostly never smokers (66%, p = 0.006) and had Del19 (66%). Patients with bone progression developed T790M in 60.4% (p = 0.014) and hepatic 27% (p = 0.012). Conclusions: We concluded that the clinical characteristics of the patients of the OPH study are consistent with the previous reported in the Caucasian population and the subgroups with the worst prognosis include the squamous histology, the G719X mutation and the liver metastasis.
End-of-life characteristics associated with short hospice length of service for patients with solid tumors enrolled on phase I clinical trials.
Authors: Ramy Sedhom, Alison Turnbull, Amanda L. Blackford, Arjun Gupta, Janet Heussner, Kelly Griffiths, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2020)

e24005 Background: Patients participating in phase I trials represent a population with advanced cancer and symptoms, with QOL implications from both disease and treatment. Transitions to end of life for these patients has received little attention. Good empirical data is needed to better understand the role of advanced care planning (ACP) and palliative care (PC) during phase I trial transitions. We investigated how physician-patient communication at time of progression, patient characteristics, and patterns of care were associated with EOL care. Methods: Retrospective chart review of all patients with solid tumors enrolled in phase I trials at a comprehensive cancer center from Jan 2015 to Dec 2017. We captured physician-patient communication during disease progression, and for all patient deaths, assessed PC referral, ACP, place of death, health care utilization in the final month of life, hospice enrollment and LOS. Factors independently associated with a short hospice LOS (defined as ≤3 days) were estimated from a multivariable model building approach. Results: Among 207 participants, median age was 61 (range 31-91), 48% were female and 20% were ethnic minorities. Predominant diagnoses were GI (40%), GU (14%), and lung cancer (15%). 40% of patients were referred from an outside institution. At the time of disease progression, 64% had goals of care documented, 57% were referred to PC, and 54% discussed hospice with their oncologist. Overall, 82% of patients died within 1 year of study enrollment. Of all patients who died, 85% enrolled in hospice and 76% died at home. In the last 30 days of life, 37% were hospitalized, 21% received chemotherapy, and 8% were admitted to the ICU. 15% had a short hospice LOS. The multivariable model revealed that increased age &gt; 65 was positively associated with short hospice length of service (odds ratio (OR) 1.12 [95% CI 1.01, 1.24], p = 0.03), while remaining at the same institution (OR 0.72 [95% CI 0.65, 0.8], p &lt; 0.001), and referral to PC before progression (OR 0.83 [95% CI 0.75, 0.92], p &lt; 0.001) were associated with a decreased risk of short hospice LOS. Conclusions: This data supports the benefit of PC for patients on phase I trials and the danger of transitions for all patients, with particular attention needed for older adults, regardless of care received. Leaving a clinical trial is a time when clear communication is paramount. Phase 1 studies will continue to be vital in advancing cancer treatment. It is equally important to advance the support provided to patients who transition off these trials.
Functional outcomes of older adults treated with radical cystectomy for muscle-invasive bladder cancer.
Authors: Chelsea K. Osterman, Allison Mary Deal, Kirsten A. Nyrop, Matthew I. Milowsky, Hyman B. Muss, Angela Smith
Journal: Journal of Clinical Oncology (2020)

e17010 Background: Older patients with muscle-invasive bladder cancer (MIBC) may not be offered standard of care treatment with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) based on their chronological age and concern for functional decline following therapy. Age-based differences in post-RC functional status or time to recovery are unknown. Methods: A total of 80 patients were included in this study. Patients ≥ 70 years were categorized as “older” and &lt; 70 years as “younger.” To measure functional status, patients completed an initial geriatric assessment (GA) post-NAC and pre-RC, which was repeated at 1, 3, and 12 months post-RC. Results: Median age was 62 years for younger patients (41-69 years; n = 42) and 75 years for older patients (70-83 years; n = 38). Clinical stage at presentation was not different between groups, but older patients were significantly less likely to receive NAC (63% vs 83%, p = 0.047). There was no significant difference between groups in any physical function measure at baseline. At 1 month post-RC, older patients had significantly lower clinician (c) and patient (p) rated Karnofsky Performance Status (KPS) than younger patients (cKPS: 70 vs 80, p = 0.02; pKPS 60 vs 80, p = 0.03), with a significantly greater decrease from baseline (20 points vs 0 points) in both KPS scores compared to younger patients (cKPS p = 0.001; pKPS p = 0.005). Both groups had a significant decline in ability to complete instrumental activities of daily living (IADLs), but older patients also had significantly increased social activity limitations. At 3 months post-RC, older patients took significantly longer to complete the timed up and go test than younger patients (10.2 secs vs 9 secs, p = 0.02), but had no other differences in physical function measures. Older patients had no significant difference in any measure at 3 months post-RC compared to baseline, while younger patients had a significant improvement in social activity over this time frame. Conclusions: Older patients with MIBC experience a greater short-term decline in functional status post-RC compared to younger patients. However, they return to their baseline status within the same time frame as younger patients.
Efficacy of single-agent epidermal growth factor receptor inhibition in the second-line setting for metastatic colorectal cancer with a goal towards retreatment strategies.
Authors: Jeremy D. Kratz, Noelle K. LoConte, Sam Joseph Lubner, Daniel Mulkerin, Nataliya Volodymyrivna Uboha, Dustin A. Deming
Journal: Journal of Clinical Oncology (2020)

e16035 Background: Advances in the understanding of colorectal cancer (CRC) biology, including clonal evolution are leading to novel treatment strategies. Epidermal growth factor receptor inhibition (EGFRi) with cetuximab or panitumumab has shown significant clinical utility in KRAS/NRAS/BRAF wildtype (wt) CRC. These inhibitors are most commonly used in the third-line treatment setting in the United States. Upon the development of resistance to EGFRi, withdrawal of the EGFR inhibitor can lead to decay of resistant clones allowing for EGFR inhibitor retreatment in additional lines of treatment. Earlier-line use of single agent EGFRi could allow more patients to utilize a retreatment strategy, however no large prospective clinical trials have assessed the clinical activity of second line EGFRi in the setting of molecular selection. Here, we assess the clinical outcomes of EGFRi monotherapy for advanced KRAS wt CRC after initial progression on a single line 5FU based chemotherapy. Methods: A retrospective chart review examined patients who received single agent EGFRi in KRAS wt CRC in the second line setting. Line of therapy was defined at time of metastatic disease or recurrence within 6 months of adjuvant therapy. Clinical outcomes of overall response rate (ORR) and progression free survival (PFS) were assessed per RECIST v1.1. Results: 20 cases were identified who received single agent EGFRi (panitumumab or cetuximab) as monotherapy in the second line setting. All pts received prior 5FU based chemotherapy. Reasons for using EGFR inhibitor monotherapy in this setting included to avoid toxicities from prior chemotherapy (largely immunosuppression and GI toxicities), bridge from recent operative management, or maintain functional performance status. Patients had median age of 62 [45, 89] and majority with ECOG PS 0-1 (78.5% of those reported). Best responses included complete response 7%, partial response 21%, stable disease 64% and progressive disease 7%, and a disease control rate of 93%. The 6 and 8 month PFS were 70% and 50%, respectively. PFS ranged from 1.5 to 17.3 months with median PFS 8.2 ± 3.6 months. Conclusions: This work demonstrates preliminary efficacy data to use single agent EGFRi in the second-line setting for KRASwt patients with CRC. Future investigations will aim to prospectively validate the benefit of this treatment strategy to facilitate EGFRi retreatment and improve patient survival.
Comparison of laparoscopic transumbilical single-port appendectomy with conventional instrumentation versus three-port appendectomy
Authors: Hui-min Xu, Zuo-cheng Sun, Wen-sheng Yu, Ying Na, Dong-mei Xu, Jia-you Xu
Journal: BMJ (2013)

Between May 2009 and February 2012, 60 patients scheduled for laparoscopic appendectomy were randomly assigned to receive either transumbilical single-port laparoscopic appendectomy (TUSPLA) or three-port laparoscopic appendectomy (TPLA). The operative duration was significantly longer in TUSPLA than TPLA cases. No statistically significant differences existed in hospital stay, visual analog scale (VAS) score, analgesia requirement or complication rate. The abdominal scar was inconspicuous for TUSPLA. It suggested that TUSPLA with conventional instrumentation is technically feasible and safe with scarless healing.


Key words: 
Laparoscopic appendectomy; Transumbilical laparoendoscopic single site surgery
The actionable genomic mutational landscape in solid tumours.
Authors: Marco Loddo, Keeda-Marie Hardisty, Robert Paul Thatcher, Tiffany Eira Haddow, Gareth Haydn Williams
Journal: Journal of Clinical Oncology (2020)

e13642 Background: The recent exponential increase in targeted agents and immunotherapies provide new therapeutic opportunities for patients with advanced cancers who have failed first line therapy. However, lack of comprehensive precision oncology testing as part of routine pathology assessment means potential therapeutic opportunities are difficult to identify or remain undiscovered for many patients. Methods: To address this unmet clinical need we established Oncofocus, a clinically validated, ISO15189/2012 and CLIA accredited, precision oncology test optimized for analysis of small diagnostic PWET clinical biopsy samples (sample acceptance 94%). Oncofocus detects actionable genetic variants in 505 genes linked to 764 anti-cancer targeted therapy protocols, either on-market FDA and EMA approved, carrying ESMO and NCCN guideline references or currently in clinical trials. Oncofocus trending data was analyzed for a real-life cohort of 1111 patients with the aim of determining the frequency of actionable mutations in this population. This cohort represent patients with advanced stage disease who underwent Oncofocus testing having failed first line treatment protocols. Results: Analysis of trending data revealed a complex mutational landscape in which 90% of solid tumors harbored actionable mutations. The majority of patients harbored one or more actionable mutations (median 2, range 0-13) affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signaling pathways, DNA-damage repair pathways and cell cycle checkpoints. Actionable genetic variants across 33 DNA Damage and Repair (DDR) genes were identified in 30% of tumors. Using a defined predictive cut point of &gt; 10% for tumor proportion score, PD-L1 expression levels were significantly raised in 19% of cases. Abrogation of DDR function and elevated PD-L1 levels were identified in 5% of patients, a subpopulation potentially more responsive to immunotherapy. Notably, many of the actionable mutations identified did not show linkage with histological type or site of origin. Conclusions: Our data indicates that comprehensive precision oncology testing should be strongly considered as part of the diagnostic work up for all patients with advanced cancers, independent of tumor type, thereby ensuring capture of all targeted therapy opportunities and accelerating “site agnostic” molecular basket clinical trials. Comprehensive precision oncology testing was performed successfully on routine biopsy samples circumventing the requirement for fresh tissue or large sample specimens.
Temporary internal iliac artery balloon occlusion in cesarean section for patients with pernicious placenta previa
Authors: Fuzhong Liu, Jinxia Xu, Yu Liu
Journal: BMJ (2017)

Clinical data of 12 patients with pernicious placenta previa admitted in our hospital from October 2015 to July 2016 were retrospectively reviewed. Bilateral internal ilia artery balloons were placed percutaneously before cesarean section. After cesarean delivery normal saline was applied to fill the balloon for temporary occlusion of bilateral iliac arteries, then placental separation and hysterorrhaphy were performed. The average volume of bleeding during cesarean section was 1 146 ml. There were no hysterectomy, pelvic organ necrosis, lower limb artery thromosis and other complications. The application of temporary internal iliac artery balloon occlusion can significantly reduce the intraoperative bleeding in cesarean section for patients with pernicious placenta previa. It provides a clear operational field for obstetricians to perform the placental separation and hysterorrhaphy, facilitating the uterine reservation.


Key words: 
Placenta previa; Ultrasonography, interventional; Balloon occlusion; Iliac artery
Impact of embedded palliative care providers compared to externally available palliative care services on the number of patients receiving palliative care referrals in a large community oncology practice.
Authors: Garrett Young, Aaron J. Lyss, Johnetta Blakely, Leah Owens, Natalie R. Dickson, Stephen Matthew Schleicher
Journal: Journal of Clinical Oncology (2020)

12103 Background: Palliative care improves quality of life and may increase overall survival in patients with solid tumor malignancies. Despite having the ability to refer patients to in-home and external palliative care services, we observed low palliative care referral rates in our practice of 90 oncologists across 30 clinics. We tested whether embedding palliative care providers directly in clinic would improve palliative care referral rates for solid tumor patients. Methods: Between 2017 and 2020, we embedded an independent palliative care provider into five clinics across middle Tennessee. Access to external palliative care services was present both before and after the intervention. Using data from our EHR and billing systems, we performed a pre-post analysis measuring palliative care referrals in the six-month periods immediately before (pre-intervention period) and after (post-intervention period) a palliative care provider was embedded in each clinic. Statistical significance was assessed using Welch’s two sample t-test. Results: 8,636 unique solid tumor patients were seen in the five clinics during the study periods (Table). Despite having the ability to refer patients to external palliative care services in the pre-intervention period, the placement of a palliative care provider into clinic increased the number of solid tumor patients that received a palliative care referral per month at all clinics (min.: 200%; max.: 990%; median: 600%). Four of the five increases were statistically significant (p-values &lt; 0.05). Conclusions: Even when external palliative care services are available, embedding palliative care providers into community oncology clinics significantly increases the rate of palliative care referrals for solid tumor patients. [Table: see text]
彩色多普勒超声诊断完全性胎盘植入三例
Authors: 石华, 陈文卫, 周青, 朱敏怡, 郭瑞强
Journal: BMJ (2004)

胎盘植入(placenta accreta)是产科少见的严重并发症,发生在妊娠中期罕见,可引起致命性产后大出血,甚至绒毛穿破子宫浆膜引起腹腔内出血.回顾性分析我院1999年12月～2002年7月处理的3例胎盘完全植入者彩色多普勒超声的特征。