tbuckley/cabot-search huggingface dataset:
Percutaneous microwave ablation under ultrasound guidance for renal cell carcinomas at clinical staging T1: A comparative study of clinical results for patients aged between less than 65 years and 65 years and older.
Authors: Zhigang Cheng, Xiao-ling Yu, Zhiyu Han, Fang-yi Liu, Jie Yu, Ping Liang
Journal: Journal of Clinical Oncology (2018)

e16574 Background: Renal cell carcinoma (RCC) is the second most common malignant tumor of the urinary system in China. With the extension of the life expectancy of the population, the incidence of kidney cancers have shown gradually increasing trends and been commonly detected in patients aged 65 years and older with the mortality rate of 67.7%, most of whom suffered poor renal functional preservation or multiple comorbidities. Compared to partial nephrectomy (PN), microwave ablation (MWA) has been considered as one of the best indications for selected clinical T1 (cT1) RCC in elder patients. The purpose of the study was to evaluate the clinical results of patients aged 65 years and older with cT1 RCCs treated by percutaneous microwave ablation under ultrasound (US) guidance, compared to those less than 65. Methods: From September 2009 to December 2016, clinical data of MWA treatment for RCCs in two groups with the similar mean diameters in baseline, Group O (65 years and older) including 75 patients with 76 RCCs and Group Y (less than 65 years) including 91 ones with 99 RCCs, were retrospectively assessed. The technical efficacy, cumulative overall survival (OS) and disease-free survival (DFS), local tumor progression (LTP), major and minor complications, and renal function including serum creatinine (Cr) and blood urea nitrogen (BUN) between the two groups were statistically evaluated by SPSS. Results: After ablation, there were no statistical significances between the two groups at technical efficacy, LTP, major and minor complications. The cumulative OS and DFS rates at 1, 3, 5 years in Group O vs. Group Y were 100%, 92.6%, 92.6% vs. 100%, 96.9%, 90.9% (p = 0.701) and 100%, 92.5%, 92.5% vs. 98.6%, 98.6%, 90.4% (p = 0.697), respectively. There were no significant differences both serum Cr and BUN between the two groups before MWA and at the last follow-up. Conclusions: Compared to those less than 65 years, US-guided percutaneous MWA for cT1 RCCs could achieve coincident clinical results in patients 65 years and older, and then can be recommended one of optimal alternative treatment for selected older patients.
Biological role of TUSC3 in non-small-cell lung cancer.
Authors: Jianxue Zhai, Siyang Feng, Di Lu, Kaican Cai
Journal: Journal of Clinical Oncology (2018)

e24213 Background: The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. But our previous research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. The main purpose of our research is to investigate the role of TUSC3 in NSCLC cells and identify the molecules and signaling pathways with which TUSC3 might interact. Methods: Immunohistochemistry and western blot analysis were performed to investigate the expression level of TUSC3 in NSCLC. Lentiviral vectors carrying TUSC3 shRNA or TUSC3 plasmid were used to manipulate the expression of TUSC3. We analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of NSCLC cell lines by CCK8、wound healing assay、Transwell assay、colony formation assay and mouse xenograft experiments. Immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays were performed to identify the molecules and signaling pathways with which TUSC3 might interact. Results: We identified high expression levels of TUSC3 in human NSCLC, particularly in those patients with lymph node metastases or advanced tumor stage. Besides, we demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. Conclusions: Our research suggest that expression of TUSC3 is significantly associated with NSCLC progression and metastasis in human patients. We also demonstrate an oncogenic role for TUSC3 in NSCLC as a promoter of EMT. Besides, we identified claudin-1 as a novel target of TUSC3 in promoting cancer metastasis. These findings suggest that TUSC3 can be utilized as a potential diagnostic biomarker for NSCLC progression, and also reveals its potential as a therapeutic target.
Differential multiparameter ultrasound diagnostics of melanocytic skin lesions using shear wave elastography.
Authors: Natalia A. Maksimova, Oleg Ivanovich Kit, Viktoria V. Pozdnyakova, Maria I. Maksimova, Maria G. Ilchenko, Natalia A. Zakharova
Journal: Journal of Clinical Oncology (2018)

e21627 Background: The purpose of the study was to improve the accuracy of the differential diagnosis of melanocytic skin lesions. Ultrasound parameters of the density of benign and atypical nevi, superficial and nodal skin melanoma were studied by shear wave elastography. Methods: We studied the data of retrospective ultrasound scans of 80 patients with melanocytic skin lesions verified histologically (40 patients with benign lesions: typical nevi – 26, dysplastic nevi – 14; 40 patients with melanoma: superficial spreading melanoma – 12, nodular melanoma – 28). Inclusion criteria were identifiable melanocytic skin lesions in the range of 5-17 MHz. The Aixplorer MultiWave Ultrasound System with a broadband linear transducer was used for multiparametric ultrasound (B-mode, color Doppler, power Doppler, Doppler velocimetry, shear wave sonoelastography). Results: The skin thickness, shape, size, echogenicity, structure, vascularization of lesions and adjacent tissues, and invasive growth were assessed by sonography prior to surgery. The elasticity of lesions (El) and normal skin (En) was measured in kilopascals by shear wave elastography with the calculation of the relative elasticity coefficient Cl/n = El/En. Cl/n≤1.2 was considered as benign lesion, 1.44≤Cl/n < 1.85 - dysplastic nevus, 1.85≤Cl/n < 2.6 - superficial spreading melanoma, Cl/n≥2.6 - nodular melanoma. The 1.2 < Cl/n < 1.44 range was uninformative (“blind diagnostic area”). The overall diagnostic effectiveness of the method showed accuracy 90.6%, sensitivity 81.25%, specificity 93.75% (p < 0.01). Conclusions: The method of the differential diagnosis of melanocytic skin lesions is an informative method of noninvasive diagnosis of pigmented skin lesions and can be used in planning a treatment strategy.
Digital Medicine: An Opportunity to Revisit the Role of Bioethicists
Authors: Karin R. Jongsma, Annelien L. Bredenoord, Federica Lucivero
Journal: The American Journal of Bioethics (2018)

"Digital Medicine: An Opportunity to Revisit the Role of Bioethicists." The American Journal of Bioethics, 18(9), pp. 69–70
Evaluation of advanced lung cancer inflammation as potential prognostic markers in patients with colorectal cancer.
Authors: Julie Haewon Rowe, Fathima Kamil, Andre Yu, Curtis Jackson Wray, Putao Cen, Syed Hasan Raza Jafri
Journal: Journal of Clinical Oncology (2017)

e15142 Background: The Advanced Lung cancer Inflammation (ALI) prognostic index evaluates the degree of systemic inflammation in cancer patients and has been validated in small cell lung and esophageal cancer. The “sidedness” of the colon primary has prognostic implications with left sided tumors having longer survival rates than right sided. Our hypothesis is that right sided colorectal cancers (CRC) will have a lower ALI. Methods: We conducted a retrospective review of newly diagnosed CRC patients who were seen and evaluated at a tertiary Cancer Center from 1/1/2005 to 12/31/2015. ALI is calculated as ALI = BMI x (serum albumin/NLR). NLR is the neutrophil to lymphocyte ratio. Logistic regression models were used to determine the association between primary colon cancer location and ALI. Results: A total of 279 patients were included in this study. 53% of patients were male and mean age was 63.4 years (SD 13.7). 52% of cancers were located on the right side. Using an ordered logistic regression, ALI was predictive of higher stage disease (p = 0.04). In those patients with stage III (n = 64) or IV (n = 136) disease, the likelihood of a low ALI was significantly higher for right-sided colon cancers (OR 2.12, 95%CI:1.18-7.76). Conclusions: The Advanced Lung Cancer Inflammation index appears to be related to both CRC stage and primary cancer location. Ongoing studies are needed to determine the relationship between ALI and CRC survival.
Apatinib plus icotinib in treating advanced non-small-cell lung cancer after icotinib treatment failure.
Authors: Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi
Journal: Journal of Clinical Oncology (2017)

e20528 Background: Icotinib, a small-molecule EGFR TKI, has been approved as the first-line therapy for treating advanced non-small-cell lung cancer (NSCLC) in China. However, treatment failures frequently occurred in NSCLC patients with EGFR-sensitizing mutations. A phase II clinical trial has reported the beneficial survival of apatinib, a new small-molecular VEGFR TKI, in treating NSCLC (Zhang et al. 2012 ASCO, 7548). This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib as second- or third-line treatment in patients with advanced NSCLC. Methods: This study comprised 27 patients diagnosed with advanced NSCLC and treated with icotinib and apatinib as the second- or third-line therapy. Patients received oral icotinib (125 mg, tid), alone initially. When disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression or unacceptable toxic effects. Efficacy was evaluated based on RECIST version 1.0 and toxic effects were assessed using the NCI-CTC version 2.0. Results: Followed up to December, 2016, the median time of apatinib treatment was 7.47 months, and 8 of 27 patients were dead. The median overall survival had not reached and the median progression-free survival (PFS) was 5.33 months (95% CI 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1% and the disease control rate (DCR) was 81.5%. Fourteen patients received icotinib and apatinib as the second-line treatment, and the RR and DCR were 7.1% and 78.6%. The remaining 13 patients received drugs as the third-line treatment, with an ORR and a DCR of 15.4% and 84.6%. Additionally, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months (95% CI 4.17-8.57 months) and 16 patients experienced icotinib monotherapy failure after 6 months with median PFS of 2.60 months (95% CI 0.00-8.54 months). The common drug-related toxic effects included hypertension (44.4%), fatigue (37.0%) and hand-foot syndromes (18.5%). Conclusions: Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.
Oxaliplatin plus capecitabine (XELOX) in the perioperative treatment of locally advanced gastric adenocarcinoma in combination with D2 gastrectomy (NEO-CLASSIC).
Authors: Tianshu Liu, Yiyi Yu, Yong Fang, Zhenbin Shen, Min Yan, Hui Cao, Yingbin Liu, Xuefei Wang, Yuehong Cui, Yan Wang, Fenlin Liu, Weidong Chen, Wei Li, Yihong Sun
Journal: Journal of Clinical Oncology (2018)

4022 Background: This multicenter, open-label study (NEO-CLASSIC) evaluated the efficacy and safety of oxaliplatin and capecitabine (XELOX), plus gastrectomy, in localized resectable gastric cancer. Methods: Patients aged 18–75 years with histologically confirmed gastric adenocarcinoma (stage T2–3/N+M0, or T4aN+M0) were given eight cycles of XELOX (four preoperatively, four postoperatively). Each 3-week cycle comprised capecitabine 1000 mg/m2 twice daily on days 1–14, and oxaliplatin 130 mg/m2 as an intravenous infusion over 2 hours on day 1. Curative D2 gastrectomy was scheduled 2–4 weeks after the last preoperative cycle. Results: Fifty-five patients were enrolled, and one was excluded because of screening failure. R0 resections were achieved in 45 of 54 intent-to-treat patients (83.3%), and four patients received R1 resections. There were no complete responses, 27 (50.0%) partial responses, 24 cases (44.4%) of stable disease, and 3 (5.6%) of progressive disease. The objective response rate was 50.0%. Median follow-up was 31.9 (range 17.4–48.1) months: 29 patients (54.7%) had disease progression, and median progression-free survival was 18.13 (95% confidence interval: 4.70, 31.56) months; median overall survival was not reached. Fifty-four patients completed 209 cycles of preoperative chemotherapy; 42 patients received 133 cycles of postoperative chemotherapy. The rate of grade 3–4 adverse events was 8.5% (29/342 cycles): the most frequent events were neutropenia (9/342 cycles) and leukopenia (4/342 cycles). Conclusions: These findings suggest that combination therapy with capecitabine and oxaliplatin as neoadjuvant chemotherapy, followed by D2 gastrectomy, is effective in late-stage, locally advanced gastric cancer. Clinical trial information: NCT01880632.Clinical response in the intent-to-treat population (n = 54). Response evaluationa Number of patients % patients Objective response rate 27 50.0 Disease control rate 49 90.7 Complete response 0 0.0 Partial response 27 50.0 Stable disease 24 44.4 Progressive disease 3 5.6 aResponse Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
A phase I/II trial of combined BRAF and EGFR inhibition in patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal (mCRC): The EViCT (Erlotinib and Vemurafenib in Combination Trial) study.
Authors: Jayesh Desai, Ben Markman, Sumitra Ananda, Niall C. Tebbutt, Michael Michael, Benjamin J. Solomon, Grant A. McArthur, Jeanne Tie, Peter Gibbs, David Ritchie, Rachel Koldej, Alan Herschtal, Ruth Columbus, David M. Ashley, Joanne Lundy, Edmond Michael Kwan, Paul Michael Waring, Ben Tran
Journal: Journal of Clinical Oncology (2017)

3557 Background: Pts with BRAFm mCRC have an exceedingly poor prognosis. Unlike melanoma, BRAF inhibitor monotherapy has limited activity in BRAFm mCRC. Preclinically, BRAF inhibition results in rapid feedback activation of EGFR and ongoing tumor proliferation, which can be readily overcome by combining BRAF and EGFR inhibition. EViCT examined the safety and efficacy of combining two oral agents targeting BRAF with Vemurafenib (Vem) and EGFR with Erlotinib (Erl), in BRAFm mCRC pts. Herein, we report safety and preliminary efficacy data. Methods: EViCT had 2 parts: a Phase I dose escalation of Erl (cohort 1: 100mg qd; cohort 2: 150mg qd) together with Vem 960mg bd, to determine the maximum tolerated dose (MTD). The Phase II component involved dose expansion at MTD using a Simon 2-stage design to treat 9 pts in stage 1 and 15 pts in stage 2. Cycles were 28 days. Eligible pts had ECOG &lt; 1, &lt; 2 lines of systemic therapy for metastatic disease, and acceptable organ function. Staging CT scans were performed every 2 cycles, response assessed using RECIST 1.1. Primary endoint was clinical benefit rate (CR, PR and SD). A number of pharmacodynamics correlates were assessed including serial ctDNA, FDG-PET and optional tumour biopsies. Pts were treated until disease progression or toxicity requiring discontinuation. Results: Between Jul-2014 and Oct-2016, 30 BRAFm mCRC pts were enrolled. The Phase I Lead-in enrolled 4 pts in cohort 1 and 7 pts in cohort 2. There was 1 DLT (grade 3 hand-foot syndrome) in cohort 2. MTD/Recommended Phase 2 Dose was Erl 150mg qd and Vem 960mg bd, the full dose for each agent. The Phase II expansion enrolled 19 pts. Overall, 23 pts are evaluable for this interim analysis. Median age was 61 years, 11 (48%) pts were male. Most pts had 1(50%) or 2 (41%) lines of prior treatment. Overall response rate was 39% (95%CI = [20%, 61%]), including 5 (22%) confirmed PR, 4 (17%) unconfirmed PR, 3 (13%) stable disease and 11 (48%) progressive disease. Conclusions: Vem and Erl can both be given safely at their individual full doses when used in combination. In BRAFm mCRC, this combination resulted in clear clinical activity. Clinical trial information: ACTRN12614000486628.
Application of a 21-gene recurrence score assay in node negative, hormone receptor positive breast cancer in a military treatment facility.
Authors: WingYee Wan, James Aden, Sandra Terrazzino, Sarah Villarreal, Wilfred P. Delacruz
Journal: Journal of Clinical Oncology (2018)

e12567 Background: Oncotype DX is a breast cancer assay of 21 genes. Its results are used to calculate a Recurrence Score: low scores ( < 18) indicate low risk of recurrence, for which hormone therapy alone is adequate, while high scores ( > 30) require adjuvant chemotherapy. Available since 2004, the Recurrence Score has become incorporated into standard of care. This study aimed to characterize our unique population subset demographically, to describe this institution’s breast cancer tumors clinicopathologically, and to analyze the effect of the Recurrence Score on treatment and patient outcome. Methods: This retrospective cohort study used an Oncotype DX database, which spanned 2007-2017 and contained scores for 149 patients. 148 were included based on the presence of hormone-positive, node-negative breast cancer. Data regarding patient and tumor characteristics, resultant adjuvant therapy, and outcomes (rate of recurrence, mortality) were collected. Results: Out of 148 patients, 47% were low risk, 41% were intermediate risk, and 12% were high risk. There was no correlation between patient age or ethnicity and score severity, while higher scores were associated with larger tumor size (p = 0.025), higher histologic grades (p < 0.001), and increased rates of recurrence (p = 0.044). Patients who had tumors with receptor status other than estrogen receptor positive, progesterone receptor positive, and Her-2 negative were all high risk. Seven percent of low risk patients were offered chemotherapy, compared to 52% of intermediate risk and 100% of high risk patients. Overall 5-year progression free survival was 94.5% (low risk: 98.6%, intermediate risk: 93.3%, high risk: 88.2%, p = 0.724). Conclusions: This characterization of practice within our military health system showed that the Recurrence Score has guided use of chemotherapy in patients with node-negative, hormone positive breast cancer, with 7% of low risk patients being offered chemotherapy, compared to 52% of intermediate and 100% of high risk patients. The rate of chemotherapy offered to intermediate risk patients is slightly above that of published literature.
PROSPER: A phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN 8143).
Authors: Lauren Christine Harshman, Maneka Puligandla, Naomi B. Haas, Mohamad Allaf, Charles G. Drake, David F. McDermott, Sabina Signoretti, David Cella, Rajan T. Gupta, Brian M. Shuch, Toni K. Choueiri, Primo Lara, Anil Kapoor, Daniel Yick Chin Heng, Michael A.S. Jewett, Viraj A. Master, M. Dror Michaelson, Bradley C. Leibovich, Deb Maskens, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2019)

TPS4597 Background: The anti-PD-1 antibody nivo improves overall survival (OS) in metastatic RCC and is well tolerated. There is no standard adjuvant (adjuv) systemic therapy that increases OS over surgery alone for non-metastatic RCC. Priming the immune system prior to surgery with anti-PD-1 has shown an OS benefit compared to a pure adjuv approach in mouse solid tumor models. Multiple ph 2 studies in bladder, lung and breast cancers have shown remarkable pathologic responses with neoadjuvant (neoadj) PD-1 blockade. Two ongoing ph 2 studies of perioperative nivo in M0 RCC patients are showing preliminary feasibility and safety with no surgical delays (NCT02575222; NCT02595918). PROSPER RCC (NCT03055013) aims to improve clinical outcomes by priming the immune system prior to nephrectomy with neoadj nivo and continued engagement with adjuv blockade in patients with high risk RCC compared to surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is currently accruing patients with clinical stage ≥T2 or TanyN+ RCC of any histology planned for nephrectomy. Oligometastases are permitted if can be rendered NED. We amended the study to enhance accrual and patient quality of life by changing nivo dosing to 480mg q4 wks and requiring baseline tumor biopsy only in the nivo arm. The investigational arm receives 1 dose of nivo prior to surgery followed by 9 adjuv doses. The control arm undergoes standard nephrectomy followed by observation. Randomized patients are stratified by clinical T stage, node positivity, and M stage. Accrual of 805 patients provides 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival (RFS) at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is powered to evaluate a significant increase in OS (HR 0.67). Critical perioperative therapy considerations such as safety, feasibility, and quality of life endpoints have been integrated. PROSPER RCC embeds a wealth of translational work aimed at investigating the impact of the baseline immune milieu, the changes induced by neoadjuvant anti-PD-1 priming, and how both may predict clinical outcomes. Clinical trial information: NCT03055013.