tbuckley/cabot-search huggingface dataset:
Contemporary trends in treatment for low-risk prostate cancer.
Authors: Jason Frankel, Fernando Caumont, Ari Pervin, Christopher R. Porter, John Paul Flores
Journal: Journal of Clinical Oncology (2019)

5082 Background: Active surveillance (AS) is the preferred management of low risk (LR) prostate cancer (PCa) to decrease morbidity associated with overtreatment. We hypothesized management trends would show AS increasing and initial definitive treatment decreasing for men with LR PCa. This study describes contemporary trends in initial treatment for LR PCa using the National Cancer Database (NCDB), which includes ~50% of new PCa diagnoses in the United States per year. Methods: NCDB was queried for all patients with LR localized PCa (2010-2015), defined as non-metastatic PCa with PSA&lt;10 ng/mL, Gleason ≤6 and clinical T1-T2a primary tumor. Staging was assigned using 2018 American Joint Committee on Cancer guidelines. Patients refusing treatment, unable to be treated due to comorbidity or with unknown treatment status were excluded. Men were grouped based on NCDB codes for initial treatment including prostatectomy (PR), radiation (RT), AS and no treatment. Those receiving initial definitive treatment were compared to those who were not using logistic regression. Multivariable analysis was conducted for factors possibly correlating with management choice. Results: Of the 645,932 patients identified, 134,540 met inclusion criteria. Of these patients, 114,183 (84.9%) underwent PR or RT compared to 20,357 (15.1%) that did not. When examined over time, 92.4% of patients underwent initial PR or RT in 2010 vs. 73.9% in 2015 (p&lt;0.001). 90% of patients seen at community cancer centers underwent definitive initial treatment compared to 78% of those seen at academic centers (p&lt;0.001). Conclusions: In this national, hospital-based cohort overall rates of definitive initial treatment for LR PCa remain high, though seem to be decreasing over time. Overtreatment of LR PCa remains a concern and illustrates the relatively slow incorporation of guideline recommendations into clinical practice at the national level. [Table: see text]
Colorectal cancer lung metastasis: Could multidisciplinary management suggest the right strategy?
Authors: Ina Valeria Zurlo, Michele Basso, Maria Teresa Congedo, Maria Letizia Vita, Leonardo Petracca Ciavarella, Lisa Salvatore, Maria Alessandra Calegari, Carmelo Pozzo, Brunella Di Stefano, Maria Bensi, Raffaella Vivolo, Carlo Barone, Alessandra Cassano, Emilio Bria, Stefano Margaritora, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2019)

e15039 Background: Unlike liver metastases surgery, the resection of colorectal cancer lung metastasis (CCLM) is not standardized and data are still poor. Therefore, we conducted a retrospective analysis to evaluate the management of CCLM at our Centre. Methods: We retrospectively analyzed patients (pts) with CCLM treated at our Institution from Jan-2007 to Jan-2017. Aim of the study was to evaluate the impact of clinical and pathological features with survival outcomes (DFS and OS). Differences were compared with the use of log-rank test and parameters considered statistically significant ( p value &lt; 0.5) at univariate were compared at multivariate analysis. Results: 141 pts were included in the analysis. 87 pts received a preoperative chemotherapy (pCT) and 54 an adjuvant (a)CT. In the whole population median DFS (mDFS) was 24 m (20-24) and median OS (mOS) 54 m (46-82), while 21 m (20-34) and 65 m (45-108) for pts undergoing pCT and 15 m (20-28) and 53 m (38 – 76) for those receiving aCT respectively, without statistically significant differences (p=0.4). Age, gender, PS, disease-free interval (DFI) (&gt; or &lt;24 months), primary tumor sidedness, mucinous histology, grading, RAS status, timing of lung metastasis (metachronous vs synchronous), number of lesions (&gt;2), metastasis location (uni vs bilateral) and liver resection were evaluated at univariate and multivariate analysis. DFS was correlated with DFI &gt; 24m (p=0.02), timing (p=0.03), number (p&lt;0,0001) of metastasis and metastasis location (p=0.01) whereas OS was associated to DFI (p=0.02), number (p=0.0005), metastasis location (p=0.037) and RAS status (p=0.05) at univariate. At multivariate analysis, number of lesions correlated to DFS (p=0.0006) while DFI (p=0.0034) and RAS status (p=0.05) to OS. Conclusions: Our single Centre retrospective experience suggests an important clinical impact from surgery of CCLM based on mOS of the whole population. These data strengthen the role of a multidisciplinary management to allow pts to achieve surgery whenever possible, regardless of previous liver surgery, metachronous vs synchronous metastasis, DFI and RAS status.
Induction of antigen specific CD8+ T cell infiltration by a novel neoadjuvant vaccine containing HSP70 and GPC3 peptides plus soluble LAG-3 and Poly-IC:LC: Interim results of a Phase I study.
Authors: Yukio Tokumitsu, Shoichi Hazama, Shun Doi, Koji Tamada, Keiko Udaka, Shiro Akinaga, Yasunari Koki, Toshinari Uematsu, Yuki Nakagami, Hiroto Matsui, Yoshitaro Shindo, Shinsuke Kanekiyo, Shinobu Tomochika, Michihisa Iida, Shin Yoshida, Nobuaki Suzuki, Shigeru Takeda, Shigefumi Yoshino, Tomio Ueno, Hiroaki Nagano
Journal: Journal of Clinical Oncology (2019)

e14306 Background: Even with curative resection, the recurrence rate of HCC is still high, and no effective adjuvant therapy is currently available. Our previous Phase I study with novel therapeutic peptides and immune adjuvants demonstrated the safety, antigen specific CTL induction in PBMC and a sign of efficacy (ASCO 2017 Abstract # 3086); thus, we started Phase I study of the same therapy as a perioperative immunotherapy setting in patients with resectable HCC (UMIN000029991). Methods: Two mg each of HLA-A*24:02, 02:01, or 02:06 restricted HSP70- and GPC3-derived peptides, in combination with hLAG-3Ig (1.0 mg) + Poly-IC:LC (1.4 mg) were injected intradermally at four sites of the inguinal and axillary regions every week for 6 weeks before surgery. Patients subsequently received 10 injections of adjuvant immunotherapy over 4 months. Surgical specimens and PBMCs were analyzed by mass cytometry (CyTOF), using 66 antibodies to monitor T cell exhaustion, T cell activation, Effector Treg induction, etc. Tumor specimens were also subjected to immunohistochemical staining of CD3, CD8, PD1, HSP70, and GPC3. The reason for early reporting is the interesting findings at the foci of HCC, and the interim analyses was approved by the Data and Safety Monitoring Committee. Results: Of the 11 screened patients, 5 completed the treatments and were analyzed. We found massive CD8+ T lymphocyte infiltration in the intratumor foci of HCC, which is usually accompanied by peritumoral lymphocytic infiltration. Moreover, the density of lymphocytes was markedly higher in areas of HSP70 or GPC3 antigen expression. One case out of five recurred 5 month after surgery and it showed low CD8+ and PD1+ cell infiltration and high effector Treg (CD4+/CD25+/CD45RA-/FoxP3 +) infiltration. This trend was not observed in PBMC, suggesting the importance of TIL analysis. The high PD1 expression was accompanied by massive intratumoral infiltration of CD8+ lymphocytes. Conclusions: The novel therapeutic peptide and immune adjuvant combination induced sustained immune cell infiltration into tumor microenvironments, especially those presenting target tumor-associated antigens. Our novel immunotherapy may convert cold tumors into hot tumors containing PD1+ lymphocytes. Thus, the combination of this novel strategy with PD (L) 1 antibody is warranted. Clinical trial information: 000029991.
Association of PD-L1 protein expression and TMB in non-small cell lung cancer.
Authors: Yaru Chen, Yanqing Zhou, Yun Xu, Xiaoni Zhang, Mingyan Xu, Charles E. Melançon, Shifu Chen
Journal: Journal of Clinical Oncology (2019)

e20009 Background: Programmed death-ligand 1 (PD-L1) protein expression and tumor mutation burden (TMB) are considered to be two of the most promising biomarkers for predicting response to PD-1/PD-L1 blockade therapy. To evaluate the association of PD-L1 expression and TMB in non-small cell lung cancer (NSCLC), we designed a study to compare PD-L1 expression levels and TMB values from the same FFPE samples. Methods: 153 NSCLC patients were enrolled between August 2018 and January 2019. An FFPE sample with at least 10 sections was taken from each patient. DNA was extracted from half of the FFPE sections, and was sequenced using a 605 gene panel to 5,000× depth. In silico analysis was conducted to compare the TMB value obtained using this 605-gene panel with that determined using whole exome sequencing (WES). The Pearson rank correlation of TMBs determined using the 605 gene panel versus those using WES was 0.9379, indicating results of the two methods are highly consistent. The other halves of the FFPE sections were used to evaluate PD-L1 expression using immunohistochemical (IHC) techniques. Because WES is considered the gold standard for determining TMB, we re-analyzed WES sequencing data obtained from all 1049 NSCLC patient samples in the TCGA database, and demonstrated that the TMB determined using the 605 gene panel was highly consistent with that obtained using WES. Results: We determined that 22.22% (34/153) of samples had high PD-L1 expression (defined as &gt; 50% of cells being PD-L1 positive), but their TMB values varied from 0.76 to 19.84. The correlation between PD-L1 expression and TMB was only 0.154, indicating that PD-L1 expression had no significant association with TMB. Conclusions: PD-L1 expression and TMB are both important biomarkers for PD-L1 therapy. Many patients were only tested for either PD-L1 expression or TMB due to cost and sample limitations. The results of our study suggest that both PD-L1 and TMB should be examined in NSCLC patients.
Bet v 1‐specific IgE levels and PR‐10 reactivity discriminate silent sensitization from phenotypes of birch allergy
Authors: Olga Elisyutina, Elena Fedenko, Raffaela Campana, Alla Litovkina, Nataliya Ilina, Dmitry Kudlay, Evgenii Egorenkov, Valeriy Smirnov, Rudolf Valenta, Christian Lupinek, Musa Khaitov
Journal: Allergy (2019)

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Feasibility of visual inspection with acetic acid (VIA) screening for cervical cancer in Tanzania with emphasis on special populations.
Authors: Justine Chinn, Ava Runge, Andreea Dinicu, Jenny Chang, Argyrios Ziogas, Justine Maher, Ariana Naaseh, Alexa Lucas, Danielle Zezoff, Kayla White, Kevin Bera, Elizabeth Crawford, Emma Cooper, Megan Bernstein, Anjali Hari, Sujata Tewari, Eugen Rutaisire, Donald Forthal, Diana Pearre, Krishnansu Sujata Tewari
Journal: Journal of Clinical Oncology (2019)

5527 Background: Following the report that VIA screening reduced cervical cancer mortality by 31% in India (ASCO LBA2 2013; Shastri SS, et al JNCI 2014), the W.H.O. endorsed VIA guidelines for Africa, where the global disease burden is highest. In Tanzania, cervical cancer is a major source of morbidity and mortality, with nearly 10,000 new cases and 7,000 deaths annually. Due to lack of resources, therapies are limited and patient outcomes are further confounded by the relatively high prevalence of concurrent HIV infection. We report on the feasibility of VIA screening in Tanzania with emphasis on unique populations. Methods: Our two 5-day VIA screen-and-treat workshops in Buzuruga and Sangabuye Health Centres in Mwanza, Tanzania were approved by the University of California, Irvine IRB and local health authorities. Participants were recruited from surrounding communities and offered free cervical VIA screening, cryotherapy when indicated, and HIV rapid testing. Acetowhite lesions and/or abnormal vascular markings were VIA+. Chi-square and Fisher exact tests were performed with statistical significance assigned at 0.05. Results: During July 2018, 825 of 917 registered participants underwent VIA screening and 25.1% (n=207) were VIA+. 147 VIA+ non-pregnant women received same day cryotherapy and 15 (1.8%) with lesions suspicious for cancer were referred to Bugando Medical Center. In the subanalysis of 64 HIV+ patients (23 diagnosed at the workshops, 41 with prior diagnosis on ART), HIV infection was not associated with VIA positivity (p=0.497). Additionally, a non-significant trend of higher VIA+ screens among newly diagnosed untreated HIV patients (27.7%) vs patients with known HIV on ART (17.5%) was observed (p=0.556). Conclusions: VIA screening for cervical cancer, while feasible in Tanzania, will require follow-up and repetitive screening. Although cervical cancer is an AIDS-defining illness, lack of correlation between HIV infection and VIA-positivity may reflect the availability of W.H.O.-subsidized ART in sub-Saharan Africa to attenuate HPV-mediated neoplastic transformation, as previously reported by others. Further study of this phenomenon is warranted.
Combinational analysis of <i>IDH1</i>/<i>IDH2</i> mutations, 1p/19q deletions and <i>MGMT</i> promoter methylation for molecular testing of glioma.
Authors: Xiaoni Zhang, Hongyue Qu, Qing Yang, Ziyang Zhu, Tanxiao Huang, Shifu Chen, Jeremy Edwards, Mingyan Xu
Journal: Journal of Clinical Oncology (2019)

e13152 Background: Mutations in IDH1 and IDH2, co-deletion of 1p and 19q, and the hyper methylation of the MGMT promoter are the most reported genetic alterations in glioma tumors. Therefore, we designed a study to analyze the prevalence of these biomarkers in glioma, and the correlation of these biomarkers with diagnosis and prognosis. Methods: From September 2018 to January 2019, eighteen patients with primary glioma were prospectively enrolled. For each patient, freshly frozen tissue or FFPE samples were collected. DNA was extracted from these samples and sequenced to at least 5,000× coverage. IDH1/IDH2 mutations and 1p/19q deletions were detected from the sequencing data, whereas MGMT promoter methylation was evaluated by real-time fluorescence qPCR. Results: Of the eighteen patients, 44.4%(8/18) and 33.3%(6/18) harbored IDH1 /IDH2 mutations and 1p/19q deletions, respectively, and 72.2%(13/18) contained MGMT promoter hyper methylation. Within these patients, we found a correlation between IDH1/IDH2 mutation and 1p/19q deletion. Namely, among the 8 patients with a IDH1/IDH2 mutation, 75%(6/8) also contained a 1p/19q deletion, whereas none of the 10 patients with wide-type IDH1/IDH2 displayed the 1p/19q deletion. There was also a correlation between mutations at the loci and MGMT promoter hyper-methylation, specifically, 87.5%(7/8) of the patients with IDH1/IDH2 mutations also exhibited hyper-methylation in MGMT, whereas only hyper-methylation was observed in only 40% (4/10) of IDH1/IDH2 negative patients. Conclusions: From our preliminary result, IDH1/IDH2 mutations may be associated with 1p/19q deletion. To further verify this result, a larger, longitudinal study is ongoing at our institution.
27-year patterns in high-risk prostate cancer treatment in a racially diverse, equal-access health care setting.
Authors: Nicholas R Rocco, Michael G Santomauro, Audry H Robertson, Huai-Ching Kuo, Timothy C. Brand, Yongmei Chen, John E Musser, Christopher R. Porter, Inger L. Rosner, Preston Gable, Jennifer Cullen, Sean P Stroup
Journal: Journal of Clinical Oncology (2019)

e16583 Background: Despite the significant stage migration of prostate cancer (CaP), a large proportion of patients harbor high-risk disease. Few CaP series provide long term outcomes with the ability to assess disparities in diverse populations. We examined 27-year outcomes among men treated for high risk CaP in a large, racially diverse, equal access system. Methods: A retrospective cohort study was conducted of patients enrolled into the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1990-2017. There were 2,241 CaP patients who were NCCN-defined high risk, had a self-reported race of Caucasian (CA) or African American (AA), and had a primary treatment of hormonal therapy (HT), radical prostatectomy (RP), radiation therapy (RT) or no treatment (NoTX). Demographic and clinico-pathological variables were evaluated and stratified by race and treatment. Primary study outcomes included temporal patterns in race-specific treatment intensity and type(s). Secondary outcomes included biochemical recurrence (BCR)-free survival (BRFS) and distant metastasis-free survival (DMFS). Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis were used. Results: Mean patient age at CaP diagnosis and follow-up time were 68.1 years and 7.8 years, respectively. AAs made up 26.9% of the study cohort. Median prostate specific antigen level was 20.9 ng/mL (IQR: 7.8 - 35.0). 52% of patients had a biopsy Gleason score of 8 or greater. 714 (31.9%) underwent RP, 966 (43.1%) underwent RT, 288 (12.9%) received primary HT, and 273 (12.2%) had NoTX. A decreasing trend of HT, with stable rates of RP and RT, was observed. Median time to BCR after RP and RT was 1.3 and 3.1 years, respectively. After RP and RT, 51.2% and 39.3% experienced BCR while 10.9% and 12.7% experienced distant metastasis, respectively. There were no significant racial differences in treatment intensity, treatment type, BRFS or DMFS. Conclusions: In this longitudinal series, there was racial comparability for all study outcomes. Moreover, in this high-risk patient series with long-term follow up (median = 6.9 years), nearly 50% did not experience BCR, and only 1 in 10 men developed metastasis.
Prognostic score for second or further line immunotherapy in advanced non-small cell lung cancer (aNSCLC): An external validation.
Authors: Arsela Prelaj, Giuseppe Lo Russo, Claudia Proto, Diego Signorelli, Roberto Ferrara, Giulia Galli, Alessandro De Toma, Giovanni Randon, Nicoletta Zilembo, Benedetta Trevisan, Michele Montrone, Vito Longo, Francesco Pesola, Niccolò Varesano, Gabriella Del Bene, Pamela Pizzutilo, Domenico Galetta, Marina Chiara Garassino, Massimo Di Maio, Annamaria Catino
Journal: Journal of Clinical Oncology (2019)

e14077 Background: Beyond PD-L1, nowadays oncologists can only use clinical characteristics to candidate patients for immunotherapy (IO). Previously, a clinical prognostic score composed by ECOG performance status (PS), sex, histology, stage, uses of platin-based therapy at first-line (1L) and response to 1L categorized 3 different prognostic groups for patients treated with second-line (2L) chemotherapy (CHT) (Di Maio, EJC. 2010 Mar;46(4):735-43.). The aim of this study is to assess if the same score is able to discriminate the outcome of aNSCLC pts treated in 2L or further-line IO, potentially helping decision making. Methods: We recorded data of patients collected from two institutional databases: Istituto Nazionale Tumori of Milan and IRCCS Oncologico Giovanni Paolo II of Bari, Italy. Overall survival (OS) was the primary endpoint and also progression-free survival (PFS) was assessed. Prognostic score was generated, and pts were divided into 3 prognostic groups: best (B: &lt; 5), intermediate (I:5-9), worst (W: &gt; 9). Results: Overall, 347 pts were included in the analysis (193 from Milan and 154 from Bari). Median age was 66 years (y) (30 – 88y), most were &lt; 70 y (67.5%), male (70.7%), smokers (79.5%) and adenocarcinoma (74.6%). ECOG PS was: 0 (23%), 1 (54.5%) and 2 (22.5%). Pts distribution was: 28%, 51% and 21% in the B, I and W groups, respectively. Median OS was 18.0 months for B group, 8.5 months for I group (HR vs B 1.83, 95%CI 1.35 – 2.47, p &lt; 0.001) and 2.6 months for W group (HR vs B 5.77, 95%CI 3.99 – 8.33, p &lt; 0.001). Median PFS was 3.4 months for B group, 3.7 months for I group (HR vs B 1.35, 95% CI 1.03 – 1.77, p = 0.032) and 1.9 months for W group (HR vs B 2.51. 95% CI 1.80- 3.50, p &lt; 0.001). Similar results were obtained stratifying the model by Institution. Conclusions: This clinical prognostic score, that was generated in patients treated with second-line chemotherapy, is able to highly predict outcomes of patients treated with IO. These results demonstrated that in pre-treated aNSCLC pts, the worst category has a dismal absolute life expectancy, and probably would not benefit from any active systemic therapy (independently if CHT or IO). Perhaps for these pts best supportive care could be the best choice.
Impact of antibiotics and proton pump inhibitors on clinical outcomes of immune check point blockers in advanced non-small cell lung cancers and metastatic renal cell cancer.
Authors: Amit Kulkarni, Manoj Kumar, Daniel Fellows Pease, Ying Wang, Todd E. DeFor, Manish Patel
Journal: Journal of Clinical Oncology (2019)

e20520 Background: Studies have suggested that antibiotics can negatively influence efficacy of immune check-point blockers (ICB) but the results are inconsistent. The impact of concomitant proton pump inhibitors (PPI) is not known. We evaluated whether antibiotic and PPI use in patients with advanced non-small-cell lung cancer (NSCLC) and metastatic renal cell cancer (RCC) affects ICB efficacy. Methods: We identified advanced NSCLC and RCC patients treated with anti-PD1/PD-L1 at our institution between 5/2015 to 1/2019. Data regarding systemic antibiotics and PPI use &lt; 1 month or during ICB treatment were collected. The primary outcome was progression free survival (PFS) per response evaluation criteria in solid tumors (RECIST 1.1). Secondary outcomes were overall survival (OS) and objective response rate (ORR). Logistic regression and cox proportional hazards model were used for statistical analysis. Results: 87/148 (58%) and 40/55 (72%) patients received antibiotics and 57/148 (39%) and 17/55 (31%) received PPI &lt; 1 month or during ICI therapy in NSCLC and RCC respectively. In RCC, antibiotic use was associated with inferior PFS (2.9 v 5.0 months, HR = 2.3 95%CI 1.0-5.0; p = 0.04) but OS and ORR were not affected. In NSCLC, antibiotic exposure was associated with superior PFS (5.0 v 2.5 months, HR = 0.5, 95% CI 0.3-0.7; p &lt; 0.01), OS (13.0 v 8.0 months, HR = 0.5, 95% CI 0.3-0.8; p &lt; 0.01) and ORR (33% v 11%, OR = 4.6, p &lt; 0.01). On univariate analysis, there was trend towards inferior OS in NSCLC (9.0 v 13.0 months, p = 0.05) with PPI use. PPI use was not associated with other primary or secondary outcomes in both the cohorts. The antibiotic effect remained significant for PFS in NSCLC and RCC in multivariate analysis. Conclusions: Antibiotic use significantly affected PFS in both NSCLC and RCC. PPI use did not affect outcomes. In contrast to previous studies, this is the first study to show that antibiotic use was associated with favorable outcomes in NSCLC. More studies are needed to explain this association. Future clinical trials with ICB should consider stratification of patients based on antibiotic exposure.