bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 476: Clinical characteristics and outcome of pathologic N0 NSCLC patients with false positive on FDG PET-CT
Authors: Yeo Changdong , Kang Hye Seon , Lee Sang Haak 
Published: July 2021

Abstract
Background Preoperative Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET-CT) is a non-invasive and useful diagnostic tool to evaluate mediastinal lymph node metastasis in lung cancer. However, there are often false-positive lymph node cases in FDG PET-CT. We enrolled patients diagnosed with clinical N1-3 on FDG PET-CT, but pathologic N0 after mediastinal lymph node dissection. We aimed to explore clinical characteristics and outcome of pathologic N0 non-small cell lung cancer patients with false positive mediastinal lymph nodes on FDG PET-CT.
Methods We enrolled total 147 patients who took pre-operative PET-CT scan and mediastinal lymph node dissection. Among them, 40 patients were diagnosed with clinical N1-3 by PET-CT. These patients were re-evaluated by post-operative pathologic nodal metastasis and divided into false-positive group and others. We retrospectively analyzed clinicopathologic features and recurrence free survival among patients diagnosed with same pathologic stage.
Results Among 40 patients diagnosed with clinical N1-3 on FDG PET-CT, 19 (47.5%) patients were pathologic N0, which means false positive lymph node by PET-CT. Preoperative absolute platelet count (279.79 x 109/L versus 218.67 x 109/L; P = 0.012) and Platelet-Lymphocyte Ratio (PLR, 16.93 versus 11.53; P = 0.012) were significantly higher in the patients with pathologic N0. Among patients with pathologic N0, the presence of lymphatic invasion was significantly lower than other group (31.6% versus 85.7%; P = 0.001). Recurrence free survival was significantly shorter in pathologic N0 patients than those with same pathologic stage (P = 0.037). In addition, cox regression analysis showed smoking status (P = 0.045) and lymphatic invasion (P = 0.047) were independent factors for recurrence, significantly.
Conclusions In conclusion, higher absolute platelet count, PLR and lower proportion of lymphatic invasion were associated with false positive mediastinal lymph node on preoperative FDG PET-CT. Furthermore, recurrence free survival was significantly shorter in these patients than those with same pathologic stage. In the future, preoperative biomarkers to predict pathologic nodal status need to be investigated.
Citation Format: Changdong Yeo, Hye Seon Kang, Sang Haak Lee. Clinical characteristics and outcome of pathologic N0 NSCLC patients with false positive on FDG PET-CT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 476.
Abstract 640: Precision cancer medicine in pediatric tumors for improved survival in African children
Authors: Adoke Kasimu Umar , Iliyasu Yawale 
Published: July 2021

Abstract
Introduction: Childhood cancers as a growing public health challenge and is increasingly being recognized worldwide, including the developing nations. Each year, the number of pediatric cancers recorded in Africa shows an increase trend with the small round blue cells of childhood been the most common. About 90 percent of children with pediatric solid tumors die either of the complications of the tumor, chemotherapy or financial burden. Since mutation rate in pediatric cancer is lower than adult cancers, with targetable mutations identified in less than 50% of cases, we believe that using precision cancer medicine and to some extent implementational science can help reduce this burden in Africa.
Methods: Forty-six cases of pediatric cancer were reviewed over a five-year period (2016- 2020). Their case notes were retrieved and data on site, tumor type, mode of diagnosis, drugs given, complications, follow-up visits and financial implications were accessed. Data was analyzed using spss version 21.
Results: Patients age ranges from 3months to 12 years with a male female ratio of 4:3. The commonest site of pediatric tumor was the jaw 12(26%), eye 7(15.2%) and upper extremities 5(10.9%). The commonest tumor type was Burkitt lymphoma, retinoblastoma, alveolar rhabdomyosarcoma, follicular lymphoma and nephroblastoma with rare types like synovial sarcoma and Ewing sarcoma also seen. Majority (70%) were diagnosed with routine H&E only with few diagnosed using immunohistochemistry. No FISH, CISH or NGS done on any of the tumors. Most patients (85%) received chemotherapy with the most common complication been tumor lysis syndrome. About 75% mortality was seen mainly due to complication of treatment.
Conclusion: Childhood cancer is a big burden and has a dismal prognosis in our setting due to several factors. Incorporation of precision cancer medicine and implementation science can go a long way in improving pediatric cancer outcomes.
Citation Format: Kasimu Umar Adoke, Yawale Iliyasu. Precision cancer medicine in pediatric tumors for improved survival in African children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 640.
Abstract 657: Folate receptor alpha expression is associated with poor prognosis in patients with cervical cancer
Authors: Takamizawa Shigemasa , Yazaki Shu , Kojima Yuki , Yoshida Hiroshi , Kitadai Rui , Shimoi Tatsunori , Nishikawa Tadaaki , Sudo Kazuki , Kato Tomoyasu , Yonemori Kan 
Published: July 2021

Abstract
Background: The folate receptor alpha (FRα) is a glycosyl-phosphatidylinositol-anchored membrane protein that binds and internalizes folate for purine and thymidine DNA biosynthesis, repair, and methylation. FRα have a role in cellular migration and invasion, and overexpression of this receptor is associated with tumor progression. FRα is known to be over-expressed in numerous epithelial malignancies and considered a potential target for anticancer treatment. However, the association between FRα expression and clinicopathologic features and prognosis in cervical cancer remains unclear.
Methods: This retrospective study included patients diagnosed with cervical cancer who underwent primary surgery between 2000 and 2020. Immunohistochemical staining of FRα was performed using Anti-Folate Binding Protein/FBP antibody (abcam, ab67422). The evaluation of FRα expression was performed by an experienced pathologist. FRα-positive was defined as &gt; 5% tumor staining. FRα-high was defined as ≥ 50% tumor staining with 2+ or 3+ intensity. A possible influence of FRα expression on survival was studied by multivariate Cox regression adjusting for established risk factors for postoperative recurrence.
Results: Overall, 123 patients were enrolled, and 136 tumor samples (13 paired primary and metastatic samples) were assessed. The histopathologic classification was squamous cell carcinoma, 67; adenocarcinoma, 27; adenosquamous carcinoma, 13; other, 16. FRα-positive was found in 100% (136/136), and FRα-high was 20.8% (15/72) of squamous cell carcinoma and 33.3% (10/30) of adenocarcinoma. The FRα expression of the metastatic tumor was significantly higher than the primary tumor (H-score, 180 vs. 105, p=0.006). In 69.2% (9/13) of cases with paired samples of primary and metastatic, FRα expression was elevated in metastatic tumors than primary.In a multivariate analysis, FRα-high was associated with poor recurrence-free survival (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.17-4.52, p=0.016) and overall survival (HR 5.45, 95% CI 1.91-15.5, p=0.002).
Conclusion: FRα was widely expressed regardless of histological subtypes. FRα expression was elevated in metastatic tumors, and its expression was independently associated with postoperative recurrence and decreased survival in patients with cervical cancer. FRα may be a potential target for therapy of cervical cancer.
Citation Format: Shigemasa Takamizawa, Shu Yazaki, Yuki Kojima, Hiroshi Yoshida, Rui Kitadai, Tatsunori Shimoi, Tadaaki Nishikawa, Kazuki Sudo, Tomoyasu Kato, Kan Yonemori. Folate receptor alpha expression is associated with poor prognosis in patients with cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 657.
Abstract 752: Neutrophil-to-lymphocyte ratio and subsequent cancer risk in the UK Biobank
Authors: Song Minkyo , Engels Eric A. 
Published: July 2021

Abstract
Background: The neutrophil-to-lymphocyte ratio (NLR), a ratio between neutrophil and lymphocyte counts in peripheral blood, is a measure of the balance between systemic levels of inflammation and immunity. NLR has been associated with cancer prognosis, but the role of NLR as a biomarker in carcinogenesis is not well established.
Methods: We evaluated 445,443 adults in the UK Biobank, who were aged 37-73 years at baseline, had measured differential blood counts, and were cancer-free and under follow-up 1 year after baseline. NLR was categorized into quartiles. Incident cancers were ascertained from cancer registries. Multivariable Cox regression was used to estimate the per quartile hazard ratio (HR), separately for 69 cancer sites. Models were adjusted for age (quartile), sex, ethnicity (white vs non-white), total WBC (quartile), smoking (never, past, current), alcohol drinking (never, past, current), and BMI (&lt;25, 25-30, ≥30 kg/m2). We present nominally significant results (p&lt;0.05) and also accounting for multiple comparison using a Bonferroni cutoff (p=0.00072).
Results: 26,294 incident cancers were diagnosed during a median of 3.3 years of follow-up. The mean NLR in the population was 2.3 (standard deviation 1.2). Increasing NLR quartile was associated with increased risk of cancers in esophagus, colon, lung, soft tissue including heart, uterus, and kidney, but decreased risk of myeloma and chronic lymphocytic leukemia [CLL] (ptrend&lt;0.05). Compared with the lowest NLR quartile, the highest NLR quartile was significantly associated with risk of cancers of the soft tissue including heart (HR 1.98, 95%CI 1.15-3.42), kidney (1.54, 1.22-1.94), uterus (1.39, 1.11-1.73), esophagus (1.27, 0.96-1.69), colon (1.22, 1.06-1.41), myeloma (0.63, 0.47-0.86) and CLL (0.11, 0.02-0.48). After Bonferroni correction, NLR associations remained significant for kidney cancer and CLL.
Conclusion: In a comprehensive analysis in a large population-based cohort, NLR was associated with subsequent risk of several cancer types. NLR may reflect the excessive inflammatory status of an individual, even in a subclinical condition, which may promote the development of cancer. On the other hand, low NLR represents a relative rise in the lymphocytes, which may be an indication of circulating premalignant cells for lymphoid malignancies.
Citation Format: Minkyo Song, Eric A. Engels. Neutrophil-to-lymphocyte ratio and subsequent cancer risk in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 752.
Abstract 926: BYON3521, a novel effective and safe c-Met targeting antibody-drug conjugate
Authors: Groothuis Patrick , Jacobs Danielle , Hermens Inge , Damming Desiree , Mattaar Ellen , Rouwette Myrthe , van der Vleuten Monique , Sesink Aloys , Dijcks Fred , Coumans Ruud , Blomenrohr Marion , Ubink Ruud , van der Lee Miranda , Dokter Wim H.A. 
Published: July 2021

Abstract
c-Met, the cell-surface receptor for HGF/SF which is widely overexpressed in various solid cancer types, is an attractive target for the development of antibody-based therapeutics. However, the apparently delicate balance between anti-tumor activity and target mediated-toxicities proved to be quite a challenge. As a result, there are currently no c-Met targeting antibodies or antibody-drug conjugates (ADCs) on the market. We developed BYON3521, a novel site-specifically conjugated, duocarmycin-based ADC, comprising a humanized, cysteine-engineered IgG1 monoclonal antibody with low pM binding affinity towards both human and cynomolgus c-Met. In vitro studies showed that BYON3521 internalizes efficiently upon c-Met binding, and induces both target- as well as bystander-mediated cell killing. BYON3521 showed good potency and full efficacy in MET-amplified and high c-Met-expressing cancer cell lines; in moderate and in low c-Met-expressing cancer cell lines partial efficacy was observed. PK/PD studies and a mouse clinical trial in patient-derived xenograft models showed significant anti-tumor activity of BYON3521 upon single dose administration in multiple tumor types. BYON3521 showed responses in non-MET-amplified tumors with low, moderate and high c-Met expression, with partial and complete tumor remission seen in several models with moderate c-Met expression. In the repeat-dose GLP safety assessment in cynomolgus monkeys BYON3521 was well tolerated. In all, BYON3521 was deemed a safe ADC with potential for clinical benefit in patients. Preparations are ongoing to start clinical Phase I in 2021.
Citation Format: Patrick Groothuis, Danielle Jacobs, Inge Hermens, Desiree Damming, Ellen Mattaar, Myrthe Rouwette, Monique van der Vleuten, Aloys Sesink, Fred Dijcks, Ruud Coumans, Marion Blomenrohr, Ruud Ubink, Miranda van der Lee, Wim H.A. Dokter. BYON3521, a novel effective and safe c-Met targeting antibody-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 926.
Abstract CT129: ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients
Authors: Cecchini Michael , Quah Cheng , Liu Shiyao , Woloski Rachel , Udyavar Akshata , Giannakis Marios 
Published: July 2021

Abstract
Background: The release of ATP from dying cancer cells in response to platinum-based chemotherapy increases immunosuppressive extracellular adenosine, which can bind and activate the A2a and A2b receptors on immune cells, diminishing the effectiveness of the anti-tumor immune response. Concomitant dual adenosine receptor blockade may therefore enhance the therapeutic efficacy of some chemotherapeutic agents. Etrumadenant (etruma, AB928) is the first clinical-stage small-molecule, selective dual antagonist of A2aR and A2bR for which combination data with mFOLFOX-6 in mCRC were previously presented1,2. Here we present updated results for safety in all patients (pts) and efficacy in 3L+ pts.
Methods: ARC-3 (NCT03720678) was a phase 1/1b, multicenter, open-label study to evaluate etruma + mFOLFOX-6 in pts with mCRC. Eligible pts had histologically confirmed mCRC with ≥1 measurable lesion. Pts received 75 mg (phase 1 only) or 150 mg etruma orally once daily (QD) + mFOLFOX-6. The primary objective was to assess the safety of the combination; secondary objectives included evaluation of clinical activity.
Results: As of 20Nov2020, 44 pts were enrolled and received etruma (75mg: n=4; 150mg: n=40) + mFOLFOX-6. Etruma-related AEs were reported in 34 pts and were mostly Grade 1 or 2; those reported in &gt;30% of pts were fatigue and nausea. One pt had an etruma-related Grade 3 acute kidney injury and there were no Grade 4-5 etruma-related SAEs. There were 22 efficacy-evaluable 3L+ subjects, all of which had received prior FOLFOX and/or FOLFIRI. In this subgroup, the ORR was 9.1% and the median PFS and OS were 3.9 and 15.7 mos respectively.
Conclusions: Updated results confirm etruma + mFOLFOX-6 was well tolerated in pts with mCRC without significant additive toxicity and was associated with disease control in heavily pretreated pts. Based on these encouraging data, a platform study (ARC-9) has been initiated to further explore this and other combinations in mCRC pts.
References 1. Cecchini M, et.al. AACR Annual Meeting 2020, Abstract# 99532. Udyavar A, et.al. SITC Annual Meeting 2020, Abstract# 338
Citation Format: Michael Cecchini, Cheng Quah, Shiyao Liu, Rachel Woloski, Akshata Udyavar, Marios Giannakis. ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT129.
Abstract LB148: Gamma delta T cells engineered with a chimeric PD-1 receptor effectively control PD-L1 positive tumors in vitro and in vivo with minimal toxicities
Authors: Barber Amorette , Wang Xiaohong , Gopisetty Anupama , Mirandola Leonardo , Chiriva-Internati Maurizio 
Published: July 2021

Abstract
Introduction. Despite the overwhelming success of anti-CD19 CAR T cell therapies in recent years, it is still impossible to date to replicate comparable results in patients with solid tumors. Such obstacle is due to many factors, but the three most relevant ones are: a) the complex and immune-suppressive tumor microenvironment, b) the lack of optimal tumor targets that are not also expressed on normal cells and c) the use of autologous, patient-derived cells, which are frequently sub-optimal due to chemotherapy. Here we investigated a novel strategy to overcome these three barriers by using unconventional, MHC-independent gamma delta T cells and a chimeric PD-1 protein that was previously validated in murine conventional alpha-beta T cells. We tested the hypothesis that our strategy could specifically target cancer cells without a CAR for a specific tumor-associated antigen by turning PD-1 immune suppression into T-cell activation and using donor-derived, “off-the-shelf” effector cells. Experimental procedures. We built a chimeric PD-1 receptor consisting of the extracellular portion of PD-1 fused to the intracellular domains of DAP10 and CD3z. Gamma delta T cells from healthy donors were expanded ex vivo and stably transduced with a gamma-retrovirus-derived viral vector carrying the chimeric construct. Cells were tested for killing efficiency, cytokines secretion, and memory differentiation in vitro. We then evaluated the in vivo efficacy and tolerability in murine xenografts. Results. chPD1-gdT cells selectively killed PDL-1+ tumor cells, with minimal on-target/off-tumor toxicities and without off-target toxicities. Cells were well tolerated in mice, without damage to normal PD-L1+ cells. Upon contact with PD-L1+ cancers, chPD1-gdT cells, but not untransduced gdT cells, expressed markers of memory phenotype and secreted inflammatory cytokines. In vivo, chPD1-gdT cells, but not untransduced gdT cells, cleared PD-L1+ tumors without significant elevation of CRS-related cytokines nor off-tumor toxicities. Conclusions. chPD1-gdT cells are potent and safe in vitro and in vivo and will be assessed in a Phase I/II clinical trial.
Citation Format: Amorette Barber, Xiaohong Wang, Anupama Gopisetty, Leonardo Mirandola, Maurizio Chiriva-Internati. Gamma delta T cells engineered with a chimeric PD-1 receptor effectively control PD-L1 positive tumors in vitro and in vivo with minimal toxicities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB148.
Abstract ND01: Discovery of INCB86550: A potent, orally bioavailable small molecule inhibitor of PDL1 for the treatment of cancer
Authors: Wu Liangxing 
Published: July 2021

Abstract
Blocking the PD-(L)1 immune checkpoint axis with therapeutic antibodies has proven to be an effective treatment modality for multiple cancer histologies. Orally bioavailable small-molecule inhibitors of the PD-1/PD-L1 interaction have been highly anticipated as a promising alternative or complementary therapeutic to the monoclonal antibodies.
This presentation will detail our discovery evolution that led to the discovery of a first-in-class small molecule PDL1 inhibitor INCB89550 which is currently in clinical trials for the treatment of cancer. The presentation will also detail our characterization of novel small molecule antagonists of the PD-(L)1 axis that function by inducing dimerization and subsequent internalization of the PD-L1 protein, effectively depleting the ligand from the cell membrane and preventing PD-1 activation on T cells.
Citation Format: Liangxing Wu. Discovery of INCB86550: A potent, orally bioavailable small molecule inhibitor of PDL1 for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr ND01.
Abstract 110: Colon Cancer in Patients under 50 in Guatemala: A Retrospective Comparative Cohort Study
Authors: Velarde Angel , Kihn-Alarcón Alba , Gay Hiram , Michalski Jeff , Ruiz Edgar , Geoffrey Hugo , de Falla Vicky , Figueroa Javier , Najera Kirk Douglas , García Carlos , Ma Kevin , Salazar Ana , Zamorano Abigail , Dávila Sonia , van Rheenen Jacaranda 
Published: July 2021

Abstract
Purpose: Describing and comparing clinico-pathological characteristics of younger (&lt;50 years) versus older (≥50 years) colon cancer patients treated at the Guatemalan Liga Nacional Contra el Cáncer e Institute of Cancer (Liga-INCAN).
Methods: This IRB-approved single-institution retrospective cohort study reviewed the medical and pathological records of patients ≥18 years diagnosed with colon cancer at the Liga-INCAN, the largest specialized oncologic hospital in Guatemala, from 2013-2019. Continuous data are presented as mean and standard deviation, categorical data as frequency and percentage. Subjects were categorized into two groups, younger group (&lt;50 years) and older group (≥50 years). Statistical analyses were performed with Chi-squared, Fisher's exact test, and Kruskal-Wallis test.
Results: Among 123 patients, 34.74% were &lt;50 and 65.26% ≥50 years. Most of patients in the younger group were male 68.83% in comparison to the older group where most were female (p&lt;0.01), patients resided in the rural area 60.47% vs 50.0% respectively (p=0.18). BMI index in younger patients was below 25 in 56.1% vs 50.64% (p=0.30). Patients &lt;50 years old were diagnosed at earlier stages (I and II) 39.54% vs 22.5% when compared with ≥50 years old patients (p&lt;0.05), tumors were more common in the left compared to the right colon in younger patients (58.14% vs 50.0%), the difference was not significant (p=0.15). Histopathological features did not show significant differences, most tumors were adenocarcinomas for both groups, but signet ring cell carcinomas were more frequent in the younger than in older patients (9.30% vs 1.25%).
Conclusion: Our findings indicate that Guatemalan patients diagnosed with colon cancer younger than fifty years old are more frequently male and are diagnosed at earlier stages compared to older patients. Although, histopathological characteristics did not show significant differences, further studies are needed to understand how these impact the prognosis of the patients in the different age groups.
Funding: None
Citation Format: Angel Velarde, Alba Kihn-Alarcón, Hiram Gay, Jeff Michalski, Edgar Ruiz, Hugo Geoffrey, Vicky de Falla, Javier Figueroa, Kirk Douglas Najera, Carlos García, Kevin Ma, Ana Salazar, Abigail Zamorano, Sonia Dávila, Jacaranda van Rheenen. Colon Cancer in Patients under 50 in Guatemala: A Retrospective Comparative Cohort Study [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 110.