bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 370: Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC)
Authors: Wang Xinan , Ricciuti Biagio , Alessi Joao V. , Nguyen Tom , Awad Mark M. , Lin Xihong , Johnson Bruce E. , Christiani David C.
Published: July 2021

Importance: Immune Checkpoint Inhibitors (ICIs) induce durable response in a subset of non-small cell lung cancer (NSCLC) patients. There is an unmet need to develop effective predictors for ICIs in metastatic NSCLC.

Objective: Define the predictive impact of smoking history (pack-years) on the clinical outcomes of ICI monotherapy and further to validate the potential clinical utility in metastatic NSCLC.

Design, setting, and participants: This study was conducted on 680 metastatic NSCLC patients treated with ICIs between April 2013 and September 2020 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. Patient TMB and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) were determined by clinical targeted Next Generation Sequencing (NGS) and immunohistochemistry (IHC) and detailed smoking history and clinicopathological characteristics were prospectively collected.

Main outcomes and measures: Evaluation of the association of smoking pack-years with objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients treated with ICI monotherapy. Assessment of time-dependent area under the curve (AUC) for predictive models of clinical outcomes.

Results: Among 680 metastatic NSCLC patients who received ICI monotherapy: 109 (16.0%) never smokers, 397 (58.4%) former smokers [median 30 pack-years], and 174 (25.6%) current smokers [median 40 pack-years]. Multivariable analysis suggested that doubling of smoking pack-years is significantly associated with better clinical outcomes of ICIs. (ORR OR = 1.20, P < 0.001; PFS HR = 0.92, P < 0.001; OS HR = 0.94, P = 0.01) Predictive models incorporating smoking pack-years yielded additional information and achieved similar model performance compared to the one using TMB.

Conclusions and Relevance: This finding suggests that detailed smoking information has a significant predictive value on clinical outcomes of ICI monotherapy independent of PD-L1 TPS. Smoking pack-years could serve as a non-invasive and consistent surrogate for TMB when it is not readily available for treatment-decision in metastatic NSCLC.

Citation Format: Xinan Wang, Biagio Ricciuti, Joao V. Alessi, Tom Nguyen, Mark M. Awad, Xihong Lin, Bruce E. Johnson, David C. Christiani. Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC) [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 370.
Abstract 382: Longitudinal C-reactive protein (CRP) as an individualized dynamic predictor for metastatic cancer patients treated with immune checkpoint inhibitors: Findings from the prospective ST-ICI cohort
Authors: Zhou Jian-Guo , Ma Hu , Gaipl Udo , Frey Benjamin , Hecht Markus , Fietkau Rainer
Published: July 2021

Background: Numerus studies already proved C-reactive protein (CRP) in pre-treat is a predictive biomarkers to for cancer patients treated with anti-PD(L)-1 antibodies. However, there aren't any study has evaluated CRP levels longitudinally in patients with immune checkpoint inhibitors (ICIs). This study provides a comprehensive investigation of CRP levels as well as its longitudinal trajectories as a dynamic predictor of treatment response and survival outcome in metastatic cancer patients undergoing immunotherapy with anti PD-1 or anti PD-L1 agents.

Methods: A total number of 104 patients were prospectively enrolled. First, multivariate survival analysis for clinical factors, which including cancer types, line of treatment, PD-L1 expression, brain metastases (BM), etc. Then, used multivariate joint modelling of longitudinal and time to event data to establish the relationship between longitudinal CRP and the overall survival (OS).

Results: 92/102 patients with more than 2 times CRP results in all of treatment timepoints. Longitudinal CRP levels combine with clinical factors emerged as independent predictors of worse OS (HR of jointed model= 1.82, 95% CI: 1.45-2.32, p < 0.001), and this dynamic biomarker achieved a high accuracy (C-index 0.81) for predicting OS. However, those clinical factors didn't impact the dynamic CRP in this jointed model (HR of PD-L1= 1.68(0.79-3.65), HR of BM= 0.82(0.42-1.64), HR of PD-L1: BM=0.76(0.30-1.89)).

Conclusion: Our study highlights longitudinal CRP serves as potential personalized dynamic predictions for immunotherapeutic benefit of metastatic cancer patients.

Keywords: metastatic cancers, immune checkpoint inhibitors, C-reactive protein, dynamic predictor

Trial registration: Prospectively registered in ClinicalTrials.gov (NCT03453892) on January 24, 2018.

Citation Format: Jian-Guo Zhou, Hu Ma, Udo Gaipl, Benjamin Frey, Markus Hecht, Rainer Fietkau. Longitudinal C-reactive protein (CRP) as an individualized dynamic predictor for metastatic cancer patients treated with immune checkpoint inhibitors: Findings from the prospective ST-ICI cohort [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 382.
Abstract 414: Efficacy of Balixafortide (POL6326) and Paclitaxel alone and in combination in humanized breast cancer PDX
Authors: Obrecht Daniel , Zimmermann Johann
Published: July 2021

Despite availability of new therapies, outcomes for patients with relapsed metastatic breast cancer is poor with moderate median overall survival. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in breast cancer (BC). Anti-cancer mechanisms of CXCR4 antagonists include inhibition of angiogenesis and metastasis, activation of immunosurveillance and chemo sensitization. Balixafortide (POL6326) is a potent, selective inhibitor of the chemokine receptor CXCR4 in PhIII for metastatic HER2-negative breast cancer (BC) in combination with tubulin-binding eribulin (NCT03786094). Clinical proof-of-concept in combination with eribulin was demonstrated in a PhI single arm dose-escalation trial in patients with metastatic HER2-negative BC (NCT01837095). The objective response rate for a dose of 5.5mg/kg balixafortide and 1.4mg/m2 eribulin) was 38% (median duration 4.4 months), and the clinical benefit rate was 63% (median duration 8.1 months). Tolerability and safety of eribulin in combination with balixafortide was comparable to that of eribulin monotherapy. Balixafortide was combined with paclitaxel in a humanized BC patient-derived xenograft (PDX) model to explore the efficacy in combination with another tubulin-binding drugs. Human immunophenotyping confirmed successful human CD34+ cell engraftment and expansion of human immune cells prior implantation of an invasive ductal carcinoma (ypT1a ypN1a R0 G3 L1 V1), ER/PR/Her-2 negative tumor. 10mg/kg paclitaxel was given 2x weekly iv. Dosing of balixafortide was 20mg/kg bid sc for 5 days with 2 days break. Total treatment duration was 28 days. Partial remission was achieved in the combination arm balixafortide+paclitaxel (T/C 13%, 87% inhibition of tumor volume vs vehicle control) which was stat. significantly better than paclitaxel monotherapy (T/C 42%). There was no decrease in tolerability in balixafortide combination vs paclitaxel alone. This data suggests combination with balixafortide is more efficacious and equally tolerated to paclitaxel single agent treatment.

Citation Format: Daniel Obrecht, Johann Zimmermann. Efficacy of Balixafortide (POL6326) and Paclitaxel alone and in combination in humanized breast cancer PDX [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 414.
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

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

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

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 > 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

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 (<25, 25-30, ≥30 kg/m2). We present nominally significant results (p<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<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

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

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 >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

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

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

Purpose: Describing and comparing clinico-pathological characteristics of younger (<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 (<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 <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<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 <50 years old were diagnosed at earlier stages (I and II) 39.54% vs 22.5% when compared with ≥50 years old patients (p<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.
Abstract 16: Presentation and Management of Egyptian Female Breast Cancer In Alexandria, Egypt: An Implementation Study
Authors: Rostom Yousri , Abdelmonem Salah , Shaker Marwa , Mahmoud Nayera , Labib Nevine , Ismail Abdelsalam A. , Soliman Maher
Published: July 2021

Purpose: Exploration of the population profile and management of female breast cancer in a representative sample from Alexandria, Egypt, to identify system inefficiencies and barriers preventing full implementation of international guidelines, negatively impacting the outcome.

Methods: The study surveyed 7125 records from three major public oncology services at Main University Hospital, Gamal Abd-elnasser Hospital and Ayadi Almostakbel Oncology Center, between 2007 and 2016.

Results: 73.4% (5236 records) of the records contained usable information. The median age was 54 years, with positive family history in 31.5%. The median duration of complaint before diagnosis was 3.1 months (IQR 1.6-7.5). 55.2% were early stage, 37.6% were locally advanced and 7.2% were stage IV. Breast surgery was performed for 4976 cases. Axillary surgery was done for 4945 cases. Most cases were hormone receptor positive. 15.3% were HER2 positive. The median duration to start chemotherapy was 1.03 months (IQR 0.7-1.6). Adjuvant chemotherapy was given to 3667 and neoadjuvant chemotherapy was given to 333. Anthracycline-based combination chemotherapy, with or without Taxanes was the commonest. 86% received hormonal treatment. 180/317 trastuzumab-eligible patients received trastuzumab. 69.5% started radiotherapy > 6 months from presentation. Conventionally and hypofractionated regimens were used in 46.6% and 53.5%, respectively. 1109 developed relapse (local in 155, distant in 130 and 794 had both). In non-metastatic cases, median overall and disease free survivals were 149.1 and 77.1 months respectively. In metastatic cases, the median progression free survival was 19.6 months.

Conclusion: The study revealed defects in the record system, delayed diagnosis and treatment, and inadherence to targeted therapy protocols in a significant part of eligible patients. Suggested implementation strategies include promotion of national or hospital based registries, information, education and communication with target populations and health carers, establishing a patient navigation system and monitoring outcomes of the interventions.

Citation Format: Yousri Rostom, Salah Abdelmonem, Marwa Shaker, Nayera Mahmoud, Nevine Labib, Abdelsalam A. Ismail, Maher Soliman. Presentation and Management of Egyptian Female Breast Cancer In Alexandria, Egypt: An Implementation 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 16.
Abstract 18: Cancer Control Assessments in Low- and Middle-Income Countries during COVID-19: The IAEA-IARC-WHO imPACT Review Hybrid Modality
Authors: Nobile Marianna , Siewert Kendall , Perpina Maria Tena , Lyamzina Yuliya
Published: July 2021

Purpose: Under the auspices of the WHO-IAEA Joint Programme on Cancer Control, the International Atomic Energy Agency's (IAEA) Programme of Action for Cancer Therapy (PACT) supports Member States through assessments of national cancer control capacities and needs (imPACT Reviews) related to the cancer continuum. imPACT Reviews are conducted jointly with the World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and other partners as appropriate. To ensure continuity of imPACT Reviews to Member States during the COVID-19 pandemic, in particular to low- and middle- income countries, a hybrid modality with a virtual component has been adopted.

Methods: With the hybrid modality, imPACT Reviews are conducted partially virtually through online meetings with stakeholders/international experts (using photos, videos and live walk-throughs of health facilities), and through in-country visits when travel restrictions are lifted to validate findings and engage with national authorities.

Results: The case studies of Senegal and Mali initiated in mid-2020 demonstrate the effectiveness of the hybrid modality. Review findings and recommendations have been consolidated into preliminary reports submitted to the respective Ministries of Health in December 2020 and considering the impact of COVID-19 on cancer-related health services. The Reviews featured a cervical and paediatric cancer focus in line with WHO global initiatives and national priorities. Immediate next steps for the countries are the development of costed national cancer control plans and support in mobilizing resources.

Conclusion: The coordinated efforts of IAEA, IARC and WHO ensured continuity of evidence-based cancer control assessments and the virtual component may be considered for future imPACT Reviews. Benefits include involving a higher number of institutions and experts, minimizing disruption to their work, visiting more health facilities, and ensuring sustained dialogue over a longer period of time. This contributes to a stronger collaborative network while enhancing government engagement and national ownership.

Citation Format: Marianna Nobile, Kendall Siewert, Maria Tena Perpina, Yuliya Lyamzina. Cancer Control Assessments in Low- and Middle-Income Countries during COVID-19: The IAEA-IARC-WHO imPACT Review Hybrid Modality [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 18.
Abstract 20: Development of International Cancer Research Partnerships Through the NCI US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet)
Authors: Brofsky Emma , House Margaret , Heckman-Stoddard Brandy , Nokta Mostafa , Gopal Satish , Sahasrabuddhe Vikrant
Published: July 2021

Purpose: Persons living with HIV have elevated risks of HPV-related cervical, anogenital, and oropharyngeal cancers. Yet, research on optimization and implementation of prevention interventions (prophylactic HPV vaccination, cervical and anogenital cancer screening and triage, and precancer therapeutics) for HPV-related cancers among persons living with HIV has been limited. With a goal to expand this evidence, and building on strong academic research partnerships developed for HIV research between institutions in the US and the Latin American and the Caribbean (LAC) region, the US National Cancer Institute (NCI) initiated ULACNet, a new Cooperative Agreement clinical trials network in 2019.

Methods: ULACNet comprises of three Partnership Centers each led by US-based institutions (University of California San Francisco, Weill Medical College of Cornell University, and Fred Hutchinson Cancer Research Center), working collaboratively with US and LAC institutions and with the NCI to develop and conduct multicenter prevention clinical trials focused on filling key scientific gaps and evaluating novel interventions.

Results: ULACNet encompasses six countries (US, Mexico, Puerto Rico, Brazil, Peru, and Dominican Republic), twenty partner institutions, and over 100 collaborating scientific investigators, clinical and public health practitioners, research staff, and patient advocates. ULACNet will collaboratively conduct nine prevention clinical trials (two prophylactic HPV vaccine trials in adults and perinatally-HIV infected adolescents, three trials for clinical validation of molecular biomarkers and imaging technologies for screening and triage, two candidate HPV therapeutic vaccine trials, and two trials of topical therapeutic agents). Facilitation across network partners is achieved via a Coordinating Committee and three Working Groups (focused on HPV testing and screening, precancer treatment, and recruitment and retention activities).

Conclusion: ULACNet seeks to leverage established academic global health partnerships to conduct high quality collaborative clinical trials to inform clinical practice and ultimately reduce the burden of highly preventable HPV-related cancers in persons living with HIV worldwide.

Citation Format: Emma Brofsky, Margaret House, Brandy Heckman-Stoddard, Mostafa Nokta, Satish Gopal, Vikrant Sahasrabuddhe. Development of International Cancer Research Partnerships Through the NCI US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet) [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 20.
Abstract 27: Trends of Cancer Patients Seeking Care in Makueni County Referral Hospital during the COVID19 Lockdown in Kenya
Authors: Maina Stephen Karuru , Odoyo Edwin , Mwatha Stephen , Musyoki Raphael , Orangi Gavin , Achieng Emmah , Asirwa Chite
Published: July 2021

Purpose: Kenya has few qualified health care workers and facilities that are dedicated to cancer treatment most of which are located in the urban centers. Patients living in rural areas are expected to travel to urban areas for treatment. However, this is obstructed by poor roads, high levels of poverty, packed cancer wards, and lack of a place to stay in the city depriving the patients of timely and appropriate medical treatment. We outline the number of patients seeking cancer treatment care from a rural County Referral Hospital in Makueni County in Kenya during the COVID19 lockdown season that prohibited the movement of people in and out of Nairobi and Mombasa.

Methods: International Cancer Institute, a non-governmental organization working in sub-Saharan Africa and based in Eldoret Kenya established partnerships with Makueni County, to offer cancer care to patients at the County Referral Hospital. Patients attending the clinic were registered every month and their treatment history taken every time they sought treatment at the clinic for their first visit and subsequent visits. The trend of the number of patients over the lockdown season was plotted using a line graph.

Results: The observed number of new patients visiting the clinic in the year 2020 increased from Jan; 8, Feb; 11, Mar; 19, Apr; 15, May; 22, Jun; 19, July; 31, Aug; 16, Sept; 12, Oct; 17, Nov; 7, Dec; 4 patients respectively. The subsequent patient visits rose from Jan; 10, Feb; 20, Mar; 37, Apr; 41, May; 45, Jun; 43, July; 90, Aug; 40, Sept; 30, Oct; 61, Nov; 32, Dec; 19 patients respectively.

Conclusion: The travel ban influenced the number of patients seen at the Makueni County Referral hospital; more patients sought treatment at the oncology during the lockdown period than any other period of the clinic in the year 2020.

Citation Format: Stephen Karuru Maina, Edwin Odoyo, Stephen Mwatha, Raphael Musyoki, Gavin Orangi, Emmah Achieng, Chite Asirwa. Trends of Cancer Patients Seeking Care in Makueni County Referral Hospital during the COVID19 Lockdown in Kenya [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 27.
Abstract 34: Delay in Diagnosis and Treatment of Breast Cancer in Vietnam
Authors: Nguyen Sang , Nguyen Quang , Nguyen Lan , Pham Anh , Luu Hung , Tran Huong , Tran Thuan , Shu Xiao-Ou
Published: July 2021

Purpose: Delay in diagnosis and initiation of treatment from the first noticeable breast cancer symptoms are associated with poor outcome. Understanding the reasons and barriers why patients delay seeking medical care is critical to mitigate the problem, particularly in low- and middle-income countries (LMICs) where breast cancer incidence is increasing.

Methods: In-person surveys were conducted in 462 incident breast cancer cases, aged 18-79, recruited from two major cancer hospitals in Northern Vietnam. Delay in diagnosis and treatment was defined as no delay (<3 months), moderate delay (3-8 months) and serious delay (≥9 months). Multivariable polynomial logistic regression was applied in data analyses.

Results: More than one quarter patients (27.5%) experienced moderate delays, and close to one-fifth (18.8%) experienced serious delays. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for moderate and serious delays were 4.81 (2.62-8.85) and 3.46 (1.72-6.97) for financial and physical barriers and 2.43 (1.14-5.21) and 2.50 (1.04-6.00) for lack of proper knowledge, respectively. Moderate delay was positively associated with behavior/belief barriers (3.36 [1.17-9.57]). The associations of financial and physical barriers, psychological barriers, and lack of proper knowledge with moderate or serious delays appeared stronger among women living in rural areas. Lack of proper knowledge was significantly associated with delay among young women (<50 years old) and those with high incomes. However, tests for multiplicative interactions were not significant.

Conclusion: Delay in diagnosis and treatment of breast cancer is common among Vietnamese women and is affected by financial and physical barriers, psychological barriers, and lack of proper knowledge. Proper policy needs to be developed accordingly to address this public health issue.

Citation Format: Sang Nguyen, Quang Nguyen, Lan Nguyen, Anh Pham, Hung Luu, Huong Tran, Thuan Tran, Xiao-Ou Shu. Delay in Diagnosis and Treatment of Breast Cancer in Vietnam [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 34.