High Rate Of Distant Metastasis Research Articles

A case report of unilateral conductive hearing loss as a consequence of malignant sinonasal melanoma: the importance of completing a full clinical history and examination

BackgroundSinonasal melanoma is a rare head and neck tumour. It is associated with a poor prognosis, high rates of loco-regional recurrence and distant metastasis. Treatment of the disease is therefore complicated, and because of limited data regarding the cancer, management is frequently tailored to the individual patient. We describe an unusual presentation of sinonasal melanoma with relevant histology, radiology and clinical photography.Case presentationThe case report describes the presentation of a 64-year-old man to the Ear, Nose and Throat department with progressive right-sided hearing loss. A thorough history highlighted other clinical symptoms including unilateral nasal obstruction and epistaxis. Clinical examination showed a right middle ear effusion with a polypoidal lesion in the right nasal cavity. Relevant imaging demonstrated a destructive process that required further assessment. An endoscopic sinus procedure was performed to obtain histological diagnosis as well as providing symptomatic relief. Histology confirmed malignant mucosal melanoma. The patient underwent maxillectomy and orbital exenteration (due to further progression of disease) at a tertiary centre with a plan for subsequent immunotherapy. This however has been delayed due to further surgery to excise a metastatic lesion to the right femur.ConclusionsThis case report highlights the importance of a thorough clinical history and examination. An unusual presentation of a sinonasal tumour can easily be missed leading to a significant delay in treatment. The case report also describes the use of functional endoscopic sinus surgery in order to obtain histological diagnosis and to debulk the tumour, providing symptomatic relief. The current literature regarding management will be discussed as well as current developments guiding future treatment.

Outcomes of Elderly Patients with Soft Tissue Sarcoma of the Extremities

Current standard of care for management of localized soft tissue sarcoma (STS) of the extremity includes aggressive local therapy including limb-salvage surgery with radiotherapy and/or chemotherapy. STS has a high incidence rate in the elderly. However, due to comorbidities associated with advanced aged, elderly patients with soft tissue sarcoma of the extremities may receive de-intensified therapy leading to adverse outcomes. We performed a single tertiary-care institution review of patients age 70 or above treated for STS to identify patient, disease, and treatment factors associated with outcomes, with a focus on the impact of treatment de-intensification in this population. Patients age 70 or older at time of biopsy-proven STS sarcoma diagnosis were identified from a single institution electronic health record from 1991-2015. Local control was calculated from time of completion of upfront local therapy (surgery and/or radiotherapy) to recurrence or last follow up. Associations between patient, disease, and treatment factors with outcome were interrogated with Fisher exact and log-rank tests. We identified 126 patients with median age of 79 (IQR 74-85) at diagnosis. The most common histologic subtypes included undifferentiated pleomorphic sarcoma (40%), liposarcoma (16%), and myxofibrosarcoma (14%). Grade distribution was 9%, 17%, and 74% for grade 1, 2, 3, respectively. Stage distribution (AJCC 7th edition) was 14%, 33%, 52% for stage I, II and III, respectively. 47% had a documented significant cardiovascular, pulmonary, or cognitive comorbidity. Among patients with high-grade (3) disease (88 patients), 93% underwent limb preservation (LP) surgery and 7% underwent amputation. In the LP subgroup, 38% had positive margins (< 1 mm). 70% of LP patients received pre- or post-operative adjuvant radiotherapy. 9% received chemotherapy. Median follow up was 17.6 months (IQR 4.4-58.2 months). Actuarial local control at one and five years was 91.9% (95% CI 79.7-96.9%) and 66.3% (95% CI 45.8-80.6%). 35% of patients developed distant recurrences. 26% of patients had late complications following combined modality therapy, predominantly lymphedema. Median overall survival was 2.8 years. On multivariate analysis, only radiotherapy was associated with local control and chemotherapy with distant control (p<0.05). While almost half of all patients had significant comorbidities, aggressive multimodal therapy for appropriately selected patients was associated with improved survival outcomes. Our institutional series affirmed the association of radiotherapy with local control in elderly patients with high-grade STS of the extremities treated with limb preservation therapy. Moreover, a high rate of distant metastases was observed potentially related to limited use of chemotherapy in patients at-risk for distant recurrences.

Watch-and-wait Strategy against Surgical Resection for Rectal Cancer Patients with Complete Clinical Response after Neoadjuvant Chemoradiotherapy

The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who achieved clinical complete response (cCR) after chemoradiotherapy. However, concerns about the oncological safety of this approach remain. This study aimed to investigate the long-term clinical outcomes of cCR rectal cancer patients who managed under watch-and-wait to those who underwent surgical resection. A total of 94 patients with stage II/III rectal adenocarcinoma who were identified as cCR after neoadjuvant chemoradiotherapy and adopted the watch-and-wait strategy were included and matched to cCR patients who underwent radical resection using 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with log rank test. Compared with cCR patients who underwent radical resection, patients who adopted the watch-and-wait strategy had more cases of local recurrence (14/94 versus 1/94), but most (12/14) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% versus 98%, P = 0.506), but the watch-and-wait group has obvious advantage in sphincter preservation, especially for patients with tumor located within 3cm from the anal verge (35/39 versus 14/34, P<0.001). Three-year distant metastases-free survival (88% in the watch-and-wait group versus 89% in the surgical group, P = 0.874), three-year disease-specific survival (99% versus 96%, P = 0.643) and overall survival (99% versus 96%, P = 0.905) were also comparable between the two groups, though a trend of high rate of distant metastases was observed in patients who developed local regrowth(5/14) in the watch-and-wait group. The watch-and-wait strategy was safe, with similar survival outcomes but superior sphincter preservation rate as compared to those who had surgery for rectal cancer patients achieving cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative approach to invasive radical surgery.

The Influence of the Pretreatment Host Immune State on Response to Radiation Therapy in High Risk Adenocarcinoma of the Prostate: A Validation Study from NRG Oncology/RTOG 0521 (Updated)

The immuno-inflammatory state has been shown in several retrospective series to be associated with poor outcomes following radiation therapy (RT) for high risk prostate cancer (PCA). We conducted an a priori designed validation study using prospectively banked serum specimens from the phase III clinical trial RTOG 0521. It was hypothesized the pre-treatment inflammatory state would correlate with clinical outcomes. Patients enrolled on RTOG 0521 had serum samples banked for future biomarker validation. This study was designed to validate previous findings (Hall 2013) showing an association between elevations in CRP levels and shorter biochemical failure-free survival after RT. CRP levels were measured in pre-treatment samples using a widely available, clinical grade assay. A panel of serum inflammatory cytokines were also measured including: monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor (TNFα). The primary endpoint examined in this a priori designed validation study was disease-free survival (DFS), defined as the time from randomization to the development of biochemical failure, local progression, distant metastases, or death from PCA, whichever occurred first. Additional endpoints included correlation with cytokine levels and toxicity events attributed to RT, namely: pollakiuria ≥grade (g) 2, cystitis ≥g 2, diarrhea ≥g 2, erectile dysfunction (ED) ≥g 2, proctitis≥g 2. Of 563 patients who enrolled in RTOG 0521, 202 had banked serum samples available. In the subsample, median age was 66 years (range 48-83), 90% of patients were white and 10% African-American. There was not an association between CRP and DFS ([HR] = 1.07 per one log increase in CRP, 95% CI: 0.84 - 1.38, p = 0.58). Pre-treatment IL-10 was significantly associated with worse DFS, both unadjusted (HR = 1.60 per log increase, p = 0.0029) and following co-variate adjustment (HR = 1.44 per log increase, p = 0.019). IL-10 was also associated with increased distant metastases (HR = 1.55 per log increase, p = 0.028). Pretreatment levels of IFN-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with g 2 or higher pollakiuria (adjusted OR = 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all p<0.05) and IL-6 was negatively associated with g 2 or higher ED (OR = 0.62, p = 0.027). Pretreatment CRP was not associated with a poorer DFS following RT. Higher baseline levels of IL-10 were significantly associated with lower rates of DFS and higher rates of distant metastases, a novel finding that warrants further exploration. Multiple cytokines were associated with the development of RT-specific toxicities, which may help with the design of precision strategies to mitigate RT-induced toxicities.

Liquid biopsy and their application progress in head and neck cancer: focus on biomarkers CTCs, cfDNA, ctDNA and EVs.

Head and neck cancer (HNC) is the sixth leading cause of cancer death worldwide. Due to the low early diagnosis rate of HNC, local recurrence and high distant metastasis rate are the main reasons for treatment failure. Therefore, it is important to establish a method of diagnosis and monitoring, which is convenient, safe, reproducible, sensitive and specific. Compared with tissue biopsy, liquid biopsy is an emerging biopsy technique, which has the advantages of re-sampling, noninvasive and cost-effectiveness, and has shown good diagnostic and prognostic value in studies for various types of malignant solid tumors. This review introduces liquid biopsy, its research progress and prospects in HNC including early diagnosis, staging, grading, prognosis assessment and disease surveillance.

Upregulation of G Protein-Coupled Estrogen Receptor by Chrysin-Nanoparticles Inhibits Tumor Proliferation and Metastasis in Triple Negative Breast Cancer Xenograft Model.

Triple-negative breast cancer (TNBC) is associated with a high mortality rate among women globally. TNBC shows a high rate of recurrence and distant metastasis. Particularly, the chemotherapy is limited because hormone therapy of breast cancer is ineffective. Thus, an effective chemotherapeutic agent is needed for tumor suppression. Chrysin-nanoparticles (chrysin-NPs) were investigated for their inhibitory effect on a MDA-MB-231-derived xenograft model. To gain insight into the underlying mechanisms, we conducted human matrix metalloproteinase (MMP) array, western blot, and immunohistochemistry analysis. Furthermore, in vivo imaging was used to monitor the chemotherapeutic efficacy of chrysin-NPs in a metastasis mouse model. Chrysin-NPs significantly inhibited the proliferation of MDA-MB-231 cells via the PI3K/JNK pathway and induced cell death through the p53-apoptosis pathway, leading to delayed MDA-MB-231-derived tumor growth. Interestingly, chrysin-NPs significantly induced G protein-coupled estrogen receptor (GPER) expression, which suppresses MMPs and NF-κB expression. Chrysin-NPs acted as effective metastasis inhibitors. Our results suggest that chrysin-NPs may be used as an effective adjuvant formulation to inhibit TNBC progression.

Expression of CXCR7 in colorectal adenoma and adenocarcinoma: Correlation with clinicopathological parameters

Colorectal carcinoma (CRC) is one of the most lethal malignancies, it ranks third in cancer-related morbidity and mortality. Although great progress has been made in early diagnosis and combined treatment of CRC, the prognosis of patients remains poor owing to the high rate of recurrence and distant metastasis. CXCR7 belongs to chemokine receptor family and has been identified as a novel receptor for CXCL12. It plays an important role in development and in progression of cancer to metastatic stage. The aim of studyTo evaluate the immunohistochemical expression of CXCR7 in colorectal adenoma and carcinoma and to analyze its correlation with clinicopathological factors. This is retrospective study including 58 colonic adenocarcinoma specimens and 18 cases of colonic adenoma. ResultsCXCR7 showed positive cytoplasmic expression in two out 18 cases of colorectal adenoma (11%) and 42 out of 58 cases of CRC (72.4%) with a significant difference between both (p < 0.001). We found a significant correlation between upregulation of CXCR7 and presence of lymphovascular tumor emboli, presence of lymph node metastasis and advanced TNM stage of the CRC. The association of the CXCR7 with patient age, sex, tumor size, depth of invasion and tumor cell differentiation was found to be non-significant. Regarding colonic adenoma, we found no significant association between CXCR7 expression on one hand and patient age, sex, tumor size, histologic type and degree of dysplasia on the other hand. ConclusionCXCR7 in CRC may act as a novel predictive indicator for prognosis and even be a potential molecular target for anticancer therapies.

A case of Stewart-Treves syndrome occurring in the abdominal wall successfully treated with eribulin: A case report.

Angiosarcoma (AS) is a rare and aggressive tumor with high rates of local recurrence and distant metastasis. Stewart-Treves syndrome (STS) is defined as AS arising in the setting of chronic lymphedema, and is extremely uncommon in the lower abdominal wall. Eribulin mesylate (eribulin) is a non-taxane microtubule inhibitor that has been approved in Japan for treating soft tissue sarcoma. The current study reports the case of a 76 year-old woman with STS in the lower abdominal wall who exhibited an excellent response to eribulin. Having undergone surgery and postoperative radiation therapy (RT) for cervical cancer 12 years earlier, the patient presented with a mass in her left lower abdominal wall, where chronic lymphedema had developed. Contrast-enhanced computed tomography revealed multiple enhancing nodules in the left lower abdominal wall and edema of the subcutaneous tissues in the whole lower abdomen. A histologic analysis of the specimens revealed AS, and she was diagnosed as STS. A total of 3 cycles of combination chemotherapy with gemcitabine and docetaxel were administered, but the patient discontinued treatment owing to severe adverse events. RT was performed for the tumor, but multiple reddish nodules appeared in the whole lower abdominal wall 3 months later. At this point, eribulin administration was offered. After 4 cycles of treatment, there was a clear reduction in the size of the nodules. All lesions were stable, no new lesions had developed, and the side effects of treatment were minor over the course of 1 year. The results reveal that eribulin may serve as a potential therapeutic option for the treatment of STS.

Prognostic Significance of Neoadjuvant Rectal Scores in Preoperative Short-Course Radiotherapy and Long-Course Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer.

This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500cGy/5 fractions), and 109 underwent preoperative CRT (4200-5080cGy/21-28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN - 3(cT - pT) + 12]2/9.61. The multivariate analysis showed that age above 65years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM). For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.

Abstract 3704: MicroRNA-3977 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting FoxM1

Abstract Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC is associated with poor prognosis, high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC requires new therapeutic approaches. The Forkhead box protein M1 (FoxM1) is a member of forkhead superfamily transcription factors that has been associated with normal cell growth and proliferation through cell cycle transition and mitotic spindle control. FoxM1 is also identified as a master regulator of tumor metastasis. Based on analysis of pooled clinical datasets derived from online accessible databases as Breast Cancer Gene-Expression Miner v4.3 and Kaplan-Meier plotter, the expression and prognostic values of FoxM1 increase in TNBC compare with other breast cancer subtypes. Directly binding to the 3'-untranslated region (3' UTR) of FoxM1 mRNAs suppress its high expression in TNBC that leads to inhibition of cell proliferation, motility, and invasion. These results implied that FoxM1 is an essential poor prognostic factor and promising candidate target in the treatment of TNBC. We identified miR-3977 as a potential regulator of FoxM1 by using in silico prediction algorithms, and we investigated its role in TNBC. In this study, we found miR-3977 expression is significantly suppressed in TNBC cell lines and inversely correlated with FoxM1 levels. We demonstrate that miR-3977 directly bound to the 3′ UTR of FoxM1 mRNA and repressed its expression. We also find reduced miR-3977 expression is associated with shorter patient survival in TNBC based on Kaplan-Meier plotter database. Moreover, in vivo delivery of miR-3977 nanoparticles inhibited FoxM1 expression and tumor growth in TNBC xenograft mouse models. In conclusion, we provide the first evidence that miR-3977 functions as a tumor suppressor and gain of miR-3977 expression leads to decrease in FoxM1 expression and inhibits to cell growth, colony formation, invasion, and progression of TNBC. Taken together, our data suggest that miR-3977-based gene therapy is a potential therapeutic strategy in TNBC. Citation Format: Selda Karamil, Nuray Altintas, Bulent Ozpolat. MicroRNA-3977 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting FoxM1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3704.

Urgent distal pancreatectomy for intraperitoneal hemorrhage due to the spontaneous rupture of a pancreatic metastatic tumor from synovial sarcoma: a case report

BackgroundSynovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy.Case presentationA 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery.ConclusionsWhile the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.

Dermatofibrosarcoma Protuberans: A Clinicopathologic and Therapeutic Analysis of 254 Cases at a Single Institution.

Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade tumor that typically does not metastasize but often recurs. Fibrosarcomatous DFSP (FS-DFSP) is associated with a substantially higher rate of metastasis and a poorer prognosis. This study sought to investigate the epidemiological, histopathological, and clinical characteristics of DFSP, especially with a particular focus on FS-DFSP. Clinical data from 254 patients treated between January 1999 and July 2018 were retrospectively reviewed. Endpoints of the study were the incidence of significant disease-related clinical events. Follow-up data from 211 patients were available for analysis, with a median follow-up time of 38 months (range: 1-196 months). The 5-year recurrence-free survival rate of patients underwent wide-local excision (WLE) was 97.1%. Patients underwent WLE exhibited a significantly decreased recurrence rate relative to patients treated through local excision (2.9% vs 37.7%; p < .001). Fibrosarcomatous DFSP had significantly higher rates of distant metastasis (66.7% [n = 4] vs 2.0% [n = 4]; p < .001) and long-term mortality (50.0% [n = 3] vs 1.5% [n = 3]; p < .001), compared with classical DFSP (C-DFSP). Wide-local excision is an effective means of reducing DFSP recurrence. Rates of metastasis are higher for FS-DFSP than for C-DFSP, with the former having significantly poorer outcomes.

Identification of prognostic and immune-related lncRNAs in hepatocellular carcinoma based on the cancer genome atlas data mining

Hepatocellular carcinoma (HCC) is a malignancy originating from hepatocytes with a high rate of distant metastasis and recurrence. HCC prognosis remains poorly understood, although its diagnosis and treatment have improved globally. Therefore, it is necessary to identify reliable predictive and prognostic indicators of HCC. HCC gene expression profiles and corresponding clinical data were downloaded from The Cancer Genome Atlas. Seven lncRNAs (C10orf91, AC011352.3, AC015722.2, AC006372.1, PICSAR, AC110285.3, and AP001972.4) associated with immune and clinicopathological features were identified as biomarker candidates for HCC prognosis based on single-sample gene set enrichment analysis, the ESTIMATE algorithm, and Cox PHR analyses. Altogether, the findings revealed that the seven immune-related lncRNAs may provide a reference for improving HCC prognosis.

Targeting EGFR Enriches Stem Cell-Like Properties in Salivary Adenoid Cystic Carcinoma by Activating the Notch1 Pathway.

BackgroundSalivary adenoid cystic carcinoma (SACC), a rare cancer arising in the salivary glands, is characterized by high rates of relapse and distant metastasis. Epidermal growth factor receptor (EGFR) has been implicated in SACC carcinogenesis. However, prospective trials of EGFR-targeting therapies in SACC are limited, and the optimum regimen is unclear.MethodsThe effects of erlotinib on cell proliferation, colony formation, ALDH enzymatic activity and tumorsphere formation were investigated in SACC cells. Expression of the cancer stem cell markers Bmi-1 and Oct4 was evaluated using Western blotting.ResultsWe found that while it robustly inhibited cell growth, targeting EGFR with erlotinib enriched the ALDH+ cell population and elevated the clonogenicity of SACC cells, suggesting an increase in stem cell-like potential. In addition, we found that suppression of EGFR kinase activity with erlotinib led to the activation of Notch1 signaling, leading to an increase in stem cell-like properties. Moreover, the γ-secretase inhibitor GSI treatment eliminated the erlotinib-induced increase in stem cell-like properties by decreasing Notch activity.ConclusionOur results provide an explanation for the worsened survival observed in some studies of erlotinib therapy in SACC and provide potential therapeutic strategies by combined blockade of the EGFR and Notch1 pathways.

The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype.

Salivary gland carcinomas (SGC) are rare, aggressive cancers with high rates of recurrence and distant metastasis. These factors, and a lack of active systemic therapies, contribute to poor clinical outcome. Response rates with immune checkpoint blockade have been low, although clinical data remain sparse. To improve the efficacy of therapies, a more comprehensive understanding of relevant molecular alterations and immunologic processes is needed. To characterize the immune microenvironment and neoantigen landscape of SGCs, we performed RNA sequencing (RNA-seq) in 76 tumors representing the three most lethal histologies: adenoid cystic carcinoma (ACC), myoepithelial carcinoma (MECA), and salivary duct carcinoma (SDC). We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction. In 37 cases also undergoing exome sequencing, we analyzed somatic mutations and neoantigens. SDCs exhibited high levels of immune infiltration, with corresponding higher levels of T-cell dysfunction, and higher mutational load. In contrast, ACCs were characterized by an immune-excluded microenvironment, the presence of M2-polarized macrophages and myeloid-derived suppressor cells, and very low mutational load. MECAs were more heterogeneous, with both immune-low and immune-high phenotypes represented. Across all SGCs, levels of immune infiltration were associated with mutation- and fusion-derived neoantigens, and with aggressive clinical behavior. These findings provide new insights into the immune microenvironment and neoantigen landscape of SGCs, showing that mechanisms of immune escape appear to differ by histology. These data nominate potential immunologic vulnerabilities and may help guide the next steps of investigation in precision immunotherapy for these difficult-to-treat cancers.

Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high rate of local invasion and early distant metastasis. Accumulating studies suggest that N6-methyladenosine methylation (m6A) is closely related to tumorigenesis. However, the relationship between m6A-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of m6A RNA methylation genes in NPC. In this study, we analyzed the differentially expressed m6A-related genes between NPC samples and normal control samples and found that two upregulated genes (YTHDF3 and IGF2BP2) and one downregulated gene (METTL3) were overlapped in GSE68799 and GSE53819. Next, we found that high expression of IGF2BP1 and low expression of METTL3 and YTHDF3 in NPC patients showed poor progression-free survival (PFS). Subsequently, the four m6A genes were selected for consensus cluster analysis, and risk models were established. The risk signature, using three genes (GF2BP1 + IGF2BP2 + METTL3), was an independent prognostic factor and predicts the clinicopathological features of NPC. Additionally, the GO, KEGG analysis, and CIBERSORT algorithm revealed that the risk signature was closely associated to immune infiltration in NPC. Finally, the expression and clinical significance of METTL3 were successfully validated in NPC tissues using immunohistochemical techniques. In conclusion, our finding revealed the potential role of m6A modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.

Efficacy and safety of carbon-ion radiotherapy for the malignant melanoma: A systematic review.

Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs.

Abstract C022: Integrated molecular approach to identify biologic factors contributing to breast cancer disparities in Chicago

Abstract African American (AA) women have a 4- to 5-fold greater risk of death from hormone receptor-positive (HR +) breast cancer (BC) compared to white women, even after controlling for stage at diagnosis, treatment, and other prognostic factors. Biologic mechanisms are activated in HR + BC arising in AA women that result in a higher rate of distant metastases and/or resistance to endocrine therapies. We are performing a metabolomic analysis of serum from AA and white women with newly diagnosed BC, as well as a racially diverse, healthy control population, to identify potential oncometabolites that promote aggressive phenotypes in HR+ BC cells. The association between candidate oncometabolites and established demographic variables related to poor outcomes in AA women with BC, including neighborhood socioeconomic deprivation and individual patient and tumor characteristics, will also be explored. AA and white women, age 20-79, with a new diagnosis of stage I-III ER+ BC who have not yet initiated treatment have been recruited from 3 cancer institutions in Chicago. Control subjects (women presenting for a screening mammogram without breast symptoms and no history of cancer) have been recruited in mammography centers. Serum for metabolite profiling and demographic data were collected. By collecting serum samples prior to initiation of any treatment, the profiles generated will also reflect the metabolome of the tumor itself. Analyses will be adjusted for tumor intrinsic subtype (Luminal A, Luminal B, HER-2 enriched and basal-like) since different molecular pathways predominate in the different subtypes and metabolite profiles are expected to vary. Target enrollment is 300 subjects; to date we have enrolled 21 AA women with HR + BC and 73 AA controls, 15 white women with HR +BC and 11 white women controls. Metabolomic analysis and demographic data and neighborhood/geo-spatial analysis will be presented with the poster. We expect to identify biochemical differences in serum that are related to race and cancer status. Associations between candidate oncometabolites and key neighborhood-level and individual-level variables that are associated with BC disparities will also be generated. Citation Format: Oana C. Danciu, Zeynep Madak-Erdogan, Hariyali Patel, Landan Banks, Jermya Buckley, Garth Rauscher, Anita Fareeduddin, Elonia Martin, Carlos Garcia, Lauren Schulte, Deanna Taiym, Julie Kim, William Gradishar, Scott Hegerty, Archana Bargaje, Joanna Frasor, Kent Hoskins. Integrated molecular approach to identify biologic factors contributing to breast cancer disparities in Chicago [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C022.

CircPDSS1 Stimulates the Development of Colorectal Cancer via Activating the Wnt/β-Catenin Signaling.

ObjectiveThis study aims to illustrate the role of circPDSS1 and the Wnt/β-catenin signaling in the development of colorectal cancer (CRC).Patients and MethodsCancerous mucosa and normal paracancerous mucosa tissues more than 5 cm away from the tumor were surgically collected from 56 CRC patients. circPDSS1 levels in collected tissues and CRC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influence of circPDSS1 on clinical features of CRC patients was analyzed. After knockdown of circPDSS1 in HCT-8 and HCT-116 cells, phenotype changes were examined by Transwell, tube formation and wound healing assay. Western blot and rescue experiments were finally performed to uncover the role of circPDSS1 and the Wnt/β-catenin signaling in the development of CRC.ResultscircPDSS1 was upregulated in CRC mucosa tissues than controls. High level of circPDSS1 predicted high rates of lymphatic metastasis and distant metastasis, and poor prognosis in CRC patients. Knockdown of circPDSS1 attenuated migratory ability and angiogenesis in CRC cells. Protein levels of key genes in the Wnt/β-catenin signaling, including β-catenin, GSK-3β, c-Myc, MMP-9 and cyclin D1 were downregulated in CRC cells transfected with sh-circPDSS1. Overexpression of β-catenin reversed the role of circPDSS1 in attenuating migratory ability and angiogenesis in CRC cells.ConclusionUpregulated circPDSS1 in CRC is closely linked to lymphatic metastasis, distant metastasis and overall survival. It stimulates the migratory ability and angiogenesis in CRC cells via activating the Wnt/β-catenin signaling.

DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level.

The aim of this study was to illustrate the role of DERL3 in regulating the development of Colorectal cancer (CRC) and the underlying molecular mechanisms. Relative levels of DERL3 in CRC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between DERL3 level and clinical indicators in CRC patients was analyzed by χ2 test. After intervening DERL3 level in HT29 and HCT-8 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8) and Transwell assay. The interaction between DERL3 and its downstream target MYCN, and their involvement in the malignant development of CRC were explored. The influence of DERL3 on in-vivo growth of CRC was determined by establishing xenograft model in nude mice bearing CRC. DERL3 was lowly expressed in CRC tissues than adjacent normal ones. Compared with CRC patients expressing a high level of DERL3, those with a low level presented high rate of lymphatic metastasis or distant metastasis. Overexpression of DERL3 in HT29 cells suppressed proliferative, migratory, and invasive capacities, and knockdown of DERL3 in HCT-8 cells yielded the opposite results. MYCN was the downstream target binding DERL3, which was upregulated in CRC tissues and cell lines. MYCN could reverse the regulatory effects of DERL3 on proliferative, migratory, and invasive capacities in CRC cells. In-vivo overexpression of DERL3 in nude mice bearing CRC inhibited tumor growth by reducing the average tumor volume and tumor weight of CRC tissues. DERL3 is downregulated in CRC samples. Its level is closely linked to lymphatic metastasis or distant metastasis rate in CRC patients. Through negatively regulating MYCN level, DERL3 suppresses proliferative, migratory, and invasive capacities in CRC.