Distribution of histopathologic types of primary pulmonary neoplasia in dogs and outcome of affected dogs: 340 cases (2010–2019)

OBJECTIVE To provide updated information on the distribution of histopathologic types of primary pulmonary neoplasia in dogs and evaluate the effect of postoperative adjuvant chemotherapy in dogs with pulmonary carcinoma. ANIMALS 340 dogs. PROCEDURES Medical records of dogs that underwent lung lobectomy for removal of a primary pulmonary mass were reviewed, and histopathologic type of lesions was determined. The canine lung carcinoma stage classification system was used to determine clinical stage for dogs with pulmonary carcinoma. RESULTS Pulmonary carcinoma was the most frequently encountered tumor type (296/340 [87.1%]), followed by sarcoma (26 [7.6%]), adenoma (11 [3.2%]), and pulmonary neuroendocrine tumor (5 [1.5%]); there was also 1 plasmacytoma and 1 carcinosarcoma. Twenty (5.9%) sarcomas were classified as primary pulmonary histiocytic sarcoma. There was a significant difference in median survival time between dogs with pulmonary carcinomas (399 days), dogs with histiocytic sarcomas (300 days), and dogs with neuroendocrine tumors (498 days). When dogs with pulmonary carcinomas were grouped on the basis of clinical stage, there were no significant differences in median survival time between dogs that did and did not receive adjuvant chemotherapy. CLINICAL RELEVANCE Results indicated that pulmonary carcinoma is the most common cause of primary pulmonary neoplasia in dogs; however, nonepithelial tumors can occur. Survival times were significantly different between dogs with pulmonary carcinoma, histiocytic sarcoma, and neuroendocrine tumor, emphasizing the importance of recognizing the relative incidence of these various histologic diagnoses. The therapeutic effect of adjuvant chemotherapy in dogs with pulmonary carcinoma remains unclear and warrants further investigation.

A 10-year Retrospective Study of Lung Cancer in Uganda

Background: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at Uganda Cancer Institute (UCI). Methodology: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. Results: Of the 207 patients enrolled, 56.5% (n=117) were female, median age was 60 years (range: 20-94), 78.7% (n=163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n=48). Majority had non-small cell lung cancer (96.6%, n=200) with 74.5% (n=149) adenocarcinoma and 19% (n=38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n=199) in stage IV. Chemotherapy (44.9%, n=93) and biological therapy (34.8%, n=72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7%, 29.7%, 11.8% and 1.7% respectively. The median survival time was 4.4 months and was not different between NSCLC and SCLC (4.5 vs. 3.9 months respectively, p=.335). Conclusion: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer predominantly occurring in females and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early screening and improve outcomes.

ET-8 Integrated diagnostic approach to predict prognosis for malignant gliomas

Previous studies indicated that MGMT promoter methylation status with IDH and TERT promotor mutation are major prognostic factors in glioma. In addition to these molecular features, we have been assessing drug sensitivity against several chemotherapeutic agents, including temozolomide (TMZ). Here, we examined if this combined information could strongly predict drug sensitivity and the prognosis in glioma patients. One hundred and twenty-five IDH wild-type gliomas (WHO grade III and grade IV) were included in this study and retrospectively analyzed. Among them, we focused on 37 patients with partial surgical resection and biopsy to assess radiological difference on MRI. The primary cultured tumor cells were exposed with several compounds for 72 hours, then ATP based cell viability assay was performed. The favorable radiological therapeutic effect was found in 6 out of 8 (75%) with MGMT promoter methylated cases, while unfavorable in 23 of 29 (79.3%) with MGMT promoter unmethylated cases (p=0.008). The drug screening assay demonstrated that 7 of 10 cases with favorable TMZ sensitivity in vitro showed response on MRI, whereas 22 of 27 (81.5%) cases with TMZ resistance in vitro indicated tumor progression (p=0.006). Of note, all 5 cases with sensitive to TMZ and methylated MGMT promoter demonstrated favorable radiological response (p=0.002). These 5 cases tended to survive longer (median survival time, 697 days) as compared to others (median survival time, 391 days, p=0.13). These data indicate that integrated approach with genomic assessment and drug screening test may predict therapeutic response to chemotherapy and contribute selecting optimal therapy in glioma patients.

Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression

Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats

Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC.Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats.Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (>360 μmol/L, n = 80) and 176.0 days in the normal serum uric acid group (<360 μmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher’s ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group.Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.

Disparities in Mantle Cell Lymphoma Outcomes in Hispanics: A Population Based Analysis in Texas and Florida

Introduction: Mantle cell lymphoma (MCL) is a rare, aggressive type of B-cell non-Hodgkin lymphoma (NHL) that accounts for approximately 7% of adult NHL's in the United States. (JCO PMID: 9704731)Although recent advancements in treatment have improved survival, prognosis remains poor. (Blood PMID: 30154113) There have been several recent studies demonstrating ethnic disparities in MCL, however, there is a paucity of survival outcome data in Hispanic (H) patients with MCL. (CLMLPMID: 31029647) The purpose of this study was to compare the demographics, treatment patterns, and survival outcomes of H and Non-Hispanic (NH) patients diagnosed with MCL, and to contrast Hispanic cohorts between Texas (TX) and Florida (FL). Methods: This is a retrospective cohort study of patients diagnosed with lymphoma (Hodgkin and Non-Hodgkin) from the Texas Cancer Registry (TCR) and the Florida Cancer Data System (FCDS) from 2006-2017. This particular analysis focuses on patients with diagnosis of MCL. Key variables included gender, race, ethnicity, birthplace, dates of diagnosis and death, primary payer at diagnosis, poverty index, stage at diagnosis, and type of treatment. The significance of variation in distribution of categorical outcomes with ethnicity [H, NH] was assessed with Fisher's Exact tests or Pearson's Chi-square as appropriate; age was assessed with T-test or Wilcoxon. Survival time was measured in years from date of primary diagnosis to date of death. Survival distributions were described with Kaplan-Meier curves and significance of variation in median survival with ethnicity was assessed with log rank testing. All statistical testing was two-sided with a significance level of 0.05. Results: We identified a total 4619 (2078 TX, 2541 FL) patients with MCL. 669 (15%) were H and 3950 (85%) were NH. In TX, the median age of diagnosis was 65.6 years (y) in H and 68.3 y in NH (p < 0.001). In FL, the median age of diagnosis was 67.56 in H and 70.06 in NH (p < 0.001). There was a statistically significant difference in poverty index between the cohorts in both TX and FL. The majority of H (50%) in TX were in the 20-100% bracket while the majority of NH (36%) in TX were in the 10-19.9% bracket (p < 0.001). The majority of H (39%) in FL were in the 10-19.9% bracket, and the majority of NH (35%) were also in the 10-19.9% bracket (p < 0.001). Interestingly, there were only 30% of H in FL in the 20-100% bracket. There was a statistically significant difference in insurance status with the most frequent insurance being government-sponsored insurance for H in TX (48%), NH in TX (58%), H in FL (48%), and NH in FL (62%). Patients were without insurance at time of diagnosis in 14% of H in TX and 9% of H in FL, in contrast to 4% of NH in TX and 2% NH in FL. The most common stage at diagnosis in both cohorts in TX and FL was Stage III/IV with 68% H in TX vs 65% NH in TX (p = 0.746) and 69% H in FL vs 67% NH in FL (p = 0.316). The most frequent chemotherapy regimen included multiple agents for all cohorts, 43% H in TX vs 37% NH in TX (p = 0.063), and 48% H in FL vs 42% NH in FL (p = 0.695). Median survival time was 3.4 y H in TX, 3.5 y NH in TX, 4.1 y H in FL, and 4.3 y NH in FL. The survival probability at 2 years was 0.636, 0.640, 0.707, 0.675 for H in TX, NH in TX, H in FL, and NH in FL, respectively. The survival probability at 5 years was 0.371, 0.379, 0.445, 0.459 for H in TX, NH in TX, H in FL, and NH in FL, respectively. The survival probability at 10 years was 0.147, 0.118, 0.276, 0.245 for H in TX, NH in TX, H in FL, and NH in FL, respectively. There was no statistically significant difference in survival probability at 2, 5, or 10 years between H and NH in TX (p = 0.68) and FL (p = 0.72). Conclusions: Our study of patients diagnosed with MCL demonstrated statistically significant differences between H and NH patients in median age of diagnosis, poverty index, and insurance status at diagnosis. These disparities were observed in patients between the cancer registries in both states. Although there were no statistically significant differences in median survival time or survival probability at 2, 5, and 10 years among the H cohorts within each state, we observed intriguing data when the two states were compared. Strikingly, H in TX had much lower survival probability at 2, 5, and 10 years compared to H in FL. In addition, H in TX were noted to have a shorter median survival time compared to H in FL. These disparities may be a direct reflection of the significantly higher rates of poverty and lack of insurance among H in TX compared to H in FL. Figure 1 Figure 1. Disclosures Diaz Duque: ADCT Therapeutics: Research Funding; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Research Funding.

Examining the Usefulness of the Charlson Comorbidity Index to Predict Early Mortality in Patients with Acute Myeloid Leukaemia

Background and aims: Acute myeloid leukaemia (AML) is a relatively rare haematological malignancy which is the most common acute leukaemia in adults. Patients with AML often have a substantial comorbidity burden. Consequently, different scores are used in clinical practice to predict outcomes in patients with multiple comorbidities. The Charlson Comorbidity Index (CCI), calculated based on 19 different medical conditions, weighs the comorbidities to measure a patient's burden of disease. Previous publications have suggested that the CCI may be useful in determining survival in AML patients. However, the CCI is not in routine use in Ireland for assessing patients with AML. In this study we examined the usefulness of the CCI to predict early mortality in AML patients, drawing on data from the Extended Blood Cancer Registration (EBCR) in Ireland. Methods: The EBCR was undertaken by National Cancer Registry Ireland registrars trained by consultant haematologists and deployed in national centres. Data collection began in 2017 and continued to 2019; 141 AML patients underwent extended data registration. Comorbidities were identified by ICD-9 codes and chart review. Kaplan Meier curves and Cox regression analyses were used to determine the usefulness of the CCI to predict early mortality in AML patients. Results: Of the 141 AML patients, 82% were between 50 and 70 years of age and 84 had died by 31/12/2019 (median survival time = 289.0 days). The median survival time for patients in the lowest tertile of the CCI was 498.5 days, compared to 246.0 and 116.5 days for subjects in tertiles 2 and 3, respectively (Figure 1. Log rank P-value <.001). In Cox regression analysis, a dose-response relationship was observed, with patients in the highest CCI tertile displaying a greater risk (HR = 4.90, 95% CI: 2.79-8.63) of mortality compared to subjects in tertile 2 (HR = 2.74, 95% CI: 1.64-4.57) and tertile 1 (reference). However, this relationship was attenuated, and non-significant, in analyses which adjusted for age at diagnosis and in a further multivariable model. Conclusions: Although results demonstrate a strong relationship between the CCI and early mortality in AML patients, our findings suggest that the CCI provides little or no additional prognostic information beyond that which is obtained from age at AML diagnosis alone. This study highlights the importance of validating risk assessment tools in order to determine their potential usefulness in a clinical setting and emphasise the importance of weighing in the treatment decision making paradigm. The Blood Cancer Network Ireland (BCNI) thank the Science Foundation of Ireland (SFI) and the Irish Cancer Society (ICS) for funding (2015-2021). We also thank our colleagues in the National Cancer Registry Ireland for assistance, advice and guidance. Figure 1 Figure 1. Disclosures Quinn: Takeda: Honoraria. O'Dwyer: Bristol Myers Squibb: Research Funding; Janssen: Consultancy; ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Szegezdi: ONK Therapeutics: Research Funding.

RBIO-02. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT IN CHILDREN WITH DIPG

OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide（TMZ） versus radiotherapy with concomitant TMZ alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of radiotherapy and TMZ in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and March 31, 2020 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant TMZ chemotherapy, and (3) with or without adjuvant TMZ chemotherapy. A total of 85 pediatric patients were eligible for the study. The Kaplan-Meier method was used for survival analysis, and a multivariable Cox proportional hazards regression model was used to assess the independent prognostic factors. RESULTS Among 85 cases with a median age of 7 years (range 2-16 years), the median follow-up was 9 months (range 3-28 months) and the median survival time was 9 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant TMZ was 10 months, longer than 6 months of the other 19 patients treated with radiotherapy with concomitant TMZ alone, with statistical differences (p=0.002). Moreover, bevacizumab and nimotuzumab didn't bring survival benefits to patients with disease recurrence or progression. The prognosis in DIPG patients with H3K27M positive expressed is poor. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant TMZ prolongs the survival time of children with DIPG.

Primary Squamous Cell Carcinomas Arising in Intracranial Epidermoid Cysts: A Series of Nine Cases and Systematic Review

ObjectivePrimary squamous cell carcinomas (PSCCs) arising in intracranial epidermoid cysts (IECs) are very rare, and their management and prognostic factors remain unclear. This study aimed to enunciate the clinical features and suggest a treatment protocol based on cases from the literature and the cases from our institution.MethodsThe clinicoradiological data were obtained from nine patients with PSCCs arising in IECs, who underwent surgical treatment at Beijing Tiantan Hospital between July 2012 and June 2018. We also searched the PubMed database using the keywords “epidermoid cyst(s)” or “epidermoid tumor(s)” combined with “malignant” or “malignancy” or “intracranial” or “brain” or “squamous cell carcinoma” between 1960 and 2020. Risk factors for overall survival (OS) were evaluated in the pooled cohort.ResultsThe mean age of our cohort was 51.2 ± 8.3 years (range: 39–61 years), which included eight males and one female. Gross total resection (GTR) was achieved in three patients, while non-GTR was achieved in six patients. Radiotherapy was administered to five patients. After a median follow-up of 16.7 ± 21.6 months (range: 3–72 months), eight patients died with a mean OS time of 9.75 ± 6.6 months (range: 3–23 months). In the literature between 1965 and 2020, 45 cases of PSCCs arising in IECs were identified in 23 males and 22 females with a mean age of 55.2 ± 12.4 years. GTR, non-GTR, and biopsy were achieved in six (13.3%), 36 (80%), and three (6.7%) cases, respectively. After a mean follow-up of 12.7 ± 13.4 months (range: 0.33–60 months), 54.1% (20/37) patients died, and recurrence occurred in 53.6% (15/28) patients. A multivariate analysis demonstrated that postoperative radiotherapy (p = 0.002) was the only factor that favored OS. The Kaplan–Meier analysis showed that, compared with no radiotherapy (median survival time: 4 months), radiotherapy (median survival time: 24 months) had significantly prolonged OS (p = 0.0011), and GTR could not improve OS (p = 0.5826), compared with non-GTR. The 1-year OS of patients with or without radiotherapy was 72.5% or 18.2%, respectively.ConclusionMalignant transformation of IEC into PSCC was prevalent in elderly patients, with slight male predominance. GTR of previous benign IECs is recommended. For remnant benign IECs, close follow-up should be performed. Postoperative radiotherapy for PSCCs could bring survival benefit. GTR of these malignant intracranial tumors is difficult when they involve important brain structures. Future studies with larger cohorts are necessary to verify our findings.

Impact of surgery on survival in breast cancer with bone metastases only: a SEER database retrospective analysis

Background It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis. Methods A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis. Results Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467–0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325–0.478, P < 0.001). Conclusion This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.