EPID-27. GEOGRAPHIC BURDEN OF CNS TUMORS AND DENSITY OF NEURO-ONCOLOGISTS IN THE UNITED STATES

CNS cancer care relies heavily on exam and imaging interpretation skills distinctive to a neurology-trained oncologist, and access to this subspecialty is increasingly more essential as targeted molecular therapies evolve. We sought to explore the supply of neuro-oncologists in terms of geographic CNS tumor incidence. Using the UCNS online directory, we generated a heat map representing the location (set to 75-mile radius) and density of active neuro-oncologists. We overlaid this data upon yearly incidence of CNS tumors per neuro-oncologist for each state using most recent CBTRUS data. We highlight the significant distance Americans outside of urban areas must travel for care and that isolation from academic centers and exclusion from clinical trials are substantial barriers to cancer care for a significant proportion of the population. Telemedicine may in part improve patient access to care and clinical trial participation, but significant state-to-state legal variability for providing telehealth services across state lines remains a national challenge. Short-term strategies for equitably meeting this subspecialty need may require policy changes that optimize employment of telemedicine, and long-term must ensure a robust fellowship pipeline with thoughtful incentivization and allocation of resources.

New Scope of Targeted Therapies in Lung Carcinoma

: Lung cancer (LC) is the leading cause of cancer deaths worldwide. Recent research has also shown LC as a genomic disease, causing somatic mutations in patients. Tests related to mutational analysis and genome profiles have lately expanded significantly in the genetics/genomics field of LC. This review summarizes the current knowledge about different signalling pathways of LC based on the clinical impact of molecular targets. It describes the main molecular pathways and changes involved in the development, progression, and cellular breakdown of LC and the molecular changes. This review focuses on approved and targeted experimental therapies such as immunotherapy and clinical trials that examine the different targeted approaches to treating LC. We aimto clarify the differences in the extent of various genetic mutations in several areas for LC patients. Targeted molecular therapies for LC can be continued with advanced racial differences in genetic changes, which have a significant impact on the choice of drug treatment and our understanding of the profile of drug susceptibility/resistance. The most relevant genes described in this review are EGFR, KRAS, MET, BRAF, PIK3CA, STK11, ERBB3, PTEN, and RB1. Combined research efforts in this field are required to understand the genetic difference in LC outcomes in the future.

Trends in new cancer treatments with targeted molecular therapies before and during the COVID-19 outbreak in Veneto, Italy: A real-world, population-based study.

e18734 Background: The COVID-19 outbreak has had a huge impact on health care services worldwide. Previous studies projected delays in cancer diagnoses and excess mortality for cancer patients as a result of the pandemic. Little is known, however, on the impact of the pandemic on the functioning of cancer services. We aimed to fill this gap by using a region-wide, population-based administrative health care data repository. Methods: We obtained data for patients initiating a targeted molecular therapy during 2017-2020 (January-September, by quarter) in Veneto. Eligible treatments were those with lapatinib, pertuzumab, TDM-1 and trastuzumab for breast cancer; with afatinib, alectinib, crizotinib, erlotinib, gefitinib and osimertinib for lung cancer; with cobimetinib, dabrafenib, trametinib and vemurafenib for melanoma; and with niraparib, olaparib and rucaparib for ovarian cancer. Patients starting more than one targeted molecular therapy in a given calendar year were included only once. We estimated the normalised difference between the number of patients for a given quarter in 2020 and the mean number of patients for the corresponding quarter during 2017-2019. Statistical significance was calculated assuming a type I error probability of 5%. Results: The study included 3,180 patients. In 2020, patients starting a targeted molecular therapy were 361 in the first quarter, 260 in the second quarter and 268 in the third quarter. The normalised difference between the number of treatments in 2020 and the mean number of treatments during 2017-2019 for all cancer types combined was statistically significant only for the first quarter, with more therapies in 2020 than in 2017-2019. In a breakdown by cancer type, differences were unremarkable for breast, lung or ovarian cancer, while there were significantly more treatments for melanoma for all the three quarters in 2020 compared to 2017-2019. Conclusions: We chose to use the rate of initiation of targeted molecular therapies as a proxy for the effectiveness of oncology services in managing cancer patients, because these therapies require that at least pathology and diagnostic facilities are fully operational. The study covered a population of nearly five million people, in a region where universal health coverage is available and where cancer care has been prioritised, by law, over non-cancer related health care services during the COVID-19 outbreak. Our findings suggest that provision of oncology care has not been substantially impacted by the pandemic in Veneto. Of note, label indications were unchanged for these drugs in 2020. The findings are also in line with the priority-based, adapted European Society for Medical Oncology recommendations. Further research is needed to assess whether delays at earlier stages of the route to cancer diagnosis (e.g. GP referrals for specialist care) may have occurred.

A Global Review of Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma is the leading cause of death in cirrhosis. Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. To review the risk factors, causes, morphology, enzymatic pathways and management strategies involved in hepatocellular carcinoma. A literature search was performed using PubMed for publications with a predetermined search string to identify relevant studies. The diagnosis and treatment schedule used for the successful management of hepatocellular carcinoma. Studies combining sorafenib with locoregional or other targeted molecular therapies are likely to improve responses and outcome.

Current State of Personalized Genitourinary Cancer Radiotherapy in the Era of Precision Medicine

Radiation therapy plays a crucial role for the management of genitourinary malignancies, with technological advancements that have led to improvements in outcomes and decrease in treatment toxicities. However, better risk-stratification and identification of patients for appropriate treatments is necessary. Recent advancements in imaging and novel genomic techniques can provide additional individualized tumor and patient information to further inform and guide treatment decisions for genitourinary cancer patients. In addition, the development and use of targeted molecular therapies based on tumor biology can result in individualized treatment recommendations. In this review, we discuss the advances in precision oncology techniques along with current applications for personalized genitourinary cancer management. We also highlight the opportunities and challenges when applying precision medicine principles to the field of radiation oncology. The identification, development and validation of biomarkers has the potential to personalize radiation therapy for genitourinary malignancies so that we may improve treatment outcomes, decrease radiation-specific toxicities, and lead to better long-term quality of life for GU cancer survivors.

Rare case of a duodenal de novo dedifferentiated gastrointestinal stromal tumour

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Dedifferentiation in these tumours occurs rarely, and when it does occurs most commonly after prolonged treatment with imatinib. We report the case of a 64-year-old man who presented with a mass of 8×7×3 cm dimensions involving the duodenum and head of the pancreas. On histopathology, areas of anaplastic tumour cells were negative for DOG-1, c-kit, CD-34, desmin and panCK along with a molecular level study showing wild-type KIT and PDGFRA (platelet-derived growth factor receptor alpha) gene. Based on focal GIST-like areas and CD117 positivity and absence of prior therapy, the diagnosis of a de novo dedifferentiated GIST was made. These tumours need to be reported as they pose a diagnostic challenge and their predicted response rated to targeted molecular therapies are unclear as compared with their c-kit positive counterparts.

Widespread reorganisation of the regulatory chromatin landscape facilitates resistance to inhibition of oncogenic ERBB2 signalling

Oesophageal adenocarcinoma (OAC) patients show poor survival rates and there are few targeted molecular therapies available. However, components of the receptor tyrosine kinase (RTK) driven pathways are commonly mutated in OAC, typified by high frequency amplifications of the RTK ERRB2. ERBB2 can be therapeutically targeted, but this has limited clinical benefit due to the acquisition of drug resistance. Here we examined how OAC cells respond to ERBB2 inhibition through altering their regulatory chromatin landscapes and rewiring their gene regulatory networks to acquire a reversible resistant state. ERBB2 inhibition triggers widespread remodelling of the accessible chromatin landscape. This remodelling is accompanied by the activation of the transcriptional regulators HNF4A and PPARGC1A. Initially, inhibition of cell cycle associated gene expression programmes is observed, with compensatory increases in the programmes driving changes in metabolic activity. PPARGC1A is instrumental in promoting a switch to dependency on oxidative phosphorylation and both PPARGC1A and HNF4A are required for the acquisition of resistance to ERBB2 inhibition. Our work therefore reveals the molecular pathways that support the acquisition of a resistant state and points to potential new therapeutic strategies to combat drug resistance.

Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.