PURPOSE To provide expert guidance to clinicians and policymakers in resource-constrained settings on the management of patients with late-stage colorectal cancer. METHODS ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines, conducted a modified ADAPTE process, and used a formal consensus process with additional experts for two rounds of formal ratings. RESULTS Existing sets of guidelines from four guideline developers were identified and reviewed; adapted recommendations from five guidelines form the evidence base and provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% on all recommendations. RECOMMENDATIONS Common elements of symptom management include addressing clinically acute situations. Diagnosis should involve the primary tumor and, in some cases, endoscopy, and staging should involve digital rectal exam and/or imaging, depending on resources available. Most patients receive treatment with chemotherapy, where chemotherapy is available. If, after a period of chemotherapy, patients become candidates for surgical resection with curative intent of both primary tumor and liver or lung metastatic lesions on the basis of evaluation in multidisciplinary tumor boards, the guidelines recommend patients undergo surgery in centers of expertise if possible. On-treatment surveillance includes a combination of taking medical history, performing physical examinations, blood work, and imaging; specifics, including frequency, depend on resource-based setting. Additional information is available at www.asco.org/resource-stratified-guidelines .
PURPOSE: The main objective of this systematic review was to identify whether mass and small media interventions improve knowledge and attitudes about cancer, cancer screening rates, and early detection of cancer in Asia. METHODS: The review was conducted according to a predefined protocol. Medline, EMBASE, CINAHL, Web of Science, Cochrane Library, and Google Scholar were searched in September 2017, and data extraction and rating of methodologic study quality (according to Joanna Briggs Institute rating procedures) were performed independently by reviewers. RESULTS: Twenty-two studies (reported across 24 papers) met the inclusion criteria. Most studies (n = 21) were conducted in high or upper-middle income countries; targeted breast (n = 11), cervical (n = 7), colorectal (n = 3), or oral (n = 2) cancer; and used small media either alone (n = 15) or in combination with mass media and other components (n = 5). Studies regarding cancer screening uptake were of medium to high quality and mainly reported positive outcomes for cervical cancer and mixed results for breast and colorectal cancer. The methodologic strength of research that investigated change in cancer-related knowledge and the cost effectiveness of interventions, respectively, were weak and inconclusive. CONCLUSION: Evidence indicated that small media campaigns seemed to be effective in terms of increasing screening uptake in Asia, in particular cervical cancer screening. Because of the limited number of studies in Asia, it was not possible to be certain about the effectiveness of mass media in improving screening uptake and the effectiveness of campaigns in improving cancer-related knowledge.
e19079 Background: Myeloproliferative neoplasms (MPN) are myeloid malignancies characterized by overproduction of mature blood cells, hyperplastic bone marrow and tendency to evolve into acute myeloid leukaemia. In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti-phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. We Investigate the expression and cellular localisation of CALR and CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), in comparison with healthy controls. Methods: Mononuclear cells were collected by Ficoll separation, from peripheral blood of 30 MPN (8 PV, 16 ET, 6 MF); 18 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples compared with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold, respectively). CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET cell membranes however, CD47 expression is reduced after cyto-reductive treatment (22% vs 16.6%), suggesting instead a prophagocytic effect. Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN, suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN. We observed a significant difference in CD47 expression across different MPN subtypes with a significant increase in CD47 expression in PV and MF but not ET. The use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response in particular in PV and MF.
75 Background: Approximately one third of hormonal receptor (HR) positive, HER2 negative early breast cancer reported disease relapse after adjuvant treatments. Both clinicopathologic features and multigene assays consider to be predicting factor of relapse. Cyclin B1, one of proliferative markers used in OncotypeDx has been explored previously for predicting recurrence in this subgroup of breast cancers. Our study aims to determine the prognostic significance of cyclin B1 in combination with clinicopathologic factors in recurrent HR positive, HER2 negative breast cancer. Methods: Two-hundred and forty-five HR positive, HER2 negative early breast cancers who were diagnosed during 2010 to 2015 in King Chulalongkorn Memorial Hospital were retrospectively reviewed. All clinicopathologic factors and level of cyclin B1 expression were evaluated. Correlation of cyclin B1 expression with clinicopathologic features was also compared in recurrence and non-recurrence group. Results: In 245 patients, 65 patients were recurrence group while 180 patients were non-recurrence group. Mean age at breast cancer diagnosis were 53 years. Recurrence group had high pathological staging, tumor grade, LVI, Ki-67 and lymph node involvement compared to non-recurrence group ( p < 0.05). Mean cyclin B1 expression was 9.61% (19.62 % in recurrence group and 5.88 % in non-recurrence group; p< 0.001). We have used cut-off of cyclin B1 expression at ≥ 10 % (7th decile) to classify high and low of expression. Cyclin B1 high expression were demonstrated in 53.4% of recurrence group compared to 22.4% of non-recurrence group. In multivariate analysis, tumor grade (OR 8.42, 95%CI 1.04-67.98; p = 0.046), receiving neoadjuvant chemotherapy (NAC) (OR 4.27, 95%CI 1.41-12.87; p = 0.010) and % cyclin B1 expression (OR 1.04, 95%CI 1.00-1.07; p = 0.013) were associated with recurrent disease. Five-year relapse free survival for cyclin B1 low and high expression were 84.9% and 60.1%, respectively. Conclusions: Tumor grade, receiving NAC and % cyclin B1 expression were associated with risk of recurrence in HR positive and HER2 negative early breast cancer.
35 Background: Most tumours harbor multiple driver genetic alterations and many driver alterations are linked to multiple targeted therapies with various level of evidence. In addition, a specific treatment can be linked to multiple genetic alterations in the same tumor. Several public and private databases and software solutions are available to link driver alterations to treatments options, but in clinical practice of precision oncology we need a solution to select the right treatment for our patients based on the highest level of evidence also in case of complex molecular profiles. Methods: We have developed an AI oncology algorithm and rule-engine to prioritise treatment options for every cancer patient based on the individual molecular of their tumor. This IT solution can now prioritise 1200 compounds in clinical use or clinical development based on the computing of 24,000 evidence-based associations (“rules”) between drivers, targets and compounds. The software calculates a numeric score, the “aggregated evidence level” for each driver alterations and compounds. We have linked this decision support software to a dynamic patient case management system, which records responds to therapy to create learning system to provide dynamic decision support through several lines of therapies of each patient and to use real-life evidence to further improve the algorithm. Results: Our first results indicate that system allows individualised decision of diagnostic option between single gene tests to comprehensive 600 gene NGS panels and identification of actionable alterations in 83% of cancer cases. Conclusions: This system can be a first working solution to standardise clinical decisions precision oncology, which also helps the real-life evaluation of novel multigene molecular diagnostic tests and therapies to find their best indications and accelerate their reimbursement by insurance companies and national health funds.
72 Background: An important side effect of immune checkpoint inhibitors (ICI) is immune related side effects, and in autoimmune diseases, the incidence is increased. For this reason, ICI for autoimmune diseases are carefully administered. However, among the malignancies that develop in autoimmune diseases, the frequency at which the (ICI) is indicated is unclear. This study is to clarify the incidence of malignancies to which ICIs are indicated in rheumatoid arthritis (RA), a typical autoimmune disease. Methods: In RA patients, the development of malignant tumors that can be indicated for IC was investigated at every year from September 2014, (September 2014 - August 2015: 2014 group; September 2015 - August 2016: Group 2015; September 2016 - August 2017: 2016 Group; September 2017 - August 2018: 2017 group). Patients with a history of malignant tumor treatment within 10 years were excluded at registration. IC adaptation was judged by the presence or absence of IC adaptation approval at diagnosis of malignant tumor. Results: The number of RA patients, age (year), disease duration (year), malignant tumor incidence (%), IC adaptive malignant tumor incidence (%) of each group are shown; [n = 479, 68(61-77), 8.8 (4.4-13.9), 9 (1.9%), 0 (0%)], [n = 504, 68 (61-77), 8.0 (3.7-12.8), 12 (2.4%), 0 (0%)], [n = 514, 68(61-77), 7.4 (3.4-12.7), 7 (1.4%), 1 (0.2%)], [n = 526、67 (60-76), 7.3 (3.1-12.6), 37 (7.0%), 9 (1.7%)]. Conclusions: The incidence of IC-adapted malignancy has increased in RA due to an increase in malignant tumor incidence, development of a new IC (methods), combined use of IC and other cancer treatment methods, and expansion of IC indication diseases. Due to the coexistence of autoimmune diseases and malignancy therapy, familiarity with malignant tumor treatment is essential for rheumatologists.
111 Background: There has been considerable research interest in recruiting immune cells of cancer patients to detect and destroy malignant cells. Various approaches have been attempted including activation of dendritic cells, chimeric antigen receptor T-cells, use of check point inhibitors and expansion and infusion of Tumor Infiltration Lymphocytes (TILs). TILs have however been successfully evaluated in only a few cancers such as Melanoma and Cervix. In order to explore the feasibility of using TILs for treatment of various solid organ cancers we hypothesized that their in vitro evaluation would establish preliminary viability of the approach. Methods: We isolated TILs from 3 patients with Ca Buccal Mucosa, 2 patients with Ca Cervix, 2 patients with Ca Breast and 1 patient each with Ca Bladder and Basal Cell Carcinoma. The explant cultures of primary/metastatic tumor tissues sections of minimum 3 mm3 size using appropriate growth medium in presence of T cell growth factor, interleukin 2 (IL2) was utilized for the propagation of TILs. TILs were expanded in meaningful numbers within three to four weeks of culture and characterized for in vitro cytotoxicity by live cell imaging and Interferon gamma release ((IGR) test. TCR gene repertoire sequencing was performed using Next Generation Sequencing (NGS) to accurately measure T cell diversity and clonal expansion. Results: TILs were isolated from 10 out of 10 patients with median number of TILs of 10 million / tissue section. The flow cytometric analysis revealed and confirmed the presence of various T cell markers in the TIL cultures generated. In vitro cytotoxicity analysis performed by live cell imaging and IGRs revealed high potency for tumor cell kill rate for the expanded TILs. TCR gene sequencing revealed clonal expansion in the TIL explant population. Conclusions: This study shows feasibility of TIL expansion from cohort of patients with multiple cancer types which can be utilized for large scale expansion and infusion in future clinical trials.
19 Background: Sustainable development goals and voluntary global NCD targets 2025 plan to achieve 80% coverage by essential NCD medicines and technologies and drug therapy and counselling coverage to the tune of 50%. This can only be achieved by making coverage wider, going to periphery and urgently creating workforce capable of doing such an activity at scale. District cancer care model (Pendharkar model) tried to involve these principles and shown a scalable acceptance by the health system. Methods: To expand the access administratively, most peripheral but medically most suitable, district hospitals, were used to create nodal cancer units. To achieve the scale, all districts of a state were targeted. For creating an alternate workforce existing medical officers and nurses were utilised. Results: Over a period of 5 years seven states of India, having a population of more than 250 million, have agreed to join the programme.176 districts have created nodal cancer units with physician and two nurses in-charge of the programme. They delivery variety of care including counselling, chemotherapy, supportive, palliative, follow up care. They serve as nodal units for public education driving government programmes including public education. At least 300-500 patients avail the services on a daily basis, including more than 200 chemotherapy procedures in a day. On world cancer day educational activities happened in all these districts simultaneously creating massive impact. Conclusions: This unique innovative model has proven that health system changes can be brought at very large scale using existing government possibilities. Available infrastructure, human resource, minimal financial changes with administrative reforms can lead to impactful change in access to cancer care at scale.
5 Background: Cost-effective analysis as part of cancer treatment decision-making. Methods: We reviewed deaths of 52 metastatic cancer patients treated with multidimensional integrative medicine (MIM) approach. Patients received standard oncologic treatment plus a MIM predefined program of emotional, cognitive and social support. The method included empathy improvement, changes on physician attitude and office environment, modulation of staff behavior supporting patient’s needs and rights, promotion of belongingness, increasing on patient’s protagonism using multimedia interactive narrative and shared decision-making. Patients were categorised according to the tumor site, pathologic, molecular and IHC characteristics, clinical stage and treatment. Observed survival was defined as the time elapsed between the detection of first metastasis and death. The observed survival for each patient was compared with the median expected survival previously reported on prospective randomised trials which had accrued patients with similar prognostic factors based on a best fit model. Treatment monthly cost for each patient was converted in American dollars (USD) on a daily exchange basis. Cost of the treatment periods were compared with those analysed in four large USA commercial managed care plans. Results: Treatment of metastatic cancer patients using MIM showed a 44% increase in median survival and a 48% decrease in cost. The estimated ICER/QALY was of 32304 USD, which represented 2.0 of Brazilian PPP. Conclusions: Despite methodological limitations, this is the first study to indicate a cost-effective survival increase in metastatic cancer patients using a MIM-behavioral modulation model. [Table: see text]
11 Background: As per global oncology workforce data published by ASCO in 2018 the new patients per oncologist ratio ranges between 700 to 10,000 in developing countries compared to 70-200 in developed ones. This gross deficit of oncologists adversely affects quality of care resulting in poor outcomes for patients. The onco.com OCPAP technology platform is designed to help patients get free standardised treatment recommendations as per standard protocols. Methods: We identified four basic input points with objective responses that could be entered by the patients/caregivers - cancer type (organ affected), treatment done so far (none, surgery, chemo, radiation), stage of disease and performance status (active, weak and bedridden). Proprietary knowledge database was created by our oncologists as per standard guidelines based on which the platform provides output in terms of specialist to be consulted (medical, radiation, surgical oncologist), recommended treatment (surgery, radiation, chemotherapy, palliation or supportive care), and diagnostic information required. Technically, OCPAP uses an online interface to capture the input from the user regarding the condition of the patient. The user interface then sends the input to our REST API based application running on a server. The server application runs our proprietary recommendation algorithm that is optimised to search our database containing proprietary knowledge graph created by our oncologists. Once a match is found, our algorithm provides the most relevant information that matches the patient’s condition. This information is then provided to the user through the same interface in simple language to help them make right treatment decisions in consultation with their treating doctor. Results: OCPAP platform has benefited 18,000 patients from 14 countries and has helped them better understand their treatment options. Majority of users are from developing countries in Indian subcontinent, Africa and Middle East. Conclusions: The OCPAP platform can help millions of cancer patients with limited access to qualified oncologists get better understanding of their treatment options.
20 Background: In recent years the impact of technology has marked a major transformation in the way society produces and generates services. Several initiatives have been developed in the health area to face this new reality. A major oncology center in Brazil carried out a project based on Design Thinking with the objective of understanding the current scenario and promoting innovative solutions for the care of cancer patients. Methods: Design Thinking is the set of ideas and insights to address problems related to information acquisition, knowledge analysis and proposal of solutions. This process took place in four stages designated as empathise (approach to the context of the problem and data collection), define (synthesis of collected information, and organization of insights in order to standardize and better understand the problem), ideate (stimulation of creativity and generation of solutions) and prototype (validation of the ideas). Results: A total of 130 interviews were carried out with hospital personnel and 46 with patients and caregivers, as well as workshops to develop the project activities. Twenty-six projects were generated, and the priorities differed according to personnel and patients. Among the projects are financial consultancy; predictability of the total cost of treatment; diversification of payment methods; customization of the food menu offered to patients; promotion of entertainment activities during waiting periods in the practice; increase interactivity of chemotherapy rooms; improvement of services offered to international patients; and development of digital tools that provide reliable information about cancer, promotes patient autonomy and strengthens patient’s relationship with the hospital personnel. Conclusions: There is a growing need to modernize oncology practices creating new products and services. The opinion of hospital personnel and patients diverged about priorities. The former have chosen projects to improve facilities and design new roles for the team while the latter have given their best evaluations to new systems and services. For patients using digital media is not only welcome but also necessary attributes to provide more information and increase their autonomy.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that typically presents as one or more cutaneous lesions with or without associated bone marrow involvement. Classification has evolved over time with several different names (CD4+ acute agranular natural killer [NK]–cell leukemia, blastic NK-cell lymphoma, blastic NK leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm/tumor) until it was discovered that this neoplasm is derived from plasmacytoid dendritic cells. The BPDCN nomenclature was adopted in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues under the category “Acute myeloid leukaemia and related precursor neoplasms,” and BPDCN is listed as its own category in the 2016 World Health Organization revision. Herein, we present what is to our knowledge the first reported case of BPDCN in a Rwandan patient.
25 Background: Cancer healthcare systems are an example of inequity and waste in low and middle income countries. Access to high quality cancer pathways focused in early diagnosis, molecular biology, proper staging and evidence based treatments are scarce and the patient`s care experience is dramatic and difficult in a majority of cases. There are no integrative healthcare models based on new technologies that improve outcomes and make more comfortable and expeditious all the patient and physician´s journey in cancer. Methods: Our team developed and trained a talkbot called MAIA (Medical Artificial Intelligence Assistant) using an algorithmic translation of medical language focused in the state or art for non small cell lung cancer. Our clinical team developed decision trees in diagnosis, staging, medical and surgical treatment and molecular biology that were incorporated in a virtual platform and then integrated onto a narrow artificial intelligence bot brain using neural networks with the proposal of generate clinical support to the physician and create a standard text using the verbal information captured in the oncological consultation and integrated images (reports) through a image edition software and then create a unique medical record without using computers by the physician. MAIA also can create medical treatment choices in first line of treatment and create alerts and alarms through an own app (MAIA Hip). Results: Our proof of concept was released in video at this link https://drive.google.com/file/d/12YtiOkhfEmIsL2bFp9T3QyfHHWxBvvKU/view?ts=5ceec096 Due to our decision trees size we can´t upload them, but are available for presentation. Conclusions: A talkbot trained as a narrow artificial intelligence interface for an integrative cancer healthcare platform (HIP) is possible through the clinical and engineer integration of languages using a neural network method and other software tools. MAIA is for now a patient and physician experience improvement, but the real impact will be in the data standarization and acquisition for advanced analytics. The final scope of MAIA HIP will be a blockchain for cancer in low and middle income countries.
PURPOSE Cervical cancer is a major public and global health problem. According to the WHO, it is the fourth leading cancer among women worldwide, with most women being from low- or middle-income countries. It is the leading cause of cancer-related morbidity and mortality among women of reproductive age in Tanzania, where approximately 4,216 women die as a result of the disease annually. Women with HIV/AIDS, multiple sexual partners, history of human papillomavirus infections, contraceptive use, and early onset of sexual activity have increased risk of the disease, including among university students. Poor knowledge and limited screening programs are major contributors. This study was aimed at assessing the level of knowledge and use of cervical cancer screening among university female students in Moshi municipality. METHODS A cross-sectional study was conducted from June to July 2018 involving undergraduate female students age 18 years and older at three different universities in the Moshi municipality. A total of 322 participants were identified using multistage sampling; data were collected through a self-administered semistructured questionnaire and analyzed using SPSS version 20. RESULTS Ninety-two participants (28.6%) had good knowledge, 104 (32.3%) had satisfactory knowledge, and 126 (39.1%) had poor knowledge. About 299 (92.9%) had heard about cervical cancer. The most frequent sources of information were the media (168 [52.2%]); family, neighbors, and friends (106 [32.9%]), health workers (102 [31.7%]); and teachers (75 [23.3%]). Few reported other sources of information. Only 31 women (9.6%) had been screened for cervical cancer. The reasons given for not attending cervical cancer screening were “I have just not decided” (114 [30.4%]), “I am healthy” (81 [21.6%]), “I’m not informed” (49 [13.0%]), and “It may be painful” (42 [11.2%]); 89 women (23.7%) reported other reasons. CONCLUSION Lack of proper knowledge about cervical cancer contributes to low-screening use. Promotion to increase awareness about cervical cancer screening through radio, television, social media, and clubs would be of great importance. Although a lot has been done by the government and other stakeholders regarding screening, the campaigns should focus not only on women but also on university students specifically, who are more likely to have multiple sexual partners and to have engaged in sexual activity at younger than 18 years.
16 Background: Social media channels, such as Twitter, represent relatively new technology platforms for scientific users to disseminate research findings and communicate their views and interpretations to colleagues and followers. To date, the associations between the use of Twitter and the scientific impact of its users are unclear. Methods: All Canadian oncologists who are full members of the American Society of Clinical Oncology were identified from the online membership directory. Users of Twitter were defined as those with an active Twitter account, as of June 2019, and posted at least one tweet within the past year. Data regarding the number of tweets, likes, and followers were collected by an online search of Twitter. Scientific impact of each individual was assessed based on a user’s h-index and number of citations from Google Scholar as well as score from Research Gate. Associations were examined with summary statistics and correlation coefficients. Results: We identified 676 eligible oncologists of whom 80 (12%) and 596 (88%) currently use and do not use Twitter. Among the users, the median number (IQR) of tweets, likes, and followers were 196 (45-865), 325 (86-1,246), and 198 (89-449), respectively. The scientific impact of Twitter users versus non-users was statistically similar (see Table). Likewise, within the group of users, there was no correlation between the number of tweets, likes, and followers and the scientific impact of individuals (correlation coefficients 0.38, 0.34, and 0.41, respectively, all p > 0.05). Conclusions: Only 1 in 10 oncologists use Twitter, but those who use Twitter leveraged this technology platform frequently. There was no association between the use of Twitter and the scientific impact of its users. Views from a minority of oncologists are represented on Twitter. Such bias underscores the need to exercise caution when using social media for scientific knowledge exchange. Regular evaluations of new technologies are warranted to ensure the quality and rigor of their scientific content. [Table: see text]
My grandmother used to say “Venezuela has it all,” and she was right. We had a stable economy, good medical schools, and hard-working physicians. Things started to change in the early 2000s with a new constitution and the introduction of socialism. An agreement with the Cuban government in the mid2000s brought Cuban physicians to Venezuela to help improve care in rural areas, but overall, cancer care remained unchanged. By the year 2010, cancer treatments were mostly limited to private hospitals, but sadly, this was still typical for a country in Latin America.
40 Background: A complete response to chemotherapy for most cancer patients is, and there are many complications caused by this toxic therapy. Therefore, we sought to determine chemotherapy responses in breast cancer at the proteome level. Methods: Candidate proteins were filtered out by the proteomic-based multiple machine-learning algorithms. Results: The MS analysis of FFPE set yielded 6,069 protein groups. The filtered dataset resulted in 539 proteins with differential abundances. We searched for biological process in the Gene Ontology (GO) enrichment analysis in each proteomic cluster. Several immune responses process, apoptotic process, DNA replication process and aminoacylation for protein translation process primarily were represented in group with complete remission. On the other hand, cell adhesion process, cytoskeleton organization process, vesicle organization process and Golgi organization process represented in breast cancer which showed poor responses to the therapy. The machine learning approaches demonstrated the highest AUC value, 0.978 (sensitivity 1.0 and specificity 0.714) with a combination of 11 proteins. Among them the finally selected tyrosine aminoacyl-tRNA synthetase (YARS) showed AUC (AUC = 0.749) in the subsequent steps of verification using immunohistochemistry in 123 patient cohorts. We identified the predictive relevance of YARS. YARS induced tumor necroptosis was greatly enhanced when it was combined synergistically with a combination of SMAC mimetics and a BCL2 inhibitor. Conclusions: This suggested that YARS expression could serve as a new therapeutic target for improving the clinical benefits of chemotherapy.
98 Background: Complete response (CR) to NACT portends favorable long term outcomes in LABC. There is a need for a tool to risk categorise patients for recurrence risk (RR), so that intensification of treatment can be offered to women with high risk of recurrence. Methods: A prospectively maintained database of LABC (between January 2007 to December 2012), who received NACT followed by definitive surgery, radiotherapy and endocrine therapy in endocrine sensitive disease was retrospectively analyzed for clinico-pathological and treatment factors affecting disease free survival (DFS). A risk scoring model was developed on the basis of beta coefficients of identified independent risk factors for DFS. Results: The incidence of loco-regional relapse was 8% and that of distant metastases was 32% in a dataset of 206 patients at a median follow-up of 47 months (IQR 24-62 mo). The independent risk factors for recurrence were index T stage [HR 1.8 (0.9-3.6)], N stage [HR 1.7 (0.4 – 4.7)], grade [HR 1.8 (0.8-4.2)], age less than and more than 40 years [HR 1.6 (0.4-0.9)], pathologic CR [HR 4.3 (1.7- 10.7)], intrinsic subtype [HR 2.2 (1.3-3.7)], and type of surgery (BCS vs MRM) [HR 2.2 (1.3-3.6)]. The ROC of the model for the prediction of recurrence was 0.67 (95 % CI: 0.61-0.75). The results of this model were validated by dividing the population into 3 risk groups: low risk (score less than 12), intermediate risk group (score between 13-15), high risk group (score 16 or more). The chances of recurrence are 16% versus 34% versus 57% in low, intermediate and high risk group respectively. Presence of three risk factors implies low risk, five intermediate and more than five high risk. Conclusions: The risk scoring model developed by us predicts RR and can be used for selecting patients for treatment intensification in high risk category.
38 Background: STS is a very heterogeneous family of orphan malignancies, characterized by morphological and genetic diversity. Tissue samples from individual STS patients are commonly used for routine diagnostic and research purposes. TMAs from multiple sarcoma tissue blocks have potential advantages over conventional tissue analysis in terms of efficiency and cost-effectiveness. We have established a comprehensive sarcoma TMA research platform. Methods: TMAs were constructed using left-over tissue from STS patients diagnosed at University Hospitals Leuven (B), Leiden University Medical Center (NL) and University Hospital Zürich (CH), and from patients with orphan sarcomas enrolled in EORTC trial 90101 “CREATE”. The clinical cases are well annotated in terms of diagnosis, treatment and follow-up. Each TMA block contains duplicate/triplicate 1.0-1.5 mm tissue cores from representative areas selected by sarcoma pathologists. The construction of TMAs was performed using TMA Grand Master (3DHistech) at University of Bern (CH) and in Leiden (NL). Results: The following subtype-specific TMAs have been created: clear cell sarcoma (CCSA, 54 cases), alveolar soft part sarcoma (ASPS, 59), inflammatory myofibroblastic tumor (IMFT, 33), alveolar rhabdomyo- (24) and leiomyosarcoma (55). For CCSA, ASPS and IMFT we have matching TMAs from clinical routine and patients entered in EORTC 90101. As a tool for broader drug- and target-screening purposes in STS we also produced a multi-sarcoma TMA combining multiple, more common subtypes on one block: angio-, dedifferentiated, pleomorphic and myxoid lipo-, leiomyo-, myxofibro-, rhabdomyo-, synovial and undifferentiated pleomorphic sarcoma, and MPNST, with 7-11 individual cases per tumor type. TMA construction is ongoing in other relevant sarcoma subtypes. Conclusions: We are currently expanding a very useful TMA platform representing the broad heterogeneity of STS, from more common to ultra-rare variants. TMAs are available for rapid, cost-effective morphological, histochemical and molecular characterization and identification of novel drug targets in collaboration with academic and commercial partners.
46 Background: Tumors reside and evolve in a complex ecosystem of immune and non-immune stromal cells. Methods: We employed multi-sectoral single-cell RNA-seq to catalogue intra-tumor heterogeneity in human hepatocellular carcinoma (HCC). Results: We generated single-cell atlas of ~76,000 cells from fourteen HCC patients, each consisting of 2-5 tumor and matched adjacent normal sectors. In total, we profiled 57 individual tumor and normal sectors consisting of HBV+ and HBV- HCC. By analysing matched normal and malignant sectors we observed intriguing remodelling of the tumor microenvironment (TME).We identify >70 distinct cells-states in HCC including novel, previously uncharacterized subpopulations. Specifically, we demonstrate remarkable heterogeneity in hepatocytes, fibroblast and endothelial cells. Most importantly, we consistently observed a marked remodellingof stromal cells suggesting a role in dynamic tumor-TME interactions. Conclusions: We present the first comprehensive single-cell atlas of HCC. This resource provides unprecedented insights into liver cancer, which will pave the way for early detection and therapeutic targeting.
