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.
