In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells’ growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind CUSP9v3, using many non-oncology CNS-penetrant drugs from general medical practice, repurposed to block tumor survival paths; (6) the concept from chess that every move creates weaknesses and strengths; (7) the principle of mass—by adding force to a given effort, the chances of achieving the goal increase; and (8) the principle of blocking parallel signaling pathways. Part two gives an example MDACT regimen, gMDACT, which uses six repurposed drugs—celecoxib, dapsone, disulfiram, itraconazole, pyrimethamine, and telmisartan—to interfere with growth-driving elements common to cholangiocarcinoma, colon adenocarcinoma, glioblastoma, and non-small-cell lung cancer. gMDACT is another example of—not a replacement for—previous multidrug regimens already in clinical use, such as CUSP9v3. MDACT regimens are designed as adjuvants to be used with cytotoxic drugs.

Background and objectives: IL27 and IL35 are regulatory T cells (T-regs) related cytokines; they were accused in eukemogenesis of acute myeloid leukemia (AML). This study aimed to assess the expression of these cytokines in de novo AML and investigate their role as biomarkers. Subjects and methods: Seventy newly diagnosed patients with primary AML and 30 matched healthy volunteers were recruited. AML diagnosis was confirmed with flowcytometric and immunophenotypic analyses, while ELISA was used to assess serum levels of IL27 and IL35 in patients and controls. Receiver operating characteristic curve analysis was used to estimate IL27 and IL35 optimum cutoff values for predicting AML. Results: Serum levels of both cytokines were significantly higher in AML patients than controls (P43, AUC (0.926) with a sensitivity 74% and specificity 96.6% (P27.8, AUC (0.972) with 88% and 98% sensitivity and specificity, respectively (P<0.001). Conclusion: Conclusively, this study proved that IL27and IL35 could identify AML patients from healthy subjects, and their overexpression denotes poor prognosis. Based on the simplicity and wide availability of their detection technique we recommend the inclusion of IL27 and IL35 in the diagnostic/prognostic workup of AML; however, further longitudinal research is needed to prove their exact prognostic value.

The optimal time sequences for chemotherapy and radiation therapy after breast surgery for patients with breast cancer remains unknown. Most of published studies were done for early breast cancer patients. However, in Egypt advanced stages were the common presentation. This retrospective analysis aimed to assess the optimum sequence for our population.

Background: Management of elderly patients with glioblastoma (GBM) is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols vs short-course radiotherapy without chemotherapy. Methods: We evaluated treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the secondary endpoint is progression-free survival (PFS); patients were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS. Results: Fifty-nine patients were recruited in our study with median age 66 (range: 60– 81) years, and 47 (80%) were males. Thirty-seven patients (62.7%) had ECOG performance status (PS) ≥ 2, and 22 patients (37.3%) had PS < 2. Gross total resection (GTR) and subtotal resection (STR) were done in 49 (82.9%) patients, and the median follow-up was 12 months. Thirty-eight (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions). The median OS was 12 months (95%CI: 9.52– 14.48). Receiving conventional Rth and completion of six months adjuvant CTR were significant factors for O.S (P=0.043 and 0.026), respectively. The median PFS was nine months (95%CI: 6.13– 11.87). For univariate analysis, PS, time to start adjuvant treatment, and completion of six months CTR were significant factors for PFS. Conclusion: Conventional Rth and completion of adjuvant CTR lead to better OS, while earlier start of adjuvant treatment and the completion of adjuvant CTR were associated with a better PFS.

E15076 Background: The prognostic significance of mucinous colorectal carcinoma (MC) is controversial, potentially due to heterogonous nature of populations studied. Clinically, we noticed that the young MC patients had more frequent and earlier recurrence compared to nom-mucinous colorectal cancer patients (NMC). We performed this study to compare the oncological outcome in young patients with MC and NMC. Methods: A single-institution prospectively maintained colorectal cancer database was queried for patients with colorectal adenocarcinoma (CRC) less than 40 years of age. Medical records were reviewed for clinicopathological characteristics, treatment, and oncologic outcomes. Patients with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. The population was categorized as MC or NMC according to the presence of mucinous histology (extracellular mucin over 50%) on pathology reports. Results: We identified 84 patients who were younger than 40 years-old and underwent resection for CRC between 2003 and 2011. The mean age was 30 years and 50% were female. 44 patients (52.4%) had rectal cancer. 41 patients (48.8%) had MC histology and 43 (51%) had NMC histology. MC patients were younger (28 ± 6 years vs. 31.5 ± 6 years, p = 0.01), and MC occurred more often in men (65% vs 35%, p = 0.02). The MC and NMC study populations were not statistically different in terms of tumor site, pathological stage, T stage, N stage, m stage, differentiation degree, or the use of neoadjuvant and adjuvant therapy. MC tumors were larger in size (4.9 ± 2.8 cm vs. 3.4 ± 2.7 cm, p = 0.01) and were more likely to have angiolymphathic invasion (27.8% vs. 7.7%, p < 0.001). Five-year disease free survival (DFS) was (20.2% vs. 38.3%, p = 0.006) and five-year overall survival (OS) was (24.7% vs 47.8%, p = 0.002) for young patients with MC compared to NMC. Multivariate analysis revealed that the mucinous pathology was independent negative prognostic factor for both DFS and OS. Conclusions: Mucinous differentiation in young CRC patients is an independent poor prognostic factor predicting more frequent and earlier recurrence and reduced overall survival. Physicians need to be attentive of this association and possible novel treatment options should be explored.

Background Identifying biomarkers for early detection of hepatocellular carcinoma (HCC) remains quite challenging. In this study we aimed to estimate the number of TIE2-expressing monocytes (TEMs) cells, which display pro-tumoral activities and are defined as CD14+, TIE2+, and angiopoietin-2; and its potential use as a possible diagnostic marker in HCC patients complicating HCV induced cirrhosis. Methods Current study was conducted on 112 patients. They were divided into two groups: Group I (78 patients) with HCC complicating HCV induced cirrhosis; and group II chronic hepatitis C patients (34 patients). Both groups were compared to (age and sex-matched) healthy persons as group III (38 persons). Result The number of the circulating TEMs: CD14+ and TIE2+ monocytes were significantly higher in the peripheral blood of HCC patients than HCV LC patients and healthy controls, sensitivity and specificity for HCC diagnosis were respectively: CD14 (89.7%, 83.3%), TIE 2 (76.9%, 83.3%), and Ang-2 (76.9%, 66.7%). Moreover, analysis of the P-value and the odd’s ratio showed that CD14 has the highest predictive value for HCC. Conclusion Our results suggest that TEMs and Ang-2can be used as diagnostic markers for HCC, especially among the high-risk group of patients.