Clinico-pathological differences between adenocarcinoma in the right and left colo-rectum play a role in determining the prognosis and response to treatment. Studies suggest that primary tumor location is more relevant as the disease progresses and reflects a possible difference in biology and response to therapy. This review aims to explore the clinico-pathological features of right and left colo-rectum and the impact of primary tumor location on prognosis of CRC as well as discuss the available clinical data on tumor sidedness in metastatic colorectal cancer. In so far as the clinical data of tumor sidedness is concerned, very few reviews have discussed the clinical implications of sidedness in heavily pre-treated metastatic colorectal cancer (second and subsequent lines of therapy in metastatic disease). This review aims to fill the current gap in this setting.

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Using the proprietary Big Data PharmGPS® Discovery platform, BioXcel has created a comprehensive relationship map between immune-evasion and immune-activation pathways, comprising interacting genes and all overlapping pharmacological agents and tumors. This map was used to identify clinically validated compounds that would act synergistically in combination with immune-checkpoint inhibitors (ICI) by remodelling the tumor micro-enviroment and transforming cold, non-inflamed tumors into hot immune-sensitive tumors. One of the several compounds thus identified is BXCL701, previously known as Talabostat/PT-100, a DPP inhibitor that by inducing a wide panel of cytokines and chemokines stimulates both the innate and acquired immune system. BXCL701 has a dual immuno-oncology related MOA. Via the Fibroblast Activator Protein (FAP) target, it inhibits the activation of immuno-suppressive fibroblasts and through an angiogenic related effect, it increases immune cell extravasation into the tumor tissue. Via the DPP8/9 targets, it depresses the immuno-suppressive activity of MDSCs by inducing a granulocytic differentiation while it stimulates the priming, migration and cytotoxicity of T-cells and NK cells and the formation of memory T-cells. The hypothesis that BXCL701 immune-mediated MOA would complement the action of ICIs was validated in-vivo in the syngeneic MC38 mouse model of colon adenocarcinoma. Co-administration of BXCL701 combined with anti-PD1 showed a synergistic inhibition of tumor growth as well as synergistic up-regulation of immuno-stimulatory cytokines, IL-2, IL12 and GM-CSF. The effects of the combination on the immune-phenotyping of the circulating and tumor infiltrated immune cells will also be presented. The findings support BXCL701 ability to transform the immune-suppressive tumour microenvironment to an immuno-permissive milieu sensitive to immune-checkpoint inhibitors. Further supporting the therapeutic potential of BXCL701, an analysis of genomic alterations in FAP, DPP8 and DPP9 across a wide range of tumors singled out castration-resistant prostate cancer with a high level of DPP9 amplification (14%) and overexpression of DPP8 in 50% of the patients which could make this patient population uniquely sensitive to the combination as shown by in-vitro and in-vivo experiments. This study provides further evidence of the capability of Big data analytics to generate in-silico hypothesis of synergistic combination effects that can be converted in validated therapeutic opportunities to benefit patients non- responsive to ICI therapy. Citation Format: Luca Rastelli, Snigdha Gupta, Akhil Dahiya, Zeenia Jagga, Krishnan Nandabalan, Sanatan Upmanyu. The synergy between BXCL701, a DPP inhibitor, and immune checkpoint inhibitors discovered using AI and Big Data analytics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2629. doi:10.1158/1538-7445.AM2017-2629

Background: The application of robotic staplers in surgeries has increased in recent years. Robotic platform enhances ability of the surgeon to directly control and manoeuvre staplers to achieve required angulation and sealing within the confines of the thorax and pelvis. Hence, in this study, we intended to learn the effectiveness of the SureForm™ SmartFire™ technology stapling system in various oncological procedures. Patients and Methods: Prospective study of 76 patients who underwent robotic-assisted total oesophagectomy, gastrectomies, hemicolectomies, low anterior resection/abdominoperineal resection and lobectomies/metastasectomy for respective malignancies for 16 months. Internal data log of the da Vinci surgical system for reload colour, reloads used, clamp attempts and staple fires used during each procedure along with patient’s post-operative outcomes were recorded. Results: One hundred and sixty-four firings have been made in 76 cases, with the majority being green reloads (76.8%) and average reloads for radical cystectomy 3.5, lobectomies/metastasectomy 3.44 and oesophagectomy 2.55. None of the cases had incomplete firings and required force-fire activation. In forty per cent of cases, the robotic stapler had to pause for sequential compression and seal. Seventy per cent of anterior resection procedures had at least one firing >45° beyond the laparoscopy limit. Collectively 52% SureForm stapler fires in anterior resection with >45° angle of fire. None of the cases had bleed or leak. Conclusion: SureForm™ SmartFire™ robotic staplers can be used for various oncological surgeries with minimal peri-operative leak and bleeding and has better articulation in closed spaces. Further case-matched comparative studies with laparoscopic or handheld powered staplers would be required for useful operative decision-making and analyse the clinical outcomes.

IntroductionThere are standard treatment guidelines for the surgical management of rectal cancer, that are advocated by recognized physician societies. But, owing to disparities in access and affordability of various treatment options, there remains an unmet need for personalizing these international guidelines to Indian settings.MethodsClinical Robotic Surgery Association (CRSA) set up the Indian rectal cancer expert group, with a pre-defined selection criterion and comprised of the leading surgical oncologists and gastrointestinal surgeons managing rectal cancer in India. Following the constitution of the expert Group, members identified three areas of focus and 12 clinical questions. A thorough review of the literature was performed, and the evidence was graded as per the levels of evidence by Oxford Centre for Evidence-Based Medicine. The consensus was built using the modified Delphi methodology of consensus development. A consensus statement was accepted only if ≥75% of the experts were in agreement.ResultsUsing the results of the review of the literature and experts’ opinions; the expert group members drafted and agreed on the final consensus statements, and these were classified as “strong or weak”, based on the GRADE framework.ConclusionThe expert group adapted international guidelines for the surgical management of localized and locally advanced rectal cancer to Indian settings. It will be vital to disseminate these to the wider surgical oncologists and gastrointestinal surgeons’ community in India.