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Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI), that acts as an agonist to toll-like receptor 3 and targets the cytosolic helicase melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I. By mimicking the effect of a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons (IFNs), induction of apoptosis and enhancement of immunogenic cell death. Clinical data are available from the first-in-human study (NCT02828098) which evaluated single intratumoral (IT) BO-112 (Part 1; N = 16) and the combination of IT BO-112 with pembrolizumab or nivolumab (Part 2; N = 28). Part 2 showed an ORR of 11% and DCR of 46% in patients with multiple tumor types. Of them, 2 out of 10 (20%) patients with melanoma resistant to anti PD-1 achieved a partial response. Safety profile of BO-112, both as single agent and in combination with anti-PD-1, is manageable and currently characterized by Grade 1 fever and other flu-like symptoms. A phase 2 clinical study of IT BO-112 in combination with pembrolizumab in patients with liver metastases from colorectal or gastric/gastro-esophageal junction cancer patients is currently ongoing. Methods: Phase 2, single arm, open label study of IT BO-112 in combination with pembrolizumab in patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment (NCT04570332). BO-112 will be administered once weekly (QW) in 1 to 8 tumor lesions, total dose 1-2 mg (depending on the number of injected lesions), for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab 200 mg will be administered Q3W. Key eligibility criteria include histologically confirmed, unresectable cutaneous or mucosal melanoma with known BRAF status. Patients must have progressed on or after treatment with an anti-PD-1/L1 mAb. At least one lesion RECIST 1.1 measurable and amenable for weekly IT injection is needed. Primary efficacy variable is ORR by RECIST 1.1, assessed by independent central radiologist (by QUIBIM Precision platform). Secondary efficacy variables include clinical activity in terms of DCR, DOR, PFS, OS, iRECIST, safety and PKs. Exploratory objectives include itRECIST and evaluation of tumor microenvironment (by Pangaea laboratory). A 1-sided alpha of 4.19% and power of 81.8% are used. A total of 40 patients will be enrolled. If less than 8 patients out of 40 have ORR, the study will not meet the statistical bar. Study was approved on 14 December in Spain; enrollment is open; two sites are active as of 18 December 2020. Nineteen sites (12 in Spain and 7 in France) are planned to be activated. Citation Format: Iván Márquez-Rodas, Miguel Fernández de Sanmamed Gutiérrez, María González Cao, Ana M. Arance, Alfonso Berrocal, Eduardo Castañon, Sofía España, Pablo Cerezuela-Fuentes, Juan F. Rodríguez-Moreno, Pilar López Criado, Juana Oramas, Luis de la Cruz Merino, Stéphane Dalle, Caroline Dutriaux, Julie Charles, Caroline Robert, Brigitte Dréno, Henri Montaudié, Philippe Saiag, Javier Sánchez-López, María Rojas, Helena Escuin-Ordinas, Vanesa Pons Sanz, Sonia Maciá, Marisol Quintero. Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT233.

Small cell lung cancer is the most common cause of paraneoplastic Cushing's syndrome. The definitive treatment consists in surgical removal of the tumour, which is not possible in most of these cases (they are often diagnosed at advanced stages), and therefore it is frequently necessary adding the drug ketoconazol. We hereby present the case of a patient diagnosed with a metastatic carcinoma of unknown origin associated with two paraneoplastic syndromes: a Cushing's syndrome and a sensitive-motor axonal neuropathy, a very uncommon association.

We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report.

he worldwide incidence of oesophageal cancer is increasing. Adenocarcinoma, associated with gastroesophageal reflux disease, Barrett's oesophagus, obesity, male sex and white race, is the most rapidly increasing type of tumour in many Western countries [1], originating in the lower third of the oesophagus or bridging the gastroesophageal junction. Squamous carcinoma, associated with tobacco and alcohol abuse, male sex and black race, has been stable or decreasing in incidence, with the majority of tumours located in the upper two thirds of the thoracic oesophagus. Oesophageal cancer, whether squamous cell or adenocarcinoma, has been managed as a single disease entity because the survival prognosis was similar. Most clinical trials included either squamous cell carcinoma only or a combination of the two histologies, such that little was learned about adenocarcinoma as a distinct entity. With the advent of newer multimodality therapeutic approaches and a greater understanding of the molecular and pathologic progression of these two entities, it is now clear that they should be studied separately with the expectation that the therapies and prognosis will diverge [2]. Historically, surgical resection as a single therapy was the standard treatment for localised squamous cell and adenocarcinoma of the oesophagus, with cure rates reported in the range of 10–20%. The question is if surgery alone is still appropriate for oesophageal cancer. In order to evaluate the real impact of multimodality treatment strategies on disease control, and to better plan the most appropriate therapeutic option, our first objective when facing oesophageal cancer should be to reach the most accurate staging. Initially, clinical history, physical exam, blood test and nutritional status evaluation should be routinely performed. Conventional endoscopy with tumour biopsy and barium radiographies (especially useful in case of stenotic lesions) are also mandatory. Endoscopic ultrasound (EUS) is the method of choice for staging T1–T3 tumours and N status, including EUS-guided fine-needle aspiration. In order to rule out infiltration of adjacent structures, distant lymphadenopathies and distant metastases, computed tomography (CT) or magnetic resonance imaging (MRI) are used; however, positron emission tomography (PET) and PET-CT are superior in this respect [3], and should be mandatory to rule out metastatic disease before planning

The majority of deaths due to breast cancer occur in the context of complications secondary to metastatic disease. Trastuzumab, as a second line treatment, has shown a 15% objective response rate in patients with metastatic breast cancer. We present the case of a patient with two breast tumours, the second of more aggressive characteristics, with negative hormone receptors and c-erb-B2 +++, and with few therapeutic options due to her hepatic insufficiency secondary to metastatic disease; she was administered herceptin as monotherapy, and she had a complete clinical response. Trastuzumab has revolutionised the management of patients with metastatic breast cancer and Her-2- neu overexpression. Its combination with chemotherapy agents achieves a synergic activity.