Hepatocellular carcinoma with tumor thrombus extends to the right atrium and portal vein : a case report

Hepatocellular carcinoma (HCC) is the most important primary malignant liver disease. A large proportion of patients with advanced HCC have macrovascular invasion. HCC tends to infiltrate vascular structures, particularly the portal vein and its branches, and more rarely, the hepatic veins. The intravascular tumor thrombus can affect the inferior vena cava (IVC) or even the right atrium (RA), the latter having a poor prognosis. HCC is one of the most aggressive malignant tumors. Tumor thrombus (TT) formation in advanced HCC stages is common and usually involves the hepatic or portal veins. Herein, we report a 69-year-old woman who presented with dyspnea to the emergency department. A ventilation/perfusion lung scan was performed, ruling out pulmonary embolism. Hepatopulmonary syndrome and portopulmonary hypertension were discarded with contrasted echocardiography, but a mass in the RA was detected and confirmed by cardiac magnetic resonance imaging. Abdominal computed tomography showed a liver mass with a dynamic enhancement pattern compatible with HCC and an intraluminal IVC mass extending from the hepatic vein into the RA. HCC with TT expansion to IVC and RA is rare and indicates poor prognosis. HCC with TT expansion to IVC and RA is rare and indicates poor prognosis. There is no consensus about anticoagulation or other interventions in these patients

Advances in immunotherapy for cervical cancer

Cervical cancer; Immunotherapy; RadiotherapyCáncer de cuello uterino; Inmunoterapia; RadioterapiaCàncer de coll uterí; Immunoteràpia; RadioteràpiaCervical cancer still represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. These figures are unacceptable since cervical cancer, an human papillomavirus-related malignancy, is a largely preventable disease by means of well-established screening and vaccination programs. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches represent a dismal prognosis population. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment landscape of this disease achieving historical overall survival improvements in both the post-platinum and frontline settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to earlier stages of the disease, as the locally advanced setting, whose standard of care has not changed in the last decades with still modest outcomes. As more innovative immunotherapy approaches are in clinical early development in advanced cervical cancer, promising efficacy data are emerging that may shape the future of this disease. This review summarizes the main treatment advances carried out in the field of immunotherapy throughout the past years

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy

Gastric cancer; Survival; TrastuzumabCàncer gàstric; Supervivència; TrastuzumabCáncer gástrico; Supervivencia; TrastuzumabBackground: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13–8.25] and 14.0 months (95% CI, 13.0–14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578–0.636) and 0.623 (95% CI, 0.594–0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints

Advances in the systemic treatment of therapeutic approaches in biliary tract cancer

Biliary tract cancer; Molecular testing; Next-generation sequencingCáncer del tracto biliar; Pruebas moleculares; Secuenciación de nueva generaciónCàncer del tracte biliar; Proves moleculars; Seqüenciació de nova generacióIntroduction Biliary tract cancers (BTCs) are a rare and heterogenous group with an increasing incidence and high mortality rate. The estimated new cases and deaths of BTC worldwide are increasing, but the incidence and mortality rates in South East Asia are the highest worldwide, representing a real public health problem in these regions. BTC has a poor prognosis with a median overall survival <12 months. Thus, an urgent unmet clinical need for BTC patients exists and must be addressed. Results The backbone treatment of these malignancies is chemotherapy in first- and second-line setting, but in the last decade a rich molecular landscape has been discovered, expanding conceivable treatment options. Some druggable molecular aberrations can be treated with new targeted therapies and have already demonstrated efficacy in patients with BTC, improving clinical outcomes, such as the FGFR2 or IDH1 inhibitors. Many other molecular alterations are being discovered and the treatment of BTC will change in the near future from our current clinical practice. Conclusions In this review we discuss the epidemiology, molecular characteristics, present treatment approaches, review the recent therapeutic advances, and explore future directions for patients with BTC. Due to the rich molecular landscape of BTC, molecular profiling should be carried out early. Ongoing research will bring new targeted treatments and immunotherapy in the near future

Combined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer

Colorectal cancer; Combined treatment; Immune checkpoint inhibitorsCáncer colorrectal; Tratamiento combinado; Inhibidores de puntos de control inmunitariosCàncer colorectal; Tractament combinat; Inhibidors de punts de control immunitarisIn recent years, deepening knowledge of the complex interactions between the immune system and cancer cells has led to the advent of effective immunotherapies that have revolutionized the therapeutic paradigm of several cancer types. However, colorectal cancer (CRC) is one of the tumor types in which immunotherapy has proven less effective. While there is solid clinical evidence for the therapeutic role of immune checkpoint inhibitors in mismatch repair-deficient (dMMR) and in highly microsatellite instable (MSI-H) metastatic CRC (mCRC), blockade of CTLA-4 or PD-L1/PD-1 as monotherapy has not conferred any major clinical benefit to patients with MMR-proficient (pMMR) or microsatellite stable (MSS) mCRC, reflecting 95% of the CRC population. There thus remains a high unmet medical need for the development of novel immunotherapy approaches for the vast majority of patients with pMMR or MSS/MSI-low (MSI-L) mCRC. Defining the molecular mechanisms for immunogenicity in mCRC and mediating immune resistance in MSS mCRC is needed to develop predictive biomarkers and effective therapeutic combination strategies. Here we review available clinical data from combinatorial therapeutic approaches using immunotherapy-based strategies for MSS mCRC

Hepatic Rupture as the Initial Presentation of an EGFR-Mutated Lung Adenocarcinoma: A Case Report

Metastatic hepatic rupture; Non-small cell lung carcinoma; Tyrosine kinase inhibitorRuptura hepática metastásica; Carcinoma de pulmón de células no pequeñas; Inhibidor de la tirosina quinasaRuptura hepàtica metastàtica; Carcinoma de pulmó de cèl·lules no petites; Inhibidor de la tirosina quinasaHepatic rupture is a rare complication of solid tumor malignancies, notably in lung adenocarcinomas, and carries an extremely poor overall prognosis. Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma predict benefit with tyrosine kinase inhibitors (TKIs). This case report describes a female patient who presented with a metastatic hepatic rupture and was subsequently diagnosed with EGFR-mutated lung adenocarcinoma. The tumor had an impressive response to TKI inhibitor treatment, reversing her extremely poor, short-term prognosis. We believe this unique case sheds light on the treatment management of hepatic ruptures and supports the high response rate seen with TKIs in EGFR-mutated lung cancers, regardless of the patient’s performance status

COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry

COVID-19; Resposta proinflamatòriaCOVID-19; Respuesta proinflamatoriaCOVID-19; Proinflammatory responseBackground Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post–COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae. Methods OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided. Results Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR = 0.57, 95% CI: 0.36 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found. Conclusions Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development.OnCovid is sponsored by Imperial College London and received direct project funding and infrastructural support by the NIHR Imperial Biomedical Research Centre (BRC)

Aggressive Pituitary Macroadenoma Treated With Capecitabine and Temozolomide Chemotherapy Combination in a Patient With Nelson’s Syndrome: A Case Report

Agressive pituitary tumors; Capecitabine; TemozolomideTumores hipofisarios agresivos; Capecitabina; TemozolomidaTumors hipofisaris agressius; Capecitabina; TemozolomidaNelson’s syndrome is considered a severe side effect that can occur after a total bilateral adrenalectomy in patients with Cushing’s disease. It usually presents with clinical manifestations of an enlarging pituitary tumor including visual and cranial nerve alterations, and if not treated, can cause death through local brain compression or invasion. The first therapeutic option is surgery but in extreme cases of inaccessible or resistant aggressive pituitary tumors; the off-label use of chemotherapy with capecitabine and temozolomide can be considered. However, the use of this treatment is controversial due to adverse events, lack of complete response, and inability to predict results. We present the case of a 48-year-old man diagnosed with Nelson’s syndrome with prolonged partial response and significant clinical benefit to treatment with capecitabine and temozolomide

Modification of BRCA1-associated breast cancer risk by HMMR overexpression

Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood. Here, we depict an interplay of molecular, cellular, and tissue microenvironment alterations that increase BRCA1-associated breast cancer risk. Analysis of genome-wide association results suggests that diverse biological processes, including links to BRCA1-HMMR profiles, influence risk. HMMR overexpression in mouse mammary epithelium increases Brca1-mutant tumorigenesis by modulating the cancer cell phenotype and tumor microenvironment. Elevated HMMR activates AURKA and reduces ARPC2 localization in the mitotic cell cortex, which is correlated with micronucleation and activation of cGAS-STING and non-canonical NF-kappa B signaling. The initial tumorigenic events are genomic instability, epithelial-to-mesenchymal transition, and tissue infiltration of tumor-associated macrophages. The findings reveal a biological foundation for increased risk of BRCA1-associated breast cancer. The effect of hyaluronan-mediated motility receptor (HMMR) expression in BRCA1-associated breast cancer risk remains unknown. Here, HMMR overexpression induces the activation of cGAS-STING and non-canonical NF-kappa B signalling, instigating an immune permissive environment for breast cancer development

A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials

Immunooncology; Predictive biomarkers; Tumor microenvironmentInmunooncología; Biomarcadores predictivos; Microambiente tumoralImmunooncologia; Biomarcadors predictius; Microambient tumoralBackground Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing. Methods We implemented VIGex using the nCounter platform (Nanostring) on a large clinical cohort encompassing 909 tumor samples across 45 tumor types. VIGex was developed as a continuous variable, with cutoffs selected to detect three main categories (hot, intermediate-cold and cold) based on the different inflammatory status of the tumor microenvironment. Findings Hot tumors had the highest VIGex scores and exhibited an increased abundance of tumor-infiltrating lymphocytes as compared with the intermediate-cold and cold. VIGex scores varied depending on tumor origin and anatomic site of metastases, with liver metastases showing an immunosuppressive tumor microenvironment. The predictive power of VIGex-Hot was observed in a cohort of 98 refractory solid tumor from patients treated in early-phase immunotherapy trials and its clinical performance was confirmed through an extensive metanalysis across 13 clinically annotated gene expression datasets from 877 patients treated with immunotherapy agents. Last, we generated a pan-cancer biomarker platform that integrates VIGex categories with the expression levels of immunotherapy targets under development in early-phase clinical trials. Conclusions Our results support the clinical utility of VIGex as a tool to aid clinicians for patient selection and personalized immunotherapy interventions.A.H.C. would like to acknowledge fellowship funding from the Spanish Society of Medical Oncology (SEOM), CRIS Contra el Cancer and Hold'em For Life Oncology Fellowship. This research has been funded by the Comprehensive Program of Cancer Immunotherapy & Immunology II (CAIMI-II) supported by the BBVA Foundation (grant 53/2021) and the 2020–2021 Division of Medical Oncology and Hematology (DMOH) Fellowship award at Princess Margaret Cancer Centre. VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment and the CERCA Programme from the Generalitat de Catalunya for their support of this research. Authors from VHIO acknowledge the State Agency for Research (Agencia Estatal de Investigación) for providing financial support as a Center of Excellence Severo Ochoa (CEX2020-001024-S/AEI/10.13039/501100011033). A.V. was the recipient of a project award from the FAECC (AVP/18/AECC/3219) and received funding from the Advanced Molecular Diagnostic (DIAMAV) program from the FERO Foundation. Graphical abstract was created with BioRender.com. Diagram in Figure 3B was created with SankeyMATIC (sankeymatic.com)