Immunotherapy Combined With Standard Therapies in Head and Neck Squamous Cell Carcinoma - A Meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is a deadly disease with a poor prognosis due to late diagnosis and limited treatment options. Immunotherapy (IT) is emerging as a promising approach, especially after the failure of standard of care therapies (STs). The objective of this systematic review and meta-analysis was to evaluate whether the addition of IT to STs improves outcomes for patients with HNSCC, including overall survival (OS), progression-free survival (PFS), and quality of life (QoL). This review employed the Population Intervention Comparison and Outcome (PICO) framework to identify relevant search terms in electronic databases, and also included supplementary hand searches. Six primary research articles were selected using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) flow chart, and were critically appraised. Data extraction from these studies was conducted, and a meta-analysis was performed to aid in the generation of forest plots. The addition of IT to standard anticancer therapies was found to enhance patient outcomes, such as OS, PFS, and QoL. The toxicity profile of IT was acceptable, with minimal treatment-related deaths. The most frequently observed adverse events (AE) were related to the skin, followed by hematological toxicities. Based on our analysis, the addition of IT to STs is a suitable treatment option and is supported by current research. However, further studies are needed to investigate factors that influence treatment effectiveness and to develop optimal therapies. To achieve this, we recommend a comprehensive treatment approach that involves the multidisciplinary team (MDT) and patient assessment tools.

The educational contribution of the college of the European school of oncology (ESCO): A survey analysis of the first three years.

In July 2020, the European School of Oncology (ESO) launched ESCO www.esco.org - the College of the European School of Oncology. ESCO provides young oncologists with a structured educational pathway and access to dedicated career development benefits. The College is organized into three progressive levels which members reach by earning credits that are awarded to them as they follow the pathway and actively improve their oncology careers. In this article, we present and evaluate the success of ESCO and highlight how its stimulating structure and personalized career development opportunities satisfy and encourage oncologists (medical, surgical and radiation) to continue to develop and improve their knowledge and skills.

Hallmarks of the Tumour Microenvironment of Gliomas and Its Interaction with Emerging Immunotherapy Modalities.

Gliomas are aggressive, primary central nervous system tumours arising from glial cells. Glioblastomas are the most malignant. They are known for their poor prognosis or median overall survival. The current standard of care is overwhelmed by the heterogeneous, immunosuppressive tumour microenvironment promoting immune evasion and tumour proliferation. The advent of immunotherapy with its various modalities-immune checkpoint inhibitors, cancer vaccines, oncolytic viruses and chimeric antigen receptor T cells and NK cells-has shown promise. Clinical trials incorporating combination immunotherapies have overcome the microenvironment resistance and yielded promising survival and prognostic benefits. Rolling these new therapies out in the real-world scenario in a low-cost, high-throughput manner is the unmet need of the hour. These will have practice-changing implications to the glioma treatment landscape. Here, we review the immunobiological hallmarks of the TME of gliomas, how the TME evades immunotherapies and the work that is being conducted to overcome this interplay.

Prognostic Factors in Patients with Metastatic Spinal Cord Compression Secondary to Lung Cancer-A Retrospective UK Single-Centre Study.

PURPOSE: Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-centre study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. METHODS AND MATERIALS: We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer through the electronic database of Medway Maritime Hospital in the United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older; 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). RESULTS: The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of diagnosis with MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were cancer type (NSCLC had improved OS), the number of involved vertebrae (one to two vertebrae involvement had improved OS), and the time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and the time taken to develop motor deficits. CONCLUSIONS: Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations who were ambulatory and possessed an ECOG performance status of 1-2 demonstrated improved OS. In both the entire cohort and the NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poor OS.

Predictive biomarkers for immune checkpoint inhibitor response in urothelial cancer.

Immune checkpoint inhibitors (ICIs) are commonly used to treat patients with advanced urothelial cancer. However, a significant number of patients do not respond to ICI, and the lack of validated predictive biomarkers impedes the success of the ICI strategy alone or in combination with chemotherapy or targeted therapies. In addition, some patients experience potentially severe adverse events with limited clinical benefit. Therefore, identifying biomarkers of response to ICI is crucial to guide treatment decisions. The most evaluated biomarkers to date are programmed death ligand 1 expression, microsatellite instability/defective mismatch repair phenotype, and tumor mutational burden. Other emerging biomarkers, such as circulating tumor DNA and microbiota, require evaluation in clinical trials. This review aims to examine these biomarkers for ICI response in urothelial cancer and assess their analytical and clinical validation.

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.

Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

Advances in adoptive T-cell therapy for metastatic melanoma.

Adoptive T cell therapy (ACT) is a fast developing, niche area of immunotherapy (IO), which is revolutionising the therapeutic landscape of solid tumour oncology, especially metastatic melanoma (MM). Identifying tumour antigens (TAs) as potential targets, the ACT response is mediated by either Tumour Infiltrating Lymphocytes (TILs) or genetically modified T cells with specific receptors - T cell receptors (TCRs) or chimeric antigen receptors (CARs) or more prospectively, natural killer (NK) cells. Clinical trials involving ACT in MM from 2006 to present have shown promising results. Yet it is not without its drawbacks which include significant auto-immune toxicity and need for pre-conditioning lymphodepletion. Although immune-modulation is underway using various combination therapies in the hope of enhancing efficacy and reducing toxicity. Our review article explores the role of ACT in MM, including the various modalities - their safety, efficacy, risks and their development in the trial and the real world setting.

Pattern and risk factors of isolated local relapse among women with hormone receptor-positive and HER2-negative breast cancer and lymph node involvement: 10-year follow-up analysis of the PACS 01 and PACS 04 trials.

PURPOSE: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up. METHODS: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of different anthracycline ± taxanes-containing regimens after modified mastectomy or lumpectomy plus axillary lymph node dissection. We analyzed the data from 2,932 women with HR + /HER2- BC to evaluate the cumulative incidence of ILR and describe the factors associated with ILR. RESULTS: After a median follow-up of 9.1 years (95% CI 9.0-9.2 years), the cumulative incidence of ILR increased steadily between 1 and 10 years from 0.2% to 2.5%. The multivariable analysis showed that older age (subhazard ratios [sHR] = 0.95, 95% CI 0.92-0.99) and mastectomy (sHR = 0.39, 95% CI 0.17-0.86) were associated with lower risk of ILR, and no adjuvant endocrine therapy (sHR = 2.73, 95% CI 1.32 7-5.67) with increased risk of ILR. CONCLUSION: In this population of high-risk patients with localized HR + /HER2- BC, the risk of ILR was low but remained constant over 10 years. Younger age at diagnosis, breast-conserving surgery, and adjuvant endocrine therapy were independent risk factors of ILR.

Impact of radiation therapy on healthy tissues.

Radiation therapy has a fundamental role in the management of cancers. However, despite a constant improvement in radiotherapy techniques, the issue of radiation-induced side effects remains clinically relevant. Mechanisms of acute toxicity and late fibrosis are therefore important topics for translational research to improve the quality of life of patients treated with ionizing radiations. Tissue changes observed after radiotherapy are consequences of complex pathophysiology, involving macrophage activation, cytokine cascade, fibrotic changes, vascularization disorders, hypoxia, tissue destruction and subsequent chronic wound healing. Moreover, numerous data show the impact of these changes in the irradiated stroma on the oncogenic process, with interplays between tumor radiation response and pathways involved in the fibrotic process. The mechanisms of radiation-induced normal tissue inflammation are reviewed, with a focus on the impact of the inflammatory process on the onset of treatment-related toxicities and the oncogenic process. Possible targets for pharmacomodulation are also discussed.

From Biology to Diagnosis and Treatment: The Ariadne's Thread in Cancer of Unknown Primary.

Cancer of unknown primary (CUP) encloses a group of heterogeneous tumours, the primary sites for which cannot be identified at the time of diagnosis, despite extensive investigations. CUP has always posed major challenges both in its diagnosis and management, leading to the hypothesis that it is rather a distinct entity with specific genetic and phenotypic aberrations, considering the regression or dormancy of the primary tumour; the development of early, uncommon systemic metastases; and the resistance to therapy. Patients with CUP account for 1-3% of all human malignancies and can be categorised into two prognostic subsets according to their clinicopathologic characteristics at presentation. The diagnosis of CUP mainly depends on the standard evaluation comprising a thorough medical history; complete physical examination; histopathologic morphology and algorithmic immunohistochemistry assessment; and CT scan of the chest, abdomen, and pelvis. However, physicians and patients do not fare well with these criteria and often perform additional time-consuming evaluations to identify the primary tumour site to guide treatment decisions. The development of molecularly guided diagnostic strategies has emerged to complement traditional procedures but has been disappointing thus far. In this review, we present the latest data on CUP regarding the biology, molecular profiling, classification, diagnostic workup, and treatment.

Antibody-Drug Conjugate Revolution in Breast Cancer: The Road Ahead.

OPINION STATEMENT: Antibody drug-conjugates (ADCs) have revolutionized the treatment of many types of cancer, including breast cancer. Recently, two new ADCs have been approved, trastuzumab deruxtecan and sacituzumab govitecan; both have demonstrated impressive improvements in overall survival, trastuzumab deruxtecan in all three subtypes of metastatic breast cancer and sacituzumab govitecan in luminal and triple negative metastatic breast cancer. These drugs are the results of significant progress and innovation in the construction of the three components of an ADC, the monoclonal antibody, the payload, and the linker, and of the discovery of new target antigens. ADC engineering has profoundly changed the paradigm of cancer treatment, on one side being effective on tumors considered inherently resistant to the payload class of drugs and on the other side demonstrating activity in tumors with very low target expression. Yet, it is likely that we are just at the beginning of a new era as the identification of new targets and the introduction of new ADC constructs and combinations will expand the field of ADC rapidly over the coming years.

Advances in Ovarian Cancer Treatment Beyond PARP Inhibitors.

Ovarian cancer has become the largest cause of gynaecological cancer-related mortality. It is typically diagnosed at a late stage and has no effective screening strategy. Ovarian cancer is a highly heterogeneous disease that can be subdivided into several molecular subsets. As a result of a greater understanding of molecular pathways involved in carcinogenesis and tumor growth, targeted agents have been approved or are in several stages of development. Poly(ADP-ribose) polymerase (PARP) inhibitors and the anti-vascular endothelial growth factor (VEGF)-A antibodies are two types of approved and most effective targeted drugs for ovarian cancer at present. With the success of bevacizumab, tyrosine kinase inhibitors which could target alternate angiogenic pathways are being studied. Furthermore, many treatments targeting the PI3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathways, are being developed or are already in clinical studies. MicroRNAs have also become novel biomarkers for the therapy and clinical diagnosis of ovarian cancer. This manuscript reviews the molecular, preclinical and clinical evidence supporting the targeting of growth-dependent pathways in ovarian cancer and assesses current data related to targeted treatments beyond PARP inhibitors.

Bevacizumab in real-life patients with recurrent glioblastoma: benefit or futility?

PURPOSE: Angiogenesis plays a key role in glioblastoma, but most anti-angiogenic therapy trials have failed to change the poor outcome of this disease. Despite this, and because bevacizumab is known to alleviate symptoms, it is used in daily practice. We aimed to assess the real-life benefit in terms of overall survival, time to treatment failure, objective response, and clinical benefit in patients with recurrent glioblastoma treated with bevacizumab. METHODS: This was a monocentric, retrospective study including patients treated between 2006 and 2016 in our institution. RESULTS: 202 patients were included. The median duration of bevacizumab treatment was 6 months. Median time to treatment failure was 6.8 months (95%CI 5.3-8.2) and median overall survival was 23.7 months (95%CI 20.6-26.8). Fifty percent of patients had a radiological response at first MRI evaluation, and 56% experienced symptom amelioration. Grade 1/2 hypertension (n = 34, 17%) and grade one proteinuria (n = 20, 10%) were the most common side effects. CONCLUSIONS: This study reports a clinical benefit and an acceptable toxicity profile in patients with recurrent glioblastoma treated with bevacizumab. As the panel of therapies is still very limited for these tumors, this work supports the use of bevacizumab as a therapeutic option.

Comparative Genomic Profiling of Second Breast Cancers following First Ipsilateral Hormone Receptor-Positive Breast Cancers.

PURPOSE: We compared the mutational profile of second breast cancers (SBC) following first ipislateral hormone receptor-positive breast cancers of patient-matched tumors to distinguish new primaries from true recurrences. EXPERIMENTAL DESIGN: Targeted next-generation sequencing using the Oncomine Tumor Mutation Load Assay. Variants were filtered according to their allele frequency ≥ 5%, read count ≥ 5X, and genomic effect and annotation. Whole genome comparative genomic hybridization array (CGH) was also performed to evaluate clonality. RESULTS: Among the 131 eligible patients, 96 paired first breast cancer (FBC) and SBC were successfully sequenced and analyzed. Unshared variants specific to the FBC and SBC were identified in 71.9% and 61.5%, respectively. Paired samples exhibited similar frequency of gene variants, median number of variants per sample, and variant allele frequency of the reported variants except for GATA3. Among the 30 most frequent gene alterations, ARIDIA, NSD2, and SETD2 had statistically significant discordance rates in paired samples. Seventeen paired samples (17.7%) exhibited common variants and were considered true recurrences; these patients had a trend for less favorable survival outcomes. Among the 8 patients with available tissue for CGH analysis and considered new primaries by comparison of the mutation profiles, 4 patients had clonally related tumors. CONCLUSIONS: Patient-matched FBC and SBC analysis revealed that only a minority of patients exhibited common gene variants between the first and second tumor. Further analysis using larger cohorts, preferably using single-cell analyses to account for clonality, might better select patients with true recurrences and thereby better inform the decision-making process.