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Ewing sarcoma (ES) is an uncommon malignant neoplasm, mostly affecting young adults and adolescents. Surgical excision, irradiation, and combinations of multiple chemotherapeutic agents are currently used as a multimodal strategy for the treatment of local and oligometastatic disease. Although ES usually responds to the primary treatment, relapsed and primarily refractory disease remains a difficult therapeutic challenge. The growing understanding of cancer biology and the subsequent development of new therapeutic strategies have been put at the service of research in recurrent and refractory ES, generating a great number of ongoing studies with compounds that could find superior clinical outcomes in the years to come. This review gathers the current available information on the treatment and clinical investigation of ES and aims to be a point of support for future research.

Checkpoint inhibitor myocarditis is a rare but life-threatening toxicity of immunotherapy, occasionally manifesting as persistent troponin elevation. Dual checkpoint blockade with ipilimumab and nivolumab has been found to induce immune-related myocarditis in patients with metastatic melanoma. We herein report a case of smoldering immune-related myocarditis in a 54-year-old male after a single infusion of nivolumab plus ipilimumab as adjuvant treatment for completely resected stage IV melanoma. High-dose steroid treatment resulted in decrease in the levels of cardiac enzymes, without any major complications.

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the virus served as a measure to limit disease spread. Given that immunotherapy has been the cornerstone of melanoma treatment over the last several decades, further innate immunity enhancement by targeted mRNA vaccines could be the next pivotal achievement in melanoma treatment. Preclinical data coming from murine cancer models have already provided evidence of mRNA vaccines' ability to induce host immune responses against cancer. Moreover, specific immune responses have been observed in melanoma patients receiving mRNA vaccines, while the recent KEYNOTE-942 trial may establish the incorporation of the mRNA-4157/V940 vaccine into the melanoma treatment algorithm, in combination with immune checkpoint inhibition. As the existing data are further tested and reviewed, investigators are already gaining enthusiasm about this novel, promising pathway in cancer therapy.

Background: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge., Summary: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions., Key Messages: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings., (© 2022 S. Karger AG, Basel.)

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations., Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries., Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population., Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Upon the onset of a debilitating rapidly evolving condition (such as cancer or a rapidly progressing myopathy, neuropathy, respiratory disease, or a severe traumatic injury), individuals have limited time to find a new home or make radical structural modifications in their residence. How the affected patients can continue sharing the same house with their families, while meeting their own special requirements, is thus rising as a critical issue. Household and daily routine rearrangements, either temporary or permanent, may be necessary, to ameliorate the life of patients with impairments, lasting for months or even years., Objectives: Interior design may provide a highly efficient "living" palliation for debilitating medical conditions directly at patients' home-site., Methods: Research of relevant literature, using keywords "debilitating conditions," "home care," "end of life care," "care of advanced cancer patients," "care of patients with mental disorders," "home care of covid-19 affected patients," and "care of patients with degenerative illnesses.", Results: We found that patients and their relatives may not be aware of the probable interior design solutions to their daily life challenges, imposed by a disease-related impairment. In parallel, interior design experts may equally be unaware of these issues, as well as of who needs the available solutions.Similarly, medical and architectural sciences are not connected, eventually failing to meet patients' everyday needs., Conclusions: Interior architecture and health scientists are called to cooperate, aiming to provide a highly efficient and meaningful support to patients and families affected by unforeseen debilitating medical conditions., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (© Davide Mauri et al., 2021; Published by Mary Ann Liebert, Inc.)

Background: The therapeutic role of immune checkpoint inhibitors (ICIs) has represented the cutting edge of clinical research in upper gastrointestinal (GI) malignancies, with these agents now included in the armamentarium of treatment options for advanced gastric and esophageal cancers., Methods: We performed a systematic literature review and pooled analysis to map out the currently available robust clinical evidence for the use of ICIs in upper GI cancers. Immunotherapy (IO), either as monotherapy or in combination with chemotherapy, and its role in first-line, maintenance, and second-line settings, as well as in specific clinical and biological subgroups, were critically appraised. All statistical tests were 2-sided., Results: ICIs, in combination with chemotherapy, have provided statistically significant overall survival benefit in the first-line setting in gastric and gastro-esophageal adenocarcinomas (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.76 to 0.90, P < .001; based on 4 studies) and esophageal squamous cell carcinoma (HR = 0.72, 95% CI = 0.64 to 0.81, P < .001; based on 3 studies), albeit with heterogeneous efficacy according to biomarker expression. Patients with esophageal squamous cell carcinoma, and in particular high programmed cell death ligand-1 expression, derive survival benefit when treated with IO in the second-line setting (HR = 0.74, 95% CI = 0.68 to 0.82, P < .001; for any level of programmed cell death ligand-1 expression). Clinical trials interrogating the combination of IO with chemotherapy in second-line treatment should be seriously considered in upper GI adenocarcinomas. The role of maintenance IO after initial disease control is still unclear and cannot be recommended. Impressive response rates and survival benefit from IO have been reported in patients with microsatellite instability-high tumors (HR = 0.33, 95% CI = 0.19 to 0.57, P < .001), and this warrants further prospective biomarker-driven studies., Conclusions: IO is changing the treatment landscape in upper GI malignancies. The rapidly developing evidence in the field needs to be critically appraised while further validation of the existing information from ongoing trials is awaited., (© The Author(s) 2021. Published by Oxford University Press.)

Purpose: Glucose-6 phosphate dehydrogenase (G6PD) deficiency has an estimated prevalence of 5 -7.5% of the global population. Administration of some drugs in G6PD deficient patients may result in clinical conditions of varying severity, including potentially fatal sequels. For these reasons, in case of G6PD deficiency, the use of high dose toxic chemotherapy regimens in potentially curable malignancies with associated risk of tumor lysis syndrome, such as in advanced germ cell tumors, raises both physicians' preoccupations and issues for safeguard patients' health. Nonetheless no systematic information is actually available for safety in premedication to be administered, chemotherapy regimens adopted, and supportive care drugs needed to be provided in some particular situations., Methods: We present a case of a patient with metastatic testicular cancer and known g6pd deficiency, admitted in our department. We also performed a literature review in tree medical libraries searching for articles addressing the overmentioned security issues., Results: Available literature is particularly scant. nonetheless, there is no evidence contradicting the administration of cytotoxic chemotherapy to G6PD deficient individuals. Our patient was able to complete the preplaned chemotherapy cycles, without any complications., Conclusion: Given the absence of data supporting the limitation of chemotherapy to G6PD deficient patients, the latter should not be deprived of the indicated antineoplastic treatment. However, certain premedication agents must be avoided. Continuous patient monitoring during treatment may alleviate physicians' and patients' anxiety and preoccupations.

Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

Immuno-oncology (IO) with immune checkpoint inhibitors (ICIs) is the new landmark in cancer treatment. However, due to its economical-related burden and the possibility of tumor pseudoprogression with late response patterns, it is imperative to find new ways for early discrimination of patients with IO-sensitive versus IO-resistant disease. ICI-mediated antitumor responses depend on tumor immune infiltration by T-cells capable of recognizing and killing tumor cells. Nevertheless, patients may experience different responses to immunotherapy according to their tumor microenvironment and inflammatory infiltration. T-cell infiltrated tumors are referred to as 'hot' and are potential candidates for a good response to ICIs, whereas 'cold' are those tumors lacking T-cell infiltration and exhibit a narrow likelihood of response to IO therapy. Gallium-67 ( 67 Ga) scintigraphy may hold potential for separating 'hot' from 'cold' tumors, thus providing an imaging tool to distinguish 'hot' ICI-induced pseudoprogression from real early 'cold' progression. Even so, various tumors (lymphomas, lung cancer, breast cancer, hepatoma, malignant melanoma) exhibit an inherent affinity for 67 Ga that is independent of the ICI-induced immune infiltration, and this raises issues about false positivity. For that reason, future investigational studies to evaluate the prospective role of this radiotracer in the early prediction of ICI response should be confined to tumors with an inherently low 67 Ga affinity (thyroid carcinoma, gastrointestinal and genitourinary tract tumors). We describe our experience with a patient with recurrent metastatic lung adenocarcinoma under ICI therapy that was submitted to 67 Ga scanning for a fever of unknown origin and we discuss the aforementioned topics, alongside current imaging trends and future perspectives in the field., (Copyright © 2021. Published by Elsevier Ltd.)

As the incidence of malignancies in young adults is increasing, fertility preservation in cancer survivors arises as a major concern. Especially among female cancer patients, pregnancy rates are estimated to be 40% lower compared to women of the same age. Nowadays oncologists are to be preoccupied not only with their patients' successful treatment, but also with the maintenance of the potential of the latter to conceive and obtain children. Chemotherapy associated ovarian failure (COF), refers to disruption of ovarian function both as an endocrine gland and as a reproductive organ, due to previous exposure to chemotherapy agents. Although the underlying mechanism is not fully understood, it is supposed that chemotherapy agents may induce either DNA damage of premature ovarian follicle or early activation and apoptosis of them, resulting into early exhaustion of available follicle deposit. Various chemotherapy agents have been associated with COF with the highest incidence being reported for patients undergoing combination regimens. Although a variety of alternatives in order to maintain ovarian function and fertility in female cancer survivors are available, adequately established practices to do so are lacking. Thus, it is of major importance to investigate further and collect sufficient evidence, aiming to guide patients and physicians in everyday clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Mauri, Gazouli, Zarkavelis, Papadaki, Mavroeidis, Gkoura, Ntellas, Amylidi, Tsali and Kampletsas.)

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, proliferation and invasion and contributing to an immunosuppressive microenvironment. In this review, we summarize the effects of the VEGF/VEGFR pathway on non-endothelial cells and the resulting implications of anti-angiogenic agents that include direct inhibition of tumor cell growth and immunostimulatory functions. Finally, we present how previously unappreciated studies on VEGF biology, that have demonstrated immunomodulatory properties and tumor regression by disrupting the VEGF/VEGFR pathway, now provide the scientific basis for new combinational treatments of immunotherapy with anti-angiogenic agents.

To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of tele-health services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits. Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening, follow-up and radical surgeries increase patients' risk of developing metastatic disease. A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients' outcomes. A present international oncologists' panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.

During anatomical dissection of a female Caucasian cadaver in our department we observed a combination of two rare arterial patterns of the upper limb bilaterally; a superficial ulnar artery of high origin in the right upper limb and some rare variations of the left axillary artery: Right arm: The superficial ulnar artery originated from the second part of the axillary artery, before the origin of the subscapular artery. It proceeded superficially in the forearm. The axillary artery continued normally in the arm as brachial artery, and finally divided into the radial and the common interosseous artery. The normal ulnar artery was absent. The presence of the superficial ulnar artery is a rare variation given that its total incidence ranges from 0.67% to 9.38%, with only 0.17% to 2% originating from the axillary artery. Left arm: The second part of the axillary artery gave rise to a first common trunk (named A), lying between the two roots of the median nerve, which divided in two new common trunks (B and C). One of these gave origin to the subscapular and the posterior circumflex humeral artery while the other gave rise to the anterior circumflex humeral artery, two muscle twigs and then continued as profunda brachii artery. The incidence of anatomic variations of the major arteries of the upper extremities ranges from 11% to 24%. Nevertheless a pattern with three common trunks comprising the origin of the profunda brachii has not yet been cited in the literature.