The Global Landscape on the Access to Cancer Medicines for Breast Cancer: The ONCOLLEGE Experience.

There is a growing global debate over barriers affecting the timely access to innovative anticancer therapies. Access to medicines is often traced back to the issue of costs: however, more commonly, the distance between valuable innovative treatments and the actual treatment of patients is far beyond the mere problem of financial barriers. A comprehensive approach to understand, assess to medicines should be pursued, to dissect the determinants and formulate solutions for all patients. In this chapter, we discuss drivers of access to innovation for patients with breast cancer, based on a case study of access to HER2-diagnositcs and therapeutics yielding a global landscape analysis, based on the efforts and expertise of the global collaborative group "ONCOLLEGE".

Global Landscape of the Attack of Predatory Journals in Oncology.

PURPOSE: Open-access publishing expanded opportunities to give visibility to research results but was accompanied by the proliferation of predatory journals (PJos) that offer expedited publishing but potentially compromise the integrity of research and peer review. To our knowledge, to date, there is no comprehensive global study on the impact of PJos in the field of oncology. MATERIALS AND METHODS: A 29 question-based cross-sectional survey was developed to explore knowledge and practices of predatory publishing and analyzed using descriptive statistics and binary logistic regression. RESULTS: Four hundred and twenty-six complete responses to the survey were reported. Almost half of the responders reported feeling pressure to publish from supervisors, institutions, and funding and regulatory agencies. The majority of authors were contacted by PJos through email solicitations (67.8%), with fewer using social networks (31%). In total, 13.4% of the responders confirmed past publications on PJo, convinced by fast editorial decision time, low article-processing charges, limited peer review, and for the promise of academic boost in short time. Over half of the participants were not aware of PJo detection tools. We developed a multivariable model to understand the determinants to publish in PJos, showing a significant correlation of practicing oncology in low- and middle-income countries (LMICs) and predatory publishing (odds ratio [OR], 2.02 [95% CI, 1.01 to 4.03]; P = .04). Having previous experience in academic publishing was not protective (OR, 3.81 [95% CI, 1.06 to 13.62]; P = .03). Suggestions for interventions included educational workshops, increasing awareness through social networks, enhanced research funding in LMICs, surveillance by supervisors, and implementation of institutional actions against responsible parties. CONCLUSION: The prevalence of predatory publishing poses an alarming problem in the field of oncology, globally. Our survey identified actionable risk factors that may contribute to vulnerability to PJos and inform guidance to enhance research capacity broadly.

Challenges in the management of colorectal cancer in low- and middle-income countries.

AIM: This narrative review aims to describe colorectal cancer (CRC) management landscape in low- and middle-income countries (LMICs), presenting the most recent and relevant papers on the topic. As a secondary aim, the authors suggest new ways of improving CRC patient care in LMICs. BACKGROUND: Several studies show that the incidence of colon cancer in low- and middle-income countries (LMICs) is rising. In addition to the increasing incidence, lack of early detection and impeded access to optimal multidisciplinary treatment may worsen survival outcomes. CONCLUSION: Developing quality diagnostic services in the proper health context is crucial for early diagnosis and successful therapy of CRC patients, and applying a resource-sensitive approach to prioritize essential treatments based on effectiveness and cost-effectiveness is key to overcoming barriers in LMICs, with clinical research collaborations between high-income countries (HICs) and LMICs being a helpful strategy to improve health indicators and prevent the burnout of health workers.

Advancements of ALK inhibition of non-small cell lung cancer: a literature review.

Background and Objective: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice. Methods: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed's published pivotal randomized Phase 3 trial results. Key Content and Findings: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive "brain-control". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents. Conclusions: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies.

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

PURPOSE: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively. CONCLUSION: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors.

The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

Immune-Checkpoint Inhibitors in Platinum-Resistant Ovarian Cancer.

Platinum-resistant ovarian cancer (OC) has limited treatment options and is associated with a poor prognosis. There appears to be an overlap between molecular mechanisms responsible for platinum resistance and immunogenicity in OC. Immunotherapy with single agent checkpoint inhibitors has been evaluated in a few clinical trials with disappointing results. This has prompted exploration of immunotherapy combination strategies with chemotherapy, anti-angiogenics, poly (ADP-ribose) polymerase (PARP) inhibitors and other targeted agents. The role of immunotherapy in the treatment of platinum-resistant OC remains undefined. The aim of this review is to describe the immunobiology of OC and likely benefit from immunotherapy, discuss clinical trial data and biomarkers that warrant further exploration, as well as provide an overview of future drug development strategies.

The Emerging Role of Liquid Biopsy in Gastric Cancer.

(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages. In the setting of localized disease, cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) qualitative and quantitative detection have the potential to inform on the risk of cancer recurrence and metastatic dissemination. In addition, gastric cancer-released exosomes may play an essential part in metastasis formation. In the metastatic setting, the levels of cfDNA show a positive correlation with tumor burden. There is evidence that circulating tumor microemboli (CTM) in the blood of metastatic patients is an independent prognostic factor for shorter overall survival. Gastric cancer-derived exosomal microRNAs or clonal mutations and copy number variations detectable in ctDNA may contribute resistance to chemotherapy or targeted therapies, respectively. There is conflicting and limited data on CTC-based PD-L1 verification and cfDNA-based Epstein-Barr virus detection to predict or monitor immunotherapy responses. (4) Conclusions: Although preliminary studies analyzing LBs in patients with advanced gastric cancer appear promising, more research is required to obtain better insights into the molecular mechanisms underlying resistance to systemic therapies. Moreover, validation and standardization of LB methods are crucial before introducing them in clinical practice. The feasibility of repeatable, minimally invasive sampling opens up the possibility of selecting or dynamically changing therapies based on prognostic risk or predictive biomarkers, such as resistance markers. Research is warranted to exploit a possible transforming area of cancer care.

The Potential of PI3K/AKT/mTOR Signaling as a Druggable Target for Endometrial and Ovarian Carcinomas.

AIMS: In this narrative review, we summarize the role and significance of PI3K-AKTmTOR (PAM) pathway in ovarian and endometrial cancers, providing the most recent and relevant literature on the topic and addressing options for targeting PAM along with future perspectives of drug development. BACKGROUND: Alterations of the PAM-pathway are common in both endometrial and ovarian cancers, and are described in specific histology-defined subtypes. PAM seems to be involved in critical steps of endometrial and ovarian carcinogenesis, often mechanistically involved in the acquisition of a phenotype of treatment resistance, which could be targetable. However, early clinical trials with PAMinhibitors (PAMi) have provided disappointing results, particularly when non isoform-specific inhibitors were tested in unselected populations, accompanied by an adverse safety profile. Since then, more encouraging observations have been collected when targeting specific isoforms of PAM proteins with more selective drugs, resulting in encouraging activity and more manageable toxicity. CONCLUSION: Although the rationale of inhibiting the PAM-pathway has been demonstrated in several promising preclinical studies, no Phase III clinical trial is available to demonstrate a significant benefit of PAM-inhibitors. A way to manage targeted agents is to tailor their use to particular subpopulations most likely to obtain a considerable benefit, namely pursuing an individualized, precision-medicine approach.

[Laser surgery of head and neck lesions at the National Institute of Oncology, Budapest]. / Lézermutétek az Országos Onkológiai Intézetben.

In spite of the continued expansion of non-surgical therapeutic modalities surgery still plays an important role in the treatment of head and neck cancer. Parallel with the use of conventional approaches, more sophisticated surgical approaches, like the use of laser in oncologic surgery, appeared with a more favorable outcome. Laser is a precise surgical tool, particularly when coupled to an operating microscope (with a variable spot size micromanipulator), allowing microprecision and hemostatic ability. The benefits of the use of laser are: bloodless operation field, high hit probability, "no touch" technique, ablasticity, support of tissue repair, and the lack of edema and scar formation. Between 1981 and 2008, 7934 surgical procedures were performed at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary. The aim is to present our results and experience with laser surgery of cutaneous lesions of the head and neck, oral, pharyngeal and laryngeal pathologies including cases of laryngotracheal stenosis.