Cancers

Meningiomas are the most common type of intracranial brain tumors in adults. The majority of meningiomas are benign with a low risk of recurrence after resection. However, meningiomas defined as grades II or III, according to the 2016 World Health Organization (WHO) classification, termed high-grade meningiomas, frequently recur, even after gross total resection with or without adjuvant radiotherapy. Boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) are novel treatment modalities for malignant brain tumors, represented by glioblastomas. Although BNCT is based on a nuclear reaction and PDT uses a photochemical reaction, both of these therapies result in cellular damage to only the tumor cells. The aim of this literature review is to investigate the possibility and efficacy of BNCT and PDT as novel treatment modalities for high-grade meningiomas. The present review was conducted by searching PubMed and Scopus databases. The search was conducted in December 2019. Early clinical studies of BNCT have demonstrated activity for high-grade meningiomas, and a phase II clinical trial is in progress in Japan. As for PDT, studies have investigated the effect of PDT in malignant meningioma cell lines to establish PDT as a treatment for malignant meningiomas. Further laboratory research combined with proper controlled trials investigating the effects of these therapies is warranted.

Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma. This review describes the molecular targets and pathogenesis as well as the current progress in chemotherapeutic development and other novel therapies in the clinical setting for the treatment of glioblastoma.

Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

The tumor suppressor and transcription factor p53 plays critical roles in tumor prevention by orchestrating a wide variety of cellular responses, including damaged cell apoptosis, maintenance of genomic stability, inhibition of angiogenesis, and regulation of cell metabolism and tumor microenvironment. TP53 is one of the most commonly deregulated genes in cancer. The p53-ARF-MDM2 pathway is deregulated in 84% of glioblastoma (GBM) patients and 94% of GBM cell lines. Deregulated p53 pathway components have been implicated in GBM cell invasion, migration, proliferation, evasion of apoptosis, and cancer cell stemness. These pathway components are also regulated by various microRNAs and long non-coding RNAs. TP53 mutations in GBM are mostly point mutations that lead to a high expression of a gain of function (GOF) oncogenic variants of the p53 protein. These relatively understudied GOF p53 mutants promote GBM malignancy, possibly by acting as transcription factors on a set of genes other than those regulated by wild type p53. Their expression correlates with worse prognosis, highlighting their potential importance as markers and targets for GBM therapy. Understanding mutant p53 functions led to the development of novel approaches to restore p53 activity or promote mutant p53 degradation for future GBM therapies.

Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies.

Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients’ quality of life.

Osteosarcoma (OS) is the most common primary bone tumor, mainly occurring in children and adolescents. Current standard therapy includes tumor resection associated with multidrug chemotherapy. However, patient survival has not evolved for the past decades. Since the 1970s, the 5-year survival rate is around 75% for patients with localized OS but dramatically drops to 20% for bad responders to chemotherapy or patients with metastases. Resistance is one of the biological processes at the origin of therapeutic failure. Therefore, it is necessary to better understand and decipher molecular mechanisms of resistance to conventional chemotherapy in order to develop new strategies and to adapt treatments for patients, thus improving the survival rate. This review will describe most of the molecular mechanisms involved in OS chemoresistance, such as a decrease in intracellular accumulation of drugs, inactivation of drugs, improved DNA repair, modulations of signaling pathways, resistance linked to autophagy, disruption in genes expression linked to the cell cycle, or even implication of the micro-environment. We will also give an overview of potential therapeutic strategies to circumvent resistance development.

Purpose: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow’s clinical feasibility and early experience in the case of 16 liver and pancreas patients. Methods: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Results: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70–90 min for a single fraction and 55–90 min for five fractions. The pancreas sessions were 54–85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9–96.1% and 99/95.4–100%, respectively. Conclusion: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

Đau xương do ung thư (CIBP) là biến chứng đau đớn và phổ biến nhất ở bệnh nhân có di căn vào xương. Nó gây ra sự giảm sút đáng kể về chất lượng cuộc sống của bệnh nhân. Các phương pháp điều trị giảm đau hiện có cho CIBP, chẳng hạn như opioid nhắm vào hệ thần kinh trung ương, đi kèm với những tác dụng phụ nghiêm trọng cũng như nguy cơ lạm dụng và nghiện. Do đó, rất cần các phương pháp điều trị thay thế cho CIBP. Mặc dù các cơ chế chính xác của CIBP vẫn chưa được làm sáng tỏ hoàn toàn, các nghiên cứu gần đây sử dụng các mô hình tiền lâm sàng đã chỉ ra vai trò của vi môi trường tủy xương (ví dụ: tế bào hủy xương, tế bào tạo xương, đại thực bào, tế bào mast, tế bào gốc trung mô và nguyên bào sợi) trong sự phát triển của CIBP. Một số thử nghiệm lâm sàng đã được thực hiện dựa trên những phát hiện này. CIBP là một tình trạng phức tạp và khó khăn hiện chưa có các phương pháp điều trị hiệu quả tiêu chuẩn ngoài opioid. Rõ ràng cần có thêm các nghiên cứu để hiểu sâu hơn về tình trạng đau đớn này và phát triển các liệu pháp nhắm mục tiêu hiệu quả và an toàn hơn.

Nền tảng: Bệnh nhân cao tuổi nhận thuốc chống ung thư có thể có nguy cơ cao hơn trong việc phát triển các độc tính liên quan đến điều trị so với những bệnh nhân trẻ hơn. Tuy nhiên, một cơ sở dược động học (PK) tiềm năng cho nguy cơ tăng lên này vẫn chưa được thiết lập một cách nhất quán. Do đó, mục tiêu của nghiên cứu này là xem xét có hệ thống ảnh hưởng của tuổi tác đến PK của các tác nhân chống ung thư thường được áp dụng cho bệnh nhân ung thư vú cao tuổi. Phương pháp: Một cuộc tìm kiếm tài liệu đã được thực hiện sử dụng cơ sở dữ liệu điện tử PubMed, Tóm tắt đặc điểm sản phẩm (SmPC) và các đánh giá phê duyệt thuốc có sẵn, như đã được công bố bởi EMA và FDA. Các công bố mô tả các hồ sơ PK liên quan đến tuổi của các thuốc chống ung thư chọn lọc trong điều trị ung thư vú, ngoại trừ các hợp chất nội tiết, đã được chọn và đưa vào xem xét. Kết quả: Bài đánh giá này trình bày một cái nhìn tổng quan về các dữ liệu có sẵn mô tả ảnh hưởng của tuổi tác tăng lên đến PK của các thuốc chống ung thư chọn lọc được sử dụng trong điều trị ung thư vú. Kết luận: Các dữ liệu được công bố chọn lọc cho thấy sự khác biệt về tác động và mức độ của tuổi tác tăng lên đến PK của một số thuốc chống ung thư. Có thể tồn tại những khác biệt PK liên quan đến tuổi có ý nghĩa lâm sàng đối với các thuốc anthracycline và các tác nhân platin. Trong phần lớn các trường hợp, tuổi không phải là một dấu hiệu thay thế tốt cho PK của thuốc chống ung thư, và trạng thái sinh lý của bệnh nhân cá thể có thể được tiếp cận tốt hơn bằng cách xem xét chức năng cơ quan, Điểm cộng đồng Charlson hoặc đánh giá chức năng lão khoa.