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Trends in the approval of cancer therapies by the FDA in the twenty-first century
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Neutron therapy of cancer
Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.
Tumor Microenvironment Targeting Nano–Bio Emulsion for Synergistic Combinational X-Ray PDT with Oncolytic Bacteria Therapy
Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano–bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF 4 :Tb,Ce@NaGdF 4 core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano–bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano–bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T1-weighted magnetic resonance imaging. Following the image-guided X-ray PDT and anaerobic C. novyi- NT combination treatment, apoptotic cell death in cancer tissues, including both peripheral and central tumor regions, is significantly higher than in the control groups. Finally, this combination therapy approach using a nano–bio therapeutic emulsion is expected to overcome the limitations of conventional cancer therapy, resulting in increased cancer-therapeutic efficacy.
Oral microbiome and mycobiome dynamics in cancer therapy-induced oral mucositis
Cancer therapy-induced oral mucositis is a frequent major oncological problem, secondary to cytotoxicity of chemo-radiation treatment. Oral mucositis commonly occurs 7–10 days after initiation of therapy; it is a dose-limiting side effect causing significant pain, eating difficulty, need for parenteral nutrition and a rise of infections. The pathobiology derives from complex interactions between the epithelial component, inflammation, and the oral microbiome. Our longitudinal study analysed the dynamics of the oral microbiome (bacteria and fungi) in nineteen patients undergoing chemo-radiation therapy for oral and oropharyngeal squamous cell carcinoma as compared to healthy volunteers. The microbiome was characterized in multiple oral sample types using rRNA and ITS sequence amplicons and followed the treatment regimens. Microbial taxonomic diversity and relative abundance may be correlated with disease state, type of treatment and responses. Identification of microbial-host interactions could lead to further therapeutic interventions of mucositis to re-establish normal flora and promote patients’ health. Data presented here could enhance, complement and diversify other studies that link microbiomes to oral disease, prophylactics, treatments, and outcome.
Exercise Therapy and Radiation Therapy for Cancer: A Systematic Review
Exercise therapy (ET) is shown to improve toxicity and surrogates of survival for patients receiving chemotherapy. Current National Comprehensive Cancer Network (NCCN) guidelines lack recommendations for concurrent radiation therapy (RT) and ET. The main objective was to determine the impact of concurrent ET + RT with respect to (1) acceptability, feasibility, safety; and (2) to demonstrate how incorporating ET in cancer treatment can enhance patient-reported outcomes (PROs) and physical function—defined as strength or exercise capacity.
Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials’ cost-effectiveness analyses and key areas for future research.
Hadron Therapy For Cancer Treatment
The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.
Initial Feasibility and Clinical Implementation of Daily MR-Guided Adaptive Head and Neck Cancer Radiation Therapy on a 1.5T MR-Linac System: Prospective R-IDEAL 2a/2b Systematic Clinical Evaluation of Technical Innovation
This prospective study is, to our knowledge, the first report of daily adaptive radiation therapy (ART) for head and neck cancer (HNC) using a 1.5T magnetic resonance imaging-linear accelerator (MR-linac) with particular focus on safety and feasibility and dosimetric results of an online rigid registration-based adapt to position (ATP) workflow.
Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy
Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.
Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer
Hypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy.
From Structure to Function: Zn/Mn-Modified Maghemite as an Advanced Nanoplatform for Magnetic Hyperthermia and Radionuclide Therapy
The development of nanoplatforms capable of efficient heat generation and stable radionuclide delivery is essential for effective bimodal cancer therapy. Here, in this study, binary (Fe–M) and ternary (Fe–M–M′) metal oxide nanoparticles were synthesized via a polyol method optimized to produce flower-like γ-Fe 2 O 3 (maghemite) structures, with M and M′ representing Zn and/or Mn. Comprehensive structural and magnetic characterization was conducted to explain the relationship between composition, defect structure, and hyperthermic performance. The analyses revealed that cation substitution induced an Fe-site vacancy, primarily at octahedral positions, leading to local structural distortions, as confirmed by powder X-ray diffraction and pair distribution function analysis. The optimized composition, with Zn/Mn/Fe = 0.040:0.182:1, exhibited the highest concentration of vacancies and structural disorder. These vacancies altered the bonding environment, enhancing magnetic interactions at tetrahedral sites while weakening those at the octahedral positions. The resulting multicore nanoflowers (20–63 nm; core size 13–18 nm) displayed strong heating performance, with intrinsic loss power ranging from 0.34 to 5.77 nHm 2 kg –1 . The optimized sample achieved a temperature increase of 30 °C within 2 min and a specific absorption rate of 369 W g –1 . This composition was further coated with citrate (CA) and successfully radiolabeled with 177 Lu, achieving a radiolabeling yield of 92.7% and excellent stability, thus forming a robust nanoplatform for combined magnetic hyperthermia and radionuclide therapy. Biological evaluation of the optimized S5 composition revealed selective cytotoxicity toward HeLa and LS174 cells, while toxicity was significantly lower to A549, A375, and normal MRC-5 cells. Citrate coating of S5 nanoparticles (S5@CA) drastically reduced their cytotoxicity across all tested cell lines (IC 50 > 200 μg mL –1 ), confirming their enhanced biocompatibility for therapeutic applications. In HeLa cells subjected to magnetic hyperthermia, the viability decreased to approximately 84% after 30 min and 61% after 60 min of treatment, demonstrating the sustained hyperthermic effect at a controlled working temperature of 48 °C. These results underscore the effectiveness of cation substitution and vacancy engineering in tailoring the functional properties of maghemite-based nanomaterials for advanced multimodal cancer therapies.
Magneto mitochondrial dysfunction mediated cancer cell death using intracellular magnetic nano-transducers
Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein, magnetic nano-transducers, which convert external magnetic fields into physical stress, are designed to induce mitochondrial dysfunction to remotely kill cancer cells. Spindle-shaped iron oxide nanoparticles were synthesized to maximize cellular internalization and magnetic transduction. The magneto-mechanical transduction of nano-transducers in mitochondria enhances cancer cell apoptosis by promoting a mitochondrial quality control mechanism, referred to as mitophagy. Furthermore, in the liver cancer animal model, nano-transducers are infused into the local liver tumor via the hepatic artery. After treatment with a magnetic field, in vivo mitophagy-mediated cancer cell death was also confirmed by mitophagy markers, mitochondrial DNA damage assay, and TUNEL staining of tissues. This study is expected to contribute to the development of nanoparticle-mediated mitochondria-targeting cancer therapy and biological tools, such as magneto-genetics.
A Prospective Randomized Trial of the Influence of Music on Anxiety in Patients Starting Radiation Therapy for Cancer
One of the most downloaded articles in 2017 from the International Journal of Radiation Oncology, Biology, and Physics was a study suggesting that music therapy during radiation therapy (RT) simulation substantially reduces anxiety. To further evaluate the potential of music's clinical efficacy in the context of radiation therapy, we conducted a randomized trial evaluating the influence of genre-based music chosen by the study participant on anxiety during the first RT treatment session with a method that is applicable to routine clinical practice.
Generating High-Quality Lymph Node Clinical Target Volumes for Head and Neck Cancer Radiation Therapy Using a Fully Automated Deep Learning-Based Approach
To develop a deep learning model that generates consistent, high-quality lymph node clinical target volumes (CTV) contours for head and neck cancer (HNC) patients, as an integral part of a fully automated radiation treatment planning workflow.
Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy
Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy.
Theoretical Evaluation of the Radiation Hazards from Cosmic Rays Within Space Vehicles
We may summarize our efforts as follows: a. Improvement of our calculations of the radial dose distribution from delta rays ejected in the passage of heavy ions through matter through the application of new data to a previous calculation by Kobetich and Katz (1968). Supplementing this calculation, we have found the radial distribution of electron energy spectra and the radial distribution of microdosimetric quantities (Cucinotta et al, 1996, 1997). b. Extension of the Katz model of cellular survival to bacteria, to lethal mutations in C. Elegans in vivo, to mutation induction in vitro, to thindown in radiobiology (observed experimentally at GSI, Darmstadt, and there called "Darmstadt hooks", predicted by Katz theory years before GSI was constructed). c. Coupling the Katz theory of RBE to the NASA theory of the diffusion of heavy ion beams in matter to yield predictions of the effects for monoenergetic heavy ion beams as well as range modulated beams used for cancer therapy. Here we have directed attention to the role of "ion-kill" (the effects produced by heavy ions passing through the nucleus of a cell), responsible for increased RBE, decreased OER, and reduced repair. We predict that the use of beams of heavy ions in cancer therapy will create late effect problems for fractionated therapy. We highlight also the damage by "ion-kill", from single heavy ions in the cosmic rays, to the central nervous system in space flight. d. The coupling of Katz theory and the NASA theory of heavy ion diffusion and penetration through matter, and knowledge of the space radiation environment, has been applied to design of shielding, to the cell damage in space flight.
Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer
Abstract Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of >530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy.