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1.
J Nanobiotechnology ; 22(1): 156, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589867

RESUMO

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.


Assuntos
Lipossomos , Neoplasias , Humanos , Lipossomos/metabolismo , Neoplasias/radioterapia , Neoplasias/metabolismo , Macrófagos/metabolismo , Imunoterapia , Etanol/metabolismo , Linhagem Celular Tumoral
2.
Ned Tijdschr Tandheelkd ; 131(4): 159-162, 2024 Apr.
Artigo em Holandês | MEDLINE | ID: mdl-38591119

RESUMO

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.


Assuntos
Neoplasias , Humanos , Criança , Neoplasias/radioterapia , Saúde Bucal , Sobreviventes , Atenção à Saúde , Fatores de Risco
3.
ACS Nano ; 18(14): 10288-10301, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38556985

RESUMO

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.


Assuntos
Ferroptose , Neoplasias , Radioterapia Guiada por Imagem , Humanos , Espécies Reativas de Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Apoptose , Peróxido de Hidrogênio , Linhagem Celular Tumoral
4.
J Med Radiat Sci ; 71 Suppl 2: 3-5, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558531

RESUMO

The nearing completion of the Australian Bragg Centre for Proton Therapy and Research marks a transformative leap in cancer care in Australia. Highlighting the precision and potential of particle therapy in reducing long-term side effects, particularly in paediatric and rare cancers, this editorial underscores Australia's commitment to integrating this innovative modality into national healthcare, despite challenges in accessibility and cost.


Assuntos
Atenção à Saúde , Neoplasias , Humanos , Criança , Austrália , Neoplasias/radioterapia
5.
Support Care Cancer ; 32(3): 201, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427125

RESUMO

BACKGROUND: After receiving radiation therapy, 60%-95% of patients with cancer develop radiodermatitis, which causes pain, wound infection, and poor quality of life. Glutamine is a popular nutritional supplement for patients with cancer. Several studies examined the usefulness of glutamine for reducing radiodermatitis. However, there is still no consolidated evidence for clinical use. METHODS: We searched PubMed, Embase, Cochrane Library, CINAHL PLUS, and the China Knowledge Resource Integrated Database for the relevant literature published up to March 2023, without language restrictions. Two reviewers screened, filtered, and appraised these articles independently, and their data were pooled using a random-effects model. RESULTS: Five randomized controlled trials (RCTs) with 218 participants were analyzed. The incidence of radiodermatitis in the glutamine group (89/110) was significantly lower than in the placebo group (99/108; risk ratio [RR], 0.90; 95% CI, 0.81-1.00; p = 0.05; I2 = 7%). The incidence of moderate to severe radiodermatitis was significantly lower in the glutamine group than in the placebo group (RR, 0.49; 95% CI, 0.32-0.76; p = 0.001; I2 = 52%). Moreover, subgroup analysis demonstrated heterogeneity (I2 = 52%) for moderate to severe radiodermatitis, the risk of which might be significantly reduced by a glutamine dose of 20-30 g/day (RR, 0.60; 95% CI, 0.41-0.87; I2 = 0%). CONCLUSION: The meta-analysis indicate that glutamine might lead to a lower incidence of radiodermatitis, and that a glutamine dose of 20-30 g/day might decrease the incidence of moderate to severe dermatitis. Thus, the serious impact of radiodermatitis on treatment follow-up makes the clinical use of glutamine even more important. PROSPERO number: CRD42021254394.


Assuntos
Neoplasias , Radiodermatite , Humanos , Glutamina/uso terapêutico , Radiodermatite/tratamento farmacológico , Radiodermatite/etiologia , Radiodermatite/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias/complicações , Neoplasias/radioterapia , Suplementos Nutricionais
6.
Yakugaku Zasshi ; 144(3): 291-297, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38432939

RESUMO

Recently, radiotheranostics, which systematically combines diagnosis by nuclear medicine imaging and treatment by internal radiotherapy, constitutes a new modality in cancer treatment, with some clinical reports showing marked effects on cancer. We have been developing multifunctional chelates containing a target recognition unit, a radiation release unit, and a radioactivity pharmacokinetics control unit in the same molecule to develop efficient agents for cancer radiotheranostics based on chemical control of radioactivity pharmacokinetics. Using these compounds, we have achieved improved cancer accumulation and reduced renal accumulation in tumor-bearing mice, and have developed novel hybrid radiotheranostic agents that can be applied to simultaneously perform target-specific molecular imaging using γ-ray emitting radionuclides and internal radiotherapy using α-particle-emitting radionuclides. For example, 111In/225Ac-labeled PSMA-DA1, which targets prostate-specific membrane antigen (PSMA) for radiotheranostics, achieved clear in vivo imaging of PSMA in tumor-bearing mice and showed marked tumor growth inhibition. In addition to PSMA, this platform for radiotheranostics has also shown efficacy against various cancer target molecules, including carbonic anhydrase IX (CA-IX), which is highly expressed in hypoxic regions of cancer, and glucagon-like peptide-1 receptor (GLP-1R), which is highly expressed in insulinomas. This review presents these recent results of our studies on radiotheranostics for cancer.


Assuntos
Neoplasias , Radioatividade , Masculino , Animais , Camundongos , Quelantes , Hipóxia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioisótopos
7.
BMC Med Educ ; 24(1): 317, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509515

RESUMO

BACKGROUND: The shortage of skilled healthcare professionals in pediatric oncology and the limited access to training programs remain significant challenges in Nigeria and sub-Saharan Africa. The the Pediatric Radiation Oncology (Virtual) Course, 'PedROC' project aims to contribute to improving pediatric cancer outcomes in Nigeria by increasing the capacity of radiation oncology professionals. To address the gap in access to pediatric radiation oncology professional development, the PedROC project was created, harnessing technology to improve radiation oncology training via a curriculum delivered through web-conferencing. This study aimed to evaluate the effectiveness of the PedROC pilot in enhancing the capacity, confidence, and skill of radiation oncologists in decision-making, prescribing, and treatment planning of radiotherapy for children diagnosed with cancer. METHODS: A multidisciplinary faculty of specialists in radiation oncology, pediatric oncology, oncology nursing, radiation therapy technology, and medical physics collaborated to identify the key learning needs in pediatric radiation oncology in the country. The team collaborated to develop a comprehensive curriculum covering the most common pediatric cancers in sub-Saharan Africa for the training program. The training course was conducted over two days, delivering twenty-four half-hour sessions for a total of 12 h, from July 31 to August 01, 2021. RESULTS: Analysis of pre and post - training surveys showed a significant increase in self-reported confidence measures across all domains among radiation oncologists. The program successfully improved participants' knowledge and confidence levels in managing common pediatric cancers using radiotherapy, particularly addressing radiotherapy-specific issues such as appropriate dose, target volume delineation, treatment planning, dose constraints, and plan evaluation. CONCLUSION: The PedROC pilot showed the efficacy of this model in enhancing the capacity and confidence of radiation oncology professionals involved in the treatment of pediatric cancer. The findings indicate that technology holds significant potential to increase pediatric radiation oncology capacity in Africa, ensuring improved access to proper treatment and ultimately improving pediatric cancer outcomes.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Criança , Radioterapia (Especialidade)/educação , Oncologia/educação , África Subsaariana , Neoplasias/radioterapia , Currículo
8.
Support Care Cancer ; 32(4): 234, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502353

RESUMO

PURPOSE: Culturally and linguistically diverse (CALD) cancer patients report unmet informational and emotional needs when receiving radiotherapy (RT). This feasibility study aimed to evaluate the clinical use of an instant translation device (ITD) to facilitate communication between Mandarin-speaking patients and radiation therapists (RTTs) within the Australian public RT setting. The primary aim was to assess the ability to convey information relating to daily patient care and build rapport using the device. METHODS: A single-arm prospective interventional trial was employed with patient and RTT participants. Eligible patient participants were aged 18 years or older, diagnosed with cancer, referred for RT with self-reported Mandarin as the primary language spoken at home. Patients who had previously received RT were excluded. Consenting patient participants completed a baseline assessment of health literacy (REALM-SF) and English proficiency (LexTALE). Surveys were administered to patients and consenting RTTs at the cessation of treatment, forming two distinct participant groups. Descriptive statistics were used to compare participant groups. RESULTS: Eleven patients and 36 RTTs were recruited to the study. Descriptive statistics demonstrated participant group agreement in conveying treatment instructions, though differing experiences were reported against general conversation. Although the reporting of technical difficulties was inconsistent, both groups recommended the application of the ITD within the RT domain. CONCLUSION: This feasibility study demonstrated encouraging accounts of patients and RTTs with regard to ITD use in the context of RT treatment. Expanded, multi-institutional recruitment is required to yield statistical significance, inform the impact of the device, and determine requisite training requirements. TRIAL REGISTRATION: HREC reference number: LNR/18/PMCC/115 (18/100L). HREC approval date: 10 July 2018.


Assuntos
Comunicação , Neoplasias , Humanos , Austrália , Idioma , Neoplasias/radioterapia , Neoplasias/psicologia , Estudos Prospectivos
9.
J Cancer Res Clin Oncol ; 150(3): 167, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546873

RESUMO

PURPOSE: The decision-making process regarding cancer treatment is emotionally challenging for patients and families, harboring the risk of decision regret. We aimed to explore prevalence and determinants of decision regret following radiotherapy. METHODS: This cross-sectional observational study was conducted at a tertiary cancer center to assess decision regret following radiotherapy. The study employed the German version of the Ottawa Decision Regret Scale (DRS) which was validated in the study population. Decision regret was categorized as absent (0 points), mild (1-25 points), and strong (> 25 points). Various psychosocial outcome measures were collected using validated questionnaires to identify factors that may be associated with decision regret. RESULTS: Out of 320 eligible patients, 212 participated, with 207 completing the DRS. Median age at start of radiotherapy was 64 years [interquartile range (IQR), 56-72], genders were balanced (105 female, 102 male), and the most common cancer types were breast (n = 84; 41%), prostate (n = 57; 28%), and head-and-neck cancer (n = 19; 9%). Radiotherapy was applied with curative intention in 188 patients (91%). Median time between last radiotherapy fraction and questionnaire completion was 23 months (IQR, 1-38). DRS comprehensibility was rated as good or very good by 98% (196 of 201) of patients. Decision regret was reported by 43% (n = 90) as absent, 38% (n = 78) as mild, and 18% (n = 38) as strong. In the multiple regression analysis, poor Eastern Cooperative Oncology Group performance status, low social support, and dissatisfaction with care were independent risk factors for higher decision regret after radiotherapy. CONCLUSIONS: The German version of the DRS could be used to assess decision regret in a diverse cohort of cancer patients undergoing radiotherapy. Decision regret was prevalent in a considerable proportion of patients. Further studies are necessary to validate these findings and obtain causal factors associated with decision regret after radiotherapy.


Assuntos
Tomada de Decisões , Neoplasias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Emoções , Neoplasias/radioterapia , Fatores de Risco , Idoso
10.
J Med Radiat Sci ; 71 Suppl 2: 6-9, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38425125

RESUMO

The burden of cancer in Asia Pacific, a region home to over four billion people, is growing. Because of sheer demographics alone, the Asia Pacific region arguably has the highest number of patients who can benefit from protons over conventional x-rays. However, only 39 out of 113 proton facilities globally are in Asia Pacific, and 11 of them are in low- and middle-income countries where 95% of the regional population reside. We draw attention to present resource distribution of proton therapy in Asia Pacific, highlight disparities in access, and suggest steps forward.


Assuntos
Neoplasias , Terapia com Prótons , Humanos , Ásia/epidemiologia , Neoplasias/radioterapia
11.
Indian J Cancer ; 61(Suppl 1): S1-S28, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424680

RESUMO

ABSTRACT: PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring disease-specific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology.


Assuntos
Neoplasias , Medicina Nuclear , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos , Fluordesoxiglucose F18
12.
Crit Rev Oncol Hematol ; 196: 104325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462151

RESUMO

Abscopal effects are characterized by the emergence of neoplasms in regions unrelated to the primary radiation therapy site, displaying a gradual attenuation or regression throughout the progression of radiation therapy, which have been of interest to scientists since Mole's proposal in 1953. The incidence of abscopal effects in radiation therapy is intricately linked to the immune system, with both innate and adaptive immune responses playing crucial roles. Biological factors impacting abscopal effects ultimately exert their influence on the intricate workings of the immune system. Although abscopal effects are rarely observed in clinical cases, the underlying mechanism remains uncertain. This article examines the biological and physical factors influencing abscopal effects of radiotherapy. Through a review of preclinical and clinical studies, this article aims to offer a comprehensive understanding of abscopal effects and proposes new avenues for future research in this field. The findings presented in this article serve as a valuable reference for researchers seeking to explore this topic in greater depth.


Assuntos
Neoplasias , Humanos , Neoplasias/radioterapia , Radioterapia/métodos
13.
Eur Biophys J ; 53(3): 123-131, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451329

RESUMO

We present a new phenomenon resulting from the interaction of magnetic beads with cancer cells in a laser trap formed on a slide containing a depression 16.5 mm in diameter and 0.78 mm of maximum depth. This phenomenon includes the apparent formation and expansion of a dark bubble that attracts and incinerates surrounding matter when it explodes, which leads to a plasma emitting intense radiation that has the appearance of a star on a microscopic scale. We have observed the star-like phenomenon for more than 4 years, and the intensity depends on the laser's power. Measuring the laser power of the dark bubble shows the entrapment of electromagnetic energy as it expands.


Assuntos
Imãs , Neoplasias , Lasers , Neoplasias/radioterapia
14.
BMC Cancer ; 24(1): 324, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459443

RESUMO

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Irã (Geográfico)/epidemiologia , Neoplasias/epidemiologia , Neoplasias/radioterapia , Aceleradores de Partículas , Inquéritos e Questionários , Radioterapia/métodos
15.
Nat Med ; 30(3): 690-698, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454124

RESUMO

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), female breast cancer (OR = 1.42, 95% CI = 1.27-1.58), thyroid cancer (OR = 1.48, 95% CI = 1.31-1.67), squamous cell carcinoma (OR = 1.20, 95% CI = 1.00-1.44) and melanoma (OR = 1.60, 95% CI = 1.31-1.96); however, the association for colorectal cancer was not significant (OR = 1.19, 95% CI = 0.94-1.52). An investigation of joint associations between PRSs and radiotherapy found more than additive increased risks of basal cell carcinoma, and breast and thyroid cancers. For survivors with radiotherapy exposure, the cumulative incidence of subsequent cancer by age 50 years was increased for those with high versus low PRS. These findings suggest a degree of shared genetic etiology for these malignancy types in the general population and survivors, which remains evident in the context of strong radiotherapy-related risk.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Carcinoma Basocelular , Neoplasias , Neoplasias Cutâneas , Neoplasias da Glândula Tireoide , Humanos , Criança , Feminino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/radioterapia , 60488 , Estudo de Associação Genômica Ampla , Fatores de Risco , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética
16.
Int Rev Cell Mol Biol ; 383: 145-190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359968

RESUMO

Radiation therapy is a cornerstone of modern cancer treatment. Treatment is based on depositing focal radiation to the tumor to inhibit cell growth, proliferation and metastasis, and to promote the death of cancer cells. In addition, radiation also affects non-tumor cells in the tumor microenvironmental (TME). Radiation resistance of the tumor cells is the most common cause of treatment failure, allowing survival of cancer cell and subsequent tumor growing. Molecular radioresistance comprises genetic and epigenetic characteristics inherent in cancer cells, or characteristics acquired after exposure to radiation. Furthermore, cancer stem cells (CSCs) and non-tumor cells into the TME as stromal and immune cells have a role in promoting and maintaining radioresistant tumor phenotypes. Different regulatory molecules and pathways distinctive of radiation resistance include DNA repair, survival signaling and cell death pathways. Epigenetic mechanisms are one of the most relevant events that occur after radiotherapy to regulate the expression and function of key genes and proteins in the differential radiation-response. This article reviews recent data on the main molecular mechanisms and signaling pathways related to the biological response to radiotherapy in cancer; highlighting the epigenetic control exerted by DNA methylation, histone marks, chromatin remodeling and m6A RNA methylation on gene expression and activation of signaling pathways related to radiation therapy response.


Assuntos
Neoplasias , Tolerância a Radiação , Humanos , Tolerância a Radiação/genética , Neoplasias/genética , Neoplasias/radioterapia , Epigênese Genética , Metilação de DNA , Reparo do DNA
17.
Lancet Oncol ; 25(2): 225-234, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301690

RESUMO

BACKGROUND: Cancer incidence and mortality is increasing rapidly worldwide, with a higher cancer burden observed in the Asia-Pacific region than in other regions. To date, evidence-based modelling of radiotherapy demand has been based on stage data from high-income countries (HIC) that do not account for the later stage at presentation seen in many low-income and middle-income countries (LMICs). We aimed to estimate the current and projected demand and supply in megavoltage radiotherapy machines in the Asia-Pacific region, using a national income-group adjusted model. METHODS: Novel LMIC radiotherapy demand and outcome models were created by adjusting previously developed models that used HIC cancer staging data. These models were applied to the cancer case mix (ie, the incidence of each different cancer) in each LMIC in the Asia-Pacific region to estimate the current and projected optimal radiotherapy utilisation rate (ie, the proportion of cancer cases that would require radiotherapy on the basis of guideline recommendations), and to estimate the number of megavoltage machines needed in each country to meet this demand. Information on the number of megavoltage machines available in each country was retrieved from the Directory of Radiotherapy Centres. Gaps were determined by comparing the projected number of megavoltage machines needed with the number of machines available in each region. Megavoltage machine numbers, local control, and overall survival benefits were compared with previous data from 2012 and projected data for 2040. FINDINGS: 57 countries within the Asia-Pacific region were included in the analysis with 9·48 million new cases of cancer in 2020, an increase of 2·66 million from 2012. Local control was 7·42% and overall survival was 3·05%. Across the Asia-Pacific overall, the current optimal radiotherapy utilisation rate is 49·10%, which means that 4·66 million people will need radiotherapy in 2020, an increase of 1·38 million (42%) from 2012. The number of megavoltage machines increased by 1261 (31%) between 2012 and 2020, but the demand for these machines increased by 3584 (42%). The Asia-Pacific region only has 43·9% of the megavoltage machines needed to meet demand, ranging from 9·9-40·5% in LMICs compared with 67·9% in HICs. 12 000 additional megavoltage machines will be needed to meet the projected demand for 2040. INTERPRETATION: The difference between supply and demand with regard to megavoltage machine availability has continued to widen in LMICs over the past decade and is projected to worsen by 2040. The data from this study can be used to provide evidence for the need to incorporate radiotherapy in national cancer control plans and to inform governments and policy makers within the Asia-Pacific region regarding the urgent need for investment in this sector. FUNDING: The Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology for Asia and the Pacific (RCA) Regional Office (RCARP03).


Assuntos
Atenção à Saúde , Neoplasias , Humanos , Ásia/epidemiologia , Países em Desenvolvimento , Neoplasias/epidemiologia , Neoplasias/radioterapia
18.
ESMO Open ; 9(2): 102217, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38320431

RESUMO

INTRODUCTION: We report results from a phase I, three-part, dose-escalation study of peposertib, a DNA-dependent protein kinase inhibitor, in combination with avelumab, an immune checkpoint inhibitor, with or without radiotherapy in patients with advanced solid tumors. MATERIALS AND METHODS: Peposertib 100-400 mg twice daily (b.i.d.) or 100-250 mg once daily (q.d.) was administered in combination with avelumab 800 mg every 2 weeks in Part A or avelumab plus radiotherapy (3 Gy/fraction × 10 days) in Part B. Part FE assessed the effect of food on the pharmacokinetics of peposertib plus avelumab. The primary endpoint in Parts A and B was dose-limiting toxicity (DLT). Secondary endpoints were safety, best overall response per RECIST version 1.1, and pharmacokinetics. The recommended phase II dose (RP2D) and maximum tolerated dose (MTD) were determined in Parts A and B. RESULTS: In Part A, peposertib doses administered were 100 mg (n = 4), 200 mg (n = 11), 250 mg (n = 4), 300 mg (n = 6), and 400 mg (n = 4) b.i.d. Of DLT-evaluable patients, one each had DLT at the 250-mg and 300-mg dose levels and three had DLT at the 400-mg b.i.d. dose level. In Part B, peposertib doses administered were 100 mg (n = 3), 150 mg (n = 3), 200 mg (n = 4), and 250 mg (n = 9) q.d.; no DLT was reported in evaluable patients. Peposertib 200 mg b.i.d. plus avelumab and peposertib 250 mg q.d. plus avelumab and radiotherapy were declared as the RP2D/MTD. No objective responses were observed in Part A or B; one patient had a partial response in Part FE. Peposertib exposure was generally dose proportional. CONCLUSIONS: Peposertib doses up to 200 mg b.i.d. in combination with avelumab and up to 250 mg q.d. in combination with avelumab and radiotherapy were tolerable in patients with advanced solid tumors; however, antitumor activity was limited. GOV IDENTIFIER: NCT03724890.


Assuntos
Neoplasias , Piridazinas , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Quinazolinas/uso terapêutico
19.
Comput Biol Med ; 171: 108139, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38394800

RESUMO

Proton arc therapy (PAT) is an advanced radiotherapy technique using charged particles in which the radiation device rotates continuously around the patient while irradiating the tumor. Compared to conventional, fixed-angle beam delivery mode, proton arc therapy has the potential to further improve the quality of cancer treatment by delivering accurate radiation dose to tumors while minimizing damage to surrounding healthy tissues. However, the computational complexity of treatment planning in PAT raises challenges as to its effective implementation. In this paper, we demonstrate that designing a PAT plan through algorithmic methods is a NP-hard problem (in fact, NP-complete), where the problem size is determined by the number of discrete irradiation angles from which the radiation can be delivered. This finding highlights the inherent complexity of PAT treatment planning and emphasizes the need for efficient algorithms and heuristics to address the challenges associated with optimizing the delivery of radiation doses in this context.


Assuntos
Neoplasias , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Prótons , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Terapia com Prótons/métodos , Neoplasias/radioterapia , Algoritmos
20.
Radiother Oncol ; 193: 110118, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316192

RESUMO

In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Neoplasias/radioterapia , Radioterapia
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