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EJNMMI Radiopharmacy and Chemistry May 2024Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our... (Review)
Review
BACKGROUND
Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups.
MAIN BODY
Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons (In, Tc, I, Pd, Pt, Pt), β-particles (Lu, Re, Re, Y, Au, I) or α-particles (Ac, Bi, Pb, At, Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity.
CONCLUSIONS
Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity.
PubMed: 38703297
DOI: 10.1186/s41181-024-00266-y -
Physica Medica : PM : An International... May 2024Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short...
PURPOSE
Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the Ra decay chain.
METHODS
The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment.
RESULTS
Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of β-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBE and RBE respectively.
CONCLUSIONS
The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.
Topics: Alpha Particles; Monte Carlo Method; DNA Damage; Radiotherapy Dosage; Radiation Dosage; Relative Biological Effectiveness; Diffusion; Brachytherapy; Humans; Linear Energy Transfer; Radiotherapy Planning, Computer-Assisted; DNA Breaks, Double-Stranded
PubMed: 38701625
DOI: 10.1016/j.ejmp.2024.103367 -
Journal of Cancer Research and... Apr 2024This study aims to observe the curative effect of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancer.
PURPOSE
This study aims to observe the curative effect of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancer.
METHODS
Data from 132 patients with head and neck malignant tumors underwent computed tomography-guided radioactive 125I seed implantation from April 2004 to August 2020 were analyzed retrospectively. The Kaplan-Meier method was used to calculate the local control and survival rates. The logarithmic rank test and the Cox proportional risk model were used for univariate and multivariate analysis, respectively.
RESULTS
A total of 132 patients were enrolled. All tumors were confirmed to be malignant through pathological analysis. Herein, we revealed that the seeds were implanted at the primary tumor site (23 cases, representing 17.4%), recurrent (9 cases, representing 6.8%), or metastatic lymph nodes (100 cases, representing 75.8%). Three months after the operation, 96 patients were evaluated as effective, whereas 36 patients were considered ineffective. The median local control time was 16 months; the local rates at 6, 12, 18, and 24 months were observed to be 75%, 47%, 35%, and 22%, respectively. The study reports a median survival period (OS) of 15 months. Additionally, the survival rates at 6, 12, 18, and 24 months were 61%, 42%, 31%, and 27%, respectively. Regarding side effects, skin or mucosal toxicity occurred in 14 patients. Grade I skin toxicity occurred in seven cases (5.3%), grade IV skin toxicity in one case (0.8%), grade I mucosal ulcer in four cases (3.0%), and grade I dry mouth in four cases (3.0%). The multivariate analysis showed that short-term efficacy and tumor site were independent prognostic factors (P < 0.001, 0.006, respectively). Additionally, the multivariate analysis showed that the independent OS influencing factors included D90, the longest tumor diameter, and short-term efficacy (P = 0.017, 0.001, <0.001).
CONCLUSION
Radioactive 125I seed implantation is a safe and effective salvage therapy for patients with inoperable or refused operation head and neck cancer.
Topics: Humans; Iodine Radioisotopes; Male; Female; Middle Aged; Head and Neck Neoplasms; Aged; Adult; Retrospective Studies; Brachytherapy; Survival Rate; Aged, 80 and over; Treatment Outcome; Follow-Up Studies; Tomography, X-Ray Computed; Neoplasm Recurrence, Local; Prognosis
PubMed: 38687935
DOI: 10.4103/jcrt.jcrt_1891_23 -
Frontiers in Endocrinology 2024To explore the clinical benefits of I seed implantation for iodine-refractory differentiated thyroid cancer (RAIR-DTC).
OBJECTIVE
To explore the clinical benefits of I seed implantation for iodine-refractory differentiated thyroid cancer (RAIR-DTC).
METHODS
A retrospective analysis was conducted on 36 patients with RAIR-DTC who underwent radioactive I seed implantation from January 2015 to February 2022, involving 73 lesions. Prescription dose: 80~120 Gy. All cases were followed up at 1, 3, and 5 months postoperatively to monitor changes in tumor size, serum thyroglobulin (Tg), and serum anti-thyroglobulin antibody levels in thyrotropin-inhibited states, pain scores, and postoperative adverse reactions. The data were processed and analyzed using IBM SPSS 26.0. LER (Local Effective Rate) and LCR (Local Control Rate) were expressed as n (%), tumor diameter, Tg, and pain scores were represented as Median (Q1, Q3). Pairwise comparisons were conducted using the Wilcoxon signed-rank test, and a p-value of less than 0.05 indicated statistical significance.
RESULTS
Tumor size was significantly reduced after treatment (all P < 0.001): tumor length diameters were 32.67 (17.70, 45.72) mm, 27.45 (12.30, 39.98) mm, 20.70 (11.98, 37.58) mm, and 20.39 (10.56, 33.20) mm in the preoperative, 1-, 3-, and 5-months postoperative periods, respectively. Additionally, two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The LER at 1-, 3-, and 5-months post-surgery was 23.73%, 38.98%, and 52.54%, respectively, while the LCR at the same time points was 98.31%, 96.61%, and 94.92%, respectively. Patients' serum Tg levels decreased significantly after surgery. (P < 0.001). Serum Tg levels were measured before surgery and 1-, 3-, and 5-months post-surgery. The results showed that serum Tg levels were 249.45 (79.39, 4718.75) ng/ml, 193.40 (44.53, 2829.00) ng/ml, 192.10 (25.58, 1758.00) ng/ml, and 136.25 (16.57, 1553.25) ng/ml, respectively. Two consecutive post-treatment results were more minor and statistically significant than the previous results (P < 0.001). The patients' pain symptoms were significantly relieved after I brachytherapy (P < 0.001). The pain scores before I seed implantation and at 1, 3, and 5 months after the operation were 5.00 (4.00, 6.00), 3.00 (2.25, 4.00), 2.00 (2.00, 3.00), and 2.00 (1.00, 3.00), respectively.
CONCLUSION
Most lesions treated with I seed implantation in RAIR-DTC patients showed shrinkage and improved pain symptoms.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov, identifier NCT06362772.
Topics: Humans; Iodine Radioisotopes; Thyroid Neoplasms; Male; Female; Middle Aged; Retrospective Studies; Adult; Aged; Brachytherapy; Thyroglobulin; Treatment Outcome; Follow-Up Studies; Young Adult
PubMed: 38686207
DOI: 10.3389/fendo.2024.1327766 -
IJU Case Reports May 2024The seeds used in brachytherapy for prostate cancer may migrate through the surrounding venous plexus to other sites in the body, most commonly to the pulmonary...
INTRODUCTION
The seeds used in brachytherapy for prostate cancer may migrate through the surrounding venous plexus to other sites in the body, most commonly to the pulmonary vasculature.
CASE PRESENTATION
A 78-year-old Japanese man received iodine-125 low-dose-rate prostate brachytherapy. Computed tomography revealed that one seed had migrated to the right kidney. No seed was observed in the ureter upon ureteroscopy. Transesophageal echocardiography confirmed a right-to-left shunt due to a patent foramen ovale, suggesting that the seed had migrated into the right renal artery. Three years after treatment, no recurrence of prostate cancer and no adverse events due to seed migration or due to the patent foramen ovale occurred.
CONCLUSION
Arteriovenous malformations and a right-to-left shunt should be suspected if a brachytherapy seed has migrated to an artery of the systemic circulatory system.
PubMed: 38686070
DOI: 10.1002/iju5.12707 -
Medicina 2024Little evidence exists on the impact of the COVID-19 pandemics on the compliance with cervical cancer treatment.
INTRODUCTION
Little evidence exists on the impact of the COVID-19 pandemics on the compliance with cervical cancer treatment.
METHODS
We carried out a population-based, before-and-after retrospective cohort study of all cervical cancer patients diagnosed in the Jujuy province public health sector (n=140), Argentina, between 2017 and 2020. Patients diagnosed in 2020 were considered exposed to the COVID-19 pandemic (n=21). We used multivariable logistic regression to assess the relationship between the pandemics and compliance with treatment. We also measured treatment duration for women who were indicated brachytherapy and time to treatment initiation by stage.
RESULTS
Compared with women diagnosed in 2017-2019 the odds ratio of non-complying with treatment was 1.77 (95%CI 0.59-5.81; p = 0.32) for women diagnosed during 2020. An increased risk of non-compliance was found in patients with prescribed brachytherapy (OR 4.14. 95%CI 1.95-9.11; p < 0.001). Median treatment duration for women with prescribed brachytherapy was 12.8 and 15.7 weeks in 2017-2019 vs. 2020 (p = 0.33); median time to treatment initiation for women with early-stage disease was 9 and 5 weeks during 2017-2019 and 2020 respectively (p = 0.06), vs 7.2 and 9 weeks in 2017-2019 and 2020 respectively (p = 0.36) for patients with stages IIB+ disease.
CONCLUSIONS
Low access to brachytherapy was a major determinant of non-compliance. irrespective of the effect of the pandemics.
Topics: Humans; Female; COVID-19; Uterine Cervical Neoplasms; Retrospective Studies; Middle Aged; Argentina; Brachytherapy; Adult; Aged; Patient Compliance; Pandemics; SARS-CoV-2; Neoplasm Staging; Time-to-Treatment
PubMed: 38683508
DOI: No ID Found -
Cureus Mar 2024To analyze the level of fear and anxiety related to radiotherapy in oncology patients treated before and during the COVID-19 pandemic, as well as to examine whether the...
OBJECTIVE
To analyze the level of fear and anxiety related to radiotherapy in oncology patients treated before and during the COVID-19 pandemic, as well as to examine whether the advancement of radiotherapy centers leads to any reduction in the patient's fear in emergency situations.
METHODS
Two cross-sectional studies were conducted in two time frames (2016 and 2022) based on the analysis of the intensity of anxiety and fear of radiotherapy in oncology patients with assistance. A questionnaire for assessing fear of radiotherapy in oncology patients and Zung's and Beck's self-reported anxiety scales were used. The first part of the research integrated all data of research interest obtained from patients treated with radiotherapy during 2016, and the second cross-sectional study included all patients treated in 2022 during the COVID-19 pandemic. The study was prepared according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist.
RESULTS
The first cross-sectional study had 154 participants who had been treated with radiotherapy, while in the second study, there were 159 patients. Patients treated in 2022 show significantly higher levels of fear and anxiety. External beam radiotherapy and brachytherapy simultaneously used in both studies increased the level of fear and anxiety.
CONCLUSION
The conducted research showed exceptional differences in the intensity of fear and anxiety in patients treated with radiotherapy in different health situations, as was the case during the COVID-19 pandemic, with a significant impact on the stability of the health system and the challenges to providing standard services.
PubMed: 38681399
DOI: 10.7759/cureus.57129 -
Asian Journal of Urology Apr 2024Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted...
OBJECTIVES
Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate cancer.
METHODS
HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were compared.
RESULTS
The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA (<0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively (<0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than HS.
CONCLUSION
The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer.
PubMed: 38680582
DOI: 10.1016/j.ajur.2022.08.006 -
Asian Pacific Journal of Cancer... Apr 2024The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial...
OBJECTIVE
The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer.
METHODS
In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05.
RESULTS
Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT.
CONCLUSIONS
Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.
Topics: Humans; Uterine Cervical Neoplasms; Female; Brachytherapy; Cisplatin; India; Middle Aged; Chemoradiotherapy; Tertiary Care Centers; Follow-Up Studies; Radiotherapy Dosage; Adult; Antineoplastic Agents; Prognosis; Carcinoma, Squamous Cell; Treatment Outcome; Combined Modality Therapy
PubMed: 38679994
DOI: 10.31557/APJCP.2024.25.4.1333 -
Cancers Apr 2024There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the...
INTRODUCTION
There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer.
MATERIAL AND METHODS
This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan-Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator.
RESULTS
The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS ( = 0.001 and = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32-3.16; = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15.
CONCLUSIONS
The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation.
PubMed: 38672624
DOI: 10.3390/cancers16081542