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Journal of Radiation Research Jan 2021The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity... (Clinical Trial)
Clinical Trial
The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.
Topics: Female; Humans; Organs at Risk; Postoperative Period; Quality Assurance, Health Care; Radiation Dose Hypofractionation; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Tomography, X-Ray Computed; Uterine Cervical Neoplasms
PubMed: 33392616
DOI: 10.1093/jrr/rraa085 -
The Cochrane Database of Systematic... Aug 2021Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). Most true... (Review)
Review
BACKGROUND
Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)).
OBJECTIVES
To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast-conserving therapy for early-stage breast cancer.
SEARCH METHODS
On 27 August 2020, we searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and three trial databases. We searched for grey literature: OpenGrey (September 2020), reference lists of articles, conference proceedings and published abstracts, and applied no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors (BH and ML) performed data extraction, used Cochrane's risk of bias tool and resolved any disagreements through discussion, and assessed the certainty of the evidence for main outcomes using GRADE. Main outcomes were local recurrence-free survival, cosmesis, overall survival, toxicity (subcutaneous fibrosis), cause-specific survival, distant metastasis-free survival and subsequent mastectomy. We entered data into Review Manager 5 for analysis.
MAIN RESULTS
We included nine RCTs that enrolled 15,187 women who had invasive breast cancer or ductal carcinoma in-situ (6.3%) with T1-2N0-1M0 Grade I or II unifocal tumours (less than 2 cm or 3 cm or less) treated with breast-conserving therapy with negative margins. This is the second update of the review and includes two new studies and 4432 more participants. Local recurrence-free survival is probably slightly reduced (by 3/1000, 95% CI 6 fewer to 0 fewer) with the use of PBI/APBI compared to WBRT (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 8 studies, 13,168 participants; moderate-certainty evidence). Cosmesis (physician/nurse-reported) is probably worse (by 63/1000, 95% CI 35 more to 92 more) with the use of PBI/APBI (odds ratio (OR) 1.57, 95% CI 1.31 to 1.87; 6 studies, 3652 participants; moderate-certainty evidence). Overall survival is similar (0/1000 fewer, 95% CI 6 fewer to 6 more) with PBI/APBI and WBRT (HR 0.99, 95% CI 0.88 to 1.12; 8 studies, 13,175 participants; high-certainty evidence). Late radiation toxicity (subcutaneous fibrosis) is probably increased (by 14/1000 more, 95% CI 102 more to 188 more) with PBI/APBI (OR 5.07, 95% CI 3.81 to 6.74; 2 studies, 3011 participants; moderate-certainty evidence). The use of PBI/APBI probably makes little difference (1/1000 less, 95% CI 6 fewer to 3 more) to cause-specific survival (HR 1.06, 95% CI 0.83 to 1.36; 7 studies, 9865 participants; moderate-certainty evidence). We found the use of PBI/APBI compared with WBRT probably makes little or no difference (1/1000 fewer (95% CI 4 fewer to 6 more)) to distant metastasis-free survival (HR 0.95, 95% CI 0.80 to 1.13; 7 studies, 11,033 participants; moderate-certainty evidence). We found the use of PBI/APBI in comparison with WBRT makes little or no difference (2/1000 fewer, 95% CI 20 fewer to 20 more) to mastectomy rates (OR 0.98, 95% CI 0.78 to 1.23; 3 studies, 3740 participants, high-certainty evidence).
AUTHORS' CONCLUSIONS
It appeared that local recurrence-free survival is probably worse with PBI/APBI; however, the difference was small and nearly all women remain free of local recurrence. Overall survival is similar with PBI/APBI and WBRT, and we found little to no difference in other oncological outcomes. Some late effects (subcutaneous fibrosis) may be worse with PBI/APBI and its use is probably associated with worse cosmetic outcomes. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver PBI/APBI. We await completion of ongoing trials.
Topics: Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Mastectomy; Mastectomy, Segmental; Radiation Dose Hypofractionation
PubMed: 34459500
DOI: 10.1002/14651858.CD007077.pub4 -
Medical Physics Jun 2022Microbeam radiation therapy (MRT) is a treatment modality based on spatial fractionation of synchrotron generated X-rays into parallel, high dose, microbeams of a few...
BACKGROUND
Microbeam radiation therapy (MRT) is a treatment modality based on spatial fractionation of synchrotron generated X-rays into parallel, high dose, microbeams of a few microns width. MRT is still an underdevelopment radiosurgery technique for which, promising preclinical results on brain tumors and epilepsy encourages its clinical transfer.
PURPOSE
A safe clinical transfer of MRT needs a specific treatment planning system (TPS) that provides accurate dose calculations in human patients, taking into account the MRT beam's properties (high-dose gradients, spatial fractionation, polarization effects). So far, the most advanced MRT TPS, based on a hybrid dose calculation algorithm, is limited to a macroscopic rendering of the dose and does not account for the complex dose distribution inherent to MRT if delivered as conformal irradiations with multiple incidences. For overcoming these limitations, a multi-scale full Monte-Carlo calculation engine called penMRT has been developed and benchmarked against two general-purpose Monte Carlo (MC) codes: penmain based on PENELOPE and Gate based on Geant4.
METHODS
PenMRT, is based on the PENELOPE (2018) MC code, modified to take into account the voxelized geometry of the patients (computed tomography [CT]-scans) and is offering an adaptive micrometric dose calculation grid independent of the CT size, location, and orientation. The implementation of the dynamic memory allocation in penMRT, makes the simulations feasible within a huge number of dose scoring bins. The possibility of using a source replication approach to simulate arrays of microbeams, and the parallelization using OpenMPI have been added to penMRT in order to increase the calculation speed for clinical usages. This engine can be implemented in a TPS as a dose calculation core.
RESULTS
The performance tests highlight the reliability of penMRT to be used for complex irradiation conditions in MRT. The benchmarking against a standard PENELOPE code did not show any significant difference for calculations in centimetric beams, for a single microbeam and for a microbeam array. The comparisons between penMRT and Gate as an independent MC code did not show any difference in the beam paths, whereas, in valley regions, relative differences between the two codes rank from 1% to 7.5% which are probably due to the differences in physics lists that are used in these two codes. The reliability of the source replication approach has also been tested and validated with an underestimation of no more than 0.6% in low-dose areas.
CONCLUSIONS
Good agreements (a relative difference between 0% and 8%) were found when comparing calculated peak to valley dose ratio values using penMRT, for irradiations with a full microbeam array, with calculated values in the literature. The high-resolution calculated dose maps obtained with penMRT are used to extract differential and cumulative dose-volume histograms (DVHs) and analyze treatment plans with much finer metrics regarding the irradiation complexity. To our knowledge, these are the first high-resolution dose maps and associated DVHs ever obtained for cross-fired microbeams irradiation, which is bringing a significant added value to the field of treatment planning in spatially fractionated radiation therapy.
Topics: Humans; Monte Carlo Method; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Reproducibility of Results; Synchrotrons; X-Ray Therapy; X-Rays
PubMed: 35342953
DOI: 10.1002/mp.15637 -
In Vivo (Athens, Greece) 2022Stereotactic radiotherapy (SRT) for spine metastases with helical tomotherapy requires a long irradiation time due to the high dose per fraction. Since helical...
BACKGROUND/AIM
Stereotactic radiotherapy (SRT) for spine metastases with helical tomotherapy requires a long irradiation time due to the high dose per fraction. Since helical tomotherapy can neither confirm nor correct the position during irradiation, a plan with a long irradiation time cannot be used in actual clinical practice, given the intra-fractional motion error. To address this problem, we devised a method called REPEAT irradiation.
PATIENTS AND METHODS
REPEtitive pAinTing (REPEAT) irradiation is a method of dividing the irradiation for a given fraction per day into several sessions and performing the irradiation after position correction using mega-voltage computed tomography images for each session. In order to evaluate how REPEAT irradiation changes irradiation time and the dose-volume histogram (DVH), a planning study with helical tomotherapy was conducted using CT images of a patient with lumbar spine metastasis.
RESULTS
In this case, we found that dividing 3 irradiation fractions into 3 sessions per day (i.e., 9 fractions=9 sessions in 3 days) using REPEAT irradiation shortened the irradiation time per session and simultaneously improved dose-volume histogram parameters.
CONCLUSION
Although the optimal number of sessions may differ depending on the patient's condition, the fixing method, the irradiation site, and the calculation parameters, REPEAT irradiation does not require any special equipment and is a simple practical treatment method.
Topics: Dose Fractionation, Radiation; Humans; Radiosurgery; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34972730
DOI: 10.21873/invivo.12706 -
Technology in Cancer Research &... 2020Spinal metastases are a common manifestation of malignant tumors that can cause severe pain, spinal cord compression, pathological fractures, and hypercalcemia, and... (Review)
Review
Spinal metastases are a common manifestation of malignant tumors that can cause severe pain, spinal cord compression, pathological fractures, and hypercalcemia, and these clinical manifestations will ultimately reduce the health-related quality of life and even shorten life expectancy in patient with cancer. Effective management of spinal bone metastases requires multidisciplinary collaboration, including radiologists, surgeons, radiation oncologists, medical oncologists, and pain specialists. In the past few decades, conventional radiotherapy has been the most common form of radiotherapy, which can achieve favorable local control and pain relief; however, it lacks precise methods of delivering radiation and thus cannot provide sufficient tumoricidal dose. The advent of stereotactic radiosurgery has changed this situation by using highly focused radiation beams guided by 3-dimensional imaging to deliver a high biologic equivalent dose to the target region, and the spinal cord can be identified and excluded from the target volume to reduce the risk of radiation-induced myelopathy. Separation surgery can provide a 2- to 3-mm safe separation of tumor and spinal cord to avoid radiation-induced damage to the spinal cord. Targets for separation surgery include decompression of metastatic epidural spinal cord compression and spinal stabilization without partial or en bloc tumor resection. Combined with conventional radiotherapy, stereotactic radiosurgery can provide better local tumor control and pain relief. Several scoring systems have been developed to estimate the life expectancy of patients with spinal metastases treated with radiotherapy. Thorough understanding of radiotherapy-related knowledge including the dose-fractionation schedule, separation surgery, efficacy and safety, scoring systems, and feasibility of combination with other treatment methods is critical to providing optimal patient care.
Topics: Combined Modality Therapy; Disease Management; Dose Fractionation, Radiation; Humans; Radiosurgery; Radiotherapy; Radiotherapy Dosage; Spinal Neoplasms; Treatment Outcome
PubMed: 32757820
DOI: 10.1177/1533033820945798 -
Lung Cancer (Amsterdam, Netherlands) Aug 2020COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. Meanwhile in Asia, where the disease began, the... (Review)
Review
COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, UK, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide. An international panel with expertise in the management of lung cancer in high-volume comprehensive centres has come together to share its experience on COVID-19 preparedness to deliver optimal care in such exceptional circumstances. A comprehensive systematic review of the literature through a PubMed search was undertaken. Twelve recommendations including, among others, the consideration of shorter courses, delays, and the omission of RT for lung cancer are proposed by the panel. In summary, we recommend the screening of every single person accessing the treatment room, the consideration of hypofractionation and to delay postoperative RT for non-small cell lung cancer, to avoid twice-daily treatments and delay or deliver prophylactic cranial irradiation during radio(chemo)therapy for limited-stage small cell lung cancer, review image guided RT images for suspicious image findings, and the use of single-fraction RT for the palliative treatment of stage IV lung cancer patients. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic.
Topics: Betacoronavirus; COVID-19; Carcinoma, Non-Small-Cell Lung; China; Coronavirus Infections; Disease Outbreaks; Dose Fractionation, Radiation; France; Humans; Italy; Palliative Care; Pandemics; Pneumonia, Viral; SARS-CoV-2; Small Cell Lung Carcinoma; Spain
PubMed: 32585497
DOI: 10.1016/j.lungcan.2020.05.029 -
BMC Cancer Jun 2023Radiotherapy (RT) is the standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%....
HYpofractionated, dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase I HYDRA trial.
BACKGROUND
Radiotherapy (RT) is the standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%. Despite strong biological rationale, combining RT with immune checkpoint inhibitors does not result in a survival benefit. Our hypothesis is that the combination of these individually effective treatments fails because of radiation-induced immunosuppression and lymphodepletion. By integrating modern radiobiology and innovative radiotherapy concepts, the patient's immune system could be maximally retained by (1) increasing the dose per fraction so that the total dose and number of fractions can be reduced (HYpofractionation), (2) redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective lymphatic field dose (Dose-redistribution), and (3) using RAdiotherapy with protons instead of photons (HYDRA).
METHODS
The primary aim of this multicenter study is to determine the safety of HYDRA proton- and photon radiotherapy by conducting two parallel phase I trials. Both HYDRA arms are randomized with the standard of care for longitudinal immune profiling. There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated immunoradiotherapy trials. The HYDRA dose prescriptions (in 20 fractions) are 40 Gy elective dose and 55 Gy simultaneous integrated boost on the clinical target volume with a 59 Gy focal boost on the tumor center. A total of 100 patients (25 per treatment group) will be recruited, and the final analysis will be performed one year after the last patient has been included.
DISCUSSION
In the context of HNSCC, hypofractionation has historically only been reserved for small tumors out of fear for late normal tissue toxicity. To date, hypofractionated radiotherapy may also be safe for larger tumors, as both the radiation dose and volume can be reduced by the combination of advanced imaging for better target definition, novel accelerated repopulation models and high-precision radiation treatment planning and dose delivery. HYDRA's expected immune-sparing effect may lead to improved outcomes by allowing for future effective combination treatment with immunotherapy.
TRIAL REGISTRATION
The trial is registered at ClinicalTrials.gov; NCT05364411 (registered on May 6th, 2022).
Topics: Humans; Photons; Protons; Radiation Dose Hypofractionation; Squamous Cell Carcinoma of Head and Neck; Immunosuppression Therapy; Head and Neck Neoplasms; Multicenter Studies as Topic
PubMed: 37312053
DOI: 10.1186/s12885-023-11031-w -
Cancer Dec 2020Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR-NPC) after high-dose radiotherapy (RT) is challenging and usually is associated with poor...
BACKGROUND
Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR-NPC) after high-dose radiotherapy (RT) is challenging and usually is associated with poor survival and severe toxicities. Because of its physical and biological advantages over photon-beam RT, carbon-ion RT (CIRT) could be a potential treatment option for patients with LR-NPC.
METHODS
Patients with LR-NPC who underwent salvage therapy using CIRT at the Shanghai Proton and Heavy Ion Center between May 2015 and June 2019 were analyzed. CIRT doses were 50 to 69 gray equivalent (GyE) (2.0-3.0 GyE per fraction). Overall survival (OS), local control, regional control, distant control, and acute and late toxicities were analyzed. Univariable and multivariable analyses of OS and local control were performed using the Cox regression model.
RESULTS
Among the 206 patients included, 139 patients (67.5%) had recurrent American Joint Committee on Cancer stage III or stage IV disease. With a median follow-up of 22.8 months, the 2-year OS, local control, regional control, and distant control rates were 83.7%, 58.0%, 87.3%, and 94.7%, respectively. Multivariable analysis revealed that older age (P = .017) was predictive of worse OS, whereas a larger tumor volume (P = .049) and a lower biological equivalent dose (P = .029) were associated with inferior local control. No patient developed an acute toxicity of ≥grade 3 during CIRT. Severe (≥grade 3) late toxicities included temporal lobe necrosis (0.97%), cranial neuropathy (0.49%), hearing loss (1.46%), xerostomia (0.49%), and mucosal necrosis (16.02%) (toxicities were graded using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria).
CONCLUSIONS
Salvage treatment using CIRT is efficacious for patients with LR-NPC and its toxicities are acceptable. CIRT may improve the survival and toxicity profiles substantially for patients with LR-NPC compared with the reported results after photon-based intensity-modulated RT.
Topics: Adolescent; Adult; Aged; Dose Fractionation, Radiation; Female; Heavy Ion Radiotherapy; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Intensity-Modulated; Treatment Outcome; Young Adult
PubMed: 32931035
DOI: 10.1002/cncr.33197 -
Clinical and Translational Radiation... Mar 2023Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If... (Review)
Review
Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If single fraction sessions are routinely used for intracranial targets, their utilization for mobile extracranial lesions is a source of debate and apprehension. Single session treatments improve patient comfort, provide a medico-economic benefit, and have proven useful in the context of the SARS-CoV 2 pandemic. However, both technical and radiobiological uncertainties remain. Experience from intracranial radiosurgery has shown that the size of the target, its proximity to organs at risk, tumor histology, and the volume of normal tissue irradiated are all determining factors in the choice of fractionation. The literature on the use of single fraction for extracranial sites is still scarce. Only primary and secondary pulmonary tumors have been evaluated in prospective randomized trials, allowing the integration of these fractionation schemes in daily practice, for highly selected cases and in trained teams. The level of evidence for the other organs is mainly based on dose escalation or retrospective trials and calls for caution, with further studies being needed before routine use in clinical practice.
PubMed: 36816840
DOI: 10.1016/j.ctro.2023.100584 -
Talanta Aug 2022A monolith of poly(methacrylic acid-co-ethylene glycol dimethacrylate) has been immobilised to a nitrocellulose strip by radical photopolymerisation to be used in the...
A monolith of poly(methacrylic acid-co-ethylene glycol dimethacrylate) has been immobilised to a nitrocellulose strip by radical photopolymerisation to be used in the extraction of psychoactive substances in biological fluids. Codeine, methylone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, butylone, norketamine, ketamine, heroin, cocaine, lysergic acid diethylamide and fentanyl were employed as model drugs and final extracts were analysed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Polymerisation parameters were adjusted in order to obtain a stable and homogeneous layer of monolith onto the nitrocellulose strip. The resulting sorptive phase was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Extraction conditions were investigated by the evaluation of sample pH, extraction and desorption times and desorption solvent volume, providing enrichment factor values ranging from 5.3 to 39.9. The proposed methodology provided limit of quantification values from 0.013 μg L for methylone to 0.057 μg L for amphetamine, and recoveries from 64 to 120%. Urine and serum certified reference materials were employed in the validation of the proposed methodology, providing results statistically comparable. The developed approach is simple and straightforward for the determination of psychoactive substances in urine and serum samples.
Topics: Amphetamine; Chromatography, High Pressure Liquid; Collodion; Polymerization; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 35580378
DOI: 10.1016/j.talanta.2022.123536