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Pathology Oncology Research : POR 2024The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is... (Review)
Review
The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Radiosurgery; Lung; Dose Fractionation, Radiation; Small Cell Lung Carcinoma; Neoplasm Staging
PubMed: 38476352
DOI: 10.3389/pore.2024.1611709 -
Clinical Oncology (Royal College of... Apr 2021Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of...
AIMS
Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance.
MATERIALS AND METHODS
A web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out.
RESULTS
In total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres.
CONCLUSION
This survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.
Topics: Dose Fractionation, Radiation; Humans; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; United Kingdom
PubMed: 33423883
DOI: 10.1016/j.clon.2020.12.011 -
Pediatric Blood & Cancer May 2023Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which... (Review)
Review
BACKGROUND
Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which has led to variations in constraints over the years. In this study, we identify these variations in dose constraints within pediatric trials both in the United States and in Europe used in the past 30 years.
PROCEDURE
All pediatric trials from the Children's Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs at risk (OAR), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US and European trials RESULTS: One hundred five closed trials were included-93 US trials and 12 European trials. Thirty-eight separate OAR were found with high-dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, the United States constraints were higher for seven OAR, lower for one, and identical for five. No OAR had constraints change systematically over the last 30 years.
CONCLUSION
Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OAR. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.
Topics: Humans; Child; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Organs at Risk; Dose Fractionation, Radiation; Radiation Injuries
PubMed: 36880707
DOI: 10.1002/pbc.30270 -
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 -
The British Journal of Radiology Jan 2019Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater...
Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Four randomised trials testing fraction sizes in the range 2.7-3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.
Topics: Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Mastectomy; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local; Radiation Dose Hypofractionation; Radiotherapy, Adjuvant
PubMed: 29345152
DOI: 10.1259/bjr.20170849 -
Magnetic Resonance Imaging Nov 2012Modern radiation therapy techniques are exceptionally flexible in the deposition of radiation dose in a target volume. Complex distributions of dose can be delivered... (Review)
Review
Modern radiation therapy techniques are exceptionally flexible in the deposition of radiation dose in a target volume. Complex distributions of dose can be delivered reliably, so that the tumor is exposed to a high dose, whereas nearby healthy structures can be avoided. As a result, an increase in curative dose is no longer invariably associated with an increased level of toxicity. This modern technology can be exploited further by modulating the required dose in space so as to match the variation in radiation sensitivity in the tumor. This approach is called dose painting. For dose painting to be effective, functional imaging techniques are essential to identify regions in a tumor that require a higher dose. Several techniques are available in nuclear medicine and radiology. In recent years, there has been a considerable research effort concerning the integration of magnetic resonance imaging (MRI) into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to computed tomography. In MRI, diffusion-weighted MRI reflects the cell density of tissue and thus may indicate regions with a higher tumor load. Dynamic contrast-enhanced MRI reflects permeability of the microvasculature and blood flow, correlated to the oxygenation of the tumor. These properties have impact on its radiation sensitivity. New questions must be addressed when these techniques are applied in radiation therapy: scanning in treatment position requires alternative solutions to the standard patient setup in the choice of receive coils compared to a diagnostic department. This standard positioning also facilitates repeated imaging. The geometrical accuracy of MR images is critical for high-precision radiotherapy. In particular, when multiparametric functional data are used for dose painting, quantification of functional parameters at a high spatial resolution becomes important. In this review, we will address these issues and describe clinical developments in MRI-guided dose painting.
Topics: Breast Neoplasms; Diagnostic Imaging; Dose Fractionation, Radiation; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Microcirculation; Neoplasms; Oxygen; Positron-Emission Tomography; Prostatic Neoplasms; Radiation Oncology; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Computer-Assisted; Reproducibility of Results
PubMed: 22770686
DOI: 10.1016/j.mri.2012.04.010 -
BioMed Research International 2013According to Leksell radiosurgery is defined as "the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the... (Review)
Review
According to Leksell radiosurgery is defined as "the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull." Before its birth in the early 60s and its introduction in clinical therapeutic protocols in late the 80s dose application in radiation therapy of the brain for benign and malignant lesions was based on the administration of cumulative dose into a variable number of fractions. The rationale of dose fractionation is to lessen the risk of injury of normal tissue surrounding the target volume. Radiobiological studies of cell culture lines of malignant tumors and clinical experience with patients treated with conventional fractionated radiotherapy helped establishing this radiobiological principle. Radiosurgery provides a single high dose of radiation which translates into a specific toxic radiobiological response. Radiobiological investigations to study the effect of high dose focused radiation on the central nervous system began in late the 50s. It is well known currently that radiobiological principles applied for dose fractionation are not reproducible when single high dose of ionizing radiation is delivered. A review of the literature about radiobiology of radiosurgery for the central nervous system is presented.
Topics: Central Nervous System; Dose Fractionation, Radiation; Humans; Models, Theoretical; Radiobiology; Radiosurgery
PubMed: 24490157
DOI: 10.1155/2013/362761 -
Radiotherapy and Oncology : Journal of... Aug 2022For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and... (Review)
Review
For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and delineation variability. For pediatric patients no standardized margins are defined. Moreover, studies on these geometrical uncertainties are relatively scarce. Therefore, this systematic review presents an overview of organ motion, applied margin sizes and delineation variability in patients <18 years. A search from January 2000 to March 2021 in Medline, Embase, Web of Science, ClinicalTrials.gov and the International Trials Registry Platform resulted in the inclusion of 117 studies reporting on organ motion, margin sizes and/or delineation variability. Studies were heterogeneous concerning age, tumor types, the use of general anesthesia, imaging modalities; image guidance techniques were reported in 39% of the studies. Inter- and intrafractional motion as reported for different organs was largest in cranio-caudal direction and ranged from -9.1 to 10.0 mm and -4.4 to 19.5 mm, respectively. Motion quantification methodologies differed between studies regarding measures of displacement and definitions of motion direction. Reported CTV-PTV margins varied from 3 to 20 mm for both thoracic and abdominal targets, and for spinal and pelvic from 3to 15 mm and 3 to 10 mm, respectively. Studies reported wide variation in interobserver variability of target volume delineation, which may affect dose distributions to both target volumes and organs at risk. Results of this review indicate possible reduction of margin sizes for children, however, wide variation in organ motion and delineation variability caused by differences in methodologies and outcomes hamper the use of standardized margins.
Topics: Child; Dose Fractionation, Radiation; Humans; Organ Motion; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided
PubMed: 35640771
DOI: 10.1016/j.radonc.2022.05.021 -
Radiotherapy and Oncology : Journal of... Sep 2023Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause anti-tumour activity. The current study investigates whether CP-506 improves outcome of radiotherapy in vivo.
MATERIALS AND METHODS
Mice bearing FaDu and UT-SCC-5 xenografts were randomized to receive 5 daily injections of CP-506/vehicle followed by single dose (SD) irradiation. In addition, CP-506 was combined once per week with fractionated irradiation (30 fractions/6 weeks). Animals were followed-up to score all recurrences. In parallel, tumours were harvested to evaluate pimonidazole hypoxia, DNA damage (γH2AX), expression of oxidoreductases.
RESULTS
CP-506 treatment significantly increased local control rate after SD in FaDu, 62% vs. 27% (p = 0.024). In UT-SCC-5, this effect was not curative and only marginally significant. CP-506 induced significant DNA damage in FaDu (p = 0.009) but not in UT- SCC-5. Hypoxic volume (HV) was significantly smaller (p = 0.038) after pretreatment with CP-506 as compared to vehicle in FaDu but not in less responsive UT-SCC-5. Adding CP-506 to fractionated radiotherapy in FaDu did not result in significant benefit.
CONCLUSION
The results support the use of CP-506 in combination with radiation in particular using hypofractionation schedules in hypoxic tumours. The magnitude of effect depends on the tumour model, therefore it is expected that applying appropriate patient stratification strategy will further enhance the benefit of CP-506 treatment for cancer patients. A phase I-IIA clinical trial of CP-506 in monotherapy or in combination with carboplatin or a checkpoint inhibitor has been approved (NCT04954599).
Topics: Humans; Animals; Mice; Carcinoma, Squamous Cell; Prodrugs; Dose Fractionation, Radiation; Hypoxia; Probability
PubMed: 37315579
DOI: 10.1016/j.radonc.2023.109738