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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 -
Cancer Radiotherapie : Journal de La... Oct 2021The abscopal effect has been mentioned since 1953. The increase in knowledge about the immune system and the development of immunotherapies support its potential... (Review)
Review
The abscopal effect has been mentioned since 1953. The increase in knowledge about the immune system and the development of immunotherapies support its potential therapeutic interest. While it is accepted that radiotherapy induces an immune response, demonstrating its systemic impact is not easy. The preclinical basis is solid but its clinical validation pending. Radiotherapy rarely induces tumor reduction at a distance from the beams, probably due to its immunosuppressive effect. This is why a synergy between radiotherapy and systemic treatments targeting these immunosuppressive mechanisms was observed. Several parameters can modulate the induction of the abscopal effect. Among these, the fractionation of the dose seems to be determining with currently a pre-eminence of hypofractionated stereotaxis. On the other hand, even if the choice of more immunogenic targets (liver, lung) should be favoured, the optimal number of lesions to be irradiated remains to be defined as well as the minimum volume allowing sufficient release of tumor antigens. The impact of radiation-induced lymphopenia on radiotherapy/immunotherapy efficacy needs to be assessed more precisely, as does the effect of radiotherapy techniques on them. Finally, the choice of immunotherapy(ies) and the combination regimen with radiotherapy remain under discussion. A sequential scheme appears to provide less toxicities but the concomitant would lead to a better response. The study of these different parameters should allow us to deliver optimized radiotherapy/immunotherapy(ies) combinations to our metastatic patients in order to benefit as many people as possible from this abscopal effect.
Topics: Antigens, Neoplasm; Combined Modality Therapy; Dose Fractionation, Radiation; Humans; Immune System; Immunosuppression Therapy; Immunotherapy; Lymphopenia; Neoplasm Metastasis; Neoplasms; Radiotherapy; Treatment Outcome
PubMed: 34462213
DOI: 10.1016/j.canrad.2021.07.002 -
International Journal of Radiation... Apr 2024In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in... (Review)
Review
PURPOSE
In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation.
METHODS AND MATERIALS
We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy.
RESULTS
Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT.
CONCLUSIONS
In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.
Topics: Humans; Female; Breast Neoplasms; Immunotherapy; Dose Fractionation, Radiation; Tumor Microenvironment
PubMed: 38195030
DOI: 10.1016/j.ijrobp.2024.01.001 -
Clinical Oncology (Royal College of... Jun 2021External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with... (Review)
Review
External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with different treatment volumes have been described with similar tumour control and, so far, clear recommendations on the optimal radiotherapy regimen and treatment volume are lacking. The current review summarises EBRT literature on dose prescription, fractionation as well as treatment volume in order to guide clinicians in their daily practice when treating patients with muscle-invasive bladder cancer. Taking into account literature on repopulation, continuous-course radiotherapy can be used safely in daily practice where a split-course should only be reserved for those patients who are fit enough to undergo a radical cystectomy in case of a poor early response. A recent meta-analysis has proven that hypofractionated radiotherapy is superior to conventional radiotherapy with regards to invasive locoregional control with similar toxicity profiles. In the absence of node-positive disease, the target volume can be restricted to the bladder. In order to compensate for organ motion, very large margins need to be applied in the absence of image-guided radiotherapy (IGRT). Therefore, the use of IGRT or an adaptive approach is recommended. Based on the available literature, one can conclude that moderate hypofractionated radiotherapy to a dose of 55 Gy in 20 fractions to the bladder only, delivered with IGRT, can be considered standard of care for patients with node-negative invasive bladder cancer.
Topics: Cystectomy; Dose Fractionation, Radiation; Humans; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 33832838
DOI: 10.1016/j.clon.2021.03.013 -
Journal of Separation Science Jan 2020Advances in the area of sample preparation are significant and have been growing significantly in recent years. This initial step of the analysis is essential and must... (Review)
Review
Advances in the area of sample preparation are significant and have been growing significantly in recent years. This initial step of the analysis is essential and must be carried out properly, consisting of a complicated procedure with multiple stages. Consequently, it corresponds to a potential source of errors and will determine, at the end of the process, either a satisfactory result or a fail. One of the advances in this field includes the miniaturization of extraction techniques based on the conventional sample preparation procedures such as liquid-liquid extraction and solid-phase extraction. These modern techniques have gained prominence in the face of traditional methods since they minimize the consumption of organic solvents and the sample volume. As another feature, it is possible to reuse the sorbents, and its coupling to chromatographic systems might be automated. The review will emphasize the main techniques based on liquid-phase microextraction, as well as those based upon the use of sorbents. The first group includes currently popular techniques such as single drop microextraction, hollow fiber liquid-phase microextraction, and dispersive liquid-liquid microextraction. In the second group, solid-phase microextraction techniques such as in-tube solid-phase microextraction, stir bar sorptive extraction, dispersive solid-phase extraction, dispersive micro solid-phase microextraction, and microextraction by packed sorbent are highlighted. These approaches, in common, aim the determination of analytes at low concentrations in complex matrices. This article describes some characteristics, recent advances, and trends on miniaturized sample preparation techniques, as well as their current applications in food, environmental, and bioanalysis fields.
Topics: Adsorption; Analytic Sample Preparation Methods; Environmental Monitoring; Environmental Pollution; Food Contamination; Liquid Phase Microextraction; Solid Phase Microextraction; Specimen Handling
PubMed: 31692234
DOI: 10.1002/jssc.201900776 -
European Journal of Surgical Oncology :... Oct 2021Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on...
BACKGROUND
Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS).
METHODS
This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review.
RESULTS
Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation.
CONCLUSIONS
A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS.
Topics: Adipose Tissue; Adiposity; Adult; Blood Vessels; Dose Fractionation, Radiation; Female; Humans; Liposarcoma, Myxoid; Magnetic Resonance Imaging; Male; Margins of Excision; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Peripheral Nerves; Preoperative Period; Prospective Studies; Radiotherapy, Adjuvant; Soft Tissue Neoplasms; Tumor Burden
PubMed: 34233858
DOI: 10.1016/j.ejso.2021.06.020 -
Cancer Radiotherapie : Journal de La... 2022Herein are presented the recommendations from the Société française de radiothérapie oncologique regarding indications and modalities of lung cancer radiotherapy....
Herein are presented the recommendations from the Société française de radiothérapie oncologique regarding indications and modalities of lung cancer radiotherapy. The recommendations for delineation of the target volumes and organs at risk are detailed.
Topics: Carcinoma, Non-Small-Cell Lung; Dose Fractionation, Radiation; France; Humans; Lung Neoplasms; Neoplasm Staging; Radiation Oncology; Radiotherapy; Radiotherapy Dosage; Radiotherapy, Image-Guided; Respiration; Small Cell Lung Carcinoma; Tumor Burden
PubMed: 34953709
DOI: 10.1016/j.canrad.2021.11.005 -
Seminars in Radiation Oncology Jul 2023Improvements in radiotherapy delivery have enabled higher therapeutic doses and improved efficacy, contributing to the growing number of long-term cancer survivors.... (Review)
Review
Improvements in radiotherapy delivery have enabled higher therapeutic doses and improved efficacy, contributing to the growing number of long-term cancer survivors. These survivors are at risk of developing late toxicity from radiotherapy, and the inability to predict who is most susceptible results in substantial impact on quality of life and limits further curative dose escalation. A predictive assay or algorithm for normal tissue radiosensitivity would allow more personalized treatment planning, reducing the burden of late toxicity, and improving the therapeutic index. Progress over the last 10 years has shown that the etiology of late clinical radiotoxicity is multifactorial and informs development of predictive models that combine information on treatment (eg, dose, adjuvant treatment), demographic and health behaviors (eg, smoking, age), co-morbidities (eg, diabetes, collagen vascular disease), and biology (eg, genetics, ex vivo functional assays). AI has emerged as a useful tool and is facilitating extraction of signal from large datasets and development of high-level multivariable models. Some models are progressing to evaluation in clinical trials, and we anticipate adoption of these into the clinical workflow in the coming years. Information on predicted risk of toxicity could prompt modification of radiotherapy delivery (eg, use of protons, altered dose and/or fractionation, reduced volume) or, in rare instances of very high predicted risk, avoidance of radiotherapy. Risk information can also be used to assist treatment decision-making for cancers where efficacy of radiotherapy is equivalent to other treatments (eg, low-risk prostate cancer) and can be used to guide follow-up screening in instances where radiotherapy is still the best choice to maximize tumor control probability. Here, we review promising predictive assays for clinical radiotoxicity and highlight studies that are progressing to develop an evidence base for clinical utility.
Topics: Male; Humans; Quality of Life; Prostatic Neoplasms; Dose Fractionation, Radiation; Radiation Tolerance; Radiation Injuries; Radiotherapy Dosage
PubMed: 37331785
DOI: 10.1016/j.semradonc.2023.03.010 -
Medical Physics Sep 2020Clinical studies in radiation therapy with conventional fractionation show a reduction in the tumor control probability (TCP) with an increase in the total and hypoxic...
PURPOSE
Clinical studies in radiation therapy with conventional fractionation show a reduction in the tumor control probability (TCP) with an increase in the total and hypoxic tumor volumes. The main objective of this article is to derive an analytical relationship between the TCP and the hypoxic and total tumor volumes. This relationship is applied to clinical data on the TCP reduction with increasing total tumor volume and, also, dose escalation to target tumor hypoxia.
METHODS
The TCP equation derived from the Poisson probability distribution predicts that both (a) an increase in the number of tumor clonogens and (b) an increase in the average cell surviving fraction are the factors contributing to the loss of local control. Using asymptotic mathematical properties of the TCP formula and the linear quadratic (LQ) cell survival model with two levels of hypoxic and oxygenated cells, we separated the TCP dependence on the total and hypoxic tumor volumes. The predicted trends in the local control as a function of total and hypoxic tumor volumes were evaluated in radiotherapy model problems with conventional dose fractionation for head and neck and non-small cell lung cancers. Tumor-specific parameters in the LQ model and the density of clonogens in the TCP model were taken from published data on predictive assays and the plating efficiency measurements, respectively.
RESULTS
Our simulations show that, at the dose levels used in conventional radiation therapy for head and neck and non-small cell lung cancers, the TCP dependence on the total tumor volume is negligible for completely oxygenated tumors. However, the presented results demonstrate that tumor hypoxia introduces a significant volume effect into estimates of the TCP. The extent of tumor hypoxia is a plausible mechanism to explain the TCP reduction with increasing total tumor volume observed in clinical studies. To achieve the same level of tumor control in a hypoxic tumor region relative to well oxygenated tumor regions, the delivered dose should, in principle, be escalated by a factor equal to the oxygen enhancement ratio (OER). The theoretically required hypoxia-targeted dose escalation could be as large as 100% because it has been estimated that hypoxic tumor regions may have an OER = 2 for conventional fractionation. However, our results indicate that clinically acceptable values of the TCP would require much lower hypoxia-targeted dose escalation (<50%) when the effects of total and hypoxic tumor volumes are taken into account.
CONCLUSIONS
The reported studies and models suggest that the effect of total tumor volume on the TCP is negligible for oxygenated head and neck and non-small cell lung tumors treated with conventional fractionation. According to our simulations, the volume effects in the TCP observed in clinical studies are defined primarily by the hypoxic volume. This information can be useful for the analysis of treatment outcomes and the dose escalation to target tumor hypoxia.
Topics: Cell Hypoxia; Humans; Hypoxia; Lung Neoplasms; Models, Biological; Probability
PubMed: 32452034
DOI: 10.1002/mp.14257 -
Physics in Medicine and Biology Aug 2023Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the...
Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the bystander effect were not yet made, the immune process presumably plays an important role in many aspects of the radiotherapy including the bystander effect. A mathematical model of immune response during and after radiation therapy is presented.Immune response of host body and immune suppression of tumor cells are modelled with four compartments in this study; viable tumor cells, T cell lymphocytes, immune triggering cells, and doomed cells. The growth of tumor was analyzed in two distinctive modes of tumor status (immune limited and immune escape) and its bifurcation condition.Tumors in the immune limited mode can grow only up to a finite size, named as terminal tumor volume analytically calculated from the model. The dynamics of the tumor growth in the immune escape mode is much more complex than the tumors in the immune limited mode especially when the status of tumor is close to the bifurcation condition. Radiation can kill tumor cells not only by radiation damage but also by boosting immune reaction.The model demonstrated that the highly heterogeneous dose distribution in spatially fractionated radiotherapy (SFRT) can make a drastic difference in tumor cell killing compared to the homogeneous dose distribution. SFRT cannot only enhance but also moderate the cell killing depending on the immune response triggered by many factors such as dose prescription parameters, tumor volume at the time of treatment and tumor characteristics. The model was applied to the lifted data of 67NR tumors on mice and a sarcoma patient treated multiple times over 1200 days for the treatment of tumor recurrence as a demonstration.
Topics: Mice; Animals; Neoplasms; Dose Fractionation, Radiation; Immunity; Radiotherapy
PubMed: 37459862
DOI: 10.1088/1361-6560/ace819