Suffice it to say that much of the residency training for radiation oncology involves navigating this complex maze of considerations to pick the right dose for the patient sitting in front of you! In fact, if you walk into a radiation clinic on an arbitrary Wednesday, you are likely to see an incredibly diverse set of doses for the patients being treated that day.
You may see:. How do radiation oncologists make sense of these numbers? First, it is important to note that both the total dose and the dose-per-fraction influence the overall intensity of the treatment. In fact, there is a formula that takes these two factors and computes a single number that quantifies the overall strength of the treatment. For instance, this formula predicts that for breast cancer, giving 45 Gy over 25 sessions is about equal to giving 40 Gy over 15 sessions.
In other words, even if radiation clinic A uses the first combination of dose and session number while radiation clinic B uses the second combination, the overall effect of the treatment on the cancer is the same in both cases. The general principle for definitive radiotherapy is to give as much radiation as it takes to maximize the probability of killing every last cancer cell in that tumor. This typically requires either a high total dose, a high fraction size, or both.
Sometimes a definitive treatment requires going up to the limit of what the normal tissues around the tumor can handle, which can make for a long treatment with more side effects.
If you have a family member or friend who underwent definitive radiotherapy for prostate cancer, you may have learned that the treatment required 7 or 8 weeks of daily therapy. Thankfully, as we mentioned in a prior post, a general trend has been to use precision technology to give more dose per session safely, which means that even definitive radiotherapy courses are moving toward shorter commitments of time.
The idea here is that surgery may remove a visible tumor, but that roots and stray cancer cells can be left behind. A middle intensity of radiation is quite effective at clearing out these leftovers after many cancer surgeries. The most common example of this is in early-stage breast cancer, where a surgeon removes the lump of cancer and a medium dose of radiation is delivered to the remaining breast tissue to clear any leftover cancer cells.
Palliative radiotherapy refers to the lowest part of the intensity range. Rather, palliative radiotherapy is meant to improve the life of the patient by shrinking a tumor that is causing the patient to suffer. Usually, a low dose of radiation is adequate to shrink a troublesome tumor and relieve a symptom like pain or bleeding. Furthermore, these low doses of radiotherapy have minimal side effects and can be delivered over short, convenient timeframes, so that the patient can spend less time in therapy and more time with their loved ones.
These categories are a helpful way to think about radiotherapy in all the different contexts that it is used, both alone and in combination with other treatments.
This framework also helps us understand how one treatment can have the versatility to treat different cancers and across different stages of disease. Sadly, many patients who need radiotherapy do not have access to it, and this occurs in both advanced and developing countries. For instance, among European countries, one out of every four patients who need radiotherapy do not have access to it 2.
And the situation is even worse in lower and middle income countries; one report found that only 4 out of of these developing countries had enough radiotherapy units to meet the needs of their population 3. Indeed, making sure that effective, affordable, life-saving radiotherapy is available to all the patients who need it is one of the major global population health challenges of our generation. Although our results are contrary to what has been previously reported, they raise interesting questions about how ultra-high dose rate RT can have a normal tissue toxicity sparing effect based upon the organ irradiated, dose used, fraction size, beam energy, and the type of radiation being tested.
From a translational research perspective, given the widespread availability of X-rays or protons, future studies should be geared towards employing these radiation beams in a fractionation and dosing format that is clinically relevant.
Current configurations of cyclotron-based accelerators, more so that synchrotron-based accelerators, can more readily deliver the ultra-high dose rates needed for FLASH RT. The optimal dose rate for sparing these normal tissues, if any, remains to be defined. Future experiments should be geared towards defining the optimal dose, dose rate, and fraction size for reducing specific normal tissue complication probabilities for specific organs irradiated in protocols that mimic clinical treatment scenarios.
KPC and Panc02 were cultured under sterile conditions and with media recommended by the supplier. All reagents were of analytical grade. This entailed use of the gun current settings for 6 MV photons, removal of the target and the flattening filter, and rigging of the gating relay to start and stop irradiation within milliseconds under automatic control.
We confirmed dose, dose rate and field uniformity using EBT3 film, thermoluminescent dosimeters TLDs , Farmer ion chambers, and a parallel plate chamber.
EBT3 film and a Farmer ion chamber measurement were used for each experimental irradiation. For the conventional irradiation, we used a Varian True Beam and delivered radiation at 0. In our ultra-high dose rate FLASH irradiation system, the mice were irradiated on a platform in the head of the linear accelerators gantry with customized lead cutouts that focused the radiation only on the areas of interest.
See Supplementary data. When colonies became visible to the naked eye, the plates were stained with 0. Each experiment was done in triplicate. All mice were quarantined for 3 days before any experiments were begun. Facial venous blood was collected for peripheral blood flow cytometry.
Then, cells were washed and fixed with 1. The cells were run through a Gallios flow cytometer and the collected data was analyzed using Kaluza software. All experiments were carried out in triplicate otherwise specified. Results are presented as means and standard errors SE. Statistically significant differences were calculated by using two-tailed unpaired t tests or by one-way analysis of variance.
An amendment to this paper has been published and can be accessed via a link at the top of the paper. Delaney, G. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer , — Article Google Scholar. Favaudon, V. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.
Sci Transl Med 6 , ra Vozenin, M. Clin Cancer Res 25 , 35—42 Montay-Gruel, P. Radiother Oncol , — X-rays can trigger the FLASH effect: Ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice. Schippers, J. Emerging technologies in proton therapy. Acta Oncol 50 , — Matsuura, T. Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau.
Med Phys 37 , — Grossman, S. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 17 , — Moon, H. Prognostic value of nutritional and hematologic markers in head and neck squamous cell carcinoma treated by chemoradiotherapy. Chadha, A. Tang, C. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes.
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Anticancer Res 36 , — Clinical status and rate of recovery of blood lymphocyte levels after radiotherapy for bladder cancer. Cancer Res 39 , — PubMed Google Scholar. Pike, L. Shiraishi, Y. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy. Saito, T. In Vivo 32 , — Fang, P. High lymphocyte count during neoadjuvant chemoradiotherapy is associated with improved pathologic complete response in esophageal cancer.
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Am J Clin Oncol 38 , — Liu, J. Radiation-related lymphopenia is associated with spleen irradiation dose during radiotherapy in patients with hepatocellular carcinoma. Radiat Oncol 12 , 90 The gray Gy is the SI International System of Units unit of absorbed radiation dose of ionizing radiation for example, X-rays , and is defined as the absorption of one joule of ionizing radiation by one kilogram of matter usually human tissue.
The radiation dose administered records the largest prescribed dose to the target. This means that for patients that have a boost treatment, the largest prescribed dose is the addition of the boost to the other phases of treatment.
Record the largest prescribed dose to the target site for all courses of radiotherapy delivered to the patient during the course of treatment.
The patient may receive more than one course of radiotherapy during the course of treatment. For example, radiotherapy may be administered to the primary site and the site of a distant metastasis. Record the radiation dose received for each course of treatment. The radiation dose administered is recorded regardless of whether the course of treatment is completed as intended, and regardless of the intent or timing of treatment.
The International Commission on Radiation Units and Measurements ICRU develops internationally acceptable recommendations regarding quantities and units of radiation and radioactivity, procedures suitable for the measurement and application of these quantities in clinical radiology and radiobiology, and physical data needed in the application of these procedures to support uniformity in reporting.
The ICRU recommends recording doses at the axis point where applicable opposed fields, four field box, wedged pairs and so on. The ICRU50 reference dose should be recorded for photon therapy if available, otherwise a description of the received dose at the centre of the planning target volume. The ICRU58 should be recorded for brachytherapy. For maximum consistency in this field, the ICRU recommendations should be followed whenever possible.
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