scholarly journals To fractionate or not to fractionate? That is the question for the radiosurgery of hypoxic tumors

2014 ◽  
Vol 121 (Suppl_2) ◽  
pp. 110-115 ◽  
Author(s):  
Iuliana Toma-Dasu ◽  
Helena Sandström ◽  
Pierre Barsoum ◽  
Alexandru Dasu

ObjectThis study aimed to investigate the impact of tumor hypoxia on treatment outcome for metastases commonly treated with radiosurgery using 1 fraction of radiation and the potential gain from reoxygenation if the treatment is delivered in a few radiation fractions.MethodsIn silico metastasis-like radiosurgery targets were modeled with respect to size, density of clonogenic cells, and oxygenation. Treatment plans were produced for the targets using Leksell GammaPlan, delivering clinically relevant doses and evaluating the tumor control probability (TCP) that could be expected in each case. Fractionated schedules with 3, 4, and 5 fractions resulting in similar biological effective doses were also considered for the larger target, and TCP was determined under the assumption that local reoxygenation takes place between fractions.ResultsThe results showed that well-oxygenated small- and medium-size metastases are well controlled by radiosurgery treatments delivering 20 or 22 Gy at the periphery, with TCPs ranging from 90% to 100%. If they are moderately hypoxic, the TCP could decrease to 60%. For large metastases, the TCPs from single-fraction treatments ranged from 0% to 19%, depending on tumor oxygenation. However, for fractionated treatments, the TCP for hypoxic tumors could significantly increase up to 51%, if reoxygenation occurs between fractions.ConclusionsThis study shows that hypoxia worsens the response to single-fraction radiosurgery, especially for large tumors. However, fractionated therapy for large hypoxic tumors might considerably improve the TCP and might constitute a simple way to improve the outcome of radiosurgery for patients with hypoxic tumors.

2021 ◽  
pp. 1-9
Author(s):  
I. Jonathan Pomeraniec ◽  
Zhiyuan Xu ◽  
Cheng-Chia Lee ◽  
Huai-Che Yang ◽  
Tomas Chytka ◽  
...  

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15505-e15505
Author(s):  
Lu Wang ◽  
Jinming Yu

e15505 Background: Based on dosimetry and radiobiology to compare treatment plans for esophageal cancer (EC) in different location using intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT) and helical tomotherapy(HT) with simultaneous integrated boost (SIB) technique. Methods: A total of 20 patients including 5 cases respectively located in the cervix, upper, middle and lower thorax were generated for IMRT, VMAT and HT plans. The dose volume histogram statistics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP) and normal tissues control probability (NTCP) were analyzed to evaluate treatment plans. Results: HT showed significantly improvement over IMRT and VMAT in terms of CI(0.93±0.03), HI(0.07±0.03) and TCP(88.08±0.82%) in cervical EC(p<0.05). IMRT greatly developed TCP(88.29±1.79%;85.11±0.79%), and offered superior CIs (0.87±0.04;0.90±0.01) and HIs(0.10±0.01; 0.06±0.01) compared with VMAT and HT in upper and middle thoracic EC(p<0.05). Meanwhile, the V30(33.30±6.49%), mean dose (2559.00±219.64cGy) and NTCP(0.50±0.61%) of heart for IMRT were significantly reduced than other two techniques in middle thoracic EC. Patients with lower thoracic EC yielded the similar CIs and HIs(all p>0.05) for the 3 techniques, but VMAT showed the lowest NTCP of lungs (0.01±0.01%) with improved TCP (84.84±1.13%). Conclusions: HT was a good option with little lung and heart involvement as it achieved superior dose conformality and uniformity. IMRT was a perfect strategy with large thoracic involvement. It significantly improved tumor local control and reduced heart dose and complications with acceptable dose to lungs. VMAT was preferred with a smaller target volume but surrounded by more heart and less lungs. Individually choosing optimal technique for EC in different location will be warranted.


2013 ◽  
Vol 119 (5) ◽  
pp. 1131-1138 ◽  
Author(s):  
Eric K. Oermann ◽  
Marie-Adele S. Kress ◽  
Jonathan V. Todd ◽  
Brian T. Collins ◽  
Riane Hoffman ◽  
...  

Object Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2–5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. Methods The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2–5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. Results There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83–6.91, p = 0.032). Conclusions Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.


2012 ◽  
Vol 12 (2) ◽  
pp. 154-162
Author(s):  
Courtney Knaup ◽  
Panayiotis Mavroidis ◽  
Carlos Esquivel ◽  
Sotirios Stathakis ◽  
Gregory Swanson ◽  
...  

AbstractPurpose: Several isotopes are available for low dose-rate prostate brachytherapy. Currently most implants use a single isotope. However, the use of dual-isotope implants may yield an advantageous combination of characteristics such as half-life and relative biological effectiveness. However, the use of dual-isotope implants complicates treatment planning and quality assurance. Do the benefits of dual-isotope implants outweigh the added difficulty? The goal of this work was to use a linear-quadratic model to compare single and dual-isotope implants.Materials & Methods: Ten patients were evaluated. For each patient, six treatment plans were created with single or dual-isotope combinations of 125I, 103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were contoured by a physician. The biologically effective dose was used to determine the tumor control probability and normal tissue complication probabilities for each plan. Each plan was evaluated using favorable, intermediate and unfavorable radiobiological parameters. The results of the radiobiological analysis were used to compare the single and dual-isotope treatment plans.Results: Iodine-125 only implants were seen to be most affected by changes in tumor parameters. Significant differences in organ response probabilities were seen at common dose levels. However, after adjusting the initial seed strength the differences between isotope combinations were minimal.Conclusions: The objective of this work was to perform a radiobiologically based comparison of single and dual-isotope prostate seed implant plans. For all isotope combinations, the plans were improved by varying the initial seed strength. For the optimized treatment plans, no substantial differences in predicted treatment outcomes were seen among the different isotope combinations.


2016 ◽  
Vol 57 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Iori Sumida ◽  
Hajime Yamaguchi ◽  
Indra J. Das ◽  
Hisao Kizaki ◽  
Keiko Aboshi ◽  
...  

Abstract The purpose of this study was to evaluate the impact of the motion interplay effect in early-stage left-sided breast cancer intensity-modulated radiation therapy (IMRT), incorporating the radiobiological gamma index (RGI). The IMRT dosimetry for various breathing amplitudes and cycles was investigated in 10 patients. The predicted dose was calculated using the convolution of segmented measured doses. The physical gamma index (PGI) of the planning target volume (PTV) and the organs at risk (OAR) was calculated by comparing the original with the predicted dose distributions. The RGI was calculated from the PGI using the tumor control probability (TCP) and the normal tissue complication probability (NTCP). The predicted mean dose and the generalized equivalent uniform dose (gEUD) to the target with various breathing amplitudes were lower than the original dose (P &lt; 0.01). The predicted mean dose and gEUD to the OARs with motion were higher than for the original dose to the OARs (P &lt; 0.01). However, the predicted data did not differ significantly between the various breathing cycles for either the PTV or the OARs. The mean RGI gamma passing rate for the PTV was higher than that for the PGI (P &lt; 0.01), and for OARs, the RGI values were higher than those for the PGI (P &lt; 0.01). The gamma passing rates of the RGI for the target and the OARs other than the contralateral lung differed significantly from those of the PGI under organ motion. Provided an NTCP value &lt;0.05 is considered acceptable, it may be possible, by taking breathing motion into consideration, to escalate the dose to achieve the PTV coverage without compromising the TCP.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5764
Author(s):  
Stephan Scheidegger ◽  
Sergio Mingo Barba ◽  
Udo S. Gaipl

There is some evidence that radiotherapy (RT) can trigger anti-tumor immune responses. In addition, hyperthermia (HT) is known to be a tumor cell radio-sensitizer. How HT could enhance the anti-tumor immune response produced by RT is still an open question. The aim of this study is the evaluation of potential dynamic effects regarding the adaptive immune response induced by different combinations of RT fractions with HT. The adaptive immune system is considered as a trainable unit (perceptron) which compares danger signals released by necrotic or apoptotic cell death with the presence of tumor- and host tissue cell population-specific molecular patterns (antigens). To mimic the changes produced by HT such as cell radio-sensitization or increase of the blood perfusion after hyperthermia, simplistic biophysical models were included. To study the effectiveness of the different RT+HT treatments, the Tumor Control Probability (TCP) was calculated. In the considered scenarios, the major effect of HT is related to the enhancement of the cell radio-sensitivity while perfusion or heat-based effects on the immune system seem to contribute less. Moreover, no tumor vaccination effect has been observed. In the presented scenarios, HT boosts the RT cell killing but it does not fundamentally change the anti-tumor immune response.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4899
Author(s):  
Pavel Stavrev ◽  
Nadejda Stavreva ◽  
Boriana Genova ◽  
Ruggero Ruggieri ◽  
Filippo Alongi ◽  
...  

Background: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. Methods: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. Results: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. Conclusions: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.


2011 ◽  
Vol 100 (3) ◽  
pp. 344-350 ◽  
Author(s):  
Christian Siedschlag ◽  
Liesbeth Boersma ◽  
Judith van Loon ◽  
Maddalena Rossi ◽  
Angela van Baardwijk ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document