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PURPOSE To assess the role of reoxygenation of hypoxic tumor cells in hypofractionated radiotherapy of prostate cancer. METHODS The considered radiobiological model is based on the assumption of two populations (compartments) of cells: oxygenated (aerobic) cells and hypoxic cells. After each fraction of radiation, some of the hypoxic cells reoxygenate while a fraction of initially aerobic cells becomes hypoxic. The kinetics of this process between successive treatments is described by coupled, first-order differential equations. To determine the effect of reoxygenation on cell kill in the treatment target, we utilize the linear-quadratic (LQ) model assuming different radiosensitivities for the aerobic and hypoxic cells. RESULTS Analytical solutions for the number of surviving malignant cells are obtained for special cases of slow and fast reoxygenation. The radiobiological effect of reoxygenation for different fractionation regimens is also evaluated numerically. CONCLUSIONS In this study, a radiobiological model for kinetics of reoxygenation in tumors is used to evaluate different fractionation schedules in radiotherapy of prostate cancer. The obtained results indicate that in the case of low alpha/beta ratio for malignant cells (e.g., α/β = 1.5 Gy), treatment schedule with 4-10 fractions and dose per fraction >4-5 Gy can result in increased cell kill in the treatment target at the same level of rectal toxicity as compared to conventional fractionation. The findings of this study also suggest that radiotherapy of the prostate with 1-3 fractions can be radiobiologically inferior to treatments with greater number of fractions.

The main method of treating rare mesenchymal tumors PEComas is surgical removal of the tumor and external-beam radiation therapy has historically been considered ineffective. However, the individual cases in the foreign literature as well as this article authors’ experience in the form of the clinical case provided in it shows the possibility of achieving some anti-tumor effect due to the use of aggressive variants of radiation therapy. The use of variations of stereotactic radiotherapy with high dose per fraction and sum dose as an neoadjuvant and definitive treatment looks promising.

Purpose\ud A graphical user interface (GUI) was developed to aid in the assessment of changes in the radiation tolerance of spinal cord/similar central nervous system tissues with time between two individual treatment courses.\ud \ud Methods\ud The GUI allows any combination of photons, protons (or ions) to be used as the initial, or retreatment, radiotherapy courses. Allowances for clinical circumstances, of reduced tolerance, can also be made. The radiobiological model was published previously and has been incorporated with additional checks and safety features, to be as safe to use as possible. The proton option includes use of a fixed RBE of 1.1 (set as the default), or a variable RBE, the latter depending on the proton linear energy transfer (LET) for organs at risk. This second LET-based approach can also be used for ions, by changing the LET parameters.\ud \ud Results\ud GUI screenshots are used to show the input and output parameters for different clinical situations used in worked examples. The results from the GUI are in agreement with manual calculations, but the results are now rapidly available without tedious and error-prone manual computations. The software outputs provide a maximum dose limit boundary, which should not be exceeded. Clinicians may also choose to further lower the number of treatment fractions, whilst using the same dose per fraction (or conversely a lower dose per fraction but with the same number of fractions) in order to achieve the intended clinical benefit as safely as possible.\ud \ud Conclusions\ud The new GUI will allow scientific-based estimations of time related radiation tolerance changes in the spinal cord and similar central nervous tissues (optic chiasm, brainstem), which can be used to guide the choice of retreatment dose fractionation schedules, with either photons, protons or ions.

Background The aim of the study was to update our experience treating patients with glottic carcinoma in situ (CIS) with curative radiotherapy (RT). Methods Fifty patients received continuous-course RT using once-daily fractionation. Twenty-eight (56%) had recurrent or persistent CIS after resection. Median total dose was 63.0 Gy; median dose per fraction was 2.25 Gy. Median follow-up was 9.6 years for all patients and 8.4 years for survivors. Results After RT, 5 patients (10%) recurred locally; salvage surgery was performed in 4 (1 refused). Five-year outcomes were as follows: local control, 91%; ultimate local control (including patients successfully salvaged after local recurrence), 100%; ultimate local control with larynx preservation, 93%; local-regional control, 91%; ultimate local-regional control, 100%; distant metastases-free survival, 100%; cause-specific survival, 100%; and overall survival, 81%. No patient experienced a severe complication. Conclusion RT is an excellent treatment for patients with CIS recurrent after transoral excision and those with previously untreated CIS who are unsuitable for partial laryngectomy.

Aims To evaluate survival outcomes and toxicology profiles in oligometastatic/oligoprogressive patients treated with SBRT for adrenal metastases. Methods We retrospectively analyzed 25 metastatic adrenal lesions in 24 oligometastatic/oligoprogressive patients undergoing ablative Stereotactic Body Radiation Therapy (SBRT) between February 2010 and November 2019 in our department. The primary endpoint was overall survival (OS). Secondary endpoints were local overall response rate (ORR), acute and late toxicities. Results The most common primary tumor was non-small cell lung cancer (54%). Twenty-one patients received chemo or immuno-therapy. The median planning target volume (PTV) was 41.7 cm3. Median SBRT dose was 36 Gy. Median dose per fraction was 15 Gy. Median survival was 35-months with OS outcomes ranging from 6-months (100%), 1-year (87.5%) and 2-years (66.7%). ORR based on RECIST criteria was 66.5%. 12 patients experienced acute toxicities, mostly grade 1-2 (8 patients, 32%). Conclusions SBRT for oligometastatic/oligoprogressive patients with adrenal metastases showed acceptable survival outcomes and a safe toxicity profile.

Strahlentherapie und Onkologie 196(8), 679 - 682 (2020). doi:10.1007/s00066-020-01635-7, Published by Springer Medizin, Heidelberg

Background/aim Radiotherapy is widely accepted as the treatment of choice for early glottic squamous cell carcinoma (EGSCC), although it varies greatly with respect to dose, dose per fraction, and treatment techniques. The study aim was to evaluate the use of accelerated fractionation strategy (AFS) for EGSCC in standard clinical practice. Patients and methods Patients treated with definitive radiotherapy for EGSCC between 2008 and 2019 were retrospectively identified and received either conventional fractionation, hypofractionation, or hyperfractionation. Results One hundred six patients were analyzed, and 19, 71, and 16 patients underwent conventional fractionation, hypofractionation, and hyperfractionation, respectively. The median follow-up was 56 months. The 5-year local control and overall survival rates were 79% and 83%; 78% and 79%; and 87% and 77%, respectively, and no significant difference was observed between the fractionation schedules. Conclusion Our findings confirmed the utility of AFS in standard clinical practice and support its use for patients with EGSCC.

Radiotherapy (RT) has been developed with remarkable technological advances in recent years. The accuracy of RT is dramatically improved and accordingly high dose radiation of the tumors could be precisely projected. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), are rapidly becoming the accepted practice in treating solid small sized tumors. Compared with the conventional fractionation external beam radiotherapy (EBRT), SABR with very high dose per fraction and hypo-fractionated irradiation yields convincing and satisfied therapeutic effects with low toxicity, since tumor cells could be directly ablated like radiofrequency ablation (RFA). The impressive clinical efficacy of SABR is greater than expected by the linear quadratic model and the conventional radiobiological principles, i.e., 4 Rs of radiobiology (reoxygenation, repair, redistribution, and repopulation), which may no longer be suitable for the explanation of SABR's ablation effects. Based on 4 Rs of radiobiology, 5 Rs of radiobiology emphasizes the intrinsic radiosensitivity of tumor cells, which may correlate with the responsiveness of SABR. Meanwhile, SABR induced the radiobiological alteration including vascular endothelial injury and the immune activation, which has been indicated by literature reported to play a crucial role in tumor control. However, a comprehensive review involving these advances in SABR is lacking. In this review, advances in radiobiology of SABR including the role of the 4 Rs of radiobiology and potential radiobiological factors for SABR will be comprehensively reviewed and discussed.

Purpose: The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved. Methods: Dose–response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test. Results: The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose–response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above. Conclusion: The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.

Purpose More than a decade of randomized controlled trials in prostate cancer has established a positive radiation dose response at moderate doses and a consistently low α/β ratio in the linear quadratic model for moderate hypofractionation. The recently published large randomized trial of ultrahypofractionated prostate cancer radiation therapy adds substantially to our current knowledge of dose response and fractionation sensitivity. Methods and Materials Randomized trials of dose escalation and hypofractionation of radiation therapy were meta-analyzed to yield the overall best estimate of the α/β ratio. Additionally, a putative saturation of dose effect previously reported at approximately 80 Gy EQD2 was investigated by mapping the relative effectiveness assessed at 5 years onto a single reference dose-response curve. Results Meta-analysis of 14 randomized trials including 13,384 patients yielded a best estimate of α/β = 1.6 Gy (95% confidence interval, 1.3-2.0 Gy) but with highly significant heterogeneity (I2 = 70%, P = .0005). Further analysis indicated an association between increasing dose per fraction in the experimental arm and increasing α/β ratio (slope, 0.6 Gy increase in α/β per Gy increase in fraction size; P = .017). This deviation from the linear quadratic model could, however, also be explained by biochemical control maxing out at doses above approximately 80 Gy. Conclusions Biochemical control data from randomized controlled trials of dose-per-fraction escalation in prostate cancer radiation therapy are inconsistent with the presence of a constant fractionation sensitivity in the linear-quadratic model and/or a monotonic dose response for biochemical control beyond 80 Gy equivalent dose. These observations have a potential effect on the optimal doses in future trials and the interpretation of ongoing trials of ultrahypofractionation.

Several studies have reported changes in dose distribution and delivery time based on the value of specific planning parameters [field width (FW), pitch, and modulation factor (MF)] in tomotherapy. However, the variation in the parameters between different facilities is unknown. The purpose of this study was to determine standard values of the above parameters for cases of head and neck cancer (HNC) and prostate cancer (PC) in Japan. In this survey, a web-based questionnaire was sent to 48 facilities performing radiation therapy with tomotherapy in March 2016. The deadline for data submission was April 2016. In the questionnaire, the values of the planning parameters usually used were requested and 23 responses were received, representing a response rate of 48% (23/48). The FW selected was 2.5 cm in most facilities, and facilities with a tomoEDGE license used dynamic FW rather than fixed FW. Facilities changed the pitch based on FW, dose per fraction, or target offset more frequently in HNC than in PC. In contrast, >50% of the facilities used the magic number proposed by Kissick et al. Median preset MFs (range, min to max) in HNC and PC were 2.4 (1.8-2.8) and 2.0 (1.8-3.0), respectively, and MF values showed large variations between the facilities. Our results are likely to be useful to several facilities designing treatment plans in tomotherapy.

Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter1 cm). As part of these treatments, effective detection and precise segmentation of lesions are imperative. Many methods based on deep-learning approaches have been developed for the automatic segmentation of gliomas, but very little for that of brain metastases. We adapted an existing 3D convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI.

The purpose of this study is to evaluate the effect of nonrigid and fractionation-corrected dose summation on total doses in radiotherapy and to demonstrate the benefits of such dose summation on clinical decision-making for planning of retreatments. Dose summation of organs at risk (OARs) was investigated for 3 clinical cases with need of retreatment to the same site: head and neck, brain, and mediastinum. Three different summation methods over old and new radiotherapy treatment plans are presented and compared: (1) rigid raw sum with rigid registration of the planning images and direct dose summing; (2) deformable raw sum with deformable image registration and direct dose summing; and (3) deformable biological sum with deformable registration and takes into account the dose per fraction in biological manner in certain critical organs. In 2 cases, a user-defined dose downscaling is applied to take into account the time between the treatments and the healing from the radiation-induced effects. Of the 3 summation methods presented, the deformable biological sum was considered to offer the most biologically plausible account of the treatment. There were remarkable differences between near-maximum doses (D0.1cc) and dose-volume histogram (DVH) curves for OARs between different summation methods. The differences between deformable raw sum and rigid raw sum D0.1cc doses are in the range from −8 Gy to 2 Gy. Similarly, the deviation was from −14 Gy to 5 Gy for the deformable biological sum compared with the rigid raw sum. These differences come from incorrect summation of doses in the rigid raw sum case, and from the dose per fraction effect in biological summation. We conclude that computing the 3-dimensional deformable biological summation could be a valuable tool for treating patients with complex retreatments. It has the potential to assist the oncologist in refining plans for maximally curative doses while respecting appropriate tissue tolerances.

Flattening filter free (FFF) beams are now commonly available with new standard linear accelerators. These beams have recognised clinical advantages in certain circumstances, most notably the reduced beam-on times for high dose per fraction stereotactic treatments. Therefore FFF techniques are quickly being introduced into clinical use. The purpose of this report is to provide practical implementation advice and references for centres implementing FFF beams clinically. In particular UK-specific guidance is given for reference dosimetry and radiation protection.

Granulocytic sarcomas, also referred to as chloromas or myeloid sarcomas, are extramedullary neoplasms that are composed of immature myeloid cells. This uncommon disease is known to be radiosensitive. However, the total dose and dose per fraction are not standardized. In addition, during the course of radiation therapy, significant reduction of the tumor is usually obtained. Thus, target volume reduction may require an intermediate radiotherapy plan evaluation for an adaptive treatment. A second plan at mid-dose is highly recommended.

Purpose To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15) consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.

339 Background: Stereotactic Body Radiotherapy (SBRT) delivers high dose per fraction radiotherapy to targets with high precision. Such hypofractionated RT appears to act as an immune adjuvant, altering the tumor infiltrating immune landscape and enriching it for lymphocytes as numerous preclinical investigations would suggest. Based on this hypothesis, hundreds of ongoing trials listed in clinicaltrials.gov currently test the combination of RT (largely SBRT) with various immunotherapies. However, studies directly measuring the representation of infiltrating immune cells after SBRT in patients are few and far between and none exist in the context of prostate cancer. We therefore sought to interrogate the tumor-immune interface after prostate SBRT using fresh tissue in patients. Methods: Fresh prostate tissue from patients (N=10) enrolled in a clinical trial of prostate SBRT (three fractions of 8 Gy directed to the prostate and seminal vesicles) in the neoadjuvant setting two weeks prior to radical prostatectomy was subjected to multicolor flow cytometry and compared to that of Gleason Grade and T stage matched controls who did not undergo neoadjuvant therapy. Results: With a threshold of significance level of 0.05 for unadjusted p-values, using two-sided two-sample t-test, myeloid cells and particularly CD14+/hiCD16+DR+ intermediate monocytes/macrophages were enriched, while lymphocytes, including T cells and CD56+16− NK cells were decreased in SBRT-treated prostates as compared to unirradiated controls. Conclusions: The immune infiltrates in prostates two weeks after SBRT demonstrates a significant lymphoid to myeloid shift consistent with a tumor microenvironment after SBRT that is likely immunosuppressive beyond what can be targeted through the PD-1/L1 or CTLA-4 axis alone. This may have implications for the design of immunotherapy trials, especially in prostate cancer, that test SBRT in combination with immunotherapies.

For prostate cancer radiation therapy, daily sessions spanning approximately 2 months has been considered the standard of care for patients managed with curative intent. In recent years, data has emerged which supports the use of higher dose per fraction schemes leading to a reduced duration of treatment. This form of radiation—generally termed moderate hypofractionation or stereotactic body radiation therapy—increasingly appears to be a safe and effective alternative to the conventional course. This review summarizes salient data from the literature on outcomes, toxicities, and future directions for this innovative strategy of care.

Objective: To evaluate the outcomes of radical intent radiation therapy in early glottic carcinoma (EGC), including local control rate (LCR), disease-free survival (DFS), death specific free survival (DSFS), and overall survival (OS) rates, in Saudi patients treated at a single institution. Materials and methods: This is an institutional review board (IRB) approved, retrospective study of 27 patients with T1-2 N0 M0, early glottic carcinoma (EGC) who were treated from 2010 to 2015 at our institution with different radiotherapy (RT) fractionation regimens. The regimens included six different fractionation schedules of radiotherapy (RT): 50 Gy (20 x 2.5 Gy) dose prescribed to 95% isodose line, 52.4 Gy (20 x 2.52 Gy), 63 Gy (28 x 2.25 Gy), 66 Gy (33 x 2 Gy), and 70 Gy (35 x 2 Gy). The cohort was stratified into two groups, ≤ 52.5 Gy (n=15) and > 52.5 Gy (n=12). The median follow-up of all patients was 31.7 months (range 7-82). Results: The mean age of the cohort was 64.5 years (median 65, range: 41-83). Eleven patients (40.7%) had a history of smoking. The majority of the cohort was with T1a EGC (70.4%, n=19), and anterior commissure invasion was seen in three patients (11.1%). The mean RT doses were 55.6 Gy (range: 50-70). The five-year LCR, DFS, DSFS, and OS rates were 83.1%, 80.0%, 96.2%, and 92.6%, respectively. The LCR rates for those receiving a dose of 52.5 Gy or less were 61.3 months compared to 89.5 months for those who received more than 52.5 Gy (p=0.994). Non-smokers and patients with an unknown smoking history achieved a five-year LCR of 100%, while patients with a positive smoking history achieved a five-year LCR of 60.6% (p=0.044). Conclusion: Radiation therapy for EGC in our patients showed reasonable five-year LCR with larynx preservation at 83.1%, DFS 80.0%, five-year OS rate 92.6%, and DSFS rate 96.2%. We found that smoking had a significant correlation with LCR. However, large prospective trials are warranted to evaluate the efficacy of overall treatment time, dose per fraction of above 2 Gy, and smoking effect.

In intensity modulated radiation therapy (IMRT), the dose in each voxel of the organs at risk (OAR) can be strongly reduced compared to conformal radiation therapy (RT). Due to the sensitivity of late side-effects to fraction size, a smaller dose per fraction in the normal tissues represent an increased tolerance to RT. This expected reduction in biological effect may then be used as an additional degree of freedom during IMRT optimization. In this study, the comparison between plans optimized with and without a voxel-based fractionation correction was made. Four patients diagnosed with a head and neck (HN), a breast, a lung or a prostate tumor were used as test cases. Voxel-based fractionation corrections were incorporated into the optimization algorithm by converting the dose in each normal tissue voxel to EQD2 (equivalent dose delivered at 2 Gy per fraction). The maximum gain in the probability of tumor control (PB), due to the incorporation of the correction for fractionation in each voxel, was 1.3% with a 0.1% increase in the probability of complications (PI) for the HN tumor case. However, in plan optimization and evaluation, when tolerance doses were compared with the respective planned EQD2 (calculated from the 3-dimensional dose distribution), PB increased by 19.3% in the HN, 12.5% in the lung, 6.2% in the breast and 2.7% in the prostate tumor case, respectively. The corresponding increases in PI were 2.3%, 6.2%, 1.0% and 0.7%, respectively. Incorporating voxel-based fractionation corrections in plan optimization is important to be able to show the clinical quality of a given plan against established tolerance constraints. To properly compare different plans, their dose distributions should be converted to a common fractionation scheme (e.g. 2 Gy per fraction) for which the doses have been associated with clinical outcomes.

Purpose: The aim of this publication is to compile available literature data and expert experience regarding skin brachytherapy (BT) in order to produce general recommendations on behalf of the GEC-ESTRO Group. Methods: We have done an exhaustive review of published articles to look for general recommendations. Results: Randomized controlled trials, systemic reviews and meta-analysis are lacking in literature and there is wide variety of prescription techniques successfully used across the radiotherapy centers. BT can be delivered as superficial application (also called contact BT or plesiotherapy) or as interstitial for tumours thicker than 5 mm within any surface, including very irregular. In selected cases, particularly in tumours located within curved surfaces, BT can be advantageous modality from dosimetric and planning point of view when compared to external beam radiotherapy. The general rule in skin BT is that the smaller the target volume, the highest dose per fraction and the shortest overall length of treatment can be used. Conclusion: Skin cancer incidence is rising worldwide. BT offers an effective non-invasive or minimally invasive and relative short treatment that particularly appeals to elder and frail population. (C) 2018 The Authors. Published by Elsevier B.V.

Purpose Aim of the work is to model biochemical free survival at five year (5 y BCFS), based on literature clinical outcome data available until now and to evaluate parameters describing dose-fractionation radiosensitivity and repopulation. Methods Twenty-six data sets published in literature reporting the 5 y BCFS, dose scheduling, androgen deprivation therapy (ADT) and clinical variables, have been considered for a total of 17949 prostate cancer patients treated with external beam radiation therapy (EBRT), with and without ADT with dose per fraction from 1.80 Gy/fr to 7.25 Gy/fr and overall treatment time (OTT) from 1 week to 10 weeks. Fifteen patients groups have been built considering the risk class and the use of ADT. At first, for each group, D50 and g50 parameters were calculated. Then, dprolif, Tprolif and α / β parameters have been evaluated considering three hypothesis: dependence and not on OTT and dependence only on OTTs difference. Results The median values of D50 and g50 were 57 Gy and 1.7 for low risk patients, 61 Gy and 1.8 for intermediate risk patients and 68 Gy and 1.9 for high risk patients. For intermediate and high risk patients, a reduction of 4 Gy for D50 and 0.5 for g50 for ADT respect to no ADT treated patients was found. Not considering OTT dependence, the median α / β value parameter was in the range 0.8 Gy–2.6 Gy for the groups analysed. Median value of the dprolif was in the range 0.0 Gy/d–0.3 Gy/d while a median value of Tprolif parameter greater than 20 days was obtained. Conclusions Low α / β values have been confirmed for each risk class and the use of ADT seems to reduce median α / β values for intermediate and high risk patients. α / β values lower than values for late normal tissue morbidity increase and support the interest of hypofractionated radiotherapy schedules for all risk groups.

Breast cancer (ВС) is a common malignant disease of the female reproductive system. Currently we have many treatment strategies given location depending on the clinical data. Radiation therapy is an important component in a comprehensive program of treatment for ВС. Despite the fact that often use a single dose fractionation regime 1.8–2 Gy daily fractions to a total of 50 Gy in 5 weeks, do not run out to try to find new modes of fractionation. According to published research results hypofractionated regimes, we can conclude that the approaches to the value of the dose per fraction, the number of fractions and the time of treatment differ. Dose per fraction ranged from 2.66 to 3.2 Gy, and more recently have been tested modes with a single dose of 6 Gy. Empirical data from these studies are important, but must also be aware of the possibility of applying mathematical methods for computing the probability of cure of the tumor and the occurrence of radiation complications. It is necessary for an individual approach to each patient, picking up for some clinical cases the optimal mode of fractionation. In addition, the search continues and improvement fractionation regimes, and the results of clinical trials can tell a lot about how good the chosen model. In work the opportunity of application of the synthesized mathematical model (SM model), intended for description of NTCP, to the description of probability of local treatment of early stages of the ВС.

Radiation therapy delivered with hypofractionation, which involves the delivery of a higher dose per fraction in fewer fractions (generally with a lower total nominal dose) over a shorter overall treatment time, is an established therapeutic option at least for a selected group of early breast cancer patients after breast-conserving surgery. Optimal delivery of the tumor bed boost dose in terms of timing, fractionation, and total dose whenever a hypofractionated schedule is employed has yet to be established. We herein present a review of the current evidence on the role of boost integration in whole breast radiotherapy.

Current protocols for delivering radiotherapy are based primarily on tumour stage and nodal and metastases status, even though it is well known that tumours and their microenvironments are highly heterogeneous. It is well established that the local oxygen tension plays an important role in radiation-induced cell death, with hypoxic tumour regions responding poorly to irradiation. Therefore, to improve radiation response, it is important to understand more fully the spatiotemporal distribution of oxygen within a growing tumour before and during fractionated radiation. To this end, we have extended a spatially-resolved mathematical model of tumour growth first proposed by Greenspan (Stud. Appl. Math., 1972) to investigate the effects of oxygen heterogeneity on radiation-induced cell death. In more detail, cell death due to radiation at each location in the tumour, as determined by the well-known linear-quadratic model, is assumed also to depend on the local oxygen concentration. The oxygen concentration is governed by a reaction-diffusion equation that is coupled to an integro-differential equation that determines the size of the assumed spherically-symmetric tumour. We combine numerical and analytical techniques to investigate radiation response of tumours with different intra-tumoral oxygen distribution profiles. Model simulations reveal a rapid transient increase in hypoxia upon re-growth of the tumour spheroid post-irradiation. We investigate the response to different radiation fractionation schedules and identify a tumour-specific relationship between inter-fraction time and dose per fraction to achieve cure. The rich dynamics exhibited by the model suggest that spatial heterogeneity may be important for predicting tumour response to radiotherapy for clinical applications.

Purpose:Lungcancerradiotherapytreatments employ a wide variety of fractionation protocols. The choice among protocols mostly depends on the size of the target volume (GTV or ITV) and the volume of normal tissue receiving a critical dose. Rigorous mathematical criteria for normal tissue (NT) dose distributions were derived to determine the type of dose per fraction schedule that maximizes linear‐quadratic tumor effect. Methods: Selecting the individual doses per fraction that maximize a linear‐quadratic effect in the tumor while constraining the normal tissue complication probability according to the Lyman‐Kutcher‐Burman model leads to an optimization problem. For time‐independent parameters, the solution is always an equal dose per fraction schedule; depending on parameter values, two different class solutions are suggested: minimal number of fractions clinically realized with hypo‐fractionation, or minimizing dose per fraction clinically realized with standard‐ or hyper‐fractionation. The value of a single scale‐free “bifurcation” number, derived from the DVH of the NT dose distribution suggests which solution is preferred for a given plan with respect to a given normal tissue. The clinical relevance of the bifurcation number in selecting fractionation schemes was tested for 30 patients previously treated for non‐small‐cell lungcancer according to various fractionation protocols. Results: The bifurcation numbers for both lung and esophagus were a good classifier for the hypofractionated and the conventional fractionation groups. The variability of the numbers within patients of the conventional fractionation group was much smaller than the variability of the treated ITV volumes or the ITV to lung volume ratios. The prescribed fractionations were also consisted with the currently accepted alpha‐beta values for tumor (10) and radiation‐induced pneumonities in the lung (4). Conclusions: Model‐based criteria such as the bifurcation number may replace the more empirical volume criteria to decide the optimal fractionation protocol once the dose distribution has been optimized.

Prostate cancer can be managed with external beam radiation therapy, delivered with either protons or photons, brachytherapy, surgery, or active surveillance. Advances in imaging and radiation therapy delivery have allowed treatment of prostate cancer using ultra-hypofractionated radiation therapy with a high dose per fraction using a technique called stereotactic body radiation therapy (SBRT). While no randomized trials have compared the efficacy of SBRT to conventionally fractionated radiation therapy (CFRT), numerous prospective trials and retrospective reviews have demonstrated the safety and efficacy of SBRT for localized prostate cancer, used either definitively or as a boost along with CFRT. Prostate cancer SBRT may be more cost effective than CFRT using intensity modulated radiation therapy (IMRT) or proton based radiation therapy.

Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors.Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B).Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS.Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Lentigo maligna (LM) incidence is increasing. LM frequently involves the face near critical anatomical structures and as a consequence clinical management is challenging. Nonsurgical therapies, including radiotherapy (RT), are increasingly used. Evidenced-based treatment guidelines are lacking. We conducted a review of previously published data analysing RT treatment of LM. A search of PubMed, Embase and Medline databases to June 2012 identified nine clinical studies that examined the use of RT for LM treatment in at least five patients. Nine studies described 537 patients with LM treated with definitive primary RT, between 1941 and 2009, with a median reported follow-up time of 3 years. Eight articles could be reviewed for oncological outcome data. There were 18 recurrences documented in a total of 349 assessable patients (5%). Salvage was successful in the majority of recurrent LM cases by using further RT, surgery or other therapies. Progression to LM melanoma (LMM) occurred in five patients (five out of 349, 1.4%) who all had poor outcomes. There were five marginal recurrences documented out of 123 assessable patients (4%). There were eight in-field recurrences documented with either LM (five) or LMM (three) out of 171 assessable patients (5%). A series of recommendations were then developed for RT parameters for treatment of LM. These parameters include treatment volume, dose, dose per fraction and outcome measures. These may be of use in prospective data collection.

Stereotactic ablative radiotherapy (SABR) is a radiotherapy technique for treating early-stage non-small cell lung cancer (NSCLC), and is characterized by high dose per fraction, few fractions, and image-guided precision. Multiple studies have consistently demonstrated high rates of local control and a low incidence of serious adverse events, making it an attractive option for patients who are medically unfit for surgery. Although a biopsy is recommended for confirmation of the diagnosis prior to treatment, it is not without its risks. Herein we review the necessity of a biopsy prior to SABR for a solitary pulmonary nodule (SPN) suspicious for early-stage NSCLC. We examine malignancy prediction tools for assessing SPNs and scenarios in which forgoing a biopsy could be reasonable.

Large doses per fraction are not recommended in daily radiotherapy due to a higher risk of late normal tissue injury. The technical refinements of modern radiotherapy and suggestions that some tumors could be sensitive to dose per fraction have renewed the interest in hypofractionated schedules. The estimation of α/β ratio value requires large samples of carefully evaluated patients in whom total and fractional doses have varied independently. Tumor repopulation has to be considered when the treatment duration is altered. Without setting aside conflicting publication, the α/β ratio values for prostate and breast (after lumpectomy) cancers could be as low as 2.5 Gy and 4 Gy, respectively. While it is too early to change our routine protocols, the time has come to conduct clinical trials comparing different fractionation schedules.

One of the core problems in intensity modulated radiation therapy (IMRT) treatment planning is the fluence map optimization (FMO) problem, which determines a fluence map (or profile) for each beam used in the delivery of treatment. Radiation therapy is administered in multiple so-called daily fractions to allow for healthy tissue to recover from damage caused by the treatment. Before the advent of IMRT, the treatment was designed to ensure a constant dose to cells in the target (the areas in the patient where cancerous cells are present or suspected). In the presence of multiple targets with different prescribed doses, this design meant that treatment had to be delivered in a sequence of unequal fractions, one per prescription dose level. For example, in case of two targets treatment would consist of an initial plan aimed at treating both targets to a lower total dose, followed by a so-called boost plan aimed at delivering the additional dose at the target with higher prescribed dose. In contrast, IMRT treatment plans are often delivered with equal treatment plan for each fraction, which means that the dose per fraction cannot be the same for all targets. The important problem of restoring traditional fractionation to IMRT treatments has not yet received much attention in the literature. In this paper we propose a new optimization model that explicitly restores fractionation into the FMO problem, yielding an optimal set of fluence maps for each fraction. We illustrate the capabilities of our approach on clinical head-and-neck cancer cases.

Objective Lower cranial neuropathy is a rare complication of radiation therapy for head and neck cancers. Little is known about the clinical and electromyographic features of this complication. Methods The records of six patients with radiation-induced lower cranial neuropathy who had undergone electromyographic study were reviewed. All patients were treated with radiation therapy for nasopharyngeal cancer. The total radiation dose was 6996–8280 cGy to the nasopharynx and 4680–7020 cGy to the neck. The dose per fraction was 180 or 212 cGy. Results Spinal accessory neuropathy occurred in all six patients, glossopharyngeal and vagus neuropathy in five patients, and hypoglossal neuropathy in five patients. The median latency between radiation therapy and lower cranial neuropathy was 61 months (range, 20–118 months). The lower cranial neuropathies developed insidiously and progressed slowly over a period of years in all patients. Myokymia was seen in three patients and myokymic discharges were demonstrated in five of six patients. Conclusions Myokymia and myokymic discharges may be common and typical features of radiation-induced lower cranial neuropathy. Significance It is important to make an effort to detect myokymia and myokymic discharges for symptomatic patients suggestive of radiation-induced lower cranial neuropathy.

PURPOSE Although the technical developments of radiotherapy have been remarkable, there are currently few reports on the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as initial treatment in this three-dimensional conformal radiotherapy era. Thus, we retrospectively evaluated the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as the initial treatment. MATERIALS AND METHODS Thirty-two patients who underwent radiotherapy were enrolled in this study. The dose per fraction was 2.0-3.5 Gy. Because the treatment schedule was variable, the biological effective dose (BED) was calculated. RESULTS Local control (LC) and overall survival (OS) rates from the completion of radiotherapy were calculated. The 1-, 2-, 3-, 4-, and 5-year LC rates were 51.5%, 24.5%, 19.6%, 19.6%, and 13.1%, respectively. LC rates were significantly higher for the high BED group (≥75 Gy10) than for the lower BED group (

Objective: The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy. Methods: 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation. Results: There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was

Stereotactic body radiation therapy (SBRT) utilizing a small number of high-dose radiation therapy fractions continues to expand in clinical application. Although many approaches have been proposed to radiosensitize tumors with conventional fractionation, how these radiosensitizers will translate to SBRT remains largely unknown. Here, we review our current understanding of how SBRT eradicates tumors, including the potential contributions of endothelial cell death and immune system activation. In addition, we identify several new opportunities for radiosensitization generated by the move toward high dose per fraction radiation therapy.

The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose,distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited.This paper examines the radiobiological mechanisms underlying the most important complications induced by radiotherapy, with the aim of identifying the essential parameters and functional relationships needed for effective predictive NTCP models. The clinical features of the complications are identified and reduced as much as possible into component parts. In a second step, experimental and clinical data are considered in order to identify the gross anatomical structures involved, and which dose distributions lead to these complications. Finally, the pathogenic pathways and cellular and more specific anatomical parameters that have to be considered in this pathway are determined. This analysis is carried out for some of the most critical organs and sites in radiotherapy, i.e. spinal cord, lung, rectum, oropharynx and heart.Signs and symptoms of severe late normal tissue complications present a very variable picture in the different organs at risk. Only in rare instances is the entire organ the critical target which elicits the particular complication. Moreover, the biological mechanisms that are involved in the pathogenesis differ between the different complications, even in the same organ. Different mechanisms are likely to be related to different shapes of dose effect relationships and different relationships between dose per fraction, dose rate, and overall treatment time and effects. There is good reason to conclude that each type of late complication after radiotherapy depends on its own specific mechanism which is triggered by the radiation exposure of particular structures or sub-volumes of (or related to) the respective organ at risk. Hence each complication will need the development of an NTCP model designed to accommodate this structure. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 79-85

Intensity modulated radiation therapy (IMRT) is one of the most widely used delivery modalities for radiation therapy for cancer patients. A patient is typically treated in daily fractions over a period of 5-9 weeks. In this paper, we consider the problem of accounting for changes in patient setup location and internal geometry between the treatment fractions, usually referred to as interfraction motion. The conventional method is to add a margin around the clinical tumor volume (CTV) to obtain a planning target volume (PTV). A fluence map optimization (FMO) model is then solved to determine the optimal intensity profiles to deliver to the patient. However, a margin-based method may not adequately model the changes in dose distributions due to the random nature of organ motion. Accounting for interfraction motion in the FMO model essentially transforms the deterministic optimization problem into a stochastic one. We propose a stochastic FMO model that employs convex penalty functions to control the treatment plan quality and uses a large number of scenarios to characterize interfraction motion uncertainties. Some effects of radiotherapy are impacted mainly by the dose distribution in a given treatment fraction while others tend to manifest themselves over time and depend mostly on the total dose received over the course of treatment. We will therefore formulate an optimization model that explicitly incorporates treatment plan evaluation criteria that apply to the total dose received over all treatment fractions and ones that apply to the dose per fraction. Particularly when many structures fall into the former category, this can lead to significant reductions in the dimension of the optimization model and therefore the time required to solve it. We test an example of our model on five clinical prostate cancer cases, showing the efficacy of our approach. In particular, compared to a traditional margin-based treatment plan, our plans exhibit significantly improved target dose coverage and clinically equivalent critical structure sparing at only a modest increase in computational effort.

Stereotactic body radiotherapy (SBRT) delivers a few high doses of radiation to a target in the body with extreme accuracy and conformality. Prostate cancer’s great sensitivity to dose per fraction allows SBRT’s hypofractionated delivery the opportunity to increase the biological equivalent dose delivered to the prostate while relatively decreasing the dose to the normal bladder and rectal tissues. In recent years, clinical outcomes supporting the safety and increasingly longer-term efficacy of SBRT have been published. This review examines the basis of hypofractionation, current SBRT delivery mechanisms, and the growing body of clinical outcomes of SBRT for prostate cancer. In addition, given the increased interest in SBRT for prostate cancer, clinical issues in the treatment of prostate cancer with SBRT and a look into the future of SBRT for prostate cancer are examined.

Purpose : The aim of this study is to evaluate howsimultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target ( BE D tar ) while biologically effective dose for the normal tissue ( BE D nt ) is fixed. Methods : In this investigation, BE D tar and BE D nt were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results : Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BE D tar while BE D nt is fixed. The dependence of biologically effective dose on fraction time is influenced by the dose rate. In this investigation we analytically determined time-varying dose rate R which minimizes BED . Changes in BED with fraction time were compared for constant dose rate and for R . Conclusions : A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.

Stereotactic radiation therapy, consisting in irradiating the tumor with a high dose per fraction, has a therapeutic potential because of excellent local control. This technique requires a high accuracy level in order to minimize the risk of normal tissue toxicity. Initially used for cerebral localization, the stereotactic radiation therapy can be used for lung and liver tumors thanks to personalized immobilization devices, time resolved tomodensitometry for tumor deformation, collimators with small size leaves, advanced dose distribution calculation algorithms and 3D imaging for patient set-up. This article will review the different clinical applications and the different aspects (mechanical, dosimetric and biological) to evaluate before implementing this complex irradiation technique using adapted or dedicated linear accelerators.

Objectives: This study is designed to present and evaluate radiobiological-based dose–volume histogram (DVH) reduction schemes to calculate normal tissue complication probability (NTCP) and tumour control probability (TCP) for intensity-modulated radiation therapy (IMRT).Methods: The proposed DVH reduction schemes were derived for 2 Gy per fraction and prescribed dose per fraction for critical organs and tumours, respectively. Sample computed tomography scans were used to generate two IMRT plans to deliver 54 Gy to PTV1 and 24 Gy to PTV2 via sequential IMRT boost (SqIB) and simultaneous integrated IMRT boost (SIB) plans. Differential DVHs were used to calculate effective volumes using published values of related parameters of critical organs and prostate.Results: NTCP values for bladder were almost zero for both IMRT plans. The plots between k and NTCP for rectum and femurs (k = 0.1–1.0) show higher NTCP for SqIB than that for SIB. The TCP decreases with increasing clonogenic cell density and is higher for SIB than that for SqIB for all clonogenic cell densities. The value of α proposed by Brenner and Hall shows very low radio sensitivity of clonogens of the prostate, which gives very low TCP for conventional doses of 70–80 Gy delivered in 7–8 weeks, even for very low clonogenic cell density in the prostate.Conclusion: The presented DVH reduction schemes have radiobiological bearing and therefore seem to be effective in calculating fairly accurate NTCP and TCP.

There is often a considerable delay from initial tumour diagnosis to the start of radiotherapy treatment. This paper extends the calculations of a previous paper on the effects of delays before the initiation of radiotherapy treatment to include results from a variety of practical fractionation regimes for three different types of tumour: squamous cell carcinoma (head and neck), breast and prostate. The linear quadratic model of radiation effect, logarithmic tumour growth (coupled with delay times where relevant) and the Poisson model for tumour control probability (TCP) are used to calculate the change in TCP for delays between diagnosis and treatment. Within the limitations of radiobiological modelling, these data can be used to tentatively assess the interactions between delays, dose fractionation and TCP. The results show that delays in the start of radiotherapy treatment do have an adverse effect on tumour control for fast-growing tumours. For example, calculations predict a reduction in local tumour control of up to 1.5% per week's delay for head and neck cancers treated following surgery. In addition, there may be a variety of fractionation regimes that will yield very similar clinical results for each tumour type. It is shown theoretically that, for the tumour types considered here, it is possible to increase the dose per fraction and decrease the number of fractions while maintaining or increasing TCP relative to standard 2 Gy fractionation regimes, although there may be some advantage to using hyperfractionated regimes for head and neck cancers in order to reduce normal tissue effects.

Background. The aim of this study was to use various theoretical methods derived from the Linear Quadratic (LQ) model to calculate the effects of number of subfractions, time intervals between subfractions, dose per subfraction, and overall fraction time on the cells’ survival. Comparison of the results with experimental outcomes of melanoma and breast adenocarcinoma cells was also performed. Finally, the best matched method with experimental outcomes is introduced as the most accurate method in predicting the cell response. Materials and methods. The most widely used theoretical methods in the literature, presented by Keall et al., Brenner, and Mu et al., were used to calculate the cells’ survival following radiotherapy with different treatment schemes. The overall treatment times were ranged from 15 to 240 minutes. To investigate the effects of number of subfractions and dose per subfraction, the cells’ survival after different treatment delivery scenarios were calculated through fixed overall treatment times of 30, 60 and 240 minutes. The experimental tests were done for dose of 4 Gy. The results were compared with those of the theoretical outcomes. Results. The most affective parameter on the cells’ survival was the overall treatment time. However, the number of subfractions per fractions was another effecting parameter in the theoretical models. This parameter showed no significant effect on the cells’ survival in experimental schemes. The variations in number of subfractions per each fraction showed different results on the cells’ survival, calculated by Keall et al. and Brenner methods (P Conclusions. Mu et al. method can predict the cells’ survival following fractionation radiotherapy more accurately than the other models. Using Mu et al. method, as an accurate and simple method to predict the cell response after fractionation radiotherapy, is suggested for clinical applications.

In-vivo dosimetry (IVD) in external beam radiotherapy is used to detect major clinically relevant differences between planned and delivered dose. Moreover, a detailed analysis of its results, when routinely reported and discussed by the radiotherapy staff, can limit the likelihood of error transmission to many treatments. A first experience of routine EPID-based IVD in a reference point has been performed in our department for 3D-CRT treatments over a three-year period. More than 14,000 images were acquired and 1287 treatment plans were verified. The IVD checks were obtained three times in the first week and then weekly. Tolerance levels of ± 5% for pelvic-abdomen, head-neck and breast irradiations and ± 6% for lung treatments were adopted for the in-vivo measured dose per fraction. A statistical analysis of the IVD results was performed grouping the data by: anatomical regions, treatment units, open and wedged fields and gantry angles. About 10% of the checked doses per fraction showed dosimetric discrepancies out of the tolerance levels. The causes of the discrepancies were 70% delivery or planning errors, 20% morphological changes and 10% procedural limitations. 41 cases (3.2%) have required special investigations because their in-vivo doses per fraction, averaged over the first three sessions, were out of the tolerance levels and in 19 cases (1.5%) the deviations gave rise to an intervention. Statistically significant differences of average variations between planned and delivered doses were observed for: (i) 30° wedged 10 MV fields with respect to those of other wedged or open 10 MV fields delivered by two linacs, due to the incorrect TPS implementation of that wedge transmission factor; (ii) anterior-posterior and posterior-anterior beams with respect to the other gantry orientations for one linac, due to the beam attenuation introduced by the treatment couch; (iii) lateral fields with respect to medial fields of breast irradiations for all linacs, due to small systematic set-up variations. The analysis of our data shows a substantial homogeneity of the IVD results for all the considered body regions and treatment units. However, the observed discrepancies have supplied indications for taking further steps in the optimization process and in some cases to adopt an adaptive approach.

Especially for SBRT technique, image-guided technique to verify the target localization is more important than the conventional radiation therapy because of the high dose per fraction and less number of fractions. Evidence of improving the clinical outcome by IGRT has been published so far, and no one doubt about the effectiveness of IGRT these days.

ObjectThe authors sought to assess the relationship between obliteration rate and different dose parameters following fractionated radiotherapy for arteriovenous malformations (AVMs). A comparison of the results of radiosurgery and radiotherapy for AVMs was made to calculate the best fit α/β value, which would then be used as a model for predicting the treatment outcome, independent of the number of fractions applied.MethodsData from 1453 patients were analyzed: 1154 treated with radiosurgery and 300 with fractionated radiotherapy. The relationships between dose and obliteration rate after 3 years were calculated, and the best fit curve to the empirical results was defined. The higher the dose per fraction, biologically effective dose, and the lower the total dose, the higher the obliteration rate. The isoeffective doses when comparing radiotherapy and radiosurgery independent of the α/β value could not be defined. The dose per fraction had the best predictive value, independent of the number of fractions.Conclusions Dose per fraction seems to be the decisive parameter for the treatment response following both radiotherapy and radiosurgery. A larger number of fractions did not increase the obliteration rate. The data indicate that higher doses per fraction should be used when irradiating AVMs.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Purpose: Non-small-cell lung cancer (NSCLC) may not be medically operable even in patients with surgically resectable disease. For patients who either refuse surgery or are medically inoperable, radiation therapy may be the best therapeutic choice. Stereotactic body radiation therapy (SBRT) employs external fixation and hypofractionation to deliver a high dose per fraction of radiation to a small target volume. Methods and Materials: Retrospective review of 75 patients treated over 5 years at Staten Island University Hospital as definitive treatment for NSCLC or presumed NSCLC. Patients received a median of 5 fractions of 8 Gy per fraction over 27 days. Results: Overall 1-, 2-, and 5-year actuarial survivals were 63%, 45%, and 17%. Patients with a gross tumor volume (GTV) less than 65 cm{sup 3} enjoyed a longer median survival (25.7 vs. 9.9 months, p < 0.003), and at 5 years, the actuarial survival for the patients with GTVs less than 65 cm{sup 3} was 24% vs. 0% for those with GTVs larger than 65 cm{sup 3}. Conclusions: Stereotactic body radiation therapy as delivered was ineffective for curing the patients whose GTVs were larger than 65 cm{sup 3}. SBRT was promising for those with GTVs less than 65 cm{sup 3}.