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PURPOSE To derive the isodose line R relative to the prescription dose below which irradiated normal tissue (NT) regions benefit from a hypofractionated schedule with an isoeffective dose to the tumor. To apply the formalism to clinical case examples. METHODS From the standard biologically effective dose (BED) equation based on the linear-quadratic (LQ) model, the BED of an NT that receives a relative proportion r of the prescribed dose per fraction for a given α/β-ratio of the tumor, (α/β)T , and NT, (α/β)NT , is derived for different treatment schedules while keeping the BED to the tumor constant. Based on this, the "break-even" isodose line R is then derived. The BED of NT regions that receive doses below R decreases for more hypofractionated treatment schedules, and hence a lower risk for NT injury is predicted in these regions. To assess the impact of a linear behavior of BED for high doses per fraction (>6 Gy), we evaluated BED also using the LQ-linear (LQ-L) model. RESULTS The formalism provides the equations to derive the BED of an NT as function of dose per fraction for an isoeffective dose to the tumor and the corresponding break-even isodose line R. For generic α/β-ratios of (α/β)T = 10 Gy and (α/β)NT = 3 Gy and homogeneous dose in the target, R is 30%. R is doubling for stereotactic treatments for which tumor control correlates with the maximum dose of 100% instead of the encompassing isodose line of 50%. When using the LQ-L model, the notion of a break-even dose level R remains valid up to about 20 Gy per fraction for generic α/β-ratios and DT=2(α/β) . CONCLUSIONS The formalism may be used to estimate below which relative isodose line R there will be a differential sparing of NT when increasing hypofractionation. More generally, it allows to assess changes of the therapeutic index for sets of isoeffective treatment schedules at different relative dose levels compared to a reference schedule in a compact manner.

Aim/objectives/background To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation. Methods The ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document. Results Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR-AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter. Conclusions This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.

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.

Simple Summary Brain metastases are one of the most frequent complications for cancer patients. Stereotactic radiosurgery is considered a cornerstone treatment for patients with limited brain metastases and the ideal dose and fractionation schedule still remain unknown. The aim of this literature review is to discuss the dose-effect relation in brain metastases treated by stereotactic radiosurgery, accounting for fractionation and technical considerations. Abstract For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.

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.

Purpose: To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study. Methods and Materials: Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR (P = .04). On univariate analysis, squamous cell carcinoma was associated with inferior OS (P

Purpose In our department, for high dose-per-fraction treatments such as stereotactic body radiation therapy, we require a physician to perform the pretreatment on-board imaging match. The purpose of this study was to determine whether patient-matching positioning performed by radiation therapists (RTTs) is as accurate as that performed by physicians. Methods and Materials Sixteen RTTs and 5 physicians participated in this study. Data were collected from 113 patients, totaling 324 measurements. A total of 60 patients were treated for bone lesions and 53 for soft-tissue lesions, such as lung and liver. Matching was performed using kV-kV imaging for bones and cone beam computed tomography for soft tissue. All treatments were delivered on Varian linear accelerators. The initial match was performed by the RTTs, and the shifts were noted. Subsequently, the match was reset, and the physician performed an independent match blinded to the RTT match. Physician shifts were applied for treatment. We used the Wilcoxon rank sum test to determine the statistical significance between RTT and physician shifts. Results The differences in patient shifts between physicians and RTTs were calculated in 3 translational 1 one rotational axis. The average vector shift was 0.88 ± 0.57 cm versus 0.91 ± 0.57 cm for RTTs versus physicians, respectively. Neither the average vector nor the individual axis shifts were statistically significantly different ( P > .2). There was no significant difference when testing for bony or soft lesion matches separately. Conclusions RTT on-board imaging matching is as accurate as physician matching for both bone and soft tissue lesions. On the basis of these results, RTTs are as qualified as physicians to perform a pretreatment match. Thus, it may be feasible for the RTTs to perform the match and the physician to review it offline after treatment without being present at the machine during treatment. Our results show that this approach does not compromise patient safety.

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.

Purpose To develop a novel biological dosimetric margin (BDM) and to create a biological conversion factor (BCF) that compensates for the difference between physical dosimetric margin (PDM) and BDM, which provides a novel scheme of a direct estimation of the BDM from the physical dose (PD) distribution. Methods The offset to isocenter was applied in 1-mm steps along left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) directions for 10 treatment plans of lung stereotactic body radiation therapy (SBRT) with a prescribed dose of 48 Gy. These plans were recalculated to biological equivalent dose (BED) by the linear-quadratic model for the dose per fraction (DPF) of d = 3-20 Gy/fr and α / β = 3 - 10 . BDM and PDM were defined so that the region that satisfied that the dose covering 95% (or 98%) of the clinical target volume was greater than or equal to the 90% of the prescribed PD and BED, respectively. An empirical formula of the BCF was created as a function of the DPF. Results There was no significant difference between LR and AP directions for neither the PDM nor BDM. On the other hand, BDM and PDM in the CC direction were significantly larger than in the other directions. BCFs of D95% and D98% were derived for the transverse (LR and AP) and longitudinal (CC) directions. Conclusions A novel scheme to directly estimate the BDM using the BCF was developed. This technique is expected to enable the BED-based SBRT treatment planning using PD-based treatment planning systems.

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.

Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

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.

Purpose: To investigate the feasibility of applying ANOVA newly proposed by Yukinori to verify the setup errors, PTV (Planning Target Volume) margins, DVH for lung cancer with SBRT. Methods: 20 patients receiving SBRT to 50 Gy in 5 fractions with a Varian iX linear acceleration were selected. Each patient was scanned with kV-CBCT before the daily treatment to verify the setup position. Two other error calculation methods raised by Van Herk and Remeijer were also compared to discover the statistical difference in systematic errors (Σ), random errors (σ), PTV margins and DVH. Results: Utilizing two PTV margin calculation formulas (Stroom, Van Herk), PTV calculated by Yukinori method in three directions were (5.89 and 3.95), (5.54 and 3.55), (3.24 and 0.78) mm; Van Herk method were (6.10 and 4.25), (5.73 and 3.83), (3.51 and 1.13) mm; Remeijer method were (6.39 and 4.57), (5.98 and 4.10), (3.69 and 1.33) mm. The volumes of PTV using Yukinori method were significantly smaller (P 0.05) among three methods. Conclusions: In lung SBRT treatment, due to fraction reduction and high level of dose per fraction, ANOVA was able to offset the effect of random factors in systematic errors, reducing the PTV margins and volumes. However, no distinct dose distribution improvement was founded in target volume and organs at risk.

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.

The objective of this paper is to evaluate the clinical impact of biological uncertainties in small field proton therapy due to the assumption of using a constant relative biological effectiveness (RBE) value of 1.1 (RBE-fixed) compared to a variable RBE (RBE-weighted). In this context the impact of the applied range margin was investigated. Eight patients with arteriovenous malformation (AVM) treated with proton radiosurgery were selected due to the small target volume. Dose distributions were compared for RBE-weighted and RBE-fixed. The impact of RBE was assessed using Monte Carlo (MC) dose calculations for stereotactic doses and doses of 2 Gy(RBE). Four different α/β ratios were investigated. Additionally, dose distributions were recalculated with reduced range margins. Applying variable RBE values for stereotactic doses resulted in an increase in the mean dose of 1.6% for a low α/β of 2 Gy, but a decrease of 2.6% for an α/β of 10 Gy. However, the mean dose increased to 17.1% and 2.1% for doses of 2 Gy(RBE) and α/β of 2 Gy and 10 Gy, respectively. Reducing range margins from 3.5% + 1 mm to 2.5% + 1 mm resulted in negligible difference in the mean RBE within the target, or 0.1% for stereotactic doses and 0.3% for doses of 2 Gy(RBE). Larger differences were seen for a range reduction to 0% + 1 mm, i.e. 1.1% and 3.0% for stereotactic doses and doses of 2 Gy(RBE), respectively. Because potential RBE effects are typically more pronounced in the distal part of a field, a bigger clinical impact of RBE uncertainties in small fields is expected. Our study shows that this could be significant for tissues with low α/β and a small dose per fraction. The uncertainty in RBE due to the uncertainty associated with the α/β ratio seems larger than the impact of the applied range uncertainty margin on RBE.

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 The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and methods The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.

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.

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2–1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed.

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.

The purpose of the study was to evaluate a treatment dose using planning computed tomography (pCT) that was deformed to pre-treatment cone beam computed tomography (CBCT) for lung stereotactic body radiation therapy (SBRT) treatment. Five lung SBRT patients were retrospectively selected, and their daily CBCTs were employed in this study. Dosimetric comparison was performed between the original and recalculated plans from the deformed pCT (dose per fraction) by comparing a target coverage and organs at risk. Dose summation of five fractions was computed and compared to the original plan. A phantom study was conducted to evaluate the dosimetric accuracy for the dose per fraction. In the phantom study, the difference between the mean Hounsfield Unit (HU) values of the original and deformed pCTs is less than 0.5%. In patient study, the mean HU deviation of the five deformed pCTs compared to that of the original pCT was within ±5%, which is dosimetrically insignificant. While the internal target volume (ITV) shrank by 17% on average among the five patients, mean lung dose (MLD) increased by up to 7%, and D95% of PTV decreased slightly but stayed within 5%. Results showed that MLD might be a better indicative metric of normal lung dose than V20Gy as the ITV volume decreases. This study showed a feasibility to use a deformed pCT for evaluation of the dose per fraction and for a possible plan adaptation in lung SBRT cases. Readers should be cautious in selecting patients before clinical application due to the image quality of CBCT.

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.

Purpose: to study the clinical, radiological, therapeutic and progressive aspects of brain radionecrosis after treatment for nasopharyngel carcinoma. Patients and methods: four patients ( two men and two women) of mean age 53.5 years were treated for UCNT( undifferentiated carcinoma of the nasopharynx), between 2009and 2014, and developed cerebral radionecrosis. All patients were treated with radical radiotherapy. The mean dose was 70 Gy. Dose per fraction was 2 Gy, one fraction daily. All patients received chemotherapy. Result: patients presented non specific neurological signs, and one case was discovered fortuitously. The mean latent periode was 46 months, brain radionecrosis was authetificated by brain imaging. The localisation was temporal in two patients and bulbomedullar in two patients. After a mean follow-up period of 14 months, clinical outcomes were favorable in one case, stabilisation in two cases and one patient died. Conclusion: brain radionecrosis is a rare iatrogenic complication for patients irradiated for UCNT. Imaging techniques play a major role in the diagnosis. Corticotherapy is the main treatment .

Purpose:Treatment planning for high dose rate (HDR) brachytherapy requires many user inputs, all of which are potential sources of error. The goal of quality assurance (QA) is to ensure that errors are not made. In this study, we developed a software program to analyze the treatment printout from the HDR treatment planningcomputer and flag any suspected errors. Methods: The treatment printout from the HDR planning computer is imported by the software. The software then performs the following checks: (1) verifies that the correct source was chosen (we have multiple in our database), (2) performs an independent decay of the Ir‐192 source, (3) verifies source step size, (4) verifies the offsets and indexer lengths in the catheter definitions based upon expected values for the applicator used, (4) performs an independent 2nd check of dose to a cloud of dose points surrounding the treatment region, (5) verifies that the dose per fraction and the number of fractions were entered correctly in the planning computer, and (6) verifies that the dose volume histogram (DVH) metrics were within acceptable tolerances. The software then prints this information to a PDF file, which is appended to the original treatment printout and placed in the patient's medical record. Results: This QA tool has now been implemented for six months in our clinic, and is a critical QA tool in our HDR program. Although each plan is checked by an independent 2nd physicist, this tool provides an additional independent check on the treatment plan. Conclusions: A simple series of automatic 2nd checks helps reduce the risk of errors occurring in the treatment planning portion of HDR brachytherapy and can easily be implemented.

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.

The use of hypofractionated stereotactic body radiotherapy (SBRT) as primary treatment modality in clinically localized prostate cancer (PCa) is emerging, because the low α/β-ratio favors the use of high dose per fraction in PCa. There is a need for more data about SBRT, especially in high-risk PCa patients. The purpose of this retrospective study was to evaluate the safety and the short-term efficacy of robotic SBRT in a clinical patient cohort with localized PCa including also high-risk patients (D'Amico risk stratification).A total of 240 consecutive patients with clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnifeNeither acute grade 3 or higher GU nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients experienced intermediate-term toxicity requiring diagnostic interventions, the rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low, 1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten (4.6%) patients. With the median follow-up time of 23 months the biochemical relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate- and high-risk group, respectively.The toxicity of robotic SBRT in a large clinical cohort of PCa patients was tolerable and the early PSA response was good in all risk groups. The hypofractionated SBRT offers a possibility to high dose per fraction and to provide the whole radiotherapy treatment within two to three weeks.

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.

PurposeThe accuracy of dose delivery and the evaluation of differences between calculated and delivered dose distributions, has been studied by several groups. The aim of this investigation is to extend the gamma index by including radiobiological information and to propose a new index that we will here forth refer to as the gamma plus (γ+). Furthermore, to validate the robustness of this new index in performing a quality control analysis of an IMRT treatment plan using pure radiobiological measures such as the biologically effective uniform dose ( D ? ? ) and complication-free tumor control probability (P+). Material and methodsA new quality assurance index, the (γ+), is proposed based on the theoretical concept of gamma index presented by Low et al. (1998). In this study, the dose difference, including the radiobiological dose information (biological effective dose, BED) is used instead of just the physical dose difference when performing the γ+ calculation. An in-house software was developed to compare different dose distributions based on the γ+ concept. A test pattern for a two-dimensional dose comparison was built using the in-house software platform. The γ+ index was tested using planar dose distributions (exported from the treatment planning system) and delivered (film) dose distributions acquired in a solid water phantom using a test pattern and a theoretical clinical case. Furthermore, a lung cancer case for a patient treated with IMRT was also selected for the analysis. The respective planar dose distributions from the treatment plan and the film were compared based on the γ+ index and were evaluated using the radiobiological measures of P+ and D ? ? . ResultsThe results for the test pattern analysis indicate that the γ+ index distributions differ from those of the gamma index since the former considers radiobiological parameters that may affect treatment outcome. For the theoretical clinical case, it is observed that the γ+ index varies for different treatment parameters (e.g. dose per fraction). The dose area histogram (DAH) from the plan and film dose distributions are associated with P+ values of 50.8% and 49.0%, for a D ? ? to the target of 54.0Gy and 53.3Gy, respectively. ConclusionThe γ+ index shows advantageous properties in the quantitative evaluation of dose delivery and quality control of IMRT treatments because it includes information about the expected responses and radiobiological doses of the individual tissues.

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.

Purpose Traditionally, radiation treatment dosimetric plans are evaluated by degree of PTV coverage by prescribed dose and the fulfillment of QUANTEC limitations on OARs. In the case of hypofractionated SBRT irradiation plans should be optimized with respect to optimal fractionation and total delivered dose. In this case one could use macroscopic radiobiological criteria, namely TCP and NTCP. The aim of the work is to optimize prostate cancer SBRT treatment basing on TCP/NTCP criteria in the range of total doses from 33.5 Gy to 38 Gy delivered in 4 or 5 fractions. Methods SBRT treatment plans based on VMAT dose delivery technique (4 full arcs) were made in Elekta MONACO planning system v. 5.10. Five patients with T1 and T2 prostate cancer were planned to total doses from 33.5 Gy to 38 Gy in four or five fractions. Differential DVHs were used for simulation of TCP values using Niemierko model and Stavrev-Niemerko model assuming that for prostate cancer α β = 1.5 ± 0.5 Gy. For calculation of NTCP the models of Niemierko and Kallman were used. All plans were compared basing on UTCP = TCP 1 - NTCP . NTCP values were calculated for the forward wall of rectum as the most irradiated OAR. Thus, using all TCP and NTCP models four variants are possible for each total dose of irradiation and fractionation. Results All plans were planned to the best of the medical physicist experience resulting in 98% of PTV covered by 98% of prescribed dose, and 100% of CTV covered by 99% of dose. CI and HI were equal to 0.99. For all five patients the best plans resulted in UTCP values 0.97–0.98 that were obtained for two variants of irradiation: 33.5 Gy in 4 fractions or 36 Gy in 5 fractions. Further increase of dose for both fractionations resulted in significant damage of the OAR. For all plans TCP values were larger than 0.97 tending to unit with increase of total dose as expected. Conclusion Simulation of TCP/NTCP values of the different VMAT irradiation plans was carried out using different models. The results allowed to find the optimal plan with respect to fractionation and dose per fraction.

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.

Purpose: To investigate the effect of variable dose rate on biologically effective dose (BED). Materials and methods: By using the linear-quadratic (LQ) model with bi-exponential repair, we analytically determine the timedependent dose rate R ~ which minimizes the effective protraction factor (G eff ) and BED under the condition of fixed fraction time and dose per fraction. Because normal tissue complication probability (NTCP) monotonically decreases with decreasing BED, the dose rate R also minimizes NTCP. Results: The dependences of G eff , BED and NTCP on fraction time were determined for different radiobiological parameters and two different dose rates: constant dose rate R 0 and varying dose rate R . Conclusion: The results of this study indicate that under certain conditions the reduction in BED for late-responding tissues due to increased fraction time can be significantly greater than the reduction in BED for tumors. Our analysis also indicates that dose rate optimization can be radiobiologically beneficial because of the resulting decrease in NTCP.

In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20-22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677-82), actually close to (18-20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149-56). Here, we compare our computed iso-TCP = 88% dose per fraction (d88) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d(-1)), reoxygenation of chronic hypoxia (ch-), at rate a (d(-1)) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603-8), we here maintained (a(d(-1)), C, OERch, OERah/OERch, AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (N(o)) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (αo/βo(Gy), λ(d(-1))) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d88(n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d88(±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D88(n) = d88(n)*n, exhibited a relative minimum around n = 8. Computed d88(n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly radioresistant cell subpopulation is properly modelled. The computed minimum D88(n) around n = 8 suggests the adoption of 6 ≤ n ≤ 10 instead of n = 3 in SBRT of small NSCLC tumours.