Search

Abstract Background Hypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits. Methods Treatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score. Results Compared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V37Gy(bladder) and V36Gy(rectum) from a mean of 7.4cm3 and 2.0cm3 to (5.9cm3, 6.1cm3, 5.2cm3) as well as to (1.4cm3, 1.4cm3, 1.0cm3), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation. Conclusion Treatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy.

Abstract Introduction The spine represents the site which is most frequently affected by bone metastases in patients with systemic cancer. Of all local treatment options, combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provides both, instantaneous stabilization and immediate pain relief. We here report on the long-term outcomes of the largest cohort treated with Kypho-IORT to date. Methods Between 2009 and 2019 a total of 104 patients underwent Kypho-IORT to vertebral tumors in the thoracic, lumbar, or sacral spine with transpedicular kyphoplasty and intraoperative irradiation with a needle-shaped electronic brachytherapy source at our center. Patients were treated either on trial, within the prospective Kypho-IORT studies (NCT01280032 and NCT02773966), or, after completion of the study, off trial but compliant with the study protocol. Follow-up and imaging with computed tomography (CT) or magnetic resonance imaging was scheduled after 3 and 6 months and then bi-annually. Results A total of 143 vertebrae (89 thoracic spine, 53 lumbar spine, and 1 sacral spine) were treated in 104 patients. The median follow-up was 14.5 months (range 0.4–109). Local progression occurred in 10 patients (10 vertebrae) after a median time of 22.3 months (range 1.5–73) resulting in local control rates of 97.1, 95.9, and 94.2% at 6, 12, and 24 months, respectively. Overall survival was 74.6, 61.7, and 50.3% at 6, 12, and 24 months, respectively. A single serious adverse event was reported. Conclusion In addition to immediate pain reduction and stabilization, Kypho-IORT shows excellent long-term local control with minimal side effects.

Abstract Background Soft tissue sarcomas (STS) treatment remains a therapeutic challenge. Intraoperative radiotherapy (IORT) resembles a safe and efficient for STS treatment. The first data on electronic-IORT (eIORT) using low-energy photons is herein presented. Methods Thirty-one patients with newly and recurrent STS were retrospectively assessed. EIORT was applied with low-energy photons during surgery. The dose was either prescribed to the applicator surface (spherical applicators) or 5 mm depth (flat applicators). Overall progression-free survival (O-PFS), local progression-free survival (L-PFS), overall survival (OS) and adverse events were evaluated. Results Median follow-up was 4.88 (1.0–8.95) years. Twenty-five patients (80.6%) had recurrent STS with prior treatment. The resection status was R1 in 25.8% and R2 in 6.5%. The distribution was 51.7% for extremities, 35.5% for abdomen and pelvis, 9.7% for thorax and 3.2% for head and neck tumors. The median O-PFS was 11.0 months, with 42.6% 5-year estimated O-PFS. The only local recurrence in the primary setting occurred after 22 months. Median L-PFS in recurrent STS was 12.5 months, with 65.5% 5-year estimated L-PFS. The 5-year OS estimated rate was 94.7% (3 events after 7 years). No G3 toxicity related to eIORT was observed. Two patients exhibited G2 acute neuropathic pain. Late neuropathic pain was seen in 6 patients being 3 graded as G1 and 3 as G2. No wound-related toxicity was found. Conclusion Electronic IORT with low-energy photons is a safe treatment option for STS, yielding similar outcomes as historical series reporting IORT with electrons or HDR brachytherapy.

Abstract Background Neoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT. Methods We retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS). Results A total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4–17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40–50.4 Gy]) and IORT (median dose: 15 Gy [15–17 Gy]). The median age was 65 years [33–82]. The median follow-up was 23 months [0–63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively). Conclusions IORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.

Abstract Background It is uncertain if whole-pelvic irradiation (WPRT) in addition to dose-escalated prostate bed irradiation (PBRT) improves biochemical progression-free survival (bPFS) after prostatectomy for locally advanced tumors. This study was initiated to analyze if WPRT is associated with bPFS in a patient cohort with dose-escalated (> 70 Gy) PBRT. Methods Patients with locally advanced, node-negative prostate carcinoma who had PBRT with or without WPRT after prostatectomy between 2009 and 2017 were retrospectively analyzed. A simultaneous integrated boost with equivalent-doses-in-2-Gy-fractions (EQD-2) of 79.29 Gy or 71.43 Gy to the prostate bed was applied in patients with margin-positive (or detectable) and margin-negative/undetectable tumors, respectively. WPRT (44 Gy) was offered to patients at an increased risk of lymph node metastases. Results Forty-three patients with PBRT/WPRT and 77 with PBRT-only were identified. Baseline imbalances included shorter surgery-radiotherapy intervals (S-RT-Intervals) and fewer resected lymph nodes in the WPRT group. WPRT was significantly associated with better bPFS in univariate (p = 0.032) and multivariate models (HR = 0.484, p = 0.015). Subgroup analysis indicated a benefit of WPRT (p = 0.029) in patients treated with rising PSA values who mostly had negative margins (74.1%); WPRT was not associated with a longer bPFS in the postoperative setting with almost exclusively positive margins (96.8%). Conclusion We observed a longer bPFS after WPRT compared to PBRT in patients with locally advanced prostate carcinoma who underwent dose-escalated radiotherapy. In subset analyses, the association was only observed in patients with rising PSA values but not in patients with non-salvage postoperative radiotherapy for positive margins.

Abstract Background Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. Methods For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. Results Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p

Abstract There is broad consensus on surgical resection being the backbone of curative therapy of gastric- and gastroesophageal junction carcinoma. Nevertheless, details on therapeutic approaches in addition to surgery, such as chemotherapy, radiotherapy or radiochemotherapy are discussed controversially; especially whether external beam radiotherapy should be applied in addition to chemotherapy and surgery is debated in both entities and differs widely between regions and centers. Early landmark trials such as the Intergroup-0116 and the MAGIC trial must be interpreted in the context of potentially insufficient lymph node resection. Despite shortcomings of both trials, benefits on overall survival by radiochemotherapy and adjuvant chemotherapy were confirmed in populations of D2-resected gastric cancer patients by Asian trials. Recent results on junctional carcinoma patients strongly suggest a survival benefit of neoadjuvant radiochemotherapy in curatively resectable patients. An effect of chemotherapy in the perioperative setting as given in the MAGIC study has been confirmed by the ACCORD07 trial for junctional carcinomas; however both the studies by Stahl et al. and the excellent outcome in the CROSS trial as compared to all other therapeutic approaches indicate a superiority of neoadjuvant radiochemotherapy as compared to perioperative chemotherapy in junctional carcinoma patients. Surgery alone without neoadjuvant or perioperative therapy is considered suboptimal in patients with locally advanced disease. In gastric carcinoma patients, perioperative chemotherapy has not been compared to adjuvant radiochemotherapy in a randomized setting. Nevertheless, the results of the recently published ARTIST trial and the Chinese data by Zhu and coworkers, indicate a superiority of adjuvant radiochemotherapy as compared to adjuvant chemotherapy in terms of disease free survival in Asian patients with advanced gastric carcinoma. The ongoing CRITICS trial is supposed to provide reliable conclusions about which therapy should be preferred in Western patients with gastric carcinoma. If radiotherapy is performed, modern approaches such as intensity-modulated radiotherapy and image guidance should be applied, as these methods reduce dose to organs at risk and provide a more homogenous coverage of planning target volumes.

Abstract Background Gene silencing of O6-methylguanine–DNA methyltransferase (MGMT) by promoter methylation improves the outcome of glioblastoma patients after combined therapy of alkylating chemotherapeutic agents and radiation. The purpose of this study was to assess the frequency of MGMT promoter methylation in soft tissue sarcoma to identify patients eligible for alkylating agent chemotherapy such as temozolomide. Findings Paraffin tumor blocks of 75 patients with representative STS subtypes were evaluated. The methylation status of the MGMT promoter was assessed by methylation-specific polymerase-chain-reaction analysis (PCR). Furthermore, immunohistochemistry was applied to verify expression of MGMT. MGMT gene silencing was assumed if MGMT promoter methylation was present and the fraction of tumor cells expressing MGMT was 20% or less. Methylation specific PCR detected methylated MGMT promoter in 10/75 cases. Immunohistochemical staining of nuclear MGMT was negative in 15/75 cases. 6/75 tumor samples showed MGMT promoter methylation and negative immunohistochemical nuclear staining of MGMT. In none of the tested STS subtypes we found a fraction of tumors with MGMT silencing exceeding 22%. Conclusion MGMT gene silencing is a rare event in soft tissue sarcoma and cannot be recommended as a selection criterion for the therapy of STS patients with alkylating agents such as temozolomide.

Abstract We present the case of an 83 year old woman with a cardiac pacemaker located close in distance to a subsequently diagnosed invasive ductal carcinoma of the left breast. Short range intraoperative radiotherapy was given following wide local excision and sentinel node biopsy. The challenges of using ionising radiation with pacemakers is also discussed.

Abstract Purpose Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR. Patients and methods 19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold) were analysed regarding overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC), acute and late toxicity. Results PTV (planning target volume)-size was 108 ± 109cm3 (median 67.4 cm3). BED2 (Biologically effective dose in 2 Gy fraction) was 83.3 ± 26.2 Gy (median 78 Gy). Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months). Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999). Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08) when a volume cut-off of 67 cm3 was used. No local relapse was observed at PTV-sizes 3 and BED2 > 78 Gy. No acute clinical toxicity > °2 was observed. Late toxicity was also ≤ °2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C-reactive protein. Conclusions A trend to statistically significant correlation of local progression was observed for BED2 and PTV-size. Dose-levels BED2 > 78 Gy cannot be reached in large lesions constituting a significant fraction of this series. Image-guided SABR (igSABR) is therefore an effective non-invasive treatment modality with low toxicity in patients with small inoperable liver metastases.

Abstract Background Radiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy). Methods Computer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116. Results IORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT. Conclusions The calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT.

Abstract Background Instable and painful vertebral metastases in patients with progressive visceral metastases present a common therapeutic dilemma. We developed a novel approach to deliver intraoperative radiotherapy (IORT) during kyphoplasty and report the first treated case. Methods/Results 60 year old patient with metastasizing breast cancer under chemotherapy presented with a newly diagnosed painful metastasis in the 12th thoracic vertebra. Under general anaesthesia, a bipedicular approach into the vertebra was chosen with insertion of specially designed metallic sleeves to guide the electron drift tube of the miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany). This was inserted with a novel sheet designed for this approach protecting the drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated after IORT and polymethylmethacrylate cement was injected. The whole procedure lasted less than 90 minutes. Conclusion In conclusion, this novel, minimally invasive procedure can be performed in standard operating rooms and may become a valuable option for patients with vertebral metastases providing immediate stability and local control. A phase I/II study is under way to establish the optimal dose prescription.

Abstract Background/Purpose Radiotherapy (RT) volumes for anal cancer are large and of moderate complexity when organs at risk (OAR) such as testis, small bowel and bladder are at least partially to be shielded. Volumetric intensity modulated arc therapy (VMAT) might provide OAR-shielding comparable to step-and-shoot intensity modulated radiotherapy (IMRT) for this tumor entity with better treatment efficiency. Materials and methods Based on treatment planning CTs of 8 patients, we compared dose distributions, comformality index (CI), homogeneity index (HI), number of monitor units (MU) and treatment time (TTT) for plans generated for VMAT, 3D-CRT and step-and-shoot-IMRT (optimized based on Pencil Beam (PB) or Monte Carlo (MC) dose calculation) for typical anal cancer planning target volumes (PTV) including inguinal lymph nodes as usually treated during the first phase (0-36 Gy) of a shrinking field regimen. Results With values of 1.33 ± 0.21/1.26 ± 0.05/1.3 ± 0.02 and 1.39 ± 0.09, the CI's for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion) and VMAT are better than for 3D-CRT with 2.00 ± 0.16. The HI's for the prescribed dose (HI36) for 3D-CRT were 1.06 ± 0.01 and 1.11 ± 0.02 for VMAT, respectively and 1.15 ± 0.02/1.10 ± 0.02/1.11 ± 0.08 for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion). Mean TTT and MU's for 3D-CRT is 220s/225 ± 11MU and for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion) is 575s/1260 ± 172MU, 570s/477 ± 84MU and 610s748 ± 193MU while TTT and MU for two-arc-VMAT is 290s/268 ± 19MU. Conclusion VMAT provides treatment plans with high conformity and homogeneity equivalent to step-and-shoot-IMRT for this mono-concave treatment volume. Short treatment delivery time and low primary MU are the most important advantages.

Abstract Background Parameter optimization in the process of inverse treatment planning for intensity modulated radiation therapy (IMRT) is mainly conducted by human planners in order to create a plan with the desired dose distribution. To automate this tedious process, an artificial intelligence (AI) guided system was developed and examined. Methods The AI system can automatically accomplish the optimization process based on prior knowledge operated by several fuzzy inference systems (FIS). Prior knowledge, which was collected from human planners during their routine trial-and-error process of inverse planning, has first to be "translated" to a set of "if-then rules" for driving the FISs. To minimize subjective error which could be costly during this knowledge acquisition process, it is necessary to find a quantitative method to automatically accomplish this task. A well-developed machine learning technique, based on an adaptive neuro fuzzy inference system (ANFIS), was introduced in this study. Based on this approach, prior knowledge of a fuzzy inference system can be quickly collected from observation data (clinically used constraints). The learning capability and the accuracy of such a system were analyzed by generating multiple FIS from data collected from an AI system with known settings and rules. Results Multiple analyses showed good agreements of FIS and ANFIS according to rules (error of the output values of ANFIS based on the training data from FIS of 7.77 ± 0.02%) and membership functions (3.9%), thus suggesting that the "behavior" of an FIS can be propagated to another, based on this process. The initial experimental results on a clinical case showed that ANFIS is an effective way to build FIS from practical data, and analysis of ANFIS and FIS with clinical cases showed good planning results provided by ANFIS. OAR volumes encompassed by characteristic percentages of isodoses were reduced by a mean of between 0 and 28%. Conclusion The study demonstrated a feasible way to automatically perform parameter optimization of inverse treatment planning under guidance of prior knowledge without human intervention other than providing a set of constraints that have proven clinically useful in a given setting.

Abstract Background Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods 39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results Fraction time was 13.6 ± 1.6 minutes. Median overall displacement vector length of 125I-seeds was 3 mm (M = 3 mm, Σ = 0.9 mm, σ = 1.7 mm; M: group systematic error, Σ: SD of systematic error, σ: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Σ = 1 mm, σ = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Σ = 1.3 mm, σ = 2.6 mm). Conclusion a) Overall displacement vector length during an IMRT session is < 3 mm. b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion. c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration.

Abstract Background Smoking is an important risk factor for the development of cancer. Smoking during radiochemotherapy therapy may have a negative influence on prognosis. We evaluated the effect of smoking during radiochemotherapy on the outcome for patients with anal cancer. Methods Sixty-eight patients (34 smokers, 34 non-smokers) treated by radiochemotherapy for anal cancer were analysed. The effect of smoking during radiochemotherapy and other risk factors (gender, T- and N category, tumor site, dose, therapy protocol) on disease-specific survival (DSS), local control (LC) and colostomy free survival (CFS) was evaluated. Results There was a significant difference in age and male:female ratio between the two groups. With a median follow up of 22 months (max. 119) DSS, LC, and CFS were 88%, 84% and 84%. A significant difference in local control between smokers (S) and non-smokers (NS) was found (S 74% vs. NS 94%, p = .03). For DSS and CFS a difference in terms of outcome between smokers and non-smokers was seen (DSS: S 82% vs. NS 96%, p = .19, CFS: S 75% vs. 91%, p = .15), which did not reach statistical significance. In multivariate analyses only gender had a significant association with LC and T category with CFS. The other risk factors did not reach statistical significance. Conclusion Even though our evaluation reached statistical significance only in univariate analysis, we suggest, that the role of smoking during radiochemotherapy for anal cancer should not be ignored. The potential negative effect on prognosis should be explained to patients before therapy.

Abstract Background The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. Methods A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. Results The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. Conclusion The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.