Complication probability model for subcutaneous fibrosis based on published data of partial and whole breast irradiation

PurposeTo extend the application of current radiation therapy (RT) based normal tissue complication probability (NTCP) models of radiation-induced fibrosis (RIF) of the breast to include the effects of fractionation, inhomogeneous dose, incomplete recovery, and time after the end of radiotherapy in partial breast irradiation (PBI).Materials and methodsAn NTCP Lyman model with biologically effective uniform dose (BEUD) with and without a correction for the effect of incomplete repair was used. The time to occurrence of RIF was also taken into account. The radiobiological parameters were determined by fitting incidences of moderate/severe RIF in published randomized studies on RT of the breast. The NTCP model was used to calculate the risk of toxicity in 35 patients treated with intensity modulated, non-accelerated PBI and the result was compared with observed incidence of RIF.ResultsWith α/β fixed at 3Gy the parameters of the model without correction for incomplete repair extracted from fitting were: 50% complication probability biologically effective dose BEUD₅₀ = 107.2 Gy (95%CI = 95.9–118.6 Gy), volume parameter n = 0.06 (95%CI = 0–0.23), and slope of dose response m = 0.22, (95%CI = 0.20–0.23). After including the correction for incomplete repair with repair halftime for subcutaneous tissue of τ = 4.4 h we obtained BEUD₅₀ = 105.8 Gy (95%CI = 96.9–114.6Gy), n = 0.15 (95%CI = 0–0.33), m = 0.22 (95%CI = 0.20–0.23). Average NTCP predicted by these models, 4.3% and 2.0% respectively, offered a good agreement with RIF incidence in our patients, 5.7%, after an average follow-up of 12 months.ConclusionThe NTCP models of RIF, incorporating the effects of fractionation, volume effect, and latency of toxicity look promising to model PBI. Clinical validation from a prospective PBI treatment study is under development and will help test this preliminary result.     

Evaluating the predictive value of quantec rectum tolerance dose suggestions on acute rectal toxicity in prostate carcinoma patients treated with IMRT

AimTo investigate the predictive value of convenience of rectum dosimetry with Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) dose limits, maximum rectum dose (Dmax), total rectal volume (TVrectum), rectal volume included in PTV (VrectumPTV) on Grade 2–3 acute rectal toxicity for utilization in clinical practice.BackgroundNumerous previous data have reported frequent acute proctitis after external-beam RT of prostate cancer. Predicting toxicity limited with dose information is inadequate in clinical practice due to comorbidities and medications used.Materials and MethodSixty-four non-metastatic prostate cancer patients treated with IMRT were enrolled. Patients were treated to a total dose of 70–76 Gy. Rectal dose volume histograms (DVH) of all patients were evaluated retrospectively, and a QUANTEC Score between 0 and 5 was calculated for each patient. The correlation between the rectal DVH data, QUANTEC score, TVrectum, VrectumPTV, rectum Dmax and Grade 2–3 rectal toxicity was investigated.ResultsIn the whole group grade 1, 2 and 3 acute rectal toxicities were 25%, 18.8% and 3.1%, respectively. In the DVH data, rectum doses of all patients were under RTOG dose limits. Statistically significant correlation was found between grade 2–3 rectal toxicity and TVrectum (p = 0,043); however. It was not correlated with QUANTEC score, VrectumPTV and Dmax.ConclusionOur results were not able to show any significant correlation between increasing convenience with QUANTEC limits and lower rectal toxicity. Conclusively, new dosimetric definitions are warranted to predict acute rectal toxicity more accurately in prostate cancer patients during IMRT treatment.     

Dosimetric and radiobiological comparison in head-and-neck radiotherapy using JO-IMRT and 3D-CRT

IntroductionDosimetric and radiobiological evaluations for the Jaws-only Intensity-modulated radiotherapy (JO-IMRT) technique for head and neck jaws-only intensity-modulated radiation therapy (JO-IMRT) and 3D conformal radiation therapy (3D-CRT). To compare the head-and-neck therapeutic approaches utilizing JO-IMRT and 3D-CRT techniques, different radiation dose indices were calculated, including: conformity index (CI), homogeneity index (HI), and radiobiological variables like Niemierko's equivalent uniform dose based tumor control probability (TCP) of planning target volume (PTV), normal tissue complication probability (NTCP) of organs at risk (OAR) (brainstem, spinal cord, and parotid grand).Materials and methodsTwenty-five nasopharynx patients were studied using the Prowess Panther Treatment Planning System (Prowess Inc). The results were compared with the dose distribution obtained using 3D-CRT.ResultsRegarding tumor coverage and CI, JO-IMRT showed better results than 3D-CRT. The average doses received by the PTVs were quite similar: 72.1 ± 0.8 Gy by 3D-CRT and 72.5 ± 0.6 Gy by JO-IMRT plans (p > 0.05). The mean doses received by the parotid gland were 56.7 ± 0.7 Gy by 3D-CRT and 26.8 ± 0.3 Gy by JO-IMRT (p > 0.05). The HI and CI were 0.13 ± 0.01 and 0.14 ± 0.05 and (p > 0.05) by 3D-CRT and 0.83 ± 0.05 and 0.73 ± 0.10 by JO-IMRT (p < 0.05). The average TCP of PTV was 0.82 ± 0.08 by 3D-CRT and 0.92 ± 0.02 by JO-IMRT. Moreover, the NTCP of the parotid glands, brain stem, and spinal cord were lower using the JO-IMRT than 3D-CRT plans. In comparison to the 3D-CRT approach, the JO-IMRT technique was able to boost dose coverage to the PTV, improve the target's CI and HI, and spare the parotid glands. This suggests the power of the JO-IMRT over 3D-CRT in head-and-neck radiotherapy.     

Comparison of the extent of hippocampal sparing according to the tilt of a patient’s head during WBRT using linear accelerator-based IMRT and VMAT

In this paper, we report the results of our investigation into whole brain radiotherapy (WBRT) using linear accelerator-based intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in lung cancer patients with a high risk of metastasis to the brain. Specifically, we assessed the absorbed dose and the rate of adverse effects for several organs at risk (OAR), including the hippocampus, according to the tilt of a patient’s head. We arbitrarily selected five cases where measurements were made with the patients’ heads tilted forward and five cases without such tilt. We set the entire brain as the planning target volume (PTV), and the hippocampi, the lenses, the eyes, and the cochleae as the main OAR, and formulated new plans for IMRT (coplanar, non-coplanar) and VMAT (coplanar, non-coplanar). Using the dose-volume histogram (DVH), we calculated and compared the effective uniform dose (EUD), normal tissue complication probability (NTCP) of the OAR and the mean and the maximum doses of hippocampus. As a result, if the patient tilted the head forward when receiving the Linac-based treatment, for the same treatment effect in the PTV, we confirmed that a lower dose entered the OAR, such as the hippocampus, eye, lens, and cochlea. Moreover, the damage to the hippocampus was expected to be the least when receiving coplanar VMAT with the head tilted forward. Accordingly, if patients tilt their heads forward when undergoing Linac-based WBRT, we anticipate that a smaller dose would be transmitted to the OAR, resulting in better quality of life following treatment.     

In silico comparison of photons versus carbon ions in single fraction therapy of lung cancer

PurposeStereotactic body image guided radiation therapy (SBRT) shows good results for lung cancer treatment. Better normal tissue sparing might be achieved with scanned carbon ion therapy (PT). Therefore an in silico trial was conducted to find potential advantages of and patients suited for PT.MethodsFor 19 patients treated with SBRT, PT plans were calculated on 4D-CTs with simulated breathing motion. Prescribed single fraction dose was 24 Gy and OAR constraints used for photon planning were respected. Motion was mitigated by rescanning and range-adapted ITVs. Doses were compared to the original SBRT plans.ResultsCTV coverage was the same in SBRT and PT. The field-specific PTV including range margins for PT was 1.5 (median, 25–75% 1.3–2.1) times larger than for SBRT. Nevertheless, maximum point dose and mean dose in OARs were higher in SBRT by 2.8 (1.6–3.7) Gy and 0.7 (0.3–1.6) Gy, respectively. Patients with a CTV >2.5 cc or with multiple lung lesions showed larger differences in OAR doses in favor of PT.ConclusionsPatients receive less dose in critical OARs such as heart, spinal cord, esophagus, trachea and aorta with PT, while maintaining the same target coverage. Patients with multiple or larger lesions are particularly suited for PT.     

Definitive,intensity modulated tomotherapy with a simultaneous integrated boost for prostate cancer patients – Long term data on toxicity and biochemical control

AimTo report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer.BackgroundDose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used.Materials and methodsIn this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76 Gy with 2.17 Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3).ResultsMedian follow-up of living patients was 66 (20–78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76 Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up.ConclusionSIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.     

Association between EBRT dose volume histograms and quality of life in prostate cancer patients

Aim

To evaluate the association between dose–volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes.

Comparative analysis of several detectors for the measurement of radiation transmission and leakage from a multileaf collimator

The multileaf collimator (MLC) is the standard device used to shape radiation beams for 3-d conformal and intensity-modulated radiation therapy (IMRT). Due to the inherent properties of MLC, there is a small amount of radiation transmitted through the leaves, called radiation transmission (RT). Accurate measurements of this radiation are required to commission and validate IMRT-capable treatment planning systems because this radiation may impact the dosimetry of IMRT-calculated dose distributions. This work compares several detectors in the measurement of RT for a micro-multileaf collimation system. The results show that there are statistically significant differences in the measured RT values between detectors from 3.5 to 12.5% for the same MLC model and less than 0.2% relative to the isocentre dose for an open reference field. However, although small in magnitude, these differences may impact the dosimetry of IMRT treatment planning by up to 1.78 Gy to the healthy tissue surrounding the target for a treatment of 60 Gy in 30 fractions. By the later, these differences must be included as a source of uncertainty in IMRT dose delivery. Also, it must be established which detector offers the most reliable results in the measurement of the RT by using Monte Carlo simulation methods.     

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization

PurposeVentricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques.MethodsECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability.ResultsThe photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively.ConclusionsOur study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.     

Effect of the normal liver mean dose on intrahepatic recurrence in patients with hepatocellular carcinoma after receiving liver stereotactic body radiation therapy

Background and purposeThis study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC).Materials and methodsA total of 76 patients with HCC who were treated with SBRT from January 2015 to May 2020 were included in this retrospective study. The main clinical endpoints considered were intrahepatic out-field free survival (OutFFS) and distant metastasis-free survival (DMFS). The target parameters and the liver were documented including tumor diameters, gross tumor volume (GTV), Liver minus GTV volume (LGV), and Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS. Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD.ResultsThe median follow-up was 28.2 months (range, 7.7–74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747–0.993); p = 0.040] and age greater than 67-year-old [HR, 0.966(0.937–0.997); p = 0.030] are two independent predictors of OutFFS, previous TACE treatment [HR, 0.117(0.015–0.891); p = 0.038] was an independent predictor of DMFS.ConclusionsThe results of this study suggested that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out-field recurrence-free survival (RFS) rate. Further study is warranted to confirm and to better understand this phenomenon.     

膀胱及小肠受量对直肠癌术后放疗副反应的影响

目的:探讨直肠癌术后放疗患者膀胱平均受量及直肠受量对放射性膀胱炎及放射性肠炎的影响。方法:收集我院2005年7月至2010年12月收治的直肠癌根治术后给予放疗的患者130例,收集临床因素、病理因素、放疗因素资料,统计放疗后6个月内放射性肠炎、放射性膀胱炎发生情况。结果:放疗因素中,膀胱壁平均照射剂量对放射性肠炎及膀胱炎的发生有显著影响(P0.05),即膀胱壁剂量越高,副反应发生率越大;当膀胱壁平均剂量达到49.12 Gy时,放射性膀胱炎的发生率显著升高。小肠平均剂量控制在50 Gy以下,其值与放射性肠炎的发生无相关性。结论:直肠癌术后放疗患者膀胱壁平均受量控制在49.12 Gy以下,对减少放射性膀胱炎的发生率有意义。     

The influence of Acuros XB on dose volume histogram metrics and tumour control probability modelling in locally advanced non-small cell lung cancer

PurposeRadiation therapy plans are assessed using dose volume metrics derived from clinical toxicity and outcome data. In this study, plans for patients with locally advanced non-small cell lung cancer (LA-NSCLC) are examined in the context of the implementation of the Acuros XB (AXB) dose calculation algorithm focussing on the impact on common metrics. Methods: Volumetric modulated arc therapy (VMAT) plans were generated for twenty patients, using the Analytical Anisotropic Algorithm (AAA) and recalculated with AXB for both dose to water (D_w) and dose to medium (D_m). Standard dose volume histogram (DVH) metrics for both targets and organs-at-risk (OARs) were extracted, in addition to tumour control probability (TCP) for targets. Results: Mean dose to the planning target volume (PTV) was not clinically different between the algorithms (within ±1.1 Gy) but differences were seen in the minimum dose, D_99% and D_98% as well as for conformity and homogeneity metrics. A difference in TCP was seen for AXB_Dm plans versus both AXB_Dw and AAA plans. No clinically relevant differences were seen in the lung metrics. For point doses to spinal cord and oesophagus, the AXB_Dm values were lower than AXB_Dw, by up to 1.0 Gy. Conclusion: Normalisation of plans to the mean/median dose to the target does not need to be adjusted when moving from AAA to AXB. OAR point doses may decrease by up to 1 Gy with AXB_Dm, which can be accounted for in clinical planning. Other OAR metrics do not need to be adjusted.     

Segmented photon beams technique for irradiation of postmastectomy patients

AimTo present the segmented photon beams technique (SPBT) for irradiation of postmastectomy patients.BackgroundIn majority of techniques for irradiation of posmastectomy patients, a few adjacent photon or electron beams were usually implemented in order to encompass different parts of the target. In the presented SPBT technique, the radiotherapy plan consists of 6 isocentric photon beams and the area CTV includes both the chest wall and the supraclavicular area. This makes it possible to provide a uniform dose to the CTV with no hot and cold points and enables the determination of doses for the entire volume of critical organs.Methods and materialThe treatment forward-IMRT plan comprises six isocentric 4 and 15 MV photon beams. Modulation of the dose distribution for each field was obtained by applying three segments on average. The total dose of 45 Gy was administered in 20 fractions. Dose distributions in target volume and organs at risk were evaluated for 70 randomly chosen patients.ResultsOn average, 94.8% of the CTV volume received doses within 95–107% of the prescribed dose. The average volume of the heart receiving a dose of 30 Gy and lager was 2% for patients with left breast cancer. The average dose to the lung on the irradiation side was always lower than 15.5 Gy and the average V20 Gy was below 35.5%.ConclusionsThe SPBT complies with requirements for high dose homogeneity within the target volume and satisfactory level of sparing of organs at risk.     

Adjuvant gamma knife surgery and image-guided,intensity-modulated radiation therapy for the treatment of sacral chordomas

AimThe aim of this study was to confirm whether patients with sacral chordoma benefit from adjuvant radiotherapy and to determine the optimal photon radiotherapy module for comprehensive treatment.BackgroundChordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 50% occur in the sacrococcygeal region. Surgical resection and adjuvant radiation therapy are recommended treatment due to the improving local control rate.Materials and methods118 patients treated by surgery and adjuvant radiotherapy from August 2003 to May 2015 were retrospectively analyzed. All patients received surgical resection after diagnosis. Among these patients, 44 were treated by exclusive surgery, and 48 were treated with adjuvant image-guided, intensity-modulated radiation therapy (IG-IMRT). In addition, 26 patients were treated with gamma knife surgery (GKS) after surgical resection. The median follow-up was 54 months for all patients. Kaplan–Meier analysis was used to calculate recurrence-free survival (RFS) overall survival (OS).ResultsPatients treated with adjuvant radiotherapy had better RFS (p = 0.014) than those treated exclusively by surgery. The patients in the IG-IMRT group exhibited better recurrence-free survival (p = 0.01) than the GKS group. Moreover, in the IG-IMRT group, patients treated by higher dose were associated with better RFS (p = 0.04). No significant difference in OS was found. No grade 3 late toxicity was found.ConclusionsWe confirmed that adjuvant radiotherapy improved RFS but not OS in sacral chordoma patients after surgery. Furthermore, favorable RFS and low adverse event rates were observed following IG-IMRT. Our results suggest that high dose IG-IMRT is an appropriate module of adjuvant radiotherapy for sacral chordoma patients.     

Cardiac Exposure in the Dynamic Conformal Arc Therapy,Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

Purpose

To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years.

Methods and Materials

A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated.

Results

The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance.

Conclusions

Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy.     

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: Is there a risk for radiation-induced malignancies?

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85–62 mSv, 0.28–1.6 mSv and 0.04–1.6 mSv, respectively. Respective ranges for cancer risk were 0–5.1, 0–0.6 and 0–1.3 cases per 10⁴ persons. Increasing the field size caused an average increase of peripheral doses by 15–20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low.