Dosimetric comparison between proton beam therapy, intensity modulated radiation therapy, and 3D conformal therapy for soft tissue extremity sarcoma.

PURPOSE/OBJECTIVES: Proton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS/METHODS: Seventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal-Wallis rank sum tests were used to get the statistical significance. A p value smaller than .05 was considered to be statistically significant. RESULTS: For the clinical target volume (CTV), D2%, D95%, D98%, Dmin, Dmax, and V50Gy, were assessed. Dmin, D1%, Dmax, Dmean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, Dmax, Dmean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p < .001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p = .022). CONCLUSION: PBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life.

Hybrid planning techniques for early-stage left-sided breast cancer: dose distribution analysis and estimation of projected secondary cancer-relative risk.

PURPOSE: The purpose of this study was to evaluate three techniques of irradiation of left-sided breast cancer patients, three-dimensional conformal radiotherapy (3D-CRT), hybrid Intensity-Modulated Radiotherapy (h-IMRT), and hybrid Volumetric-Modulated Arc Therapy (h-VMAT, h-ARC), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim was to estimate the projected relative risk of radiation-induced secondary cancers for hybrid techniques. MATERIALS AND METHODS: Three treatment plans were prepared in 3D-CRT, h-IMRT, and h-VMAT techniques for each of the 40 patients, who underwent CT simulation in deep inspiration breath-hold (DIBH). For hybrid techniques, plans were created by combining 3D-CRT and dynamic fields with an 80%/20% dose ratio for 3D-CRT and IMRT or VMAT. Cumulative dose-volume histograms were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], left and right lung [LL, RL], right breast [RB]). Projected risk ratios for secondary cancers were estimated relative to 3D-CRT using the organ equivalent dose (OED) concept for the Schneider's linear exponential, plateau, and full mechanistic dose-response model. RESULTS: All plans fulfilled the PTV criterium: V95%≥95%. Compared to 3D-CRT, both hybrid techniques showed significantly better target coverage (PTV: V95%>98%, p < 0.001), and the best conformality was achieved by h-ARC plans (CI: 1.18 ± 0.09, p < 0.001). Compared to 3D-CRT and h-ARC, h-IMRT increased the average sum of monitor units (MU) over 129.9% (p < 0.001). H-ARC increased the mean dose of contralateral organs and the LL V5Gy parameter (p < 0.001). Both hybrid techniques significantly reduced the Dmax of the heart by 5 Gy. Compared to h-IMRT, h-ARC increased secondary cancer projected relative risk ratios for LL, RL, and RB by 18, 152, and 81%, respectively. CONCLUSIONS: The results confirmed that both hybrid techniques provide better target quality and OARs sparing than 3D-CRT. Hybrid VMAT delivers less MU compared to hybrid IMRT but may increase the risk of radiation-induced secondary malignancies.

Radiotherapy for Meningioma.

Meningiomas are the most common primary intracranial brain tumor, and have a heterogeneous biology and an unmet need for targeted treatment options. Existing treatments for meningiomas are limited to surgery, radiotherapy, or a combination of these depending on clinical and histopathological features. Treatment recommendations for meningioma patients take into consideration radiologic features, tumor size and location, and medical comorbidities, all of which may influence the ability to undergo complete resection. Ultimately, outcomes for meningioma patients are dictated by extent of resection and histopathologic factors, such as World Health Organization (WHO) grade and proliferation index. Radiotherapy is a critical component of meningioma treatment as either a definitive intervention using stereotactic radiosurgery or external beam radiotherapy, or in the adjuvant setting for residual disease or for adverse pathologic factors, such as high WHO grade. In this chapter, we provide a comprehensive review of radiotherapy treatment modalities, therapeutic considerations, radiation planning, and clinical outcomes for meningioma patients.

Dosimetric evaluation of a spinal cord dose-limiting 3D-CRT technique for radiotherapy of spinal metastases.

BACKGROUND: To evaluate the possible advantages of a simple spinal cord (SC) dose-limiting three-dimensional conformal radiotherapy (3D-CRT) technique in comparison to conventional two-dimensional (2D) techniques and other 3D-CRT techniques for spinal bone irradiation. METHODS: For 41 spinal target volumes, seven different techniques were evaluated, using a standard schedule of 30 Gy in 10 fractions. The SC dose-limiting 3D-CRT technique 1F2S-18MV using a single posterior field (F) supplemented by two anterior segment fields (S) and 18-MV photon beams was compared to two conventional 2D techniques (a single posterior field, PA, and two opposed anterior-posterior fields, APPA), three other 3D-CRT techniques (a single posterior field supplemented by four segment fields, 1F4S; two wedged fields, WD, and the SC dose-limiting variant using 6 MV, 1F2S-6MV) along with the original clinically applied plans. RESULTS: 1F2S-18MV demonstrated notably better results for all target volume parameters compared to the conventional 2D techniques (p < 0.001). Limitation of the SC dose was significantly superior with 1F2S-18MV in comparison to PA and APPA (SC Dmean: 28.9 ± 0.4  vs. 30.1 ± 0.6 Gy and 30.1 ± 0.4 Gy; SC Dmax: 30.9 ± 0.7  vs. 32.5 ± 1.0 Gy and 31.8 ± 0.7 Gy; SC D1cm3 : 30.1 ± 0.6  vs. 31.7 ± 0.9 Gy and 31.1 ± 0.6 Gy; p < 0.001). Likewise, lower mean SC doses with 1F2S-18MV were observed in comparison to the more treatment time-consuming 3D-CRT techniques (1F4S, WD) and the original plans without relevant compromises on the dose homogeneity in the target volume and the dose exposure to the other OARs. CONCLUSION: In treatment planning of spinal metastases, simple variants of 3D-CRT-techniques like 1F2S-18MV can offer a significant dose limitation to the SC while providing a sufficient dose coverage of the target volume. Especially in patients with favorable life expectancy and potential need for re-irradiation, such SC dose-limiting 3D-CRT techniques may be a reasonable approach.

The institutional experience of the implementing 4DCT in NSCLC radiotherapy planning.

Background: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation. Materials and methods: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins. Results: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT. Conclusions: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.

Impact of radiation techniques on lung toxicity in patients with mediastinal Hodgkin's lymphoma.

PURPOSE: Mediastinal radiotherapy (RT), especially when combined with bleomycin, may result in substantial pulmonary morbidity and mortality. The use of modern RT techniques like intensity-modulated radiotherapy (IMRT) is gaining interest to spare organs at risk. METHODS: We evaluated 27 patients who underwent RT for Hodgkin's lymphoma between 2009 and 2013 at our institution. For each patient, three different treatment plans for a 30-Gy involved-field RT (IFRT) were created (anterior-posterior-posterior-anterior setup [APPA], 5­field IMRT, and 7­field IMRT) and analyzed concerning their inherent "normal tissue complication probability" (NTCP) for pneumonitis and secondary pulmonary malignancy. RESULTS: The comparison of different radiation techniques showed a significant difference in favor of standard APPA (p < 0.01). The risk of lung toxicity was significantly higher in plans using 7­field IMRT than in plans using 5­field IMRT. The absolute juxtaposition showed an increase in risk for radiation pneumonitis of 1% for plans using 5­field IMRT over APPA according to QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) parameters (Burman: 0.15%) and 2.6% when using 7­field IMRT over APPA (Burman: 0.7%) as well as 1.6% when using 7­field IMRT over 5­field IMRT (Burman: 0.6%). Further analysis showed an increase in risk for secondary pulmonary malignancies to be statistically significant (p < 0.01); mean induction probability for pulmonary malignoma was 0.1% higher in plans using 5­field IMRT than APPA and 0.19% higher in plans using 7­field IMRT than APPA as well as 0.09% higher in plans using 7­field IMRT than 5­field IMRT. During a median follow-up period of 65 months (95% confidence interval: 53.8-76.2 months), only one patient developed radiation-induced pneumonitis. No secondary pulmonary malignancies have been detected to date. CONCLUSION: Radiation-induced lung toxicity is rare after treatment for Hodgkin lymphoma but may be influenced significantly by the RT technique used. In this study, APPA RT plans demonstrated a decrease in potential radiation pneumonitis and pulmonary malignancies. Biological planning using NTCP may have the potential to define personalized RT strategies.

Risk for second bladder and rectal malignancies from cervical cancer irradiation.

The objective of this study was to estimate the risk of developing second malignancies to partially in-field organs from volumetric modulated arc therapy (VMAT) of cervical cancer and to compare the above risks with those from the conventional three-dimensional conformal radiotherapy (3D-CRT). Seventeen consecutive patients with uterine cervix carcinoma were selected. VMAT and 3D-CRT plans were generated with 6 and 10 MV photons, respectively. The prescribed tumor dose was 45 Gy given in 25 fractions. Differential dose-volume histogram data from the treatment plans were obtained for the partially in-field organs such as bladder and rectum. These data were used to estimate the patient-specific lifetime attributable risk (LAR) for bladder and rectal cancer induction with a non-linear model based on a mixture of plateau and bell-shaped dose-response relationships. The estimated risks per 10000 people were compared with the baseline risks for unexposed population. The patient-specific rectal cancer risk estimates from VMAT were significantly lower than those from 3D-CRT (P = 0.0144). The LARs for developing bladder malignancies from VMAT were significantly high compared to those from conventional irradiation (P = 0.0003). The mean difference between the patient-specific LARs for radiation-induced bladder and rectal malignancies as derived from 3D-CRT and VMAT plans was 6.6% and 2.0%, respectively. The average LAR for developing bladder and rectal malignant diseases due to VMAT was 9.2 × 10-4 and 43.7 × 10-4 , respectively. The corresponding risks following 3D-CRT were 8.6 × 10-4 and 44.6 × 10-4 . These average risks showed that pelvic irradiation increases the baseline probability for cancer induction by 12.6-19.1%. The differences in the second cancer risks associated with the VMAT and 3D-CRT for cervical cancer were found to be small. Both treatment techniques resulted in considerable increased probabilities for developing bladder and rectal malignancies relative to those of unirradiated population.

Dosimetric study of Hounsfield number correction effect in areas influenced by contrast product in lungs case.

BACKGROUND: The aim of the study was dosimetric effect quantification of exclusive computed tomography (CT) use with an intravenous (IV) contrast agent (CA ), on dose distribution of 3D-CRT treatment plans for lung cancer. Furthermore, dosimetric advantage investigation of manually contrast-enhanced region overriding, especially the heart. MATERIALS AND METHODS: Ten patients with lung cancer were considered. For each patient two planning CT sets were initially taken with and without CA. Treatment planning were optimized based on CT scans without CA. All plans were copied and recomputed on scans with CA. In addition, scans with IV contrast were copied and density correction was performed for heart contrast enhanced. Same plans were copied and replaced to undo dose calculation errors that may be caused by CA. Eventually, dosimetric evaluations based on dose volume histograms (DVHs) of planning target volumes (PTV) and organs at-risk were studied and analyzed using the Wilcoxon's signed rank test. RESULTS: There is no statistically significant difference in dose calculation for the PTV maximum, mean, minimum doses, spinal cord maximum doses and lung volumes that received 20 and 30 Gy, between planes calculated with and without contrast scans (p > 0.05) and also for contrast scan, with manual regions overriding. CONCLUSIONS: Dose difference caused by the contrast agent is negligible and not significant. Therefore, there is no justification to perform two scans, and using an IV contrast enhanced scan for dose calculation is sufficient.

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients.

BACKGROUND: This study aimed to evaluate short term clinical outcomes of accelerated hypofractionated radiotherapy (AHR T) regarding locoregional response (LRR), symptoms relief and acute toxicities in non-small cell lung cancer (NSCLC) patients. The radical treatment for inoperable NSCLC is intolerable for some patients. An alternative RT regime should be considered for them. MATERIALS AND METHODS: Inoperable NSCLC patients who could not tolerate radical treatment were treated with AHRT (45 Gy in 15 fractions over three weeks) by using the 3-dimensional conformal (RT) technique. The LRR was assessed by chest computed tomography (CT) performed before and 6 weeks after RT. Relief of symptoms such as cough, dyspnoea and chest pain was evaluated during RT and 6 and 12 weeks after RT, compared with the status before RT. Treatment-related acute toxicities such as dysphagia and radiation dermatitis were observed during and 6 and 12 weeks after RT. RESULTS: Total 65 patients (seven patients of stage II and fifty-eight patients of stage III) were included. Partial response was seen in 70.8% of patients, and stable disease was seen in 29.2% while there was neither complete response nor progressive disease after RT. Statistically significant associations were found between tumour response vs. pre-treatment tumour size and tumour response vs. performance status of the patients. Satisfactory symptom relief was found after RT, but severe acute dysphagia and radiation dermatitis (more than grade 3) were not observed. CONCLUSION: Satisfactory LRR, symptom relief and acute toxicities were achieved by this regime. Long term studies are recommended to evaluate late toxicities and survival outcome further. TRIAL REGISTRATION NO: TCTR20200110001.

Biochemical relapse free survival rate in patients with prostate cancer treated with external radiotherapy: outcomes obtained at the CMN Siglo XXI Hospital de Oncología, CMN 20 de Noviembre and Hospital General de México of the México City.

AIM: Biochemical relapse-free survival (bRFS) rate is determined by a cohort of Mexican patients (n = 595) with prostate cancer who received treatment with external radiotherapy. BACKGROUND: Patients with prostate cancer were collected from CMN Siglo XXI (IMSS), CMN 20 de Noviembre (ISSSTE), and Hospital General de México (HGM). For the IMSS, 173 patients that are treated with three-dimensional conformal radiation therapy (3D-CRT) and 250 with SBRT, for the ISSSTE 57 patients are treated with 3D-CRT and on the HGM 115 patients are managed with intensity modulated radiation therapy (IMRT). The percentage of patients by risk group is: low 11.1%, intermediate 35.1% and high 53.8%. The average follow-up is 39 months, and the Phoenix criterion was used to determine the bRFS. MATERIALS AND METHODS: The Kaplan-Meier technique for the construction of the survival curves and, the Cox proportional hazards to model the cofactors. RESULTS: (a) The bRFS rates obtained are 95.9% for the SBRT (7 Gy fx, IMSS), 94.6% for the 3D-CRT (1.8 Gy fx, IMSS), 91.3% to the 3D-CRT (2.65 Gy fx, IMSS), 89.1% for the SBRT (7.25 Gy fx, IMSS), 88.7% for the IMRT (1.8 Gy fx, HGM) %, and 87.7% for the 3D-CRT (1.8 Gy fx, ISSSTE). (b) There is no statistically significant difference in the bRFS rates by fractionation scheme, c) Although the numerical difference in the bRFS rate per risk group is 95.5%, 93.8% and 89.1% for low, intermediate and high risk, respectively, these are not statistically significant. CONCLUSIONS: The RT techniques for the treatment of PCa are statistically equivalent with respect to the bRFS rate. This paper confirms that the bRFS rates of Mexican PCa patients who were treated with conventional vs. hypofractionated schemes do not differ significantly.

Transitioning from conformal radiotherapy to intensity-modulated radiotherapy after radical prostatectomy: Clinical benefit, oncologic outcomes and incidence of gastrointestinal and urinary toxicities.

AIM: The purpose of this study was to review genitourinary (GU) and gastrointestinal (GI) toxicity associated with high-dose radiotherapy (RT) delivered with 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) or volumetric arc therapy (VMAT) following radical prostatectomy (RP). BACKGROUND: RP is a therapeutic option for the management of prostate cancer (PrCa). When assessing postoperative RT techniques for PrCa, the published literature focuses on patients treated with 2-dimensional conventional methods without reflecting the implementation of 3D-CRT, IMRT, or VMAT. MATERIALS AND METHODS: A total of 83 patients were included in this analysis; 30 patients received 3D-CRT, and 53 patients received IMRT/VMAT. Acute and late symptoms of the GU and lower GI tract were retrospectively graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer radiation toxicity grading systems. The relapse failure-free rate and overall survival were also evaluated. RESULTS: The rate of acute GU toxicity was 9.4% vs. 13.3% for the IMRT/VMAT and 3D-CRT groups (p = 0.583). The 5-year actuarial rates of late GI toxicity for IMRT/VMAT and 3D-CRT treatments were 1.9% and 6.7%, respectively. The rate of late GU toxicity for the IMRT/VMAT and 3D-CRT treatment groups was 7.5% and 16.6%, respectively (p = 0.199). We found no association between acute or late toxicity and the RT technique in univariate and multivariate analyses. CONCLUSION: Postprostatectomy IMRT/VMAT and 3D-CRT achieved similar morbidity and cancer control outcomes. The clinical benefit of highly conformal techniques in this setting is unclear although formal analysis is needed.

Exposure of remote organs and associated cancer risks from tangential and multi-field breast cancer radiotherapy.

PURPOSE: With the ever-increasing cure rates in breast cancer, radiotherapy-induced cancers have become an important issue. This study aimed to estimate secondary cancer risks for different treatment techniques, taking into account organs throughout the body. MATERIAL AND METHODS: Organ doses were evaluated for a tangential three-dimensional conformal (3D-CRT) and a multi-field intensity-modulated radiotherapy (IMRT) plan using a validated, Monte Carlo-based treatment planning system. Effects of wedges and of forward versus inverse planning were systematically investigated on the basis of phantom measurements. Organ-specific cancer risks were estimated using risk coefficients derived from radiotherapy patients or from the atomic bomb survivors. RESULTS: In the 3D-CRT plan, mean organ doses could be kept below 1 Gy for more remote organs than the lung, heart, and contralateral breast, and decreased to a few cGy for organs in the lower torso. Multi-field IMRT led to considerably higher mean doses in organs at risk, the difference being higher than 50% for many organs. Likewise, the peripheral radiation burden was increased by external wedges. No difference was observed for forward versus inverse planning. Despite the lower doses, the total estimated secondary cancer risk in more remote organs was comparable to that in the lung or the contralateral breast. For multi-field IMRT it was 75% higher than for 3D-CRT without external wedges. CONCLUSION: Remote organs are important for assessment of radiation-induced cancer risk. Remote doses can be reduced effectively by application of a tangential field configuration and a linear accelerator set-up with low head scatter radiation.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Middle or Lower Esophageal Cancer Using Elective Nodal Irradiation: Comparison with 3D Conformal Radiotherapy.

We investigated the feasibility of simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) using elective nodal irradiation (ENI) for middle or lower esophageal cancer and compared it with three-dimensional conformal radiotherapy (3D-CRT). The study included 15 patients. The prescribed doses included a standard dose (50.4 Gy) and a high dose (60 Gy) for the planning target volume (PTV) of the involved lesions. The objective of the whole lung volume receiving ≥ 20 Gy (V20Gy) was < 30%, and the mean lung dose (MLD) was < 20 Gy. The volumes of the lung receiving 5 Gy (V5Gy) and the heart receiving 30-50 Gy (V30-50Gy) were kept as low as reasonably achievable. As a result, SIB-VMAT showed superior dose conformity for the PTV (p<0.001). Although the lung V5Gy was significantly increased (p<0.001), the V20Gy and MLD showed no significant increase. The heart V30-50Gy showed a > 20% reduction in the mean against 3D-CRTs. Our results demonstrate the feasibility of SIB-VMAT for the treatment of middle or lower esophageal cancer with ENI. Although attention should be paid to the low-dose area of the lungs, SIB-VMAT would be a promising treatment option with improved outcomes for esophageal cancer.

On the use of AAA and AcurosXB algorithms for three different stereotactic ablative body radiotherapy (SABR) techniques: Volumetric modulated arc therapy (VMAT), intensity modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3D-CRT).

AIM: The purpose of this study was to investigate the dosimetric characteristics of three stereotactic ablative body radiotherapy (SABR) techniques using the anisotropic analytical algorithm (AAA) and Acuros XB algorithm. The SABR techniques include coplanar volumetric modulated arc therapy (C-VMAT), non-coplanar intensity modulated radiation therapy (NC-IMRT) and non-coplanar three-dimensional conformal radiotherapy (NC-3D CRT). BACKGROUND: SABR is a special type of radiotherapy where a high dose of radiation is delivered over a short time. The treatment outcome and accuracy of the dose delivered to cancer patients highly depend on the dose calculation algorithm and treatment technique. MATERIALS AND METHODS: Twelve lung cancer patients underwent 4D CT scanning, and three different treatment plans were generated: C-VMAT, NC-IMRT, NC-3D CRT. Dose calculation was performed using the AAA and Acuros XB algorithm. The dosimetric indices, such as conformity index (CI), homogeneity index, dose fall-off index, doses received by organs at risk and planning target volume, were used to compare the plans. The accuracy of AAA and Acuros XB (AXB) algorithms for the lung was validated against measured dose on a CIRS thorax phantom. RESULTS: The CIs for C-VMAT, NC-IMRT and NC-3D CRT were 1.21, 1.28 and 1.38 for the AAA, respectively, and 1.17, 1.26 and 1.36 for the Acuros XB algorithm, respectively. The overall dose computed by AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm. The overall dose computed by the AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm. CONCLUSION: This study showed that the treatment planning results obtained using the Acuros XB algorithm was better than those using the AAA algorithm in SABR lung radiotherapy.

Cardiotoxicity of mediastinal radiotherapy.

AIM: To explore available recent literature related to cardiotoxicity following mediastinal radiation. BACKGROUND: Radiotherapy-related heart injury is well documented, with no apparent safety threshold dose. The number of long-term cancer survivors exposed to mediastinal radiotherapy at some point of their treatment is increasing. Heart dosimetric parameters are of great importance in developing a treatment plan, but few data are available regarding radiosensitivity and dose-volume constraints for specific heart structures. MATERIALS AND METHODS: In October 2018, we identified articles published after 1990 through a PubMed/MEDLINE database search. The authors examined rough search results and manuscripts not relevant for the topic were excluded. We extracted clinical outcomes following mediastinal radiotherapy of childhood cancers, lymphoma, medulloblastoma, thymic cancers and hematopoietic cell transplantation survivors and evaluated treatment planning data, whenever available. RESULTS: A total of 1311 manuscripts were identified in our first-round search. Of these manuscripts, only 115 articles, matching our selection criteria, were included. CONCLUSIONS: Studies uniformly show a linear radiation dose-response relationship between mean absorbed dose to the heart (heart-Dmean) and the risk of dying as a result of cardiac disease, particularly when heart-Dmean exceeds 5 Gy. Limited data are available regarding dose-volume predictors for heart substructures and the risk of subsequent cardiac toxicity. An individual patient's cardiotoxicity risk can be modified with advanced treatment planning techniques, including deep inspiration breath hold. Proton therapy is currently showing advantages in improving treatment planning parameters when compared to advanced photon techniques in lymphoma, thymic malignancies, malignant mesothelioma and craniospinal irradiation.

Thymic tumors and results of radiotherapy.

AIM: The aim of this study was to evaluate thymic epithelial tumors (TETs) for treatment outcomes and prognostic factors on survival. BACKGROUND: TETs are very rare neoplasms and multidisciplinary approach is recommended according to prognostic factors. MATERIALS AND METHODS: Between 1995 and 2013, 31 patients were treated with median 5400 cGy (range: 1620-6596 cGy) radiotherapy (RT). Eleven patients received adjuvant or concurrent chemotherapy. There were 25 thymomas, 4 thymic carcinomas and 2 thymic neuroendocrin carcinomas. According to Masaoka, staging and WHO classification, cases were divided to good (n: 10), moderate (n: 9) and poor (n: 12) prognostic risk groups. Survival was calculated from diagnosis. RESULTS: In January 2016, 22 cases were alive with median 51.5 months (range: 2-170.5) follow-up. Recurrences were observed in 29% of patients in median 29.5 months (range: 6.5-105). Local control, mean overall (OS) and disease-free survival (DFS) rates were 86%, 119 and 116 months, respectively. There was a significant difference for R0 vs. R+ resection (81% vs. 43%, p = 0.06, and 69% vs. 46%, p = 0.05), Masaoka stage I-II vs. III-IV (75% vs. 52%, p = 0.001, and 75% vs. 37%, p < 0.001), and also prognostic risk groups (100% vs. 89% vs. 48%, p = 0.003, and 100% vs. 87% vs. 27%, p = 0.004) in terms of 5-year OS and DFS, respectively. CONCLUSION: In our study, prognostic risk stratification was shown to be a significant predictor of survival. There is a need to investigate subgroups that may or may not benefit from adjuvant RT.

A phase II trial of concurrent 3D-CRT/IMRT and oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) in gastric cancer patients with R0 gastrectomy and D2 lymph node dissection.

BACKGROUND: To evaluate the safety and efficacy of a concurrent three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) plus oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) regimen in completely resected gastric cancer patients with D2 lymph node dissection. MATERIALS AND METHODS: Patients with stage IB-IIIC gastric cancer (per the AJCC, 7th edition) who had undergone R0 and D2 gastrectomy were recruited. Two cycles of FOLFOX with concurrent 3D-CRT or IMRT (50.4 Gy/28f) were administered. One and an additional five cycles of FOLFOX were delivered before and after concurrent chemoradiotherapy, respectively. Primary endpoints were relapse-free survival (RFS) and overall survival (OS), with adverse events as secondary endpoints. RESULTS: From 2008 to 2011, 110 patients were evaluable. The 1-, 2- and 3-year RFS and OS were 86.2, 72.2, 67.8 and 94.7, 87.2, 77.6%, respectively. On multivariate analysis, stage (≤ IIIA vs. >IIIA) was a statistically significant factor affecting both RFS and OS. Additionally, the T-category (≤ T4a vs. = T4b) was a statistically significant factor affecting only the RFS. The most commonly observed grade 3 or 4 adverse events were nausea and vomiting, decreased appetite, leukopenia/neutropenia and fatigue, each of which occurred in 14.5, 11.8, 9.1 and 6.4% patients, respectively. CONCLUSIONS: Adjuvant 3D-CRT/IMRT to a dose of 50.4 Gy/28f with concurrent FOLFOX is safe and effective in patients following radical gastrectomy with D2 lymph node dissection.

Dosimetric and clinical toxicity comparison of critical organ preservation with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and RapidArc for the treatment of locally advanced cancer of the pancreatic head.

PURPOSE: We compared dosimetry and clinical toxicity for 3-dimensional conformal radiotherapy (3D-crt), intensity-modulated radiotherapy (imrt), and RapidArc (Varian Medical Systems, Palo Alto, CA, U.S.A.) in locally advanced pancreatic cancer (lapcc). We hypothesized that the technique with better sparing of organs at risk (oars) and better target dose distributions could lead to decreased clinical toxicity. METHODS: The study analyzed 280 patients with lapcc who had undergone radiotherapy. The dosimetry comparison was performed using 20 of those patients. Dose-volume histograms for the target volume and the oars were compared. The clinical toxicity comparison used the 280 patients who received radiation with 3D-crt, imrt, or RapidArc. RESULTS: Compared with 3D-crt, RapidArc and imrt both achieved a better conformal index, homogeneity index, V95%, and V110%. Compared with 3D-crt or imrt, RapidArc reduced the V10, V20, and mean dose to duodenum, the V20 of the right kidney, and the liver mean dose. Compared with 3D-crt, RapidArc reduced the V35, and V45 of duodenum, the mean dose to small bowel, and the V15 of right kidney. The incidences of grades 3 and 4 diarrhea (p = 0.037) and anorexia (p = 0.042) were lower with RapidArc than with 3D-crt, and the incidences of grades 3 and 4 diarrhea (p = 0.027) were lower with RapidArc than with imrt. CONCLUSIONS: Compared with 3D-crt or imrt, RapidArc showed better sparing of oars, especially duodenum, small bowel, and right kidney. Also, fewer acute grades 3 and 4 gastrointestinal toxicities were seen with RapidArc than with 3D-crt or imrt. A technique with better sparing of oars and better target dose distributions could result in decreased clinical toxicities during radiation treatment for lapcc.

Treatment outcomes with hypofractionated high-dose radiation therapy for prostate cancer.

AIM: To report the treatment results of a retrospective cohort of prostate cancer patients treated with Hypo-RT with a high equivalent biological effective dose (BED). BACKGROUND: Hypofractionated radiotherapy (Hypo-RT) has gained popularity and interest in the treatment of prostate cancer. However, there are few experiences with adequate follow-up reporting treatment results using high equivalent dose with Hypo-RT. MATERIALS AND METHODS: We assigned 149 men with low-, intermediate- and high-risk prostate cancer to receive Hypo-RT with a total dose of 69 Gy/23 fractions. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified RTOG criteria. Biochemical no evidence of disease (bNED) was defined as the nadir prostate-specific antigen level plus 2 ng/mL. RESULTS: The median follow-up was 53 months. For the entire cohort, the 5-year bNED rate was 94.6%, and for low-, intermediate- and high-risk patients the 5-year bNED was 100%, 96.4%, and 86% (p = 0.007), respectively. The 5-year overall survival rate was 92%. Only 1 patient died from the disease at 48 months after treatment, giving a 5-year cancer-specific survival of 98%. The worst grade ≥2 rate GI and GU toxicity was 13.4% and 14%, respectively. No grade >3 toxicity was observed. The presence of grade ≥2 GI and GU toxicity at the last follow-up was only 1.3% and 3%, respectively. CONCLUSIONS: Hypo-RT (69 Gy/23 fractions) with a high equivalent BED produces excellent rates of biochemical control for low, intermediate and high-risk prostate cancer. The long term GU and GI toxicity rates were considered low and acceptable.

Treatment planning study of Volumetric Modulated Arc Therapy and three dimensional field-in-field techniques for left chest-wall cancers with regional lymph nodes.

AIM: This study aims to investigate whether there are dosimetric advantages to using VMAT (Volumetric Modulated Arc Therapy) for left-sided chest-wall patients over the three-dimensional conformal field-in-field (FinF) technique. BACKGROUND: There is a lack of dosimetric studies dedicated for chest-wall patients. Potential dosimetric advantage could be obtained using VMAT due to complex geometry of PTVs (Planning Target Volumes) and OARs (Organs at Risk) in chest-wall and lymph nodes. MATERIALS AND METHODS: VMAT and FinF plans were generated and evaluated based on DVHs (Dose Volume Histograms) for both PTVs and OARs for 22 left-sided chest-wall patients with involved regional nodes. PTV HIs (Homogeneity Indices) and CIs (Conformity Indices), and EUDs (Equivalent Uniform Doses) for PTVs and OARs were also evaluated for comparisons between VMAT and FinF. RESULTS: FinF planning met PTV criteria adequately in all cases except two. In these two cases, VMAT was able to meet PTV criteria adequately. VMAT demonstrated significant reduction in left lung V20 Gy in chest-wall patients compared to FinF plans. The volumes of the right lung and right breast receiving 5 Gy were much higher in VMAT than those in FinF for all patients. CONCLUSIONS: Compared to the FinF technique, there is a generally limited benefit using VMAT for left-sided chest-wall patients due to large low-dose-bath to OARs with insignificant improvement in PTV coverage. In case where FinF planning cannot meet dose constrains, VMAT provides a viable option. The use of VMAT planning over the FinF technique in chest-wall cancers should be carefully analyzed on an individual basis.