Radiotherapy for Nonmalignant Eye Diseases: Graves' Ophthalmopathy - Pseudotumor Orbitae.

Comparison of the Dosimetry of Spinal Fields in Craniospinal Irradiation using Two Dimensional, Three Dimensional and Intensity Modulated Radiation Therapy Planning Techniques

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Classification of Eye Changes of Graves' Disease

Interleukin-1 (IL-1) plays an important role in the pathogenesis of Graves' ophthalmopathy (GO). Impaired antagonism of the proinflammatory cytokine IL-1 by the naturally occurring IL-1 receptor antagonist (IL-1RA) has been implicated in the initiation and perpetuation of various autoimmune diseases and may play a role in the evolution of GO. Cigarette smoking appears to adversely affect the course of GO. We have evaluated the course of IL-1 alpha, IL-1 beta, and soluble IL-1RA (sIL-1RA) serum levels in smokers and nonsmokers with GO undergoing orbital radiotherapy (OR). We prospectively studied the eye status of 27 randomly selected patients (mean age 47.3 +/- 11.0 yr; 20 females; 18 smokers) with active, moderately severe GO before and 3 and 6 months following OR, respectively. None had received any previous treatment for GO, and all patients were kept euthyroid on carbimazole. Serum concentrations of IL-1 alpha, IL-1 beta, and sIL-1RA were measured using highly sensitive enzyme linked immunosorbent assay systems. Baseline sIL-1RA levels were negatively correlated with the number of cigarettes smoked before and following OR (P < 0.0001). Patients with no or minor therapeutic response to OR (n = 8), all of whom were smokers, revealed mean baseline sIL-1RA levels of 114 +/- 85 pg/mL, which increased to 172 +/- 103 pg/mL at 3 months and 149 +/- 96 pg/mL at 6 months after initiation of OR, respectively. By contrast, patients with a good clinical response (n = 19, 9 nonsmokers), revealed significantly higher baseline sIL-1RA levels at 294 +/- 148 pg/mL (P = 0.004), which increased to 845 +/- 668 pg/mL at 3 months (P = 0.01) and 634 +/- 337 pg/mL at 6 months (P < 0.001), respectively, following initiation of OR. Serum concentrations of IL-1 alpha IL-1 beta were below 3.9 pg/mL in all patients with GO who were studied, and were not correlated with gender, age, smoking status, clinical course, or outcome. Low baseline levels and impaired surge of sIL-1RA serum levels following OR were strongly correlated with smoking status and a less favorable therapeutic outcome in patients with active, moderately severe GO. Measurement of sIL-1RA may contribute to predict the therapeutic response to OR in patients with active, moderately severe GO. Strategies designed to raise local or systemic concentrations of sIL-1RA may be of benefit to patients with GO.

To compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of Graves' ophthalmopathy (GO) based on the dosimetric data. 19 patients diagnosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Dosimetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed. Homogeneity index (HI) was superior in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs protection especially for the left and right lenses, optic nerves and eyeballs (p<0.05). VMAT and IMRT are both feasible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homogeneity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

Impact of Pelvic Intensity-modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

External beam radiotherapy can be delivered more precisely by using three Dimensional Conformal Radiotherapy (3D-CRT) technique, which is a traditional method used for whole breast radiotherapy. 3D-CRT includes standard wedged tangents (two opposed wedged tangential photon beams), which is based on three Dimensional images (3D) from a special computed tomography (CT scan). Overseas notification form advent of CT scans and more powerful computers have improved dose calculation algorithms and Multi-leaf Collimators (MLCs). Consequently, 3D-CRT is able to shape the Radiotherapy Beam (RTB) closely to match the target shape and volume. Intensity Modulated Radiation Therapy (IMRT) technique has the ability to improve sparing of normal tissues and treatment results of radiotherapy (RT). RT is a standard adjuvant therapy in conservative treatment of breast cancer (BC). The IMRT technique is used for many treatment sites, allowing for improved normal tissue sparing, more conformal dose distributions and prevention of secondary cancer. The purpose of this study is to verify and evaluate between the outcome of Radiation Treatment Plans (RTP) of left-sided whole breast irradiation of IMRT technique, and 3D-CRT technique to organs at risk (OAR) that are proximal to the target volume during breast radiotherapy. These include left lung, right lung, heart, and spinal cord by different numbers of beam in left sided breast at Zhianawa cancer center (ZCC) – Sulaimany-KR-Iraq. A second aim is to establish a guideline for breast cancer radiotherapy planning at ZCC. Thirteen patients with left-sided, breast carcinoma who had received radiotherapy were selected for this study. The dose prescriptions for the patients were different according to each patient’s cancer stage, using 6, 18 MV photons. The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, left lung, right lung, heart, and spinal cord tissues as OAR. The two different planning techniques were analyzed for 13 patients with left-sided breast conserving surgery. Plans were compared on the basis of planning target volume (PTV) dose conformity index (CI), homogeneity index (HI) and the volumes of normal tissues treated based on dose-volume histograms (DVHs). DVHs were calculated for the PTV, heart, left lung, right lung, spinal cord and soft tissue surrounding the breast PTV (VOB) volume. IMRT techniques slightly improved homogeneity ( HI) than 3D (0.16.04 vs. 0.22, p<0.068). However, there was no significant difference between IMRT and 3D-CRT plans regarding CI. No significant difference was noted in CI by 3D and IMRT as both showed similarity, p< 0.190 ); IMRT technique benefited patients more than 3D-CRT by reducing the high-dose (40.05 Gy) volume for the heart. The heart’s mean dose was significantly lower in 3D compared to IMRT (3.58 Gy vs. 10.07Gy, respectively; p < 0.0001). Both the mean dose of the left lung and right lung, were significantly lower for 3D compared to IMRT (10.18Gy vs. 14.26Gy and 0.34 vs. 4.17 respectively; p < 0.001), and p< 0.0001. Cord Max. Cord Max dose was significantly lower in 3D compared to IMRT (6.83Gy % vs. 20.89 Gy%, p < 0.0001). IMRT plans improved by increasing low-dose volume (Lift lung, and Spinal cord soft tissue surrounding the breast) compared with 3D-CRT plans (P<0.0001) but with Right lung P<0.575. However, 3D-CRT plans were improved by increasing low-dose volume (heart) compared with IMRT plans (P<0.230)

Objective To compare the planning quality and volume of organ at risk (OAR) between volumetric-modulated arc therapyv(VMAT) and nine-field dynamic intensity-modulated radiation therapy (IMRT) in radiotherapy for cervical cancer patients, explore the best way to cervical cancer radiotherapy. Methods Selected 20 patients with cervical cancer were divided into 2 groups, 10 cases for each group. Cervical cancer patients with no surgery was performed for A group (group A), received the radical radiotherapy, prescription dose gross tumor volume (GTV) 56 Gy, clinical target volume (CTV) 50 Gy. Another group of patients with cervical cancer radical surgery (group B), giving the whole basin lymph node auxiliary radiation therapy, prescription dose CTV 50 Gy. Each cervical cancer patient received VMAT and IMRT program designs, the differences in dose volume histogram (DVH), irradiated volume of organ at risk (OAR), heterogeneity index (HI), conformity index (CI), maximum dose (PTVmax), minimum dose (PTVmin) and mean dose (PTV mean) were compared between two plans in 2 groups. Results Two kinds of radiation technology in target area dosimetry were not statistical difference between two groups (P>0.05). In endanger organs on the protection of two groups of VMAT planning groups in the small intestine V20 and left femoral head V20 had obvious advantages with statistically significance (P<0.05). Conclusions Two groups of dosimetry between VMAT and IMRT program design are similar in cervical cancer. Two groups of VMAT planning groups to protect endanger organ slightly better than that of IMRT group, but VMAT planning group shortens treatment time and improves the accuracy and efficacy of treatment. Key words: Uterine cervical neoplasms/RT; Radiotherapy, intensity-modulated/MT; Radiotherapy dosage

Objective To explore the correlation between the respiration-induced clinical target volume (CTV) motion and volume variation and the dosimetric variation of planning target volume (PTV) and organs at risk (OAR) during free-breathing (FB) with whole breast intensity-modulated radiotherapy (IMRT).Methods Seventeen patients with breast conserving surgery underwent respiration-synchronized four-dimentional computed tomography (4DCT) simulation scans on the state of FB.The treatment plan was constructed using the end-inspiration phase scan,then copied and applied to the other respiratory phases.The dose distribution was calculated separately to evaluate the dose-volume histograms parameters for the PTV,ipsilateral lung and heart.Results During FB,the CTV motion vector was (2.09 ±0.74) mm,and the volume variation was (3.05 ± 0.94) ％.There was no correlation between the volume variation of CTV and dosimetric variation of PTV/OAR ( r =-0.390 -0.480,P =0.182 -0.775 ).In anteroposterior (AP),superoinferior (SI) and vector directions,the CTV movement correlated well with the PTV mean dose,conformal index,and the lung volume receiving high dose (V20,V30,V40,and V50;r=-0.975-0.791,P =0.000 -0.041 ).In SI and vector directions,the CTV displacement only correlated with the heart volume receiving ＞ 5 Gy ( V5 ) ( r =-0.795,0.687,P =0.006,0.028 ).The lung volume variation and the lung volume receiving high dose correlated reasonably well (r=0.655 -0.882,P=0.001-0.04 0).The heart volume variation only correlated with the V5 of heart (r =-0.701,P =0.024).Conclusions During free-breathing,the effect of breast volume variation can be ignored for whole breast IMRT,and whole breast IMRT assisted with breath-hold may improve the accuracy of dose delivery during radiotherapy. Key words: Radiotherapy,whole breast; Radiotherapy,intensity-modulated; Dosimetry

Our purpose in this study was to implement three-dimensional (3D) gamma analysis for structures of interest such as the planning target volume (PTV) or clinical target volume (CTV), and organs at risk (OARs) for intensity-modulated radiation therapy (IMRT) dose verification. IMRT dose distributions for prostate and head and neck (HN) cancer patients were calculated with an analytical anisotropic algorithm in an Eclipse (Varian Medical Systems) treatment planning system (TPS) and by Monte Carlo (MC) simulation. The MC dose distributions were calculated with EGSnrc/BEAMnrc and DOSXYZnrc user codes under conditions identical to those for the TPS. The prescribed doses were 76 Gy/38 fractions with five-field IMRT for the prostate and 33 Gy/17 fractions with seven-field IMRT for the HN. TPS dose distributions were verified by the gamma passing rates for the whole calculated volume, PTV or CTV, and OARs by use of 3D gamma analysis with reference to MC dose distributions. The acceptance criteria for the 3D gamma analysis were 3/3 and 2 %/2 mm for a dose difference and a distance to agreement. The gamma passing rates in PTV and OARs for the prostate IMRT plan were close to 100 %. For the HN IMRT plan, the passing rates of 2 %/2 mm in CTV and OARs were substantially lower because inhomogeneous tissues such as bone and air in the HN are included in the calculation area. 3D gamma analysis for individual structures is useful for IMRT dose verification.

Comparative Analysis of Dose Distribution and Acute Toxicity with Intensity Modulated Radiation Therapy (IMRT) vs. Conventional Radiation Therapy in Gastric Carcinoma

Larynx-sparing Techniques using Intensity Modulated Radiation Therapy for Head and Neck Cancer Treatment

The pathogenesis of Graves' ophthalmopathy has not been yet clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an enigma. The natural course and effects of different treatment regimens are poorly documented. The mean observation period was 3.23 years (1-8.9 years) for all 196 patients, and 2.85 years (1-8.9 years) for the 81 patients with Graves' ophthalmopathy. The gender distribution was 77% female and 23% male in patients with Graves' disease and ophthalmopathy, and 81% female and 19% male in those patients without ophthalmopathy (p = 0.57). Seventy per cent of the patients developed Graves' ophthalmopathy within 12 months before or after the onset of the hyperthyroidism. Among the 81 patients with ophthalmopathy 53 (65%) received no therapy or only local protective agents. Twenty-five of these patients improved substantially, 26 did not change, and 2 deteriorated progressively. These results were independent of the severity of the EO (p = 0.42). Among the 11 patients initially treated with systemic corticosteroids 7 improved, 3 did not change, and 1 worsened. Five patients received initially orbital irradiation. Three improved and 2 did not change after radiotherapy. Orbital decompression was performed in 3 patients. Nine patients received a combination treatment. In conclusion, our study of a relatively large patient sample revealed the known epidemiological facts regarding Graves' disease and endocrine ophthalmopathy. The majority of patients needed no therapy or only local protective agents, and 47% improved spontaneously. Systemic corticosteroids and orbital irradiation appear to be equally effective as initial treatment in patients with more severe forms of Graves' ophthalmopathy.

The pathogenesis of Graves' ophthalmopathy has not been yet clarified, and from a therapeutic standpoint Graves' ophthalmopathy remains an enigma. The natural course and effects of different treatment regimens are poorly documented. The mean observation period was 3.23 years (1-8.9 years) for all 196 patients, and 2.85 years (1-8.9 years) for the 81 patients with Graves' ophthalmopathy. The gender distribution was 77% female and 23% male in patients with Graves' disease and ophthalmopathy, and 81% female and 19% male in those patients without ophthalmopathy (p = 0.57). Seventy per cent of the patients developed Graves' ophthalmopathy within 12 months before or after the onset of the hyperthyroidism. Among the 81 patients with ophthalmopathy 53 (65%) received no therapy or only local protective agents. Twenty-five of these patients improved substantially, 26 did not change, and 2 deteriorated progressively. These results were independent of the severity of the EO (p = 0.42). Among the 11 patients initially treated with systemic corticosteroids 7 improved, 3 did not change, and 1 worsened. Five patients received initially orbital irradiation. Three improved and 2 did not change after radiotherapy. Orbital decompression was performed in 3 patients. Nine patients received a combination treatment. In conclusion, our study of a relatively large patient sample revealed the known epidemiological facts regarding Graves' disease and endocrine ophthalmopathy. The majority of patients needed no therapy or only local protective agents, and 47% improved spontaneously. Systemic corticosteroids and orbital irradiation appear to be equally effective as initial treatment in patients with more severe forms of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is clinically associated with autoimmune thyroid disease, and autoantibodies to thyroidal antigens, especially to the TSH-receptor (TRAb), might be involved in the disease process. While there is mounting evidence that TRAb are associated with GO at the onset of the disease, so far no studies have looked at the association between thyroidal autoantibodies and the clinical outcome of GO therapy. The aim of this retrospective study was to evaluate whether TSH binding inhibitory immunoglobulins (TBII) and thyroid stimulating antibodies (TSAb) are still associated with the clinical activity and severity of GO after the completion of anti-inflammatory therapy. In addition, we wanted to elucidate whether thyroid peroxidase (TPO) or thyroglobulin (TG) autoantibodies (TPOAb and TGAb) are in any way related to GO. DESIGN PATIENTS AND MEASUREMENTS: Clinical activity score (CAS) and the severity of GO (modified NOSPECS score) were assessed in 108 patients with GO after steroid therapy and, if indicated, orbital irradiation. Patients were grouped according to their clinical presentation and autoantibody levels (TBII, TSAb, TPOAb and TGAb) were measured. After therapy for hyperthyroidism, all patients were clinically euthyroid but showed clear heterogeneity for GO 4-12 months after the end of anti-inflammatory therapy. Fifty-two patients had inactive GO, 41 had moderately active and 15 still had very active (non-responsive) GO. Concerning severity, 27 patients had mild GO, 64 moderately severe and 17 severe GO. TBII titres were still positive in 14 (93%) of 15 patients in the non-responsive group (CAS > 6) compared to 22 (42%) of 52 patients (P < 0.001) with post-therapeutic inactive GO (CAS </= 2). A similar result was seen between TBII levels and the NOSPECS score. The simultaneous presence of TBII and TSAb was associated with significantly higher activity and severity [odds ratios: 4.9 (activity); 9.0 (severity)] than the presence of TBII without measurable TSAb [odds ratios: 2.1 (activity), 2.0 (severity)] in comparison to absence of both antibodies. Only TBII and TSAb, but not TPOAb or TGAb medians, increased statistically significantly with CAS or NOSPECS scores. Both scores were positively associated with TBII (CAS: r = 0.31 P < 0.001; NOSPECS: r = 0.38, P < 0.0001) and, to a lesser degree, with TSAb (CAS: r = 0.27, P < 0.007, and NOSPECS: r = 0.29, P < 0.003). This association was independent of the treatment of hyperthyroidism, although highest levels of TBII were seen after radioiodine treatment. The NOSPECS score was negatively associated with TGAb (r =-0.27, P < 0.01) but not with TPOAb, while both showed no association with the CAS score. We conclude that the persistence of TBII and TSAb levels in patients with therapy-resistant disease in comparison to patients with inactive disease supports the role of TRAb in the pathogenesis of GO. Furthermore, the fact that, even after anti-inflammatory therapy, TBII and TSAb levels and prevalence still correlate with the severity and activity of GO suggests not only a trigger but also a possible role in the maintenance of the autoimmune process in the orbits.