Radiogenic Side Effects Research Articles

Secondary cancer risk assessment in healthy organs following craniospinal irradiation

Introduction Medulloblastoma is a central nerves tumor that often occurs in pediatrics. The main radiotherapy technique for this tumor type is craniospinal irradiation (CSI), through which the whole brain and spinal cord are exposed to radiation. Due to the immaturity of healthy organs in pediatrics, radiogenic side effects such as second cancer are more severe. Accordingly, the current study aimed to evaluate the risk of secondary cancer development in healthy organs following CSI. Materials and methods Seven organs at risk (OARs) including skin, eye lens, thyroid, lung, liver, stomach, bladder, colon, and gonads were considered and the dose received by each OAR during CSI was measured inside an anthropomorphic RANDO phantom by TLDs. Then, the mean obtained dose for each organ was used to estimate the probability of secondary malignancy development according to the recommended cancer risk coefficients for specific organs. Results The results demonstrated that the stomach and colon are at high risk of secondary malignancy occurrence, while the skin has the lowest probability of secondary cancer development. The total received dose after the treatment course by all considered organs was lower than the corresponding tolerable dose levels. Conclusions From the results, it can be concluded that some OARs during CSI are highly at risk of secondary cancer development. This issue may be of concern due to organ immaturity in pediatrics which can intensify the radiogenic effects of radiation exposure. Accordingly, strict shielding the OARs during craniospinal radiotherapy and/or sparing them from the radiation field through modern techniques such as hadron therapy is highly recommended.

Radiation therapy of breast cancer in the Nahe Breast Center: first results of an analysis in the context of health services research.

The first evaluation of radiotherapy results in patients with breast cancer treated as part of amultimodal oncologic therapy in the Nahe Breast Center is presented. Analysis of the results was performed using an in-practice registry. From September 2016 to December 2017, 138 patients (median age 62.5years; range 36-94years) with breast cancer (right side, n = 67; left side, n = 71) received adjuvant radiation therapy. Of these, 103 patients received gyneco-oncologic care at the Nahe Breast Center, and 35were referred from outside breast centers. The distribution into stages was as follows: stageI, n = 48; stageII, n = 68; stageIII, n = 19; stageIV, n = 3. Neoadjuvant chemotherapy was given to 19and adjuvant chemotherapy to 50patients. Endocrine treatment was given to 120 patients. Both 3D conformal (n = 103) and intensity-modulated (n = 35) radiotherapy were performed with amodern linear accelerator. With amedian follow-up of 60months (1-67), local recurrence occurred in 4/138 (2.9%) and distant metastasis in 8/138 (5.8%) patients; 7/138 (5.1%) patients died of their tumors during the follow-up period. The actuarial 5‑year local recurrence-free survival of all patients was 97.1%, and the actuarial 5‑year overall survival of all patients was 94.9%. We observed no grade3 or4 radiogenic side effects. The results of radiotherapy for breast carcinoma at the Nahe Breast Center are comparable to published national and international results. In particular, the local recurrence rates in our study, determined absolutely and actuarially, are excellent, and demonstrate the usefulness of radiotherapy.

Clinical aspects and care of radiogenic treatment side effects on the eye

Malignant tumors of the eye can be successfully treated with radiotherapy, which, however, can lead to radiogenic side effects in the surrounding healthy tissues. A distinction can be made between two forms of irradiation, external radiotherapy (teletherapy) and brachytherapy with aradiation source close to the tumor. The radiation dose is important for the occurrence of side effects. Acute damage usually results from inflammatory processes initiated at the cellular level. In contrast, late side effects are rather due to the reaction of the tissue with repair and remodeling processes . Acute side effects often resolve completely, especially under corresponding treatment, whereas late side effects tend to be irreversible. The aim of this article is to present risk factors as well as the clinical signs of periocular and ocular radiogenic side effects for the relevant tissue structures of the eye in anarrative review to facilitate ophthalmologic follow-up and, if necessary, treatment measures for these patients during everyday practice.

Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience

Background To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. Material and methods A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. Results The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. Conclusion Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.

Cost-effectiveness analysis of advanced radiotherapy techniques for post-mastectomy breast cancer patients

BackgroundPrior cost-effectiveness studies of post-mastectomy radiotherapy (PMRT) only compared conventional radiotherapy versus no radiotherapy and only considered tumor control. The goal of this study was to perform cost-effectiveness analyses of standard of care (SOC) and advanced PMRT techniques including intensity-modulated radiotherapy (IMRT), standard volumetric modulated arc therapy (STD-VMAT), non-coplanar VMAT (NC-VMAT), multiple arc VMAT (MA-VMAT), Tomotherapy (TOMO), mixed beam therapy (MIXED), and intensity-modulated proton therapy (IMPT).MethodsUsing a Markov model, we estimated the cost-effectiveness of various techniques over 15 years. A cohort of women (55-year-old) was simulated in the model, and radiogenic side effects were considered. Transition probabilities, utilities, and costs for each health state were obtained from literature and Medicare data. Model outcomes include quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER).ResultsFor the patient cohort, STD-VMAT has an ICER of $32,617/QALY relative to SOC; TOMO is dominated by STD-VMAT; IMRT has an ICER of $19,081/QALY relative to STD-VMAT; NC-VMAT, MA-VMAT, MIXED are dominated by IMRT; IMPT has an ICER of $151,741/QALY relative to IMRT. One-way analysis shows that the probability of cardiac toxicity has the most significant impact on the model outcomes. The probability sensitivity analyses show that all advanced PMRT techniques are more cost-effective than SOC at a willingness-to-pay (WTP) threshold of $100,000/QALY, while almost none of the advanced techniques is more cost-effective than SOC at a WTP threshold of $50,000/QALY.ConclusionAdvanced PMRT techniques are more cost-effective for breast cancer patients at a WTP threshold of $100,000/QALY, and IMRT might be a cost-effective option for PMRT patients.

Pilot study: protective effect on mucosal tissue using dental waterjet and dexpanthenol rinsing solution during radiotherapy in head and neck tumor patients

Radiogenic side effects are frequently seen in patients undergoing radiotherapy for head and neck tumors. Intensified dental and mucosal care reduce oral hygienic deficits. The aim of this study was the optimization of mouth hygiene using dexpanthenol rinsing solution applied with a dental waterjet system (DWS). 30 consecutive head and neck tumor patients (44–75 years) were analyzed, who received intensity-modulated radiation treatment (IMRT; total dose range: 54–66 Gy) with helical Tomotherapy HiArt II. The group under investigation (n = 10) additionally received a professional DWS using dexpanthenol mouthrinse (Bepanthen). The first control group received dexpanthenol mouthrinse alone. The second control group only performed the standardized mouth hygiene protocol. Grade of xerostomia, taste, dysphagia, thrush, and mucositis was evaluated on a daily basis. 29 of 30 patients completed radiation therapy. Change in taste occurred in all patients in all groups, however, with a delay in the study group. The occurrence of grade III stomatitis and Xerostomia grade II was significantly reduced in the study arm. No patient suffered from grade III xerostomia in the study arm versus four patients in the control groups. Dysphagia grade II was observed significantly less frequent in the study group (p = 0.0004). Thrush occurrence showed a delay in the study group. Our study underlines the importance of an intensified mouth hygiene during radiation therapy. The combination of dexpanthenol rinsing solution + DWS reduces the incidence of high-grade early side effects which often lead to a reduced quality of life and abortion of the treatment.

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease

IntroductionLangerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis.Methods and materialEight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined.ResultsA total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed.ConclusionIn the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.

Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

Therapy-Associated Late Effects after Irradiation of Malignant Diseases in Childhood and Adolescence. Feasibility Analyses of a Prospective Multicenter Register Study

Radiogenic late effects in children and adolescents have been evaluated retrospectively in most analyses, with small patient numbers. The German Group of Pediatric Radiation Oncology (APRO) has generated a concept for a prospective evaluation of radiation-associated late effects in childhood. The aim of this study was to evaluate the feasibility of a nationwide central database for the documentation of radiation parameters and side effects of all children treated within therapy protocols of the German Society of Pediatric Oncology and Hematology (GPOH). A study center has been implemented in Muenster, the documentation has started in July 2001 in few centers in a pilot phase. Since February 2004 the documentation is done countrywide. Detailed documentation forms have been designed for treatment parameters and for doses applied at organs at risk. Furthermore, a uniform toxicity documentation, according to the RTOG/EORTC criteria, was chosen. Patients were reported from the study centers of the GPOH to the study center. All information was collected and analyzed in the study center. Till July 31, 2005, 438 documentations of radiation and 579 toxicity documentations of side effects have been collected in the study center. 46 centers for radiotherapy in Germany and one center each in Austria and in Switzerland took part in the documentation. The quality of documentation regarding completeness and plausibility fulfilled the expected criteria in most cases. This feasibility analysis showed that important information about organ dose levels and side effects was documented in a large number of patients (Figures 1 and 2). This prospective evaluation of radiotherapy and radiogenic side effects in children and adolescents will allow correlating doses at organs at risk and the incidence of acute and late sequelae in Germany. Further documentations and a longer follow-up are necessary to obtain powerful results.

Surgical oncology from a radio-oncological perspective

BACKGROUND: Oncological surgery and radiotherapy (RT) are both used in most malignant tumours. Multidisciplinary cooperative treatment design is the appropriate setting to effectuate consensual individually tailored therapy. Contrary to a pure referral system, specific diagnostic steps and treatment sequences are fine-tuned in multidisciplinary conferences. This not only results in improved outcome, but also better orientation for physicians and patients, who are not interested in disciplines but in overall treatment plans. METHODS: Review. RESULTS: Various topics for cooperation are identified. Perioperative RT permits limited resection (breast cancer, soft tissue sarcoma) and improves local control rates without widening the resection (breast cancer, rectal cancer, soft tissue sarcoma). Placing clips in the excision cavity requires communication between surgeon and pathologist to be helpful for RT. Limitations of surgery leading to incomplete resections and limits of RT leading to geographical miss or underdosage of the tumour are due to different factors: tissue boundaries versus tumour-volume and radiation tolerance of normal tissue. The time dimension of serious surgical and radiogenic side-effects is also different, surgical problems arising early, radiogenic problems arising over months and years after treatment. RT resembles systemic antineoplastic treatment regarding the way of action, and it resembles surgery with respect to its target orientation. CONCLUSIONS: Clinically relevant progress in oncological therapy is to be expected not only by progress in the various treatment modalities themselves, but also by improvements in the coordination of multimodality treatment.

Radiotherapy is effective in the treatment of symptomatic vertebral hemangiomas (SVH): Long-term results of a multicenter study in germany

Radiotherapy is effective in the treatment of symptomatic vertebral hemangiomas (SVH): Long-term results of a multicenter study in germany

LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical experience.

To study local tumor control and radiogenic side effects after fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma. Between June 1997 and March 2001, 90 patients suffering from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized with a modified stereotactic frame system (BrainLAB). For stabilization of the eye position a light source was integrated into the mask system in front of the healthy or the diseased eye. A mini-video camera was used for on-line eye movement control. Tumors included in the study were either located unfavorably with respect to macula and optical disc (<3 mm distance) or presented with a thickness >7 mm. Median tumor volume was 305+/-234 mm3 (range 70-1430 mm3), and mean tumor height was 5.4+/-2.3 mm (range 2.7-15.9 mm). Total doses of 70 (single dose 14 Gy @ 80% isodose) or 60 Gy (single dose 12 Gy @ 80% isodose) were applied in five fractions within 10 days. The first fractionation results in total dose (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding values for the second fractionation schedule are 135 and 180 Gy, respectively. After a median follow-up of 20 months (range 1-48 months) local control was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and 37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases. Secondary enucleation was performed in seven patients (7.7%). Long term side effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and secondary neovascular glaucoma (8.8%). Fractionated LINAC based stereotactic photon beam therapy in conjunction with a dedicated eye movement control system is a highly effective method to treat unfavorably located uveal melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be sufficient to achieve good local tumor control.

Fractionated stereotactic radiotherapy with linear accelerator for uveal melanoma--preliminary Vienna results.

To study local tumor control and radiogenic side-effects after fractionated stereotactic radiotherapy for uveal melanoma. Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with stereotactic 6 MeV LINAC (Saturne 43, General Electric, France) in conjunction with a stereotactic frame system (BrainLAB, Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0 +/- 2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment. After a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed. Optical fixation of the eye allows high precision stereotactic radiotherapy with small safety margins. Fractionated stereotactic radiotherapy and 70 Gy total dose delivered in 5 fractions seems to be appropriate for local tumor control in uveal melanoma. Further long-term studies with extended number of patients will be necessary to conclude on the use of linac-based fractionated stereotactic radiotherapy for uveal melanoma.

Optimization of irradiation time in the treatment of malignant melanoma of the choroid with beta applicators (106Ru/106Rh)

Brachytherapy with 106Ru/106Rh necessitates protracted irradiation because the applicators have to be sutured to the sclera. Protracted radiotherapy causes more intensive damage in tumor cells with increased metabolism and a higher mitosis rate than in normal tissue. Beta irradiation of rabbit eyes with 0.258-0.231 Gy/min produced more extensive exudative reactions and morphological damage of the retina than a lower dosage rate with 0.035-0.026 Gy/min and the same total dose of 650 Gy. For the study reported here 75 patients suffering from choroidal melanoma and irradiated with 106Ru/106Rh plaques between 1967 and 1977 were evaluated. They developed more exudative and hemorrhagic side effects after a short period of irradiation (1-6 days) than after a longer one (7-14 days). Spontaneous recovery of the radiation-induced retinal detachment was seen in all cases. Complete tumor regression with development of a flat scar was achieved with almost equal success with both short-term and protracted irradiation. To minimize radiogenic side effects the duration of irradiation recommended hitherto, i.e., 7-14 days, should be adhered to when treating malignant melanomas of the choroid with beta-ray applicators.