Adapting a practical EPR dosimetry protocol to measure output factors in small fields with alanine.

PURPOSE: Modern radiotherapy techniques often deliver small radiation fields. In this work, a practical Electron Paramagnetic Resonance (EPR) dosimetry protocol is adapted and applied to measure output factors (OF) in small fields of a 6 MV radiotherapy system. Correction factors and uncertainties are presented and OFs are compared to the values obtained by following TRS-483 using an ionization chamber (IC). METHODS: Irradiations were performed at 10 cm depth inside a water phantom positioned at 90 cm source to surface distance with a 6 MV flattening filter free photon beam of a Halcyon radiotherapy system. OFs for different nominal field sizes (1 × 1, 2 × 2, 3 × 3, 4 × 4, normalized to 10 × 10 cm2 ) were determined with a PinPoint 3D (PTW 31022) IC following TRS-483 as well as with alanine pellets with a diameter of 4 mm and a height of 2.4 mm. EPR readout was performed with a benchtop X-band spectrometer. Correction factors due to volume averaging and due to positional uncertainties were derived from 2D film measurements. RESULTS: OFs obtained from both dosimeter types agreed within 0.7% after applying corrections for the volume averaging effect. For the used alanine pellets, volume averaging correction factors of 1.030(2) for the 1 × 1 cm2 field and <1.002 for the larger field sizes were determined. The correction factor for positional uncertainties of 1 mm was in the order of 1.018 for the 1 × 1 cm2 field. Combined relative standard uncertainties uc for the OFs resulting from alanine measurements were estimated to be below 1.5% for all field sizes. For IC measurements, uc was estimated to be below 1.0%. CONCLUSIONS: A practical EPR dosimetry protocol is adaptable for precisely measuring OFs in small fields down to 1 × 1 cm2 . It is recommended to consider the effect of positional uncertainties for field sizes <2 × 2 cm2 .

Impact of dimethyl sulfoxide on irradiation-related DNA double-strand-break induction, -repair and cell survival.

Dimethyl sulfoxide (DMSO) is an effective radical scavenger and, when added to cells, reduces the initial number of radiation-induced DNA double-strand breaks (DSB). The aim of this study was to investigate modification by DMSO of both DSB induction and DSB repair by means of pulsed-field gel electrophoresis (PFGE) as well as gamma-H2AX immunofluorescence staining. WiDr cells (human colon carcinoma provided by DKFZ) were incubated with 2% DMSO for 2 h (or mock-treated) prior to irradiation with varying X-ray doses and subsequent incubation for repair. Sample processing for PFGE analysis or counting of γ-H2AX foci was performed according to standard protocols. Effects on apoptosis induction and cell survival were investigated additionally by standard protocols. DMSO reduced DSB yield after 20-80 Gy measured by PFGE. A qualitatively similar result was found after low-dose irradiation (1 Gy) using γ-H2AX immunofluorescence staining. During incubation for repair, both DNA fragment rejoining (PFGE) as well as γ-H2AX foci removal occurred at a reduced rate when cells had been pre-treated with DMSO. But this effect was clearly more pronounced for the PFGE-analyzed double-strand breakage, particularly at early repair times. WiDr cells treated with DMSO (2%) showed a significantly increased clonogenic survival after irradiation doses above 8 Gy. Apoptosis rates were not changed by DMSO. The radio-protective effect of DMSO, well known from other PFGE studies, could be confirmed for the formation of γ-H2AX foci. DSB generated in the presence of DMSO were less rapidly repaired. DMSO showed radio-protective effects on clonogenic survival but not on apoptosis.

Successful radiation treatment of chylous ascites following pancreaticoduodenectomy.

Chylous ascites is a rare complication following pancreaticoduodenectomy. We report on a case of chylous ascites following pancreaticoduodenectomy in a 76-year-old patient diagnosed with pancreatic cancer. There are various known conservative management strategies, including dietary measures or total parenteral nutrition. Unfortunately, conservative treatment-with total parenteral nutrition and fasting over a period of 4 weeks-was not successful in the present case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on clinical experiences with successfully treated lymphocutaneous fistulas, low-dose radiotherapy was initiated. External beam radiotherapy comprising a total dose of 8.0 Gy to the paraaortic lymph node region was administered in daily single fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in complete resolution after 2 weeks. There was no clinical evidence of chylous ascites on follow-up. As a result of this experience, we believe that external beam radiotherapy should be considered as an alternative therapy in refractory cases of chylous ascites.

Dosimetric effects of swelling or shrinking tissue during helical tomotherapy breast irradiation. A phantom study.

During radiation therapy of the female breast, the actual target volume compared to the planning target volume may change due to swelling or shrinking of the tissue. Under- or overdosage is to be expected, especially when performing IMRT or tomotherapy techniques. The objective of this study is to develop a model-based quantification of these dose effects, with a particular focus on the changes in the surface dose. A cylindrical phantom was used as an artificial surrogate of the human torso. By adding and removing Superflab layers of various thicknesses, both radial breast swelling and shrinking could be simulated. The effects on dose distribution were evaluated using film dosimetry. The results were compared to dose calculations. To estimate the true surface doses, we subtracted the influence of the film material on air measurements. During a swelling of 5, 10, and 15 mm, the planning target volume was consistently underdosed by 2%, 5%, and 7% of the prescribed dose, respectively. Swelling led to reduced dose values of up to 72%, 55%, and 50% at the outer edge of the actual target volume. The measured surface dose decreased successively from 31% to 23%. During shrinking, the dose in the planning target volume increased successively from 100% to 106%. The measured surface doses increased from 29% to 36%. The calculated dose values agreed with the measured values within error limits. During radiotherapy of the female breast, new planning appears to be essential for radial tissue swelling of 5 mm or more because of severe underdosing. Shrinking leads to moderate overdosing and an increased surface dose. In addition, caution is advised when removing bolus material with respect to the planned situation.

Towards liquid EPR dosimetry using nitroxides in aqueous solution.

Objective. Water-equivalent dosimeters are desirable for dosimetry in radiotherapy. The present work investigates basic characteristics of novel aqueous detector materials and presents a signal loss approach for electron paramagnetic resonance (EPR) dosimetry.Approach. The proposed principle is based on the radiation dose dependent annihilation of EPR active nitroxides (NO·) in aqueous solutions. Stable nitroxide radicals (3-Maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (MmP), 3-Carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (CmP)) in aqueous solutions containing dimethyl sulfoxide (DMSO) as an additive were filled in glass capillaries for irradiation and EPR readout. Radiation doses ranging from 1 to 64 Gy were applied with a clinical 6 MV flattening filter free photon beam. EPR readout was then performed with a X-band benchtop spectrometer. The dose response, temporal stability and reproducibility of the samples' EPR signal amplitudes as well as the influence of the nitroxide concentration between 10 and 160µM on the absolute signal loss were investigated using MmP. CmP was used to examine the dependence of the dose response on DMSO concentration between 0 and 10 vol%. An indirect effect model was fitted to the experimental data assuming irradiation induced radical reactions as the underlying mechanism.Main results. For an initial MmP concentration of 20µM, absolute EPR signal loss is linear up to a dose of 16 Gy with a yield G(-NO·) of approximately 0.4µmol J-1. Within five weeks upon sample irradiation to doses between 0 and 32 Gy relative EPR signal fluctuations were on average (126 readouts) below 1% (1σ). For c(MmP) ≥ 20µM, absolute signal loss is only weakly dependent on c(MmP), whereas it increases strongly with increasing c(DMSO) in the range 0-5 vol%. An indirect effect model is applicable to describe the reaction mechanism resulting in the observed dose response curve.Significance. Liquids consisting of nitroxides in aqueous solution and small amounts of DMSO (2 vol%) show promising basic characteristics for application as water-equivalent EPR dosimeter materials in radiotherapy. The EPR signal loss is based on an indirect effect mediated by diffusing radicals originating from the radiolysis of the water/DMSO mixture.

Long-term Outcome After Helical Tomotherapy Following Breast Conserving Surgery for Ductal Carcinoma In Situ.

Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.

Primary and adjuvant intensity-modulated radiotherapy in oropharyngeal carcinoma patients from a single institution.

BACKGROUND: To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT). METHODS: Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03. RESULTS: The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema. CONCLUSION: Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events.

Treatment of squamous cell carcinoma of the mobile tongue or tongue margins: an interdisciplinary challenge.

BACKGROUND: Standard treatment is surgery with stage dependent postoperative radio(chemo)therapy, however, for organ preservation preoperative radio(chemo)therapy is used as an individual approach. The present analysis was performed to access outcome and toxicity of radiotherapeutical treatment of squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Sixty-six patients (median age 55 years) with cancer of the mobile tongue (n=30) or tongue margins (n=36) treated between 1982 and 2006 were retrospectively analyzed. Treatment consisted of definitive- (n=13, median dose 66 Gy), adjuvant- (n=31, median dose 60 Gy) or neoadjuvant radiotherapy (n=22, median dose 40 Gy) and chemotherapy (n=34) or immunotherapy (n=1). RESULTS: After a median follow-up of 29 months the three- and five-year overall survival (OS) rates were 59% and 46%, respectively. The median OS was 54 months. Forty-two patients achieved complete remission whereas 14 patients showed partial remission. The one- and two-year loco-regional progression-free survival (LRPFS) rates were 76% and 58%, respectively. The median LRPFS time was 36 months. In χ(2)-test, T-stage showed a trend towards impact on local recurrence (Pearson, p=0.082). In multivariate analysis, alcohol consumption (p=0.003) and gender (p=0.031) were prognostic. Grade III/IV acute toxicity was seen in 52% of patients. None of the locally controlled patients reported grade IV or higher late toxicity. CONCLUSION: No statistically significant differences between treatment modalities were found, but one should keep in mind that organ preservation plays a major role for quality of life. None of the locally controlled patients reported grade IV or higher late toxicity. However, tumor recurrence is common, especially in advanced tumor stage. Interdisciplinary concepts, further increasing the chance of tumor control are warranted.

In Vitro Carbon Ion Beam and Gemcitabine Chemoradiation in a Mucoepidermoid Carcinoma Cell Line.

BACKGROUND/AIM: To determine the interaction of gemcitabine in chemoradiotherapy with heavy carbon ions in vitro in a mucoepidermoid carcinoma (MEC) cell line. MATERIALS AND METHODS: The human lymphatic MEC metastasis cell line NCI-H292 was used. The cells were treated with photons, carbon ions, and gemcitabine. Survival fractions (SF), apoptosis, and cell cycle progression were analyzed. A paired two-sided t-test was used. Significance was defined as p<0.05. RESULTS: Cell proliferation assays showed a significant reduction in SF for combined photon chemoradiation versus photons only. The linear-quadratic fits of combined therapy with carbon ion dose of 0 to 2.5 Gy led to reductions of mean 15% in SF. The LD50 (lethal radiation dose required to reduce cell survival by 50%) for carbon ions only was 0.7 Gy and for carbon ions with gemcitabine 0.6 Gy. The LD50 for photons (with gemcitabine) was 2.8 Gy (2.0 Gy) and for carbon ions (with gemcitabine) 0.7 Gy (0.6 Gy), resulting in a relative biological effectiveness at 10% cell survival (RBE10) of 3.0 (2.7). Carbon ions and photons reduced S phase and increased G2/M phase cell distribution. Isolated treatment with gemcitabine as well as combination with photons led to prolonged S phase transit, whereas combined treatment with carbon ions led to early accumulation in G2/M phase. A significant increase in the sub-G1 population as a hint of relevant number of apoptotic cells was not observed. CONCLUSION: Gemcitabine showed radiosensitizing effects in combination with photons. The combination of gemcitabine and carbon ions had independent additive effects. Carbon ions only had a RBE10 of 3.0, compared to photons only. The combination of gemcitabine, photon, and carbon ions in patients with MEC seems promising and warrants further investigation.

Helical Tomotherapy of Lymph Node-negative Early-stage Breast Cancer After Breast-conserving Surgery: Long-term Results.

BACKGROUND/AIM: Adjuvant radiotherapy is an integral part of the interdisciplinary curative treatment of breast cancer. We aimed to examine the long-term clinical results of helical tomotherapy in female patients with local restricted, lymph node negative breast cancer after breast-conserving surgery. PATIENTS AND METHODS: In this single-centre analysis, 219 female patients with early-stage breast cancer (T1/2) and no lymph node metastasis (N0) following breast-conserving surgery and sentinel-node biopsy were treated with adjuvant fractionated whole breast radiation therapy using helical tomotherapy. When boost irradiation was indicated, it was administered sequentially or using the simultaneous-integrated boost technique. Local control (LC), metastasis and survival rates, acute toxicity, late toxicity, and secondary malignancy rates were analysed retrospectively. RESULTS: The mean follow-up time was 71 months. The 5- and 8-year overall survival (OS) rates were 97.7% and 92.1%, respectively. The 5- and 8-year LC rates were 99.5% and 98.2%, while the 5- and 8-year metastasis-free survival (MFS) rates of 97.4% and 94.3%, respectively. Patients with G3 grading or negative hormone receptor status did not show significantly different results. Acute erythema occurred in 79% (grade 0-2) and 21% (grade 3) of the patients. Lymphedema of the ipsilateral arm and pneumonitis occurred in 6.4% and 1.8% of the treated patients. None of the patients developed >grade 3 toxicities during follow-up, while 1.8% developed a secondary malignancy during follow-up. CONCLUSION: Helical tomotherapy showed excellent long-term results and low toxicity rates. The incidence rates of secondary malignancy were relatively low and correlated with pre-existing data on radiotherapy, suggesting wider implementation of helical tomotherapy in adjuvant radiotherapy for breast cancer patients.

IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer.

PURPOSE: In this retrospective investigation, the outcome and toxicity after reirradiation with concurrent cetuximab immunotherapy of recurrent head and neck cancer (HNC) in patients who had contraindications to platinum-based chemotherapy were analyzed. MATERIALS AND METHODS: Ten patients with locally advanced recurrent HNC were retrospectively evaluated. In 9 cases, histology was squamous cell carcinoma, in one case adenoid cystic carcinoma. External beam radiotherapy was part of the initial treatment in all cases. Reirradiation was carried out using step-and-shoot intensity-modulated radiotherapy (IMRT) with a median dose of 50.4 Gy. Cetuximab was applied as loading dose (400 mg/m(2)) 1 week prior to reirradiation and then weekly concurrently with radiotherapy (250 mg/m(2)). RESULTS: The median overall survival time after initiation of reirradiation was 7 months; the 1-year overall survival (OS) rate was 40%. Local failure was found in 3 patients, resulting in a 1-year local control (LC) rate of 61%. The 1-year locoregional control (LRC) rate was 44%, while the 1-year distant metastasis-free survival (DMFS) was 75%. Acute hematological toxicity was not observed in the group. Severe acute toxicity included one fatal infield arterial bleeding and one flap necrosis. Severe late toxicities were noted in 2 patients: fibrosis of the temporomandibular joint in 1 patient and stenosis of the cervical esophagus in another. CONCLUSIONS: IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent HNC is feasible with acceptable acute toxicity. Further investigations are necessary to determine the clinical role of this therapy concept.

Prospective superficial EPR in-vivo dosimetry study during hypofractionated radiotherapy of breast cancer patients treated with helical tomotherapy.

BACKGROUND: In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). METHODS: In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient's skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. RESULTS: Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. CONCLUSION: Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

A practical EPR dosimetry system for routine use in radiotherapy: uncertainty analysis of lithium formate dosimeters at the therapeutic dose level.

In electron paramagnetic resonance (EPR) dosimetry, solid dosimeter materials such as alanine (AL) or, more recently, lithium formate monohydrate (LFM) are typically used. These materials offer high potential for applications in radiotherapy based on their favorable dosimetric properties. Nevertheless, EPR dosimetry is not widespread in the clinics. This work presents an uncertainty analysis of EPR dosimetry in the dose range from 1 to 70 Gy using a compact spectrometer and applying a practical procedure being suitable for routine use in radiotherapy. The performances of self-pressed LFM pellets and commercial AL pellets are compared side by side. All pellets had a diameter of 4 mm and a height of 2 mm (AL) or 4 mm (LFM). The mean pellet mass was 35.81 mg and 73.81 mg for AL and LFM, respectively. Before irradiation, the pellets were stored for at least 8 weeks at 34 ± 2% relative humidity. For irradiation, the pellets were put inside an airtight capsule. In total, 25 pellets per material were examined. The pellets were irradiated at a temperature of 25 ± 2.5 (2σ) °C to doses of either 1, 5, 20, 50 or 70 Gy (five pellets per dose value and material) by a clinical 6 MV photon beam. Measurement uncertainties were obtained from five independent readouts per pellet within five weeks following irradiation using a benchtop EPR spectrometer. The measurement time of a single readout was restricted to 10 min per pellet. Dose values were derived from EPR signal amplitudes using a specifically developed spectral fitting procedure. Signal fading characteristics were analyzed and taken into account during evaluation. The relative dose uncertainties (1σ) for a single readout at doses ≥ 5 Gy are below 2.8% (AL) and 1.1% (LFM) but increase to 12.3% (AL) and 2.6% (LFM) at 1 Gy. By averaging five independent readouts, the uncertainties at 1 Gy decrease to 2.6% (AL) and 0.8% (LFM). In terms of dose uncertainty, the LFM pellets are superior to the commercial AL pellets owing to their narrower EPR spectrum and approximately doubled mass resulting in higher EPR signal intensities. In case of the LFM pellets, the EPR dosimetry system shows a high level of precision (< 3%) down to 1 Gy being preferable for applications in radiotherapy. The uncertainties can be further decreased by averaging multiple dose values from independent readouts.

Suitability of superficial electron paramagnetic resonance dosimetry for in vivo measurement and verification of cumulative total doses during IMRT: A proof of principle.

PURPOSE: The present study investigates superficial in vivo dosimetry (IVD) by means of a previously proposed electron paramagnetic resonance (EPR) dosimetry system aiming at measuring and verifying total doses delivered by complex radiotherapy treatments. In view of novel regulatory requirements in Germany, differences between measured and planned total doses to the EPR dosimeters are analyzed and compared to reporting thresholds for significant occurrences. METHODS: EPR dosimeters, each consisting of one lithium formate monohydrate (LFM) and one polycrystalline l-alanine (ALA) pellet, were attached to the surface of an anthropomorphic head phantom. Three head and neck treatments with total target doses ranging from 30 to 64Gy were fully delivered to the phantom by helical tomotherapy. During each treatment, eight EPR dosimeters were placed at distinct spots: (i) within or next to the planning target volume (PTV), (ii) near to organs at risk including the parotids and the lenses, (iii) at the thyroid lying out-of-field. EPR read out was always performed after all fractions were delivered. EPR results were compared to thermoluminescence dosimeter (TLD) measurements and to the planned total doses derived from the treatment planning system (TPS). Planned total doses to the EPR dosimeters ranged from about 2 to 64Gy. RESULTS: By taking uncertainties into account, the measured and planned doses were in good agreement. Exceptions occurred mainly at the thyroid (out-of-field) and lenses (extreme sparing). The maximum total dose difference between EPR results and corresponding planned doses was 1.3Gy occurring at the lenses. Remarkably, each LFM and ALA pellet placed within or next to the PTV provided dose values that were within ±4% of the planned dose. Dose deviations from planned dose values were comparable for EPR and TLD measurements. CONCLUSION: The results of this proof of principle study suggests that superficial EPR-IVD is applicable in a wide dose range and in various irradiation conditions - being a valuable tool for monitoring cumulative total doses delivered by complex IMRT treatments. EPR-IVD in combination with helical tomotherapy is suitable to reliably detect local dose deviations at superficial dosimeter spots in the order of current national reporting thresholds for significant occurrences (i.e. 10%/4Gy).

Hypofractionated Radiotherapy With Simultaneous-integrated Boost After Breast-conserving Surgery Compared to Standard Boost-applications Using Helical Tomotherapy With TomoEdge.

BACKGROUND/AIM: This comparative plan study examines a range of boost-radiation methods in adjuvant radiotherapy of breast cancer using helical intensity-modulated radiotherapy with TomoEdge-technique. Impact of hypofractionated radiation with simultaneous-integrated boost (SIB) and influence of differing assumed α/ß-values were examined. PATIENTS AND METHODS: For 10 patients with left-sided breast cancer each four helical IMRT-plans with TomoEdge-technique were created: hypofractionated+SIB (H-SIB) (42.4/54.4 Gy, 16 fractions), normofractionated+SIB (N-SIB) (50.4/64.4 Gy, 28 fractions), hypofractionated+sequential-boost (H-SB) (42.4 Gy/16 fractions+16 Gy/8 fractions), normofractionated+ sequential-boost (N-SB) (50.4 Gy/28 fractions+16 Gy/8 fractions). Equivalent doses (EQD2) to organs-at-risk (OAR) and irradiated mammary-gland were analysed for different assumed α/ß-values. RESULTS: The mean EQD2 to OAR was significantly lower using hypofractionated radiation-techniques. H-SIB and H-SB were not significantly different. H-SIB and N-SIB conformed significantly better to the breast planning-target volume (PTV) and boost-volume (BV) than H-SB and N-SB. Regarding BV, mean EQD2 was significantly higher for all α/ß-values investigated when using H-SIB and N-SIB. Regarding PTV, there were no clinically relevant differences. CONCLUSION: Relating to dosimetry, H-SIB is effective compared to standard-boost-techniques.

In Vivo Evaluation of Combined CK2 Inhibition and Irradiation in Human WiDr Tumours.

BACKGROUND/AIM: Casein kinase 2 (CK2) which sustains multiple pro-survival functions in cellular DNA-damage response, is strictly regulated in normal cells but elevated in cancer. CK2 is considered as a potential therapeutic target, and its inhibition has been associated with radiosensitization in mammalian cells in vitro. Here, we investigated potential radiosensitization by CK2 inhibition in vivo. MATERIALS AND METHODS: The effect of CK2 inhibition in vivo was investigated in human WiDr-xenograft tumours grown subcutaneously on BALB/c nu/nu mice with and without fractionated irradiation. CK2 inhibition was performed using the specific inhibitor tetra-bromobenzotriazole (TBB). Histological examinations included staining for apoptosis and double-strand breaks. RESULTS: Both TBB treatment alone and radiation alone significantly reduced tumour growth, which was reflected by increased apoptosis rates. However, TBB treatment did not boost radiation-induced tumour growth suppression in combined treatment, although the apoptosis rate increased and repair of double-strand breaks was reduced. This was in stark contrast to previous data on in vitro radiosensitization. CONCLUSION: The absence of radiosensitization by CK2 inhibition should be investigated in different tumour models.

New multileaf collimator with a leaf width of 5 mm improves plan quality compared to 10 mm in step-and-shoot IMRT of HNC using integrated boost procedure.

PURPOSE: To investigate whether a new multileaf collimator with a leaf width of 5 mm (MLC-5) over the entire field size of 40 x 40 cm(2) improves plan quality compared to a leaf width of 10 mm (MLC-10) in intensity-modulated radiotherapy (IMRT) with integrated boost for head and neck cancer. PATIENTS AND METHODS: A plan comparison was performed for ten patients with head and neck cancer. For each patient, seven plans were calculated: one plan with MLC-10 and nine beams, four plans with MLC-5 and nine beams (with different intensity levels and two-dimensional median filter sizes [2D-MFS]), and one seven-beam plan with MLC-5 and MLC-10, respectively. Isocenter, beam angles and planning constraints were not changed. Mean values of common plan parameters over all ten patients were estimated, and plan groups of MLC-5 and MLC-10 with nine and seven beams were compared. RESULTS: The use of MLC-5 led to a significantly higher conformity index and an improvement of the 90% coverage of PTV1 (planning target volume) and PTV2 compared with MLC-10. This was noted in the nine- and seven-beam plans. Within the nine-beam group with MLC-5, a reduction of the segment number by up to 25% at reduced intensity levels and for increased 2D-MFS did not markedly worsen plan quality. Interestingly, a seven-beam IMRT with MLC-5 was inferior to a nine-beam IMRT with MLC-5, but superior to a nine-beam IMRT with MLC-10. CONCLUSION: The use of an MLC-5 has significant advantages over an MLC-10 with respect to target coverage and protection of normal tissues in step-and-shoot IMRT of head and neck cancer.

Lack of Relevant Haemogram Changes During Percutaneous Radiotherapy of Localised Prostate Cancer.

BACKGROUND/AIM: In percutaneous radiotherapy dose-distribution and volumetric-load of normal tissue varies in different radiation-techniques. Haematotoxicity may lead to deficiencies of the immune and blood system or to secondary malignancies. Therefore, regular blood-counts are carried out during fractionated radiotherapy. The aim was to investigate patient haemogram courses during radiotherapy of localised prostate-cancer treated with different radiation-techniques (n=3). PATIENTS AND METHODS: In this prospective study, blood count changes were examined during fractionated radiotherapy (3D-conformal-RT/step-and-shoot-IMRT/helical-IMRT) on the prostate-region in localised prostate-cancer cases (n=50). RESULTS: The whole patient group displayed a small but significant reduction in leukocytes. This reduction was higher in the two IMRT groups compared to the 3D-group but without any case of leukopenia. Haemoglobin- or thrombocyte-levels did not significantly change. CONCLUSION: Regardless of the delivery mode used, localised fractionated irradiation of prostate region did not cause any clinically relevant haemogram changes in this study. These findings question the necessity of regular blood counts during fractionated radiotherapy of the prostate region for patients without any risk factors.

EPR imaging of magnetic field effects on radiation dose distributions around millimeter-size air cavities.

New hybrid radiotherapy treatment systems combining an MRI scanner with a source of ionizing radiation are being introduced in the clinic. The strong magnetic fields of MRI considerably affect radiation dose distributions, especially at tissue-air interfaces due to the electron return effect (ERE). Experimental investigation of the ERE within a sub-millimeter thick surface layer is still highly challenging. In the present work, we examine and quantify the magnetic field induced perturbations of dose distributions within a 0.5 mm layer surrounding millimeter-size air cavities by applying electron paramagnetic resonance imaging (EPRI). Air-filled fused quartz tubes (inner diameter 3 or 4 mm) mimic small air cavities and serve as model systems. The tubes were irradiated inside a PMMA phantom by a 6 MV photon beam. The irradiations were performed in the presence or absence of a transverse, magnetic field providing a magnetic field strength of 1.0 Tesla. The spatial distributions of radiation induced paramagnetic defects in the quartz tubes were subsequently determined by applying field-swept echo-detected EPRI and were then converted to relative dose distributions. The transverse magnetic field leads to considerable local dose enhancements and reductions (up to 35%) with respect to the mean dose within the quartz tubes. The experimentally determined dose distributions are in good quantitative agreement with Monte Carlo radiation transport simulations. The results of this work demonstrate the feasibility of field-swept echo-detected EPRI to measure magnetic field induced perturbations of dose distributions within a sub-millimeter thick surface layer at the dosimeter-air interface.

Breast cancer occurrence after low dose radiotherapy of non-malignant disorders of the shoulder.

Stochastic long-term damages at relatively low doses have the potential for cancer induction. For the first time we investigated the occurrence of breast cancer in female patients after radiotherapy of non-malignant disorders of the shoulder and made a comparison with the estimated spontaneous incidence of mammary carcinoma for this cohort. In a geographically defined district with a population of approximately 100.000 inhabitants, comprehensive data of radiological diagnostics and radiotherapy were registered nearly completely for 41 years; data included mammography and radiotherapy of breast cancer patients as well as of non-malignant disorders. Within this population a collective of 158 women with radiotherapy of the shoulder was investigated. Radiotherapy was performed with cobalt-60 photons (Gammatron) with an average cumulative-dose of 6 Gy. The average follow-up time was 21.3 years. Patients were 55 years old (median) when radiotherapy of the shoulder was performed. Seven patients (4.4%) developed breast cancer after a median of 21 years. According to the incidence statistics, 9.4 +/- 1.8 (95%CI) cases (5.9%) would be expected. In regard to the irradiated shoulder neither the ipsilateral nor the contralateral breasts showed increased rates of breast cancer. An induction of additional breast cancer caused by radiation of non-malignant disorders of the shoulder wasn't detected in the investigated cohort.