Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles.

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm-2) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 µg mL-1. A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

MRS Shimming: An Important Point Which Should not be Ignored.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) is a well-known device for analyzing the biological fluids metabolically. Obtaining accurate and reliable information via MRS needs a homogeneous magnetic field in order to provide well-defined peaks and uniform water suppression. There are lots of reasons which can disturb the magnetic field homogeneity which can be corrected by a process known as shimming. This study is intended to recall the importance of shimming and also the significant role of quality control (QC) in achieving an accurate quantification. MATERIAL AND METHOD: An acrylic cylindrical quality control phantom was designed as an analog of brain MRS test phantoms in order to control the accuracy of the obtained signal of a 1.5 T Siemens MRI system which belonged to one of Shiraz hospitals. The signal of NAA, Cho, Cr, the combination of these metabolites and also the distilled water, which was used in this study, was evaluated using separate phantoms. A QC test was performed using Siemens QC phantom and a standard test phantom. RESULTS: The spectrum of our home- made phantom had a significant difference with the expected spectrum. The results of checking the spectrum of metabolites separately also confirmed that there was a systemic problem that affects all the signals originated from all metabolites and even the pure distilled water. The MRS system could not pass QC tests, and peak broadening was common in all spectra. The complex spectrum of standard test phantom was not produced successfully by the MRS system. DISCUSSION: By a simple check of the water peak characteristics, lots of information can be obtained, one of which is the status of shimming that has a considerable effect on the accuracy of the spectrum. Thus, performing an automatic or manual shimming is not a criterion of the spectrum accuracy, and performing a periodic quality control using a test phantom by a specialist is necessary. CONCLUSION: Briefly, the quality control of MRS and all the other clinical device must be taken seriously. Sometimes QC can be the boundary of a right or a wrong decision for the patient.

Effect of age-dependent bone electron density on the calculated dose distribution from kilovoltage and megavoltage photon and electron radiotherapy in paediatric MRI-only treatment planning.

OBJECTIVE: MRI-only treatment planning (TP) can be advantageous in paediatric radiotherapy. However, electron density extraction is necessary for dose calculation. Normally, after bone segmentation, a bulk density is assigned. However, the variation of bone bulk density in patients makes the creation of pseudo CTs challenging. This study aims to assess the effects of bone density variations in children on radiation attenuation and dose calculation for MRI-only TP. METHODS: Bone contents of <15-year-old children were calculated, and substituted in the Oak Ridge National Laboratory paediatric phantoms. The percentage depth dose and beam profile of 150 kVp and 6 MV photon and 6 MeV electron beams were then calculated using Xcom, MCNPX (Monte Carlo N-particle version X) and ORLN phantoms. RESULTS: Using 150 kVp X-rays, the difference in attenuation coefficient was almost 5% between an 11-year-old child and a newborn, and ~8% between an adult and a newborn. With megavoltage radiation, the differences were smaller but still important. For an 18 MV photon beam, the difference of radiation attenuation between an 11-year-old child and a newborn was 4% and ~7.4% between an adult and a newborn. For 6 MeV electrons, dose differences were observed up to the 2 cm depth. The percentage depth dose difference between 1 and 10-year-olds was 18.5%, and between 10 and 15-year-olds was 24%. CONCLUSION: The results suggest that for MRI-only TP of photon- or electron-beam radiotherapy, the bone densities of each age group should be defined separately for accurate dose calculation. Advances in knowledge: This study highlights the need for more age-specific determination of bone electron density for accurate dose calculations in paediatric MRI-only radiotherapy TP.

Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells.

BACKGROUND: Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to explore the potential synergistic effects of N-Myc Downstream-Regulated Gene 2 (NDRG2) overexpression, a newly identified candidate tumor suppressor gene, with radiotherapy against proliferation of prostate LNCaP cell line. MATERIALS AND METHODS: In this study, LNCaP cells were exposed to X-ray radiation in the presence or absence of NDRG2 overexpression using plasmid PSES- pAdenoVator-PSA-NDRG2-IRES-GFP. The effects of NDRG2 overexpression, X-ray radiation or combination of both on the cell proliferation and apoptosis of LNCaP cells were then analyzed using MTT assay and flow cytometery, respectively. RESULTS: Results of MTT assay showed that NDRG2 overexpression and X-ray radiation had a synergistic effect against proliferation of LNCaP cells. Moreover, NDRG2 overexpression increased apoptotic effect of X-ray radiation in LNCaP cells synergistically. CONCLUSION: Our findings suggested that NDRG2 overexpression in combination with radiotherapy may be an effective therapeutic option against prostate cancer.

Adaptive Response Induced by Pre-Exposure to 915 MHz Radiofrequency: A Possible Role for Antioxidant Enzyme Activity.

BACKGROUND: Over the past few years, the rapid use of high frequency electromagnetic fields like mobile phones has raised global concerns about the negative health effects of its use. Adaptive response is the ability of a cell or tissue to better resist stress damage by prior exposure to a lesser amount of stress. This study aimed to assess whether radiofrequency radiation can induce adaptive response by changing the antioxidant balance. MATERIALS AND METHODS: In order to assess RF-induced adaptive response in tissues, we evaluated the level of GSH and the activity of GR in liver. 50 rats were divided into 5 groups. Three groups were pre-exposed to 915 MHz RF radiation, 4 hours per day for one week at different powers, as low, medium and high. 24 hours after the last exposure to radiation, they were exposed to 4 Gy sublethal dose of gamma radiation and then sacrificed after 5 hours. Their livers were removed, washed and were kept at -80o C until used. RESULTS: Our finding showed that pre-exposure to 915 MHz radiofrequency radiation with specific power could induce adaptive response in liver by inducing changes in the activity and level of antioxidant enzymes. CONCLUSION: It can be concluded that pre-exposure to microwave radiation could increase the level of GSH and the activity of GR enzyme, although these increases were seen just in low power group, and the GR activity was indicated in medium power group. This increase protects tissue from oxidative damage induced by sublethal dose of gamma radiation.

Revision of orthovoltage chest wall treatment using Monte Carlo simulations.

PURPOSE: Given the high local control rates observed in breast cancer patients undergoing chest wall irradiation by kilovoltage x-rays, we aimed to revisit this treatment modality by accurate calculation of dose distributions using Monte Carlo simulation. METHODS AND MATERIAL: The machine components were simulated using the MCNPX code. This model was used to assess the dose distribution of chest wall kilovoltage treatment in different chest wall thicknesses and larger contour or fat patients in standard and mid sternum treatment plans. Assessments were performed at 50 and 100 cm focus surface distance (FSD) and different irradiation angles. In order to evaluate different plans, indices like homogeneity index, conformity index, the average dose of heart, lung, left anterior descending artery (LAD) and percentage target coverage (PTC) were used. Finally, the results were compared with the indices provided by electron therapy which is a more routine treatment of chest wall. RESULT: These indices in a medium chest wall thickness in standard treatment plan at 50 cm FSD and 15 degrees tube angle was as follows: homogeneity index 2.57, conformity index 7.31, average target dose 27.43 Gy, average dose of heart, lung and LAD, 1.03, 2.08 and 1.60 Gy respectively and PTC 11.19%. Assessments revealed that dose homogeneity in planning target volume (PTV) and conformity between the high dose region and PTV was poor. To improve the treatment indices, the reference point was transferred from the chest wall skin surface to the center of PTV. The indices changed as follows: conformity index 7.31, average target dose 60.19 Gy, the average dose of heart, lung and LAD, 3.57, 6.38 and 5.05 Gy respectively and PTC 55.24%. Coverage index of electron therapy was 89% while it was 22.74% in the old orthovoltage method and also the average dose of the target was about 50 Gy but in the given method it was almost 30 Gy. CONCLUSION: The results of the treatment study show that the optimized standard and mid sternum treatment for different chest wall thicknesses is with 50 cm FSD and zero (vertical) tube angle, while in large contour patients, it is with 100 cm FSD and zero tube angle. Finally, chest wall kilovoltage and electron therapies were compared, which revealed that electron therapy produces a better dose distribution than kilovoltage therapy.

Fast and accurate Monte Carlo modeling of a kilovoltage X-ray therapy unit using a photon-source approximation for treatment planning in complex media.

To accurately recompute dose distributions in chest-wall radiotherapy with 120 kVp kilovoltage X-rays, an MCNP4C Monte Carlo model is presented using a fast method that obviates the need to fully model the tube components. To validate the model, half-value layer (HVL), percentage depth doses (PDDs) and beam profiles were measured. Dose measurements were performed for a more complex situation using thermoluminescence dosimeters (TLDs) placed within a Rando phantom. The measured and computed first and second HVLs were 3.8, 10.3 mm Al and 3.8, 10.6 mm Al, respectively. The differences between measured and calculated PDDs and beam profiles in water were within 2 mm/2% for all data points. In the Rando phantom, differences for majority of data points were within 2%. The proposed model offered an approximately 9500-fold reduced run time compared to the conventional full simulation. The acceptable agreement, based on international criteria, between the simulations and the measurements validates the accuracy of the model for its use in treatment planning and radiobiological modeling studies of superficial therapies including chest-wall irradiation using kilovoltage beam.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

INTRODUCTION: Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. MATERIALS AND METHODS: Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. RESULTS: Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). CONCLUSION: Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

Monte Carlo N Particle code - Dose distribution of clinical electron beams in inhomogeneous phantoms.

Electron dose distributions calculated using the currently available analytical methods can be associated with large uncertainties. The Monte Carlo method is the most accurate method for dose calculation in electron beams. Most of the clinical electron beam simulation studies have been performed using non- MCNP [Monte Carlo N Particle] codes. Given the differences between Monte Carlo codes, this work aims to evaluate the accuracy of MCNP4C-simulated electron dose distributions in a homogenous phantom and around inhomogeneities. Different types of phantoms ranging in complexity were used; namely, a homogeneous water phantom and phantoms made of polymethyl methacrylate slabs containing different-sized, low- and high-density inserts of heterogeneous materials. Electron beams with 8 and 15 MeV nominal energy generated by an Elekta Synergy linear accelerator were investigated. Measurements were performed for a 10 cm × 10 cm applicator at a source-to-surface distance of 100 cm. Individual parts of the beam-defining system were introduced into the simulation one at a time in order to show their effect on depth doses. In contrast to the first scattering foil, the secondary scattering foil, X and Y jaws and applicator provide up to 5% of the dose. A 2%/2 mm agreement between MCNP and measurements was found in the homogenous phantom, and in the presence of heterogeneities in the range of 1-3%, being generally within 2% of the measurements for both energies in a "complex" phantom. A full-component simulation is necessary in order to obtain a realistic model of the beam. The MCNP4C results agree well with the measured electron dose distributions.

Ulexite-galena intermediate-weight concrete as a novel design for overcoming space and weight limitations in the construction of efficient shields against neutrons and photons.

Recently, due to space and weight limitations, scientists have tried to design and produce concrete shields with increased attenuation of radiation but not increased mass density. Over the past years, the authors' had focused on the production of heavy concrete for radiation shielding, but this is the first experience of producing intermediate-weight concrete. In this study, ulexite (hydrated sodium calcium borate hydroxide) and galena (lead ore) have been used for the production of a special intermediate-weight concrete. Shielding properties of this intermediate-weight concrete against photons have been investigated by exposing the samples to narrow and broad beams of gamma rays emitted from a 6°Co radiotherapy unit. Densities of the intermediate-weight concrete samples ranged 3.64-3.90 g cm⁻³, based on the proportion of the ulexite in the mix design. The narrow-beam half-value layer (HVL) of the ulexite-galena concrete samples for 1.25 MeV 6°Co gamma rays was 2.84 cm, much less than that of ordinary concrete (6.0 cm). The Monte Carlo (MC) code MCNP4C was also used to model the attenuation of 6°Co gamma-ray photons and Am-Be neutrons of the ulexite-galena concrete with different thicknesses. The 6°Co HVL calculated by MCNP simulation was 2.87 cm, indicating a good agreement between experimental measurements and MC simulation. Furthermore, MC-calculated results showed that thick ulexite-galena concrete shields (60-cm thickness) had a 7.22 times (722 %) greater neutron attenuation compared with ordinary concrete. The intermediate-weight ulexite-galena concrete manufactured in this study may have many important applications in the construction of radiation shields with weight limitations such as the swing or sliding doors that are currently used for radiotherapy treatment rooms.

EchoSeed Model 6733 Iodine-125 brachytherapy source: improved dosimetric characterization using the MCNP5 Monte Carlo code.

This study primarily aimed to obtain the dosimetric characteristics of the Model 6733 (125)I seed (EchoSeed) with improved precision and accuracy using a more up-to-date Monte-Carlo code and data (MCNP5) compared to previously published results, including an uncertainty analysis. Its secondary aim was to compare the results obtained using the MCNP5, MCNP4c2, and PTRAN codes for simulation of this low-energy photon-emitting source. The EchoSeed geometry and chemical compositions together with a published (125)I spectrum were used to perform dosimetric characterization of this source as per the updated AAPM TG-43 protocol. These simulations were performed in liquid water material in order to obtain the clinically applicable dosimetric parameters for this source model. Dose rate constants in liquid water, derived from MCNP4c2 and MCNP5 simulations, were found to be 0.993 cGyh(-1) U(-1) (±1.73%) and 0.965 cGyh(-1) U(-1) (±1.68%), respectively. Overall, the MCNP5 derived radial dose and 2D anisotropy functions results were generally closer to the measured data (within ±4%) than MCNP4c and the published data for PTRAN code (Version 7.43), while the opposite was seen for dose rate constant. The generally improved MCNP5 Monte Carlo simulation may be attributed to a more recent and accurate cross-section library. However, some of the data points in the results obtained from the above-mentioned Monte Carlo codes showed no statistically significant differences. Derived dosimetric characteristics in liquid water are provided for clinical applications of this source model.

Independent evaluation of an in-house brachytherapy treatment planning system using simulation, measurement and calculation methods.

Accuracy of treatment planning systems may significantly influence the efficacy of brachytherapy. The purpose of this work is a detailed, varied and independent evaluation of an in-house brachytherapy treatment planning software called STPS. Operational accuracy of STPS was investigated. Geometric tests were performed to validate entry and reconstruction of positional information from scanned orthogonal films. MCNP4C Monte Carlo code and TLDs were used for simulation and experimental measurement, respectively. STPS data were also compared with those from a commercial planning system (Nucletron PLATO). Discrepancy values between MCNP and STPS data and also those of PLATO and STPS at Manchester system dose prescription points (AL and AR) of tandem and ovoid configurations were 2.5% ± 0.5% and 5.4% ± 0.4%, respectively. Similar results were achieved for other investigated configurations. Observed discrepancies between MCNP and STPS at the dose prescription point and at 1 cm from the tip of the vaginal applicator were 4.5% and 25.6% respectively, while the discrepancy between the STPS and PLATO data at those points was 2.3%. The software showed submillimeter accuracy in its geometrical reconstructions. In terms of calculation accuracy, similar to PLATO, as attenuation of the sources and applicator body is not considered, dose was overestimated at the tip of the applicator, but based on the available criteria, dose accuracy at most points were acceptable. Our results confirm STPS's geometrical and operational reliability, and show that its dose computation accuracy is comparable to an established commercial TPS using the same algorithm.

A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas.

BACKGROUND: The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. METHODS: Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles of induction chemotherapy with docetaxel (75 mg/m(2)), cisplatin (40 mg/m(2)) (days 1-2), and 5-FU (500 mg/m(2), days 1-3), repeated every 21 days. Following induction chemotherapy, all patients underwent concurrent chemoradiotherapy using weekly cisplatin (30 mg/m(2)) and a median total dose of 70 Gy was delivered. Clinical response rate and toxicity were the primary and secondary end-points of the study. RESULTS: There were 31 men and 15 women. All patients had non-metastatic stage IV (T2-3N2-3 or T4N0-3) of disease. Overall and complete response rates were 74% and 24% respectively. Advanced T4 classification was associated with poorer response rate (p value=0.042). The major (grade 3-4) treatment-related toxicities were myelosuppression (78%), anorexia (13%), diarrhea (7%), emesis (11%) and stomatitis/pharyngitis (24%). CONCLUSION: In comparison with the data of historical published trials of the PF regimen, the TPF regimen was more effective. However, the TPF regimen appears to be associated with a higher incidence of major toxicities. Therefore, our limited findings support the TPF regimen as an alternative chemotherapeutic regimen for advanced head and neck carcinomas.

High-performance heavy concrete as a multi-purpose shield.

Concrete has long been used as a shield against high-energy photons and neutrons. In this study, colemanite and galena minerals (CoGa) were used for the production of an economical high-performance heavy concrete. To measure the gamma radiation attenuation of the CoGa concrete samples, they were exposed to a narrow beam of gamma rays emitted from a (60)Co radiotherapy unit. An Am-Be neutron source was used for assessing the shielding properties of the samples against neutrons. The compression strengths of both types of concrete mixes (CoGa and reference concrete) were investigated. The range of the densities of the heavy concrete samples was 4100-4650 kg m(-3), whereas it was 2300-2600 kg m(-3) in the ordinary concrete reference samples. The half-value layer of the CoGa concrete samples for (60)Co gamma rays was 2.49 cm; much less than that of ordinary concrete (6.0 cm). Moreover, CoGa concrete samples had a 10 % greater neutron absorption compared with reference concrete.

Squamous cell carcinoma of the oral tongue: a 25-year, single institution experience.

AIM: To report the characteristics, prognostic factors and treatment outcomes of 102 patients with squamous cell carcinoma of the oral tongue treated and followed up at a single institution over a 25-year period. PATIENTS AND METHODS: This retrospective study was carried out by auditing the medical records of 102 patients diagnosed with squamous cell carcinoma of the oral tongue and treated at our institution between 1982 and 2007. Patient follow up ranged from nine to 310 months (median 35 months). Fifty per cent of the patients were treated with surgery followed by a combination of chemotherapy and radiotherapy (43.1 per cent received concurrent chemoradiation and 6.9 per cent received sequential chemotherapy and radiotherapy), whereas 29.4 per cent received surgery followed by adjuvant radiotherapy alone. The remaining patients (20.6 per cent) did not undergo surgery and were treated with definitive radiotherapy with or without chemotherapy. RESULTS: There were 48 men and 54 women. The age at presentation was 19-85 years (median 57 years). The peak incidence was observed between 60 and 70 years. Resection margins were clear in 75 per cent of patients and involved in 25 per cent. Stage I disease was found in 11.8 per cent of patients, stage II in 34.3 per cent, stage III in 22.5 per cent and stage IV in 31.4 per cent. The five-year disease-free survival and overall survival were 65.7 and 72.5 per cent, respectively. Thirty-five patients suffered recurrence after treatment, 74.0 per cent of them at the site of initial cervical nodal involvement. Univariate analysis for overall survival revealed the following as prognostic factors: treatment schedule (surgical vs non-surgical; p < 0.001); age (<60 years vs >or=60 years; p = 0.038); extent of cervical lymph node involvement (p = 0.015); primary tumour stage (p < 0.001); node stage (p = 0.034); and disease stage (p = 0.013). However, on multivariate analysis, only non-surgical treatment (p = 0.001) and advanced disease stage (p = 0.05) were found to have a negative influence on survival. CONCLUSIONS: Our limited data suggest that, in Iran, squamous cell carcinoma of the oral tongue tends to present at a locally advanced stage, with a high frequency of locoregional failure and a poor outcome. Combined modality therapy should be considered for the majority of patients with squamous cell carcinoma of the tongue.

An evaluation of conformal and intensity-modulated radiotherapy in whole ventricular radiotherapy for localised primary intracranial germinomas.

AIMS: To evaluate different treatment techniques in whole ventricular radiotherapy (WVRT) for localised intracranial germinomas with respect to target volume and organ at risk (OAR) dose. As a second end point, a comparison of OAR doses between WVRT and whole brain radiotherapy was made. MATERIALS AND METHODS: Co-registered computed tomography-magnetic resonance images (MRI) of five patients were studied. Planning target volumes for whole ventricles (phase 1, PTV(1)) and boost to the primary tumour (phase 2, PTV(2)) were prescribed to 24 and 16 Gy. For phase 1, lateral parallel-opposed pairs (PP), non-coplanar three- and four-field (3F and 4F) and optimised four- and seven-field intensity-modulated radiotherapy (4FIMRT and 7FIMRT) plans were compared. A conformal non-coplanar six-field technique was used for phase 2. RESULTS: For phase 1, statistically significant high-dose sparing of normal brain was achieved with increasing treatment complexity for supratentorial brain (STB) minus PTV(1) (STB-PTV(1)) and infratentorial brain (ITB) minus PTV(1) (ITB-PTV(1)). Median pituitary gland dose sparing was 1 Gy with IMRT techniques (P=not significant). CONCLUSION: WVRT using 7FIMRT is the most conformal technique, which offers significant sparing of normal brain from high-dose irradiation, a mean reduction of 1 Gy in the pituitary gland (P<0.05) with no significant reduction in other OARs. Yet even with the most complex technique the absolute reduction in mean dose to normal brain tissue achieved was modest in clinical terms. Whether this could translate into a reduction in late sequelae in a predominantly adolescent patient population remains hypothetical.

Quantification and reduction of cardiac dose in radical radiotherapy for oesophageal cancer.

Chemoradiation is increasingly used in the management of localized oesophageal cancer and has been shown in randomized controlled trials to improve overall survival. Although early toxicity of radiotherapy is well documented, this is not the case for late toxicity. As patients with oesophageal cancer have a high incidence of co-morbidities including cardiac problems, the aim of this paper was to quantify the extent of cardiac radiation and discuss the influence of beam arrangement to reduce this. Eight patients with localized oesophageal cancer treated with radical chemoradiation were selected. The mean cardiac dose and the volumes of heart receiving 30 Gy, 40 Gy and 45 Gy from the conventional two-phase technique were compared with those of single-phase 3-field and 4-field conformal beam arrangements. The 4-field arrangement reduced the mean cardiac dose by at least 3.3 Gy compared with the other two beam arrangements (p=0.01). The mean volume of heart receiving high doses between the three techniques widened as the dose increased in the range 30-45 Gy. There is no statistically significant difference in volumes receiving more than 30 Gy and 40 Gy. 65% of the cardiac volume received more than 45 Gy using a two-phase technique, compared with 57% using three fields and 26% using four fields (p<0.01). With a 4-field beam arrangement, therefore, there is a significant reduction in cardiac dose compared with the other two techniques. Cardiac toxicity and a 4-field beam arrangement should be considered when planning radical radiotherapy for localized oesophageal cancer.

Radiotherapy of localised intracranial germinoma: time to sever historical ties?

The optimum management of localised intracranial germinoma remains controversial. Cure rates for this rare CNS tumour, which arises mainly in adolescents, exceed 90% at 10 years, and limitation of treatment-related late morbidity is therefore essential. Craniospinal radiotherapy plus boost is perceived to be the gold-standard treatment, but there have been suggestions that reduced-volume radiotherapy could be adequate for cure. We reviewed publications since 1988 to compare patterns of disease relapse and cure rates after craniospinal radiotherapy, reduced-volume irradiation alone (i.e., whole-brain or whole-ventricular irradiation followed by a boost), and focal or localised irradiation alone. The recurrence rate after whole-brain or whole-ventricular radiotherapy plus boost was 7.6% compared with 3.8% after craniospinal radiotherapy, with no predilection for isolated spinal relapses (2.9% vs 1.2%). We challenge the consensus that craniospinal radiotherapy is the best treatment for localised germinomas and conclude that reduced-volume radiotherapy plus boost should replace craniospinal radiotherapy when a radiotherapy-only approach is used.

Commissioning and quality assurance of the Pinnacle(3) radiotherapy treatment planning system for external beam photons.

The commissioning of a Pinnacle(3) treatment planning system is described. Four Elekta linear accelerators were commissioned for external beam photons. Measured data were used to derive parameter values for the Pinnacle(3) beam model by (1). fitting a Monte Carlo model of the accelerator head to measured data and then extracting the parameters for the Pinnacle(3) beam model, and by (2). using the auto-modelling facility within Pinnacle(3). Both of these methods yielded dose distributions in accord with published recommendations. A separate small-field beam model, customized for an in-house compact blocking system, was also created, which satisfied appropriate acceptance criteria for stereotactically guided conformal brain treatments. Inhomogeneous, oblique, asymmetrical and irregular fields were also assessed, with calculated and measured doses agreeing to within +/-3%. Dose-volume histogram calculation was found to be accurate to within +/-5% dose or volume for a grid size of 4 mm x 4 mm x 4 mm, with better accuracy being achieved for finer grids. Isocentric doses were compared between Pinnacle(3)'s collapsed cone convolution algorithm and the Bentley-Milan algorithm within the Target-2 treatment planning system. Dose differences were generally less than 3% in the dose prescribed, with larger values for breast plans, where the Pinnacle(3) algorithm calculated scatter more accurately. Pelvic and thoracic plans were also verified using an anthropomorphic phantom, with local dose differences between calculated and delivered dose of up to 8%, but mainly less than 3%, and with no systematic difference. Ionization chamber verifications using START and RT-01 trial procedures demonstrated differences between calculated and measured doses of less than 2%. Following satisfactory performance in the commissioning process, Pinnacle(3) has now been introduced into routine clinical use.