Microwave hyperthermia in conjunction with radiotherapy in superficial tumours: correlation of thermal parameters with tumour regression.

OBJECTIVE: The aim of the present study is to evaluate the correlation between the thermal parameters of hyperthermia and the clinical outcome in patients with superficial tumours. METHODS: In this study, 20 patients were included with either submandibular lymph nodes from head and neck cancer, or breast cancer relapses post-mastectomy. They were treated with radiation in combination with one session of 433 MHz microwave hyperthermia (1 hour, 42.5 °C-46 °C). The dose of irradiation ranged from 54 to 60 Gy. The thermal parameters calculated were the minimum volume temperature, the maximum volume temperature and the time interval where the volume temperature was greater than 44 °C. RESULTS: All patients responded positively to the combined treatment and 60% of the patients showed a complete response. Of the three parameters tested, the only parameter that was found to correlate with the reduction of the tumour diameter was the time with volume temperatures greater than 44 °C (p < 0.001, Spearman rho). No moderate toxicity was observed. CONCLUSION: Microwave heating should be over 44 °C for favourable treatment response, when combined with radiotherapy. More patients are needed to confirm the above results.

Evaluation of efficacy and toxicity in two different hypofractionated 3D-conformal external beam radiotherapy schedules in localised muscle invasive bladder cancer.

PURPOSE: To evaluate the efficacy as well as acute and late toxicity of two different accelerated hypofractionated 3D-conformal radiotherapy (Hypo-3DCRT) schedules in patients with bladder cancer. METHODS: Between February 2006 and June 2011, 50 elderly patients with cT1-2N0 bladder carcinoma were treated with Hypo-3DCRT. Mean age was 75 years. All patients were medically inoperable, with poor performance status, who couldn't tolerate either cystectomy or radical external beam irradiation on a daily basis. A dose of 36 Gy in 6 weekly fractions (arm A, N=39) or 39.96 Gy of 3.33 Gy twice daily, once a week, for 6 weeks (arm B, N=11) were prescribed. The primary study endpoints were the evaluation of acute/late gastrointestinal (GI) toxicity according to the EORTC/RTOG scale together with the visual analogue bladder-related pain score (VAS). RESULTS: The GI acute toxicities were: grade 1: arm A 24/39 (61.5%), arm B 9/11 (81.8%); grade 2: arm A 14/39 (35.9%), arm B 1/11 (9.1%); grade 3: arm A 1/39 (9.1%) (x(2), p=0.29). Only grade 1 late GI toxicity was seen and was significantly higher in arm A: arm A 17/39 (43.6%) and arm B 1/11 (9.1%) (x(2), p=0.037). The reduction of VAS score was similar in both arms (p=0.065). The median relapse free survival (RFS) was 15 and 16 months for arm A and B, respectively (log rank, p=0.71). CONCLUSIONS: Beyond the non-randomized design of the trial, the Hypo-3DCRT schedules used appear to be an acceptable alternative to the traditional longer radiotherapy (RT) schedules for elderly patients unfit for daily irradiation.

Metastatic bone involvement in vulvar cancer: report of a rare case and review of the literature.

PURPOSE: Bone metastasis secondary to vulvar carcinoma is an infrequent clinical entity. Only ten cases have been published in the literature. We describe a case of squamous vulvar carcinoma, that presented with cervical vertebral involvement, as a part of distant spread. CASE: A 69-year-old woman presented with radicular pain and a painful cervical mass. MRI of the cervical spine was performed, showing an osteolytic lesion with spinal cord compression. CONCLUSION: This case was unique in presenting vertebral metastasis eight months after chemotherapy and radiotherapy.

Conventional versus virtual simulation for radiation treatment planning of prostate cancer: final results.

PURPOSE: Radiotherapy is widely used to treat patients with prostate cancer. Using conventional x-ray simulation is often difficult to accurately localize the extent of the tumor, to cover exactly the lymph nodes at risk and shield the organs at risk. We report on the results of a study comparing target localization with conventional and virtual simulation. METHODS: One hundred prostate cancer patients underwent both conventional and virtual simulation. The conventional simulation films were compared with digitally reconstructed radiographs (DDRs) produced from the computed tomography (CT) data. All patients underwent target localization for radical prostate radiotherapy. The treatment fields were initially marked with a conventional portal film on linear accelerator (LINAC), plain x-ray film and available diagnostic imaging. Each patient then had a CT and these simulated treatment fields were reproduced within the virtual simulation planning system. The treatment fields defined by the clinicians using each modality were compared in terms of field area and implications for target coverage. RESULTS: Virtual simulation showed significantly greater clinical tumor volume coverage and less normal tissue volume irradiated compared with conventional simulation (p <0.001). CONCLUSION: CT localization and virtual simulation allow more accurate definition of the clinical target volume. This could enable a reduction in geographical misses, reducing at the same time treatment-related toxicity.

Comparison of conventional and virtual simulation for radiation treatment planning of prostate cancer.

PURPOSE: radiotherapy is widely used to treat patients with prostate cancer. Using conventional x-ray simulation is often difficult to accurately localize the extent of the tumor, to cover exactly the lymph nodes at risk and shield the organs at risk. We report the initial results of a study conducted to compare target localization with conventional and virtual simulation. METHODS: fifty patients with prostate cancer underwent target localization for radical prostate radiotherapy using conventional and virtual simulation. The treatment fields were initially marked with a conventional portal film on LINAC, plain x-ray film and available diagnostic imaging. Each patient then had a computed tomography (CT) and these simulated treatment fields were reproduced within the virtual simulation planning system. The treatment fields defined by the clinicians using each modality were compared in terms of field area and implications for target coverage. RESULTS: there was significantly greater clinical tumor volume coverage using virtual simulation compared with conventional simulation and less normal tissue volume irradiated (p<0.001). CONCLUSION: CT localization and virtual simulation allow for more accurate definition of the clinical target volume. This could enable a reduction in geographical misses, while also reducing treatment-related toxicity.

Three dimensional printed electron beam modifier for total skin electron treatments.

Total Skin Electron Beam (TSEB) treatment, despite its proven effectiveness in skin malignancies, is a rather exhausting irradiation method, especially for feeble patients. In an effort to reduce treatment time by creating a clinically acceptable single TSEB field, various beam modifiers of different materials and shapes were tested. Using the TSEB immobilization device of our department and 3D printing technology, aluminum and thermoplastic modifiers were designed and constructed, according to the resulting profiles at treatment distance. Electron beam characteristics were measured and calculated both at SSD = 100 cm and at treatment level. Aluminum scatterers of the same thickness caused different modification according to the area of blocking. Aluminum modifiers reduced significantly central dose deposition for the same amount of MUs and therefore they expanded treatment time in undesirable levels. Plastic modifiers offer a good combination of field dimensions and treatment time. The final 3D printed modifier shaped the electron beam as desired resulting to a clinically acceptable 6 MeV field of 176 × 70 cm field with 10% inhomogeneity in vertical and 3% in the lateral dimension with adequate skin coverage at SSD = 400 cm. This modification offered approximately a two-minute treatment time reduction compared to the current technique. Underdosed areas appear near the edge of the field, but in regions that are far from the torso of the patient. Bremsstrahlung radiation was kept at clinically accepted levels (< 5%). This modification of the original six dual-field technique of our hospital could probably benefit fragile patients who could not easily tolerate a twenty-minute standing position without compromising the quality of their treatment.

Hypofractionated irradiation for gliomas with 45.5Gy in 13 fractions: a retrospective study.

AIM: The aim of the present retrospective study was to evaluate the efficacy and toxicity of a hypofractionated radiotherapy (HFRT) schedule for grade IV glioblastoma multiforme (GBM). METHODS: Fourteen elderly patients with KPS less than 70, received 13 fractions of 350cGy with 3D-conformal technique (3DCRT) and non-coplanar fields. Acute and late skin and CNS toxicity was graded according to EORTC/RTOG criteria. RESULTS: The median follow-up was 9 months. All patients completed the irradiation without interruptions due to toxicity and received temozolomide (TMZ) after the completion of 3DCRT. The KPS during RT and at follow-up was not significantly changed (P=0.108). The median overall survival was 7 months. No severe skin acute or late toxicity was noted. In terms of CNS toxicity, only one patient presented grade III toxicity requiring hospitalization for two days. The irradiation schedule of 45.5Gy in 13 fractions seems effective and without moderate or severe toxicity. CONCLUSION: The suggested HFRT schedule might be an alternative one, for elderly patients with dismal prognosis, unfit for six weeks of daily irradiation. Prospective studies are needed for further validation of our results, especially with the use of TMZ.

Use of a general inverse technique for the conformational stereotactic treatment of complex intracranial lesions.

PURPOSE: The stereotactic irradiation of intracranial lesions constitutes an excellent example of conformational therapy whose purpose is to adapt the dose envelope to the target volume with great precision and at the same time to deliver as low a dose as possible to the healthy tissues. We propose the mathematical analysis of the singular values decomposition (SVD) as an inverse planning process to find the optimal minibeam weightings that permit the calculation of the most conformational dose distribution. METHODS: For the radiosurgical treatment of complex lesions, we realize a division of the lesion into several elliptic volumes using the "Associated Target Methodology." This division allows the definition of an irradiation configuration: the number of isocenters, the position of the isocenters, and the diameter of each collimator. For this defined irradiation configuration, we use SVD to find the optimal minibeam weightings. This analysis enables us to understand better the ill-conditioning of the multi-isocentric irradiation and the influence of irradiation parameters on the process of reconstruction minibeam weightings. RESULTS: In this paper, the SVD analysis and the reconstruction technique have been evaluated for the first time on practical cases. We present, as an example, a complex lesion compartmentalized into 3 subvolumes according to our Associated Target Methodology. This analysis allows us to study the ill-conditioning of the example and proposes a large number of solutions from among which we have to choose the most conformational physical solution. This choice is based on the dose-volume histograms. CONCLUSION: We use the SVD procedure as a computer-aided planning system and obtain good solutions, i.e., healthy tissue protection and lesion coverage similar to or better than an experimented planner solution.

Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients.

PURPOSE: To present the SALT group results using Linac radiosurgery (RS) for AVM in 169 evaluable patients treated from January 1990 thru December 1993. METHODS AND MATERIALS: Median age was 33 years (range 6-68 years). Irradiation was the only treatment in 55% patients. Other treatment modalities had been used prior to RS in 45%: one or more embolizations in 36%, surgery in 6%, and embolization and surgery in 3% patients. Nidus were supratentorial in 94% patients, infratentorial in 6% patients. Circular 15 MV x-ray minibeams (6-20 mm) were delivered in coronal arcs by a GE-CGR Saturne 43 Linac. Patient set-up included a Betti arm-chair, a Talairach frame. Prescribed peripheral dose was 25 Gy on the 60%-70% isodose (max dose 100%). Arteriographic results were reassessed in December 1997 at 48 to 96 months follow-up. RESULTS: The overall obliteration rate (OR) was 64% (108/169). AVM volumes ranged from 280 to 19,920 mm(3), median 2460 mm(3). OR was 70% for AVM

A computerized dosimetric database for conformal stereotactic irradiations.

An innovative computerized dosimetric database (DDB) is proposed to enable the analysis of the stereotactic radiosurgical dose distributions; it contains relationships between the irradiation parameters and the dose-volume data. Dose-volume data provide guidance to the physicist-physician team by facilitating the initialization of the irradiation parameters and the treatment planning. The presented DDB contains dose-volume data such as the 70% isodose widths and the 70%-30% isodose penumbra along the right-left, anterior-posterior, and superior-inferior directions as a function of the irradiation parameters defined by the user. In order to demonstrate the usefulness of the DDB, the effects of the collimator diameter, the number of arcs, and their length on the shape of the prescription isodose surface are shown and are related to practical considerations for the treatment plan. However, the presented DDB is one example that can be generated by the DDB system. The planner can define as many different DDBs as he/she wishes, which can then be used for different investigations. This type of DDB enables us to investigate the irradiation technique used, to compare different irradiation techniques, to inspect the feasibility of planning different lesion types, or to define some dosimetric rules. The DDB provides useful interactive guidelines for the treatment planning process and replaces the voluminous dosimetric atlas. It has now been in clinical use for a year in a conformal procedure which automatically proposes collimator diameters, arc positions, and lengths allowing rapid conformal planning.

[Progress in optimizing dosimetry plans in stereotactic radiotherapy in the Salt Group (Saint-Anne-Lariboisière-Tenon]. / Les progrès dans l'optimisation des plans dosimétriques en radiothérapie en conditions stéréotaxiques dans le groupe Salt. Saint-Anne-Lariboisière-Tenon.

We began intracranial stereotactic irradiation under the direction of O Betti 11 years ago. At the present time, we believe it is interesting to present the methodologies of the SALT (Saint-Anne-Lariboisière-Tenon) group. Up to the present time we have irradiated 693 patients using a single fraction. Arteriovenous malformations (AVMs) represented the majority (90%) of treated lesions. Irradiation protocol has little changed since 1986, and the localization of the target volume was performed in the neurosurgery department of St Anne Hospital, France. The stereotactic images (computerized tomography [CT], angiography) were sent to the radiotherapy department of Tenon Hospital through the French public digital network NUMERIS. Protocol was realized using the stereotactic ARTEMIS-3D/Dosigray TPS. The lesion volume was filled by one or more spherical or elliptical subvolumes using the "Associated Target Methodology". The interactive adjustment of subvolumes was based on the 3D graphical representations of the lesion. The direct optimization of the irradiation space was performed by managing parameters provided by the DDB (Dosimetric Data Base) such as the number of arcs, their angular position, as well as the starting and the ending point of each arc. The evaluation of the calculated dose distribution was made using quantitative parameters. The second method of optimization was based on the minibeam intensity modulation using a mathematical theory of inverse problems and singular value decomposition (SVD) analysis. At the present time, due to technical reasons, linear accelerators do not permit the modulation of intensity of arctherapy. Thus we transformed the profiles of irregular forms into rectangular profiles of modulated ponderation, with each optimized plan being evaluated before its implementation. The criteria of evaluation were derived from the differential and cumulative dose volume histograms (DVH). The DVHs permitted the evaluation of the volumes of underdosage and overdosage inside the lesion and in the healthy tissue, respectively. Using DVHs, we have defined parameters such as the conform factor and the homogeneity index. We stress that the methodology of protocol optimization is valid for single or multiple fractions as well as for intra- and extra-cranial irradiation.

[Implementation of receiver operating characteristics for the quantitative evaluation of stereotactic radiotherapy treatment plans]. / Adaptation de l'analyse receiver operating characteristics pour l'évaluation quantitative des plans de traitement en radiothérapie stéréotaxique.

The definition of criteria and of a methodology dedicated to the quantitative evaluation of conformal stereotactic treatment plans is presented. We implemented the 'Receiver Operating Characteristics' (ROC) analysis, already used in medical imaging, for the quantitative evaluation of irradiation treatment plans. This implementation is based on data provided by dose-volume histograms (DVH). Three techniques, each one using a different dosimetric criterion, were defined for the choice of a reference isodose for a given treatment plan. We used this ROC analysis for the selection of the most conformal treatment plan and its reference isodose among the treatment plans proposed for one patient. This study revealed the interest of ROC analysis based on dose-volume histograms for the quantitative evaluation of treatment plans.

Combined chemoradiotherapy with local microwave hyperthermia for treatment of T3N0 laryngeal carcinoma: a retrospective study with long-term follow-up.

The purpose of our study was to test the efficacy and toxicity of hyperthermia in conjunction with chemoradiotherapy for T3N0 laryngeal cancer. From 1997-2006, 25 patients diagnosed with T3N0 laryngeal carcinoma who denied laryngectomy were selected for this retrospective study. Patients received a total dose of 70 Gy (2 Gy per fraction, 5 days per week) in combination with 6 weekly sessions of hyperthermia, in addition to weekly cisplatin chemotherapy. The hyperthermia device was operated as a 433 MHz microwave heating with water loaded and water-cooled waveguides. The temperature was monitored subcutaneously in the skin under the aperture of the waveguide. The median follow-up was 60 months, while 23 of 25 patients (92%) presented complete response to treatment. The two patients that did not respond to thermoradiotherapy underwent total laryngectomy, and during follow-up were alive and free of disease. According to EORTC/RTOG criteria, toxicity was mild: three patients (12%) presented grade III, eight (32%) presented grade II and 14 (56%) presented grade I acute skin toxicity. Grade III laryngeal late toxicity (vocal cord malfunction due to severe oedema) was noted in two patients (8%) at 6-8 months post-thermo-chemoradiotherapy. Tmin was correlated (Spearman rho, p < 0.05) with response to treatment as well as with acute skin toxicity and laryngeal function. When a patient with T3N0 laryngeal carcinoma denies laryngectomy, an alternative treatment is combined thermo-chemoradiotherapy which seems to be effective and generally tolerable with radiation-induced skin toxicity and/or late side effects. A larger patient cohort is needed to confirm these results.

Radiotherapy in conjunction with superficial and intracavitary hyperthermia for the treatment of solid tumors: survival and thermal parameters.

Hyperthermia is an effective modality for the treatment of cancer, which is mainly used in conjunction with radiotherapy as this combined treatment offers a better clinical outcome. There are many ways that hyperthermia can be applied and depends on the kind of tumor of the patients. The great advantage of this method is that it is tolerable for the majority of patients without severe toxicity. Many clinical trials have been realized in order to prove that hyperthermia in addition to radiotherapy offers an advantage in the survival and local control of patients in comparison to radiotherapy alone. Many studies have also investigated if exists any correlation between the thermal parameters of hyperthermia and the clinical outcome. This is a review of these studies and it concerns superficial hyperthermia for superficial tumors-melanoma, head and neck, breast cancer-and intracavitary hyperthermia for rectal cancer, esophageal cancer and prostate carcinoma.

Sucralfate gel as a radioprotector against radiation induced dermatitis in a hypo-fractionated schedule: a non-randomized study.

External beam radiotherapy with high doses provokes many acute skin reactions, such as erythema and moist desquamation. Many topical preparations are used in radiation oncology departments in the skin care. Sucralfate humid gel, a colloidal physical form of the anti-ulcer drug sucralfate, promotes epithelial regeneration and activates cell proliferation. Based on this knowledge, we performed a non-randomized clinical trial to evaluate the efficacy of topical sucralfate gel in 30 breast cancer patients receiving postoperative accelerated hypofractionated photon beam therapy. The comparison was performed with 30 patients as historical controls. The acute reaction of the skin was significantly lower in the group receiving the sucralfate gel (p<0.05, Mann Whitney test), while 90% of the patients had no evidence of radiation induced skin toxicity. There was no sucralfate gel related toxicity reported by any patient in this study. More patients in a randomized way are needed for more definite results.

First application of total skin electron beam irradiation in Greece: setup, measurements and dosimetry.

Total Skin Electron Beam (TSEB) irradiation is considered as the treatment of choice for cutaneous T-cell lymphoma internationally, for either curative purposes or palliative care. An attempt for the first application of this external radiation therapy technique in Greece took place at the Radiation Therapy Unit of 2(nd) Department of Radiology of University of Athens at University General Hospital "Attikon". TSEB modality was developed on a linear accelerator VARIAN Clinac 2100C. To create a uniform and sufficiently large field (≈200 cm × 80 cm) at SSD=380 cm, two symmetrical 6 MeV electron beams are combined with 17.5° tilts concerning the horizontal direction. An immobilization system was constructed to support patient during treatment and to modulate the composite electron field. Irradiation procedure demands a standing patient that takes, in total, six treatment positions. For the confirmation of treatment suitability and the determination of physical features of the clinical electron field, specific measurements were carried out using a parallel-plate ionization chamber and TLDs at water equivalent plastic and anthropomorphic phantoms. Measurements at the referred conditions showed a homogeneous total field with intensity variation of ±2% in the longitudinal axis and ±4% at horizontal axis. The mean energy of the composite field (E¯(o)) is 3.4 MeV, the most probable energy (E(p,0)) is 4.4 MeV and the half-value depth in water (R(50)) is 1.5 g/cm(2). The maximum X-ray background of the TSEB field is 2.1% at head and feet. The above results lead us to conclude that TSEB treatment using "Six-dual-field" technique can be applied in our department safely.

Clinical implementation of total skin electron beam (TSEB) therapy: a review of the relevant literature.

Total skin electron beam therapy has been in medical service since the middle of the last century in order to confront rare skin malignancies. Since then various techniques have been developed, all aiming at better clinical results in conjunction with less post-irradiation complications. In this article every available technique is presented in addition to physical parameters of technique establishment and common dose fractionation. This study also revealed the preference of the majority of institutes the last 20 years in "six dual field technique" at a high dose rate, which is a safe and effective treatment.

Hypofractionated radiotherapy in non small cell lung cancer: a review of the current literature.

Hypofractionated irradiation has an established role in the palliative treatment of patients with advanced medically inoperable non - small cell lung cancer (NSCLC ) and poor performance status. Also hypofractionated radiotherapy merits careful consideration in the curative treatment of patients with Stage I and II disease using contemporary technology. The biological effect of radiation on tumours is increased as the overall treatment time is shortened. Hypofractionated field radiotherapy offers acceptable palliation with minimal toxicity. The rates of palliation for hemoptysis , chest pain , cough and dyspnea reported from studies with very short regimen ( 8,5 Gy x 2 ), are comparable to those of other trials that used more protracted palliative treatment . The observed toxicity is minimal, and no cases of oesophagitis, pneumonitis, or radiation myelopathy developed. The minimal toxicity is a reflection of both the low biologic total dose and the tight RT design. Therefore the radiation side effects appear to be related to the technique of RT delivered rather than the patient's PS. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, has to be re-evaluated for hypofractionated radiation therapy. As well there is data suggesting that the small stages I - II NSCLC are likely to benefit from hypofractionated regimens too. Hypofractionated stereotactic radiotherapy is a new technically complex approach to the treatment of early-stage nonsmall cell lung cancer. It is capable to deliver much higher doses to the cancer than is possible with standard techniques, and as a result, rates of tumour control are high and similar to what can be achieved by surgical resection. Refinements of technique and dose as well as randomized data are required before stereotactic radiotherapy can be endorsed as a standard of care for patients with inoperable peripherally located T1 non small cell lung cancer. A clear advantage of the very short hypofractionated palliative regimen is that it allows patients with a short expected survival time to spend more of their remaining time away from the hospital.