Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial.

OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012. All patients enrolled (41) received in 25 fractions a total dose of 67.5 Gy (2.7 Gy/fraction) to the prostatic volume, 56.25 Gy (2.25 Gy/fraction) to the seminal vescicles, and 50 Gy (2.0 Gy/fraction) to the pelvic lymph nodes (LN) chains with concurrent androgen deprivation therapy (ADT). The image-guided radiotherapy (IGRT) procedure was performed using three gold seeds. RTOG late gastrointestinal and genitourinary toxicities and 6-year biochemical relapse-free survival (BRFS) were assessed in combination of their statistical correlation with clinical factors and dosimetric parameters. RESULTS: Rate of late genitourinary toxicity grade 2 was 9.8%, while rates of late gastrointestinal toxicity were 14.6% and 2.4%, for grade 1 and 2, respectively. Diabetes and maximum doses to rectum appeared to be statistically relevant risk factors for late rectal toxicity. Five-year BRFS was 95.1%. CONCLUSIONS: In our study, we observed positive results in terms of toxicity and good efficacy in a cohort of high-risk prostate cancer patients treated with a multimodality therapy approach comprising hypofractionation, irradiation of pelvic nodes (common iliac nodes included), and concurrent ADT. These favorable results may merit further investigation in a phase III randomized trial to confirm that whole pelvic radiation therapy (WPRT) combined with moderate hypofractionation and ADT could be performed safely and effectively.

Use of parallel-plate ionization chambers in reference dosimetry of NOVAC and LIAC® mobile electron linear accelerators for intraoperative radiotherapy: a multi-center survey.

PURPOSE: LIAC® and NOVAC are two mobile linear accelerators dedicated to intraoperative radiation therapy (IORT), generating electron beams in the energy range of 3-12 MeV. Due to high dose-per-pulse (up to 70 mGy per pulse), in 2003 the Italian National Institute of Health (ISS) stated that "for the measure of dose to water in reference conditions, ionization chambers cannot be employed and no published dosimetry protocol can be used". As a consequence, ferrous sulphate (or, alternatively alanine) dosimetry was recommended. Based on a retrospective multi-center survey, a comparison with ferrous sulphate dosimetry is now used to validate the parallel-plate ionization chambers for reference dosimetry of NOVAC and LIAC. METHODS: The IAEA TRS-398 dosimetry protocol was applied except for the reference irradiation setup and the determination of the ion-recombination correction factor ks . Moreover the depth of maximum dose (R100 ) instead of zref as measurement depth was chosen by the majority of centers, thus implying a renormalization of the beam-quality correction factor kQ,Qo , based on water-air stopping power ratios. Regarding the ks determination, a previously published method, independent of ferrous sulphate dosimetry, was adopted. All the centers participating in this study had used both ferrous sulphate dosimeters and ionization chambers in water phantoms for dosimetry under reference conditions. RESULTS: The mean percentage difference between ionization chambers and ferrous sulphate dosimetry was -0.5% with a dispersion of 3.9% (2σ). Moreover, the uncertainty analysis allowed the agreement between ionization chambers and ferrous sulphate dosimetry to be verified. These results did not show any significant dependence on electron energy, thus indirectly confirming kQ,Qo renormalization. The results from the centers using zref as the measurement depth were similar to the other data, but further focused studies could aim at investigating possible dependences of the dose differences on the chosen reference depth. CONCLUSION: The present study confirms that parallel-plate ionization chambers can properly and accurately substitute ferrous sulphate detectors in reference dosimetry of LIAC and NOVAC mobile linear accelerators. Therefore, we hope that the most commonly used protocols for reference dosimetry in external-beam radiotherapy will be updated in order to provide guidance in the calibration of electron beams from linear accelerators dedicated to IORT, so that users may benefit from specific, authoritative and up-to-date recommendations.

Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience.

BACKGROUND: Hilar cholangiocarcinoma (Klatskin tumor-KT) accounts for about 0.5-1.5% of all gastrointestinal cancers and for 40-60% of all biliary malignancies. Tumor resection is attainable in about 30-50% of patients. When resection is not possible other treatment options have little or no impact on survival. We present the results of hypofractionated Stereotactic Body Radiotherapy (SBRT) on a small series of non resectable locally advanced KT patients. MATERIALS AND METHODS: Ten patients with histologically proven KT underwent SBRT plus gemcitabine. Radiotherapy (30Gy) was delivered in three fractions. Treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE v. 3.0). Alive patients with less than 1 year of follow up were excluded from the present study. Local control was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Two grade 1 and Two grade 2 acute toxicities were observed, moreover one grade 2 late toxicity was recorded. The overall local response ratio was 80% (4 PR+2 SD). SBRT showed a good efficacy in achieving local control. Median time to progression was 30 months. Two-year survival was 80% and four-year survival 30%. Six patients developed metastatic disease. Response to treatment and nodal metastases were the only independent indicators of prolonged survival. CONCLUSIONS: The chemoradiation given by SBRT plus gemcitabine is a promising treatment for non-metastatic unresectable KT. High local control rates, even compared to historical data from conventional radiotherapy, can be achieved with minimal toxicity.

Direct tumor in vivo dosimetry in highly-conformal radiotherapy: a feasibility study of implantable MOSFETs for hypofractionated extracranial treatments using the Cyberknife system.

PURPOSE: In highly-conformal radiotherapy, due to the complexity of both beam configurations and dose distributions, traditional in vivo dosimetry is unpractical or even impossible. The ideal dosimeter would be implanted inside the planning treatment volume so that it can directly measure the total delivered dose during each fraction with no additional uncertainty due to calculation models. The aim of this work is to verify if implantable metal oxide semiconductors field effect transistors (MOSFETs) can achieve a sufficient degree of dosimetric accuracy when used inside extracranial targets undergoing radiotherapy treatments using the Cyberknife system. METHODS: Based on the preliminary findings of this study, new prototypes for high dose fractionations were developed to reduce the time dependence for long treatment delivery times. These dosimeters were recently cleared and are marketed as DVS-HFT. Multiple measurements were performed using both Virtual Water and water phantoms to characterize implantable MOSFETs under the Cyberknife beams, and included the reference-dosimetry consistency, the dependence of the response on the collimator size, on the daily delivered dose, and the time irradiation modality. Finally a Cyberknife prostate treatment simulation using a body phantom was conducted, and both MOSFET and ionization readings were compared to Monte Carlo calculations. The feasibility analysis was conducted based on the ratios of the absorbed dose divided by the dose reading, named as "further calibration factor" (FCF). RESULTS: The average FCFs resulted to be 0.98 for the collimator dependence test, and about 1.00 for the reference-dosimetry test, the dose-dependence test, and the time-dependence test. The average FCF of the prostate treatment simulation test was 0.99. CONCLUSIONS: The obtained results are well within DVS specifications, that is, the factory calibration is still valid for such kind of treatments using the Cyberknife system, with no need of further calibration factors to be applied. The final accuracy of implantable MOSFETs when used for such kind of treatments was estimated to be within +/- 4%. Additional investigations using dose/fraction higher than 12 Gy, different beam configurations, and tracking systems could extend the present findings to other kind of treatments. MOSFET technology was proven to have high versatility in fast adaptation of existing detectors to new applications. It is plausible to expect a general feasibility of implantable MOSFET technology for in vivo dosimetry of the extracranial-targets treatments using the Cyberknife, provided each particular application will be validated by suitable both physical and clinical studies.

Application of a Monte Carlo-based method for total scatter factors of small beams to new solid state micro-detectors.

The scope of this work was to apply a method for estimation of total scatter factors of the smallest beams of the Cyberknife radiosurgery system to newly available solid-state detectors: the PTW 60008 diode, the SunNuclear EdgeDetector diode, and the Thomson and Nielsen TN502RDM micromosfet. The method is based on a consistency check between Monte Carlo simulation of the detectors and experimental results, and was described in a recent publication. Corrected total scatter factors were in excellent agreement with the findings of the former study. The results showed that the diodes tend to overestimate the total scatter factor of small beams, probably due to excessive scatter from the material surrounding the active layer. The correction factor for diodes and for the micromosfet, however, was found to be independent of the electron beam width. This is a desirable characteristic because it allows standard correction factors to be used for treatment units of the same type, without the need of case-by-case Monte Carlo simulation.

Cyberknife radiosurgery for benign meningiomas: short-term results in 199 patients.

OBJECTIVE: To present initial, short-term results obtained with an image-guided radiosurgery apparatus (CyberKnife; Accuray, Inc., Sunnyvale, CA) in a series of 199 benign intracranial meningiomas. METHODS: Selection criteria included lesions unsuitable for surgery and/or remnants after partial surgical removal. All patients were either symptomatic and/or harboring growing tumors. Ninety-nine tumors involved the cavernous sinus; 28 were in the posterior fossa, petrous bone, or clivus; and 29 were in contact with anterior optic pathways. Twenty-two tumors involved the convexity, and 21 involved the falx or tentorium. One hundred fourteen patients had undergone some kind of surgical removal before radiosurgery. Tumor volumes varied from 0.1 to 64 mL (mean, 7.5 mL) and radiation doses ranged from 12 to 25 Gy (mean, 18.5 Gy). Treatment isodoses varied from 70 to 90%. In 150 patients with lesions larger than 8 mL and/or with tumors situated close to critical structures, the dose was delivered in 2 to 5 daily fractions. RESULTS: The follow-up periods ranged from 1 to 59 months (mean, 30 months; median, 30 months). The tumor volume decreased in 36 patients, was unchanged in 148 patients, and increased in 7 patients. Three patients underwent repeated radiosurgery, and 4 underwent operations. One hundred fifty-four patients were clinically stable. In 30 patients, a significant improvement of clinical symptoms was obtained. In 7 patients, neurological deterioration was observed (new cranial deficits in 2, worsened diplopia in 2, visual field reduction in 2, and worsened headache in 2). CONCLUSION: The introduction of the CyberKnife extended the indication to 63 patients (>30%) who could not have been treated by single-session radiosurgical techniques. The procedure proved to be safe. Clinical improvement seems to be more frequently observed with the CyberKnife than in our previous linear accelerator experience.

Characterization of a new MOSFET detector configuration for in vivo skin dosimetry.

The dose released to the patient skin during a radiotherapy treatment is important when the skin is an organ at risk, or on the contrary, is included in the target volume. Since most treatment planning programs do not predict dose within several millimeters of the body surface, it is important to have a method to verify the skin dose for the patient who is undergoing radiotherapy. A special type of metal oxide semiconductors field-effect transistors (MOSFET) was developed to perform in vivo skin dosimetry for radiotherapy treatments. Water-equivalent depth (WED), both manufacturing and sensor reproducibility, dependence on both field size and angulation of the sensor were investigated using 6 MV photon beams. Patient skin dosimetries were performed during 6 MV total body irradiations (TBI). The resulting WEDs ranged from 0.04 and 0.15 mm (0.09 mm on average). The reproducibility of the sensor response, for doses of 50 cGy, was within +/-2% (maximum deviation) and improves with increasing sensitivity or dose level. As to the manufacturing reproducibility, it was found to be +/-0.055 mm. No WED dependence on the field size was verified, but possible variations of this quantity with the field size could be hidden by the assessment uncertainty. The angular dependence, for both phantom-surface and in-air setups, when referred to the mean response, is within +/-27% until 80 degree rotations. The results of the performed patient skin dosimetries showed that, normally, our TBI setup was suitable to give skin the prescribed dose, but, for some cases, interventions were necessary: as a consequence the TBI setup was corrected. The water-equivalent depth is, on average, less than the thinnest thermoluminescent dosimeters (TLD). In addition, when compared with TLDs, the skin MOSFETs have significant advantages, like immediate both readout and reuse, as well as the permanent storage of dose. These sensors are also waterproof. The in vivo dosimetries performed prove the importance of verifying the dose to the skin of the patient undergoing radiotherapy.