Prognostic factors in patients treated with stereotactic image-guided robotic radiosurgery for brain metastases: a single-center retrospective analysis of 223 patients.

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4-51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p = 0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.

Evaluation of the dose perturbation around gold and steel fiducial markers in a medical linac through Geant4 Monte Carlo simulation.

OBJECTIVE: Purpose of this work was to study the dose perturbation within the target volume of a external MV radiation therapy when using metal fiducials. METHODS: We developed a Monte Carlo simulation in Geant4 of a cylindrical fiducial made either of gold or of steel and simulated the photon irradiation beam originating from a medical Linac operating at 6, 10 or 15 MV. For each energy, two different irradiation schemes were simulated: a single 5 × 5-cm square field in the -x direction, and five 5 × 5-cm fields at 0°, 80°, 165°, 195° and 280°. RESULTS: In a single beam irradiation scheme, we observed a dose reduction behind fiducials varying from -20% for gold at 6 MV to -5% for steel at 15 MV, and a dose increment in front of the fiducial ranging from +33% for gold at 15 MV to +10% for steel at 6 MV. When five beams were employed, a dose increment ranging from +28% to +46% has been found around gold. Around a steel fiducial, an average increment of +17% was found, irrespective of the photon energy. CONCLUSIONS: When using a single beam, the decrement of dose behind both steel and gold markers increases with the photon energy. This effect vanishes when a multifield treatment is delivered; in this instance there is a dose increment around fiducials, according to both fiducial material and photon energy, with lower values for steel and 6 MV. This energy represents the best choice when fiducial markers are present inside the irradiated volume.

Integration of functional neuroimaging in CyberKnife radiosurgery: feasibility and dosimetric results.

OBJECT: The integration of state-of-the-art neuroimaging into treatment planning may increase the therapeutic potential of stereotactic radiosurgery. Functional neuroimaging, including functional MRI, navigated brain stimulation, and diffusion tensor imaging-based tractography, may guide the orientation of radiation beams to decrease the dose to critical cortical and subcortical areas. The authors describe their method of integrating functional neuroimaging technology into radiosurgical treatment planning using the CyberKnife radiosurgery system. METHODS: The records of all patients who had undergone radiosurgery for brain lesions at the CyberKnife Center of the University of Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients with brain lesions in critical areas, treatment planning with the integration of functional neuroimaging was performed in 25 patients. Morphological and functional imaging data sets were coregistered using the Multiplan dedicated treatment planning system. Treatment planning was initially based on morphological data; radiation dose distribution was then corrected in relation to the functionally relevant cortical and subcortical areas. The change in radiation dose distribution was then calculated. RESULTS: The data sets could be easily and reliably integrated into the Cyberknife treatment planning. Using an inverse planning algorithm, the authors achieved an average 17% reduction in the radiation dose to functional areas. Further gain in terms of dose sparing compromised other important treatment parameters, including target coverage, conformality index, and number of monitor units. No neurological deficit due to radiation was recorded at the short-term follow-up. CONCLUSIONS: Radiosurgery treatments rely on the quality of neuroimaging. The integration of functional data allows a reduction in radiation doses to functional organs at risk, including critical cortical areas, subcortical tracts, and vascular structures. The relative simplicity of integrating functional neuroimaging into radiosurgery warrants further research to implement, standardize, and identify the limits of this procedure.

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas.

BACKGROUND: Stereotactic radiosurgery (SRS) can be a useful adjunct to the treatment of recurrent glioblastoma multiforme (GBM). Its combination with chemotherapy is attractive for the possible radiosensitization effect and cytotoxicity on tumor cells in distant areas. The aim of this study was to evaluate the efficacy and toxicity of CyberKnife SRS alone and combined with a "dose-dense" administration of temozolomide (TMZ) for recurrent GBM. METHODS: Between July 2007 and July 2010, 23 patients underwent CyberKnife SRS. In 12 patients irradiation was combined with TMZ at 75 mg/m(2)/day for 21 days every 28 days. The median prescription dose in this group was 20 Gy (mean 20.7 ± 4 Gy) with a median number of fractions of 2. The median dose for the 11 patients who underwent SRS alone was 20 Gy (mean 19.9 ± 4.4 Gy; p = NS). RESULTS: The median survival was 12 months for patients who underwent SRS/TMZ and 7 months for those who received SRS alone (p < 0.01). The 6-month progression-free survival (PFS) of the SRS/TMZ group was 66.7% vs. 18% for those who underwent SRS alone (p = 0.03). The median time to progression (TTP) was 7 months for patients who underwent SRS/TMZ and 4 months for those who underwent SRS alone (p = 0.01). Corticosteroid dependency was developed by most patients; radionecrosis was evident in one patient (4.3%) receiving TMZ. Grade 3 hematological toxicity was recorded in >40% of patients receiving chemotherapy. CONCLUSIONS: The results suggest that Cyberknife re-treatments are relatively safe using selected dose/fraction schemes. The combination with TMZ improved patients' outcomes with OS and 6-month PFS that favorably compares with alternative treatments, but the incidence of major adverse effects was >40%. Further studies are warranted.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Protecting venous structures during radiosurgery for parasagittal meningiomas.

Symptomatic edema is a potential complication of meningioma radiosurgery. Parasagittal meningiomas are at a particular risk for symptomatic edema, suggesting a role for a venous occlusive complication. The authors sought to develop a strategy to optimize CyberKnife stereotactic radiosurgical treatment parameters to reduce the irradiation of the peritumoral venous system. Multislice CT venography with 3D reconstructions was performed and coregistered with thin-section, contrast-enhanced, volumetric MR images. The tumor and critical volumes were contoured on the MR images. Venous anatomical details obtained from the CT venographic study were then exported onto the MR imaging and fused MR imaging-CT study. Target and critical structure volumes and dosimetric parameters obtained with this method were analyzed. The authors found that reducing the irradiation of veins that course along the surface of the meningioma, which may be at risk for radiation-induced occlusion, is feasible in parasagittal meningioma radiosurgery without compromising other treatment parameters including conformality, homogeneity, and target coverage. Long-term follow-up is needed to assess the clinical validity of this treatment strategy.

CyberKnife multisession stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for perioptic meningiomas: intermediate-term results and radiobiological considerations.

Single fraction radiosurgery is conventionally precluded for lesions lying <2-3 mm of the anterior visual pathway because of the radiosensitivity of the optic nerve. We analyzed a series of 64 patients with "perioptic" meningiomas treated by CyberKnife multisession radiosurgery and hypofractionated stereotactic radiotherapy (hSRT). Between July 2007-May 2010, patients were treated using conventional multisession Cyberknife schemes (2-5 fractions) and results were retrospectively analyzed. A radiobiological model was then developed to estimate the best tumor control probability (TCP)/ normal tissue complication probability (NTCP) for these lesions. Resulting dose/fraction schemes were applied to patients treated between May 2010 and July 2014. Data were prospectively collected Twenty-five patients were included in the retrospective part of the study. Median tumor volume was 4.95 cc; median dose was 23.0 Gy and median number of fraction was 5 (range 2-5). No patient had visual deterioration at mean follow-up of 60 ± 12 months. Tumor control was achieved in all cases. Thirty-nine patients were treated according the radiobiology model and results prospectively analyzed. Median tumor volume was 7.5 cc, median dose 25.0 Gy and mean number of fraction 5 (range 3-15). No patient had visual deterioration or tumor progression at mean follow-up of 17 ± 10 months. Conventional multisession CyberKnife treatments (2-5 fractions) provided satisfactory results. Nonetheless, our estimation of TCP suggests the use of higher doses to grant long-term disease control. To achieve higher equivalent doses without significantly increasing the NTCP, we suggest the use of a greater number of fractions, moving to hSRT, in tumors in which the encasement of optic nerves is presumed.

Muscle-invasive bladder cancer in elderly-unfit patients with concomitant illness: can a curative radiation therapy be delivered?

AIMS AND BACKGROUND: There is no standard treatment for elderly-unfit patients with muscle-invasive bladder cancer. Pelvic irradiation alone is an usual approach in this instance, and some reports have demonstrated that curative radiotherapy is feasible in elderly patients. To our knowledge, no data exist about the feasibility of a curative treatment in elderly patients with concomitant illness and a Charlson Comorbidity Index (an index of comorbidity that includes age) greater than 2. The main purpose of the present study was to establish the feasibility of irradiation in a cohort of elderly patients in poor general condition. METHODS: The records of 45 elderly-unfit patients (median age, 75 years; range, 70-85), with a comorbid Charlson score >2, treated with curative dose, planned continuous-course, external beam radiotherapy for muscle-invasive bladder cancer were reviewed. The patients were treated to a median total dose of 60 Gy (range, 56-64), with an average fractional dose of 190 +/- 10 cGy using megavoltage (6-15 MV). All patients were treated with radiation fields encompassing the bladder and grossly involved lymph nodes with a radiographic margin of at least 1.5 cm. RESULTS: No treatment-related mortality and clinically insignificant acute morbidity was recorded. No patient was hospitalized during or after the irradiation because of gastrointestinal or urogenital side effects. In one patient a week rest from therapy was necessary due a febrile status. Median survival was 21.5 months; overall 3- and 5-year survival was 36% and 19.5%, respectively. CONCLUSIONS: Elderly-unfit patients with comorbidities and >70 years of age can be submitted to radical pelvic irradiation. The results observed in this retrospective analysis have encouraged us to use non-palliative radiotherapy doses in these patients with muscle-invasive bladder cancer.

Treatment of periocular basal cell carcinoma using an advanced stereotactic device.

Basal cell carcinoma (BCC) is the most common malignant periocular tumor. When periorbital invasion exists, orbital exenteration is necessary. A 73-year-old man with recurrent BCC of the inner canthus of the left eye with diffusion to the extrinsic muscles of the orbit and periorbital fat was treated with CyberKnife in stereotactic body radiation therapy (SBRT) modality. The treatment resulted in rapid tumor regression, with a complete remission after six months without toxicities. To the best of our knowledge, this is the first report in the English literature describing a locally advanced BCC treated with SBRT alone.

Three-dimensional treatment planning for vaginal cuff brachytherapy: dosimetric effects on organs at risk according to patients position.

PURPOSE: Aim of this study was to evaluate dose distribution within organs at risk (OARs) and planning target volume (PTV) based on three-dimensional treatment planning according to two different setup positions in endometrial carcinoma patients submitted to postoperative brachy-radiotherapy on vaginal vault. METHODS AND MATERIALS: Patients with endometrial cancer necessitating of adjuvant brachytherapy on vaginal vault were enrolled. Pelvic computed tomography studies were prospectively obtained in two different setup positions: extend legs (A position) and gynecological (B position). Contoured OARs were bladder, rectum, and small bowel. The PTV was identified as applicator's surface with an isotropic 5-mm margin expansion. Radiation dose delivered in 1 cc (D1cc) and 2 cc (D2cc) of OAR were calculated. RESULTS: Coverage of PTV and values of D1cc and D2cc obtained for bladder and small bowel were similar in the two positions. For rectum, both D1cc and D2cc had statistically significant lower values in A with respect to B position. CONCLUSIONS: Both in A and B positions, radiation doses delivered do not exceed the dose constraints. However, A setup seems to significantly reduce doses to rectum while obtaining the same PTV coverage. The findings from our study provide evidence supporting the use of A position setup for delivering vaginal vault brachytherapy.

Breast cancer bone metastases: an epidemiologic study in selected radiation departments.

AIMS: To quantify radiation treatments for bone metastases from breast cancer in three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general population and the incidence and prevalence of breast cancer in this macro-area in a 8-year period. METHODS: All bone metastasis patients treated using radiotherapy in 8 radiation departments operating in the provinces of Messina, Catania and Ragusa were collected. Among these, metastases from breast carcinoma were analyzed according to year of irradiation. An analysis of breast cancer incidence and prevalence with respect to inhabitants in this macro-area was conducted using literature and census data. RESULTS: From January 2004 to December 2011, irradiation was delivered in 4419 bone metastasis patients. Among these, 1617 had a primary breast cancer with a median treatment per year of 206.5 (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004, there were 1,048,957 female residents in the three provinces and 1,065,422 in 2011. The reported breast cancer incidence and prevalence in Sicily was respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and 1091.29/100,000 in 2010. CONCLUSIONS: There has been an increase in both incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that there was no increment in skeletal-related events requiring irradiation in such patients in eastern Sicily radiation departments.

Predictive factors for oropharyngeal mycosis during radiochemotherapy for head and neck carcinoma and consequences on treatment duration. Results of mycosis in radiotherapy (MIR): a prospective longitudinal study.

BACKGROUND AND PURPOSE: Oropharyngeal mycosis (OPM) is a complication of radiotherapy (RT) treatments for head and neck (H&N) cancer, worsening mucositis and dysphagia, causing treatment interruptions and increasing overall treatment time. Prophylaxis with antifungals is expensive. Better patient selection through the analysis of prognostic factors should improve treatment efficacy and reduce costs. MATERIALS AND METHODS: A multicentre, prospective, controlled longitudinal study, with ethics committee approval, examined H&N cancer patients who were candidates for curative treatments with radio-chemotherapy. Patients were divided in groups according to OPM appearance: before the starting of RT (cases), during RT (new cases) and never (no cases). RESULTS: Of 410 evaluable patients, 20 were existing cases, 201 new cases and 189 did not report OPM. In our study OPM appears in 42.4% of people >70years and in 58.2% of younger individuals (p=0.0042), and in 68.6% of women versus 50.8% of men (p=0.0069). Mucositis and dysphagia were higher and salivation reduced among people with OPM (p<0.0000). Patients with OPM had longer hospitalization (p=0.0002) and longer (>12days) treatment interruptions (p=0.0288). CONCLUSIONS: Patients with OPM had higher toxicity and a greater number of long treatment interruptions. Analyses of prognostic factors can help clinicians understand OPM distribution and select patients with the highest probability of OPM for antifungal prophylaxis.

Radiotherapy and temozolomide in anaplastic astrocytoma: a retrospective multicenter study by the Central Nervous System Study Group of AIRO (Italian Association of Radiation Oncology).

Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.

Integration of three-dimensional rotational angiography in radiosurgical treatment planning of cerebral arteriovenous malformations.

PURPOSE: Accuracy in delineating the target volume is a major issue for successful stereotactic radiosurgery for arteriovenous malformations. The aim of the present study was to describe a method to integrate three-dimensional (3D) rotational angiography (3DRA) into CyberKnife treatment planning and to investigate its potential advantages compared with computed tomography angiography (CTA) and magnetic resonance angiography. METHODS AND MATERIALS: A total of 20 patients with a diagnosis of cerebral arteriovenous malformation were included in the present study. All patients underwent multislice computed tomography and 3D-volumetric CTA, 3DRA, and 3D magnetic resonance angiography. The contouring of the target and critical volumes was done separately using CTA and thereafter directly using 3DRA. The composite, conjoint, and disjoint volumes were measured. RESULTS: The use of CTA or 3DRA resulted in significant differences in the target and critical volumes. The target volume averaged 3.49 ± 3.01 mL measured using CTA and 3.26 ± 2.93 mL measured using 3DRA, for a difference of 8% (p < .05). The conjoint and disjoint volume analysis showed an 88% volume overlap. The qualitative evaluation showed that the excess volume obtained using CTA was mostly tissue surrounding the nidus and venous structures. The mean contoured venous volume was 0.67 mL measured using CTA and 0.88 mL (range, 0.1-2.7) measured using 3DRA (p < .05). CONCLUSIONS: 3DRA is a volumetric angiographic study that can be integrated into computer-based treatment planning. Although whether 3DRA provides superior accuracy has not yet been proved, its high spatial resolution is attractive and offers a superior 3D view. This allows a better 3D understanding of the target volume and distribution of the radiation doses within the volume. Additional technical efforts to improve the temporal resolution and the development of software tools aimed at improving the performance of 3D contouring are warranted.

A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres.

PURPOSE: A prospective observational multicentre trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and to evaluate the use of antiemetic drugs in patients treated with radiotherapy or concomitant radio-chemotherapy. The application in clinical practice of the Multinational Association of Supportive Care in Cancer guidelines was also studied. MATERIALS AND METHODS: Forty-five Italian radiation oncology centres took part in this trial. The accrual lasted for 3 consecutive weeks and only patients starting radiotherapy or concomitant radio-chemotherapy in this period were enrolled. Evaluation was based on diary card filled in daily by patients during treatment and one week after stopping it. Diary card recorded the intensity of nausea/vomiting and prophylactic/symptomatic antiemetic drug prescriptions. RESULTS: A total of 1020 patients entered into the trial, and 1004 were evaluable. Vomiting and nausea occurred in 11.0% and 27.1% of patients, respectively, and 27.9% patients had both vomiting and nausea. In multifactorial analysis, the only statistically significant patient-related risk factors were concomitant chemotherapy and previous experience of vomiting induced by chemotherapy. Moreover, two radiotherapy-related factors were significant risk factors for RIE, the irradiated site (upper abdomen) and field size (>400 cm(2)). An antiemetic drug was given only to a minority (17%) of patients receiving RT, and the prescriptions were prophylactic in 12.4% and symptomatic in 4.6%. Different compounds and a wide range of doses and schedules were used. CONCLUSIONS: These data were similar to those registered in our previous observational trial, and the radiation oncologists' attitude in underestimating RIE and under prescribing antiemetics was confirmed.

Patterns of care and survival in a retrospective analysis of 1059 patients with glioblastoma multiforme treated between 2002 and 2007: a multicenter study by the Central Nervous System Study Group of Airo (italian Association of Radiation Oncology).

OBJECTIVE: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years. METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTS: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001). CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

Enlarged axillary nodes and position of the arms in axillary irradiation--a computed tomography and magnetic resonance imaging evaluation.

The purpose of this study was to evaluate the axillary node displacement away from chest wall and their anatomical location in relation to the humeral head, according to the position of the arms, when the axilla is the site of enlarged nodes. In 13 patients with enlarged axillary nodes, the anatomical span of the nodes according to two arms positions, akimbo (A) and up over the head (U), was prospectively evaluated using computed tomography (CT) and magnetic resonance imaging (MRI). The nodes were classified into two groups, i.e. the lower and upper groups. The mean distances of the lower node group from the chest wall when the patients were in A, and U positions were 3 cm and 6.4 cm, respectively (p = 0.002). The upper group nodes showed a smaller difference in the distance from the chest wall: in A position, mean 2.1 cm; in U position 2.8 cm (p = 0.03). In U position, there was always a node of the lower group that was displaced in front of the humeral head. This study demonstrates the displacement of enlarged axillary nodes according to the position of the arms. In patients with axillary node involvement, CT planning should be considered when they have their arms held up over their heads.