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Brain metastases (BM) represent the most common intracranial malignancy in adults. Limitations of existing prognostic models reduce their predictivity and clinical applicability. The aim of this study is to validate the cumulative intracranial tumour volume prognostic assessment (CITVPA) as a new prognostic score system for patients with BM treated by Stereotactic Radiosurgery (SRS). Between January 2001 and December 2015, 1894 patients underwent Gamma Knife SRS treatment. The CITVPA model was implemented and validated as follows: the CITV cut-offs were identified thanks to a receiver-operating characteristic (ROC) curve analysis; the survival predictive factors were selected through a Cox proportional hazard model; its prognostic power was compared to RPA, SIR and GPA through the Harrel concordance index (HCI). According to the ROC curve analysis, the CITV cut-off values were set at 1.5 and 4.0 cc. Based on the multivariate analysis, the CITVPA model included: age (OR 1.010, 95% CI 1.005–1.015, p < 0.001), KPS (OR 0.960, 95% CI 0.956–0.965, p < 0.001), extracranial metastases (OR 1.287, 95% CI 1.154–1.437, p < 0.001), BM number (OR 1.193, 95% CI 1.047–1.360, p = 0.008), and CITV (OR 1.028, 95% CI 1.020–1.036, p < 0.001). A score between 0 and 1 was attributed to each prognosticator; a global CITVPA score ranging from 0 to 5 was assigned with higher results corresponding to worse outcomes. The CITVPA (HCI = 0.64) exhibited a significantly (p < 0.001) higher prognostic power compared to RPA (HCI = 0.55), SIR (HCI = 0.55) and GPA (HCI = 0.61). The CITVPA represents a reliable prognostic system for patients with BM treated by SRS. However, further prospective and multicentric studies are necessary before its applicability in clinical practice.

Objective To assess effectiveness of Gamma Knife Radiosurgery (GKRS) in improving quality of life (QoL) in patients with idiopathic trigeminal neuralgia (TN). Methods Between January 2001 and October 2013, 166 patients with medically resistant TN were treated at our institution with GKRS. Patients were divided into 2 groups: patients with typical TN (TTN) and patients with atypical TN (ATN). All patients underwent clinical evaluation using Marseille and Barrow Neurological Institute pain and numbness scales; in addition, they completed the Short-Form 36 Health Survey, Activities of Daily Living, and Excellent Good Fair Poor questionnaires and underwent psychological and neurologic examination. Results Mean follow-up time was 64.7 months. All Short-Form 36 domains were significantly improved in both groups after treatment, with an evident trend to reach the median values of healthy Italian population. Mean postoperative Activities of Daily Living score in the TTN group and ATN group were 5.8 and 5.4, respectively, and Karnofsky Performance Status increased to 94.2 and 86.4, respectively. Pain recurrence negatively affected patients' QoL and psychofunctional performance without reaching statistical significance. At the last follow-up, 73% of patients were clustered in the pain-relief group. Conclusions GKRS significantly improves QoL and functional and psychosocial performance of patients with idiopathic trigeminal neuralgia. A trend was observed toward a more favorable outcome in patients with TTN, compared with patients with ATN, without reaching a statistically significant distinction.

Purpose: To define the efficacy and complications of multisession Gamma Knife radiosurgery (MGKRS) delivered in three consecutive sessions for the treatment of residual or recurrent pituitary adenomas (PAs). Methods: This was a retrospective study of data from the Neurosurgery and Gamma Knife Radiosurgery Department at San Raffaele Hospital between May 2008 and September 2017. We recruited 47 consecutive patients undergoing MGKRS in three consecutive fractions for residual or recurrent PA with a distance from the anterior optic pathway inferior to 2–3 mm. Results: Thirty-eight (80.8%) patients had a nonfunctioning-PA (NFPA) while 9 (19.2%) had a hormone-secreting PA (HSPA). Tumor control was achieved in 100% of patients. Tumor shrinkage was seen in 33 out of 44 (75.0%) patients with a radiological follow-up. Mean tumor volume before MGKRS was 3.93 cm 3 . The mean tumor volume at last follow-up was 2.11 cm 3 , with a mean tumor shrinkage of 50.2%, as compared with baseline. One case of suspected radiation-induced optic neuropathy (RION) was documented while new-onset hypopituitarism for any axis occurred in 12 of the 31 (38.7%) patients at risk. The mean follow-up was 44.6 ± 4.0 months (range, 6–111 months). Conclusions: MGKRS is a valid alternative to external fractionated radiotherapy and other types of stereotactic radiosurgery for the treatment of PAs, achieving a high tumor control rate with a low risk of visual deterioration. Moreover, the majority of patients showed a significant reduction of tumor size in the long term.

Gamma Knife radiosurgery is often used in pituitary adenomas. Aim of our study is to describe the characteristics and long-term outcome of patients with adenoma recurrence after Gamma Knife radiosurgery. We conducted a retrospective analysis of patients with pituitary adenoma treated by Gamma Knife radiosurgery between 1994 and 2014. Tumor recurrence was labeled as “in field” when the tumor growth occurred adjacent or within the prescribed isodose, whereas it was classified as “out of field” when the tumor growth occurred outside the prescribed isodose. Five hundred forty-three patients were included, 272 (50.1 %) had a nonfunctioning pituitary adenoma (NFPA) and 271 (49.9 %) patients had a hormone secreting-pituitary adenoma. The median follow-up after GKRS was 78 months (IQR, 36-125 months). Thirty-nine patients (7.2 %) had recurrence of disease and it was more frequent in patients with NFPA than in patients with hormone secreting adenomas (9.6 % vs. 4.8 %). The 10-yr progression-free survival in patients with NFPA was 78.7 % (95 % CI 69.5 – 87.9 %), as compared with 93.3 % (95 % CI 89.3 – 97.3 %; p < 0.01) in hormone secreting adenomas. Tumor recurrence was “in field” in 17 cases (43.6 %) and “out of field” in 22 cases (56.4 %). Seven of the 39 patients with recurrence died despite further treatments. Six of these patients had an “in field” recurrence. Recurrence of a pituitary adenoma after GKRS may occur several years after initial treatment. Distinction between “in field” and “out of field” tumor recurrence probably reflects two different pathophysiological mechanisms and may have prognostic importance. © 2016 Springer Science+Business Media New York

Background Glomus tumors are rare and benign hypervascular tumors. Surgery represented the mainstay of their treatment, even if it has been associated with high morbidity and mortality rates. Recently, the treatment shifted to a multimodal approach and Gamma Knife radiosurgery represents one of the treatment options. Methods Authors retrospectively analyzed the clinical and radiological outcome of a series of patients who underwent Gamma Knife radiosurgery for glomus tumors. Results Thirty patients underwent Gamma Knife radiosurgery. Mean tumor volume was 7.69 cc (range 0.36-24.6). Mean tumor margin dose was 16 Gy (range 13-18). Median follow-up was of 91 months (mean 90; range 11-172). Overall clinical control rate was 100%; overall volumetric tumor control rate was 96.6%. Patients' and tumors' characteristics, treatment data, and outcome have been analyzed. Conclusion Gamma Knife radiosurgery represents a safe and effective treatment for glomus tumors. Longer follow-up and larger cohort studies are needed to definitively outline the role of Gamma Knife radiosurgery for glomus tumors.

AimsThe aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM).Materials and methodsMedical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications.ResultsThe fraction of the posterior segment receiving more than 20Gy (V20), Bruch’s membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch’s membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested.ConclusionsWe found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset.

Objective First-line therapy for low-grade gliomas (LGGs) is surgery, in some cases followed by radiotherapy and chemotherapy. Gamma Knife radiosurgery (GKRS) has gained more relevance in the management of these tumors. The aim of this study was to assess efficacy and safety of GKRS for treatment of LGGs. Methods Between 2001 and 2014, 42 treatments were performed on 39 patients harboring LGGs; 48% of patients underwent previous surgery, and 20.5% underwent previous radiotherapy. Mean tumor volume was 2.7 cm 3 , and median margin dose was 15 Gy. Results Mean follow-up was 60.5 months (range, 6–164 months). Actuarial progression-free survival was 74.9%, 52.8%, and 39.1% at 1 year, 5 years, and 10 years; actuarial overall survival was 97.4%, 94.6%, and 91.8% at 9 months, 1 year, and 5 years. Solid tumor control was achieved in 69.2% of patients, whereas cystic enlargement was recorded in 12.9% of cases. At last follow-up, volume reduction was recorded in 57.7% of cases, and median volume decreased by 33.3%. Clinical improvement was observed in 52.4% of patients. Karnofsky performance scale score was improved in 15 patients (45.5%), unchanged in 17 patients (51.5%), and worsened in 1 patient (3%). Mean posttreatment scores of 36-item short form health survey domains did not significantly differ from scores in a healthy Italian population. Conclusions This study confirms safety and effectiveness of GKRS for LGGs in controlling tumor growth, relevantly improving patients' overall and progression-free survival. GKRS improved patients' functional performance and quality of life, optimizing social functioning and minimizing disease-related psychological impact.

Objective Complete removal of vestibular schwannomas (VS) is not always achievable without any risk of disabling postoperative complications, especially in terms of facial nerve function. Moreover, even after gross total removal, a relevant rate of recurrence has been reported. The aim of this study is to validate Gamma Knife radiosurgery (GKRS) as an effective strategy to treat tumor regrowth after previous surgery. Methods Ninety patients treated with GKRS for VS after previous microsurgery were included in the present study. GKRS was performed at a median of 31 months (range, 4–174 months) postoperatively. Mean tumor volume was 3.35 cm 3 (median, 2.5 cm 3 ; range, 0.027–13 cm 3 ) and median marginal dose was 13 Gy. Results At a mean follow-up of 77.2 months, tumor control was achieved in 90% of patients: 2 patients underwent repeated GKRS, and 7 patients underwent further microsurgery. Tumor shrinkage at last follow-up was recorded in 80.3% of cases. The complication rate was low and many consisted of a transient worsening of preexisting symptoms. The overall incidence of persisting facial nerve deficit and trigeminal nerve impairment was, in both cases, 3.3%. Two of 5 patients (40%) preserved functional hearing at last follow-up. One patient (1.1%) underwent ventriculoperitoneal shunting 12 months after GKRS. Conclusions GKRS is a safe and effective treatment for growing residual and recurrent VSs, with tumor control obtained in 90% of cases and a low morbidity rate. Moreover, the possibility of treating patients with major medical comorbidities constitutes a significant advantage over repeated surgery.

ObjectSince the 1990s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect–related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS.MethodsOf 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm3 (median 1.2 cm3, range 0.013–14.3 cm3), and the median margin dose was 13 Gy (range 11–15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics.ResultsControl of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years.ConclusionsGamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

Background Gamma Knife radiosurgery (GKRS) represents a well-accepted treatment for small-medium vestibular schwannomas (VS); however, its application in larger VS is still controversial. Methods Among the 523 patients treated at our institution for VS between 2001 and 2010, we included 59 patients with a VS larger than 25 mm, treated by GKRS as primary treatment, not affected by neurofibromatosis type 2, and with a clinical follow-up of at least 36 months. Five patients underwent ventriculoperitoneal shunt placement before radiosurgery. Clinical follow-up (mean, 79.4 months) was obtained in all patients. Patients’ age ranged from 24 to 85 years (mean, 63.8 years). Mean tumor volume was 5.98 cm3 (maximum, 14.3 cm3) and median marginal dose was 13 Gy. A statistical analysis was performed to correlate clinical outcome with tumor radiologic features, dose-planning parameters, and patients’ characteristics. Results Tumor control was achieved in 98.3% of cases. At last follow-up, 86.4% of VS showed volume reduction. Recorded complications were 3 cases (5.1%) of new permanent facial nerve deficit, 4 cases (6.8%) of new or worsened trigeminal impairment, and 10 new cases (18.5%) of hydrocephalus requiring ventriculoperitoneal shunt. Larger tumor size was significantly associated with a subsequent ventricular enlargement. Overall, functional hearing preservation rate was 31.3% (66.7% among patients with Gardner-Robertson I). Conclusions Surgical resection remains the primary approach for large VS with symptomatic brainstem compression. GKRS can be considered a safe and effective option in particular in patients who are not good candidates for surgery. © 2016 Elsevier Inc Background Gamma Knife radiosurgery (GKRS) represents a well-accepted treatment for small-medium vestibular schwannomas (VS); however, its application in larger VS is still controversial. Methods Among the 523 patients treated at our institution for VS between 2001 and 2010, we included 59 patients with a VS larger than 25 mm, treated by GKRS as primary treatment, not affected by neurofibromatosis type 2, and with a clinical follow-up of at least 36 months. Five patients underwent ventriculoperitoneal shunt placement before radiosurgery. Clinical follow-up (mean, 79.4 months) was obtained in all patients. Patients’ age ranged from 24 to 85 years (mean, 63.8 years). Mean tumor volume was 5.98 cm3 (maximum, 14.3 cm3) and median marginal dose was 13 Gy. A statistical analysis was performed to correlate clinical outcome with tumor radiologic features, dose-planning parameters, and patients’ characteristics. Results Tumor control was achieved in 98.3% of cases. At last follow-up, 86.4% of VS showed volume reduction. Recorded complications were 3 cases (5.1%) of new permanent facial nerve deficit, 4 cases (6.8%) of new or worsened trigeminal impairment, and 10 new cases (18.5%) of hydrocephalus requiring ventriculoperitoneal shunt. Larger tumor size was significantly associated with a subsequent ventricular enlargement. Overall, functional hearing preservation rate was 31.3% (66.7% among patients with Gardner-Robertson I). Conclusions Surgical resection remains the primary approach for large VS with symptomatic brainstem compression. GKRS can be considered a safe and effective option in particular in patients who are not good candidates for surgery.

Background and purpose Gamma Knife Surgery (GKS) can be an adjunctive option to surgery in the case of pituitary adenomas. The effect of dosimetric variables on the incidence of new anterior pituitary deficits after GKS requires better definition. Materials and methods This retrospective study considered 130 patients with a follow up after GKS >6months. The diagnosis was nonfunctioning pituitary adenoma (NFPA) in 68 patients and secreting pituitary adenoma (SPA) in 62 patients. Median margin dose was 15/25Gy for NFPA and SPA, respectively. The endocrinological median follow-up was 60months. Hypopituitarism was defined as a new pituitary deficit in (at least) one of the three hormonal axes (hypogonadism, hypothyroidism and hypoadrenalism). The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses. Results Sixteen patients (12.3%) showed a new pituitary deficit in one or more axes. Multivariate analysis confirmed that the mean dose to the stalk/pituitary and the amount of healthy tissue within the high dose region were strong independent predictors of pituitary dysfunction; their best cut-off values were around 15.7Gy, 7.3Gy and 1.4cm 3 , respectively. Conclusions Our data showed a dose-dependent incidence of new hormonal deficits after GKS for pituitary adenoma. During planning definition, the risk of hypopituitarism could be reduced using the outlined safe dose–volume values.

Purpose: To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Results: Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. Conclusions: This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients. (C) 2009 Elsevier Inc.

A quantitative estimate of the impact of prostatectomy on pelvic anatomy is unavailable, even if it would be an important prerequisite for a precise definition of clinical target volume (CTV) in post-prostatectomy radiotherapy. The purpose of this study was to investigate the impact of prostatectomy on the definition of CTV, on the position of bladder and rectum and their implications for three-dimensional conformal radiotherapy (3-D CRT).Six patients eligible for radical retropubic prostatectomy were considered. Each patient underwent a planning CT between 1 week and 1 month before surgery (CTpre), and then CT was repeated in the same positioning 1-2 months after surgery (CTpost). For each patient the CT(pre/post) scans were matched; rectum, bladder and CTV were contoured on both CT scans for each patient by one observer. Two different CTVs were contoured: CTV1: prostate + seminal vesicles in CTpre; prostate + seminal vesicles surgical bed in CTpost; CTV2: prostate in CTpre; prostate surgical bed in CT(post). After image registration, the contours of rectum, bladder and CTV1/2 drawn on CTpost were transferred on CTpre. The corresponding planning target volumes (PTVs) were generated, and for each PTV, a conformal four field technique using 18-MV X-rays was planned. The volumes of CTV1, CTV2, PTV1, PTV2, rectum and bladder pre- and post-surgery were compared. Differences in 3-D position of these structures before and after surgery were analyzed by beam's eye view (BEV) images. Pre- and post-surgery dose-volume histograms (DVHs) of rectum and bladder were compared together with the fraction of rectum/bladder receiving at least 95% of the ICRU dose (V95), the treated volume (TV, body included in the 95% isodose) and the irradiated volume (IV, body included in the 50% isodose).For both CTV1 and CTV2, the volumes were significantly reduced after prostatectomy (average reduction around 30 cm3 for both; range 0-60 cm3). This reduction was mainly due to a more caudal definition of the cranial edge of CTV after prostatectomy (average difference for CTV2: 1.5 cm; range 0-2.5 cm). Concerning the bladder, a systematic posterior shift of the bladder base (average: 1.5 cm) was found and was correlated with a significant reduction of V95 for bladder (around 10 cm3; p = 0.03). V95 of the rectum, TV and IV also resulted to be significantly lower after surgery. The average reduction of V95 for the rectum was relatively small (2.5 cm3 of rectal wall).The impact of prostatectomy on CTV definition is high. A significant reduction of CTV, PTV, TV and IV may be expected after surgery with a consequent reduction of the portions of rectum/bladder irradiated with adjuvant radiotherapy.

BACKGROUND The authors performed a randomized trial comprising patients with metastatic breast carcinoma (MBC). They used a noninferiority design to evaluate whether the results of sequential administration of epirubicin and paclitaxel were not markedly worse than the concomitant administration in terms of objective response rates (ORRs). Toxicity profile, quality of life (QOL), and pharmacoeconomic evaluations were evaluated as well. METHODS In the current study, 202 patients with MBC were randomized to receive either the combination of epirubicin at a dose of 90 mg/m2 plus paclitaxel at a dose of 200 mg/m2 for 8 cycles (concomitant arm, n = 108) or epirubicin at a dose of 120 mg/m2 for 4 cycles followed by paclitaxel at a dose of 250 mg/m2 over 3 hours for 4 cycles every 21 days (sequential arm, n = 94). RESULTS The authors rejected the null hypothesis that the sequential treatment is less active than the standard concomitant regimen (ORRs: concomitant = 58.5%, sequential = 57.6%). The median progression-free and overall survival periods were 11.0 months (95% confidence interval [95% CI], 9.7–12.3) and 20.0 months (95% CI, 17.2–22.6), respectively, in the concomitant arm and 10.8 months (95% CI, 7.9–13.6) and 26 months (95% CI, 18.1–33.8), respectively, in the sequential arm (P = not significant). Patients who received the sequential regimen experienced a higher incidence of Grade 3/4 (according to the World Health Organization grading system) neutropenia (62.2% of courses vs. 50.62%; P = 0.003) and Grade ≥ 2 neuropathy (45.5% vs. 30.4% of patients; P = 0.03), whereas 6 patients who received the concomitant regimen developed Grade II cardiotoxicity according to New York Heart Association criteria. QOL analyses failed to provide clear differences. CONCLUSIONS The sequential administration of epirubicin and paclitaxel at full doses was found to be as active as their association. Therefore, both the sequential and the combined administration were acceptable options. Cancer 2004. © 2004 American Cancer Society.

Investigating the correlation between dosimetric/clinical parameters and late rectal bleeding in patients treated with adjuvant or salvage radiotherapy after radical prostatectomy.Data of 154 consecutive patients, including three-dimensional treatment planning and dose-volume histograms (DVHs) of the rectum (including filling), were retrospectively analyzed. Twenty-six of 154 patients presenting a (full) rectal volume100 cc were excluded from the analysis. All patients considered for the analysis (n = 128) were treated at a nominal dose equal to 66.6-70.2 Gy (ICRU dose 68-72.5 Gy; median 70 Gy) with conformal (n = 76) or conventional (n = 52) four-field technique (1.8 Gy/fr). Clinical parameters such as diabetes mellitus, acute rectal bleeding, hypertension, age, and hormonal therapy were considered. Late rectal bleeding was scored using a modified Radiation Therapy Oncology Group scale, and patients experiencingor=Grade 2 were considered bleeders. Median follow-up was 36 months (range 12-72). Mean and median rectal dose were considered, together with rectal volume and the % fraction of rectum receiving more than 50, 55, 60, and 65 Gy (V50, V55, V60, V65, respectively). Median and quartile values of all parameters were taken as cutoff for statistical analysis. Univariate (log-rank) and multivariate (Cox hazard model) analyses were performed.Fourteen of 128 patients experiencedor=Grade 2 late bleeding (3-year actuarial incidence 10.5%). A significant correlation between a number of cutoff values and late rectal bleeding was found. In particular, a mean doseor=54 Gy, V50or=63%, V55or=57%, and V60or=50% was highly predictive of late bleeding (por= 0.01). A rectal volume60 cc and type of treatment (conventional vs. conformal) were also significantly predictive of late bleeding (p = 0.05). Concerning clinical variables, acute bleeding (p0.001) was significantly related to late bleeding, and a trend was found for hypertension (p = 0.11). After patients were grouped into those with V50or=63% and those with V5063% (DVH grouping), data were fitted with a Cox regression hazard model using DVH grouping, rectal volume, and the main clinical parameters as independent variables. Results of the analysis showed that DVH grouping (relative risk 3.3; p = 0.04) and acute bleeding (relative risk 7.1; p = 0.001) are independently predictive of late bleeding.DVHs of the rectum are significantly correlated with late bleeding for patients irradiated at 66.6-70.2 Gy after radical prostatectomy.

Since the 1990 s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect-related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS.Of 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm(3) (median 1.2 cm(3), range 0.013-14.3 cm(3)), and the median margin dose was 13 Gy (range 11-15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics.Control of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years.Gamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

Background and purpose: Accurate contouring of the clinical target volume (CTV) is a fundamental prerequisite for successful conformal radiotherapy of prostate cancer. The purpose of this study was to investigate intra-and inter-observer variability in contouring prostate (P) and seminal vesicles (SV) and its impact on conformal treatment planning in our working conditions. Materials and methods: Inter-observer variability was investigated by asking five well-trained radiotherapists of contouring on CT images the P and the SV of six supine-positioned patients previously treated with conformal techniques. Short-term intra-observer variability was assessed by asking the radiotherapists to contour the P and SV of one patient for a second time, just after the first contouring. The differences among the inserted volumes were considered for both intra-and inter-observer variability. Regarding intra-observer variability, the differences between the two inserted contours were estimated by taking the relative differences in correspondence to the CT slices on BEV plots (antero-posterior and left-right beams). Concerning inter-observer variability, the distances between the internal and external envelopes of the inserted contours (named projected diagnostic uncertainties or PDUs) and the distances from the mean inserted contours (named mean contour distances or MCDs) were measured from BEV plots (i.e. parallel to the CT slices). Results: Intra-observer variability was relatively small (the average percentage variation of the volume was similar to 5%; SD of the differences measured on BEV plots within 1.8 mm). Concerning inter-observer variability, the percentage SD of the inserted volumes ranged from 10 to 18%. Differences equal to 1 cm in the cranio-caudal extension of P + SV were found in four out of six patients. The largest interobserver variability was found when considering the anterior margin in the left-right beam of P top (MCD = 7.1 mm, 1 SD). Relatively high values for MCDs were also found for P bottom, for the posterior and lateral margins of P top (2.6 and 3.1 mm, respectively, 1 SD) and for the anterior margin of SV (2.8 mm, 1 SD). Relatively small values were found for P central (from 1.4 to 2.0 mm, 1 SD) and the posterior margin of SV (1.5 mm, 1 SD). Conclusions: The application of larger margins taking inter-observer variability into account should be taken into consideration for the anterior and the lateral margins of SV and P top and for the lateral margin of P. The impact of short-term intra-observer variability does not seem to be relevant. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

Since its discovery in 1979, the prostatic specific antigen (PSA) has proved to be a most valuable tumour marker (1, 2), influencing clinical management of prostate cancer (3). PSA is an independent prognostic tool on which to base important therapeutic decisions and, because it is able to detect relapsing disease before it becomes clinically apparent, is a useful instrument for the follow-up and monitoring of the disease (4-6). Furthermore, PSA assay is a simple method for estimating the usefulness of new treatment strategies. Various policies have been proposed for studying PSA modification before, during and after radiotherapy (RT). Unfortunately, the short follow-up of most of these studies, the limited number of patients involved and the diversity of patient characteristics preclude firm conclusions. This paper outlines our current knowledge of the prognostic value of RSA determinations before, during and after RT for prostatic carcinoma.

Background and purpose: Comparing some isocentric coplanar techniques for conformal irradiation of prostate and seminal vesicles. Materials and methods: Five conformal techniques have been considered: (A) a 3-fields technique with an antero-posterior (AP) field and two lateral (LAT-LAT) 30 degrees wedged fields; (B) a 3-fields technique with an AP field and two oblique posterior (OBL) 15 degrees wedged fields with relative weights of 0.8, 1 and 1, respectively; (C) a 4-fields technique (AP-PA and LAT-LAT); (D) a 6-fields technique (LAT-LAT and four OBL at gantry angles 45 degrees, 135 degrees, 235 degrees and 315 degrees) with all the fields having the same weight; (E) the same 6-fields technique with lateral fields double-weighted with respect to the oblique fields. The conformal plans have been simulated on 12 consecutive patients (stages B and C) by using our 3D treatment planning system (Cadplan 2.7). The contours of the rectum, the bladder and the left femoral head were outlined together with the clinical target volume (CTV) which included the prostate and the seminal vesicles. A margin of 10 mm was added to define the planning target volume (PTV) through automatic volume expansion. Then a 7 mm margin between the PTV and block edges was added to take the beam penumbra into account. Dose distributions were normalised to the isocentre and the reference dose was considered to be 95% of the isocentre dose. Dose-volume histograms and dose statistics of the rectum, the bladder and the left femoral head were collected for all plans. For the rectum and the bladder the mean dose (Dm) and the fraction of volume receiving a dose higher than the reference dose (V95) were compared. For the femoral head, the mean dose together with the fraction of volume receiving a dose higher than 50% (V50) were compared. Results: Differences among the techniques have been found for all three considered organs at risk. When considering the rectum, technique A is better than the others both when considering Dm and V95 (P = 0.002), while technique D is the worst when considering Dm (P < 0.002) and is also worse than techniques A, E (P = 0.002) and C (P = 0.003) when considering V95. Technique E is the best when considering the bladder mean dose (P = 0.002 against A and D, P < 0.01 against B and C) and technique C is the worst (P < 0.012). No relevant differences were found for the bladder V95. in the femoral heads, techniques A and E are worse than B, C and D (P < 0.003) when considering Dm and V50. Moreover, techniques B and D are better than C (P < 0.004) when considering V50. Conclusions: There is no technique that is absolutely better than the others. Technique A gives the best sparing of the rectum; the bladder is better spared with technique E. These results are reached with a worse sparing of the femoral heads which should be carefully taken into account. (C) 1997 Elsevier Science Ireland Ltd.

Introduction Uveal melanoma (UM) is a life threatening intraocular malignant tumor. Gamma Knife Stereotactic Radiosurgery (GKSRS) is a well-assessed strategy for conservative treatment of UM providing good results for survival, local control and eye preservation. Purpose Our aim is to develop predictive models for radio-induced effects in UM patients treated with exclusive GKSRS. Materials and methods Medical records and 3D dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for most clinically relevant GKSRS-related complications: radiation vasculopathy(RV), radiation papillopathy (RP) and neovascular glaucoma(NVG), visual acuity(VA) reduction >20% (VA20%) and complete loss of basal VA (VA100%). ROC curve analysis allowed predicting cutoff values of significant variables. Results The 2 years incidences were: RV 10%, RP 12%, NVG 14%, VA20% 59% and VA100% 27%. A clear relationship with D1% to optic nerve (ON) was found for RP and RV. Also, for RV, the prescription isodose-ON distance (PIOND) and the anterior to equator position of the tumor resulted as protective variables. The V20 of posterior segment and tumor thickness were predictive for NVG. Multivariate analyses resulted in two variables predictive model both for VA20% and VA100%, including tumor largest diameter and D1% to ON. A second predictive model, including PIOND, was found for VA100%. Conclusion We found clinical and dosimetric variables to predict the risk of main side effects after GKSRS for UM. These results may provide new dose constraints to critical structures potentially able to reduce toxicities. Disclosure Antonella del Vecchio has a contract as starter-up with Elekta Instrument AB. No other conflict of interest to declare for the other authors.

The goal of establishing prompt localization of the malignant spread or recurrence of a tumor has found a powerful solution in the definition of follow-up protocols, which include the indication for CT scans on an annual or semiannual basis. In the case of long-surviving patients, however, this approach will lead to a considerable integrated dose level over a period of several years after recovery from the illness. Pathologies treated primarily by surgery and/or chemotherapy have been considered, not taking into account cancers treated with adjuvant or radical radiotherapy. Given that the most likely protocols for these cancers often call for total body scans, an estimation of the consequent effective and organ doses can be performed with acceptable accuracy. The data acquired from five centers have been collected and the related effective and organ doses calculated by means of IMPACT software. Use of the effective dose concept, however, has lately become the subject of criticism, and the recently proposed Effective Risk Model has therefore also been applied. The evaluated absolute additional risk of second tumor induction ranges between 0.1% and 10%, depending primarily on age and pathology. These results depict this additional risk as an issue of significant importance for clinical practice. A revision of follow-up and scan parameter protocols, as well as the introduction of new algorithms for dose reduction, could significantly improve the risk-benefit ratio for all the pathologies studied.

Purpose: To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. Patients and Methods: Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant (n = 556; median radiation dose, 70.2 Gy) or salvage (n = 186; median radiation dose, 72 Gy) intent. Results: After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was almost identical (23.9% vs. 23.7% and 12% vs. 10%) in the adjuvant and salvage cohorts, respectively. On univariate analysis, acute toxicity was significantly predictive of late Grade 2 or greater sequelae in both subgroups (p 72 Gy (8-year risk, 19% vs. 6%, p = .007) and age >71 years (8-year risk, 16% vs. 6%,p = .006) in the salvage subgroup. Multivariate analysis confirmed the independent predictive role of all the covariates indicated as statistically significant on univariate analysis. Conclusions: The risk of late Grade 2 or greater and Grade 3 urinary toxicity was almost identical, regardless of the RT intent. In the salvage cohort, older age and greater radiation doses resulted in a worse toxicity profile, and younger, hypertensive patients experienced a greater rate of severe late sequelae in the adjuvant setting. The causes of this latter correlation and apparently different etiopathogenesis of chronic damage in the two subgroups were unclear and deserve additional investigation. (C) 2012 Elsevier Inc.

To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non-small cell lung cancer (NSCLC).Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS ≥ 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up (3 months). Thirty-five patients belonged to recursive partitioning analysis (RPA) Class I, 307 patients were in RPA Class II, 7 patients were in RPA Class III. Median tumor volume was 3.6 cm(3). Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm(3) and 15.8 cm(3), respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries.Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression.Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.

Background: Recent large, prospective, randomised studies have demonstrated that adjuvant radiotherapy (RT) is a safe and effective procedure for preventing disease recurrence in locally advanced prostate cancer (PCa) patients. However, no study has ever tested the role of adjuvant RT in node-positive patients after radical prostatectomy (RP). Objective: We hypothesised that adjuvant RT with early hormone therapy (HT) might improve long-term outcomes of patients with PCa and nodal metastases treated with RP and extended pelvic lymph node dissection (ePLND). Design, setting, and participants: This retrospective study included 250 consecutive patients with pathologic lymph node invasion. We assessed factors predicting long-term biochemical recurrence (BCR)-free and cancer-specific survival (CSS) in node-positive PCa patients treated with RP, ePLND, and adjuvant treatments between 1988 and 2002 in a tertiary academic centre. Intervention: All patients received adjuvant treatments according to the treating physician after detailed patient information: 129 patients (51.6%) were treated with a combination of RT and HT, while 121 patients (48.4%) received adjuvant HT alone. Measurements: BCR-free survival and CSS in patients with node-positive PCa. Results and limitations: mean follow-up was 95.9 mo (median: 91.2). BCR-free survival and CSS rates at 5, 8, and 10 yr were 72%, 61%, 53% and 89%, 83%, 80%, respectively. In multivariable Cox regression models, adjuvant RT and the number of positive nodes were independent predictors of BCR-free survival (p = 0.002 and p = 0.003, respectively) as well as of CSS (p = 0.009 and p = 0.01, respectively). Moreover, there was significant gain in predictive accuracy when adjuvant RT was included in multivariable models predicting BCR-free survival and CSS (gain: 3.3% and 3%, respectively; all p < 0.001). Conclusions: Our data showed excellent long-term outcome for node-positive PCa patients treated with radical surgery plus adjuvant treatments. This study is the first to report a significant protective role for adjuvant RT in BCR-free survival and CSS of node-positive patients. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. Background: Recent large, prospective, randomised studies have demonstrated that adjuvant radiotherapy (RT) is a safe and effective procedure for preventing disease recurrence in locally advanced prostate cancer (PCa) patients. However, no study has ever tested the role of adjuvant RT in node-positive patients after radical prostatectomy (RP). Objective: We hypothesised that adjuvant RT with early hormone therapy (HT) might improve long-term outcomes of patients with PCa and nodal metastases treated with RP and extended pelvic lymph node dissection (ePLND). Design, setting, and participants: This retrospective study included 250 consecutive patients with pathologic lymph node invasion. We assessed factors predicting long-term biochemical recurrence (BCR)-free and cancer-specific survival (CSS) in node-positive PCa patients treated with RP, ePLND, and adjuvant treatments between 1988 and 2002 in a tertiary academic centre. Intervention: All patients received adjuvant treatments according to the treating physician after detailed patient information: 129 patients (51.6%) were treated with a combination of RT and HT, while 121 patients (48.4%) received adjuvant HT alone. Measurements: BCR-free survival and CSS in patients with node-positive PCa. Results and limitations: mean follow-up was 95.9 mo (median: 91.2). BCR-free survival and CSS rates at 5, 8, and 10 yr were 72%, 61%, 53% and 89%, 83%, 80%, respectively. In multivariable Cox regression models, adjuvant RT and the number of positive nodes were independent predictors of BCR-free survival (p = 0.002 and p = 0.003, respectively) as well as of CSS (p = 0.009 and p = 0.01, respectively). Moreover, there was significant gain in predictive accuracy when adjuvant RT was included in multivariable models predicting BCR-free survival and CSS (gain: 3.3% and 3%, respectively; all p < 0.001). Conclusions: Our data showed excellent long-term outcome for node-positive PCa patients treated with radical surgery plus adjuvant treatments. This study is the first to report a significant protective role for adjuvant RT in BCR-free survival and CSS of node-positive patients. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Object Treatment options for patients with brain metastasis include tumor resection, whole-brain radiation therapy, and radiosurgery. A single treatment is not useful in cases of multiple tumors, of which at least 1 is a cystic tumor. The purpose of this study was to assess the role of stereotactic drainage and Gamma Knife surgery (GKS) in the treatment of cystic brain metastasis. Methods Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 ± 11 years, range 38–75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score ≥ 70; and 5) histological diagnosis of a malignant tumor. Results Non–small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8–68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2–32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12–25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3–64.1%) and 34.2% (95% confidence interval 23.1–45.3%). Local tumor control was achieved in 91.3% of the patients. Conclusions The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis.

Sarcoidosis is a chronic disease of unknown etiology characterized by the presence of T lymphocytes, mononuclear phagocytes, and noncaseating epithelioid granulomas in the tissues. Central nervous system involvement occurs in about 5% of the cases. The chronic form of neurosarcoidosis is particularly resistant to medical treatments. No universally accepted therapeutic protocols are currently available. Corticosteroids are the first line of therapy, but other immunosuppressive treatments are frequently added to the patient's regimen, although this strategy is not adequately supported by controlled clinical trials. For patients resistant to or not tolerating multiple alternate immunotherapeutic drugs, some authors suggest central nervous system radiotherapy. We present a case of a patient with neurosarcoidosis involving the hypothalamo-hypophyseal region and causing panhypopituitarism who had a poor response to and experienced severe side effects from conventional immunosuppressive treatments. The patient experienced a good clinical response to cranial irradiation. We review the literature on this subject.

Adenoid cystic carcinoma, also called cylindroma, is the second most common histological type of tracheal malignancy but represents 1% of all respiratory tract cancers. We report a case of a 59-year-old patient submitted to an incomplete resection of the trachea and subsequently treated with adjuvant tomotherapy. There have been no reports in the literature regarding intensity-modulated radiation therapy with linac or tomotherapy systems in adenoid cystic carcinoma of the trachea. The present clinical case demonstrates the feasibility of adjuvant intensity-modulated radiation therapy techniques for optimizing the dose coverage of the tumor bed while sparing surrounding normal tissues. A dosimetric comparison between the tomotherapy plan and a 3-dimensional conformal radiotherapy plan is also reported. We demonstrate that tomotherapy permits an increase in the dose per fraction without important acute adverse effects. At 24 months’ follow-up, our patient shows no evidence of disease with negative histological findings.

In 2005, a 62-year-old man was diagnosed with stage IIIB non-small cell lung cancer and treated with sequential chemoradiotherapy. Approximately 2 years later, he was treated with the endothelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib. Eight days after starting getitinib therapy, he experienced grade 3 skin toxicity on the chest and shoulders but not in the previous radiotherapy field (Figure 1).1,2 Despite the severity of the skin toxicity, the patient did not obtain any benefit from this treatment. In reviewing the existing literature on this topic, we observed that the sequential approach of radiotherapy followed by EGFR-TKI does not seem to have a synergic or additive effect, as observed with the concomitant approach. Conversely, this effect seems to be detrimental, perhaps by inducing a decrease in expression and activity of EGFR. This effect seems to be milder if EGFR-TKI is administered immediately after radiotherapy (within 3 weeks) and much stronger when administered after a longer time from radiotherapy.3,4 These data suggest that the decrease of EGFR expression after radiotherapy may have a dramatic role in explaining the negative preliminary results of SWOG 0023, which is the only clinical study available so far.5 This observation raises the question of whether skin toxicity sparing can be considered a surrogate of lack of tumor response to EGFR-TKIs.

Background and purpose: To investigate the usefulness of vesicourethral anastomotic biopsy (VUBx) in patients who are candidates for salvage radiotherapy (SalvRT) after radical prostatectomy (RRP). Material and methods: From 1992 to 2001, 98 patients with a PSA failure (PSAf) after RRP underwent SalvRT to the prostatic bed (median dose 70 Gy). In 50/98 patients the VUBx was positive, in 26 negative; 22 patients underwent salvRT without a prior VUBx. The prognostic impact on biochemical disease-free survival (bNEDs) of histologic confirmation of the local failure was evaluated retrospectively. Results: In the 40 patients with pre-RT PSA

Purpose: To evaluate the clinical benefit deriving from early (within 6 months) radiotherapy (ERT) after pelvic lymphadenectomy and radical retropubic prostatectomy for localized/locally advanced adenocarcinoma of the prostate in a single-institution series. Methods and Materials: We retrospectively analyzed 415 patients who underwent pelvic lymphadenectomy and radical retropubic prostatectomy between 1986 and 1998 for pT2b-pT4, pN0-pN1 prostate carcinoma. Of the 415 patients, 237 underwent ERT for adverse pathologic findings and 178 patients did not receive RT or underwent salvage RT less than or equal to6 months (salvage or no RT [SNRT]). Results: After a median follow-up of 62 months, the 8-year actuarial freedom from biochemical, local and systemic failure, and cause-specific survival rate was 69% vs. 31% (p

BACKGROUND. Brain metastases (BM) are frequent sites of initial failure in patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing multi-modality treatments (MMT). New treatment and follow-up strategies are needed to reduce the risk of BM and to diagnose them early enough for effective treatment. METHODS. The incidence rate of BM as the first site of recurrence in 112 patients with LAD-NSCLC treated with the same MMT protocol was calculated. The influence of patient, disease, and treatment-related factors on the incidence of BM and on the time-to-brain recurrence (TBR) was analyzed. RESULTS. BM as the first site of failure was observed in 25 cases (22% of the study population and 29% of all recurrences). In 18 of those cases, the brain was the exclusive site of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was 29%. Central nervous system (CNS) recurrence was more common in patients younger than 60 years (P = 0.006) and in whom bulky (greater than or equal to 2 cm) mediastinal lymph nodes were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of age, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. CONCLUSIONS. Our study confirmed a high rate of BM in patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were isolated and occurred within 2 years of initial diagnosis. Age younger than 60 years was associated with an increased risk of BM and reduced TBR, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. Although our data require further validation in future studies, our results suggest that additional trials on prophylactic cranial irradiation and on intensive radiologic follow-up should focus on these high-risk populations. (C) 2002 American Cancer Society.

Docetaxel has been implicated as a causative agent in peripheral neuropathy, but pathological changes in peripheral nerve have not been described. During docetaxel treatment a 54-year-old man developed a sensorimotor polyneuropathy when the overall docetaxel dosage was 540 mg/m(2). Neurophysiological investigation revealed a sensorimotor axonal neuropathy. Fascicular sural nerve biopsy showed an axonal neuropathy with a preferentially loss of large myelinated fibers. There was evidence of considerable fiber regeneration. Sensory and motor symptoms progressively improved after docetaxel withdrawal.

Primary cardiac sarcoma (PCS) is a rare disease with a poor prognosis, because of diagnostic delay, therapeutic difficulties, and high metastatic potential. Surgery is the standard treatment. A case of PCS in pregnancy is reported, with a review of published surgical series of PCSs, focusing on the role of surgery and adjuvant therapy. Prompt surgery improved cardiac function and patients' outcome in comparison with untreated cases. The role of adjuvant treatment was analyzed only in a few series, mainly without distinction between postoperative chemotherapy and radiotherapy; adjuvant therapy improved survival in the larger series of resected PCSs. Only three other cases of PCS in pregnancy were reported. In the present case, resection was performed with no major complication for the mother and the infant. Even if the patient's survival was short, cardiac surgery allowed prolonging of pregnancy until an acceptable possibility of fetal survival was reached. Although resection is not curative in most cases, surgery remains the treatment of choice for PCS and has a definite palliative significance. The role of postoperative chemotherapy and radiotherapy is difficult to ascertain; however, adjuvant chemotherapy seems advisable in high-grade tumors.

Background: Conformal radiotherapy requires reduced margins around the clinical target volume (CTV) with respect to traditional radiotherapy techniques. Therefore, high set-up accuracy and reproducibility are mandatory. Purpose: To investigate the effectiveness of two different immobilization techniques during conformal radiotherapy of prostate cancer with small fields. Materials and methods: 52 patients with prostate cancer were treated by conformal three- or four-held techniques with radical or adjuvant intent between November 1996 and March 1998. In total, 539 portal images were collected on a weekly basis for at least the first 4 weeks of the treatment on lateral and anterior Is MV X-ray fields. The average number of sessions monitored per patient was 5.7 (range 4-10). All patients were immobilized with an alpha-cradle system; 25 of them were immobilized at the pelvis level (group A) and the remaining 27 patients were immobilized in the legs (group B). The shifts with respect to the simulation condition were assessed by measuring the distances between the same bony landmarks and the held edges. The global distributions of cranio-caudal (CC), posterior-anterior (PA) and left-right (LR) shifts were considered; for each patient random and systematic error components were assessed by following the procedure suggested by Bijhold et al. (Bijhold J, Lebesque JV, Hart AAM, Vijlbrief RE. Maximising set-up accuracy using portal images as applied to a conformal boost technique for prostatic cancer. Radiother. Oncol. 1992;24:261-271). For each patient the average isocentre (3D) shift was assessed as the quadratic sum of the average shifts in the three directions. Results: Group B showed a better accuracy and reproducibility than group A for PA shifts (2.6 versus 4.4 mm, 1 SD), LR shifts (2.4 versus 3.6 mm, 1 SD) and CC shifts (2.7 versus 3.3 mm, 1 SD). Furthermore, group B showed a rate of large PA shifts (>5 mm) equal to 4.4% with respect to the 21.6% of group A (P < 0.0001). This value was also better than the corresponding value found in a previously investigated group of 21 non-immobilized patients (Italia C, Fiorino C, Ciocca M, et al. Quality control by portal film analysis of the conformal radiotherapy of prostate cancer: comparison between two different institutions and treatment techniques (abstract). Radiother. Oncol. 1997;43(Suppl. 2):S16, 16.8%, P = 0.001). For both groups there was no clear prevalence of one component (systematic or random) with respect to the other. The average isocentre shifts (averaged on all patients) were 3.0 mm (+/-1.4 mm, I SD) for group B and 5.0 mm (+/-2.8 mm, 1 SD) for group A against a value of 4.4 mm (+/-2.4 mm, I SD) for the previously investigated non-immobilized patient group. Conclusions: Immobilization of the legs with an alpha-cradle system seems to improve both the accuracy and reproducibility of the positioning of patients treated for prostate cancer with respect to alpha-cradle pelvic-abdomen immobilization. Based on these data, we decided to use the legs immobilization system and to reduce the margin around the CTV (from 10 to 8 mm) in the PA direction. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

Aims and background Accuracy and reproducibility of patient setup during radiotherapy for prostate cancer were investigated in two different Institutions (A and B), within their Quality Assurance programs. The purpose of the study was to evaluate and compare setup accuracy and reproducibility in Institutions A and B, which adopt different patient positioning and treatment techniques for prostate irradiation. Materials and methods A retrospective analysis of portal localization films taken during the treatment course was performed: 30 and 21 patients in Institutes A and B, respectively, entered the study. In Institute A, patients were treated in a prone position, utilizing an individualized immobilization cast (either an alpha cradle or a heat and vacuum-formed cellulose acetate cast) with an open table top and individual abdominal wall compressor to minimize small bowel irradiation; a 5-field conformal technique was used. In Institute B, patients were treated in a supine position without any immobilization device; a 6-field BEV-based technique (conformal only for patients treated with a radical aim) was adopted. A total of 598 portal films (420 from Institute A and 178 from Institute B) were analyzed. The mean number of films per patient was 12 (range, 4-29). Systematic and random setup errors were estimated utilizing the statistical method suggested by Bijhold et al. (1992). Results When patients with a mean (systematic) error larger than 5, 8 and 10 mm in craniocaudal, lateral and posterior-anterior directions, respectively, were compared, no statistically significant difference between the two groups was observed. Similarly, when comparing portal films, a significant difference ( P 5 mm: Institute A = 24%; Institute B = 11%). In both Institutes, the SD of random and systematic error distribution ranged from 1.8 to 4.2 mm, with a small prevalence of systematic errors. Only for craniocaudal shifts in Institute A was the random error larger than the systematic error, and it was significantly worse than in Institute B (1 SD, 4.2 mm in Institute A vs 1.8 mm in Institute B). Conclusions Setup errors observed in Institutes A and B were similar and in accord with data reported in the literature. In Institute B, satisfactory geometrical treatment quality was achieved without patient immobilization. In Institute A, the goal of minimizing small bowel irradiation and prostate motion through the aforementioned technique, which makes patient position less comfortable, did not seem to considerably increase daily setup uncertainty.

Background and purpose : The effect of random set-up errors on tumor control probability (TCP) and rectum complication probability (NTCP) on 3D conformal treatment planning of prostate cancer has been investigated by applying the convolution method originally proposed by Leong (Leong, J. Implementation of random positioning error in computerized radiation treatment planning systems as a result of fractionation. Phys. Med. Biol. 32: 327–334, 1987). Materials and methods : The combined influence of the standard deviation of the random shifts probability distribution (σ) of the dose and of the Beam's-eye-view margin ( M ) between the clinical target volume (CTV) and the edge of the blocks have been investigated in two patients. Results and conclusions : Random set-up error has been found to decrease TCP (for a typical 70 Gy CTV mean dose) by up to 6% for a 1 cm margin ( σ = 7 mm). When M is equal to or larger than 1.5 cm, no relevant effects on TCP are obtained. Maximum acceptable TCP values (corresponding to a rectum NTCP equal to 5%) have been derived and the dependence on σ and M has been investigated.

Aims and BackgroundNeoadjuvant systemic chemotherapy in infiltrating transitional cell carcinoma of the bladder has proved to be effective and to provide a pathologic complete response in about 30% of patients. No survival benefit has yet been proved.MethodsWe analyzed the outcome of 75 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0) treated from 1985 to 1993 at two institutions in the same geographic area with 2 or 3 cycles of neoadjuvant CMV (cisplatin, methotrexate and vinblastine) chemotherapy plus cystectomy. Transurethral resection of the tumor was expressly avoided in order to keep the tumor intact as a marker lesion to evaluate response to chemotherapy.ResultsAt the time of analysis, the median follow-up of 67 assessable patients was 51.5±3.9 (SE) months. Forty-six patients (69%) had clinical evidence of extravesical spread of the bladder tumor and 6 of lymph node metastases at presentation. After cystectomy, a pathologic complete response (pT0, pN0) was achieved in only 6 cases (9%) and a pathologic partial response in 32 patients (48%). The overall 5-year survival rate of all patients was 61 ±6%. Those patients who had a major response to chemotherapy (pCR + pPR) had a 5-year disease-free survival rate of 74%, which was statistically higher (P=0.0021) than the 44% for the remaining nonresponding patients (pNR). Overall, 43% of the patients with stage T2-T3a disease achieved tumor downstaging (CR, 5%; PR, 38%) compared with 63% of the patients with T3b-T4 (CR, 11%; PR, 52%), although there was no significant difference in 5-year survival curves between the two groups.ConclusionsA pathologic complete response was achieved in less than 10% of the cases without a preoperative tumor resection. Unfortunately, most of the responses were only partial. Even though the study appears to suggest a survival advantage for those patients who achieved a downstaging, CMV chemotherapy had a limited curative potential in most of the patients. It seems unlikely that determinant proof will be obtained that neoadjuvant chemotherapy may improve survival over a nontreatment control arm. The intrinsic chemoresistance or the suboptimal response to chemotherapy of bladder cancer remains the most adverse prognostic factor.

A retrospective series of 13 immunocompetent patients with histological diagnosis of primary central nervous system lymphoma (PCNSL) is presented. The series was divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7 patients treated with chemotherapy and radiotherapy. Clinicopathological patterns were similar for the two groups. In Group A, 4 patients achieved complete remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died within 21 months of diagnosis. 4 Group B patients received chemotherapy followed by radiotherapy, and three who received a methotrexate-containing regimen are alive and disease-free at 34, 42 and 45 months, while the fourth died after 11 months. The other 3 subjects in this group were treated with radiotherapy followed by chemotherapy, and died within 15 months of diagnosis. Although radiotherapy is the standard treatment, chemotherapy has potentially an important role in the management of PCNSL. The sequence of combined treatment could be crucial to improvement of outcome.