Cumulative intracranial tumour volume prognostic assessment: a new predicting score index for patients with brain metastases treated by stereotactic radiosurgery.

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.

Safety and efficacy of multisession gamma knife radiosurgery for residual or recurrent pituitary adenomas.

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 cm3. The mean tumor volume at last follow-up was 2.11 cm3, 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 for glomus tumors: Long-term results in a series of 30 patients.

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.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

PURPOSE: The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. METHODS: We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. RESULTS: There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8 year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3 cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3 Gy. During a mean follow-up of 74.6 ± 8.4 months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. CONCLUSIONS: GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.

Effectiveness of Gamma Knife Radiosurgery in Improving Psychophysical Performance and Patient's Quality of Life in Idiopathic Trigeminal Neuralgia.

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.

Predictors of radio-induced visual impairment after radiosurgery for uveal melanoma.

AIMS: The 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 METHODS: Medical 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. RESULTS: The 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. CONCLUSIONS: We 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.

Gamma Knife Radiosurgery for Low-Grade Gliomas: Clinical Results at Long-Term Follow-Up of Tumor Control and Patients' Quality of Life.

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 cm3, 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.

Gamma Knife Radiosurgery for Residual and Recurrent Vestibular Schwannomas After Previous Surgery: Clinical Results in a Series of 90 Patients and Review of the Literature.

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 cm3 (median, 2.5 cm3; range, 0.027-13 cm3) 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.

Frequency, pattern, and outcome of recurrences after gamma knife radiosurgery for pituitary adenomas.

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.

Gamma Knife Radiosurgery as Primary Treatment for Large Vestibular Schwannomas: Clinical Results at Long-Term Follow-Up in a Series of 59 Patients.

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.

Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dosimetric factors associated with pituitary function after Gamma Knife Surgery (GKS) of pituitary adenomas.

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 >6 months. The diagnosis was nonfunctioning pituitary adenoma (NFPA) in 68 patients and secreting pituitary adenoma (SPA) in 62 patients. Median margin dose was 15/25 Gy for NFPA and SPA, respectively. The endocrinological median follow-up was 60 months. 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 15.7 Gy, 7.3 Gy and 1.4 cm(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.

Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients.

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 <.0001 in both cases), and hypertension (p = .02) and whole-pelvis radiotherapy (p = .02) correlated significantly in the adjuvant cohort only. The variables predictive of late Grade 3 sequelae were acute Grade 2 or greater toxicity in both groups and whole-pelvis radiotherapy (8-year risk of Grade 3 events, 21% vs. 11%, p = .007), hypertension (8-year risk, 18% vs. 10%, p = .005), age ≤ 62 years at RT (8-year risk, 16% vs. 11%, p = .04) in the adjuvant subset, and radiation dose >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.

Gamma knife radiosurgery for treatment of cerebral metastases from non-small-cell lung cancer.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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 volume >5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression. CONCLUSIONS: 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.

Inflammatory pseudotumor of mediastinum treated with tomotherapy and monitored with FDG-PET/CT: case report and literature review.

Mediastinal inflammatory pseudotumor is a rare disease with reactive pseudoneo-plastic features and a proven capacity for local invasion. The radiographic appearance of inflammatory pseudotumor is quite non-specific and the definitive diagnosis is based on the histological evaluation of tissue specimens. Resection of the lesion is the treatment of choice. However, nonsurgical treatments such as radiotherapy and steroids have been employed in the setting of incomplete surgical resection, tumor recurrence, and patients being unfit for surgery. The case described here is being reported because of the rare mediastinal location and atypical treatment approach including salvage irradiation and monitoring with FDG-PET/CT. Because of the irregular target volume inside the mediastinum as defined by FDG-PET/CT and the significant pulmonary comorbidity, it was deemed necessary to optimize dose delivery with intensity-modulated radiation therapy (IMRT). A possible gain by means of daily control of patient setup with image-guided radiation therapy was also hypothesized and we used tomotherapy to irradiate the lesion. The first FDG-PET/CT after treatment confirmed further reduction of the metabolic activity followed by stable disease in the mediastinum, with no new occurrence of disease 16, 24 and 30 months after tomotherapy.

Need for high radiation dose (>or=70 gy) in early postoperative irradiation after radical prostatectomy: a single-institution analysis of 334 high-risk, node-negative patients.

PURPOSE: To determine the clinical benefit of high-dose early adjuvant radiotherapy (EART) in high-risk prostate cancer (hrCaP) patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy. PATIENTS AND METHODS: The clinical outcome of 334 hrCaP (pT3-4 and/or positive resection margins) node-negative patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy before 2004 was analyzed according to the EART dose delivered to the prostatic bed, <70.2 Gy (lower dose, median 66.6 Gy, n = 153) or >or=70.2 Gy (median 70.2 Gy, n = 181). RESULTS: The two groups were comparable except for a significant difference in terms of median follow-up (10 vs. 7 years, respectively) owing to the gradual increase of EART doses over time. Nevertheless, median time to prostate-specific antigen (PSA) failure was almost identical, 38 and 36 months, respectively. At univariate analysis, both 5-year biochemical relapse-free survival (bRFS) and disease-free survival (DFS) were significantly higher (83% vs. 71% [p = 0.001] and 94% vs. 88% [p = 0.005], respectively) in the HD group. Multivariate analysis confirmed EART dose >or=70 Gy to be independently related to both bRFS (hazard ratio 2.5, p = 0.04) and DFS (hazard ratio 3.6, p = 0.004). Similar results were obtained after the exclusion of patients receiving any androgen deprivation. After grouping the hormone-naïve patients by postoperative PSA level the statistically significant impact of high-dose EART on both 5-year bRFS and DFS was maintained only for those with undetectable values, possibly owing to micrometastatic disease outside the irradiated area in case of detectable postoperative PSA values. CONCLUSION: This series provides strong support for the use of EART doses >or=70 Gy after radical retropubic prostatectomy in hrCaP patients with undetectable postoperative PSA levels.

Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy.

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.

Evaluation of different score index for predicting prognosis in gamma knife radiosurgical treatment for brain metastasis.

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.

Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis.

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 >or= 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.

Adenoid cystic carcinoma of trachea treated with adjuvant hypofractionated tomotherapy. Case report and literature review.

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.