Prostate-specific antigen nadir within 1 year of radiotherapy combined with hormone therapy predicts cancer-specific mortality and biochemical recurrence-free survival in prostate cancer patients.

BACKGROUND: In this study, we investigated the ability of prostate-specific antigen (PSA) 12 months after (nPSA12) external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) to predict biochemical recurrence-free survival (BRFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) in intermediate- and high-risk prostate cancer patients. METHODS: We retrospectively reviewed the clinical data of 338 intermediate- and high-risk prostate cancer patients treated with EBRT with ADT at our institution between 2000 and 2018. The median radiation dose was 76 Gy, the median initial PSA level was 17 ng/mL (range, 1-228 ng/mL), and the median duration of ADT was 24 months (range, 6-167 months). The median PSA level 1 months after EBRT was 0.06 ng/mL (range, 0-25.6 ng/mL). Univariate and multivariate analyses were performed. Patient survival was assessed using the Kaplan-Meier method and Cox proportional hazards regression analyses. RESULTS: The median follow-up time was 5 years (range, 1-20 years). Multivariate analysis revealed that nPSA was an independent and significant factor associated with OS, PCSM, and BRFS (P = 0.008, P = 0.001, P = 0.04). Furthermore, the time to nPSA12 was an independent predictor of PCSM and BRFS (P = 0.042, P = 0.021). Pelvic irradiation was also significantly associated with worse OS and PCSM (P = 0.004, P = 0.01). Additionally, age (≤ 70 or > 70 years) and hormone therapy duration (6 months, 1-3 years, or > 3 years) were significantly associated with OS and PCSM, respectively (P = 0.004, P = 0.02). For high risk, nPSA and nPSA12 were an independent predictor for BRFS. (P = 0.021, P = 0.029) CONCLUSION: The nPSA12 level of > 0.06 ng/mL may independently predict worse PCSM and BRFS in intermediate- and high-risk prostate cancer patients undergoing EBRT and ADT. Additionally, for high risk, nPSA > 0.06 ng/mL and nPSA12 > 0.06 ng/mL may independently predict worse BRFS.

Long-term results of gamma knife radiosurgery for foramen magnum meningiomas.

Outcomes of 37 patients of foramen magnum meningioma (FMM) were evaluated, and the related literature was reviewed to determine the efficacy of Gamma Knife radiosurgery (GKRS) for treating patients with FMM. We present the largest series reported from a single institution with the longest follow-up to date. The database of patients who underwent GKRS for FMM between 2007 and 2019 was evaluated retrospectively. A total of 37 patients with radiological and pathological features consistent with FMM were included in this series. Thirty-three patients were female, and 4 were male. The median age was 58 years (range, 23-74 years). The most common symptom at diagnosis was headache (64.9%). Twelve patients had a history of microsurgical resection. The median duration from the initial onset of symptoms to GKRS was 12 months (range 1-140 months). Among the 37 tumors, eight (21.6%) were located ventrally, 24 (64.9%) laterally, and five (13.5%) dorsally. The median target volume was 3.30 cm3 (range, 0.6-17.6 cm3). Thirty-five patients (95%) were treated with single fraction GKRS, and two patients (5%) were treated with hypofractionated GKRS. The median clinical follow-up was 80 months (range, 18-151 months), while the median radiological follow-up was 84 months (range, 18-144 months). At the last clinical follow-up after GKRS, 27 patients (73%) had improved symptoms, and none had worsened pre-GKRS symptoms. At the last radiological follow-up after GKRS, 23 tumors (62.2%) remained stable, 13 (35.1%) decreased in size, and 1 (2.7%) increased in size. Tumor control, including stable and regressed tumors, was achieved in 97.3% of patients. Our cohort demonstrates that GKRS is an effective and safe treatment for patients with either primary or recurrent/residual FMM.

Hormonal and radiologic outcomes after gamma knife radiosurgery for nonfunctioning pituitary adenomas.

BACKGROUND: Gamma knife radiosurgery (GKRS) is an established treatment option for residual and recurrent nonfunctioning pituitary adenoma (NFPA). This investigation assessed hormonal and radiologic outcomes after adjuvant and primary GKRS for NFPAs. METHODS: This retrospective study included 252 patients with NFPA who underwent GKRS at a single center between 2005 and 2016. GKRS was performed as adjuvant procedure in 216 (85.8%) patients and as primary procedure in 36 (14.2%) patients. Characteristics of these two groups were compared. RESULTS: Mean age was comparable between adjuvant and primary GKRS groups (48.3 ± 12.6 vs. 52.2 ± 13.2 years, respectively, p > 0.05). Adjuvant GKRS and primary GKRS groups were similar in terms of the mean prescribed radiation dose and tumor volume (15.1 ± 2.7 vs. 15.3 ± 1.9 Gy and 4.2 ± 3.6 vs. 3.1 ± 2.5 cm3, respectively, p > 0.05 for both). The rate of endocrine deficiency during 5-year follow-up showed similar trend in adjuvant and primary GKRS groups (3.7%, 8.7%, and 14.8% vs. 5.6%, 13.9%, and 27.8% at first, third, and fifth year time points, respectively). Tumor control rates were also similar (98.6%, 96.3%, and 93% vs. 100%, 97.3%, and 94.5% at first, third, and fifth year time points, respectively). In both groups, tumor volume >5 cm3 was associated with higher rate of hypopituitarism and tumor progression. CONCLUSIONS: GKRS was effective both as adjuvant and primary procedure in patients with NFPA. Radiation dose of ≤13.5 Gy was associated with lower tumor control rate and tumor volume >5 cm3 was associated with higher rates of hypopituitarism and tumor progression.

Integration of arterial spin labeling into stereotactic radiosurgery planning of cerebral arteriovenous malformations.

PURPOSE: To test whether the combined use of 4D arterial spin labeling angiography (4D ASL) and contrast-enhanced magnetic resonance angiography (4D CE-MRA) can work as a prospective alternative to digital subtraction angiography (DSA) for the delineation of the arteriovenous malformation (AVM) nidus in stereotactic radiosurgery (SRS) planning. MATERIALS AND METHODS: A custom 4D ASL sequence and a proof-of-concept software tool to integrate 4D ASL data to SRS planning were implemented. Ten AVM patients were scanned at 3T. Two observers independently contoured niduses in two separate sessions. Reference niduses were contoured using DSA, 4D ASL, and 4D CE-MRA. Test niduses were contoured using 4D ASL and 4D CE-MRA only. Reference and test niduses from both observers were compared in terms of volume, distance between centers of volumes (dCOV), and the Jaccard index (JI). RESULTS: In volume comparisons, excellent intraobserver and interobserver agreements were obtained (intraclass correlation coefficients: 0.99 and 0.98, respectively). Median dCOV, JIs between reference and test niduses were 0.55 mm, 0.78 for Observer 1 and were 0.6 mm, 0.78 for Observer 2. None of the dCOV and JI parameters varied significantly among the delineation methods or the observers (P = 0.84, P = 0.39). CONCLUSION: Our preliminary results indicate that reproducibility of the target volumes with high agreement levels is achievable without using DSA. The combined use of high temporal resolution 4D ASL and high spatial resolution and vessel-to-background contrast 4D CE-MRA provided sufficient spatiotemporal angiographic information for the delineation of AVM niduses. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1718-1727.

Treatment of brainstem metastases with gamma-knife radiosurgery.

The aim was to investigate the efficacy and safety of gamma-knife stereotactic radiosurgery (SRS) for treating brainstem metastases. The cases of 44 patients who underwent SRS as treatment for 46 brainstem metastases were retrospectively evaluated. The median age was 57 years (range 42-82 years) and the median Karnofsky performance score (KPS) was 80 (range 60-90). The primary tumor was lung carcinoma in 28 cases, breast carcinoma in 7 cases, colon carcinoma in 3 cases, renal cell carcinoma in 3 cases, malignant melanoma in 1 case, and unknown origin in 2 cases. Of the 46 metastases, 30 were in the pons, 14 were in the mesencephalon, and 2 were in the medulla oblongata. The median volume of the 46 metastases was 0.6 cc (range 0.34-7.3 cc). The median marginal dose of radiation was 16 Gy (range 10-20 Gy). Twenty-three patients (52 %) received whole brain radiotherapy prior to SRS, and 6 (14 %) received this therapy after SRS. In the remaining 15 cases (34 %), SRS was applied as the only treatment. Recursive partitioning analysis, graded prognostic assessment, and basic score for brain metastases were used to predict survival time. Local control was achieved for all but two of the 46 metastases (96 %). The overall survival time after SRS was 8 months. Female gender, KPS >70, mesencephalon tumor location, and response to treatment were associated with longer survival. Basic score for brain metastases class I and recursive partitioning analysis classification were associated with better prognosis. Peri-tumoral changes were detected radiologically at 2 (4 %) of the metastatic lesion sites but neither of these patients exhibited symptoms. Gamma-knife radiosurgery is effective for treating brainstem metastases without a higher risk for radiation necrosis.

Magnetic Resonance Imaging-Guided Stereotactic Body Radiation Therapy for Medically Inoperable Endometrial Cancer.

Endometrial carcinoma is the most frequently diagnosed gynecological cancer among women aged 50 and older in developed countries. In patients who are not amenable to surgery, radiotherapy results in improved survival with acceptable adverse effect profiles. Definitive stereotactic body radiotherapy (SBRT) as a monotherapy remains an unaddressed concept in the literature. Here, we present the case of an 86-year-old woman who was diagnosed with early-stage endometrial carcinoma and was medically inoperable due to cardiac comorbidities. She was treated with magnetic resonance imaging-guided online adaptive radiotherapy-based SBRT. She tolerated the treatment well, with mild increased vaginal discharge. Complete metabolic and radiological responses were obtained. She continues to be disease free in the first year of treatment with no long-term side effects. Our protocol presents promising results with a safe toxicity profile for inoperable early-stage endometrial cancer. Future studies are warranted in light of the current knowledge.

Efficacy of whole-sellar gamma knife radiosurgery for magnetic resonance imaging-negative Cushing's disease.

BACKGROUND: Corticotroph adenoma delineation in Cushing's disease (CD) patients with previous surgery can be challenging. This study investigated the outcome of whole-sellar gamma knife radiosurgery (GKRS) in MRI-negative, but hormone-active CD patients with prior failed treatment attempts. METHODS: We retrospectively analyzed data of nine CD cases who underwent whole-sellar GKRS between April 2008 and April 2020 at a single center. Remission was determined as normal morning serum cortisol, normal 24-hour urinary free cortisol (UFC) or extended postoperative requirement for hydrocortisone replacement. RESULTS: Median age was 35.0 years, and most of the cases were female (89%). All subjects had undergone previous surgery. The mean pre-GKRS morning serum cortisol and 24-hour UFC were 27.5 µg/dL and 408.0 µg, respectively. Target volume varied from 0.6 to 1.8 cc, and the median margin dose was 28 Gy. The median duration of endocrine follow-up was 105 months, and initial endocrine remission was achieved in eight subjects (89%) at a median time of 22 months. The actuarial initial remission was 44% at two years, 67% at four years, and 89% at six years. The mean recurrence-free survival was 128 months. Age and pre-GKRS morning serum cortisol was found to be predictors for initial and durable endocrine remissions. New-onset hypopituitarism was observed in two of five patients (40%). None of the patients developed new neurological deficits and had GKRS-related adverse events during the follow-up. CONCLUSIONS: Whole-sellar GKRS is a safe and efficient method to manage MRI-negative CD and provides similar GKRS outcome rates as in MRI-positive CD.

Gamma knife radiosurgery for jugular foramen schwannomas.

Jugular foramen schwannomas are very rare tumors. Advances in skull base surgery have led to more aggressive resection of these tumors, but surgery may associate with development of new neurological deficits. In this report, we analyze the long-term results for 17 patients with newly diagnosed or residual/recurrent jugular foramen schwannoma who underwent gamma-knife treatment. During a mean 64 months of follow-up, magnetic resonance imaging revealed reduced tumor size in 13 cases and no size change in four cases. The tumor growth control rate was 100% and only one patient had transient hoarseness. For patients who have small- to moderate-sized jugular foramen schwannomas, gamma-knife radiosurgery is associated with good tumor control and carries minimal risk of adverse radiation effects.

Limited field adaptive radiotherapy for glioblastoma: changes in target volume and organ at risk doses.

OBJECTIVE: This study aimed to investigate the tumor volume changes occurring during limited-field radiotherapy (RT) for glioblastoma patients and whether a volume-adapted boost planning approach provided any benefit on tumor coverage and normal tissue sparing. MATERIALS AND METHODS: Twenty-four patients underwent simulation with magnetic resonance (MR) and computed tomography (CT) scans prior to RT (MR_initial, CT_initial) and boost treatment (MR_adapt, CT_adapt). For the boost phase, MR_initial and MR_adapt images were used to delineate GTV2 and GTV2_adapt, respectively. An initial boost plan (Plan_initial) created on CT_initial for PTV2 was then reoptimized on CT_adapt by keeping the same optimization and normalization values. Plan_adapt was generated on CT_adapt for PTV2_adapt volume. Dose volume histogram parameters for target volumes and organs-at-risk were compared using these boost plans generated on CT_adapt. Plan_initial and Plan_adaptive boost plans were summed with the first phase plan and the effect on the total dose was investigated. RESULTS: Target volume expansion was noted in 21% of patients while 79% had shrinkage. The average difference for the initial and adaptive gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) volumes were statistically significant. Maximum dose differences for brainstem and optic chiasm were significant. Healthy brain tissue V10 and ipsilateral optic nerve maximum doses were found to decrease significantly in Plan_adaptive. CONCLUSION: Results of this study confirm occurrence of target volume changes during RT for glioblastoma patients. An adaptive plan can provide better normal tissue sparing for patients with lesion shrinkage and avoid undercoverage of treatment volumes in case of target volume expansion especially when limited-fields are used.

The effect of tumor shape irregularity on Gamma Knife treatment plan quality and treatment outcome: an analysis of 234 vestibular schwannomas.

The primary aim of Gamma Knife (GK) radiosurgery is to deliver high-dose radiation precisely to a target while conforming to the target shape. In this study, the effects of tumor shape irregularity (TSI) on GK dose-plan quality and treatment outcomes were analyzed in 234 vestibular schwannomas. TSI was quantified using seven different metrics including volumetric index of sphericity (VioS). GK treatment plans were created on a single GK-Perfexion/ICON platform. The plan quality was measured using selectivity index (SI), gradient index (GI), Paddick's conformity index (PCI), and efficiency index (EI). Correlation and linear regression analyses were conducted between shape irregularity features and dose plan indices. Machine learning was employed to identify the shape feature that predicted dose plan quality most effectively. The treatment outcome analysis including tumor growth control and serviceable hearing preservation at 2 years, were conducted using Cox regression analyses. All TSI features correlated significantly with the dose plan indices (P < 0.0012). With increasing tumor volume, vestibular schwannomas became more spherical (P < 0.05) and the dose plan indices varied significantly between tumor volume subgroups (P < 0.001 and P < 0.01). VioS was the most effective predictor of GK indices (P < 0.001) and we obtained 89.36% accuracy (79.17% sensitivity and 100% specificity) for predicting PCI. Our results indicated that TSI had significant effects on the plan quality however did not adversely affect treatment outcomes.

Dosimetric evaluation of VMAT and helical tomotherapy techniques comparing conventional volumes with clinical target volumes based on new ESTRO ACROP post-mastectomy with immediate implant reconstruction contouring guidelines.

BACKGROUND: The ESTRO-ACROP Consensus Guideline (EACG) recommends implant excluded clinical target volume (CTVp) definitions for post-mastectomy radiation therapy after implant-based immediate breast reconstruction (IBR). The purpose of this study is to investigate the effectiveness of Helical Tomotherapy (HTp) and Volumetric Modulated Arc Therapy (VMATp) treatment techniques in terms of CTVp coverage and reduced organ at risk (OAR), normal tissue and implant doses when CTVp was used for treatment planning as the target structure instead of conventional CTV. METHODS: Eight left-sided and eight right-sided breast cancer patients who underwent IBR after mastectomy were included in this study. Planning CT data sets were acquired during free breathing and patients were treated with HT technique targeted to conventional CTV. Retrospectively, CTVp was delineated based on EACG by the same radiation oncologist, and treatment plans with HTp and VMATp techniques were generated based on CTVp. For each patient, relevant dosimetric parameters were obtained from three different treatment plans. RESULTS: There was no statistically significant difference on target coverage in terms of, PTVp-D95, PTVp-Vpres, homogeneity index (p > 0.05) between HTp and VMATp plans. But, the conformity numbers were significantly higher (HTp vs VMATp, 0.69 ± 0.15 vs 0.79 ± 0.12) for VMATp (Z = - 2.17, p = 0.030). While HTp significantly lowered Dmax and Dmean for LAD (LAD-Dmax: χ2 = 12.25, p = 0.002 and LAD-Dmean: χ2 = 12.30, p = 0.002), neither HTp nor VMATp could reduce maximum and mean dose to heart (p > 0.05). Furthermore, heart volume receiving 5 Gy was significantly higher for VMATp when compared to HTp (21.2 ± 9.8 vs 42.7 ± 24.8, p: 0.004). Both techniques succeeded in reducing the mean dose to implant (HTp vs HT, p < 0.001; VMATp vs HT, p < 0.001; VMATp vs HTp, p = 0.005). CONCLUSION: Both HTp and VMATp techniques succeeded to obtain conformal and homogeneous dose distributions within CTVp while reducing the mean implant dose. HTp was found to be superior to VMATp with regards to lowering all OAR doses except for CB.

Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma.

The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.

Gamma knife radiosurgery for high-risk lactotroph adenomas: Long-term results.

Gamma Knife radiosurgery (GKRS) for lactotroph adenomas (LAs) or prolactinomas is limited due to the effectiveness of medical treatments and surgery. Cases who are refractory to medical treatment and/or surgery may be managed with GKRS. We aimed to describe the effectiveness of GKRS for high-risk lactotroph adenomas (HRLAs) and LAs that were medically and surgically refractory. We analyzed our series of patients with HRLAs and LAs who were managed with GKRS following failed medical treatment and surgery and who had at least three years of follow-up. A total of 52 patients (22 HRLAs and 30 LAs) were included in the analysis of radiological, endocrine, and clinical outcomes. Radiological control was achieved in 68.2% of subjects in the HRLA group and 96.7% of subjects in the LA group. Hormonal control was achieved in 68.2% of patients in the HRLA group and 80% of patients in the LA group. On univariate analysis, hormonal control was significantly associated with pre-treatment volume (p = 0.007), higher margin dose (p = 0.002) and Ki-67 proliferative index (p = 0.007). Complications involved new pituitary hormone deficiencies in 19.2% of patients and asymptomatic peripheral visual field defect in 1.9% of patients. To the best of our knowledge, this is the first study to examine the effectiveness of GKRS in LAs and HRLAs, with the highest median follow-up in the literature. High hormonal control rate, even in HRLAs, and lower complication rates suggest that GKRS should be part of the techniques for managing treatment refractory LAs.

Stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic patients: initial clinical experience.

PURPOSE: We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic disease. MATERIALS AND METHODS: Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits. RESULTS: The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course. CONCLUSION: SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity.

OBJECTIVE: Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response. METHODS: 50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. RESULTS: The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. CONCLUSION: In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. ADVANCES IN KNOWLEDGE: MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.

Is prophylactic breast radiotherapy necessary in all patients with prostate cancer and gynecomastia and/or breast pain?

PURPOSE: We investigated the efficacy of prophylactic radiotherapy for gynecomastia/breast pain induced by 150 mg bicalutamide in a prospective, randomized, multi-institutional trial. MATERIALS AND METHODS: After definitive treatment for localized prostate cancer 125 patients were randomized to 12 Gy radiotherapy before bicalutamide as prophylactic radiotherapy (53) or bicalutamide only for nonprophylactic radiotherapy (72). The incidence of gynecomastia, breast pain and tenderness, and discomfort perceived by the patients was assessed by physical examination and direct questioning at 3, 6 and 12 months of followup. RESULTS: At the end of 12 months the gynecomastia rate was 15.8% in the prophylactic group and 50.8% in the nonprophylactic group (p <0.001). On patient evaluation the breast enlargement rate was 34.4%. The severity of breast pain and tenderness was not different between the groups. The breast pain rate was 36.4% and 49.2% by 12 months in the prophylactic and nonprophylactic groups, and the rate of patients who felt discomfort from gynecomastia was 11.4% and 29.5%, respectively. CONCLUSIONS: In this prospective study the incidence of gynecomastia was not as high as previously believed. Although prophylactic breast irradiation seemed to decrease the gynecomastia rate in patients on 150 mg bicalutamide, our study proves that not all patients need prophylaxis since only 52% were significantly bothered by gynecomastia. Thus, individual assessment is needed to select patients who need prophylactic radiation while on 150 mg bicalutamide.

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study.

INTRODUCTION: In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated. MATERIALS AND METHODS: Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated. RESULTS AND CONCLUSION: No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.

Long-term results of Gamma Knife radiosurgery for facial nerve schwannomas.

OBJECTIVE: Long-term outcomes of eleven cases of facial nerve schwannoma were evaluated and the related literature was reviewed to determine the efficacy of Gamma Knife radiosurgery for treating patients with facial nerve schwannoma. METHODS: Eleven patients with facial nerve schwannoma (7 women and 4 men; mean age, 44.2 years; range, 19-73 years) underwent Gamma Knife radiosurgery. The most common symptoms were facial palsy (n = 10) and hearing loss (n = 7). Five patients presented with headache. Two patients had undergone prior resection. The patients' clinical and radiographic data were evaluated retrospectively. RESULTS: For the 11 cases of facial nerve schwannoma, mean tumor volume was 3.1 cm3 (range, 0.4-7.4 cm3) and the mean marginal dose applied was 11.9 Gy (range, 11-13 Gy). The mean follow-up period was 84.3 months (range, 66-117 months). Tumor control was achieved in all patients. At the time of writing, four patients experienced tumor volume regression and the other seven were in stable condition. During follow-up, nine patients experienced no change in their facial function, two experienced deteriorated facial function, and none developed new facial palsy. Ten patients who had serviceable hearing prior to Gamma Knife radiosurgery retained their hearing. CONCLUSIONS: Gamma Knife radiosurgery achieves excellent results with respect to tumor control for 7 years on average. In addition, Gamma Knife radiosurgery provides good results in facial nerve and hearing function at long term. Our series demonstrates that Gamma Knife radiosurgery is an effective and safe treatment for patients with either primary or residual facial nerve schwannoma.

Efficacy of gamma knife radiosurgery in the treatment of intraventricular meningiomas.

Intraventricular meningiomas (IVMs) are notably limited tumors and express one of the most challenging tumors in neurosurgery. Gamma Knife radiosurgery (GKRS) as an alternative for IVMs has been reported only in a few case series. We aimed to present six patients with IVMs who were treated with GKRS and do a literature review. The data of patients were retrospectively reviewed. All patients underwent a single session of GKRS with a median marginal dose of 12 Gy (range, 11-13). Target volume ranged from 1.2 to 9.5 cc. Routine imaging with contrast-enhanced MRI scans was performed every six months initially and thereafter yearly. New neurological deficits and symptoms stated or observed during follow-up were recorded and investigated. The mean age was 41.3 years (range, 30-71). GKRS was used as a primary treatment in five patients and as adjunctive treatment in one patient. The most common presenting symptom was a headache. The median duration of symptoms was 30 months (range, 5-240). Four tumors (67%) were located in the left lateral ventricle, and two were in the right lateral ventricle. During a median follow-up of 71.5 months (range, 23-139), tumor volume was noted to have shrunk (median = 59.6%) in all patients (100%). One patient experienced post-GKRS peritumoral edema that resolved after a short course of steroids. The mean progression-free survival was 117.5 months (95% CI, 81-154 months). Neurologic symptoms and signs improved in all patients. GKRS may be a feasible treatment alternative in patients with small IVMs with low morbidity.

Lymph node ratio as an independent prognostic factor for breast cancer-related mortality in patients with node-positive breast cancer.

AIM: This study assessed whether prognostic information could be obtained in patients with lymph node (LN)-positive breast cancer based on their LN ratios (LNRs) and explored the relationships between other potential prognostic factors and survival. SETTING AND DESIGN: This was a retrospective clinical study. MATERIALS AND METHODS: This study included 608 women with node-positive nonmetastatic breast cancer. Clinical and pathologic data were retrospectively evaluated. The median age was 51 years (range: 23-84 years). All patients received adjuvant radiotherapy after radical surgery. A total dose of 50 Gy was administered to the chest wall or breast and LN regions with 2 Gy daily fractions. A 10-Gy boost was administered to the breast tumor bed. The cutoff value of LNR was defined as low risk (<0.21) in 278 patients, intermediate risk (0.21-0.65) in 217 patients, and high risk (>0.65) in 113 patients. Prognostic variables included patient characteristics, disease characteristics, and interventional factors. The primary endpoint was overall survival and the secondary endpoint was breast cancer-related mortality. STATISTICAL ANALYSIS USED: Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis. P value was required to be <0.05. RESULTS: Within a median follow-up period of 95.4 months (range: 5-232.4 months), overall survival rates for 10 and 15 years were 66% and 53%, respectively. Multivariate analysis revealed that LNR (P = 0.026), estrogen receptor status (ERS) (P = 0.021), age (P = 0.04), and smoking (P = 0.024) were independent significant prognostic factors for overall survival. Breast cancer-related mortality rates at 10 and 15 years were 70.7% and 60%, respectively. LNR (P = 0.03) and ERS (P = 0.002) were independent significant prognostic factors for breast cancer-related mortality. CONCLUSIONS: LNR and ERS were significant prognostic factors for survival at all endpoints.