Associations among parental and romantic attachment, personality disorder symptoms, and physical health.

The relations of parental and romantic attachment with physical health symptoms and the mediating role of personality disorder symptoms in those relations were examined in an online survey of US young adults. Latent class analysis identified two groups: occasionally sick and healthier. Insecure attachment was related to being occasionally sick and to personality disorder symptoms (poor reality testing, primitive defenses, and diffused identity). Primitive defenses/identity diffusion mediated relations between insecure parental attachment and physical symptoms. Maternal and paternal attachment each provided unique information about these relations. Romantic attachment was not associated with physical symptoms after adjusting for parental attachment and personality disorder symptoms.

AMP-activated protein kinase promotes human prostate cancer cell growth and survival.

The molecular mechanisms underlying the development and progression of prostate cancer are poorly understood. AMP-activated protein kinase (AMPK) is a serine-threonine kinase that is activated in response to the hypoxic conditions found in human prostate cancers. In response to energy depletion, AMPK activation promotes metabolic changes to maintain cell proliferation and survival. Here, we report prevalent activation of AMPK in human prostate cancers and provide evidence that inhibition or depletion of AMPK leads to decreased cell proliferation and increased cell death. AMPK was highly activated in 40% of human prostate cancer specimens examined. Endogenous AMPK was active in both the androgen-sensitive LNCaP cells and the androgen-independent CWR22Rv1 human prostate cancer cells. Depletion of AMPK catalytic subunits by small interfering RNA or inhibition of AMPK activity with a small-molecule AMPK inhibitor (compound C) suppresses human prostate cancer cell proliferation. Apoptotic cell death was induced in LNCaP and CWR22Rv1 cells at compound C concentrations that inhibited AMPK activity. The evidence provided here is the first report that the activated AMPK pathway is involved in the growth and survival of human prostate cancer and offers novel potential targets for chemoprevention of human prostate cancer.

Security amidst stigma: Exploring HIV and sexual minority stressors through an attachment-based psychotherapy group.

Despite strides in HIV prevention and lesbian, gay, bisexual, and transgender care, comprehensive care centers are of critical importance for lesbian, gay, bisexual, and transgender communities and people with HIV/AIDS who continue to contend with intersecting stigmas and chronic minority stressors. Building on the integrated attachment and sexual minority stress model, we discuss these themes by highlighting a group vignette from an urban psychiatric clinic that has provided affirmative psychotherapy to marginalized communities affected by HIV/AIDS for over 2 decades. The authors have rotated at the clinic as cofacilitators of a weekly, process-oriented group for sexual minority men who are HIV positive or are affected by HIV. In this article, we provide a theoretical foundation for HIV-affirming group psychotherapy and clinical integration of minority stress and attachment-based interventions. Group psychotherapy provides a rare opportunity to bond an often-isolated community by evoking factors of universality, cohesiveness, and catharsis. It simultaneously enables us to confront individual existential concerns with serostatus disclosure, grief, and feelings of victimization, as well as challenge internalized stigma and rejection sensitivity. We apply these issues to a verbatim clinical exchange, analyzing attachment-related themes and issues pertaining to minority stress and stigma, as well as discuss group mechanisms for attachment interventions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

A novel method to display [gal alpha1, 3 gal] antigens on human leukemic cells for preparation of anti-leukemia vaccines.

BACKGROUND: Expression of the immunostimulatory xenoantigen alphaGal on malignant cells is being investigated as a means to formulate anticancer vaccines. Expression methods have been limited to gene transfer using viral vectors and enzymatic manipulation. We report here a novel method using polyethylene glycol (PEG) to induce plasma membrane fusion between malignant human hematological cells and alphaGal(+) porcine blood cells (PBC) in order to display alphaGal antigens on human cells. MATERIALS AND METHODS: Freshly isolated white blood cells (WBC) were obtained from patients with malignant hematological disease and combined with diluted PBC. Cell mixtures were labeled with human CD mAbs, followed by IB4 lectin or M86 mAb to detect alphaGal antigens and then co-incubated with PEG. Back-gated, dual-color flow cytometry was used to detect alphaGal on human cells. RESULTS: alphaGal antigens were detected on sizeable numbers of human WBC (approximately 45%) after incubation with PEG. Antigen expression was profuse as assessed by the strong fluorescent intensity demonstrated by IB4-FITC and M86 labeling. Human cells combined with PBC without PEG were not reactive with IB4-FITC or M86. CONCLUSION: Our method provides an effective, highly reproducible means to efficiently express alphaGal antigens on cells obtained from patients with a spectrum of hematological malignancies. This method can provide a simple, safe alternative to viral-mediated gene transfer or enzymatic alteration to express alphaGal antigens on human tumor cells. By virtue of its simplicity, our technique presents a novel approach to the preparation of polyvalent autologous or syngeneic anticancer vaccines.

Complications of thoracic computed tomography-guided fiducial placement for the purpose of stereotactic body radiation therapy.

PURPOSE: This study examined the complication rates associated with percutaneous fiducial placement for the purpose of stereotactic body radiation therapy of primary and metastatic lung neoplasms. PATIENTS AND METHODS: This is a retrospective review of computed tomography (CT) scans and follow-up chest radiographs of 48 consecutive patients who underwent CT-guided percutaneous fiducial placement. The effect of age, sex, number of fiducials placed, and performance of a concomitant biopsy on the complication rates were assessed. RESULTS: Of 48 patients with a total of 221 fiducials placed, 16 (33%) had a procedure-related pneumothorax. There was no significant difference in pneumothorax rate based on age (P = 0.16), sex (P > 0.99), and number of fiducials placed (P = 0.21). Overall, 6 of 48 patients (12.5%) required a thoracostomy tube. Performance of a concomitant core needle biopsy at the time of fiducial placement was associated with pneumothorax rates of 64% compared with 26% without biopsies (P = 0.03). Postprocedural CT demonstrated hemorrhage in 9 patients (19%). Two patients had hemoptysis; one required admission. Patients' age, sex, number of fiducials placed, and performance of concomitant biopsy had no statistically significant implications on parenchymal hemorrhage incidence. CONCLUSION: Approximately one third of the patients develop a pneumothorax during CT-guided fiducial placement. Most are asymptomatic and do not require a thoracostomy. A concurrent biopsy at the time of fiducial placement is associated with an increased risk of pneumothorax. Hemorrhage occurs but is usually clinically insignificant.

CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life.

OBJECT: The authors conducted a study to assess safety, pain, and quality of life (QOL) outcomes following CyberKnife radiosurgical treatment of spinal tumors. METHODS: Data obtained in all patients with spinal tumors who underwent CyberKnife radiosurgery at Georgetown University Hospital between March 2002 and March 2003 were analyzed. Patients underwent examination, visual analog scale (VAS) pain assessment, and completed the 12-item Short Form Health Survey (SF-12) before treatment and at 1, 3, 6, 8, 12, 18, and 24 months following treatment. Fifty-one patients with 72 lesions (58 metastatic and 14 primary) were treated. The mean follow-up period was 1 year. Pain was improved, with the mean VAS score decreasing significantly from 51.5 to 21.3 at 4 weeks (p < 0.001). This effect on pain was durable, with a mean score of 17.5 at 1 year, which was still significantly decreased (p = 0.002). Quality of life was maintained throughout the study period. After 18 months, physical well-being was 33 (initial score 32; p = 0.96) and mental well-being was 43.8 (initial score 44.2; p = 0.97). (The mean SF-12 score is 50 +/- 10 [standard deviation].) Adverse effects included self-limited dysphagia (three cases), diarrhea (two cases), lethargy (three cases), paresthesias (one case), and wound dehiscence (one case). CONCLUSIONS: CyberKnife radiosurgery improves pain control and maintains QOL in patients treated for spinal tumors. Early adverse events are infrequent and minor. The authors await long-term follow-up data to determine late complications and tumor control rates.

Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC) because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT. METHODS: A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED) was 105.6 (range 37.50-180), and the median age was 73 (65-90 years). No patient received concurrent chemotherapy. RESULTS: With a median follow up of 13 months (range, 4-40 months), the actuarial median overall survival (OS) and progression-free survival (PFS) were 32 months, and 19 months, respectively. The actuarial median local control (LC) time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02), while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04). Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05). Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006). There were no prognostic indicators of PFS that reached statistical significance. No acute or subacute high-grade toxicities were documented. CONCLUSION: SBRT is a safe, feasible, and effective treatment option for elderly patients with inoperable early stage NSCLC. BED, histology, and tumor size are predictors of local control, while tumor size and gender predict OS.

Frameless fractionated stereotactic radiosurgery for vestibular schwannomas: a single-institution experience.

OBJECTIVE: To examine tumor control, hearing preservation, and complication rates after frameless fractionated stereotactic radiosurgery (SRS) in patients with vestibular schwannomas (VS). METHODS: Thirty-seven patients treated with fractionated SRS from 2002 to 2011 were retrospectively analyzed. Ninety-five percent were treated with 25 Gy in five fractions, targeting a median tumor volume of 1.03 cc (range 0.14-7.60). RESULTS: With a median follow-up of 4.25 years (range, 15 months-9 years), no tumors required an additional treatment resulting in 100% tumor control rate. Radiographic control rate was 91% in 32 patients at a median follow-up of 3 years. Of the 14 patients with serviceable hearing and with audiograms, the hearing preservation rate was 78% at a median follow-up of 18 months. Twenty-six patients with serviceable hearing pretreatment, were evaluated by a phone survey with a hearing preservation rate of 73% at a 5 year median follow-up. There were two cases that developed both new increased trigeminal parasthesias and facial spasms but there were no cases of facial weakness. Patient had 96% of good to excellent satisfaction rate with the treatment at a median follow-up of 5 years. CONCLUSION: Frameless fractionated SRS treatment of VS results in good rate of tumor control. Hearing preservation rate and rates of cranial nerve toxicity are comparable to what is reported in the literature. Patients choose this modality because of its non-invasive nature and are generally very satisfied with their long term outcome.

Malignant melanoma and radiotherapy: past myths, excellent local control in 146 studied lesions at Georgetown University, and improving future management.

INTRODUCTION: Once thought to be radioresistant, emerging cellular and clinical evidence now suggests melanoma can respond to large radiation doses per fraction. MATERIALS AND METHODS: We conducted a retrospective study of all patients treated with stereotactic radiosurgery and stereotactic body radiotherapy at Georgetown University Hospital from May 2002 through November 2008 and studied the classic extrapolated total dose corrected for volume (ETD(vol)) model for predicting melanoma tumor response. Region-specific tumor outcomes were categorized by RECIST criteria and local control curves were estimated and analyzed when stratified by ETD(vol) thresholds by use of the Kaplan-Meier method. RESULTS: Follow-up information was available for 78 lesions (49 intracranial, 8 spinal, and 21 body) with mean follow-up period of 9.2 (range, 2-36) months. 1-year local control rates for intracranial, spinal, and body tumors were 84, 100, and 72%, respectively. Treatments in general were well-tolerated. Increased ETD(vol) (p < 0.001) among intracranial sites resulted from larger (p < 0.001) doses per fraction combined with smaller (p < 0.001) tumor diameters. Intracranial 6-, 12-, and 24-month local control rates when treated above ETD(vol) threshold of 230 Gy were all 90 vs. 89, 80, and 53% below this threshold. Body 6- and 12-month local control rates when treated above ETD(vol) threshold of 100 Gy were 100 and 80% vs. 74 and 59% below this threshold. DISCUSSION: By tailoring to melanoma's unique radiobiology with large radiation doses per fraction, favorable local control was safely achieved. The ETD(vol) model combines the important factor of dose per fraction in melanoma treatment with a volume correction factor to predict tumor response. Although limited sample size may have prevented reaching statistical significance for local control improvements using ETD(vol) thresholds, optimal thresholds may exist to improve future tumor responses and further research is required.

Scoring system predictive of survival for patients undergoing stereotactic body radiation therapy for liver tumors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors. This study evaluated outcomes after SBRT to identify prognostic variables and to develop a novel scoring system predictive of survival. METHODS: The medical records of 52 patients with a total of 85 liver lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty-four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT. The median prescribed dose was 30 Gy (range, 16 - 50 Gy) in a median of 3 fractions (range, 1-5). RESULTS: With median follow-up of 11.3 months, median overall survival (OS) was 12.5 months, and 1 year OS was 50.8%. In 42 patients with radiographic follow up, 1 year local control was 74.8%. On univariate analysis, number of lesions (p = 0.0243) and active extralesional disease (p < 0.0001) were predictive of OS; Karnofsky Performance Status (KPS) approached statistical significance (p = 0.0606). A scoring system for predicting survival was developed by allocating 1 point for each of the three following factors: active extralesional disease, 2 or more lesions, and KPS ≤ 80%. Score was associated with OS (p < 0.0001). For scores of 0, 1, 2 and 3, median survival intervals were 34, 12.5, 7.6, and 2.8 months, respectively. CONCLUSIONS: SBRT offers a safe and feasible treatment option for liver tumors. A prognostic scoring system based on the number of liver lesions, activity of extralesional disease, and KPS predicts survival following SBRT and can be used as a guide for prospective validation and ultimately for treatment decision-making.

Single-session and multisession CyberKnife radiosurgery for spine metastases-University of Pittsburgh and Georgetown University experience.

OBJECT: The authors compared the effectiveness of single-session (SS) and multisession (MS) stereotactic radiosurgery (SRS) for the treatment of spinal metastases. METHODS: The authors conducted a retrospective review of the clinical outcomes of 348 lesions in 228 patients treated with the CyberKnife radiosurgery at the University of Pittsburgh Cancer Institute and Georgetown University Medical Center. One hundred ninety-five lesions were treated using an SS treatment regimen (mean 16.3 Gy), whereas 153 lesions were treated using an MS approach (mean 20.6 Gy in 3 fractions, 23.8 Gy in 4 fractions, and 24.5 Gy in 5 fractions). The primary end point was pain control. Secondary end points included neurological deficit improvement, toxicity, local tumor control, need for retreatment, and overall survival. RESULTS: Pain control was significantly improved in the SS group (SSG) for all measured time points up to 1 year posttreatment (100% vs 88%, p = 0.003). Rates of toxicity and neurological deficit improvement were not statistically different. Local tumor control was significantly better in the MS group (MSG) up to 2 years posttreatment (96% vs 70%, p = 0.001). Similarly, the need for retreatment was significantly lower in the MSG (1% vs 13%, p < 0.001). One-year overall survival was significantly greater in the MSG than the SSG (63% vs 46%, p = 0.002). CONCLUSIONS: Single-session and MS SRS regimens are both effective in the treatment of spinal metastases. While an SS approach provides greater early pain control and equivalent toxicity, an MS approach achieves greater tumor control and less need for retreatment in long-term survivors.

Stereotactic body radiation therapy for liver metastases from colorectal cancer: analysis of safety, feasibility, and early outcomes.

INTRODUCTION: Colorectal cancer (CRC) is the third leading cause of cancer-related death in the U.S. Many patients with CRC develop hepatic metastases as the sole site of metastases. Historical treatment options were limited to resection or conventional radiation therapy. Stereotactic body radiation therapy (SBRT) has emerged as a rational treatment approach. This study reviews our experience with SBRT for patients with liver metastases from CRC. MATERIALS AND METHODS: Fourteen histologically confirmed hepatic CRC metastases in 11 consecutive patients were identified between November, 2004 and June, 2009 at Georgetown University. All patients underwent CT-based treatment planning; a few also had MRI or PET/CT. All patients had fiducial markers placed under CT guidance and were treated using the CyberKnife system. Treatment response and toxicities were examined; survival and local control were evaluated. RESULTS: Most patients were treated to a single hepatic lesion (n = 8), with a few treated to two lesions (n = 3). Median treatment volume was 99.7 cm(3), and lesions were treated to a median BED(10) of 49.7 Gy (range: 28-100.8 Gy). Median follow-up was 21 months; median survival was 16.1 months, with 2 year actuarial survival of 25.7%. One year local control was 72%. Among patients with post-treatment imaging, eight had stable disease (80%) and two had progressive disease (20%) at first follow-up. The most common grade 1-2 acute toxicities included nausea and alterations in liver function tests; there was one grade 3 toxicity (elevated bilirubin), and no grade 4-5 toxicities. DISCUSSION: SBRT is safe and feasible for the treatment of limited hepatic metastases from CRC. Our results compare favorably with outcomes from previous studies of SBRT. Further studies are needed to better define patient eligibility, study the role of combined modality treatment, optimize treatment parameters, and characterize quality of life after treatment.

Risk factors for posttreatment edema in patients treated with stereotactic radiosurgery for meningiomas.

BACKGROUND: Peritumoral edema is a recognized complication following stereotactic radiosurgery (SRS). OBJECTIVE: To evaluate the risk of posttreatment peritumoral edema following SRS for intracranial meningiomas and determine predictive factors. METHODS: Between 2002 and 2008, 173 evaluable patients underwent CyberKnife or Gamma Knife SRS for meningiomas. Eighty-four patients (49%) had prior surgical resections, 13 patients had World Health Organization grade II (atypical) meningiomas, and 117 patients had a neurological deficit before SRS. Sixty-two tumors were in parasagittal, parafalcine, and convexity locations. The median tumor volume was 4.7 mL (range, 0.1-231.8 mL). The median prescribed dose and median prescribed biologically equivalent dose were 15 Gy (range, 9-40 Gy) and 67 Gy (range, 14-116 Gy), respectively. Ninety-seven patients were treated with single-fraction SRS, 74 received 2 to 5 fractions, and 2 received >5 fractions. RESULTS: The median follow-up was 21.0 months. Thirteen patients (8%) developed symptomatic peritumoral edema, with a median onset time of 4.5 months (range, 0.2-9.5 months). The 3-, 6-, 12-, and 24-month actuarial symptomatic edema rates were 2.9%, 4.9%, 7.7%, and 8.5%, respectively. The crude tumor control rate was 94%. On univariate analysis, large tumor volume (P = .01) and single-fraction SRS (P = .04) were predictive for development of posttreatment edema. CONCLUSION: SRS meningioma treatment demonstrated a low incidence of toxicity; however, large tumor volumes and single-fraction SRS treatment had an increased risk for posttreatment edema. Risk factors for edema should be considered in meningiomas treatment.

Pulse interleukin-2 with famotidine induces CD56+ lymphocytes in the peripheral blood of patients with metastatic melanoma or kidney cancer.

Increased lymphokine-activated killer (LAK) cell numbers and cytotoxicity against tumor cell lines have been seen in patients receiving high-dose continuous and bolus infusion interleukin-2 (IL-2) regimens. LAK are CD56 positive on flow cytometry. Daily intravenous doses of IL-2 of 18-21.6 MIU/m(2) over 15-30 minutes ("pulses") have been developed to attempt to lessen the toxicity of this therapy. It has been previously shown that the patients with metastatic melanoma or kidney cancer may be treated safely with pulse IL-2 daily for 5 days preceded by intravenous famotidine. Cycles were repeated every 21 days. Because LAK numbers have not been previously described with this regimen, the present study has examined CD56 numbers via peripheral blood flow cytometry in 11 patients with samples scheduled at baseline, after two cycles, and after four cycles. Eight (8) patients had melanoma and 3 had kidney cancer. Median CD56 counts after two cycles was significantly higher than baseline (p = 0.001). Similarly, CD56 counts at 2 months later were also greater than baseline (p = 0.009). There was no difference between median values after two cycles versus after four cycles. Patients who were clinical responders had a median CD56 count of 650 after two cycles when compared with nonresponders who had a median CD56 count of 290 (p = 0.005). CD56 counts are significantly elevated in patients treated with pulse IL-2 with famotidine and clinical responders have significantly higher CD56 than nonresponders.

Fractionated stereotactic radiosurgery for reirradiation of head-and-neck cancer.

PURPOSE: Stereotactic radiosurgery (SRS) is an appealing treatment option after previous radiotherapy because of its precision, conformality, and reduced treatment duration. We report our experience with reirradiation using fractionated SRS for head-and-neck cancer. METHODS AND MATERIALS: From 2002 to 2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8), nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n = 23). Thirty-eight patients were treated definitively and 27 patients with metastatic disease and/or untreated local disease were treated palliatively. Nine patients underwent complete macroscopic resection before SRS. Thirty-three patients received concurrent chemoradiation. The median initial radiation dose was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5 fractions. RESULTS: Median follow-up for surviving patients was 16 months. Fifty-six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had partial, and 11 (20%) had no response. Median overall survival (OS) for all patients was 12 months. For definitively treated patients, the 2-year OS and locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate analysis demonstrated that higher total dose, surgical resection, and nasopharynx site were significantly associated with improved LRC; surgical resection and nonsquamous histology were associated with improved OS. Seven patients (11%) experienced severe reirradiation-related toxicity, including one treatment-attributed death. CONCLUSION: SRS reirradiation for head-and-neck cancer is feasible. This study demonstrates encouraging response rates with acceptable toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select patients warrants further study.

Treatment of spinal tumors using cyberknife fractionated stereotactic radiosurgery: pain and quality-of-life assessment after treatment in 200 patients.

OBJECTIVE: Benign and malignant tumors of the spine significantly impair the function and quality of life of many patients. Standard treatment options, including conventional radiotherapy and surgery, are often limited by anatomic constraints and previous treatment. Image-guided stereotactic radiosurgery using the CyberKnife system (Accuray, Inc., Sunnyvale, CA) is a novel approach in the multidisciplinary management of spinal tumors. The aim of this study was to evaluate the effects of CyberKnife stereotactic radiosurgery on pain and quality-of-life outcomes of patients with spinal tumors. METHODS: We conducted a prospective study of 200 patients with benign or malignant spinal tumors treated at Georgetown University Hospital between March 2002 and September 2006. Patients were treated by means of multisession stereotactic radiosurgery using the CyberKnife as initial treatment, postoperative treatment, or retreatment. Pain scores were assessed by the Visual Analog Scale, quality of life was assessed by the SF-12 survey, and neurological examinations were conducted after treatment. RESULTS: Mean pain scores decreased significantly from 40.1 to 28.6 after treatment (P < 0.001) and continued to decrease over the entire 4-year follow-up period (P < 0.05). SF-12 Physical Component scores demonstrated no significant change throughout the follow-up period. Mental Component scores were significantly higher after treatment (P < 0.01), representing a quality-of-life improvement. Early side effects of radiosurgery were mild and self-limited, and no late radiation toxicity was observed. CONCLUSION: CyberKnife stereotactic radiosurgery is a safe and effective modality in the treatment of patients with spinal tumors. CyberKnife offers durable pain relief and maintenance of quality of life with a very favorable side effect profile.

Treatment of chordomas with CyberKnife: georgetown university experience and treatment recommendations.

OBJECTIVE: To determine the efficacy and safety of chordoma treatment with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (CK/SRS). METHODS: Eighteen patients with chordoma were treated with CK/SRS as a primary adjuvant (17 patients) or the only treatment (1 patient). The series included 24 lesions (28 treatments). The median age of the patients was 60 years (range, 24-85 years). Forty-four percent of the tumors were located in the mobile spine, 39% inside the cranium, and 17% in the sacral region. The male-to-female ratio was 1:1. The mean tumor volume was 128.0 mL (range, 12.0-457.3 mL), and the median dose of 35 Gy (range, 24.0-40.0 Gy) was delivered in 5 sessions. The median follow-up period was 46 months (range, 7-65 months). RESULTS: There were 3 significant complications in patients with previous irradiation, including infection in the surgical/radiation site (2 patients) and decreased vision (1 patient). Improvement in pain and quality of life did not reach statistical significance (alpha = 0.05). Seven patients experienced recurrence at a median of 10 months (range, 5-38 months), and 4 patients with disseminated disease died 7 to 48 months after therapy. Two patients had a partial response, whereas 9 others had stable disease. The local control rate at 65 months was 59.1%, with an overall survival of 74.3% and disease-specific survival of 88.9%. We estimated an alpha/beta ratio of 2.45 for chordomas, which supports hypofractionation. CONCLUSION: The CK/SRS safety and efficacy profile compares favorably with those of other treatment delivery systems. CK/SRS appears to reduce tumor volume, given an adequate dose. The authors recommend treatment with 40 Gy in 5 sessions to the clinical treatment volume, which includes the gross tumor volume and at least a 1-cm margin.

Treatment of malignant tumors of the skull base with multi-session radiosurgery.

OBJECTIVE: Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base. METHODS: Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves. RESULTS: Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife radiosurgery. CONCLUSION: Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.

Cyberknife radiosurgery for breast cancer spine metastases: a matched-pair analysis.

BACKGROUND: There are few options for breast cancer patients with spinal metastases recurrent within a previous radiation treatment field. CyberKnife radiosurgery has been used in our institution to treat such patients. To evaluate their outcomes, as there are no comparable radiation treatment options, the outcomes were compared between 18 patients with spinal metastases from breast cancer treated with CyberKnife stereotactic radiosurgery, 17 of which had prior radiotherapy to the involved spinal region and were progressing, and 18 matched patients who received conventional external beam radiotherapy (CRT) up-front for spinal metastases. METHODS: Radiosurgery was delivered in 3 to 5 fractions to doses ranging from 2100 to 2800 cGy. Women were matched to patients in a CRT group with respect to time from original diagnosis to diagnosis of metastases, estrogen receptor / progesterone receptor (ER/PR) status, presence or absence of visceral metastases, prior radiotherapy, and prior chemotherapy. Survival and complications were compared between treatment groups. Surviving patients were followed out to 24 months. RESULTS: The CyberKnife and CRT groups were comparable along all matching dimensions and in performance status before treatment. Outcomes of treatment were similar for patients in both groups; ambulation, performance status, and pain worsened similarly across groups posttreatment. Survival and the number of complications appeared to favor the CyberKnife group, but the differences did not reach statistical significance. CONCLUSIONS: The statistical comparability of the CyberKnife and CRT groups reflects the small sample size and stringent requirements for significance of the matched-pair analysis. Nevertheless, comparability in these difficult cases shows that salvage CyberKnife treatment is as efficacious as initial CRT without added toxicity.

Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors.

BACKGROUND: Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. METHODS: Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3-5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45-60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. RESULTS: Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. CONCLUSION: Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.