Use of flucinolone acetonide for patients with diabetic macular oedema: patient selection criteria and early outcomes in real world setting.

INTRODUCTION: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. METHOD: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. RESULTS: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 µm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. CONCLUSION: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents.

Use of Radiation Therapy for the Treatment of Breast Cancer in 2019 Versus 2020.

Purpose: The COVID-19 pandemic disrupted medical care. Little is known about how radiation therapy (RT) ordering behavior changed during the pandemic. This study examined (1) whether there was a change in the rate at which orders for lumpectomy were followed by orders for RT and (2) whether there was a change in the percentage of RT orders for hypofractionated (HF) RT rather than conventionally fractionated (CF) RT. Methods and Materials: Prior authorization order data from 2019 and 2020, pertaining to patients with commercial and Medicare Advantage health plans, were reviewed to determine whether patients had an order for RT in the 90 days after lumpectomy and if it was for CF or HF RT. Univariate analyses were conducted using χ2 tests, and adjusted analyses were conducted using multivariate logistic regression, controlling for patient age, urbanicity, local median income, region, if the lumpectomy facility was academic, and if the lumpectomy facility was a hospital. Results: In 2019, 47.7% of included lumpectomy orders (2200/4610) were followed by an RT order within 90 days, in contrast to 45.6% (1944/4263) in 2020 (P = .048). Of the RT orders meeting this study's definition of CF or HF, 75.3% of orders placed in 2019 (1387/1843) and 79.0% of orders placed in 2020 (1261/1597) were for HF (P = .011). Adjusted analysis found patients receiving a lumpectomy order in the first quarter of 2020 had significantly reduced odds (odds ratio, 0.84; 95% CI, 0.71-0.99) of receiving an order for RT after lumpectomy, relative to those with orders placed in the first quarter of 2019. Adjusted analysis likewise found significant evidence of increased use of HF RT during the pandemic. Conclusions: In the population examined, physicians were less likely to order RT after lumpectomy in 2020 than in 2019, and if they did, were more likely to order HF RT.

A Conceptual Framework to Predict Mental Health Patients' Zoning Classification.

Zoning classification is a rating mechanism, which uses a three-tier color coding to indicate perceived risk from the patients' conditions. It is a widely adopted manual system used across mental health settings, however it is time consuming and costly. We propose to automate classification, by adopting a hybrid approach, which combines Temporal Abstraction to capture the temporal relationship between symptoms and patients' behaviors, Natural Language Processing to quantify statistical information from patient notes, and Supervised Machine Learning Models to make a final prediction of zoning classification for mental health patients.

Real-World Outcomes in Diabetic Macular Edema for the 0.2 µg/Day Fluocinolone Acetonide Implant: Case Series from the Midlands, UK.

AIM: To investigate real-world effectiveness and safety of fluocinolone acetonide (FAc) implant over three years of treatment in eyes with diabetic macular edema (DME) in a population with large ethnic diversity. METHODS: This audit of three large treatment centres in the UK involved retrospective collection of outcome data (best recorded visual acuity [BRVA] by Early Treatment Diabetic Retinopathy Study [ETDRS] letters, central retinal thickness [CRT], intraocular pressure [IOP] and use of supplementary treatments) from patients with DME treated with 0.2 µg/day FAc intravitreal implant with three-year follow-up expected. RESULTS: A total of 96 eyes were included. Ninety (93.8%) eyes had received prior intravitreal treatment. Increases in mean BRVA were significant at one, two and three years (p<0.05). Overall, 78.1% of eyes gained or maintained BRVA; just over 50% gained ≥5 letters, representing a functional response. Eleven (11.6%) patients lost ≥10 letters by year three. Decreases in central retinal thickness (CRT) nearing 200 µm in the first year were sustained to three years (p < 0.0001). Patients with baseline VA ≥60 letters maintained their BRVA throughout follow-up, while significant improvements at month 12 (p<0.0001) in those with baseline BRVA <60 letters were maintained through month 36 (p < 0.005). Fifty-three (55.2%) eyes required no supplementary therapy during follow-up. Increases in IOP to ≥30 mmHg and ≥25 mmHg were seen in 12 (12.5%) and 23 (24.0%) eyes, respectively. CONCLUSION: This study confirms the effectiveness and tolerability of FAc implant up to 36 months in a real-world setting, highlighting the importance of early treatment for sustaining functional vision for patients.

The American Brachytherapy society consensus statement for skin brachytherapy.

PURPOSE: Keratinocyte carcinoma (KC, previously nonmelanoma skin cancer) represents the most common cancer worldwide. While surgical treatment is commonly utilized, various radiation therapy techniques are available including external beam and brachytherapy. As such, the American Brachytherapy Society has created an updated consensus statement regarding the use of brachytherapy in the treatment of KCs. METHODS: Physicians and physicists with expertise in skin cancer and brachytherapy created a consensus statement for appropriate patient selection, data, dosimetry, and utilization of skin brachytherapy and techniques based on a literature search and clinical experience. RESULTS: Guidelines for patient selection, evaluation, and dose/fractionation schedules to optimize outcomes for patients with KC undergoing brachytherapy are presented. Studies of electronic brachytherapy are emerging, although limited long-term data or comparative data are available. Radionuclide-based brachytherapy represents an appropriate option for patients with small KCs with multiple techniques available. CONCLUSIONS: Skin brachytherapy represents a standard of care option for appropriately selected patients with KC. Radionuclide-based brachytherapy represents a well-established technique; however, the current recommendation is that electronic brachytherapy be used for KC on prospective clinical trial or registry because of a paucity of mature data.

Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin: Executive Summary of an American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: This guideline reviews the evidence for the use of definitive and postoperative radiation therapy (RT) in patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on indications for RT in the definitive and postoperative setting for BCC and cSCC, as well as dose-fractionation schemes, target volumes, basic aspects of treatment planning, choice of radiation modality, and the role of systemic therapy in combination with radiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The guideline recommends definitive RT as primary treatment for patients with BCC and cSCC who are not surgical candidates while conditionally recommending RT with an emphasis on shared decision-making in those situations in which adequate resection can lead to a less than satisfactory cosmetic or functional outcome. In the postoperative setting, a number of indications for RT after an adequate resection are provided while distinguishing the strength of the recommendations between BCC and cSCC. One key question is dedicated to defining indications for regional nodal irradiation. The task force suggests a range of appropriate dose-fractionation schemes for treatment of primary and nodal volumes in definitive and postoperative scenarios. The guideline also recommends against the use of carboplatin concurrently with adjuvant RT and conditionally recommends the use of systemic therapies for unresectable primaries where treatment may need escalation. CONCLUSIONS: Defining the role of RT in the management of BCC and cSCC has been hindered by a lack of high-quality evidence. This document synthesizes available evidence to define practice guidelines for the most common clinical situations. We encourage practitioners to enroll patients in prospective trials and to approach care in a multidisciplinary fashion whenever possible.

Initial outcomes analysis for large multicenter integrated cancer network implementation of intensity modulated radiation therapy for breast cancer.

To analyze the initial clinical outcomes for breast cancer patients treated with intensity-modulated radiation therapy (IMRT) in a large integrated cancer center network. A total of 495 patients with breast cancer received IMRT following breast conserving surgery among nine cancer centers. Seven community cancer centers span a 100-mile radial distance from the two central academic sites. All nine cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of breast cancer. IMRT planning for all centers was performed at one central location, D3 Advanced Radiation Planning Service. The median IMRT prescription dose was 50 Gy followed by a boost with median dose of 10 Gy. The median breast volume was 918 cm(3). The median Dose Homogeneity Index (DHI) was 93%. The median % of ipsilateral lung volume receiving >20 Gy was 4.6%. For left breast IMRT, the median % heart volume receiving more than 5% of prescription dose was 13.1. There was no statistical difference in the mean DHI, heart and lung dose between the academic and community sites. For all patients, NCI CTC Grades 0,1,2,3 for acute skin erythema was 16%, 55%, 28%, and 1%, respectively. The rates of Grade 0,1,2,3 acute skin desquamation were 75%, 20%, 4%, and 1%, respectively. There was no statistically significant difference in acute skin toxicities (>grade 2) among the academic and community cancer centers. With centralized processes, IMRT can be safely and effectively delivered in a large health system with an admixture of academic and community centers but long-term follow-up is necessary.

What do patients want from their radiation oncologist? Initial results from a prospective trial.

PURPOSE: To assess patients' initial physician preferences using a newly developed instrument. METHODS AND MATERIALS: A total of 182 patients with a primary diagnosis of prostate, breast, or lung cancer referred for consultation to the University of Pittsburgh Cancer Institute Department of Radiation Oncology enrolled in our institutional review board-approved protocol. All patients completed patient preference instrument surveys before meeting their radiation oncologist. Survey responses to 10 statements were categorized into three groups (agree, neutral, or disagree), and the association of survey responses by cancer site was tested with chi-squared tests. RESULTS: Ninety-nine percent of all patients preferred to be addressed by their first name in encounters with their radiation oncologist. There were significant associations of Item 3 (hand holding) with gender (p = 0.039) and education (p = 0.028). The responses to Item 5, a statement that patients would feel uncomfortable if the radiation oncologist offered to hug them at the end of treatment, was significantly associated with disease site (p < 0.0001). Further analysis was performed for Item 5 and revealed that the male lung cancer patients had a much higher rate of disagreement with Item 5 compared with prostate cancer patients (37% vs. 18%). CONCLUSIONS: Results of this study may afford greater insight and foster better understanding of what patients want from their radiation oncologist. For breast, lung, and prostate cancer patients, initial preferences for their radiation oncologist are generally similar, according to this tool. However, there are important difference among cancer sites (and gender) regarding physical contact at the end of treatment.

Breast skin doses from brachytherapy using MammoSite HDR, intensity modulated radiation therapy, and tangential fields techniques.

Skin doses from brachytherapy using MammoSite HDR, Intensity Modulated Radiation Therapy (IMRT), and conventional tangential fields techniques were compared. For each treatment technique, skin doses were measured using paired thermoluminescent dosimeters placed on the patient's skin: (i) directly above the balloon catheter during MammoSite HDR brachytherapy treatments and (ii) 4 cm inside the treatment borders during the IMRT and conventional breast treatments. The mean dose measured was about 58% of the prescription dose for the patients treated using the MammoSite technique. On the other hand, for patients treated with IMRT and tangential fields, the mean dose was found to be about 69% and 71% of the corresponding prescription dose. This study suggests that in breast cancer radiation treatments the MammoSite HDR technique reduces skin doses compared to IMRT and tangential field techniques.

Skin surface brachytherapy: A survey of contemporary practice patterns.

PURPOSE: The aim of this study was to define current patterns of care among radiation oncologists who use skin surface brachytherapy for the treatment of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) in academic and community settings. METHODS AND MATERIALS: A 30-question electronic survey was administered to clinician members of the American Brachytherapy Society. The respondents were asked to provide details regarding their clinical practice and their approach to skin surface brachytherapy. RESULTS: A total of 16 surveys were returned. Among the respondents, aggregate experience varied from 8 to 1800 cases. Most preferred brachytherapy over external beam radiation because of shorter treatment course, conformality of treatment for irregular or curved targets, and shallow dose deposition. Of the total, 60% of respondents routinely estimated lesion depth via ultrasound before initiating treatment. Treatment margin on gross disease varied widely (range, 3-15 mm; median, 5 mm). Hypofractionation was the preferred dose schedule. Prescribed doses ranged from 30 Gy in five fractions to 64 Gy in 32 fractions (EQD2, 40 Gy-65 Gy). There was a tendency to increase the number of fractions for larger targets, although some used the same fractionation regardless of anatomic location or lesion size. There was no consensus on dosimetric constraints, and some respondents reported cases of severe toxicity, particularly when treating the pretibial skin. CONCLUSIONS: This pattern of care study suggests that skin brachytherapy can be a convenient and safe tool for treatment of BCC and cSCC. Prospective trials and the development of expert consensus guidelines would be beneficial for optimizing skin surface brachytherapy and reducing practice variation.

A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats.

Recent evidence has demonstrated that long-term estrogen deprivation using aromatase inhibitor therapy in postmenopausal women with breast cancer results in bone loss and increased fracture risk. Bisphosphonates are potent inhibitors of bone resorption and have demonstrated efficacy in preventing bone loss in postmenopausal women with low bone mineral density (BMD) and in patients with breast cancer receiving estrogen deprivation therapy. Therefore, this study investigated the effects of the bisphosphonate zoledronic acid on BMD and bone strength in rats treated with the aromatase inhibitor, letrozole. Peripheral quantitative computed tomography demonstrated that treatment of rats with daily oral letrozole (1 mg/kg) induced significant bone loss and cortical thinning compared with control animals (P < 0.01). A single prior intravenous dose of zoledronic acid dose dependently protected against letrozole-induced bone loss and cortical thinning, with the highest evaluated dose (20 microg/kg) resulting in BMD values that were not significantly different from controls over the 24 weeks of letrozole treatment. Furthermore, biomechanical testing of the distal femoral metaphysis demonstrated that zoledronic acid (20 microg/kg) significantly prevented the decrease in stiffness and elastic modulus induced by letrozole treatment. Taken together, these data support the use of zoledronic acid for the prevention of bone loss in women with breast cancer receiving aromatase inhibitor therapy.

Stereotactic radiosurgery for four or more intracranial metastases.

PURPOSE: To evaluate the outcomes after a single stereotactic radiosurgery procedure for the care of patients with 4 or more intracranial metastases. METHODS AND MATERIALS: Two hundred five patients with primary malignancies, including non-small-cell lung carcinoma (42%), breast carcinoma (23%), melanoma (17%), renal cell carcinoma (6%), colon cancer (3%), and others (10%) underwent gamma knife radiosurgery for 4 or more intracranial metastases at one time. The median number of brain metastases was 5 (range, 4-18) with a median total treatment volume of 6.8 cc (range, 0.6-51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with whole brain radiotherapy (46%) or after failure of whole brain radiotherapy (38%). The median marginal radiosurgery dose was 16 Gy (range, 12-20 Gy). The mean follow-up was 8 months. RESULTS: The median overall survival after radiosurgery for all patients was 8 months. The 1-year local control rate was 71%, and the median time to progressive/new brain metastases was 9 months. Using the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classification system, the median overall survivals for RPA classes I, II, and III were 18, 9, and 3 months, respectively (p < 0.00001). Multivariate analysis revealed total treatment volume, age, RPA classification, and marginal dose as significant prognostic factors. The number of metastases was not statistically significant (p = 0.333). CONCLUSION: Radiosurgery seems to provide survival benefit for patients with 4 or more intracranial metastases. Because total treatment volume was the most significant predictor of survival, the total volume of brain metastases, rather than the number of metastases, should be considered in identifying appropriate radiosurgery candidates.

The Role for intensity modulated radiation therapy (IMRT) in pediatric population.

The purpose of this study was to evaluate our initial experience on the use of IMRT in children with tumors in eloquent or critical locations. Twenty-two children with a median age of 12 years (range 1-17) were treated using IMRT for tumors which were within 2 cm of a critical structure. The treatment locations were spine [2], head and neck [5], abdominopelvic [8], and intracranial [7]. Eighty-two percent (82%) of patients were treated with curative intent despite most patients having advanced or metastatic disease and two patients having previously received standard external beam radiation. IMRT was delivered with a 6MV linear accelerator using dynamic multileaf collimators with a median of six fields. The median follow-up was five months [1-21]. The median administered dose was 45 Gy. The median planning treatment volume (PTV) was 105.4 cc. For the intracranial lesions, the mean doses to the pituitary, brainstem, cochlea, optic nerve, and lens were 31%, 42%, 17%, 27%, and 6% of the total dose, respectively. For the head and neck tumors, the mean doses to the spinal cord and parotid glands were 47% and 49%, respectively. For the pelvic tumors, the mean dose to the bladder, rectum, and small bowel were 51%, 63%, and 22%, respectively. Local failure occurred in one patient. IMRT resulted in substantial sparing of surrounding critical structures and acceptable local control rate for these tumors in children. Further follow-up is needed to assess long-term local control and late effects.

High-dose-rate interstitial brachytherapy for gynecologic malignancies.

PURPOSE: The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). METHODS AND MATERIALS: Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6-50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed-Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6-69 months). RESULTS: Median cumulative biologic effective dose (EBRT+HDRB) to tumor volume was 78.9 Gy10 with the range of 72.5-85.2Gy10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy3 (range, 79.6-107.8 Gy3) and 96.4 Gy3 (range, 78.3-105.3 Gy3), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. CONCLUSIONS: Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.

Pearl necklace sign in diabetic macular edema: Evaluation and significance.

PURPOSE: (1) The purpose of this study was to describe significance and prevalence of the newly reported pearl necklace spectral domain optical coherence tomography (SDOCT) sign, in diabetic macular edema (DMO), (2) to track the course of this sign over a period of at least 10 months. MATERIALS AND METHODS: The pearl necklace SDOCT sign refers to hyperreflective dots in a contiguous ring around the inner wall of cystoid spaces in the retina, recently described for the first time in 21 eyes with chronic exudative maculopathy. A retrospective analysis was performed of SDOCT images of all patients presenting to the DMO referral clinic of a tertiary eye care center, over a period of 24 months. Images of patients displaying this sign were sequentially analyzed for at least 10 months to track the course of the sign. RESULTS: Thirty-five eyes of 267 patients (13.1%) were found to display the pearl necklace sign. Twenty-eight eyes responded to intravitreal ranibizumab treatment with resolution of edema. In 21 eyes, the dots coalesced to form a clump, visible in the infrared fundus photograph as hard exudates; in seven eyes, dots disappeared without leaving visible exudates. In three eyes, the sign was seen in subfoveal cystoid spaces, with subsequent development of hard exudates, and drop in visual acuity of 20 letters or more. CONCLUSION: Pearl necklace SDOCT sign is not infrequent in DMO. This sign is a precursor to hard exudates in the majority of cases. If this sign is seen subfoveally, drop in visual acuity can be expected, despite treatment.

High-dose Rate Electronic Brachytherapy: A Nonsurgical Treatment Alternative for Nonmelanoma Skin Cancer.

The authors summarized data from a group of physicians with experience using high-dose rate electronic brachytherapy for the treatment of nonmelanoma skin cancer. The data have been published or presented in abstract format at national dermatology and radiation oncology meetings. The data included 1,822 treated lesions from 2009 to 2014 in patients ranging in age from 52 to 104 years. Most lesions were basal cell carcinoma (57%) or squamous cell carcinoma (38%) less than 2cm in size (97%). Median follow-up at the various centers ranged from 4 to 16 months, and results yielded an extremely low recurrence rate of less than one percent. Results show that within the confines of this follow up period, electronic brachytherapy is an effective, convenient, nonsurgical treatment option for patients with nonmelanoma skin cancer with few recurrences and excellent cosmetic results.

Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.

PURPOSE: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months. RESULTS: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001). CONCLUSION: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases.

PURPOSE: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS. METHODS AND MATERIALS: We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). RESULTS: At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets. CONCLUSIONS: In this retrospective study of 1-year survivors of SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated with an improved local control rate in patient subsets with tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and specifically lung cancer metastases. A trend was noted for improved distal intracranial control for patients having nonradioresistant tumors. Distant intracranial relapse >1 year posttreatment is a significant problem with or without initial WBXRT.

Perineural invasion of squamous cell carcinoma of the lip with occult involvement of the infra-orbital nerve detected by PET-CT and treated with MRI-based IMRT: a case report.

A 51 year old male with a history of right facial numbness developed progressive upper lip swelling for one year, but an MRI of the head was unremarkable. A wide local excision of the upper lip was performed and pathology revealed a 1.7 cm mass, poorly differentiated squamous cell carcinoma with perineural invasion. Surgical margins were free of tumor. Two months postoperatively, a hybrid PET-CT of the whole body was performed due to the persistent right facial numbness. The CT portion identified an equivocal lesion at the base of the right orbit correlating to the right infraorbital nerve. However, the PET-CT image revealed avid uptake in this location suggesting perineural invasion which was confirmed with biopsy of the right infraorbital nerve demonstrating carcinoma. Subsequently, the patient was treated with Intensity Modulation Radiation Therapy (IMRT) using MRI fusion for proper delineation of the right infraorbital nerve to its origin in the base of skull. This case exemplifies the superiority of hybrid PET-CT over CT or MRI alone in head and neck imaging which can lead to significant impact on management for patients with head and neck cancer.

CyberKnife Frameless Radiosurgery for the treatment of extracranial benign tumors.

Limited data exists for the use of radiosurgery for benign extracranial tumors. The purpose of this study was to evaluate the feasibility, toxicity, and local control of patients with benign extracranial lesions treated with the CyberKnife Frameless Radiosurgery System. From September 2001 thru January 2004, 59 benign tumors in 44 patients were treated using the CyberKnife a frameless image-guided radiosurgery system. Of these tumors, there were 21 neurofibromas, ten schwannomas, eight meningiomas, eight hemangioblastomas, seven paragangliomas, two hemangiopericytomas, one pseudotumor, one ependymoma, and one arteriovenous malformation (AVM). The anatomic locations of these tumors were spinal (25 cervical, four thoracic, 14 lumbar, and two sacral), neck (eight), orbital (three), brainstem (one), and foramen magnum (one). All patients were treated in a single fraction except three lesions were treated in a fractionated manner. The median treatment delivery time per fraction was 59 minutes (range 11-194). Twenty three lesions initially underwent surgical resection. Ten lesions received prior external beam radiation with a median dose 48 Gy (range 40-54 Gy), and one lesion received two prior CyberKnife treatments for a total dose of 32 Gy to the 80% isodose line. The median follow-up was eight months (range 1-25 months). Acute and late toxicity was graded using the National Cancer Institute Common Toxicity Criteria (CTC) scale. Symptomatic response was documented as "improved," "stable," or "progression". The median tumor dose delivered was 16.0 Gy to the 80% isodose line (range 10-31 Gy). The median tumor volume was 4.3 cc (range 0.14-98.6 cc). The median spinal cord volume receiving more than 8 Gy was 0.035 cc (range 0-2.5 cc) and the median maximum spinal cord dose 11.5 Gy (range 0-19.8 Gy). There were no patients that suffered a significant (Grade 3, 4, or 5) acute toxicity. There was no observed late toxicity. 78% of patients experienced an improvement of their pre-treatment symptoms while only one patient experienced symptom progression. Of the 26 patients who underwent follow-up imaging, the local control rate was 96%. This study suggests that CyberKnife Radiosurgery is a safe and efficacious treatment modality for benign tumors, even for those patients with recurrent previously irradiated lesions.