Survival and Radiation Dose Differences Between Single Versus Multi-Session Gamma Knife Stereotactic Radiosurgery in Patients Treated for Multiple (≥10) Brain Metastases.

OBJECTIVE:  To explore whether treatment with multiple Gamma Knife sessions (mGK) resulted in different survival outcomes or cumulative radiation doses compared to single session Gamma Knife (sGK) in patients who have been treated for ≥10 brain metastases (BMs). METHODS:  Thirty-five patients with ≥10 BMs treated with Gamma Knife stereotactic radiosurgery (GK SRS) were identified and separated into sGK vs. mGK cohorts. Survival outcomes and dosimetry data were compared between the two groups. Recursive partitioning analysis (RPA) classes were used to further stratify patients. RESULTS:  mGK patients survived longer from the first GK treatment (p<0.009). By RPA class, patients with class 1 had a prolonged survival from BM diagnosis than those in classes 2 and 3 (p=0.004). However, survival was not significantly different between the classes from the first GK treatment (p=0.089). Stratified by mGK vs. sGK and RPA classes, sGK patients in RPA class 1 had the longest survival from BM diagnosis but the worst survival from GK treatment. mGK patients in any RPA class had the best survival from the first GK treatment. For patients with RPA class 2+3, mGK was associated with longer survival from both BM diagnosis and first treatment. Statistical but not clinical differences between the mGK vs. sGK groups were observed in the max dose to the targets and cochlea, and the V40Gy whole brain dose. CONCLUSIONS:  mGK may be beneficial if GK is initiated early at first BM diagnosis vs. sGK initiated late. Future research is required to confirm these findings and explore additional areas of interest, such as quality-of-life and economic considerations.

Relationship between gene expression profile class and tumor thickness regression after plaque brachytherapy for choroidal melanoma.

BACKGROUND AND OBJECTIVE: To examine the relationship between gene expression profile class and tumor thickness reduction as measured by ultrasonography in response to plaque brachytherapy using a single-center, retrospective cohort study. METHODS: A total of 15 patients with choroidal melanoma who underwent biopsy for gene expression profiling and were treated with plaque brachytherapy from a single institution from 12/8/14 through 12/19/19 were retrospectively reviewed for clinical characteristics and rate of tumor regression. Ultrasonographic B-scan tumor height was recorded just prior to plaque placement and following plaque removal in the patient's chart to assess percent reduction in tumor thickness from baseline. RESULTS: A total of 15 patients met inclusion criteria and were analyzed in this study. Minimum follow-up was 6 months after plaque removal. The percent regression in tumor thickness from baseline as measured by ultrasonography was greater for class 2 tumors than for class 1 tumors at 12-month follow up after treatment, and this difference was statistically significant (P = 0.012). There was no statistical significance in reduction at 3 months (P = 0.46) and 9 months (P = 0.10) after plaque brachytherapy. Although not statistically significant, class 2 tumors appeared to regress more rapidly than class 1 tumors in response to radiation. CONCLUSIONS: In this study, class 2 choroidal melanoma tumors show a more rapid anatomic response to treatment than class 1 tumors at 12 months post plaque brachytherapy.

Tufts Medical Center Experience With Long-Term Follow-Up of Vestibular Schwannoma Treated With Gamma Knife Stereotactic Radiosurgery: Novel Finding of Delayed Pseudoprogression.

PURPOSE: Our purpose was to evaluate the long-term outcomes of patients with vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (GKSRS) with modern techniques, with attention to posttreatment tumor growth dynamics, dosimetric predictors, and late toxicities. METHODS AND MATERIALS: One hundred twelve patients with VS were treated with GKSRS with a median dose of 12.5 Gy to the 50% isodose line treated between 2004 and 2015, with patients followed up to 15 years. Target and organ-at-risk doses were recorded, and tumor diameter/volume, audiologic decline, and trigeminal/facial nerve preservation were tracked from treatment onward. RESULTS: GKSRS yielded local control of 5, 10, and 15 years at 96.9%, 90.0%, and 87.1% respectively. Pseudoprogression was found in 45%, with a novel pattern detected with peak swelling at 31 months. Pseudoprogression was associated with smaller tumor diameter at treatment and fewer treatment isocenters, but not with the development of any toxicity, nor was it predicted by any dosimetric factor. Median time to hearing loss was 3.4 years with actuarial hearing preservation at 2, 5, and 10 years of 66.5%, 43.1%, and 37.6%, with rate of hearing loss correlating with maximum cochlea and modiolus doses. Trigeminal and facial nerve preservation rates were 92.7% and 97.6%, respectively. Increasing maximum tumor dose was associated with facial paresthesia. CONCLUSIONS: Modern GKSRS is a safe and effective treatment for VS on long-term follow-up, with high levels of facial and trigeminal nerve preservation. A novel pattern of pseudoprogression has been identified suggesting longer imaging follow-up may be needed before initiating salvage in those without symptomatic progression. Several tumor and dosimetric predictors have been suggested for the development of different toxicities, requiring further evaluation.

Gamma Knife radiosurgery for locally recurrent choroidal melanoma following plaque radiotherapy.

BACKGROUND: For the majority of eyes with choroidal melanoma, radiation therapy is the treatment of choice. Local recurrence after radiation therapy can occur, however, and when it does, salvaging the globe with useful vision is atypical. CASE PRESENTATION: We report a case of late, local failure 7 years following previous brachytherapy successfully managed with Gamma Knife radiosurgery (GKR). With 3 years of follow up after GKR, the visual acuity is 20/20 and there is no evidence of systemic metastases. CONCLUSION: To our knowledge, this is the first report of successful salvage GKR therapy after brachytherapy failure in an eye with choroidal melanoma. GKR is an option for select cases of local recurrence after radiation plaque brachytherapy.

Brachytherapy vs. external beam radiotherapy for choroidal melanoma: Survival and patterns-of-care analyses.

PURPOSE: No modern randomized trials exist comparing external beam radiotherapy (EBRT) and plaque brachytherapy (BT) for choroidal melanoma, and the optimal treatment modality is currently unknown. This study compares the patterns of care and efficacy of EBRT vs. BT based on data in the Surveillance, Epidemiology, and End Results database. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for patients aged 20-79 diagnosed with choroidal melanoma from 2004 to 2011, treated with EBRT or BT; included patients were clinically T1-T4, N0, and M0. Overall survival and cause-specific survival curves were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were performed in the survival and patterns-of-care analyses. RESULTS: A total of 1004 cases (380 EBRT and 624 BT) were included in the survival analysis. There was no difference in the 5-year overall survival (83.3% EBRT vs. 82.5% BT, p = 0.69) and 5-year cause-specific survival (88.3% EBRT vs. 88.3% BT, p = 0.92). In the survival analysis, older age and advanced tumor stage were predictors of increased risk of death. In the patterns-of-care analysis, later year of diagnosis and smaller tumor stage were predictors of BT use. CONCLUSIONS: Advanced tumor stage and older age seem to be independent predictors for risk of death from choroidal melanoma. The use of BT favors smaller tumors and later year of diagnosis. There is no difference in survival between those treated with EBRT or BT, and the utilization of BT is increasing.

Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer.

PURPOSE: Stereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern. METHODS AND MATERIALS: Individuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression. RESULTS: Fifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm (P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease. CONCLUSIONS: Local control following SRS for SCLC metastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.

Salvage Gamma Knife Radiosurgery after failed management of bilateral trigeminal neuralgia.

BACKGROUND: The incidence of bilateral trigeminal neuralgia (TN) is 1-6% of total number of TN cases. Gamma Knife Radiosurgery (GKRS) is effective in treating unilateral TN; however, outcomes of bilateral TN treated by GKRS have not been well evaluated. The purpose of this study is to evaluate the long-term GKRS outcomes of bilateral TN at our institution and compare with our published treatment outcomes of unilateral TN. METHODS: Between 2000 and 2006, eight patients with bilateral TN were treated with GKRS. Data available on seven patients were collected. Facial pain outcomes were defined using the Barrow Neurological Institute pain intensity scale. Outcomes and toxicities were compared to published outcomes of unilateral TN patients treated with GKRS at our institution. RESULTS: The incidence of bilateral TN in our series is 2.3%. Treatment outcomes were excellent in 5/14, good in 1/14, and poor in 8/14. Median follow-up time was 58 months. Median time-to-failure was 38 months. Pain control rate was 80% at 12 months and 65% at 36 months. Bothersome side effects were seen in 4/14 nerves treated. Compared with our long-term unilateral TN cohort, there was no statistically significant difference in outcome, time-to-failure, or rate of toxicity. CONCLUSION: Bilateral TN is rare, and effective treatment is crucial to improve the quality of life of those afflicted. Salvage GKRS is a reasonable treatment modality for individuals with bilateral TN.

Use of cone-beam computed tomography angiography in planning for gamma knife radiosurgery for arteriovenous malformations: a case series and early report.

BACKGROUND: The effectiveness of Gamma Knife radiosurgery (GKR) for cerebral arteriovenous malformations (AVMs) is predicated on inclusion of the entire nidus while excluding normal tissue. As such, GKR may be limited by the resolution and accuracy of the imaging modality used in targeting. OBJECTIVE: We present the first case series to demonstrate the feasibility of using ultrahigh-resolution C-arm cone-beam computed tomography angiography (CBCT-A) in AVM targeting. METHODS: From June 2009 to June 2013, CBCT-A was used for targeting of all patients with AVMs treated with GKR at our institution. Patients underwent Leksell stereotactic head frame placement followed by catheter-based biplane 2-dimensional digital subtraction angiography, 3-dimensional rotational angiography, as well as CBCT-A. The CBCT-A dataset was used for stereotactic planning for GKR. Patients were followed at 1, 3, 6, and 12 months and then annually thereafter. RESULTS: CBCT-A-based targeting was used in 22 consecutive patients. CBCT-A provided detailed spatial resolution and sensitivity of nidal angioarchitecture enabling treatment. The average radiation dose to the margin of the AVM nidus corresponding to the 50% isodose line was 15.6 Gy. No patient had treatment-associated hemorrhage. At early follow-up (mean, 16 months), 84% of patients had a decreasing or obliterated AVM nidus. CONCLUSION: CBCT-A-guided radiosurgery is feasible and useful because it provides sufficient detailed resolution and sensitivity for imaging brain AVMs.

Local control and results of Leksell Gamma Knife therapy for the treatment of uveal melanoma.

BACKGROUND AND OBJECTIVE: To evaluate the effectiveness of Leksell Gamma Knife stereotactic radio-surgery (Elekta, Stockholm, Sweden) with respect to local tumor control, visual acuity, and radiation side effects for uveal melanoma. PATIENTS AND METHODS: Retrospective, non-comparative case series of 23 patients with uveal melanoma treated with Gamma Knife stereotactic radiosurgery at Tufts Medical Center from 2000 to 2012. Patients received single-fraction stereotactic radiation therapy of 20-25 gray (Gy) (mean: 21.7 Gy), primarily at the 50% isodose line. Follow-up was 4 to 121 months (median: 41.5 months). Main outcome measures included local tumor control, metastasis, visual acuity, and complications of therapy. RESULTS: In 21 of 23 patients (91%), local control was achieved with a single session of Gamma Knife therapy. Both patients who did not have local control, as well as a third patient (three of 23, 13%) developed liver metastases. Visual acuity was 20/200 or better in eight of 23 patients (35%) at last follow-up. Radiation side effects severe enough to cause vision loss were present in 14 of 23 patients (61%). CONCLUSION: Gamma Knife therapy may be an effective alternative to enucleation in patients with uveal melanoma who are deemed less satisfactory candidates for brachytherapy or wish to avoid surgery.

BEDVH-A method for evaluating biologically effective dose volume histograms: application to eye plaque brachytherapy implants.

PURPOSE: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. METHODS: A reference eye geometry and 16 mm COMS eye plaque loaded with (103)Pd, (125)I, or (131)Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( (TUMOR)D(90)) and 10% of the organ at risk volumes ( (OAR)D(10)) were calculated. The BED equation from Dale and Jones and published α/ß and µ parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e., (TUMOR) (7)BED(10) and (OAR) (7)BED(10)). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on (TUMOR)BEDVH and (OAR)BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. RESULTS: (TUMOR)D(90) values were 102, 112, and 110 Gy for (103)Pd, (125)I, and (131)Cs, respectively. Corresponding (TUMOR) (7)BED(10) values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected, (TUMOR) (7)BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused (TUMOR) (7)BED(10) to deviate by up to 46%. Over the range of (OAR)α/ß values, (OAR) (7)BED(10) varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively. CONCLUSIONS: BEDVH permits evaluation of the relative biological effectiveness for brachytherapy implants. For eye plaques, (TUMOR)BEDVH and (OAR)BEDVH were sensitive to implant duration, which may be manipulated to affect outcomes.

Analysis of visual toxicity after gamma knife radiosurgery for treatment of choroidal melanoma: identification of multiple targets and mechanisms of toxicity.

OBJECTIVES: Identification of the targets of radiation damage after radiosurgical treatment of ocular melanoma will potentially allow for sparing of vision with improved treatment planning. MATERIALS AND METHODS: Six patients with ocular melanoma, who had useful vision before therapy, were treated with gamma knife stereotactic radiosurgery with curative intent. Dosimetric analysis of functional targets of radiation damage including the fovea, optic nerve, lens, and iris was carried out. Serial testing of visual acuity and fundoscopic examination were carried out after treatment. RESULTS: Visual sparing was achieved in 3 of 6 patients at last followup with a median follow-up of 2 years. The causes of loss of vision in those patients who lost useful vision were retinal detachment, neovascular glaucoma, and optic neuropathy. CONCLUSIONS: Preradiosurgical size and location are likely predictors of posttreatment visual outcomes.

A 17-year retrospective study of institutional results for eye plaque brachytherapy of uveal melanoma using (125)I, (103)Pd, and (131)Cs and historical perspective.

PURPOSE: To compare overall survival, local and distant failure rates, ocular toxicity, and vision preservation in patients treated with eye plaque brachytherapy at Tufts Medical Center with those in the published literature. METHODS AND MATERIALS: Records were reviewed for 53 patients with the diagnosis of uveal melanoma treated with plaque brachytherapy at Tufts Medical Center over the past 17 years. American Joint Committee on Cancer staging (T1, T2, or T3) were 4, 39, and 10 patients, respectively. All the patients were treated using (125)I (n=37), (103)Pd (n=5), or (131)Cs (n=11) to a dose of 85Gy (documented as 100Gy before 1996 for the same physical dose). RESULTS: With a mean followup of 75 months, 38 of 53 patients were still alive. Five patients (all (125)I) developed liver metastases (9%) with no evidence of local failure. There were 10 definitive local failures and four additional transpupillary thermo-therapy procedures performed to ensure local control for lesions slow to respond. Twelve patients (23%) required enucleation. At most recent followup, 32 patients (71%) maintained 20/200 vision or better in the treated eye. In this first report of (131)Cs plaque therapy with a mean followup of 20 months, there were two transpupillary thermo-therapy procedures and one definitive failure requiring enucleation after 10 months. CONCLUSIONS: Our disease control and ocular results were comparable to those in the literature given the extended followup. We are developing a multi-institutional, prospective clinical protocol for considering radionuclide selection and other prescriptive criteria.

Multifocal Stevens-Johnson syndrome after concurrent phenytoin and cranial and thoracic radiation treatment, a case report.

A 46 year old male patient with metastatic prostate cancer developed Stevens-Johnson syndrome (SJS), initially in three well-demarcated areas on his scalp, chest and back, corresponding to ports of radiation therapy while on phenytoin. The rash spread from these locations and became more generalized and associated with pain and sloughing in the mucous lining of the mouth. There is a documented association between phenytoin administration with concurrent cranial radiation therapy and development of SJS. Erythema multiforme (EM) associated with phenytoin and cranial radiation therapy (EMPACT) is the term that describes this reaction. However, this term may not cover the full spectrum of the disease since it describes EM associated with phenytoin and only cranial radiation therapy. This case report presents evidence that SJS may be induced by radiation to other parts of the body in addition to the cranium while phenytoin is administered concomitantly. With increasing evidence that phenytoin and levetiracetam are equally efficacious for seizure treatment and prophylaxis, and since there is no link identified so far of an association between levetiracetam and SJS, we believe that levetiracetam is a better option for patients who need anticonvulsant medication(s) while undergoing radiation therapy, especially cranial irradiation.

Adjuvant Gamma Knife radiosurgery following surgical resection of brain metastases: a 9-year retrospective cohort study.

Given the potential morbidity of whole brain radiation therapy (WBRT), there has been an increasing trend to defer WBRT and deliver Gamma Knife stereotactic radiosurgery (GKS) to cerebral metastatic lesions. We analyzed our experience delivering GKS to the tumor cavity following surgical resection of brain metastases and compared our results to patients receiving WBRT after surgical resection of a metastatic lesion. We performed a retrospective review of patients undergoing surgical resection of at least one brain metastasis between December 1999 and December 2008. Both univariate and multivariate Cox proportional hazards regression were utilized to analyze the influence of various prognostic factors on survival. Twenty-five patients had a metastatic lesion resected followed by adjuvant GKS to the resection cavity while another 18 had surgical resection followed by WBRT. Aside from a disparity in gender distribution (72% of GKS patients were female while women only constituted 28% of the WBRT group), no significant differences existed between groups. The median survival for patients receiving GKS was 15.00 months as compared to 6.81 months among those receiving WBRT (P = 0.08). Univariate Cox regression analysis identified the number of metastases (HR 1.65, 95% CI 1.07-2.54, P = 0.02) and regional recurrence (RR 5.23, 95% CI 1.78-15.38, P = 0.003) as poor prognostic factors. Multivariate regression analysis showed that regional recurrence (HR 5.17, 95% CI 1.69-15.78, P = 0.004) was again strongly associated with worse survival. Although limited by the retrospective nature of our study and lack of some clinical measures, patients undergoing GKS to the resection cavity had a trend towards longer median survival.

Outcomes following single-treatment Gamma Knife surgery for trigeminal neuralgia with a minimum 3-year follow-up.

OBJECT: Gamma Knife surgery (GKS) has been shown to be effective in treating trigeminal neuralgia (TN). Existing studies have demonstrated success rates of 69.1-85% with median follow-up intervals of 19-60 months. However, series with uniform long-term follow-up data for all patients have been lacking. In the present study the authors examined outcomes in a series of patients with TN who underwent a single GKS treatment followed by a minimum follow-up of 36 months. They used a clinical scale that simplifies the reporting of outcome data for patients with TN. METHODS: Fifty-three consecutive patients with typical, intractable TN received a median maximum radiation dose of 80 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and questionnaire. Outcome results were categorized into the following classes (in order of decreasing success): Class 1A, complete pain relief without medications; 1B, complete pain relief with either a decrease or no change in medications; 1C, > or = 50% pain relief without medications; 1D, > or = 50% pain relief with either a decrease or no change in medications; and Class 2, < 50% pain relief and/or increase in medications. Patients with Class 1A-1D outcome (equivalent to Barrow Neurological Institute Grades I-IIIb) were considered to have a good treatment outcome, whereas in patients with Class 2 outcome (equivalent to Barrow Neurological Institute Grades IV and V) treatment was considered to have failed. RESULTS: A good treatment outcome from initial GKS was achieved in 31 (58.5%) patients for whom the mean follow-up period was 48 months (range 36-66 months). Outcomes at last follow-up were reflected by class status: Class 1A, 32.1% of patients; 1B, 1.9%; 1C, 3.8%; 1D, 20.8%; and Class 2, 41.5%. Statistical analysis showed no difference in outcomes between patients previously treated with microvascular decompression or rhizotomy compared with patients with no previous surgical treatments. Thirty-six percent of patients reported some degree of posttreatment facial numbness. Anesthesia dolorosa did not develop in any patient. CONCLUSIONS: Despite a time-dependent deterioration in the success rate of GKS for medically intractable TN, the authors' study showed that > 50% of patients can be expected to have a good outcome based on their scoring system, with approximately 33% having an ideal outcome (pain free with no need for medications). Long-term data, as those presented here, are important when counseling patients on their treatment options.

Intracardiac chloroma.

Chloromas are not frequently seen in patients with acute myelogenous leukemia and chloromas involving cardiac structures have only been rarely reported in the literature. We report a complete radiographic response to low-dose fractionated radiotherapy in a patient with an intracardiac chloroma.

Retreatment of trigeminal neuralgia with Gamma Knife radiosurgery: is there an appropriate cumulative dose? Clinical article.

OBJECT: Trigeminal neuralgia (TN) is a disorder of the trigeminal nerve that results in intense episodic pain. Primary treatment with Gamma Knife surgery (GKS) is well established; however, a significant number of patients experience recurrence of TN over time. Repeat GKS can be performed, but the retreatment dose has not been well established. In this study, the authors present their institutional retreatment results and compare them with other series. METHODS: Between December 2003 and January 2006, 28 patients were treated at Tufts Medical Center with repeat GKS for recurrence of TN. All patients had been initially treated with GKS at this institution, and only those with significant pain improvement were offered retreatment. The maximum dose was prescribed using a single isocenter; the 4-mm collimator was used. The initial median GKS dose was 80 Gy, the median retreatment dose was 45 Gy, and the median cumulative dose was 125 Gy. The median time between GKS procedures was 18.1 months. Facial pain outcomes were defined using the Marseille scale. Excellent outcome was defined as no pain (with or without medications), and good outcome was defined as > 50% pain relief. Toxicity was categorized as none, mild, or bothersome. The median clinical follow-up after the second GKS was 19.7 months. Our clinical outcomes were compared with 8 previously reported retreatment series (including 1 abstract), both for rate of pain control and for rate of complications. RESULTS: Outcomes after the second GKS were excellent in 29% (8 patients), good in 32% (9), and poor in 39% (11). Four patients (14%) experienced no improvement after repeat GKS. Eight patients (29%) experienced new trigeminal nerve dysfunction, including numbness (11%), paresthesia (14%), dysesthesia (4%), taste alteration (11%), and bite weakness (4%). None of these were bothersome. No patient developed corneal numbness. Univariate analysis failed to reveal any significant predictors of pain control or complications. Seven published peer-reviewed retreatment series and the authors' data (total 215 patients) were analyzed. There was a cumulative dose-response relationship for both pain control (p = 0.04) and new trigeminal dysfunction (p = 0.08). Successful pain control was strongly correlated with development of new dysfunction (p = 0.02). A cumulative dose > 130 Gy was more likely to result in successful (> 50%) pain control, but was also more likely (> 20%) to result in development of new dysfunction. CONCLUSIONS: Successful retreatment of patients in whom the initial GKS treatment fails is feasible. Patients who respond initially may be at a higher risk of retreatment-related complications. There appears to be a dose-response relationship for both pain control and development of new side effects. It is important to counsel and treat patients individually based on this dose-response relationship.

Dose de-escalation with gamma knife radiosurgery in the treatment of choroidal melanoma.

PURPOSE: Single-fraction targeted radiation therapy delivered by the Leksell Gamma Knife system is a minimally invasive treatment option for choroidal melanoma that has been used as an alternative to enucleation, proton beam therapy, or brachytherapy. Previously reported Gamma Knife series involved the treatment of choroidal melanomas with a dose of 40 to 50 Gy at the tumor margin. We report our institutional experience using a significantly lower dose. METHODS AND MATERIALS: Fourteen patients with choroidal melanoma were treated with the Leksell Gamma Knife at our institution over a 7-year period. The treatment and clinical data were analyzed in a retrospective fashion after a mean follow-up of 32.2 months. RESULTS: The mean dose to the tumor margin was 22.2 +/- 2.4 Gy (range, 20- 25 Gy). Mean treated tumor volume was 1.1 +/- 1.2 cc. Local control was achieved in 13 cases (93%). In 1 patient both intraocular spread and distant metastatic disease developed after treatment. Visual function of the affected eye was preserved in 5 patients (36%) at latest follow-up, in 9 patients (64%) visual loss ensued. Mild to moderate radiation toxicity developed in 8 patients. CONCLUSIONS: Choroidal melanoma can be safely and effectively treated using Leksell Gamma Knife stereotactic radiosurgery with a marginal dose of less than 25 Gy.

Local recurrence after mastectomy in patients with T3pN0 breast carcinoma treated without postoperative radiation therapy.

OBJECTIVE: The need for comprehensive adjuvant radiotherapy in patients with T3pN0 breast cancer is controversial. This retrospective analysis was performed to assess the frequency of local and distant recurrence in patients treated with mastectomy without postoperative radiation. MATERIALS AND METHODS: A single institution database of 2362 patients with breast carcinoma treated from 1974 to 1994 yielded 101 patients who had T3pN0 disease and did not receive chest wall or nodal irradiation. The median follow-up time was 93 months (range, 10-256 months). Sites of first failure were categorized as isolated chest wall (CWF), regional lymph nodes (RNF, which in this case were considered to be either axillary or supraclavicular), or distant sites (DF). CWF and/or RNF were considered local recurrences. Patients with simultaneous CWF and DF or RNF and DF were scored as DF. A comparison was made to 286 T2pN0 patients, also treated between 1974 and 1994. RESULTS: Twenty-two T3N0 patients developed recurrent disease. Site of first recurrence was isolated local recurrence in 11 patients and distant in 11 patients. Four patients had simultaneous local and distant recurrences. Site of isolated local recurrence was CWF in 5 patients and RNF in 6 patients. Median tumor size was 6 cm (range, 5-10.5 cm). There was no difference in local recurrence for tumor sizes < or =7 cm versus >7 cm (P = 0.07). The crude recurrence rate for T3pN0 patients treated by mastectomy was similar to T2pN0 patients treated in similar fashion (P = 0.3). CONCLUSION: The risk of isolated local recurrence in patients with T3pN0 breast cancer and negative margins is moderately low and similar to T2pN0 patients. These results suggest that routine use of postoperative chest wall and nodal irradiation in all T3pN0 patients may not be required.