Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors.

Patients with brain metastasis from renal cell carcinoma (RCC) or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS) can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS) for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT) in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS), number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months) than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024). Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90-100), with median survival times of 5.80 ± 2.46 months (p < 0.001) and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5) and lower KPS were statistically significant predictors of a lower OS prognosis.

Gamma knife treatment of brainstem metastases.

The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control.

Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.

BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS). RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed. CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.

Intensity-modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study.

OBJECTIVES: To assess toxicity and efficacy of intensity-modulated radiation therapy (IMRT) for anal cancer. METHODS: Records of 152 patients were reviewed retrospectively from multiple institutions. Data on disease control and toxicity were collected as well as patient and treatment characteristics. Acute (<6 mo) and late (≥6 mo) severe toxicity (grade ≥3) were graded. Four patients were excluded due to the presence of metastatic disease or stage TX. Late toxicity data were available for 120 patients. RESULTS: Median cumulative IMRT dose was 51.25 Gy (median, 28 fractions). All but 2 patients received chemotherapy. With median follow-up of 26.8 months, local control at 3 years was 87%, worse for patients with T3-T4 than T1-T2 disease on univariate analysis (79% vs. 90%; P=0.04). Regional control, distant control, and overall survival were 97%, 91%, and 87%, respectively, at 3 years. Nodal status was associated with regional control, distant control, and overall survival (P<0.01 for each). Most common severe acute toxicity was hematologic (41%), skin (20%), and gastrointestinal tract (11%). Two grade 5 toxicities occurred (hematologic and gastrointestinal tract). Severe late toxicity affected skin (1%) and gastrointestinal tract (3%). CONCLUSIONS: IMRT with chemotherapy resulted in excellent local control. Although T stage predicted worse local control, most T3-T4 disease was controlled with IMRT. Nodal status predicted regional and distant control and overall survival. Severe toxicity was acceptable.

Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery.

BACKGROUND: Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS. METHODS: Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS. RESULTS: Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70-80 showed significantly shorter survival than those with KPS 90-100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779). CONCLUSION: SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients.

Prolonged Survival following Repetitive Stereotactic Radiosurgery in a Patient with Intracranial Metastatic Renal Cell Carcinoma.

Patients with metastatic renal cell carcinoma (RCC) to the brain have a very poor prognosis of three months if left untreated. SRS is an effective treatment modality in numerous patients. This case exemplifies the utility of stereotactic radiosurgery (SRS) in prolonging survival and maintaining quality of life in a patient with RCC. This 64-year-old female patient initially presented to her primary care physician 22 months after a left nephrectomy for RCC with complaints of mild, intermittent headaches and difficulty with balance. An MRI revealed five cerebellar lesions suspicious for intracranial metastasis. The patient's first GKRS treatment targeted four lesions with 22 Gy at the 50% isodose line. She underwent a total of seven GKRS treatments over the next 60 months for recurrent metastases to the brain. 72 months and 12 months have now passed since her brain metastases were first discovered and since her last GKRS treatment, respectively, and this woman is alive with considerable quality of life and no evidence of metastatic reoccurrence. This case shows that repeated GKRS treatments, with minimal surgical intervention, can effectively treat multiple intracranial lesions in select patients, prolonging survival and avoiding iatrogenic neurocognitive decline while maintaining a high quality of life.

Use of intraoperative radiotherapy for upper-extremity soft-tissue sarcomas: analysis of disease outcomes and toxicity.

OBJECTIVES: To review outcomes for patients who received intraoperative radiotherapy (IORT) for upper-extremity sarcoma. METHODS: We identified patients with upper-extremity tumors who were treated with external beam radiotherapy, surgery, and IORT, with or without chemotherapy. Kaplan-Meier estimates for overall survival (OS), central control (CC), local control (LC), and distant control (DC) were obtained. RESULTS: Sixty-one patients were identified. Median age was 50 years (range, 13 to 95 y). Median follow-up was 5.9 years. Eleven patients had gross (R2; n=1) or microscopic (R1; n=10) disease at the time of IORT. IORT doses ranged from 7.50 to 20.00 Gy. External beam radiotherapy doses ranged from 19.80 to 54.00 Gy. OS at 5 and 10 years was 72% and 58%, respectively. LC at 5 and 10 years was 91% and 88%, respectively. DC at 5 and 10 years was 80% and 77%, respectively. Patients treated for recurrent disease had inferior 5-year OS compared with patients with first diagnoses (63% vs. 74%; P=0.02) and lower 5-year LC (67% vs. 94%; P<0.01). For patients with R1 or R2 resections, LC at 5 and 10 years was 100% and 86%, respectively; for patients with R0 resections, LC was 89% at both 5 and 10 years (P=0.98). Severe toxicity attributable to treatment was noted for 4 patients (7%). CONCLUSIONS: For upper-extremity sarcoma, treatment including IORT was associated with excellent LC, limb preservation, and survival. LC rates were excellent for patients with positive margins after resection. Patients with recurrent disease had worse outcomes, but limb preservation was achievable for most patients.

Long-term outcomes and role of chemotherapy in adults with newly diagnosed medulloblastoma.

OBJECTIVE: To assess the survival and role of adjuvant chemotherapy in adult medulloblastoma. METHODS: We reviewed outcomes of 66 patients (aged 18 y or more; median age, 33 y) with medulloblastoma. Forty-four (67%) patients had M0 disease, 9 had M1-M4, and 13 had MX. Thirty-one patients each for whom risk stratification was available were classified as high risk or standard risk. Fifty-six patients had histologic results: classic histology was the most common (n=46 [84%]), followed by desmoplastic (n=9), and large cell/anaplastic (n=1). Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier curves and log-rank tests. Cox regression analysis was used to compare recurrences. RESULTS: Median follow-up was 6.7 years. The estimated 5-year OS and PFS were 74% and 59%, respectively. High-risk versus standard-risk classification was associated with worse OS (61% vs. 86%; P=0.03) and recurrence (hazard ratio, 2.56; P=0.05) and a trend for worse PFS (49% vs. 69%; P=0.13). Gross total resection was associated with improved OS (P=0.03) and a trend toward improved PFS (P=0.09). No chemotherapy benefit could be demonstrated for the group as a whole. For high-risk patients with classic histology (n=25), chemotherapy was associated with a trend for improvement in 5-year PFS from 36% to 71% (P=0.10) and in 5-year OS from 49% to 100% (P=0.08). CONCLUSIONS: In adult patients with medulloblastoma, the extent of resection and risk classification predicts the outcome. These results suggest a chemotherapy benefit for high-risk patients with classic histology.

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed.

Concurrent chemotherapy and intensity modulated radiation therapy in the treatment of anal cancer: A retrospective review from a large academic center.

PURPOSE: To assess the toxicity and efficacy of intensity modulated radiation therapy (IMRT) combined with chemotherapy in treatment of anal cancer. METHODS AND MATERIALS: We examined the records of 34 consecutive patients who received chemoradiation therapy with IMRT as initial treatment for squamous cell carcinoma of the anus between June 2005 and January 2009. The median radiation dose was 50.4 Gy (range, 48.6-57.6 Gy). Chemotherapy was given concurrently: 5-fluorouracil alone in 1 patient and combination 5-fluorouracil and mitomycin C in all others. Endpoints included local control and survival, as well as toxicity. Acute and late toxicity was scored with the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Twenty-eight patients presented with T1 and T2 disease and 6 with T3 and T4 disease. Fourteen patients had regional nodal metastases. The median age was 59 years (range, 46-85 years). Median follow-up in surviving patients was 22 months. The estimated 2-year survival was 93% (95% confidence interval, 76%-98%). Three patients (9%) had local relapse (estimated 2-year local control, 90%; 95% confidence interval, 74%-97%). One patient had relapse in a regional node. Acute grade 3-4 hematologic toxicity was observed in 20 patients (59%). Other acute grade 3 or grade 4 toxicity included the gastrointestinal tract in 3 patients (9%) and skin in 5 patients (15%). Two patients (6%) had late grade 3 or grade 4 gastrointestinal tract toxicity. CONCLUSIONS: Treatment of anal squamous cell carcinoma with IMRT and chemotherapy is effective and has an acceptable toxicity profile.

A role for radiotherapy in the management of advanced medullary thyroid carcinoma: the mayo clinic experience.

Outcomes of external beam radiotherapy (EBRT) in advanced medullary thyroid carcinoma (MTC) are largely unknown. Retrospective review of data from patients with MTC, diagnosed from June 1, 1970, through December 31, 2007. Overall survival and locoregional tumor control rates were calculated. Seventeen patients had adjuvant or palliative EBRT delivered to 41 sites. Six patients initially had adjuvant EBRT (median, 60.80 Gy); none had relapse in the treated area. Five patients with locoregional recurrence after surgery were treated (median, 59.40 Gy), and durable disease control was achieved in 3. Twelve patients received palliative EBRT to 29 sites of metastatic disease (median, 30.00 Gy), which provided sustained symptom relief at 45% of sites. Five- and ten-year overall survival rates were 44% and 19%, respectively. Adjuvant EBRT may be most effective for prevention of locoregional recurrence. EBRT may provide sustained control of advanced, metastatic disease in select patients.

Gamma knife radiosurgery treatment for metastatic melanoma of the trigeminal nerve and brainstem: a case report and a review of the literature.

Objective and Importance. Brainstem metastases (BSMs) are uncommon but serious complications of some cancers. They cause significant neurological deficit, and options for treatment are limited. Stereotactic radiosurgery (SRS) has been shown to be a safe and effective treatment for BSMs that prolongs survival and can preserve or in some cases improve neurological function. This case illustrates the use of repeated SRS, specifically Gamma Knife radiosurgery (GKRS) for management of a unique brainstem metastasis. Clinical Presentation. This patient presented 5 years after the removal of a lentigo maligna melanoma from her left cheek with left sided facial numbness and paresthesias with no reported facial weakness. Initial MRI revealed a mass on the left trigeminal nerve that appeared to be a trigeminal schwannoma. Intervention. After only limited response to the first GKRS treatment, a biopsy of the tumor revealed it to be metastatic melanoma, not schwannoma. Over the next two years, the patient would receive 3 more GKRS treatments. These procedures were effective in controlling growth in the treated areas, and the patient has maintained a good quality of life. Conclusion. GKRS has proven in this case to be effective in limiting the growth of this metastatic melanoma without acute adverse effects.

Long-Term Survival and Improved Quality of Life following Multiple Repeat Gamma Knife Radiosurgeries for Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature.

The management of glioblastoma multiforme (GBM) is in most cases complex and must be specifically tailored to the needs of the patient with the goals of extended survival and improved quality of life. Despite advancements in therapy, treatment outcomes remain almost universally poor. Salvage treatment options for the recurrence of the disease is an area of intense study. The following case highlights the utility of Gamma Knife Radiosurgery (GKRS) as a salvage treatment. In this clinical situation, three sequential GKRS treatments led to prolonged survival (beyond four years after diagnosis) and improved quality of life in a patient who was unable to receive further chemotherapy regimens and was unwilling to undergo further aggressive resection. To date, there have been few reports of three or more sequential GKRS treatment sessions utilized as salvage therapy for recurrent GBM in patients who can no longer tolerate chemotherapy. This report provides evidence that aggressive local treatment with GKRS at the time of recurrence may be appropriate, depending on a patient's individual clinical situation, and can lead to prolonged survival and improved quality of life.

Intensity-modulated radiotherapy for squamous cell carcinoma of the anal canal: efficacy of a low daily dose to clinically negative regions.

BACKGROUND: We aimed to assess outcomes of patients with anal cancer who underwent intensity-modulated radiotherapy (IMRT) and received less than 1.80 Gy/day. METHODS: We retrospectively reviewed our experience using a low fractional dose (< 1.80 Gy) of IMRT to elective nodal areas for patients receiving chemoradiotherapy for anal cancer. Three-year freedom from any disease relapse and overall survival were estimated using Kaplan-Meier curves. We documented the daily dose that was delivered to clinically uninvolved regions and to areas of gross disease. Incidence of regional failures in high (≥ 1.80 Gy) and low (< 1.80 Gy) daily dose regions was assessed. RESULTS: Thirty-four consecutive patients (median age, 59 years) received IMRT from June 2005 through January 2009. Median follow-up duration was 22 months. Twenty-eight patients had T1 or T2 disease and 6 had T3 or T4 disease. Fourteen patients had nodal metastases. Median treatment dose was 50.40 Gy (range, 48.60-57.60 Gy) in 25 to 32 fractions. The range of fractional doses to clinically negative volumes was 1.28 to 1.80 Gy. Seventeen patients (50%) received a fractional dose of less than 1.60 Gy, 13 (38%) received less than 1.50 Gy, and 9 (26%) received less than 1.40 Gy to at least a portion of the clinically negative volume. Three-year freedom from relapse was 80%, and 3-year overall survival was 87%. No patient had treatment failure in the clinically negative volume that received a low daily dose. CONCLUSIONS: Our data support using doses between 1.50 and 1.80 Gy/day to clinically uninvolved regions.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

BACKGROUND AND PURPOSE: Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. MATERIAL AND METHODS: A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. RESULTS: With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. CONCLUSIONS: Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.