Spurious progression in pediatric brain tumors.

In this study, we sought to characterize post-therapy MRI changes mimicking progression, which we refer to as "spurious progression" (SP) in children with brain tumors. We analyzed whether SP is associated with particular tumor types or therapeutic modalities. Between 2000 and 2009, we identified 181 consecutive children <21 years of age at our center who were treated for brain tumors and had at least three MRI scans within a year after completing therapy. SP was defined as MRI abnormalities characterized by increase in size, enhancement, edema, or cystic changes within 12 months following therapy, and stabilization or improvement on subsequent imaging. One-hundred forty-one patients with brain tumors were evaluable. Fifty-six (40%) had imaging abnormalities initially suggestive of disease progression; of these, 34 (24%) had true disease progression (TP). The remaining 22 (16%) had SP based on either stability, decrease in enhancement, edema, size, or disappearance of these cystic or non-cystic abnormalities. SP occurred in patients with low grade (n = 20) and high grade lesions (n = 2). Median time to SP was 2.4 months (range, 0.7-8.3 months), with time to stability, decrease, or disappearance at a median of 4 months (range 1.4-7.7 months). Five patients were clinically symptomatic from SP and were treated with steroids, cyst drainage, and/or surgery. Therefore, SP occurs more commonly in children with low grade tumors, but can also occur with high grade brain tumors, regardless of therapeutic approach.

Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy.

PURPOSE: Prospective pilot study to assess patient outcome after stereotactic body radiation therapy (SBRT) for limited metastases from breast cancer. METHODS: Forty patients with < or =5 metastatic lesions received curative-intent SBRT, while 11 patients with >5 lesions, undergoing SBRT to < or =5 metastatic lesions, were treated with palliative-intent. RESULTS: Among those treated with curative-intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free survival of 38% and lesion local control of 89%. On univariate analyses, 1 metastatic lesion (versus 2-5), smaller tumor volume, bone-only disease, and stable or regressing lesions prior to SBRT were associated with more favorable outcome. Patients treated with palliative-intent SBRT were spared morbidity and mortality from progression of treated lesions, though all developed further metastatic progression shortly (median 4 months) after enrollment. CONCLUSIONS: SBRT may yield prolonged survival and perhaps cure in select patients with limited metastases. Palliative-intent SBRT may be warranted for symptomatic or potentially symptomatic metastases.

Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose.

PURPOSE: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. METHODS AND MATERIALS: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). RESULTS: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. CONCLUSIONS: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases.

PURPOSE: To evaluate the feasibility and efficacy of hypofractionated stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver lesions treated with SBRT between April 2001 and October 2004 were reviewed. The most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5 (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2 cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor volume with a minimum margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of SBRT. The actuarial overall infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20 months, respectively. The median overall survival time was 14.5 months. The progression-free survival rate was 46% and 24% at 6 and 12 months, respectively. None of the patients developed Grade 3 or higher toxicity. CONCLUSION: Hypofractionated SBRT provides excellent local control with minimal side effects in selected patients with limited hepatic metastases.

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

Stereotactic body radiotherapy for treatment of adrenal metastases.

PURPOSE: To investigate the dosimetry and outcomes of patients undergoing stereotactic body radiotherapy (SBRT) for metastases to the adrenal glands. METHODS AND MATERIALS: At the University of Rochester, patients have been undergoing SBRT for limited metastases since 2001. We retrospectively reviewed 30 patients who had undergone SBRT for adrenal metastases from various primary sites, including lung (n = 20), liver (n = 3), breast (n = 3), melanoma (n = 1), pancreas (n = 1), head and neck (n = 1), and unknown primary (n = 1). RESULTS: Of the 30 patients, 14 with five or fewer metastatic lesions (including adrenal) underwent SBRT, with the intent of controlling all known sites of metastatic disease, and 16 underwent SBRT for palliation or prophylactic palliation of bulky adrenal metastases. The prescribed dose ranged from 16 Gy in 4 fractions to 50 Gy in 10 fractions. The median dose was 40 Gy. Of the 30 patients, 24 had >3 months of follow-up with serial computed tomography. Of these 24 patients, 1 achieved a complete response, 15 achieved a partial response, 4 had stable disease, and 4 developed progressive disease. No patient developed symptomatic progression of their adrenal metastases. The 1-year survival, local control, and distant control rate was 44%, 55%, and 13%, respectively. No patient developed Radiation Therapy Oncology Group Grade 2 or greater toxicity. CONCLUSION: SBRT for adrenal metastases is well tolerated. Most patients developed widespread metastases shortly after treatment. Local control was poor, although this was a patient population selected for adverse risk factors, such as bulky disease. Additional studies are needed to determine the efficacy of SBRT for oligometastatic adrenal metastases, given the propensity of these patients to develop further disease progression.

A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.

BACKGROUND: It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS: The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS: Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT.

Low-dose radiosurgery for benign intracranial lesions.

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.