Foote, Robert L.

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.

Object Stereotactic radiosurgery (SRS) is an important treatment option for patients with cavernous sinus meningiomas (CSM). To analyze factors associated with local tumor control and complications after single-fraction SRS, the authors reviewed cases involving patients treated with Gamma Knife SRS between 1990 and 2008. Methods Excluded were patients with WHO Grade II or III tumors, radiation-induced tumors, multiple meningiomas, neurofibromatosis Type 2, and prior or concurrent radiotherapy. Five patients were lost to follow-up and 3 patients refused research authorization. The remaining 115 patients (29 men, 86 women) had either histologically confirmed WHO Grade I (n = 46, 40%) or presumed (n = 69, 60%) CSM. The median treatment volume was 9.3 cm3 (range 1.3–42.2 cm3). The median margin dose was 16 Gy (range 12–20 Gy). The median follow-up after SRS was 89 months (range 12–251 months). Thirty-nine patients (34%) had 10 or more years of follow-up after SRS. Results Six patients (5%) had tumor progression (in field, n = 3; marginal, n = 3) at a median of 74 months (range 42–145 months) after SRS. The local tumor control rate was 99% at 5 years and 93% at 10 years after SRS. No analyzed factor was associated with local control after SRS. Fourteen patients (12%) had permanent complications at a median onset of 23 months (range 2–146 months) including trigeminal dysfunction (n = 9), diplopia (n = 2), ischemic stroke (n = 2), and hypopituitarism (n = 1). The 2-year, 5-year, and 10-year rates of complications were 7%, 10%, and 15%, respectively. Multivariate analysis found larger treatment volume (HR 1.1, 95% CI 1.02–1.2, p = 0.01) to be associated with complications after SRS. The complication rate for patients with a treatment volume of 9.3 cm3 or less was 3% (2 of 58 cases) compared with 21% (12 of 57 cases) for patients with a treatment volume greater than 9.4 cm3. Conclusions Single-fraction SRS at the radiation doses used in this series provided durable tumor control for patients with benign CSM. Larger tumor volume remains the primary factor associated with complications after single-fraction SRS of benign CSM despite advancements in SRS technique.

The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Object Gamma Knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors. Methods Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm3 (range 5.3–19.1 cm3). The median maximum posterior fossa diameter was 2.8 cm (range 2.5–3.8 cm). The median tumor margin dose was 12 Gy (range 12–14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26–121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection. Results Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction. Conclusions Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.

AbstractOBJECTIVEOur aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be “radioresistant” on the basis of histological examination.METHODSWe reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases.RESULTSThe median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027).CONCLUSIONWell-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Object The decline in cranial nerve morbidity after radiosurgery for vestibular schwannoma (VS) correlates with dose reduction and other technical changes to this procedure. The effect these changes have had on tumor control has not been well documented. Methods The authors performed a retrospective review of 293 patients with VSs who underwent radiosurgery between 1990 and 2004 and had a minimum of 24 months of imaging follow-up (90% of the entire series). The median radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as progressive tumor enlargement noted on 2 or more imaging studies. The mean postradiosurgical follow-up was 60.9 ± 32.5 months. Results Tumor growth was noted in 15 patients (5%) at a median of 32 months after radiosurgery. Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years after radiosurgery. Univariate analysis revealed 2 factors that correlated with failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and tumor margin radiation doses ≤ 13 Gy (p = 0.02). Multivariate analysis showed that only an increasing number of isocenters correlated with failed VS radiosurgery (hazard ratio 1.1, 95% CI 1.02–1.32, p < 0.05). The tumor margin radiation dose (p = 0.22) was not associated with tumor growth after radiosurgery. Conclusions Distortion of stereotactic MR imaging coupled with increased radiosurgical conformality and progressive dose reduction likely caused some VSs to receive less than the prescribed radiation dose to the entire tumor volume.

Object The best approach to the management of vestibular schwannoma (VS) remains controversial. The aim of this study is to analyze the initial and follow-up costs of resection and stereotactic radiosurgery for patients with VS. Methods Initial and follow-up costs in 53 cases in which patients with unilateral, previously unoperated VSs > 3 cm underwent resection (21 cases) or radiosurgery (32 cases) at the Mayo Clinic from June 2000 until July 2002 were analyzed for 36 months. Follow-up treatment-specific utilization records were gathered prospectively for patients not returning to the Mayo Clinic after treatment. Six-month moving averages of incremental follow-up costs were calculated for the 2 patient groups. Results The mean cost of surgery in the microsurgery group was $23,788 (95% confidence interval $22,280–$24,842) compared with $16,143 (95% confidence interval $15,277–$17,545) for the radiosurgical group. Mean incremental follow-up costs per month for patients in the microsurgery group started just > $1000 per month, decreased steadily, and remained < $70 per month by the 10th month of follow-up. Mean incremental follow-up costs per month for patients in the radiosurgery group were <$10 per month for the first few months and thereafter increased to as much as $200 per month. Conclusions Although the total cost of microsurgery is higher due to the costs of hospitalization, follow-up costs for radiosurgery are greater in general. From a societal perspective, radiosurgery is less expensive than microsurgical resection provided that the rate of tumor progression after radiosurgery remains low with long-term follow-up.