Upfront boost Gamma Knife "leading-edge" radiosurgery to FLAIR MRI-defined tumor migration pathways in 174 patients with glioblastoma multiforme: a 15-year assessment of a novel therapy.

OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22-87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5-220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6-14 Gy) at the 50% isodose line. RESULTS The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1-3 grades in 10% due to symptomatic treatment-related imaging changes. CONCLUSIONS LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.

Durable complete response of refractory, progressing metastatic melanoma after treatment with a patient-specific vaccine.

A patient with metastatic melanoma who experienced a durable complete response after treatment with a patient-specific vaccine has been described in this article. This 59-year-old woman presented with cervical spine metastases and, within the year, had experienced local disease progression and, despite various therapies, metastases to the axilla, rectum, gall bladder, and multiple soft-tissue sites. She had previously received radiation therapy, combination chemotherapy, interleukin-2 plus interferon biotherapy, and gamma knife radiosurgery, and undergone multiple surgical resections. At the time vaccine therapy was initiated, she had multiple, new, measurable, soft-tissue metastases that were increasing in size. She was treated with a vaccine consisting of autologous dendritic cells incubated with irradiated tumor cells from an autologous tumor cell line and suspended in granulocyte-macrophage colony stimulating factor (GM-CSF), with subcutaneous injections once a week for 3 weeks and monthly for 5 months. There was evidence of disease regression by the completion of therapy. A few months later a complete response was documented by radiologic scans, and subsequently reconfirmed at 6-month intervals. She remains in complete remission >2.5 years after starting the vaccine, and >2 years after completing the vaccine, and survives >4 years after her initial presentation with bone, bowel, and lymph node metastases. This is the first time she has been in a complete remission since her initial diagnosis. Patient-specific vaccines can sometimes induce durable complete regression of progressing soft-tissue melanoma metastases.

Adjuvant external-beam radiotherapy in patients with high-risk well-differentiated thyroid cancer.

The role of adjuvant external-beam radiation therapy (EBRT) in well-differentiated thyroid cancer is not well delineated. Many clinicians rely solely on iodine 131 (131I) to destroy thyroid remnants following thyroidectomy. However, the lesser uptake of isotope in tumor cells suggests that 131I alone may not be sufficient to eradicate microscopic residual disease when no gross thyroid tissue remains. We conducted a retrospective study to examine the potential benefit of adjuvant EBRT in patients at high risk for microscopic residual disease following thyroidectomy. Between 1973 and 2001, 44 patients with well-differentiated papillary or follicular thyroid cancer were found to have extracapsular extension following thyroidectomy. These patients were divided into 2 groups based on the type of treatment; 11 patients had received adjuvant EBRT (with or without 131I) and 33 patients had not received EBRT (i.e., they received adjuvant 131I only). We reviewed their medical records and compiled data on local recurrence and overall survival (Kaplan-Meier analysis). Despite having a less favorable prognosis, the EBRT group experienced no local recurrences during a mean follow-up of 7.8 years; in contrast, 9 local recurrences were seen in the no-EBRT group. Also, the median survival for patients without a local recurrence was longer than that for those who had failed locally (425 vs. 317 mo). Although our population was not large enough for these differences to achieve statistical significance, our study did show that adjuvant EBRT provided excellent results. We hypothesize that a reciprocal irradiation effect between cancer cells and normal cells may be necessary in order for 131I to be tumoricidal. If so, a patient with microscopic residual disease would not have enough cancer cells to sufficiently concentrate 131I. Because EBRT does not depend on such a mechanism, it may be more effective than 131I in controlling disease in the setting of microscopic disease. Larger studies are needed to validate our results. In the meantime, we believe that adjuvant EBRT should play an important role in the treatment of patients with high-risk well-differentiated thyroid cancer.