Examination of the Dose-Effect Relationship of Radiation-Induced Hypopituitarism: Results of a Case-Control Study.

PURPOSE: Previous reports have documented a dose-effect relationship for radiation-induced hypopituitarism in patients receiving therapy near or at the base of the skull. We aimed to characterize this long-term endocrinopathy further by examining the effect of dose on both the incidence and severity of toxicity, as well as exploring a possible dose threshold for this effect. METHODS AND MATERIALS: Out of an initial 346 patients who had received radiation therapy to the base of the skull, 53 patients with adequate endocrine evaluation were found. Of these, 19 patients who subsequently developed at least 1 endocrinopathy (cases) as well as 17 patients who did not (controls) were identified, for a total of 36. Patients' charts were reviewed, and endocrinologic laboratory tests recorded. Treatment plans were reviewed and doses to the hypothalamus and pituitary gland were calculated. One-way analysis of variance was used to determine differences between cases and controls, and Pearson's correlation coefficient was used to relate mean pituitary dose to serum free thyroxine, insulin-like growth factor 1, prolactin, cortisol, and luteinizing hormone. RESULTS: There were 20 men and 16 women, with a median age of 58. Median follow-up was 32 months (range, 18- 85 months). Median total plan dose delivered was 54 Gy (range, 50.4-70 Gy). Independent sample t tests as well as univariate analysis showed a significantly greater dose to the hypothalamus and pituitary of the cases compared with the controls, while other factors were not significantly different between the 2 groups. There was a statistically significant negative correlation (Pearson's correlation coefficient = -0.65, P = .001) between the mean dose to the pituitary gland and the serum free thyroxine. No case of endocrine toxicity was observed at a mean dose to the pituitary below 30 Gy. CONCLUSIONS: Our results suggest that late endocrinopathy is a true deterministic effect, with a dose threshold, and with both the incidence and severity of toxicity being related to the dose.

A retrospective study of head and neck re-irradiation for patients with recurrent or second primary head and neck cancer: the McGill University experience.

BACKGROUND: We report our experience with patients who received re-irradiation to the head and neck area for locoregional recurrences (LRR) or second primaries (SP) in a previously irradiated field. METHODS: We reviewed 27 consecutive patients with a diagnosis of LRR or SP head and neck carcinoma treated with a second course of radiotherapy between April 2004 and July 2012. The main outcome measures were local control, overall survival, and complications. The results are expressed as actuarial values using the Kaplan-Meier estimates. RESULTS: The median follow-up time was 24.7 months (range: 11 days-79.3 months). There were 23 males and four females with a median age of 61 years (range: 40-87 years). The actuarial overall survival rates at 1, 2, and 5 years were 77, 59, and 57%, respectively. The actuarial local control rate was 80, 52, and 52% at 1, 2, and 5 years, respectively. Three patients developed systemic metastases. The rate of grade 3 toxicity was 26%, and that of grade 4 toxicity was 3%. There were two treatment-related deaths (grade 5 toxicity). CONCLUSIONS: Continuous course re-irradiation in patients with LRR or SP head and neck cancer is feasible with acceptable toxicity. With current encouraging rates of local control and overall survival, this option should be discussed with patients who have few alternative therapeutic options.

Kinetics of myxoid liposarcoma radiation response and effects on radiation dose delivery.

PURPOSE: Recent reports have described the radioresponsiveness of myxoid liposarcomas (MLS). We sought to describe the kinetics of these changes during image guided radiation therapy and determine the effect of these changes in volume on the dose distribution. METHODS AND MATERIALS: We reviewed the images of all patients with the diagnosis of MLS who had undergone preoperative radiation therapy using image guidance at our institution. All patients received a dose of 50 Gy in 25 fractions. Tumor volume was measured on each patient's computed tomographic (CT) simulation scan, on weekly CT images performed for image guidance, as well as on postradiation imaging. Dose distributions were recalculated using the last treatment CT images. RESULTS: Fifteen patients, 9 men and 6 women with a median age of 48 years, were identified in our database. All tumors were located in the lower extremity. During treatment, all tumors decreased in volume (P = .001). The median change in volume from CT simulation to the last image guided radiation therapy image set was -42% (-142 cm(3) median absolute reduction). Volume reduction ranged from -8% to -69%. The median rate of volume change was -5.5 cm(3)/day (range, -0.4 to -14.1). Five patients were clinically judged to require replanning during the course of treatment, all of them during the first 3 weeks. Shrinkage was typically greatest in the transverse direction. The dose distribution did not change significantly when the volumetric changes were taken into account, except for a higher maximal dose to adjacent bone. CONCLUSIONS: Our results confirm that MLS shrink significantly during radiation treatment. In spite of the large volumetric changes, we found little change in the dose to the tumor and surrounding structures. Routine treatment replanning may not be required in these patients but the interval from CT simulation to first treatment should be minimized to avoid the need for early replanning due to tumor progression.

FDG PET/CT in Initial Staging of Adult Soft-Tissue Sarcoma.

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.

Volumetric measurement of vestibular schwannoma tumour growth following partial resection: predictors for recurrence.

Vestibular schwannomas (VS) have a higher risk of recurrence following subtotal resection than following near-total resection. We measured tumor remnant growth volumetrically in an attempt to determine potential predictors for postoperative recurrence following subtotal resection. We reviewed the charts of patients who had undergone VS surgery between 1998 and 2007. Thirty patients had an incomplete resection. The principal outcome measure was change in tumor volume (TV) on serial imaging. At a median follow-up of 6.8 years, volumetric measurements showed that 12 patients (40%) developed further tumor growth, while 18 patients remained with stable residual disease. The median rate of growth was 0.53 cm(3)/year. Two-dimensional measurements confirmed growth in only eight of these patients. The postoperative residual TV correlated significantly with subsequent tumor growth (p = 0.038). All patients with residual volumes in excess of 2.5 cm(3) exhibited recurrence. On univariate analysis, only postoperative TV was significantly associated with growth. Median time to failure was 21.5 months. This is the first report of volumetric measurements of VS tumor growth postoperatively. Volumetric measurements appear to be superior to two-dimensional measurements in documenting VS growth and patients with residual tumors >2.5 cm(3) have a significantly higher rate of recurrence.