The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Early gene expression profile in mouse brain after exposure to ionizing radiation.

Acute changes in the gene expression profile in mouse brain after exposure to ionizing radiation were studied using microarray analysis. RNA was isolated at 0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA microarrays, and data were analyzed using GeneSpring and Significant Analysis of Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy, respectively. The expression profiles showed dose- and time-dependent changes in both expression levels and numbers of differentially modulated genes and ESTs. Seventy-eight genes were modulated at two or more times. Differentially modulated genes were associated with 12 different classes of molecular function and 24 different biological pathways and showed time- and dose-dependent changes. The change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3 was observed in another mouse strain. In mouse brain, there was an increase of Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene profile in the brain after irradiation are complex and are dependent on time and dose, and genes with diverse functions and pathways are modulated.

Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study.

PURPOSE: To analyze the factors that affect survival in patients with brain metastases (BM) from breast cancer who were treated with whole brain radiotherapy (WBRT). METHODS AND MATERIALS: We identified 116 women with breast cancer who were treated with WBRT alone between February 1984 and September 2000. All patients had treatment and follow-up data available in their medical charts, which we extracted for this retrospective study. We evaluated a number of potential predictors of survival after WBRT: age, primary tumor stage, control of primary tumor, presence of other systemic metastases, site of systemic metastases, Karnofsky performance status, Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, total dose of WBRT, and number of BM. Eighteen patients received a total dose >3000 cGy and 7 received a partial brain boost. RESULTS: For the entire cohort, the median survival from the start of WBRT was 4.2 months. The 1-year survival rate was 17%, and the 2-year survival rate was 2%. Using univariate analysis, only Karnofsky performance status (p = 0. 0084), recursive partitioning analysis class (p = 0. 0147), and total WBRT dose (p = 0.0001) were predictive of longer survival. In multivariate analysis, Karnofsky performance status was the only significant predictor. CONCLUSION: Overall survival in breast cancer patients with BM treated with WBRT is poor. We recommend breast cancer patients with BM be enrolled in prospective trials to improve results.

Brain metastases from bladder carcinoma: presentation, treatment and survival.

PURPOSE: We report the presentation of brain metastases from bladder carcinoma. We investigated the role of whole brain radiation therapy for treating this disease. MATERIALS AND METHODS: Between January 1982 and November 1999, 16 patients with brain metastases from bladder carcinoma were treated at our institution. We reviewed patient and tumor characteristics at the time of the primary diagnosis and the brain metastasis diagnosis. We analyzed treatment results in regard to survival and local metastasis control. RESULTS: Brain metastases from bladder carcinoma were commonly accompanied by uncontrolled systemic metastases. Multiple brain lesions developed in 14 of the 16 patients. Of the 16 patients 14 received radiation therapy with or without surgery, 1 was treated surgically and 1 did not receive any treatment. The 11 patients treated with whole brain radiation therapy had a median survival of only 2 months (range 0.5 to 11). A patient who received stereotactic radiosurgery survived 12 months after the brain metastasis diagnosis and 2 treated with radiation therapy after surgery survived 12.75 and 2.75 months, respectively (median 7.75). The patient treated with surgery alone survived 1.25 months after the brain metastasis diagnosis and 1 who received no treatment survived 1.75 months. Patients with multiple brain metastases had shorter survival than those with a single metastasis. CONCLUSIONS: Overall survival after brain metastasis development in patients with bladder carcinoma was poor. Although the number of patients in this study was small, results indicate that radiation therapy alone is inadequate treatment. Therefore, when possible, we advocate more effective treatment by combining radiation therapy with other treatment modalities, as recommended in ongoing clinical trials.

Recurrent head-and-neck chemodectomas: a comparison of surgical and radiotherapeutic results.

PURPOSE: To compare the outcome of salvage radiotherapy (RT) and surgery for recurrent head-and-neck chemodectomas. MATERIALS AND METHODS: We retrospectively studied 70 patients with benign chemodectomas of the head and neck treated with surgery at the Cleveland Clinic between July 1969 and August 1999; 29 of these patients were diagnosed with recurrent tumors. Salvage RT was used in 12 patients (gamma knife radiosurgery for 7, conventional external beam RT for 4, and intensity-modulated RT for 1 patient). The median follow-up was 55 months for the entire group of 70 patients. RESULTS: The median time to recurrence was 36 months. Of the recurrences, 16 were glomus jugulare, 7 were carotid body tumors, 5 were glomus tympanicum, and 1 was thyroid paraganglioma. RT was used in 12 patients (9 patients with glomus jugulare, 2 with glomus tympanicum, and 1 with thyroid paraganglioma). Surgery was performed in 17 patients (7 patients with glomus jugulare, 7 with carotid body, and 3 with glomus tympanicum). For patients with glomus jugulare and glomus tympanicum tumors, the 5-year freedom from disease progression was 100% for patients treated with RT vs. 62% for those treated with surgery (p = 0.0124). Seven patients with carotid body tumors and 1 patient with thyroid paraganglioma were treated successfully with surgery and RT, respectively. No significant side effects were associated with RT; however, postoperative complications occurred in 8 of the 17 surgery patients (new cranial nerve palsies, meningitis, infection, and cerebrospinal fluid leak). CONCLUSION: Salvage RT appears superior to surgery and should be considered the treatment of choice for patients with recurrent glomus jugulare and glomus tympanicum tumors. For recurrent carotid body tumors, surgery produced excellent local control, most likely because of the easier resectability in this location.

Brain metastases from gynecological cancers: factors that affect overall survival.

We retrospectively reviewed factors that affected overall survival for patients with gynecological cancers that had metastasized to the brain. Between January 1985 to November 1999, we treated 25 patients with brain metastases from gynecological malignancies (cervix n=6, endometrium n=10, and ovary n=9). Various patient and tumor characteristics were identified and analyzed for their significance. Median age was 46 years old (range, 37-78 years) with the majority of tumors being adenocarcinoma (20/25 patients). The treatment consisted of whole brain radiation therapy (WBRT) in 11 patients, focal therapy (surgery and/or stereotactic radiosurgery [SRS]) in 6 patients, and combination therapy (WBRT and surgery and/or SRS) in 8 patients and resulted in median survivals of 6 months, 7 months and 11 months, respectively. Overall median survival was 7.3 months (range, 1 to 88 months). Cause of death was systemic in 9, neurologic in 8 and progression of primary in 2. Those with single lesions had better median survivals compared to those with multiple lesions (17 months vs. 3 months, p=0.017). Our results suggest that patients with a single lesion had improved outcomes. We encourage enrollment of patients with brain metastases onto prospective clinical trials.

Radiation therapy for Cushing's disease: a review.

Because patients with Cushing's disease have an increased morbidity and an age-corrected mortality, treatment is generally started as soon as possible. The goal of treatment in these patients is to induce remission. Although a variety of treatments are available, pituitary radiation is a good option for aggressive Cushing's disease that fails to respond to surgery, disease that invades the cavernous sinus, and disease that relapses following an initial remission. Conventional radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, and brachytherapy with Yttrium-90 (Y 90) and Gold-198 (Au 198) have been used successfully to treat ACTH-secreting pituitary adenomas in specialized centers. Conventional radiation therapy is the most frequently used method of radiation therapy for Cushing's disease. Stereotactic radiosurgery may be used as an alternative in patients with adenomas that are smaller than 30 mm and located at least 3 to 5 mm from the optic chiasm. Fractionated stereotactic radiation therapy is an alternative to radiosurgery while interstitial pituitary irradiation is an alternative to surgical resection in invasive tumors. Hypopituitarism is the most common side effect of pituitary irradiation. This article will review the role of radiation in the primary and secondary treatment in patients with Cushing's disease caused by pituitary adenomas.