Neurosurgical management of single brain metastasis

A series of 74 consecutive cases undergoing craniotomy for single brain metastasis in the Beilinson Medical Center between October 1975 and October 1981 were reviewed. All patients underwent radiation therapy after craniotomy. The most common metastasis was that of unknown origin (35%), followed by lung (24%) and breast (16%). Overall median survival after craniotomy was 6.6 months. Overall 1- and 2-year survival rates were 30 and 15%, respectively. Operative mortality (30 days) was 15%. For the patients with metastases to the lung, median survival was 7.5 months and 1-year survival rate was 33%. It appears from this report that two dominant factors affect the prognosis of these patients. The first is the long latent interval (time between diagnosis of primary tumor and detection of metastasis). The second is the location of the metastasis; those with lesions in the cerebral hemispheres had a far better outcome than those with cerebellar lesions (p less than 0.0001).     

Two autopsied cases of radiation-induced gliosarcoma

Two autopsied cases of radiation induced gliosarcoma are presented in detail with a review of the literatures. Case 1 was that of a 36-year-old female who was found to have a metastatic choriocarcinoma in the right occipital lobe and received radiation therapy of 45 Gy. Four years later CT scan showed a new enhanced tumor in the cerebellum within the previously irradiated field. Total removal was performed and histological diagnosis of the tumor was a gliosarcoma. She died 12 months after the operation. Case 2 was that of a 63-year-old male who had a protoplasmic astrocytoma in the left temporal lobe and received radiation therapy of 60 Gy after surgery. The tumor recurred in the left temporal base after 9 years. Histological finding of the surgical specimens showed gliosarcoma. The patient died 2 months after he was operated on. The tumors had obviously two defined neoplastic components. One was gliomatous features with anaplastic glial cells which stained for glial fibrillary acidic protein. The other was malignant mesenchymal features with spindle shaped fibrosarcoma cells which contained numerous reticulin fibers. Postmortem examination revealed these similar features. Criteria for identifying a tumor as a radiation induced neoplasm have been proposed by Fajado. The main criterion is that the induced tumor should occur in the previously irradiated field. Secondly, it should appear after a latent period. Thirdly, the pathology should be different from the initial neoplasm. Our cases fulfil these criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma

Summary A rare case of fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma is reported. A review of similar cases in the literature was undertaken in an attempt to find a correlation between the dose of radiation, the length of the latent period, and the nature of the neoplasm. A significantly shorter latent period was found for sarcomas. No relationship was observed between the radiation dose and the latent period. The present case is unique in that the post-irradiation neoplasm (PIN) occurred in a predominantly extracranial site after treatment for a desmoplastic medulloblastoma and had a remarkably short latent period.     

Does transurethral resection of prostatic carcinoma promote tumor spread?

122 patients with prostatic carcinoma treated by radiation therapy were reviewed. An actuarial analysis was done on survival comparing patients treated by transurethral resection (TURP) prior to radiation to those diagnosed by needle biopsy. Survival rates were not significantly different between groups. TURP was also without effect on interval free of distant or local recurrence. Survival and time to distant or local recurrence were analyzed by tumor stage and grade. A multivariate analysis with the Cox model was made by which the effects of TURP and tumor grade and stage were examined simultaneously. TURP was without effect on survival rates and interval to distant or local recurrence after adjustments had been made for the effects of stage and grade.     

Radiation-induced soft-tissue sarcoma

Twenty patients with soft-tissue sarcomas arising within previously irradiated fields have been analysed. The initial radiation dose ranged from 8.8 to 70 Gy, comprising either orthovoltage or megavoltage treatment. The latent interval following radiotherapy ranged from 7 to 45 years (mean 16.8 years). The commonest histological subtype was malignant fibrous histiocytoma. Four patients required forequarter amputation. The 5-year survival was only 14 per cent. The high morbidity and mortality accompanying post-radiation sarcomas must be borne in mind when the choice between therapeutic options for potentially curable cancers is finely balanced.     

Definitive radiation therapy for prostatic carcinoma: Mayo clinic experience

Primary radiation therapy for clinically localized prostatic cancer is effective and safe. Of our 147 patients treated between 1964 and 1973, 144 were evaluated 5 years after the initial date of radiation therapy. At 5 years the over-all survival rate was 80 per cent and the rate of survival free of disease was 63 per cent. More than 70 per cent of the patients were free of progression 5 years after the date of the first radiation treatment. Analysis revealed a highly significant association between tumor grade and patient survival (p less than 0.001), and between tumor grade and the interval free of disease (p less than 0.002). The relationship between tumor stage and time to progression of disease also was significant (p approximately equal to 0.01) but there was no relationship between lower stage and longer survival. Of the 142 patients who completed treatment only 20 (14 per cent) had local recurrence of the prostatic cancer after radiation therapy, representing a local control rate of 86 per cent 5 years after treatment. A few of the patients underwent post-treatment prostatic biopsy after radiation therapy. If a biopsy is done for increased prostatic induration and the results are positive adjuvant treatment is recommended. In the absence of urologic symptoms of progressive induration of the prostate gland biopsy is not instrumental in predicting the course of the cancer.     

What Is the Optimal Interval Between Chemoradiation and Esophagectomy?

Locally advanced esophageal cancer requires multimodality therapy-most commonly induction chemoradiation followed by esophagectomy. There is a paucity of literature on the optimal time interval between induction treatment and resection. Patient readiness and healthy tissue, as well as tumor responses to radiation, are factors to consider. Two recent retrospective large-center studies on this topic are reviewed.     

Secondary thyroid neoplasms in pediatric cancer patients: increased risk with improved survival

Between 1973 and 1983, eight children who had undergone successful multimodal management of malignant tumors developed secondary thyroid neoplasms. The primary tumors were acute lymphocytic leukemia in three, Wilms' tumor in two, and Hodgkin's disease, rhabdomyosarcoma, and ganglioneuroblastoma in one each. During this period, 174 long-term survivors with these five diagnoses were enrolled in our tumor registry, yielding a 4.6% incidence of secondary thyroid neoplasms. All eight patients received both radiation and chemotherapy. The mean radiation dose was 2,700 r with a calculated thyroid dose of 2,140 r (range, 5 to 4,200 r). Age of diagnosis of the primary tumors ranged from 1 to 8 2/12 years (mean, 5 years), and the latent period between treatment and development of the thyroid lesions averaged 6 1/2 years. Thyroid neoplasms presented at an average age of 11 4/12 years. Five patients developed solitary adenomas, one presented with multiple adenomas, and two had follicular carcinoma with regional lymph node metastases. Although thyroid neoplasms are rare in childhood, clinically apparent thyroid tumors have been observed in up to 2.5% of children following radiation exposure (mean follow-up, 24 years). The reported latent period before the development of thyroid neoplasms in irradiated patients is at least 10 years, with the peak incidence occurring 20 to 25 years after exposure. This study documents a 4.6% incidence of subsequent thyroid neoplasms in pediatric cancer patients within a relatively short follow-up period (mean, 11 years). These thyroid tumors occurred at an earlier age (mean, 11.5 years) and with a shorter latent period (mean, 6.5 years) than would be predicted from previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histology and clinical outcomes in patients with bilateral testicular germ cell tumors: the Memorial Sloan Kettering Cancer Center experience 1950 to 2001

PURPOSE: The optimal management of bilateral testicular tumors continues to evolve. We examined the incidence, characteristics, histology, treatment and clinical outcomes of patients with bilateral testicular cancer. MATERIALS AND METHODS: Between 1950 and 2001, 3,984 patients with testicular cancer were treated at our center. A total of 58 patients with bilateral testicular germ cell tumors were identified. The clinical records of these 58 patients were reviewed for age, histology of the 2 tumors, stage at presentation of the first and second tumor, interval between tumors, treatment and clinical outcome. Median followup was 60 months. RESULTS: Ten of the 58 patients (17%) had synchronous tumors, while the other 48 (83%) had metachronous tumors with a median interval between tumors of 50.5 months. Overall seminoma was the most common histology of the synchronous and metachronous tumors. Most patients in the synchronous and metachronous tumor groups presented with low stage disease. Of the 58 patients 52 (89%) had no evidence of disease and 6 (11%) were dead of disease at the last followup. Treatment of the second tumor appeared to be influenced by therapy for the first tumor in 16.7% of cases. CONCLUSIONS: Patients with a history of testicular germ cell tumor require careful long-term monitoring of the contralateral testicle due to the risk of bilateral disease and potentially long latent period between the first and second tumors. Overall the clinical outcome is good in these patients when they are treated appropriately for histology and stage. In patients with metachronous tumors treatment of the contralateral tumor is rarely altered by prior treatment of the initial tumor.     

Postradiation sarcoma involving the spine

Postradiation sarcomas arising many years after treatment of cancer are long term sequelae of therapy. We describe the clinical features, radiographic findings, and results of treatment in 13 patients with such sarcomas encountered over a 6-year period. Of these patients, 9 had bone sarcomas and the remaining 4 had paraspinal tumors arising from adjacent soft tissue and nerve. The primary cancer for which radiation was given included Hodgkin's disease (4 patients), breast cancer (2 patients), cervix cancer (2 patients), and a variety of others (5 patients). The latent interval to the occurrence of the second neoplasm varied from 6 to 30 years (median, 10 years) after treatment of the original tumor. Despite aggressive treatment, the overall prognosis was poor. The median survival was 8 months, with only 3 surviving more than 2 years. Although rare, postradiation sarcoma should be considered in the differential diagnosis of patients presenting with late onset of spinal pain or neurological symptoms after clinical remission of an original cancer.     

Salvage cystectomy following failed definitive radiation therapy for transitional cell carcinoma of bladder

Between 1971 and 1983 we performed 18 salvage cystectomies on patients with recurrent transitional cell bladder cancer initially treated with definitive radiation therapy (5,500-6,820 R). The interval between tumor diagnosis and radiation ranged from zero to twenty-one years (mean 3.5 years), and the interval between radiation therapy and cystectomy ranged between six months and twelve years (mean 2.5 years). Early major complications occurred in 5 patients, and there was one early and one late postoperative death. The overall patient survival from the time of diagnosis to death or the present (1985) ranged from two to thirty-one years (mean 9.8 years), and from the time of radiation to the present or death ranged from one to nineteen years (mean 6.2 years). The overall crude five-year survival from the time of cystectomy excluding 2 patients operated on in 1982 and 1983 was 50 per cent, however 3 of these patients died of cancer after five years. Breakdown of survival of these patients by stage demonstrated the best survival in patients with carcinoma in situ and Stage A or no neoplasm at the time of cystectomy. This report confirms the value of salvage cystectomy after radiation failure in invasive transitional cell bladder cancer.     

Melanoma: A review of thirty-two cases admitted to the Brooklyn Cancer Institute during a five-year period

Melanoma is defined as a malignant tumor of pigment producing cells. Its relationship to the benign naevus is discussed. The microscopic appearance and different theories as to origin of melanotic cells are outlined. Racial and hereditary characteristics are discussed.Thirty-two cases of melanoma entered at the Brooklyn Cancer Institute in the five-year interval between 1936 and 1942 are reviewed and results summarized. From these records it appears that this tumor most frequently metastasizes first to the regional lymph nodes. This spread may occur after an interval of from three months to six years. The most frequent site of distant metastasis was found to be lung, liver and bone. The latent period before the development of distant metastases was two years eight months.The best results were obtained in this series by radical local removal. The authors, however, agree that this should be followed whenever possible by regional lymph node dissection as recommended by Pack¹. Radiation therapy is discouraged except for treatment from a palliative angle.     

Radiation-induced fibrosarcomas rapidly appeared more than 20 years after radiation therapy for germ cell tumors: report of two cases

Radiation-induced brain tumor is a rare but serious and potentially fatal complication. We report two cases of radiation-induced fibrosarcomas which occurred more than 20 years after whole brain radiation therapy (60 Gy) for intracranial germinomas. Although both of them underwent imaging examination every year, the symptomatic sarcomas developed rapidly within a year. Eight months after total removal, the tumor recurred in the one case. Second surgery and gamma knife surgery could not prevent the tumor progression. In the other case, tumor regrowth was not observed during the five months follow-up after total removal surgery. It is important to keep in mind the possibility of a postradiation sarcoma that might have developed very aggressively after a long latent period.     

Epidemiologic and Clinical Evaluation of Thyroid Cancer in Children from the Gomel Region (Belarus)

p = 0.001); there was no significant correlation between the age of each child at the time of the accident and the latent period before the onset of carcinoma. The aggressiveness of the tumor, evaluated on the basis of T stage, lymph node status, and lung metastases, did not correlate with age at the time of the first diagnosis or with the age at the time of the accident. The susceptibility of the thyroid to the carcinogenetic effects of radiation, particularly during the first years of life (< 5 years) has clearly been demonstrated. However, there appears to be no correlation between the aggressiveness of the tumor and the age of the patients.     

Neurogenic fibrosarcoma following radiation therapy for seminoma

We report a case of radiation-induced neurogenic fibrosarcoma that developed in a patient who received radiation therapy for seminoma. The sarcoma developed within the irradiated field after a latency period of nineteen years. Although the occurrence of a secondary neoplasm is unusual, this possibility should be included in the differential diagnosis of patients who present with tumor growth after a long interval following radiation therapy.     

治疗放射性臂丛神经损伤的临床分析

目的探讨在行臂丛神经松解术的同时用健康软组织覆盖创面对治疗放射性臂丛神经损伤（乳腺癌术后进行放射治疗引起）的疗效。方法对1997年9月-2006年2月间治疗的9例放射性臂丛神经损伤患者进行随访及回顾性病例分析。术后随访时间为1个月-8年，平均37．9个月。结果作单纯神经松解术者2例，术后症状无明显改善1例，加重1例。作神经松解及背阔肌皮瓣转移术者5例，术后症状改善3例，无明显改善1例，死亡1例。作神经松解及胸大肌皮瓣转移术者2例，术后症状改善1例，无明显改善1例。同时观察到症状改善者的放射治疗潜伏期长，出现症状至手术时间间隔短。结论对放射性臂丛神经损伤患者行臂丛神经松解术的同时覆盖背阔肌皮瓣（胸大肌皮瓣）可缓解症状，提高患者的生存质量；而且越早诊治其疗效越好。     

Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence?

Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 (131I) treatment. In seven cases 131I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with 131I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from 131I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context.     

Hearing restoration with auditory brainstem implants after radiosurgery for neurofibromatosis type 2.

The auditory brainstem implant (ABI) is designed to restore useful auditory sensations in patients with neurofibromatosis Type 2 (NF2). The implantation is usually performed at the time of tumor removal in patients who do not undergo radiation treatment. The authors evaluated the performance of ABIs in three patients with NF2 in whom vestibular schwannoma continued to grow after radiation treatment. These three patients with NF2 received a 21-channel ABI; a translabyrinthine approach was used for both the tumor removal and the ABI placement. The interval between radiosurgery and the tumor removal plus device implantation ranged from 2 to 11 years. In all cases, the tumor was growing and the patients presented with total deafness. The mean number of active electrodes in these three patients was equivalent to the average results reported in other patients who received ABIs. The patients in this study used the ABI regularly for everyday life and obtained useful levels of environmental sound recognition. It is concluded that hearing function can be rehabilitated using ABIs in patients with NF2, even if radiosurgery fails to control the tumor growth.     

The Interval Between Preoperative Radiation and Surgery Is Not Associated with Overall Survival for Soft-tissue Sarcomas: An Analysis of the National Cancer Database

BackgroundMost cancer centers prefer preoperative radiation therapy (preRT) over postoperative therapy to treat soft-tissue sarcoma (STS) to limit long-term fibrosis, joint stiffness, and edema. Surgery is often delayed after preRT to allow for tissue recovery and to reduce wound complications. However, the association between the time interval between preRT and surgery and survival is unknown.Questions/purposes(1) What factors are associated with the preRT-surgery interval in patients with STS? (2) Is the preRT-surgery interval associated with overall survival?MethodsThe National Cancer Database, a nationwide registry that includes 70% of all new cancers in the United States with 90% follow-up, was reviewed to identify 6378 patients who underwent preRT and surgical resection for a localized extremity or pelvic STS from 2004 to 2014. Patients were excluded if they had lymphatic or metastatic disease at diagnosis (23%; n = 1438), underwent neoadjuvant chemotherapy (24%; 1531), were missing vital status (8%; 487), had chemosensitive histologies (9%; 603), underwent radiation other than external beam (1%; 92), were missing preRT-surgery interval (1%; 45), or had a preRT-surgery interval greater than 120 days (< 1%; 6). A total of 2176 patients were included for analysis, with a mean preRT-surgery interval of 35 ± 16 days. A multiple linear regression model was generated to assess demographic, clinicopathologic, and treatment characteristics associated with the preRT-surgery interval. A Kaplan-Meier survival analysis was then conducted, stratified by the preRT-surgery interval, to assess survival over 10 years. Finally, a multivariate Cox regression analysis model was constructed to further evaluate the association between the preRT-surgery interval and overall survival, adjusted for demographic, clinicopathologic, and treatment characteristics.ResultsA longer preRT-surgery interval was associated with higher age (β = 0.002 per year [95% CI 0.0 to 0.004]; p = 0.026), tumor location in the pelvis (compared with the lower extremity; β = 0.15 [95% CI 0.082 to 0.22]; p < 0.001), and malignant peripheral nerve sheath tumor subtype (compared with undifferentiated pleomorphic sarcoma; β = 0.17 [95% CI 0.044 to 0.29]; p = 0.008). A shorter preRT-surgery interval was associated with higher facility volume (β = -0.002 per case [95% CI -0.003 to -0.002]; p = 0.026) and higher tumor stage (compared with Stage I; β = -0.066 [95% CI -0.13 to -0.006]; p = 0.03 for Stage II; β = -0.12 [95% CI -0.17 to -0.065]; p < 0.001 for Stage III). The 5-year overall survival rates were similar across all preRT-surgery interval groups: less than 3 weeks (66% [95% CI 60 to 72]), 3 to 4 weeks (65% [95% CI 60 to 71]), 4 to 5 weeks (65% [95% CI 60 to 71]), 5 to 6 weeks (66% [95% CI 60 to 72]), 6 to 7 weeks (63% [95% CI 54 to 72]), 7 to 9 weeks (66% [95% CI 58 to 74]), and more than 9 weeks (59% [95% CI 48 to 69]). Over 10 years, no difference in overall survival was observed when stratified by the preRT-surgery interval (p = 0.74). After controlling for potentially confounding variables, including age, sex, Charlson/Deyo comorbidity score, histology, tumor size, stage and surgery type, the preRT-surgery interval was not associated with survival (hazard ratio = 1 per day [95% CI 1 to 1]; p = 0.88).ConclusionWith the numbers available, this study demonstrates that a delay in surgery up to 120 days after radiation is not associated with poorer survival. Therefore, clinicians may be able to delay surgery to minimize the risks of wound complications and modifiable comorbidities without affecting overall survival.Level of Evidence Level III, therapeutic study.     

Liposome-encapsulated hemoglobin ameliorates tumor hypoxia and enhances radiation therapy to suppress tumor growth in mice

We hypothesize that liposome‐encapsulated hemoglobin with high O₂ affinity (P₅₀0₂ = 12 mm Hg, h‐LEH) may increase O₂ delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h‐LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h‐LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h‐LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h‐LEH and hypoxia‐inducible factor‐1α (HIF‐1α). h‐LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h‐LEH or EL. Tumor growth was most suppressed when the interval between h‐LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h‐LEH infusion 30 min prior to radiation prolonged 5‐fold tumor‐growth time from 20.0 days (radiation and EL) to 26.5 days, P < 0.01, synergy ratio 1.42. While human hemoglobin (h‐LEH) was detected in tumors 0.5 to 24 h after administration, HIF‐1α accumulation was sparse and became significantly reduced compared to controls 48 and 72 h after h‐LEH infusion. h‐LEH (10 mL/kg) was highly effective in enhancing radiation therapy synergistically under ambient respiration against tumor growth in mice. Decreased accumulation of HIF‐1α in h‐LEH‐treated tumor may suggest targeted tumor oxygenation as a potential mechanism.