Radiotherapeutic management of primary thyroid lymphoma

The purpose of this study was to evaluate the radiotherapeutic management of 38 patients, with malignant lymphoma of the thyroid, seen at the Mayo Clinic between 1965 and 1979. There were 8 males and 30 females with ages ranging from 34 to 90 years (mean age of 65 years). A tissue diagnosis was made in all patients and tissue was available for reclassification under the "Working Formulation" in 31 of the 38 patients. Twenty-six patients had intermediate grade histology, four low grade and one indeterminate. Twenty patients were clinical Stage IE, 14 patients Stage IIE, one patient Stage IIIE, one patient Stage IV and two patients were unstaged. All patients were treated with approximately 4000 rad megavoltage irradiation (range 2400-6000 rad) to the neck only (10 patients) or neck and mediastinum (28 patients). Twenty patients received subdiaphragmatic radiotherapy and four patients received adjuvant chemotherapy. Median follow-up was 56 months with minimum follow-up of 30 months. Overall disease-free survival at five years was 59%. Of 14 patients who experienced a recurrence, 10 (71%) failed in two or more sites. The most common site of failure was in para-aortic lymph nodes. One year survival following recurrence was 29%; however, four of six patients receiving salvage therapy survived at least two years. Patients receiving radiation treatment to the neck and mediastinum and those with no gross residual disease at the initiation of radiotherapy were less likely to develop a recurrence. Patients receiving a planned break during the course of therapy did not have reduced overall disease-free survival. However, 4 of 20 patients (20%) who received split course therapy failed within the radiation fields compared to 2 of 18 patients (11%) who had no treatment break. Only 1 of 4 patients (25%) receiving adjuvant chemotherapy survived one year. Side effects of radiotherapy were minimal. We believe the radiotherapeutic management of clinical Stage IE and IIE primary thyroid lymphoma should include treatment of the neck, axillae and mediastinum to a dose of approximately 4000 rad using a continuous course technique. Additionally, gross total removal of the disease surgically may be beneficial.     

Radiotherapeutic management of cancer of the supraglottis

One hundred eighty-five patients with cancer of the supraglottis were treated with curative intent by radiotherapy alone or combined with surgery over a 14-year period. Minimum follow-up was 3 years. Sixty-eight percent had Stage III or IV disease. Moderate-dose radiotherapy, with surgery in reserve, was the policy for the early lesions, and yielded a 3-year locoregional control rate of 76% for T1 N0/N1, T2 N0/N1, and T3 N0/N1 lesions combined. In this group, 84% of patients with locoregional control retained laryngeal function. The major complication rate was 4%. Patients with advanced disease were treated with preoperative radiotherapy and surgery, resulting in an overall 3-year no evidence of disease rate of 72%. Adverse prognostic factors in supraglottic cancer were the extent of the primary lesion and the presence of N2 or N3 nodes. Neither vocal cord fixation nor N1 nodes had a negative influence on survival in T3 and T4 disease.     

Prognostic factors and management of intracranial ependymomas

Between the years 1960 and 1983, 26 patients with the diagnosis of ependymoma were treated at our institution. Twenty-one patients received postoperative radiotherapy, of whom six patients had supratentorial tumors and 15 had infratentorial tumors. The median dose to the brain was 53.75 Gy with a range of 30-60 Gy. The median dose to the spine was 37.5 Gy with a range of 10-46 Gy. The median survival time for all 26 patients is two years. The median survival time for patients less than 10 years old is two years as compared to six years for patients older than 15 years at the time of diagnosis (0.05 less than p less than 0.10). Patients had a median survival time of greater than five years if the primary tumor was completely resected as compared to two years in the incompletely resected or biopsy only group (p less than 0.25). The median survival time MST for the low grade tumors is 9 years as compared to one year for the high grade tumors (p less than 0.01). The five-year survival was 38% in patients with infratentorial tumors who received craniospinal irradiation as compared to 33% with whole brain and 0% with partial brain radiation including the spine. All five patients with high grade infratentorial tumors subsequently failed in the cerebrospinal axis despite cranio-spinal irradiation in two and partial brain plus whole spine in another two of the patients. In conclusion, the favorable prognostic factors (in order of increasing importance) for patients with intracranial ependymomas are: age greater than 15 (marginal), complete resection and low histological grade.     

Radiotherapeutic management of brain metastases from breast cancer

We have reviewed the medical records of 28 breast cancer patients with brain metastases who were treated with radiotherapy at our clinic from 1980 through 1994 (4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Ten patients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumors ranged from 32 Gy to 60 Gy (mean, 49 Gy) in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients (92%) with complete response (CR) in 1 2 patients (46%) and partial response (PR) in 1 2 patients (46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years (median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years (median survival time, 6 months). Performance status tended to be associated with survival (p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival (p=0.056). Two patients suffered severe chronic complications. One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.     

Radiotherapeutic strategies in the management of hepatocellular carcinoma

Although potentially curative therapies for hepatocellular carcinoma (HCC) are well established, they are offered only to a limited number of patients. For advanced HCC, sorafenib is now the treatment of choice. Radiotherapy technology has evolved remarkably during the past decade and can be precisely delivered, thereby permitting higher doses to the tumor and reduced doses to surrounding normal tissues. According to the Korean Liver Cancer Study Group (KLCSG) practice guidelines, radiation therapy is considered appropriate for unresectable, locally advanced HCC without extrahepatic metastasis, Child-Pugh class A or B, and tumors occupying less than two thirds of the liver with level II evidence. In this review, we discuss the radiotherapeutic strategies for each clinical setting in patients with HCC.     

Radiotherapeutic management of locally advanced head and neck cancer

Head and neck cancer management has undergone several paradigm shifts for several relevant reasons. From the dismal experience with the use of radiotherapy as the sole modality in the treatment of this group of patients with advanced disease, radiotherapy has been evaluated as an adjuvant for the same group of patients who had undergone successful surgery. Although there is no level 1 evidence to support postoperative adjuvant radiation, several studies have demonstrated that adjuvant radiotherapy reduces the local failures and, thereby, improves survival. Predictors of recurrence after surgical resection are: positive margins of resection; extranodal spread in involved nodes; perineural invasion; and presence of two or more involved regional lymph nodes. Realization of the advantages of a combination of chemotherapy with radiotherapy has had a major impact on the management of these cancers. There is emerging evidence for the use of adjuvant concurrent chemoradiotherapy in the group with high-risk features. Multiple organ conservation strategies in the management of locally advanced head and neck cancers have evolved over the years. However, the meta-analyses of impact of chemotherapy in various settings reveal that concomitant chemoradiotherapy is superior to any of the other regimens. Increasing use of computed tomography, magnetic resonance imaging and positron emission tomography scan images has resulted in better visualization of target volumes and critical structures. Delineation of these structures is of paramount importance and has resulted in a profound change in conformal treatment planning. Better understanding of the physical aspects of delivery of radiotherapy and the advent of modern treatment planning systems have led to the development of conformal techniques. Although the benefit of these techniques on survival have yet to be demonstrated, there is evidence to suggest that they reduce treatment-related toxicities significantly and facilitate dose escalation. Increased knowledge of radiobiology has led to the development of various altered fractionation regimens in the management of locally advanced head and neck cancers. Discovery of cell-cycle kinetics and signal transduction pathways has led to the unearthing of several potential targets for targeted therapy. The epidermal growth factor receptor gene has emerged as the most promising target. The role of biological radiation response modifiers is evolving. All of these approaches to improve the therapeutic gain would be incomplete without evaluating their effect on the quality of life of these patients.     

乳腺癌根治术后区域淋巴结复发放射治疗疗效分析

目的：探讨乳腺癌根治术后区域淋巴结复发患者放射治疗和其他综合治疗手段的合理联用以及影响局部控制率和生存率的预后因素。方法：回顾性分析了1994～2003年期间在我院放疗科收治的77例乳腺癌根治术后区域淋巴结复发作为术后第一次治疗失败的患者，其中45例为锁骨上淋巴结，16例腋下淋巴结，6例内乳淋巴结，10例同时有2个淋巴结区累及。中位随访时间为34．4个月。所有患者均接受放射治疗。12例在放疗前接受复发灶手术切除。照射剂量范围为50-74Gy，中位剂量为60Gy。结果：本组患者中位生存期为4．67年，二年、五年和八年生存率分别为77．8％、47．4％和31．5％。无病间期、激素受体状态为影响生存率的独立的预后因素。总计有30例(39％)发生再次局部和(或)区域性复发，其中4例发生在原复发部位，26例发生在其他部位，胸壁是发生率最高的二次复发部位，总计有18例(23％)患者发生的再次复发部位中包括胸壁。首次术后病理腋淋巴结转移数目是影响局部控制率的预后因素。结论：放射治疗是乳腺癌术后区域淋巴结复发的有效治疗手段。23％的患者治疗后发生后续的胸壁复发，建议对患侧胸壁作预防性照射。首次术后病理腋淋巴结转移数目4个及以上的患者作胸壁预防的意义更大。无病间期2年及以上，激素受体阳性的患者是相对预后较好的患者群。全身治疗在改善生存率方面的意义尚不明确。     

Radiotherapeutic management of medulloblastoma in a pediatric patient with ataxia telangiectasia

Ataxia telangiectasia (AT) is a genetic disorder with a predisposition to malignancy. Cells from patients with AT demonstrate an increased sensitivity to ionizing radiation which creates a problem when these patients require treatment for their malignant disease. An eleven-year-old boy with a previous diagnosis of AT was seen in consultation following partial resection of medulloblastoma in the posterior fossa. To estimate how much the conventional radiation dose might have to be reduced, we compared the radiosensitivity of bone marrow myeloid progenitor cells from this patient to that of cells from the marrow of normal individuals, using colony formation in an agar culture assay system as the endpoint (CFU-Cs). Neither radiation dose-survival curve exhibited a shoulder--each displayed an extrapolation number of 0.99. The survival curve of normal cells displayed a steep slope with a D0 of 0.98 Gy (0.83-1.19 Gy, 95% confidence limits); the slope for the AT cells was considerably steeper with a value for D0 of 0.32 Gy (0.29-0.35 Gy). The ratio of D0's indicated that these AT cells were approximately 3X more radiosensitive than normal cells. Based on this, the daily dose was reduced from 1.8 to 0.6 Gy and the radiation was restricted to 25 treatments to the posterior fossa rather than the conventional cranio-spinal treatment. An additional 5 treatments at 1.0 Gy per day were given to the whole brain. The patient's skin responded to these reduced fraction sizes and doses to a similar degree as normal patients' skin following a standard schedule and the patient is doing well nine months after initiation of treatment.     

Radiotherapeutic management of brain metastases: a systematic review and meta-analysis

BACKGROUND: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness. METHODS: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity. RESULTS: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive. CONCLUSION: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.     

Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT)

Background  

To assess the role of Fractionated Stereotactic Radiotherapy (FSRT) in the management of ependymomas.     

Radiotherapeutic enhancement by razoxane

Razoxane blocks cell division in the G2/M phase of the cell generation cycle and appears to normalize tumour neovasculature development. These were the principal reasons for the examination and probably for the demonstration of the radiosensitizing activity of Rz. Specially intriguing has been the finding that radiation of primary tumour implants in animals treated with Rz has a powerful potentiating effect on the antimetastatic activity of the combination. This concept has not yet received any clinical examination. Clinical trials with radiotherapy and Rz have demonstrated the clearest beneficial effects in terms of response rates and maintained local control in soft tissue sarcomas and possibly in recurrent rectal and in bladder carcinomas. Interesting heightened activity has also been found in hepatic metastases from gastrointestinal tumours. Carcinomas of the cervix, bronchus and head and neck, however, have not shown any benefit from the combination compared with radiotherapy alone.     

乳腺癌术后骨转移的放射治疗和预后因素

背景与目的:放射治疗是乳腺癌骨转移姑息性治疗的有效方法,本文通过对乳腺癌骨转移接受放射治疗患者的临床特征、治疗情况的分析,探讨了影响局部控制及生存率的预后因素.方法:回顾性分析了复旦大学附属肿瘤医院放疗科2000年1月-2005年8月收治的186例乳腺癌术后因骨转移而接受放射治疗的患者,其中323处骨转移灶接受了放疗,316处有临床症状.放疗技术采用单一野或前后对穿野的 60Co或6MV X线,照射剂量范围为20～60 Gy,中位剂量30 Gy.结果:乳腺癌骨转移好发部位在胸腰椎、肋骨和髂骨.全组患者中位生存时间为34个月,术后首发为单纯骨转移的112例患者,中位生存时间为37.5个月.放疗后临床缓解(PR CR)者占90.8%(287/316处),完全缓解者占42.1%(133/316处).临床症状缓解起始时间在4周以内者占75.3%(238/316),缓解持续中位时间为23个月.生物等效剂量达到39 Gy及以上剂量组患者的中位缓解时间在22个月及以上,而30 Gy及以下者仅为8个月.多因素分析显示激素受体情况、转移淋巴结数目、内脏转移情况、初发单/多发骨转移情况是影响乳腺癌骨转移患者生存率的独立预后因素.结论:放射治疗是乳腺癌骨转移患者姑息治疗的有效方法,大部分患者能达到临床缓解,缓解时间约占中位生存时间的2/3.生物等效剂量达到39 Gy及以上能获得更长的缓解时间.激素受体情况、转移淋巴结数目、内脏转移情况、初发单/多发骨转移情况是影响乳腺癌骨转移患者生存率的独立预后因素.     

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy

Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group’s initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms’ Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting.