Local Field Irradiation Research Articles

Complications of Treatment with Local Field External Beam Radiotherapy for Localized Prostate Cancer

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT.The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation.RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.

The significance of radiotherapy treatment duration in intracranial ependymoma

Purpose: To determine if radiation therapy treatment duration has an impact on the outcome of intracranial ependymoma. Methods and Materials: From 1965 to 1997, 34 patients with intracranial ependymoma were seen and treated with postoperative radiotherapy (RT). There were 26 male and 8 female patients with a median age of 14 years (range, 18 months to 60 years). Tumor location was infratentorial in 23 (67.6%) and supratentorial in 11 (32.4%). Pathology was low-grade in 25 (73.5%) and high-grade in 9 (26.5%). Two (5.9%) patients had M+ disease at initial diagnosis. Gross total resection was achieved in 12 (35.3%), subtotal resection in 19 (55.9%), and biopsy alone in 3 (8.8%). Median RT dose to the primary site was 5400 cGy (range, 4500 cGy to 6600 cGy). The entire neuraxis was treated in 14 (41.2%), whole brain in 9 (26.5%), and the primary site alone in 11 (32.4%). Median radiotherapy treatment duration was 43 days (range, 26 to 122 days). Patients treated with craniospinal RT were more likely to have treatment duration of ≥50 days. Median follow-up was 108 months (range, 24 to 252 months). Results: The 5-, 10-, and 15-year overall survival rates were 71.5%, 63.3%, and 55.4%. Local control rates at 5, 10, and 15 years were 61.8%, 57.7%, and 57.7%. For patients with RT treatment duration <50 days, the 5-, 10-, and 15-year overall survivals were 85.5%, 78.9%, and 65.7% whereas for those with treatment duration ≥50 days, the corresponding rates were 45.5%, 36.4%, and 36.4% ( p = 0.01, log-rank test). Local control rate at 5, 10, and 15 years was 70.6% for patients with RT treatment duration <50 days and 45.5%, 36.4%, and 36.4% for patients with RT treatment duration ≥50 days ( p = 0.05, log-rank test). Age, gender, tumor location, tumor grade, degree of surgical resection, RT volume, and RT dose (4500–5399 cGy vs. 5400–6600 cGy) were not found to have a statistically significant impact on overall survival, disease-free survival, or local control. The most common site of failure was local, found in 13 (38.2%) patients. Three patients also had spinal failure in addition to a primary site failure. There were no isolated nonprimary site brain or spine failures. Conclusions: Radiation therapy treatment duration is an important prognostic factor for survival and local control with patients having treatment duration <50 days having a better outcome than those with treatment duration ≥50 days. Because the overwhelming site of failure was local, we recommend local field irradiation in patients with M0 disease.

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer.

This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.

Radiotherapy in the management of cutaneous B-cell lymphoma. Our experience in 25 cases

Purpose: To report our results in the treatment with radiation therapy of 25 patients affected by B-cell lymphoma with initial cutaneous presentation. Materials and methods: From October 1978 to June 1997, we have treated 25 patients with cutaneous B-cell lymphoma (CBCL) by cutaneous irradiation. There were 17 males and eight females, aged from 23 to 89 years (median age 50 years). The mean follow-up time for the series was 3.9 years (range from 0.2 to 15 years) from the completion of radiation therapy. All patients were staged as follows: in group 1, single lesion; group 2, multiple lesions; group 3, disseminated lesions. There were six (24%) patients in group 1, 15 (60%) patients in group 2, and four (16%) in group 3. There were nine patients with head and neck lesions, 11 patients with trunk lesions, and five patients with leg lesions. Thirteen patients (52%) had previously received chemotherapy for CBCL. Extended field irradiation was used to treat six patients (24%). Localized field irradiation (LFI) was performed for the other 19 patients (76%). Results: The overall survival rate at 5 years was 73%. The complete response (CR) to the treatment for our series was 92%. The length of complete remission ranged from 2 to 180 months. There were three patients (8%) who obtained partial response (PR). Disease-free survival (DFS) at 1 year was 91%, and at 5 years was 75%. Radiotherapy was generally well tolerated. Conclusions: Localized field irradiation is an effective treatment for some localized forms of primary cutaneous B-cell lymphoma and can obtain prolonged remissions. The patients with wide-spread skin involvement are usually candidates for extended field irradiation and/or chemotherapy. For the advanced stages of cutaneous B-cell lymphoma, where the chemotherapy is the treatment of choice, some good palliation can be achieved using local field irradiation.

LOCAL AND SYSTEMIC RADIATION FOR PALLIATION OF METASTATIC DISEASE

Many radiotherapeutic treatment options are available for the palliation of patients with metastatic prostate cancer. These include local field radiotherapy to symptomatic sites of metastasis and the use of radioisotope therapy either alone or in combination with local field radiotherapy. To date, the majority of patients treated with radioisotope therapy have been treated with 89Sr. Other agents, such as 153Sm-EDTMP are available now, also. Combined radioisotope therapy, cytotoxic chemotherapy, and biphosphonates hold great promise.

There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a pediatric oncology group phase III trial comparing conventional vs. hyperfractionated radiotherapy

Purpose: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy.Methods and Materials: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2.Results: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2–15 months) and the median time to death 8.5 months (range 3–24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1–12 months) and 8 months (range 1–23 months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively. Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108 patients and revealed a complete response in 1 patient of each Rx arm, a partial response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm 2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm 2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The pattern of failure was local in all patients. Morbidity of treatment was similar in both Rx arms, with no significant toxicity (including hearing loss) reported. Autopsy was performed in 6 patients, and confirmed the presence of extensive residual tumor in these cases.Conclusion: The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.

Radiotherapeutic Management of Osseous Metastases: A Survey of Current Patterns of Care

Purpose: Radiotherapy plays a major role in the management of painful osseous metastases. This survey was conducted to study the current approaches to this clinical problem in the radiotherapy community. Methods and Materials: A questionnaire was sent to 2500 members of the American Society for Therapeutic Radiology and Oncology. It consisted of 30 multiple-choice questions regarding four hypothetical clinical scenarios likely to be encountered in daily practice. Questions related to the technique of choice [local field (LF) vs. hemibody radiotherapy (HBI)], the use of systemic radionuclides (SR), fractionation schemes, dose, the integration of modalities, and the follow-up of these patients. The analysis is based on 817 (33%) responses received regarding 3268 cases. Results: Local field is the most common form of therapy. Overall, LF was used, alone or in combination with other forms of therapy, in 54% and 74% of patients, respectively. LF was used more frequently in patients with breast cancer than in patients with prostate cancer (79% vs. 45%; p = 0.0001). Long fractionation schemes were used by 90% of physicians in 96% of cases. Short fractionation schemes were used by 7% of physicians in 4% of cases. This tendency was more pronounced in private practice than in the university or government/multidisciplinary settings ( p = 0.008) and in physicians starting their practice before 1982 ( p = 0.05). The most common schedule was 30 Gy in 10 fractions, used by 77% of physicians in 64% of cases. HBI was used, alone or in combination with other forms of therapy, in 1% and 2% of patients, respectively. It was used more frequently in patients with prostate cancer than in patients with breast cancer (1.2% vs. 0.1%, respectively; p < 0.0001). SR were used alone or in combination with local-field irradiation in 21% and 40% of cases, respectively. SR were used more frequently in patients with prostate cancer than in those with breast cancer (28% vs. 0.2%, respectively; p < 0.00001). The most common radionuclide in use is Sr-89 (99%) at a dose of 4 mCi (73%) or 10.8 mCi (26%). Conclusions: Although LF remains the mainstay of therapy, our results demonstrate the emergence of a new pattern of practice: LF to the painful site in combination with SR for clinically occult metastases. Despite an ongoing academic debate regarding fractionation schemes, the vast majority of American practitioners advocate long schedules.

Endoluminal brachytherapy for recurrent laryngeal carcinoma

Early-stage squamous cell carcinoma of the larynx is usually treated with local field radiotherapy. Surgery is used for salvage following recurrence. Further recurrences present a more difficult therapeutic problem which requires individualized management. The aims of local control, survival, maintenance of function and minimizing side effects all need to be balanced according to the site and extent of disease. The present case study looks at the management of a 54-year-old man with multiple recurrences from a squamous cell carcinoma of the larynx. It describes a technique of endoluminal brachytherapy using an iridium-192 wire spiralled around the outer part of a tracheostomy tube that achieves good local control while enabling self-insertion and self-cleaning during the procedure. The dose given was 2500 cGy at 5 mm over 25.2 h and was achieved with minimal early or delayed side effects. The patient had no further symptoms relating to the stomal recurrence until his death from metastatic disease 6 months later.

Radiotherapy for palliation of symptoms in incurable cancer

Approximately one half of prescribed radiotherapy is given for palliation of symptoms due to incurable cancer. Distressing symptoms including pain, bleeding, and obstruction can often be relieved with minimal toxic effects. Painful osseous metastasis is common in oncologic practice. Ninety percent of patients with symptomatic bone metastases obtain some pain relief with a lowdose, brief course of palliative radiotherapy. One half of the responding patients may experience complete pain relief. A single dose of 800 cGy in the setting of painful bone metastasis may provide pain control comparable to more protracted treatment at a higher dose of radiation. Patients with lytic disease in weight-bearing bones, particularly in the presence of cortical destruction, should be considered for prophylactic surgical stabilization of their condition. Routinely a brief, fractionated course of radiotherapy is given postoperatively. Pain due to multiple bone metastases uncontrolled by analgesics can be managed with single doses of halfbody irradiation. Doses of 600 cGy delivered to the upper half-body (above the umbilicus) and 800 cGy to the lower half-body (from the umbilicus to the middle of the femur) will provide some pain relief in 73% of patients. Half-body techniques have been investigated as prophylactic treatment, as a complement to local-field irradiation, and as fractionated rather than singledose therapy. Although intravenous administration of strontium 89 has been associated with myelosuppression, this treatment has been shown (a) to relieve pain due to bone metastasis and (b) to delay development of new painful sites. Recent data from phase III trials demonstrated that bisphosphonates have a role in reducing skeletal morbidity due to bone metastasis. Bone pain was reduced, and the incidence of pathologic fracture and the need for future radiotherapy was decreased. Radiotherapy relieves clinical symptoms in 70% to 90% of patients with brain metastases. Brief treatment schedules (e.g., 2000 cGy in five fractions over 1 week) are as effective as more prolonged therapy. Patients with solitary brain metastasis and no extracranial disease or controlled extracranial disease should be considered for surgical resection, because phase III data indicate enhanced survival with such an approach. Whole-brain radiotherapy is routinely administered postoperatively. A phase III study is examining the impact of accelerated fractionated doses of radiotherapy (two treatments per day) on survival of patients with brain metastases. Stereotaxic radiosurgical treatment is becoming increasingly available and permits delivery of radiation to metastatic intracranial tumor with minimal exposure of normal surrounding brain This treatment is most commonly used at the time of a solitary recurrence of disease in patients who previously received whole-brain radiotherapy. A role for this modality in newly diagnosed brain metastases remains to be defined. Chest symptoms are common in patients with locally advanced lung cancer and are effectively palliated with one 1000 cGy or two 850 cGy one fraction doses of radiation to the thoracic inlet and mediastinum. Chest pain and hemoptysis are more effectively palliated than cough and dyspnea. In patients with stage III cancer there is no compelling evidence that radiotherapy confers a survival advantage, and it may be reasonable to administer thoracic radiotherapy only when the patient has significant symptoms and the goal is to achieve control of these symptoms. Approximately 75% of the cases of superior vena cava syndrome are due to lung cancer, and small-cell lung cancer is the most common histologic type. A histologic diagnosis should be obtained before treatment is started, because detection of lymphoma or small-cell carcinoma would necessitate systemic therapy. Eighty percent of the patients with vena cava syndrome due to malignant disease achieve symptom relief with a brief, fractionated, palliative course of rad

107C Non-Hodgkin's lymphoma - Part I: Etiology, pathology, diagnostic evaluation and principles of management

This course will review some of the basic mechanisms involved in the genesis of bone pain. A comparative analysis of the clinical trials of local field irradiation on bone m&stases including dose and fractionation schedules, response rates, duration and evaluation of response will be discussed. The role of large field hemibody and systemic irradiation (e.g. isotopestiontium) in the treatment of metastatic disease will be presented. The topics include the response rates and duration of response of symptomatic metastases, the effect of each technique on the delay in progression of overt symptomatic disease as well as a delay in the appearance of new disease and the morbidity associated with each treatment modality. The design of several current trials will be presented as well as concepts for an expanding role of large field and systemic radiation techniques will be presented. The current managed care climate has brought to the forefront some basic issues regarding the economic impact of palliative radiotherapy. Therefore, this course will present an analysis of radiotherapeutic and non-radiotherapeutic management of pain associated with bone metastases as well as discussion of the basic techniques of economic analyses. Techniques of costmininiization, cost-utility, cost-benefit, and cost-effective analyses and the appropriateness of each type of analyses will be presented. A discussion of which costs and benefits to include in the analyses will also be presented.

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain.

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after 89Sr administration. Patients received 2 MBq/kg (118-148 MBq) of 89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%-66% reduction in white cell count and a 14%-75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that 89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

Radiotherapy in the treatment of low-grade astrocytomas. II. The physical and cognitive sequelae.

The purpose of the present study was to define the late effects, both physical and psychological, of treating low-grade astrocytomas with radiotherapy. Fifty patients, half of whom received radiotherapy, underwent an assessment of neurological and neuropsychological function. There was no difference in neurological function between the two groups. The radiotherapy recipients, including those with cerebellar tumours, performed significantly worse on measures of intelligence and information processing. In addition, there was a greater incidence of special education needs in the irradiated group. We conclude that children with low-grade astrocytomas who receive radiotherapy have no greater neurological deficit but that the use of radiotherapy carries a penalty in terms of long-term cognitive function and confirmed the findings of many previous reports that supratentorial irradiation is detrimental. More surprisingly, it has been demonstrated that local field irradiation to the posterior fossa can also produce significant cognitive impairment.

External beam radiotherapy: hard facts and painful realities.

In comparison to whole brain radiotherapy, local field radiotherapy in a consecutive series of 100 patients with malignant astrocytoma resulted in remarkably less toxicity. Survivorship is not different; the advantage is limited to the 7% long term survivors (defined as living 100% or more beyond median) since toxicity from brain radiation does not occur until a year or more after treatment.

Radiotherapy in the management of epidemic Kaposi's sarcoma

Purpose : This study is presented to help define the role of radiotherapy in the management of epidemic Kaposi's sarcoma. Methods and Materials : Between June 1986 and June 1993, we treated 453 patients who had acquired immunodeficiency syndrome related Kaposi's sarcoma. Two hundred fifty-two patients (55.6%) had received previous treatment for their Kaposi's sarcoma: 228 (55.3%) with interferon, and 116 (25.6%) with Vinblastine. Depending on both tumour size and location, patients were treated with extended cutaneous irradiation using 4 MeV electron beam energy and/or localized irradiation using 45–100 kV x-ray (cutaneous lesions), or 4 MV x-ray (oral tumours). A total of 5015 courses of radiation therapy was given. The intention of the treatment was closely linked to the anatomic sites. Multiple courses of treatment ranging from 10 to 20 Gy (2.5 Gy/fraction, 4 times/week) were used for Kaposi's sarcoma involving conjunctiva ( n = 32 treatments), eyelids ( n = 306), lips ( n = 170), hands ( n = 208), feet ( n = 417), penis ( n = 131), oral mucosa ( n = 43), and anal region ( n = 5). A second group including other cutaneous sites (face, trunk, limbs) was treated with a dose of 30 Gy (20 Gy in 2 weeks followed by 2 weeks rest and then a second series of 10 Gy in 1 week). Results : For the first group, tolerance was generally good excluding oral cavity irradiation, with an effective palliation of symptoms (87.8% overall rate of objective responses); an enhanced mucosal reactions was noted in patients receiving oropharyngeal irradiation. For the second group, a complete regression rate of 85% was observed; tolerance was acceptable: complications were severe epidermitis with skin ulceration (5%), exsudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (9%). There was a significant correlation between risk of recurrence (overall recurrence rate of 71% after an average of 7.5 months) and occurrence of opportunistic infections: 85% of recurrences appeared concomitantly with accelerated course of acquired immunodeficiency syndrome. Conclusions : We conclude that radiotherapy is an efficient treatment for epidemic Kaposi's sarcoma (EKS): doses of 15.2 Gy for oral lesions and 20 Gy for lesions involving conjunctiva, eyelids, lips, hands, feet, penis, and anal region were sufficient to produce shrinkage of the tumour and good palliation of symptoms. For the other cutaneous sites, 30 Gy local field irradiation could be safely given with better short-term response. Prophylactic measures with antifungal treatment should be systematically associated with oropharyngeal irradiation, to improve tolerance to the treatment.

Treatment of intracranial ependymomas of children: review of a 15-year experience

Purpose : There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. Methods and Materials : Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12–197 months with a median of 54 months. Results : The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3–72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. Conclusion : Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.

Strontium-89 (Metastron) in the treatment of prostate cancer metastatic to bone.

Bone metastases that develop in patients with advanced prostate cancer often cause deep, unremitting pain. Palliative options for the control of this pain include analgesic support, cytotoxic chemotherapy and external-beam radiotherapy. In addition to external irradiation, interest in intravenously injected radioisotopes that are preferentially localized to bone has been mounting. Metastron (an isotope of strontium) imitates the biodistribution of calcium in vivo and is avidly taken up into bony metastases where it has a biological half-life of just over 50 days. The biological half-life in undiseased bone is far shorter, approximately 14 days. Various studies have been conducted to evaluate the role of Metastron in metastatic prostate cancer. An optimum dose has yet to be finalized, but it is clear that the change of haematological toxicity becomes more significant at much larger doses. In the large, randomized Trans Canada study in which Metastron or placebo was given to patients as an adjunct to local field irradiation, those patients treated with Metastron had a significantly reduced intake of analgesics. Furthermore, progression of pain, as measured either by sites of new pain or by the requirement for further palliative radiotherapy, demonstrated statistically significant differences in favour of Metastron. There is thus increasing evidence of a useful role for Metastron in the treatment of prostate cancer metastatic to bone.

Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer

Purpose : A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. Methods and Materials : The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. Results : One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor markers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. Conclusions : It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

Intracranial ependymoma long term outcome, patterns of failure.

We analyzed 31 patients with intracranial ependymoma, all verified by secondary neuropathology review. There were 12 patients with ependymomas and 19 patients with anaplastic ependymoma by the WHO classification. Eight patients received craniospinal irradiation, 22 patients received cranial irradiation alone, and one patient was treated with chemotherapy alone. The median follow-up time was 11 years. The 5- and 10-year progression-free survivals (PFS) were 60% and 48%. Those with anaplastic tumors had a decreased 10 year PFS over those with low grade lesions: 26% vs. 55% (p = 0.02). Delivering spinal irradiation in addition to cranial irradiation did not improve outcome. There were relapses in 16 patients. All patients relapsed at the primary intracranial sites with no spinal failures. Patients treated with whole brain irradiation had decreased 10 year PFS over those treated with local fields: 19% vs. 64% (p = 0.006). Those patients treated to > or = 50 Gy had an improved long-term PFS (p = 0.04). Multivariate analysis was undertaken with the following variables: extent of cranial irradiation, pathology, anatomic site of ependymoma, cranial irradiation dose, extent of surgery, and whether spinal irradiation was given. With PFS as the endpoint, only extent of cranial irradiation (favoring local fields) and pathology (favoring low grade ependymoma) were significant prognosticators. We conclude that carefully outlined local field irradiation is the therapy of choice, and elective spinal irradiation is of questionable benefit.

Intracranial ependymoma in children: analysis of prognostic factors.

Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

A report of RTOG 8206: A phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases

Hemibody irradiation (HBI) in a single exposure is an effective and safe technique for palliation of symptoms due to widespread bony metastases (RTOG 78-10). The present study (82-06) sought to explore the possibility that HBI added to local-field irradiation might delay the onset of metastases in the hemibody effected, as assessed by bone scans and X rays, and decrease the frequency of further treatment. The results of this clinical trial establish that 800 cGy of HBI is indeed causes micro-metastases to regress, perhaps completely. A total of 499 patients were randomized to receive either HBI or no further treatment following completion of standard palliative local field irradiation (300 cGy × 10) to the symptomatic site. Improvement was seen in time-to-disease progression at one year, 35% for local + HBI versus 46% on the local-only control arm. Time-to-new disease in the targeted hemibody was also improved. At one year, 50% of patients on the local + HBI arm showed new disease compared to 68% on the local-only arm. Furthermore, the median time-to-new disease within the targeted HBI area was 12.6 months for the local + HBI arm versus 6.3 months for patients in the local-only arm. Time-to-new treatment within the hemibody segment was also delayed. At one year, 76% of the local only group had been retreated versus 60% in the local + HBI arm. There were no fatalities and no radiation pneumonitis was seen in the local + HBI arm. Overall, the incidence of toxicities was low (5–15%). The occurrence of severe hematopoetic toxicities were significantly different in the local + HBI arm, but they were transitory. One life-threatening thrombocytopenia occurred, for a limited time, indicating excellent tolerance to HBI. This clinical trial demonstrates that HBI has the potential to be used to treat systemic and occult metastases, particularly if both halves of the body can be treated.