Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas

The vast majority of patients treated for malignant gliomas with surgery, conventional radiation therapy, and systemic chemotherapy recur within 2 cm of their original disease site as documented by CT scanning. We have analyzed the clinical patterns of failure in patients treated with stereotactic interstitial irradiation (brachytherapy) for malignant gliomas in order to determine if this modality has altered the recurrence pattern in this disease. Between December 1985 and December 1989, 53 patients with malignant glioma were treated with stereotactic interstitial irradiation using temporary high activity iodine-125. Thirty-three patients were treated as part of a primary treatment protocol that included 5940 cGy external beam prior to implantation. Twenty patients were treated at time of recurrence. The median dose of radiation given at implantation was 5040 cGy for the primary lesions and 5450 cGy for the recurrent lesions. Twenty-two patients have suffered relapse as documented by clinical and radiographic studies. The predominant patterns of failure in these 22 patients were in the margins of the implant volume (8) and distant sites (10) within the CNS (distant ipsilateral or contralateral hemisphere, spinal axis) or extraneural. Thus, marginal and distant recurrences accounted for 82% of the relapses in our patients. We conclude stereotactic interstitial irradiation has changed the recurrence pattern in patients with malignant glioma with true local recurrence no longer being the predominant pattern of failure as is seen with conventional therapy.     

显微手术切除后瘤腔植入缓释5-氟尿嘧啶化疗联合125I增敏放疗治疗恶性脑胶质瘤

 目的　探讨外科显微手术切除后瘤床内植入5-氟尿嘧啶（5-Fu）多聚缓释体局部化疗联合125I粒子局部增敏放疗治疗恶性脑胶质瘤的临床疗效。方法　对65例脑胶质瘤患者行开颅显微手术切除,术中于瘤床周围植入5-Fu多聚缓释体和125I粒子,术后（3个月～1年）立体定向引导下再次植入1～2次。随访6～36个月,观察疗效、瘤周水肿情况和患者不良反应。并与同时期经随访的40例接受显微镜下全切后常规放化疗的脑胶质瘤患者相比较。结果　术后1周内患者头痛明显,脑脊液WBC不同程度升高,瘤周水肿较单纯手术明显,经治疗所有患者都顺利出院。44例患者获完全随访,生存期明显延长,半年内复发4例（9.1 %）,无死亡;1年内复发14例（31.8 %）,无死亡;2年内复发20例（45.5 %）,死亡12例（27.6 %）;3年内复发29例（65.9 %）,死亡20例（45.5 %）。未发现明显的不良反应,患者生存质量得到明显改善。结论　显微镜下手术全切肿瘤是治疗的关键,术后于瘤床内植入5-Fu多聚缓释体局部化疗联合125I局部增敏放疗,是一种可供选择的治疗人类脑恶性胶质瘤的安全有效方法。     

Treatment of malignant gliomas with interstitial irradiation and hyperthermia.

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.     

Recurrent gliomas: Comparison of computed tomography (CT)-guided ( 125) I seed implantation therapy and traditional radiochemotherapy

Background: Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomography (CT)-guided interstitial ( 125) I seed implantation with traditional radiochemotherapy for treatment of recurrent gliomas. Results: The response rate at 1, 3, 6 and 12 months after ( 125) I seed implantation was 68.6, 74.3, 77.1 and 62.8% respectively, which was significantly higher than the group treated with the conventional chemoradiation protocol (p < 0.05). Patients exposed to ( 125) I seed implantation had a median survival of 29.0 months, whereas the median survival of those treated with traditional radiochemotherapy was 19.0 months. The difference observed between the two groups was significant. There were no severe complications or mortality associated with either treatment, except for one case of intracerebral hemorrhage around the tumor area in the ( 125) I seed implants group. Methods: From November 2002 to May 2010, 73 consecutive patients with recurrent gliomas were treated with CT-guided ( 125) I seed implantation (35 cases) or traditional radiochemotherapy (38 cases). Patients were followed up after treatment and the therapeutic effect was evaluated by comparing the response and survival rates of the two groups. In particular, patients treated with ( 125) I seed implantation were monitored for adverse side effects. Conclusions: CT-guided ( 125) I seed implantation is safe and well-tolerated and more importantly, shows superior efficacy compared with conventional radiochemotherapy. This suggests that CT-guided ( 125) I seed implantation could be an alternative approach for recurrent gliomas.     

High activity iodine-125 interstitial implant for gliomas.

A total of 307 adult patients with glioma were treated with high-activity removable iodine-125 interstitial brain implants at the University of California at San Francisco from December 1979 to June 1990. Recurrent gliomas underwent brain implant alone whereas previously untreated (primary) tumors underwent brain implant boost after external beam radiotherapy. Of these patients, 106 had primary glioblastoma multiforme, 68 had primary non-glioblastoma glioma, 66 had recurrent glioblastoma multiforme and 67 had recurrent nonglioblastoma glioma. Median follow-up for living patients was 143 weeks. Median survival from diagnosis for primary glioblastoma multiforme and high and low grade nonglioblastoma glioma was 88 weeks, 142 weeks, and 226 weeks, respectively. Median survival measured from the date of implant for recurrent glioblastoma multiforme and high and low grade nonglioblastoma glioma was 49 weeks, 52 weeks, and 81 weeks, respectively. Ninety-two percent of patients had no toxicity or transient acute side effects. Severe acute toxicity was seen in 6% of patients, life threatening acute toxicity in 1% of patients, and fatal toxicity in less than 1% of patients. Forty percent of patients with malignant glioma underwent reoperation at a median of 33 weeks after brain implant, with tumor found in 95% of specimens at reoperation. This large experience demonstrates that interstitial implant is well-tolerated and prolongs survival in patients with primary and recurrent glioblastoma multiforme, as evidenced by the 3-year survival rates of 22% and 15%, respectively.     

Permanent and removable implants for the brachytherapy of brain tumors

Thirty-seven patients harboring primary or metastatic brain tumors were treated with 40 implantations of radioactive sources (¹⁹²Ir, ¹⁹⁸Au, or ¹²⁵I) using stereotactic neurosurgical techniques. Most tumors had recurred after surgery, whole brain irradiation, and treatment with all feasible chemotherapeutic agents. Sixteen of the 40 implants were permanent; 24 were mounted in plastic catheters for removal after the desired dose had been delivered. One or more sources were placed in each tumor to deliver 3500–7350 rad to the tumor's periphery for ¹⁹⁸Au, 4,000–12,000 rad for ¹⁹²Ir, and 3,000–20,000 rad for ¹²⁵I. Three of the six patients treated with ¹⁹²Ir had objective responses for 2, 4, and 12 months, and two stabilized for 8 and 11 months. Seven of the 11 patients treated with ¹⁹⁸Au were evaluable: three responded for 3, 5, and 37 + months, one deteriorating patient with a recurrent tumor stabilized for 6 months, and two deteriorated despite treatment. One patient received an interstitial “boost” dose with ¹⁹⁸Au, after whole brain irradiation and stabilized for 15 months before developing spinal metastases. Six patients received permanent implants with low activity ¹²⁵I. Three of these patients had glioblastomas or anaplastic astrocytomas; all continued to deteriorate despite the interstitial irradiation, presumably because the does rate was too low. One patient with a low-grade astrocytoma (optic chiasm) responded dramatically to permanent, low activity ¹²⁵I implants (11 + months). Another (hypothalamic glioma) had a permanent ¹²⁵I implant, responded, and was stable at 9 months when external irradiation was administered. One patient with a suprasellar “teratoid” tumor stabilized for 10 months. Seventeen removable high activity ¹²⁵I sources were implanted in 15 patients who had recurrent malignant primary or metastatic tumors. Twelve of these patients are currently evaluable; eight patients responded for 4 to 8 months, three patients stabilized for 3,7, and I1 months, and one patient harboring a metastatic melanoma failed to improve despite two implants 8 weeks apart.     

Strahlentherapie bei Hirngliomen im Erwachsenenalter

Low grade and highly malignant gliomas are normally characterized by a primary single site formation of a tumor with an aggressive growth form along the nerve sheath. The role of radiotherapy for low grade gliomas is currently undergoing a change in the indications due to the introduction of chemotherapy. Risk factors, however, still remain the most important instrument for the decision on therapy. The indications for inoperable progressive tumors or malignant transformation are indisputable. Gliomas with high grade malignancy (grades III and IV) are with 30% the most common and also the most aggressive brain tumors and lead to death within a few weeks if they remain treated. In addition to the primary operation the value of postoperative percutaneous radiation in the treatment of malignant gliomas is indisputable. Alternative radiation techniques are heavy ion therapy and stereotactic interstitial brachytherapy for small inoperable brain tumors.     

Thermoradiotherapy of recurrent malignant brain tumors.

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.     

Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma

BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that participates in multiple cell functions; it promotes proliferation, motility, and morphogenesis of epithelial cells. Some malignant tumors, such as breast carcinoma, bronchogenic carcinoma, and multiple myeloma, overexpress it and its receptor. Hepatocyte growth factor is also present in normal astrocytes; therefore, it is important to investigate whether HGF participates in the pathophysiology of malignant gliomas and other brain tumors. Intratumoral concentration of HGF in human intracranial neoplasms was measured and correlated with prognosis, tumor recurrence, vasogenic edema, cell proliferation index, and vascular density. METHODS: Hepatocyte growth factor concentration was measured in 62 intracranial tumors, including 16 anaplasic astrocytomas (AA), 16 glioblastoma multiformes (GM), 11 meningiomas, 9 hypophyseal adenomas, 7 oligodendrogliomas, and 3 cordomas, and in 4 samples of nonneoplastic brain tissue. The following parameters were correlated with HGF values: survival and tumor recurrence, cell proliferation index and vascular density as determined by immunohistopathologic analysis, and peritumoral edema as seen by magnetic resonance imaging. RESULTS: Hepatocyte growth factor concentration (pg/mL) was significantly higher in malignant gliomas (AA and GM) than in adenomas, oligodendrogliomas, and nonneoplastic brain tissue, but it was similar to that of meningiomas. Mean survival of patients with AA was 16.5 +/- 3.6 months and for patients with GM 12.3 +/- 1.3 months. Hepatocyte growth factor concentration was higher in GM than in AA (15,844 +/- 2504 vs. 7499 +/- 1703, P = 0.0375) and was correlated with the cell proliferation index and with poor prognosis. Likewise, mean tumoral concentration of HGF was higher in meningiomas that relapsed than in those without recurrence (22,887 +/- 6489 vs. 2090 +/- 497, P = 0.008). CONCLUSIONS: Intratumoral concentration of HGF in gliomas is associated with malignancy and poor prognosis. High HGF is also found in meningiomas and is related with long term recurrence. The current findings suggest that the routine measurement of HGF may be used as a predictive factor for planning therapeutic strategies in both malignant gliomas and meningiomas. The potential use of HGF inhibitors or antagonists for therapy of these tumors should be explored.     

Inhibition of human malignant glioma growth in vivo by human recombinant plasminogen kringles 1-3.

Human malignant gliomas are highly vascularized and aggressive tumors. Angiogenesis inhibitors have been shown to induce regression of a variety of primary and metastatic tumors in vivo. However, their usefulness in treating brain tumors is not well understood. Angiostatin, a multiple kringle (1-4 of 5)-containing fragment of plasminogen, is one of the highly effective natural cryptic angiogenesis inhibitors. In our study, the therapeutic efficacy of non-glycosylated and small molecular size recombinant kringles 1-3 (rPK1-3) was examined in the treatment of brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days post-implant were treated daily with rPK1-3 (100 mg/kg) s.c. for 21 days. Treated animals showed suppressed brain tumor growth by greater than 71.2% along with a 3-fold increase of apoptotic index and suppressed vascularization by 78.9%, without any observable signs of toxicity. Analysis of bFGF and VEGF expression in the tumors of treated animals using immuno-histochemical methods showed near complete absence of growth factors. Our results indicate that the non-glycosylated, small molecular size rPK1-3 is an efficient tumoristatic agent for the treatment of intracranial human glioma xenografts in mice and might provide new strategies for the treatment of brain tumors.     

I 125放射性粒子植入在口腔颌面部恶性肿瘤治疗中的应用

  目的  研究I125放射性粒子组织间近距离植入治疗口腔颌面部恶性肿瘤的近期疗效及副反应, 探讨其在恶性肿瘤综合治疗中的应用价值。   方法  根据制定的相应放射性粒子植入治疗计划, 对38例口腔颌面部恶性肿瘤患者应用手术配合I125粒子植入治疗或单纯粒子植入治疗, 术后随访观察疗效及副反应。   结果  所有病例随访12~28个月, 平均20个月, 其中23例手术配合粒子植入者局部未见明显新生肿物, 15例单纯粒子植入病例均见病灶不同程度缩小, 不适症状有所减轻。除2例患者出现局部皮肤色素沉着, 1例患者咽部不适1周后缓解, 余病例均未出现明显粒子植入后副反应。   结论  放射性粒子植入治疗对口腔颌面部恶性肿瘤的近期疗效显著, 为综合治疗口腔颌面部恶性肿瘤提供了新的发展方向。      

Extraneural metastatic glioblastoma after interstitial brachytherapy

PURPOSE: This is a report of 3 cases of extraneural metastasis of glioblastoma after interstitial radiation and assessment of pertinent literature addressing concern over an increased risk of these events with this therapy. METHODS AND MATERIALS: In a series of 82 patients treated with (125)I brachytherapy for primary malignant brain tumors over a 7-year interval, 3 cases of extraneural glioblastoma were identified. The multicatheter technique for delivery of (125)I sources was utilized in all. Extraneural metastases were documented by imaging studies or biopsy. Over the same period, 310 patients with primary malignant brain tumors were treated without brachytherapy. RESULTS: Biopsy-proven scalp and skull metastases occurred in 2 patients, at 3 and 8 months following brachytherapy. Each developed radiographic evidence of systemic metastases at 7 and 14 months postbrachytherapy, respectively. The third patient developed biopsy-proven cervical node involvement 4 months after brachytherapy. No patients with malignant gliomas undergoing craniotomy or stereotactic biopsy, but not brachytherapy, during the same time period developed extraneural metastases. Incidence in previously reported series commenting on this otherwise rare process range from 0% to 4.3%. The incidence of extraneural metastases in this series is 3.7% (3/82) and is comparable to those reports. CONCLUSIONS: Percutaneous catheter-delivered brachytherapy may be associated with an increased incidence of extraneural metastatic glioma.     

手术切除联合间质内缓释化疗治疗复发性脑胶质瘤

目的 探讨外科手术切除与瘤床问质内缓释化疗治疗复发性脑胶质瘤的疗效。方法 对30例复发性恶性脑胶质瘤患者行开颅手术全切除,术中在瘤床植入Vp-16多聚缓释体,用量为100～150mg。随访3～24个月,观察肿瘤再次复发率和患者死亡率,并与以前随访的46例再次手术的恶性脑胶质瘤结果相对比。结果 30例患者均获随访,3个月复发5例(16．7％),死亡2例(6．7％);6个月复发9例(30．0％),死亡6例(20．0％);12个月复发15例(50．0％),死亡12例(40．0％);24个月复发25例(83．3％),死亡21例(70．0％);全部患者均无化疗不良反应。结论 力争手术全切除联合瘤床间质内缓释化疗,可提高药物在瘤灶处的浓度和作用时间,从而提高复发性脑胶质瘤的疗效。     

Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases

To analyze treatment results of supratentorial malignant gliomas in the megavoltage era, all the histologic specimens were reviewed and glioblastoma multiforme (GBM) was distinguished from anaplastic astrocytoma (AA) by the presence of necrosis. Among those who had completed radiotherapy and who had been followed for at least one year, 135 GBM and 43 AA patients were found. The median survival time (MST) after operation was 12 months for GBM and 18 months for AA. The 5-year survival rate was 0.9% for GBM and 18% for AA. The size of radiation field had little influence on survival time; MST was 12 months for GBM patients treated with a local field covering tumor plus less than 2 cm margin, 12 months for those treated with a generous field (2 cm or more margin), and 13 months for those treated to whole brain. Also for AA, whole brain radiation did not prolong survival. Initial relapse of GBM and AA developed within the irradiated volume in 86% of the cases treated with a generous field. Whole brain radiation seemed useless for the treatment of malignant gliomas. Survival time appeared to be dose-dependent; MST was 10, 13, and 16 months for GBM patients who received 45-57, 57-63, and 63-72 Gy, respectively. Extensive surgical resection was associated with a better prognosis in GBM. AA patients 60 years old or older had a poorer prognosis than younger patients, but age was not a significant prognostic factor for GBM. Chemotherapy appeared to prolong survival slightly without improving long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of the RTOG recursive partitioning analysis to validate the benefit of iodine-125 implants in the primary treatment of malignant gliomas.

PURPOSE: To date, numerous retrospective studies have suggested that the addition of brachytherapy to the conventional treatment of malignant gliomas (MG) (surgical resection followed by radiotherapy +/- chemotherapy) leads to improvements in survival. Two randomized trials have suggested either a positive or no survival benefit with implants. Critics of retrospective reports have suggested that the improvement in patient survival is due to selection bias. A recursive analysis by the RTOG of MG trials has stratified MG patients into 6 prognostically significant classes. We used the RTOG criteria to analyze the implant data at Wayne State University to determine the impact of selection bias. METHODS AND MATERIALS: Between July 1991 and January 1998, 75 patients were treated with a combination of surgery, radiotherapy, and stereotactic I-125 implant as primary MG management. Forty-one (54.7%) were male; 34 (45.3%) female. Median age was 52 years (range 4-79). Twenty-two (29.3%) had anaplastic astrocytoma (AA); 53 (70.7%), glioblastoma multiforme (GBM). Seventy-two patients had data making them eligible for stratification into the 6 RTOG prognostic classes (I-VI). Median Karnofsky performance status (KPS) was 90 (range 50-100). There were 14, 0, 14, 31, 12, and 1 patients in Classes I to VI, respectively. Median follow-up time for AA, GBM, and any surviving patient was 29, 12.5, and 35 months, respectively. RESULTS: At analysis, 29 (40.3%) patients were alive; 43 (59.7%), dead. For AA and GBM patients, 2-year and median survivals were: 58% and 40%; 38 and 17 months, respectively. For analysis purposes, Classes I and II, V and VI were merged. By class, the 2-year survival for implanted patients compared to the RTOG data base was: III--68% vs. I--76%; III--74% vs. 35%; IV--34% vs. 15%; V/VI--29% vs. V--6%. For implant patients, median survival by class was (in months): I/II--37; III--31; IV--16; V/VI--11. CONCLUSION: When applied to MG patients receiving permanent I-125 implant, the criteria of the RTOG recursive partitioning analysis are a valid tool to define prognostically distinct survival groups. As reflected in the RTOG study, a downward survival trend for the implant patients is seen from "best to worse" class patients. Compared to the RTOG database, median survival achieved by the addition of implant is improved most demonstrably for the poorer prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with I-125 implant and would contradict the notion that the patients most eligible for implant are those gaining the most benefit from the treatment. In light of the contradictory results from two randomized studies and given the present results, further randomized studies with effective stratification are required since the evidence for a survival benefit with brachytherapy (as seen in retrospective studies) is substantial.     

Effect of dose rate on local control and complications in the reirradiation of head and neck tumors with interstitial iridium-192

Interstitial Iridium-192 was used as the sole treatment for 23 previously irradiated patients with recurrent or second primary malignancy in the head and neck region. Doses used in initial external beam treatment ranged from 50.0 to 72.0 Gy, in daily fractions of 180 to 200 cGy. Retreatment with interstitial implant using the Quimby system delivered total doses between 38.5 and 60 Gy, with hourly dose rates of 30 to 66 cGy. Local control in the implanted volume was seen in 21 of 23 patients at 5 to 34 months post-implant (median 10 months). Dose rate (hourly dose delivered at 0.5 cm beyond the periphery of the implanted tumor volume) did not affect local control, but did have a significant impact on severe complications (soft tissue necrosis and fistulae; p = 0.26). No effect on either local control or complication rate was found for volume of implant, initial external beam radiation dose, time to recurrence, or anatomic site of treatment. These findings suggest that interstitial irradiation is effective treatment for head and neck cancers in previously irradiated sites. Dose rates as low as 32 cGy/hr provided adequate local control, with few long-term complications to date; doses above 42 cGy/hr may be associated with severe and even fatal complications.     

Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: the UCSF experience.

Although interstitial brachytherapy appears to be effective in treating recurrent malignant gliomas, it has been studied less extensively in patients with newly diagnosed tumors. To examine the effect of this treatment when used at the time of primary diagnosis, we retrospectively reviewed the records of 88 patients who received temporary interstitial implants of 125I for newly diagnosed malignant gliomas. This brachytherapy was preceded by a course of external radiation therapy and followed, in some cases, by chemotherapy. The median duration of survival after the beginning of external radiation therapy was 87 weeks in patients with glioblastoma multiforme and 160 weeks in those with anaplastic gliomas. In 46% of patients with glioblastoma multiforme and 56% of those with anaplastic gliomas, a second operation was necessary to remove symptomatic radiation necrosis, recurrent tumor, or both. Our results support the conclusion that interstitial brachytherapy used at the primary diagnosis lengthens survival in selected patients with glioblastoma multiforme. However, the toxicity is significant in terms of the need for surgical resection of symptomatic necrosis. In patients with anaplastic gliomas, the toxicity associated with the treatment probably outweighs its advantages.     

New treatment strategies for malignant gliomas

Malignant gliomas are the most prevalent type of primary brain tumor in adults. Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. The median survival of patients with glioblastoma muhiforme, the most common grade of malignant glioma, is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Essentially, tumor recurrence is inevitable. Salvage treatments upon recurrence are palliative at best and rarely provide significant survival benefit. Therapies targeting the underlying molecular pathogenesis of brain tumors are urgently required. Common genetic abnormalities in malignant glioma specimens are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy.     

Customized Gynecologic Interstitial Implants: CT-Based Planning, Dose Evaluation, and Optimization Aided by Laparotomy

Purpose: Interstitial perineal implants may be utilized to deliver a high local radiation dose in the treatment of advanced gynecologic malignancies. Lack of knowledge of the precise anatomic relationships between the implant and the target and critical organs may limit efficacy and increase complication risks. Computed tomography (CT)-based planning, dose evaluation, and optimization of customized interstitial implants, aided by laparotomy, have been developed to overcome these limitations.

Methods and Materials: Twenty patients with locally advanced gynecologic malignancies treated between May 1990 to October 1996 with external irradiation and one or two implants. Interstitial implants were performed when intracavitary brachytherapy was judged to be inadequate or when the response to external radiation and an intracavitary implant was not satisfactory. Customized interstitial implants were planned using preimplantation CT to determine catheter angles and paths that best implanted the target while avoiding pelvic bones and organs. Laparotomy aimed at lysing bowel adhesions, placement of omental carpet, and refining needle placement. Postimplantation CT was used for loading optimization and dose evaluation.

Results: Catheter angles 15–25° were found to adequately implant anteriorly laying targets while avoiding pubic bones and bladder. Adhesiolysis of bowel loops from the vaginal apex was required in patients with prior hysterectomy. Small modifications in catheter placements were made during laparotomy in all implants. Postimplantation CTs showed deviations of the catheter positions compared with the planning CTs and were essential in determining target and organ doses and loading optimization. At a median follow-up of 42 months (range: 9–80 months), local control rate is 55% and disease-free survival 40%. Late complications occurred in 2 of 11 of patients without local recurrence.

Conclusions: CT-based planning, loading optimization, and dose evaluation of customized implants improve radiation dose delivery. Laparotomy enhances implant accuracy and safety. Local tumor control rate is still unsatisfactory. It reflects the shortcomings of technical advances alone in poor prognosis tumors like those selected for this series.     

Reoperation in recurrent high-grade gliomas: literature review of prognostic factors and outcome.

Two percent of cancer deaths are caused by malignant primary brain tumors, and most of these are high-grade gliomas. Despite the treatment given, malignant gliomas recur early. Mean survival is less than 12 months, and only 20% of patients survive for more than 2 years. This rapid course induces some physicians to resort to all the therapeutic options available and, at recurrence, to reevaluate the patient for a second intervention. Others consider reoperation to be an overtreatment. The debate is ongoing, and an answer likely will be found only through better identification of the prognostic factors that will identify patients who will benefit from reoperation.