Thallium-201 SPECT as response parameter for PCV chemotherapy in recurrent glioma

Combination chemotherapy with procarbazine, CCNU and vincristine (PCV) may be effective in patients with recurrent glioma. Response monitoring is mandatory, but radiological response evaluation is often difficult. We evaluated Thallium-201 (201Tl) SPECT as a response parameter in ten patients treated with intensive PCV chemotherapy for recurrent glioma. 201Tl-SPECT studies showed early changes (decreasing volume and intensity) in nine patients and these changes were more pronounced than radiological findings. 201Tl-SPECT results after completion of chemotherapy seemed to correlate with clininal findings during follow up. We conclude that 201Tl-SPECT may contribute to the assessment of response in patients treated with PCV chemotherapy for recurrent glioma.     

Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas

A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6 000 rads after possibly radical removal of tumors. CCNU administration in the dosis of 100 mg/sq m of body surface every 6–8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61±7 weeks, while in those receiving additional chemotherapy was 56±4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality. Address for offprints: T Trojanowski, Department of Neurosurgery, Medical School, Jaczewskiego 8, 20-950 Lublin, Poland     

Chemotherapy in the treatment of malignant gliomas

Malignant gliomas are one of the most difficult tumors to treat, with only modest advances being made in the past few decades. Surgery and radiation have had the greatest impact, increasing survival. Chemotherapy modestly increases survival. The use of chemotherapy in the treatment of malignant gliomas is the focus of this paper and the more commonly used agents at diagnosis and relapse are reviewed. Since most patients fail first-, second- and even third-line agents that are commercially available, some of the more relevant new biological compounds will also be discussed. As treatments for brain tumors evolve, it is likely that optimal therapies will come from combination therapies that incorporate target-specific and chemotherapeutic agents.     

99mTc-MIBI SPECT compared with201TI SPECT for the detection of breast cancer and lymph node metastasis

A comparative study of²⁰¹Tl and^99mTc-methoxy-2 isobutyl isonitrile (^99mTc-MIBI) was performed in 39 breast tumors.²⁰¹Tl scintigraphy was carried out in 24 breast tumors and^99mTc-MIBI scintigraphy in 15. The sensitivity of²⁰¹Tl for malignant tumors was 100% (22/22), but specificity was 0% (0/2). On^99mTc-MIBI scintigraphy, the sensitivity for malignant tumors was 83.3% (10/l2) and specificity was 100% (3/3).^99mTc-MIBI might be more useful for the diagnosis of breast tumors, because the tumor/background ratio of^99mTc-MIBI was significantly higher than that of²⁰¹T1. In addition,²⁰¹Tl scintigraphy and^99mTc-MIBI scintigraphy showed the same degree of accuracy (93.3%) in detecting lymph node metastasis. Moreover, when either ultrasonography (US) with²⁰¹Tl or^99mTc-MIBI scintigraphy was positive for lymph node metastasis, the accuracy of detection became 94.4%. The combined use of ultrasonography and scintigraphy might improve the accuracy of diagnosis of lymph node metastasis.     

201Thallium SPECT and 1H-MRS Compared with MRI in Chemotherapy Monitoring of High-grade Malignant Astrocytomas

Purpose To compare chemotherapy treatment monitoring in astrocytoma by ²⁰¹thallium single photon emission computed tomography (SPECT) and photon magnetic resonance spectroscopy (¹H-MRS) with magnetic resonance imaging (MRI), and to evaluate the influence of morphological tumor changes on cerebral ²⁰¹thallium uptake and metabolic changes in ¹H-MRS. Materials and methods Six patients with highly malignant astrocytomas were followed with quantitative ²⁰¹thallium SPECT, MRI, and ¹H-MRS during chemotherapy. Maximum follow-up included six examinations per patient by either method during 18 months. Criteria were set for: (1) regression ( 25% tumor reduction), (2) status quo (< 25% reduction and < 25% increase), and (3) progression of disease ( 25% tumor increase). Results were compared with the clinical state of disease. Changes of tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were compared to changes in ²⁰¹thallium uptake volumes and ¹H-MRS metabolite ratios. Results Six patients were followed with a total of twenty-four examinations with ²⁰¹thallium SPECT, MRI and ¹H-MRS, respectively, between February 1997 and October 1998. Five patients developed clinical progression of disease, 4 out of 5 cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2 interpretable cases ¹H-MRS progression at final assessment before clinical deterioration. During the phase of clinically stable disease; (A) the criterion for regression or status quo was met in 10 out of 13 assessments with SPECT, 11 out of 13 with MRI, and 8 out of 9 interpretable ¹H-MRS; (B) the criterion for progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of 9 interpretable ¹H-MRS. The accuracy of SPECT, MRI, and ¹H-MRS in identifying changes of tumor burden concordant with patients' clinical course was 78%, 83%, and 82%, respectively. SPECT regression was associated with MRI decrease of tumor size, contrast enhancement, edema and hemorrhage. SPECT progression was associated with MRI increase of the same parameters and the increase of necrosis. ¹H-MRS regression was associated with decrease of edema. ¹H-MRS progression was associated with increase of tumor size, hemorrhage, and increase or decrease of contrast enhancement. Conclusions Both ²⁰¹thallium SPECT and ¹H-MRS evaluation showed sensitivity for detection of astrocytoma progression. We did not find a higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy monitoring. Treatment induced MRI changes were associated with ²⁰¹thallium uptake variations. ¹H-MRS was difficult to apply for astrocytoma treatment monitoring. Improvements regarding size of measurement area such as multivoxel MRS and fat suppression pulses appeared desirable, and also the use of functional techniques with superior resolution such as dual isotope SPECT. However, our results suggest that ²⁰¹thallium SPECT and ¹H-MRS can provide additional information to MRI for chemotherapy efficacy evaluation in selected cases.     

The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin)

Malignant gliomas continue to be a significant sourceof mortality in young and middle aged adults.The introduction of new treatment strategies and multidisciplinaryapproaches has improved the outcome of patients withthese tumors only slightly. Because retinoic acid hasgrowth inhibitory activity against glioma and neuroblastoma cellsin cultures, we assessed the efficacy of all-trans-retinoicacid in the treatment of recurrent cerebral gliomas.Thirty-six patients with recurrent cerebral gliomas were enteredin the study and treated with 120 or150 mg/m²/day of all-trans-retinoic acid as a singleagent. The drug was given for 3 weeksfollowed with one week of rest. Two blocksof 4 weeks constituted one course of treatment.One (3%) of 34 evaluable patients had aminor response and 14 (41%) had stable disease.In the rest of the patients (56%), tumorscontinued to progress despite treatment. The median timeto progression of all evaluable patients was 8weeks, and for the responders was 17 weeks.The higher dose level (150 mg/m²) was associatedwith high incidence of headache, which responded todose reduction. The lower dose level was verywell tolerated, with mild, mainly dermatological toxicity.All-trans-retinoic acid as a single agent has nosignificant activity against recurrent cerebral gliomas.     

Management of Atypical and Malignant Meningiomas: Role of High-dose, 3D-conformal Radiation Therapy

Objective Atypical and malignant meningiomas are at high risk for local failure. The role of radiation therapy (RT) and dose levels required to improve tumor control are poorly defined. This study reviews our experience with RT. Material and methods Thirty-one patients underwent fractionated RT for atypical (AM, 15 patients) or malignant meningioma (MM, 16 patients) of the cranium. Sixteen patients presented with primary and 15 with recurrent disease. Eight patients received RT following total resection, 21 patients after subtotal resection and 2 patient following biopsy only. RT was given using megavoltage photons in 15 patients and combined photons and 160MeV protons in 16 patients. Total target doses ranged from 50 to 68 (AM, mean 62) and from 40 to 72 (MM, mean 58) Gy or CGE (= cobalt-gray-equivalent). Results With mean observation time of 59 months (range: 7–155 months) actuarial local control rates at 5- and 8-years were similar for both histologies (38% and 19% for AM and 52 and 17% for MM). However, significantly improved local control was observed for proton versus photon RT (80% versus 17% at 5 years, p = 0.003) and target doses 60Gy for both, atypical (p = 0.025) and malignant meningioma (p = 0.0006).At time of analysis, 14/15 patients (93%) with AM and 6/16 (38%) with MM were alive. Three patients (19%) with MM developed distant metastasis. Actuarial 5- and 8-year survival rates for MM were significantly improved by use of proton over photon RT and radiation doses 60CGE. Three patients developed symptomatic radiation damage after 59.3, 68.4 and 72Gy/CGE. Conclusion Conformal, high dose RT resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma.     

The use of molecular assays to establish definitively the clonality of ipsilateral breast tumor recurrences and patterns of in-breast failure in patients with early-stage breast cancer treated with breast-conserving therapy

BACKGROUND: Results from numerous trials have indicated that breast-conserving therapy (BCT) produces outcomes equivalent to those produced by mastectomy in terms of both locoregional control and survival. However, conservative treatment has resulted in the dilemma of how best to address recurrences when they appear in a breast treated previously with radiation therapy. Attempts have been made to characterize ipsilateral breast tumor recurrences (IBTRs) as either true recurrences of the treated malignancy or new primary carcinomas, because cancers that represent new primary tumors may be associated with a more favorable prognosis compared with cancers that represent true recurrences. METHODS: The authors studied the clonality of IBTRs relative to the initial invasive carcinomas by using a polymerase chain reaction loss-of-heterozygosity molecular comparison assay in 29 patients who received breast-conserving therapy (BCT). RESULTS: Twenty-two IBTRs (76%) were related clonally to the initial carcinoma, and 7 IBTRs (24%) were clonally different. Clonally related IBTRs were more frequently higher grade (72.2% vs 14.3%; P = .009) and developed sooner after initial treatment (mean time to IBTR, 4.04 years in clonally related IBTRs vs 9.25 years in clonally different IBTRs; P = .002). Six patients subsequently developed distant metastases, and 5 of those patients (83.3%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 30% of all patients. The proportion of IBTRs that were related clonally at 5 years, 10 years, and 15 years after BCT were 93%, 67%, and 33%, respectively. CONCLUSIONS: Clinical classifications of IBTRs were unreliable methods for determining clonality in many patients. Molecular clonality assays provided a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and also provided a more accurate assessment of the efficacy of various forms of local therapy.     

Recent trends in the radiotherapy of pediatric gliomas

The management of pediatric gliomas is controversial, and is greatly influenced by the site of origin of the tumor. For example, cerebellar low grade tumors are often cured by surgery alone. This is in contrast to the hypothalamic and optic system tumors which are usually not amenable to complete resection. For the low grade astrocytomas, the usual indications for adjuvant treatment include: recurrent tumors after initial complete resection or symptomatic tumors that have been incompletely excised. In addition, treatment is generally indicated in tumors with growth on follow-up imaging, even in the absence of symptoms. In selecting the optimal treatment, the relative efficacies of surgery, chemotherapy and irradiation must be balanced by the potential complications of therapy. The potential risks of delayed intervention include irreversible neurologic impairment and potential lower probability of tumor control. This chapter reviews recent trends in the radiotherapeutic management of pediatric low-grade and malignant astrocytomas, particularly the new more conformal techniques that hold the promise of reduced toxicity in children requiring irradiation.     

Clinical results of breast conserving therapy for stage I and II breast cancers: Assessment of local recurrences in relation to surgical margins

Background Because of previously reported shortened follow-up periods, breast conserving therapy is still not prevalent for patients with breast cancer in Japan. This is a report of clinical trial results. Methods Between November 1987 and October 1995, breast carcinomas in 462 patients were treated with breast conserving therapy (BCT). Three hundred and sixty-four patients with follow-up periods of longer than 1 year, excluding simultaneous bilateral breast carcinomas, were analyzed. There were 19 stage 0,211 stage I, 132 stage II, and 2 stage III tumors according to the 1987 UICC classification. A total dose of 50 Gy was delivered over 5 weeks to the preserved breast using⁶⁰Co γrays. The primary site was boosted with a total dose of 10 Gy in 5 fractions in 40 of the 83 patients whose tumor margins were either positive or close. Results In a follow-up period of 12 to 96 months with a median of 35 months, 8 patients developed a breast recurrence. The actuarial overall, relapse-free, and breast-recurrence-free survival at 5 years were 99.0%, 92.3%, and 97.8%, respectively. The difference in the local control rate was significant between patients with negative margins and those with positive margins (P<0.0001), and between the patients with negative margins and those with close margins (P=0.0284). Conclusions The 5-year results of our trial were similar to those of other reported series. Positive and close margins are risk factors for breast recurrence. Improvements in optimal methods of radiation therapy including boost irradiation are needed.     

Cerebral metastases in pleural mesothelioma: Case report and review of the literature

A case of malignant mesothelioma metastatic to the brain is described. A 52-year old woman, with no known exposure to asbestos, presented with a biphasic mesothelioma of the left parietal pleura. Following resection, the thorax was irradiated with 4000 cGy, and all symptoms subsided. Three months later, a left temporal lobe tumor was diagnosed and subsequently resected. Despite neurological improvement, she died 10 days postoperatively from constrictive pericardial disease. The authors have reviewed the 54 reported cases of brain metastases from mesothelioma and have noted that the histologic appearance of brain metastases from mesothelioma may be similar to glioblastoma multiforme. Because brain metastasis from mesothelioma is rare, procedures to clarify the nature of the tumor should be performed.     

重离子（12 C6＋）治疗恶性黑色素瘤的临床研究现状

恶性黑色素瘤（ malignant melanoma,MM）是一种恶性程度高、迁徙能力强的皮肤肿瘤。其发病率在全球范围呈现上升趋势,正日益威胁着人类的生命健康。放射治疗在不能手术切除的恶性黑色素瘤中起着重要作用,然而MM细胞对低LET射线（ x、γ）具有显著的抗拒性限制了常规射线放疗在MM中的应用。重离子由于其特有的物理学特性和生物学优势,使其在肿瘤治疗领域展现出良好的应用前景。本文就重离子在MM中的应用做一综述。     

Localized proton spectroscopy of inoperable brain gliomas. Response to radiation therapy

Within vivo 1H-MRS resonances of several metabolites were simultaneously measured in cerebral gliomas and adjacent normal brain. 15 patients with inoperable brain gliomas all histologically verified were monitored with 1H-MRS and MRI before and after radiotherapy. 11 patients were evaluable. 1H-MRS technique evolved from single volume measurements to one dimensional and two dimensional 1H spectroscopic imaging. In all patients N-acetyl-aspartate signals were decreased in tumour areas compared to the normal brain hemisphere. No recovery was seen after radiotherapy. Choline signals were increased in tumour margins of high grade gliomas and more diffusely in low grade gliomas. In 5 patients the choline resonance decreased after radiotherapy, accompanied by a shrinkage of tumour diameter on MRI. Lactate signals were present in high grade and unspecified astrocytomas and absent in most low grade gliomas. In 3 patients the lactate signal disappeared after radiotherapy. These observations indicate the feasibility of 1H-MRS in monitoring metabolic responses on radiotherapy of brain gliomas.     

康肤霜治疗恶性肿瘤急性放射性皮肤损伤的临床研究

目的：观察康肤霜治疗恶性肿瘤急性放射皮肤损伤的疗效。方法：对2007年8月-2010年10月我院60例Ⅱ级以上放射性皮肤损伤恶性肿瘤患者,随机分为两组,治疗组30例用我院烧伤科自制的康肤霜治疗;对照组30例用羊毛脂软膏治疗,比较两组患者放射皮肤损伤治疗效果、愈合时间及体力状况。结果：60例患者均可进行结果分析。治疗组、对照组总有效率分别为100.0%（30/30）、80.0%（24/30）,两组差别有统计学意义（P〈0.05）。两组平均愈合时间分别为治疗组（7.5±1.7）d,对照组（9.6±3.5）d,治疗组皮肤愈合时间明显比对照组短（P〈0.01）,生存质量高于对照组。结论：康肤霜可有效促进急性放射性皮肤损伤的愈合,是一种经济有效的方法。     

Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery

BACKGROUND:

The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC).

METHODS:

A retrospective review of stage III NSCLC patients treated at who were treated at the Dana‐Farber Cancer Institute/Brigham and Women's Cancer Center was done with institutional review board approval. Patients were followed for toxicity, local and distant failure, and overall survival. Multivariate Cox logistic regression analysis was used to determine the factors associated with treatment outcome.

RESULTS:

Between August 2000 and November 2006, 144 patients received concurrent chemoradiation (CRT) for stage III NSCLC. Eighty of 144 patients were men (56%), and the median age was 61 years (range, 33‐81 years). Sixty‐two patients (43%) had stage IIIA NSCLC, and 82 patients (57%) had stage IIIB NSCLC. Radiotherapy (RT) was given concurrently with chemotherapy to all patients; 100 patients (69%) received CRT without surgery, and 44 patients (31%) received with neoadjuvant CRT followed by surgical resection. The median RT dose was 60 grays (Gy) (range, 46‐70 Gy). The median follow‐up was 15 months (range, 3‐64 months), the median potential follow‐up was 37 months (range, 12‐84 months), and the median overall survival was 22 months (95% confidence interval, 15‐28 months). The 1‐year and 2‐year survival rates were 68% and 47%, respectively. Among the 44 patients who underwent resection, the median survival was 61 months, and the 2‐year survival rate was 73%. On multivariate analysis, stage at the time of treatment (stage IIIA vs stage IIIB) and use of surgery were the only factors associated with improved outcome (P = .01 and P = .001, respectively).

CONCLUSIONS:

In this retrospective series, those patients who were able to undergo resection appeared to have improved outcome after induction CRT. Cancer 2009. © 2009 American Cancer Society.     

99mTc-DTPA SPECT 在脑转移瘤全颅放疗中的应用研究

目的 利用99mTc-DTPA SPECT在全脑放疗过程中研究脑转移瘤血-脑屏障变化规律,为放疗疗效预测和化疗的适时介入提供影像学依据.方法19例60Coγ线全脑外照射的脑转移瘤患者,在放疗前、中(20Gy)、后行99mTc-DTPA核素脑断层显像,分别计算放疗前、中时的肿瘤区与对侧正常脑组织区放射性计数比值(T/N)值.结果1)放疗前、中32枚脑转移瘤T/N值分别为1.892±1.094和2.167±1.637(P＜0.05);2)T/N升高组和不升高组中的脑转移瘤在放疗后有效率分别为94.1%(16/17)和46.7%(7/15)(P＜0.05).结论在全脑放疗20 Gy时,脑转移瘤的血-脑脊液屏障开放程度要高于正常脑组织,T/N值升高,预示放疗效果佳.     

Malignant gliomas of the cerebellum: An analytic review

Using an analytical review, the demographic data on malignant cerebellar gliomas such as length of survival, and those factors associated with prolonged survival were examined. Seventy-one cases of malignant cerebellar glioma reported since 1975 were combined and reviewed with the seven cases treated at our institution since that time. Thirty-seven patients (47%) had grade III tumors and 41 (53%) had grade IV tumors. Fifty-nine percent of the tumors were located in the hemispheres and 41% were found in the vermis. Median survival for patients with grade III anaplastic astrocytomas was 32 months compared to 11 months for those with grade IV glioblastomas multiforme (P = 0.0257). For the entire cohort, patients with grade III tumors, those who had a surgical resection, and those that had received radiation therapy for treatment of their tumor had prolonged survival on multivariable analysis. Radiation therapy was associated with extended survival for patients with grade III tumors by uni- and multivariate analysis. For grade IV tumors, univariate analysis revealed prolonged survival for those patients who had surgical resection compared to those who had biopsy alone (P=0.0036) and for those who received external beam radiation therapy (P=0.0001). Patients with malignant gliomas of the cerebellum had length of survival comparable to their supratentorial counterparts. Prompt diagnosis and treatment may explain the similarity in survival found between supra- and infratentorial malignant gliomas despite an expected shorter survival because of treatment limitations. Surgical resection followed by radiation therapy is recommended for patients with malignant gliomas of the cerebellum.     

84例肺癌脑转移患者生存分析

[目的]探讨影响肺癌脑转移预后的相关因素,为肺癌临床治疗提供参考依据。[方法]回顾性分析本院2006～2007年84例肺癌脑转移患者的临床资料,放疗采用6MV-X全脑姑息放疗,剂量30Gy/2周。生存分析采用Kaplan-Meier法并进行Log-Rank检验,通过比例风险模型（Cox模型）进行多因素分析。[结果]单因素分析显示患者的行为状态（PS评分）、病理类型、脑转移时间和近期疗效等对生存期有影响（P〈0.05）,同步脑转移组和后发脑转移组的1年生存率分别为75.6%、39.5%。多因素分析显示脑转移时间和近期疗效与预后有关（P〈0.05）。[结论]PS评分、脑转移时间和近期疗效是肺癌脑转移独立的预后因素。后发脑转移及近期疗效呈CR、PR者是肺癌脑转移良好的预后因素,这些患者的生存期较长,是潜在的治疗获益人群。     

Malignant gliomas: strategies to increase the effectiveness of targeted molecular treatment

Recently, there has been increasing interest in the use of targeted molecular agents for the treatment of malignant gliomas. These agents are generally well tolerated but have demonstrated only modest activity. In this article, the current status of targeted molecular agents for malignant gliomas will be reviewed and strategies to improve their effectiveness will be discussed.