Meningioma: Current treatment options and future directions

Opinion statement Benign meningiomas can be observed if not symptomatic or growing. When treatment is indicated, the options are surgery, radiosurgery, fractionated radiation therapy, or a combination of these modalities. Except in certain cases, such as large tumors that require debulking for relief of symptoms, we do not recommend the routine use of combination therapy. Intracranial meningiomas have usually been treated with surgical resection with an expected durable local control of 80% to 90% when a gross total resection (GTR) is obtained. Patients who have inoperable disease, refuse surgery, undergo less than a GTR, or who have aggressive histology should instead be considered candidates for radiation therapy or radiosurgery. While benign meningiomas can be successfully treated definitively or postoperatively with either fractionated radiation therapy or single fraction radiosurgery, atypical or malignant lesions are best treated with fractionated radiation therapy with conventional dosimetric margins. The role of systemic therapy is not yet defined, but multiple agents are being investigated in early phase trials for patients with recurrent or progressive disease after standard therapy has failed.     

Brain necrosis following intraoperative radiation therapy or interstitial brachytherapy

We have experienced 8 cases of radiation necrosis which occurred following radiation therapy of malignant brain tumors. In all 8 cases, necrosis developed in the brain tissue adjacent to the tumor after intraoperative radiation or interstitial radiation therapy. Considering that the extent of necrosis usually coincides with the extent of the radiation therapy, this type of necrosis is thought to be the expected result of radiation therapy. A differential diagnosis between radiation necrosis and the recurrence of a brain tumor has been thought to be difficult to achieve. Yet with the use of a dynamic CT or an Xe-enhanced CT, differential diagnosis between these two lesions was clearly accomplished.     

Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (less than or equal to 3 cm) stage IB cervical carcinoma

One hundred and three women with FIGO stage IB cervical carcinoma were treated either by radical hysterectomy and bilateral pelvic lymphadenectomy, or external pelvic radiation and intracavitary brachytherapy to deliver greater than or equal to 6000 rads to point A. Surgical therapy was to be limited to stage IB tumors measuring less than or equal to 3 cm in greatest diameter, Patients with lesions greater than 3 cm, medical contraindications to surgery, or advanced age were to be treated by radiation therapy. Of the 55 women treated surgically, 3 (5.6%) were found on final histologic evaluation to have tumors greater than 3 cm. The 5-year estimated disease-free interval was 92.3% for patients treated by surgery and 91.1% for patients treated by radiation therapy. Similar rates were achieved for the 5-year disease-free interval for lesions greater than 1 cm, 1-3 cm, and less than 3 cm in diameter by either surgery or radiation. It is tentatively concluded that radical hysterectomy and pelvic lymphadenectomy or radiation therapy as outlined above provide equally good disease-free intervals for stage IB cervical tumors measuring less than or equal to 3 cm in diameter. Because of a bias against patients treated with radiation, it is possible that radiation could lead to better results than surgery in comparable (younger, healthier, thinner) population. The advantage of surgical treatment in the younger patient is preservation of ovarian function.     

Overview: Where does radiation therapy fit in the spectrum of liver cancer local-regional therapies?

Experience with radiation therapy for the treatment of hepatocellular carcinoma (HCC) and liver metastases has increased rapidly in the past decade. This is principally because of advances in imaging and radiation techniques that can conform high doses to focal cancers and to a better understanding of how to avoid radiation-induced liver toxicity. Guidelines on how to use radiation therapy safely are becoming more clearly established, and reports of tumor control at 2 to 5 years show the potential for cure after radiation therapy for early-stage HCC and liver metastases. For both HCC and liver metastases, the best outcomes after radiation therapy are found in patients with fewer than 3 lesions that are <6 cm in size, with intact liver function and no extrahepatic metastases. There is a strong rationale for using radiation therapy in patients unsuitable for or with expected poor outcomes after standard local-regional therapies. These patients tend to have advanced tumors (large, multifocal, or invading vessels) and/or impaired liver function, reducing the chance of cure and increasing the chance of toxicity. In these patients, the benefits of radiation therapy over systemic therapy or best supportive therapy should be established in randomized trials.     

Intracranial germ cell tumors

Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological information, but a subgroup of tumors will secrete specific tumor markers, including alpha-fetoprotein and beta-human chorionic gonadotropin, which may obviate the need for surgical intervention. The management of intracranial germ cell tumors in both children and adults remains unsettled. Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy. The dose and volume of radiation therapy needed for disease control is not well established, and controversy exists concerning the need for whole brain or craniospinal radiation therapy for localized tumors. Germinomas are also chemosensitive and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy. The outcome for patients with nongerminomatous germ cell tumors is less favorable. Radiation therapy alone will result in disease control in 40%-60% of patients. The addition of chemotherapy to radiation therapy may improve the rate of survival.     

The management of superior sulcus tumors

Lung cancers arising from the extreme apex of the lung-superior sulcus tumors (SST)-have distinct symptoms and signs at presentation and a characteristic appearance on imaging. However, in their early stages, these tumors are often missed by traditional anterior/posterior chest X-rays. Recent advances in computed tomography (CT) and magnetic resonance imaging (MRI) have made selection of patients with potentially resectable of SST more accurate. If mediastinoscopy reveals no mediastinal lymph nodes involved, the patient can be treated with surgery followed by radiation therapy with or without chemotherapy. If mediastinoscopy reveals microscopic mediastinal lymph node involvement, the patient can be treated with induction radiation therapy and concurrent chemotherapy followed by surgery. If mediastinoscopy reveals gross mediastinal lymph node involvement (N2), or if CT reveals N3 or T4 lesions, the patient can be treated with concurrent chemotherapy and radiation therapy to relieve symptoms; the outcome of such treatment appears to be better than that of sequential chemotherapy followed by radiation therapy. Whenever possible, to enhance the patient's quality of life, surgery should be considered to improve function and relieve pain.     

Targeting epidermal growth factor receptor: novel therapeutics in the management of cancer

Overexpression of epidermal growth factor receptor (EGFR) in epithelial tumors, including head and neck, lung, breast, colon and other solid tumors, has frequently been correlated with poor prognosis, thus stimulating efforts to develop new cancer therapies that target EGFR. Monoclonal antibodies and tyrosine kinase inhibitors specifically targeting EGFR are the most well-studied and hold substantial promise of success. Several compounds of monoclonal antibodies and tyrosine kinase inhibitors targeting EGFR have been studied and clinical trials are now underway to test the safety and efficacy of these targeting strategies in several human tumors. This review will address each of these agents alone or in combination with radiation or chemotherapy and highlight some of these promising developments. Cetuximab (Erbitux) is being evaluated in combination with radiation or chemotherapy in Phase III trials. Other compounds such as h-R3, ABX-EGF, EMD-55900 and ICR-62 have proved to be effective in targeting malignant cells alone or in combination with traditional therapies. Tyrosine kinase inhibitors targeting the intracellular domain of EGFR, including ZD-1839 (gefitinib, Iressa), OSI-774 (Erlotinib/Tarceva), PD-153053, PD-168393 and CI-1033, have been studied in clinical setting alone or in combination with radiation or chemotherapy. ZD-1839 is being studied in a Phase III trial in patients with advanced non-small cell lung cancer. EGFR targeted treatment by monoclonal antibodies and tyrosine kinase inhibitors have been proven to sensitize tumor cells to the effects of chemotherapy and radiation therapy. The synergistic activities and nonoverlapping toxicities of these compounds allow concomitant administration with cytotoxic therapy. Challenges of evaluating EGFR targeted agents exist in selecting the optimal dosages and determining long-term toxicity.     

Radiotherapy for anaplastic esophageal cancer

We report our experience with radiation therapy in 2 patients with anaplastic esophageal cancer with extensive distant metastases. Radiotherapy was given to the primary esophageal lesions and in both patients the tumors completely disappeared after irradiation with 2000 to 3000 rads. However, the metastatic lesions of the bone and liver did not respond despite the administration of BLM + PT -207 + BEMP in one case and METVFC + FT -207 in the other. Both patients died 4 and 5 months, respectively, after beginning the treatment. Effective chemotherapy of metastases needs to be developed because the primary lesions of anaplastic esophageal cancer are highly sensitive to radiation therapy.     

Postoperative radiation therapy for "early" carcinoma of the breast.

Two hundred and twenty-five cases of "early" carcinoma of the breast, showing no evidence of axillary lymph node metastasis, are presented. One hundred and thirty-six of these patients were treated by radical mastectomy only, and 89 received postoperative radiation therapy to the ipsilateral internal mammary and supraclavicular regions. The routine use of postoperative radiation therapy of all patients in this group is not warranted. Patients with inner quadrant and central or subareolar primary lesions benefit from postoperative radiation therapy with a 10 to 21% increase in the disease-free survival at ten years. Deep-seated tumors, irrespective of size and location, should also be considered for postoperative radiation therapy to the regional lymphatic chain and the ipsilateral chest wall.     

Radiation therapy for lung cancer

Radiation therapy is one of the most important modalities for the treatment of lung cancer. Current progress of radiation therapy in cooperation with the development of physics and biology is remarkable. The techniques of three-dimensional treatment planning and three-dimensional conformal radiotherapy (3D-CRT) have facilitated the use of higher radiation doses. Patients with early-stage non-small cell lung cancer (NSCLC) are candidates for curative surgical resection. However, the number of elderly patients has been increasing, and these patients often have medical contraindications that prevent curative surgery. Recently, several clinical trials on stereotactic body radiotherapy (SBRT) using the 3D-CRT technique for solitary lung tumors have been reported. The local control rate for stage I disease is more than 90%, and survival rates are promising. Now a prospective multi-institutional trial is ongoing to determine whether this modality can become a standard treatment for inoperable patients or an alternative to lobetectomy. For locally advanced NSCLC, unfortunately, recent studies have demonstrated that conventional therapies may have reached a therapeutic plateau. Now several radiation dose escalation studies utilizing conventional fractionation and 3D-CRT techniques are ongoing. The strategies of almost all of these trials are to eliminate elective nodal irradiation and deliver a higher dose of radiation to gross tumor volume while sparing normal tissues. Preliminary experience has resulted in promising survival, but should be developed to integrate into the combined treatment to completely control both local disease and other microscopically involved lesions. The combination of novel chemotherapeutic agents and molecular targeting therapies with radiation therapy is being investigated. Development of molecular imaging techniques is expected to facilitate more selective dose escalation in tumors.     

Chemotherapy for cranial base tumors

Summary The tumors I will discuss in this chapter on chemotherapy will be ethesioneuroblastoma, salivary gland tumors, chordoma and nasopharyngeal carcinoma. Due basically to the rarity of these lesions, with the exception of nasopharyngeal carcinoma, there have been no multi-institutional studies of chemotherapy use reported in the literature. As a result, there is no clear-cut consensus on the standard of care as it relates to chemo-therapy for these tumors. As with most authors who have previously reviewed these tumor types, I believe it is important for us to propose protocols of therapy and test these in arenas where we can accumulate enough patients for meaningful results. In this way, we can test the apparently active agents and combinations in relapsed or extensive disease. We might also begin to explore concurrent therapy (i.e., concurrent radiation and chemotherapy after the surgical procedure, for example).     

Oligodendroglioma of the posterior fossa in childhood

Oligodendrogliomas are uncommon intracranial tumors of childhood, especially when these tumors arise in the posterior fossa. Oligodendrogliomas are usually treated with local radiation therapy. The authors report four children, median age 7.5 years, cared for over a 7-year period, who had oligodendrogliomas (all histologically malignant) of the cerebellar region. Three patients received local radiation therapy and all had recurrent disease at a median of 11 months posttreatment outside their radiation field; at the time of relapse, disease at the primary tumor site was stable. One child treated with craniospinal and local radiation therapy is disease-free 15 months after diagnosis. These results suggest that oligodendrogliomas of the posterior fossa should be considered potentially malignant lesions and treated with local plus presymptomatic craniospinal radiation therapy.     

颅底脊索瘤的治疗进展

脊索瘤(chordoma)是来源于原始脊索组织的肿瘤,其发生部位也多见于残余脊索常见部位即骶尾部(50%)、颅底斜坡区(35%)及椎体(15%)。本文主要复习了颅底脊索瘤,重点讨论其手术治疗和放射治疗的适应证、治疗时机和疗效。通过复习国内外近期文献报道,我们认为,尽管脊索瘤的生物学行为及其治疗存在很多争论,争取根治性切除,术后辅以质子束放疗是目前最佳治疗方案。     

Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast

A small number of patients with early stage breast cancer are found on presentation to have two or more separate carcinomas within the breast. To assess the effectiveness of conservative surgery and radiation therapy in these patients we compared treatment outcome among 10 patients with multiple lesions (21 cancers) and 707 patients with single lesions, treated at the Joint Center for Radiation Therapy between 1968-1981. Median follow-up was 64 months and 75 months for the multiple and single lesion groups, respectively. In each patient with multiple lesions, both (or all 3) lesions had similar histologic features. Eight of these ten patients (80%) had an infiltrating ductal carcinoma (IDC) compared to 72% of patients with single lesions. Six of these 8 patients with IDC had at least 1 lesion with an extensive intraductal component (EIC), compared to a 33% incidence of an EIC in solitary lesions. All lesions were grossly excised. Radiotherapy was given to the entire breast in all patients, with the majority also receiving a boost dose to the tumor bed site. Four of the 10 patients with multiple lesions recurred in the treated breast (40%) compared to 77 of the 707 patients (11%) with single lesions (p = 0.019, Fisher exact test). In the six patients with multiple lesions who had an EIC, three developed a local failure. In comparison, 43 of 167 patients (26%) with a single lesion with EIC developed a local failure. In patients with multiple lesions, 0 of 2 with IDC without an EIC, and 1 of 2 with histologies other than IDC had recurrence in the treated breast compared to 19 of the 342 (6%) and 15 of the 198 (8%) patients with single lesions with similar histologic features, respectively (p = NS). These results suggest that the presence of 2 or more separate primary tumors in the breast is associated with a high likelihood of local recurrence after treatment with conservative surgery and radiation therapy, even when all identified tumors are grossly resected. This may reflect the common finding of an EIC in these tumors. We conclude that the use of conservative surgery and radiation therapy for patients with more than one primary cancer in the breast should be considered with caution.     

Management of pineal region tumors

Opinion statement Tumors of the pineal region represent a diverse collection of tumors with a variety of natural histories. This diversity necessitates accurate histologic diagnosis to allow rational therapeutic planning. Evaluation of a pineal lesion should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF). Whereas certainty of the histologic diagnosis is now a requirement for treatment in Western nations, some Asian centers continue to recommend a test dose of radiation therapy based on the high incidence of germinoma in those countries. If there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or endoscopic biopsy may be pursued. All other lesions should be referred for open biopsy with microsurgical techniques. This approach provides adequate tissue for diagnosis, may be curative in low-grade tumors, and may substantially improve survival in patients with malignant tumors. If open surgery is not desired by the patient or practitioner, stereotactic or endoscopic biopsy may be followed by radiosurgery for localized, well-demarcated tumors. Radiation therapy is the first-line therapy for germinomas. Although the optimal radiation dosage and volume have not been decided, the current Children's Oncology Group trial may offer definitive evidence to address this dilemma in germ cell tumors. Evidence of CSF seeding requires craniospinal radiation and adjuvant chemotherapy regardless of tumor type. Diagnosis of any of the malignant tumors (non-germ cell tumors, pineoblastomas, and parenchymal tumors of intermediate determination) also requires craniospinal radiation (with local tumor doses of at least 50 Gy) and adjuvant chemotherapy (generally platinum based). Patients with tectal gliomas may undergo excision with or without postoperative radiation; however, they also may be observed with vigilant follow-up alone.     

Tumors of the small intestine

Tumors of the small intestine offer a unique challenge. As a result of their infrequent occurrence, they invariably present difficult problems in diagnosis and management. Although the prognosis for benign lesions is excellent, malignant small bowel tumors are perhaps the most devastating GI malignancies; at the time of diagnosis, only approximately 50% of these lesions are completely resectable for cure. Symptoms are often absent until the tumor has progressed to produce a complication. Even then, the presentation is often vague and nonspecific, intermittent pain, obstruction, and chronic anemia. The cornerstone of diagnosis is the contrast radiograph. However, in practice only about 50% of these lesions are diagnosed radiographically before surgery. This situation is further complicated by the variety of small bowel tumors, each with different symptoms and manifestations. Surgical excision is the treatment of choice for almost every small intestinal neoplasm. For most benign lesions simple excision is adequate. In contrast, for malignancies, segmental resection including as much adjacent mesentery as is reasonable, is required. In the duodenum, these tumors may necessitate pancreaticoduodenectomy; in the ileum, right colectomy may be required. In the case of advanced disease, palliative resection to relieve bleeding or obstruction may be indicated. The challenge of the future will be to reduce the morbidity and mortality of small bowel neoplasms not only by earlier recognition, diagnosis, and therapy but also through the development of alternative or adjunctive therapy for patients in whom surgical cure is not possible. This will require not only a high index of suspicion when confronted with patients with vague abdominal complaints but also an aggressive approach to diagnosis in the face of normal initial studies. In addition, multi-institutional trails of chemotherapy and radiation therapy of these tumors are needed.     

Four cases of an extramedullary plasmacytoma of the head and neck]

From 1987 to 1988, four patients with solitary, extramedullary plasmacytomas of the head and neck were seen at the Gunma Cancer Center Hospital. With reference to such plasmacytomas, we have reviewed the medical literature regarding these tumors and mainly present the results of radiation therapy with respect to these patients. One patient, who had a local recurrence after surgical treatment, underwent radiation therapy (36Gy in four weeks) that resulted in good local control of the disease. Two patients developed multiple painful bone lesions during their long follow-up periods without manifesting any abnormal laboratory findings, suggesting multiple myeloma. It was found that radiation therapy (less than 30 Gy) was useful for the palliation of painful lesions.     

Radiation-induced schwannomas of the neuraxis. Report of three cases.

We report 3 cases of possible radiation-induced schwannomas observed in our Department. Their salient clinical and pathogenetic features are analyzed and the role of radiation therapy in the oncogenesis of these lesions is discussed. Several cases of radiation-induced tumors, including some of the nervous system, have been reported, but schwannomas have only occasionally been reported in connection with ionizing radiation. The possible adjuvant role of antineoplastic drugs is also discussed, and the literature on this topic is reviewed.     

TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors.

PURPOSE: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. PATIENTS AND METHODS: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 x 10(7) particle units [pu] to 4 x 10(11) pu) in patients with solid tumors being treated with radiation. RESULTS: Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. CONCLUSION: This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.     

Internal radiation therapy for malignant neoplasm]

Internal radiation therapy selectively targets beta- or alpha-emitting radionuclides to the area of the tumor tissue, and is therefore capable of treating disease regardless of the location and number of foci. The biological effect of internal radiation therapy is thought to be different from that of conventional external beam radiation. Thyroid cancer: The local recurrence and metastatic lesions from differentiated thyroid cancers can be controlled with 131I administration. Even though the patient does not have macroscopic disease, 131I is also utilized for thyroid remnant ablation in locally advanced cases. Recently, the maximum tolerable dose can be calculated based on the dosimetry of each patient, and safely administered. The therapeutic effect of this method is superior to the fixed dose method. 131I-MIBG: 131I-MIBG is taken up by sympathetic neurons as well as a group of tumors originating in the neural crest, especially phecromocytomas and neuroblastomas. The various symptoms caused by the hypersecretions of hormone-producing tumors can be improved. Pain palliation of bone metastases: Pain palliation using 89Sr is a very promising option in treating patients with painful bone metastases. The pain palliation mechanism of 89Sr is different from other drugs; therefore, complimentary usage is reasonable. The symptomatical improvement can last for several months, thus helping to maintain the quality of life of the patient.