Patterns of Practice in Palliative Radiotherapy in Africa – Case Revisited

AimsTo investigate patterns of practice in palliative radiotherapy in Africa.Materials and methodsFifteen centres in Africa provided detailed information about radiotherapy in both metastatic and locally advanced disease via a questionnaire. Information included general information (institution status, equipment, staff, patient number), radiotherapy and other treatment characteristics in bone metastasis, brain metastasis, metastatic spinal cord compression, lung and liver metastasis, as well as locally advanced tumours.ResultsThe number of patients annually seen/treated ranged from 285 to 5000. Breast, cervix, head and neck, gastrointestinal and prostate cancer were the top five cancers overall. Eight (53%) institutions were without linear accelerators, four (27%) had a single one, whereas one institution each had two, three and four linear accelerators. The number of cobalt machines ranged from 0 to 2 (median 1). Most centres still prefer to use fractionated radiotherapy regimens over single-fraction regimens in bone metastasis, although most centres are now using single-fraction radiotherapy in retreatments. Radiotherapy in brain metastasis and metastatic spinal cord compression mostly conform to worldwide standards. Lung and liver metastases are rarely irradiated, largely as a consequence of the lack of modern radiotherapy technology. Locally advanced disease in various tumour sites was mostly palliated, in agreement with current evidence-based practices.ConclusionsAfrican countries still lack adequate staffing and equipment to adequately address their clinical burden, being palliative in most cases. Emphasis should also be made on more rationally using existing capacities by using more of the single-fraction radiotherapy regimens, especially in bone metastasis.     

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background:Gross target volume of primary tumor (GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ifnd a suitable cut?off value of GTV?P for prognosis prediction. Methods:Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic (ROC) curves were used to identify the cut?off values of GTV?P for the prediction of different end?points [overall survival (OS), local relapse?free survival (LRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system. Results:The 358 patients with locally advanced NPC were divided into two groups by the cut?off value of GTV?P as determined using ROC curves: 219 (61.2%) patients with GTV?P≤46.4mL and 139 (38.8%) with GTV?P>46.4mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P≤46.4mL than in those with GTV?P>46.4mL (allP<0.05). Multivariate analysis indicated that GTV?P>46.4mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriifed that the predictive ability of GTV?P was superior to that of T category (P<0.001). The cut?off values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4mL, respectively. Conclusion:In patients with locally advanced NPC, GTV?P>46.4mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.     

联合放化疗与单纯放疗治疗65例局部中晚期鼻咽癌比较研究

[目的]探讨诱导化疗联合放疗和辅助化疗治疗中晚期鼻咽癌的疗效。[方法]65例中晚期鼻咽癌分为治疗组45例,采用放疗前诱导化疗1次＋根治性放疗＋辅助化疗3～5次;对照组20例,行单纯行根治性放疗。化疗方案为氟尿嘧啶（5-Fu）0.5g/m^2,d1～3;表柔比星（EPI）60mg/m^2,d1;顺铂（DDP）30mg/m^2,d1～3;静脉滴注。两组放疗方法、时间和剂量分割均相同。[结果]治疗组与对照组3年无瘤生存率分别为71.0%、35.0%（P〈0.05）,远处转移率分别为46.7%、75.0%（P〈0.05）。无不可耐受的毒副反应发生。[结论]诱导化疗联合放疗和辅助化疗治疗局部中晚期鼻咽癌能提高生存率,降低远处转移率。     

Rare case of intramedullary spinal cord metastasis from nasopharyngeal carcinoma

IntroductionCentral nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is rare and presents with high morbidity and mortality. As a rare entity, a few patients with CNS metastasis from NPC have been reported, and no studies were available on treatment and prognosis. Based on our clinical experience, early diagnosis with incorporation of a clear palliative plan is imperative in providing holistic care for patients with locally-invasive and metastatic nasopharyngeal carcinoma.Case reportOur study reports a case of a 48-year-old Filipino male with known NPC Stage IVB who developed acute symptoms of constipation, urinary retention, and bilateral lower limb weakness and numbness. Magnetic resonance imaging showed intramedullary lesions in multiple segments of the spinal cord. Steroid and radiotherapy of the spine were initiated with noted transient improvement of the motor strength. Subsequently, he developed cancer-related stroke. The patient progressively deteriorated despite best medical care.     

Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression

The records of all patients receiving palliative radiotherapy for malignant melanoma metastatic to brain, to bone, or with spinal cord compression were reviewed. The median survival of 77 patients with brain metastases from the initiation of radiotherapy was 14 weeks. A statistically improved survival was observed only in the 10 patients who underwent subtotal to total resection of a solitary brain metastasis prior to radiotherapy (median = 36 weeks). No improved survival was observed in the 12 patients with a solitary brain metastasis treated by radiotherapy alone (median = 16 weeks). Multivariate analysis revealed that fraction size, total dose, patient age, sex, and duration of the interval between initial diagnosis and appearance of brain metastases did not significantly influence survival, but the use of chemotherapy was associated with a decreased survival. Twenty six patients with symptomatic and radiographic evidence of 39 bone metastases showed a palliative response rate of 85%. 18 of 20 bony lesions treated with high-dose-per-fraction (greater than or equal to 400 cGy) and 15 of 19 bony lesions treated with conventional fractionation (less than or equal to 300 cGy) were palliated. Total dose, patient age, sex, interval between initial diagnosis of malignant melanoma and the appearance of bone metastases, prior or concurrent chemotherapy, or lesion location did not significantly influence palliation. Seventeen patients were identified with symptomatic and myelographic evidence of spinal cord compression. Complete palliation was observed in 47% (8/17) and partial palliation was observed in 24% (4/17). The overall palliation response rate for neurologic symptoms due to spinal cord compression of 71% appeared to be independent of fraction size and total dose.     

Prophylactic cranial irradiation with combined modality therapy for patients with locally advanced non-small cell lung cancer

Central nervous system (CNS) metastasis is a significant problem for many patients with non-small cell lung cancer (NSCLC). The earlier data reported a high incidence of CNS metastasis in patients with locally advanced NSCLC who were treated with radiotherapy alone. However, poor control of both thoracic and extracranial systemic disease dominated the results of the early trials. The risk for CNS metastasis as the first site of failure remains a significant concern for patients who have completed modern combined modality therapy. With improvements in the treatment of thoracic and systemic disease, there is renewed interest in prophylactic cranial irradiation (PCI). The results from the Radiation Therapy Oncology Group (RTOG) trial of PCI to prevent CNS relapse in patients with locally advanced NSCLC are anticipated.     

鼻咽癌放疗后放射性脑干和脊髓损伤的磁共振表现

背景与目的:鼻咽癌(nasopharyngealcarcinoma,NPC)放射治疗后脑干和颈髓放射性损伤的诊断相当重要。磁共振(magneticresonanceimaging,MRI)用于诊断鼻咽癌放疗后放射性脑损伤已有较多报道,但脑干和颈髓放射性损伤的MRI表现文献报道较少。本研究旨在分析鼻咽癌放疗后脑干和颈髓放射性损伤的MRI特征。方法:对60例鼻咽癌患者在放射治疗后6个月至5年内进行了MRI检查,MRI检查序列包括T1-weightedimage(T1WI)、T2-weightedimage(T2WI)、fluidattenuatedinversionrecovery(FLAIR);所有患者均做了MRI增强扫描。结果:6例为颈髓放射性损伤;54例为脑干放射性损伤,其中脑桥20例,桥脑基底部与延髓上段26例,中脑受累3例,延髓5例。病灶在MRI上T1WI表现为等信号和低信号,T2WI上为高信号,增强后病灶无强化者11例(18.3%),强化者49例(81.7%)。强化者有2种强化形式:均匀斑片状强化(21例,42.9%)和不均匀的既有环形又有斑片状的强化(28例,57.1%)。结论:MRI可以清晰地显示脑干和脊髓放射性损伤的病灶,结合病史可以确诊。     

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 half-body irradiation. Doses of 600 cGy delivered to the upper half-body (above 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 localfield 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 were 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 superior vena cava syndrome due to malignant disease achieve symptom relief with a brief, fractionated, palliative course of radiotherapy to the thoracic inlet and mediastinum.Spinal cord compression requires emergency radiotherapy. This condition must be diagnosed and treated early to prevent irreversible neurologic injury. Central back pain usually precedes neurologic deficit, which can evolve to paraplegia within hours or days. Magnetic resonance imaging gives the most complete information when symptoms suggest spinal cord compression. The best predictor of neurologic outcome is pretreatment neurologic status. There are no data to demonstrate a difference in neurologic outcome when spinal cord compression is managed with radiotherapy alone or with laminectomy followed by radiotherapy. In specific clinical situations, initial surgical treatment is preferred to radiotherapy.Abdominal pain secondary to hepatic distention from metastatic disease is relieved by radiotherapy to the whole liver in 75% to 90% of patients. One half of the patients may obtain complete pain relief. Doses of 2000 to 3000 cGy in 200 to 300 cGy fractions are used.Metastases to the eye are the most common malignant intraocular tumors. Palliative radiotherapy is effective in relieving visual symptoms produced by uveal metastases or at least in preventing further deterioration. In symptomatic adrenal metastasis, radiotherapy appears to be effective in palliating pain, with minimal morbidity, in the majority of patients.Recurrent gynecologic and colorectal cancers can cause severe pelvic symptoms including pain, bleeding, and discharge. Brief courses of pelvic radiotherapy, including a single dose of 1000 cGy, have been shown to control these symptoms, with minimal morbidity, for a substantial proportion of the remaining survival time. In ovarian cancer, radiotherapy is effective in control of pain, bleeding, and discharge, despite resistance of the disease to cisplatin-based chemotherapy.     

Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study

The results of radiotherapy alone for patients with locally advanced (stage III or IV) nasopharyngeal cancer (NPC) are poor in spite of the initial complete clearance. Twenty-seven patients (26 stage IV) were treated with concurrent standard radiotherapy and cisplatin 100 mg/m2 intravenously on day 1 and every 3 weeks for three courses. In 24 (89%) patients, complete response (CR) was achieved. The CR rate was higher for poorly undifferentiated cancer (100%). The major side effects were leukopenia (97%), anemia (54%), nausea and vomiting (81%), stomatitis (92%), and renal impairment (52%). Most of these side effects were either mild or moderate and reversible. All patients finished the radiotherapy dose (greater than 6,450 cGy), 19 (70%) had three courses of cisplatin, and eight had only two courses, six due to drug toxicity. Twenty-six patients with stage IV disease were compared with 78 patients treated with radiotherapy alone by the Radiation Therapy Oncology Group (RTOG). The disease-free survival (DFS), overall survival, and the incidence of distant organ metastasis appear to be better in the combined group. It was concluded that the combination of chemo-radiotherapy in patients with locally advanced NPC needs to be evaluated in a phase III randomized trial.     

Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung

Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response.     

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study

BACKGROUND:

The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.

METHODS:

Eighty‐one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m²/d on Days 1 and 22) was administered.

RESULTS:

The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow‐up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5‐year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5‐year disease‐free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow‐up were grade 1‐2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted.

CONCLUSIONS:

IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long‐term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted. Cancer 2011. © 2010 American Cancer Society.     

Carcinoma showing thymus-like element (CASTLE) of thyroid: combined modality treatment in 3 patients with locally advanced disease.

OBJECTIVES: To examine the value of chemotherapy, radiotherapy and surgery for treatment of locally advanced carcinoma showing thymus-like element (CASTLE) of the thyroid. METHODS: Retrospective analysis of 3 Chinese patients in a tertiary referral center in Hong Kong. RESULTS: CASTLE is a rare thyroid malignancy with a frequency of only 0.15% (3/2033 patients) in our center. Three patients (M:F=2:1) aged 43, 49 and 62 years were studied. All 3 patients had advanced T4 disease with extensive tracheal infiltration and airway compression. None had lymph node or distant metastasis. Total thyroidectomy, combined with chemotherapy and radiotherapy, was effective in local control and symptom relief. Etoposide and carboplatin were tried in 2 patients with positive response. Neoadjuvant chemotherapy shrank the tumor rapidly and relieved symptoms of airway compression. All 3 patients had external radiotherapy resulting in good local control. In a patient with inoperable disease, chemotherapy and radiotherapy rendered the disease operable. All 3 patients were symptom-free and alive at 6, 2.5 and 1.8 years after diagnosis. CONCLUSIONS: CASTLE is locally infiltrative and presents at advanced T stage in this small series. Chemotherapy and radiotherapy, apart from surgery, are effective treatment modalities. In cases of inoperable disease or advanced local disease, they can be employed in combination with surgery. Organ preservation of larynx and trachea may be achieved. Chemotherapy can be very useful for rapid relief of symptoms, especially in shrinking tumor to prevent airway obstruction.     

Postoperative radiotherapy for primary mucosal melanoma of the head and neck

BACKGROUND: Primary head and neck mucosal melanoma (HNMM) has a poor prognosis with a low local control rate and frequent distant metastases. The objective of the current study was to determine the impact of postoperative radiotherapy on local control and survival. METHODS: One hundred forty-two patients with primary HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with confirmed primary mucosal melanoma, absence of metastatic disease, and definitive management by surgery with or without postoperative radiotherapy and follow-up at the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4 patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17 patients had regional lymph node metastases after pathologic examination (pN > 0). Thirty patients underwent surgery alone and 39 received postoperative radiotherapy. Patients with locally advanced tumors had received postoperative radiotherapy more frequently than those with small tumors (P = 0.02). RESULTS: Thirty-seven patients (54%) experienced local disease recurrence and 47 patients (68%) developed distant metastasis. The overall survival rates were 47% at 2 years and 20% at 5 years. In the Cox multivariate analysis, patients with early T-classification tumors who received postoperative radiotherapy had a better local disease-free survival (P = 0.004 and P = 0.05, respectively) compared with patients with late T-classification tumors who did not receive postoperative radiotherapy. Patients with advanced T-classification and pN > 0 stage had a shorter distant metastasis disease-free survival compared with patients with early T-classification and pN < 0 stage. Patients with advanced T-classification tumors had a shorter overall survival compared with patients with early T-classification tumors (P = 0.003). CONCLUSIONS: The prognosis of patients with HNMM was poor. Patients had a high rate of distant metastasis and a low rate of local control. The current study suggested that postoperative radiotherapy increased local control even for patients with small tumors.     

鼻咽癌放疗前CT或MRI检查分期与预后关系的比较

背景与目的:影像学检查结果是鼻咽癌临床分期和确定治疗靶区的重要依据.本研究试图分析放疗前按CT或MRI检查分期与鼻咽癌患者预后的关系.方法:445例病理确诊的无转移初治鼻咽癌患者.根据治疗前影像学检查手段的不同,分为CT组230例,MRI组215例.全组患者均行常规放疗,局部晚期患者加用化疗.用Kaplan-Meier和Log-rank法计算和比较两组生存率,用Cox模型分析影响预后的凶素.结果:CT组1、2、3年生存率分别为96.9%,90.3%,85.3%,MRI组分别为98.6%,94.3%,92.3%,两组比较差异有显著性(x2=6.305,P=0.012).CT组与MRI组的l,2,3年无瘤生存率和无复发生存率比较差异均有显著性(P<0.05),MRI组优于CT组.单因素分析结果显示临床分期、N分期、分期方法和化疗是影响鼻咽癌预后的因素,多因素分析结果显示临床分期和分期方法是影响鼻咽癌患者预后的独立因素.结论:鼻咽癌放疗前行MRI检查分期较CT检查分期来确定放疗靶区可提高鼻咽癌患者的生存率和局控率,临床分期和分期方法是影响鼻咽癌患者预后的独立因素.     

Intramedullary spinal cord metastases in breast carcinoma: report of two cases and review of the literature

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Breast cancer is one of the most common solid tumors with a high propensity of CNS dissemination. In the present report we describe two new cases with advanced breast cancer developing ISCM after a variable disease course. One of these patients had brain metastases at presentation, while at relapse developed leptomeningeal carcinomatosis which was treated successfully, but followed shortly, as a terminal event, by ISCM and parenchymal brain recurrence. The other patient was treated initially for locally advanced breast cancer and after multiple locoregional relapses, she developed liver metastases and subsequent ISCM and asymptomatic parenchymal brain deposits. Both patients experienced a rather rapidly evolving disease course leading to death 2 and 4 months, respectively, after widespread neuraxis dissemination of their cancer. Both these cases, added to the list of the anecdotally reported cases of ISCM after breast cancer, undermine the ominous prognosis and limited treatment options available for this disease manifestation, and an extensive literature review and discussion of similar cases is provided.     

CNS metastasis in primary breast cancer

The development of CNS metastasis in patients with solid malignancies represents a turning point in the disease process. The prevalence of CNS metastasis from breast cancer may be increasing due to improved systemic therapy for stage IV breast cancer. The standard treatment for multiple brain lesions remains whole-brain radiation for symptom control, with no improvement in survival. The therapy for a single brain metastasis remains either surgery or radiosurgery, with conflicting information as to the benefit of prior whole-brain radiation. The role of chemotherapy remains investigational in this setting. Leptomeningeal metastasis is conventionally treated with intrathecal chemotherapy, but may provide short-term symptom control. This review focuses on the treatment options available for both brain and leptomeningeal metastasis from breast cancer, including some investigational therapies that may be of importance in patient management in the near future.     

CNS metastasis in primary breast cancer

The development of CNS metastasis in patients with solid malignancies represents a turning point in the disease process. The prevalence of CNS metastasis from breast cancer may be increasing due to improved systemic therapy for stage IV breast cancer. The standard treatment for multiple brain lesions remains whole-brain radiation for symptom control, with no improvement in survival. The therapy for a single brain metastasis remains either surgery or radiosurgery, with conflicting information as to the benefit of prior whole-brain radiation. The role of chemotherapy remains investigational in this setting. Leptomeningeal metastasis is conventionally treated with intrathecal chemotherapy, but may provide short-term symptom control. This review focuses on the treatment options available for both brain and leptomeningeal metastasis from breast cancer, including some investigational therapies that may be of importance in patient management in the near future.     

The treatment of brain metastases from malignant melanoma

Metastasis to the CNS develops in nearly half of patients with advanced melanoma; in 15% to 20% of these patients, the CNS is the first site of relapse. While systemic therapy for metastatic melanoma produces objective responses in 15% to 50% of patients, the available drugs do not penetrate well into the CNS, and these patients rarely benefit from systemic therapy. Although brain metastasis may be treated with surgery and/or stereotactic radiosurgery (SRS) when disease is limited to approximately one to three lesions, treatment for patients with large or multiple metastases is limited to whole brain irradiation (WBRT). While formal response and survival analyses of the impact of WBRT in melanoma have not been reported, the estimated median survival time for unselected patients with CNS metastases is only 2 to 4 months, with 1-year survival rates of less than 13%. In a selected population of patients with limited CNS involvement, surgical resection alone or in combination with WBRT appears to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports of patients with melanoma CNS metastases, treatment with surgical resection alone or in combination with WBRT has been demonstrated to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports, patients with CNS metastases from melanoma treated with a combination of WBRT plus SRS or SRS alone had median survivals and rates of control in the CNS superior to published reports for traditional WBRT. Most of these patients died from progressive extracranial disease with locally controlled CNS disease. Investigation of the contribution of newer systemic agents to the control of melanoma metastatic to the CNS has been based on the identification of drugs that have antitumor activity and the ability to cross the blood-brain barrier. Fotemustine is a nitrosourea that produced similar activity in CNS metastasis as in systemic disease, with a response rate of about 25%. Temozolomide (TMZ) is an oral alkylating agent that acts via the same mechanism as dacarbazine (DTIC), the most active single agent in melanoma. TMZ, which is highly active in brain tumors, has also been associated with activity in systemic and CNS metastases in melanoma patients, also in the 25% range. Efforts are underway to assess the additive benefit of TMZ and other drugs to WBRT or focused radiotherapy in this disease.     

Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma

PURPOSE: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. RESULTS: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. CONCLUSION: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.     

Central nervous system as exclusive site of disease in patients with melanoma: treatment and clinical outcome of two cases

The central nervous system (CNS) is a favourite site of metastasis in advanced melanoma and, despite the improvement obtained in the control of brain metastasis, most patients die as a result of extracranial progression of the disease. CNS primary malignant melanoma is a rare entity and the diagnosis is generally made after the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma, as differential histological diagnosis between primary and metastatic origins is often difficult. From a review of the literature, patients with primary brain melanoma or exclusive (and limited) brain metastasis in the absence of extracranial melanoma present a relatively good prognosis if adequately treated with aggressive locoregional treatments (neurosurgery and/or radiotherapy) and, later, with drugs able to cross the blood-brain barrier (i.e. fotemustine). In this letter, we describe the history, treatment and favourable clinical outcome of two patients with melanoma and CNS as the exclusive site of disease.