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Even a small percent increase in survival rates after treatment for lung cancer can produce a large benefit in terms of absolute numbers of lives saved, due to the very high incidence of the disease. Clinical results after surgery alone or radiotherapy alone are far from being satisfactory. Therefore, the integration of surgery with radiotherapy (both in the preoperative and in the postoperative setting) has been increasingly tested in the clinic. Radio-chemotherapeutic approaches progressively more effective have been developed for patients with inoperable disease, but also in combination with surgery. This review focuses on the current practice and on the ongoing clinical research in this field. The important issue of the short- and long-term toxicity of combined modality treatments in these patients is also emphasized, along with the research efforts for minimizing toxicity, especially as far as radiotherapy is concerned.

High-grade malignant gliomas (HGG) are the most common and malignant primary central nervous system tumors. Despite therapeutic efforts and advances in biologic knowledge, these diseases remain lethal. Standard treatment of HGG is based on surgery and radiotherapy, usually followed by adjuvant chemotherapy. Many randomized trials addressing the role of post-radiation or "adjuvant" chemotherapy have been conducted in the last three decades, yielding inconclusive results. However, a statistically significant survival benefit with adjuvant chemotherapy has been demonstrated in two meta-analyses with nitrosourea-based adjuvant chemotherapy and a recent phase III trial has demonstrated a survival advantage for radiotherapy with concomitant and adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma. Since high-grade malignant gliomas can seldom be cured, the primary aim of treatments for recurrent disease is to improve progression-free survival (PFS), and to improve or preserve neurological functions. TMZ showed activity even in the treatment of recurrent HGG with a good toxicity profile, whether few data are available for effective treatments in patients treated with adjuvant TMZ. As a result, new agents and novel approaches are required. Furthermore, molecular studies to evaluate chemosensitivity predictors are necessary for patients' selection. Brain metastases are estimated to occur in 20% to 40% of cancer patients, with a higher risk in lung cancer, breast cancer and melanoma. The incidence of brain metastases is rising as results of better imaging procedures and improvements in treatments which leave more cancer patients at risk as survival increases. The prognosis is dependent on a number of factors such as histology of primary tumor, performance status, localization number and size of brain metastases and status of extra cranial disease. Surgery and radiotherapy are indicated in controlled disease with isolated brain metastases. Systemic chemotherapy represents he optimal treatment in chemosensitive tumors with multiple or isolated brain metastases.

In consideration of the complexity of tumours, the modern and also the best approach to treat the neoplastic diseases is multi-modality therapy. Evidence suggests that this approach to cancer offers a patient the greatest change of survival. Actually, the involvement of a team of specialists warrants different expertise for the formulation of an appropriate treatment plan individualized for each patient, based upon tumour stage, medical conditions and patient preferences. Treatments are continually being updated and improved and the new treatment options provide fresh opportunities for controlling tumours and reducing morbidity and mortality. New developments in molecular biology and drug discovery are continually moving from the laboratory to clinical practice. This article reviews the role of integrated treatments in breast cancer, a common malignancy in women, and in head and neck cancers, that encompass a diverse group of uncommon tumours and frequently are aggressive in their biological behaviour. Careful evaluation of biological prognostic factors, performance status along with determination of life expectancy and preferences, represent the relevant information on which the oncologists should ground their decision for integrated treatments or attenuated or palliative measures, in order to maximize the balance of benefits and toxicities. Improving quality of life for patients with incurable disease remains an important goal for oncologists and is equally important as cure.

The sensitivity to chemotherapy of oligodendroglioma (OD) is the major clinical distinction between oligodendroglial and astrocytic tumours. In particular, chemotherapy with alkylating agents (PCV chemotherapy, temozolomide) in recurrent OD is of proven efficacy, with 50 to 70% of patients responding. The value of adjuvant chemotherapy in newly diagnosed tumours still remains to be proven. The efficacy of radiotherapy (RT) has never been proven in a phase III trial on OD, but based on historical phase III trials on anaplastic glioma this generally considered part of standard treatment of these tumours. Recent molecular biological studies show that OD are characterised by a combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19 q). This combined loss of 1p and 19 q also identifies a group of tumours with a better response to chemotherapy and a longer survival after RT. It is expected that this knowledge will change the diagnostic criteria for OD and will help to select patients for specific treatments. However, improvement of the currently available treatments is needed, as the outcome of these patients remains dismal.

The best therapeutic management in primary central nervous system lymphomas remains to be defined because of current knowledge on these malignancies results from small retrospective series with a short follow-up, a limited number of prospective studies with some methodological pitfalls and a single published randomised trial. This review focuses on the current therapeutic approaches, most commonly used drugs, role of intrathecal chemotherapy, and indications for consolidation radiotherapy, providing recommendations for ordinary clinical practice. Some important therapeutic issues, such as the management of meningeal and intraocular lymphomas, as well as the relevance of salvage therapy as a playground for evaluation of new drugs are also analysed. Finally, the main open questions, as well as current and expected investigation trends are discussed.

Metastatic spread of tumour cells detached from melanoma into the central nervous system (CNS) occurs haematogenously since lymphatic drainage is absent in the brain. CNS metastases occur in 10 to 40% of melanoma patients in clinical studies and up to 90% in autopsy studies. Headache is the most common presenting symptom, but brain metastases should be suspected in all melanoma patients with new neurologic findings. Magnetic resonance imaging is the best diagnostic technique for detecting CNS metastases. Median survival of melanoma patients with CNS metastases ranges between 2 and 8 months. The optimal treatment of melanoma patients with CNS metastases depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy are used in combination to obtain longer remissions and optimal symptom relieve.

The incidence of melanoma continues to rise at a rate greater than all other cancers. Survival in melanoma varies widely by stage, and is affected by a number of prognostic factors including tumour thickness, ulceration and lymph node involvement. New AJCC staging criteria adopted in the 6(th) edition reflect the prognostic value of tumour ulceration, the number of positive lymph nodes as a better prognostic indicator than the size of nodal metastasis, and the similar prognostic value provided by nodal, in-transit and local recurrences. It also recognises the pathologic information about staging provided by lymphatic mapping and sentinel lymphadenectomy. High-risk resected melanoma is defined as disease that after surgery is at higher than 40 to 50% risk of recurrence and death. The urgency to the effort to develop effective therapy for melanoma has led to a wide variety of approaches that have been tested over the years in the high-risk adjuvant setting. Among the many therapeutic modalities tested, the only agent that has shown a significant and reproducible benefit in terms of survival and relapse-free interval has been high-dose interferon-alpha2b. We here review the evidence that has led to the regulatory approval of this regimen, as well as ongoing studies using high-dose interferon-alpha in the high-risk adjuvant setting. We also present selected ongoing trials testing potential future therapies that may prove effective for patients with high-risk resected melanoma.

In the past decade, the characterisation of tumour antigens recognised by T cells has revolutionised the cancer-vaccine approach, providing for the first time the opportunity to immunise patients against cancer by using well-defined antigens. Because melanoma is one of the prototypic immunogenic tumours, a number of early-phase clinical trials have been conducted on melanoma. Some tumour regressions have been documented, mainly for patients with metastatic disease. Recent advances include new tools for monitoring the anti-cancer immune response and the development of adjuvants aimed at inducing a robust anti-melanoma immune response. Together, these developments should allow an optimal vaccination modality to be selected within the next few years.

Epidemiology: Meningiomas constitute the largest subgroup of all intracranial tumours. Their incidence is about 2-3/100,000/yr, with a 3:2 to 2:1 female:male ratio, with a peak incidence in the sixth and the seventh decade of life. Meningiomas are usually slow growing, benign neoplasms, causing symptoms by compression of adjacent structures or by increased cranial pressure, the specific symptoms depending on the location of the tumour.

Risk factors: Meningiomas can be induced by radiation to the head, even by low dose radiation as used for dental radiographic examination after up to 35 yrs interval. The female preponderance in meningioma patients as well as the expression of progesterone receptor on the cell membranes of more than 50% of meningiomas is argument for an influence of gestagene in meningioma proliferation. The most frequent genetic predisposition of meningiomas is associated with neurofibromatosis 2 (NF-2); at least 40% of meningiomas show a deletion in the NF-2 gene.

Treatment: To date, surgical resection is the mainstay of meningioma therapy. The completeness of the resection is the single most important prognostic factor for recurrence. In case of incomplete resection or recurrence, radiation therapy with 54 Gy (1.8 to 2 Gy/fraction) yields comparable results to total resection. Radiosurgery is a valuable alternative to radiotherapy (RT), maybe in the future also for surgery, as recently demonstrated. In the rare meningioma patients, that have exhausted the possibilities of surgery and RT, there have been some successful small series using hydroxyurea or interferon alpha. Future therapeutic options might consist in octreotide isotopic therapy or targeted therapy directed against tumour neo-angiogenesis or other proliferation associated markers in meningiomas.