The records of 209 patients with small cell bronchogenic carcinoma were reviewed to define the problem of CNS metastases. CNS metastases were documented in 102 of these patients (49%) and 55 of 85 autopsied patients had CNS metastases (65%). The probability of developing a CNS metastasis increased with lengthening patient survival to a level of 80% after 2 years.As in other series, the cerebrum was the most frequently involved site. In addition, leptomeningeal, spinal, pituitary, and cerebellar metastases, and multiple sites of involvement were far more common than in previously reported series. Patients with bone marrow and liver metastases at initial staging were more likely to develop CNS metastases than those without these metastases. Bone marrow involvement was strongly associated with the development of leptomeningitis. Systemic chemotherapeutic agents which cross the blood brain barrier did not prevent the high frequency of CNS metastases. Pathologic studies suggested cerebral and leptomeningeal metastases may arise via hematogenous spread or via penetrating vessels from bone marrow to the subarachnoid space. Therapy for CNS metastases provided adequate palliation, and the majority of deaths were due to systemic rather than neurologic disease. Nevertheless, prophylactic therapy appears necessary at present to prevent the morbidity associated with these metastases. As further improvements in systemic therapy evolve, CNS prophylaxis may also be required for "cure" of patients with small cell lung cancer.Cancer 44:1885-1893, 1979.N THE PAST DECADE, there has been an in-I creasing awareness that central nervous system (CNS) metastases are a frequent complication of malignancies, particularly in lung, breast and hematologic cancers.5*9*24,25,26~30 In lung cancer patients, these metastases were more common in the small cell carcinoma of the lung (SCCL) than in the other histologic types.1~21~22'24,32,34 Autopsy studies demon- Accepted for publication November 24, 1978. strated brain metastases in as many as 50% of patients with SCCL.',21*22*32,34 Eighty percent of these metastases were clinically apparent, resulting in devastating morbidity and frequent mortality for these patients. CNS metastases in areas other than brain (leptomeningeal or spinal) were uncommon with an autopsy incidence of less than 5%.21,22Hansen suggested that the incidence of CNS metastases increased with lengthening s~rvival.'~ This phenomenon is reminiscent of the problem encountered in the treatment of hematologic malignancies in which intensive combination chemotherapy regimens controlled systemic diseases but did not affect CNS sanctuary sites.30 Prophylactic craniospinal radiotherapy andor prophylactic cranial irradiation (PCI) and intrathecal methotrexate therapy dramatically reduced the incidence of these CNS metastases, the majority of which were l e p t~m e n i n g e a l .~~
Objectives: To estimate the direct cost components of pulmonary arterial hypertension (PAH) in a Turkish setting. MethOds: Delphi-technique was used. An expert-panel consisting of members from cardiology, pulmonology and cardiovascular surgery met to discuss the disease management processes in PAH. The global and local-literature and guidelines have been reviewed and local clinical practices questionnaires (separately for functional classes (FC)) have been completed. All costcomponents, including medications, surgical treatment, hospitalization, screening and outpatient follow-up procedures were reviewed. February-2016 local prices released by Ministry of Health and Social Security Institution in Turkey were used as references. February-2016 currency rate was used. Results: The total-costs, excluding disease-specific medications, of PAH/year for patients in FC-II, FC-III and FC-IV were calculated as 576€ , 1,005€ and 5,542€ , respectively. The corresponding costs of disease-specific medications were 8,864€ , 17,920€ and 17,920€ (panel experts noted that disease-specific drugs are given in similar combinations and doses in FC-III and FC-IV). Therefore, the total annual-costs of PAH in FC-II, FC-III and FC-IV were estimated as 9,440€ , 18,925€ and 23,462€ , respectively. Costs of other components per annum, used in calculating the total-cost in FC-II, FC-III and FC-IV were as follows: follow-up: 101€ , 199€ and 1,355€ ; medications for palliation: 116€ , 156€ and 1,867€ ; non-pharmacologic treatment: 126€ , 366€ and 366€ ; laboratory tests: 232€ , 283€ and 1,211€ , respectively. Cost of lung-transplantation was found as 742€ in FC-IV (percentage of FC-IV patients assumed to be transplanted "lung" and "heart-lung" is 2.5% and 0.1%, respectively and price of each operation is 28,550€ [28,550x2.5%+28,5 50x0.1%= 742€ ]). cOnclusiOns: The main driver of direct cost components in PAH is the cost of disease-specific drugs. The total direct cost components increase when the functional class of the patients progresses from FC-II to FC-IV. Consequently, improving diagnosis rate and ensuring to start appropriate treatment in early stages in PAH patients may help to decrease the costs of treatment.
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