PubMed Health⌕ Search

Biomedical subjects

S Culine

Publications and source records attributed to S Culine.

At least 37 records · Page 2Linked to original sources
PubMed2001

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Adult↗
PubMed2001

Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse.

There is no consensus about a reproducible prognostic model capable of distinguishing between clinical stage I non-seminomatous germ cell tumour (NSGCT) carrying a high and low risk of relapse. The aim of this study was to assess the prognostic value of histological parameters in patients with stage I NSGCT undergoing surveillance after orchiectomy. We retrospectively evaluated tumour specimens from 88 consecutive stage I NSGCT patients undergoing surveillance in our institution between 1984 and 1996. 24 patients relapsed (27%). Multivariate analysis singled out vessel invasion (VI) (relative risk (RR)=3.8; 95% confidence interval (CI) 1.4-10.4) and the presence of mature teratoma (RR= 0.2; 95% CI 0.1-0.6) as independently correlated with relapse-free survival (RFS). Patients can be classified accordingly into three prognostic groups with a low (27 patients with mature teratoma but without VI), intermediate (34 patients with both VI and mature teratoma or with neither VI or mature teratoma) and a high risk (23 patients with VI, but without mature teratoma) of relapse. Relapse rates in these three groups were 0%, 29% (95% CI: 23-35%) and 61% (95% CI: 55-67%), respectively. This prognostic index, based on two standard pathological parameters, identified a subgroup with a very low risk of relapse that represents approximately one third of stage I patients. Patients who belong to this subgroup should be managed by surveillance only, instead of retroperitoneal lymph node dissection (RPLND) or adjuvant chemotherapy.

Adolescent↗
PubMed2001

Salivary and plasma pharmacokinetics of topotecan in patients with metastatic epithelial ovarian cancer.

The comparative saliva/plasma pharmacokinetics of topotecan were investigated in 13 patients with metastatic epithelial ovarian cancer receiving topotecan (30-min intravenous (i.v.) infusion) on a five consecutive day schedule every 3 weeks. During the first and the second courses of treatment, each patient underwent pharmacokinetic evaluation. Quantitation of the total topotecan (lactone plus carboxylate form) was assessed by a highly specific high-performance liquid chromatographic (HPLC) method. Large patient-to-patient variations in the plasma and saliva concentrations were observed. Plasma and saliva pharmacokinetics could be described using a biexponential pattern. From the saliva data, the half-life of the terminal part of the curve was 2.64 h, it was of the same order of magnitude as the topotecan elimination half-life determined from the plasma data, 3.18 h. Topotecan concentrations were higher in the saliva than in the plasma, the saliva/plasma concentration ratio averaged 2.31 and the ratio area under the parotid saliva (AUC(s)) over plasma (AUC(p)) concentration-time curve (AUC(s)/AUC(p)) averaged 2.11. For each individual, a significant relationship was found between topotecan concentrations in the saliva and in the plasma, the coefficients of correlation ranged from 0.75 to 0.92 according to the patient. Myelosuppression, especially granulocytopenia was the most frequent toxicity encountered during the trial. The percent decrease in the leucocyte count, absolute neutrophil count and platelet count were related to the AUCp/day using sigmoidal E(max) models. The high values of the Hill constant found reflect the very steep AUC-haematoxicity relationship observed. In most cases, abdominal pain occurred in patients presenting high saliva concentrations. One patient with high salivary concentrations (mean S/P ratio=4.60) had grade 1 mucositis. In conclusion, the concentration of topotecan in saliva appeared to be useful as an indirect, non-invasive estimation of the levels of topotecan in the plasma; thus, saliva concentrations could be a good predictor of the behaviour of topotecan in the body.

Adult↗
PubMed2001

Intensive and timely chemotherapy, the key of success in testicular cancer.

More than 90% of patients with advanced germ cell tumors (GCT) are curable since the introduction of cisplatin-based chemotherapy, but only half of them with poor-risk characteristics and less than a quarter after the first relapse are cured by conventional chemotherapy. In this review, we have studied the results of dose-intensity in conventional chemotherapy and high-dose chemotherapy (HDCT) in the treatment of GCT patients. In first line, only one randomized trial of HDCT was performed and no benefit was demonstrated. One US randomized trial is ongoing. In first salvage treatment, no randomized trial was performed, and a European trial (IT94) is ongoing. In the refractory situation, there is no indication of high-dose chemotherapy. In conclusion, high-dose chemotherapy is not a standard treatment for different situations. New strategies are needed to improve the survival rate of poor prognosis germ cell tumor patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Metachronous gonadal and extragonadal primaries, or late relapse of germ cell tumor?

We report five distinct cases of apparently metachronous extragonadal and gonadal germ cell tumors (GCT) occurring in the same patient. Two patients had metachronous GCT of the central nervous system and the testis. One of these patients had been successfully treated for a germinoma of the pineal gland and developed a nonseminomatous GCT of the testis 10 years later. The second patient had a primary seminoma of the testis treated by orchiectomy followed by radiotherapy and developed a germinoma of the sphenoidal sinus 17 months later. Three other patients had an apparently metachronous retroperitoneal and testicular GCT with 22, 44, and 66 months elapsing, respectively, between the first and second neoplasms. These cases suggest that the remaining testis is not only at risk for a second primary GCT, but that a second GCT may emerge at an extragonadal site. A genetic predisposition may account for some of these cases and the occurrence of bilateral testicular GCT. In none of these cases, however, could we ascertain whether testicular GCT was truly a second primary or a relapse of a "primary" retroperitoneal GCT in our cases.

Journal Article↗
PubMed2001

Cytotoxicity of iridals, triterpenoids from Iris, on human tumor cell lines A2780 and K562.

Six different triterpenoids (known iridals) extracted from Iris germanica L. were purified and bioassayed on two cultured human tumor cell lines: A2780 and K562 (and for each one a drug-sensitive and a drug-resistant cell line). All of the tested iridals had an IC50 in the 0.1 to 5.3 microg/ml range. Some of them were shown to be more effective than doxorubicine. Toxicity of iridals on multi-drug resistance (MDR) expressing cell lines seemed to indicate that the effects of these triterpenoids are less affected by MDR than those of doxorubicine or taxol.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations.

Breast cancer heterogeneity can be related directly to its variability at the genetic level. Thus, tumor genotyping could be a valuable approach to define breast tumor subtypes. It has been shown that it is possible to delineate subgroups of breast tumors according to specific sets of DNA amplifications. The aim of the present work was to study the prognostic significance of these DNA amplifications. We studied DNA amplification at eight genes or loci (AIB1, CCND1, EMS1, ERBB2, FGFR1, MDM2, MYC, and RMC20C001) as well as p53 mutations in a series of 640 breast cancer patients who had not received presurgical therapy and analyzed the correlations with survival DNA amplification was assessed by Southern blotting and was scored positive when exceeding three to five copies. Mutations in the p53 gene were searched by four-color fluorescent single. strand conformational polymorphism, using an automated sequencer. Of the nine genetic alterations tested, four (CCND1, EMS1, FGFR1, and p53 mutations) showed a significant association with reduced disease-free (DFS) and/or overall survival (OVS) in the unselected set of patients by univariate test. Correlations for p53 were found only when selecting mutations in exons 5 or 7. Analysis of node-negative and -positive subgroups of patients showed that MDM2 amplification and p53 mutations bore prognostic significance in node-negative patients, whereas amplification of CCND1, EMS1, and FGFR1 correlated with poor outcome in node-positive patients. Multivariate analysis on an unselected set of patients retained significance for the amplification of EMS1, FGFR1, and MDM2 with DFS, of CCND1 with OVS, and of RMC20C001 with both DFS and OVS. Interestingly, stratified analysis according to nodal status confirmed results obtained in the univariate tests: significance of MDM2 amplification and p53 mutations in node-negative and that of CCND1, EMS1, and FGFR1 in node-positive patients. We also observed an association between the number of genetic alterations observed in a tumor and poor prognosis. Patients with two or more amplified loci had a worsened outcome. Strongly correlating coamplifications such as CCND1 and FGFR1, as well as ERBB2 and MYC, were associated with a significant reduction of patient survival, thus indicating cooperative effects. Our data support the idea that genetic alterations in breast cancer are not only helpful for phenotyping purposes, but can also represent powerful prognostic indicators in the clinical practice.

Breast Neoplasms↗
PubMed2000

Population pharmacokinetics of topotecan: intraindividual variability in total drug.

The inter- and intraindividual variabilities in topotecan clearance (CL) were explored using a population pharmacokinetic approach. Total (lactone + hydroxy acid) topotecan plasma concentrations were obtained in 31 women with metastatic epithelial ovarian cancer treated by the 30-min intravenous infusion on 5 subsequent days. The data corresponding to three occasions (days 1 and 5 of cycle 1, and day 1 of cycle 2), were analyzed using the nonlinear mixed effect model program. A large interindividual variability was observed, with CL varying from 9.1 to 42.51 per hour (mean 21.0). Topotecan CL was related to serum creatinine level, and age. A close relationship was also observed between topotecan CL and creatinine clearance. Intraindividual variability both within cycle 1 and between the two first cycles was limited, with a mean variation of -2+/-17%, and + 5+/-20%, respectively. A limited sampling strategy using Bayesian estimation based on two samples (5 min before the end of the 30-min infusion, and 4 h after the end of infusion) was developed. The results of this study combine relationships between topotecan pharmacokinetic parameters and patient covariates that may be useful for a priori dose adjustment, and convenient sampling procedure that can be used for further studies and drug monitoring.

Aged↗
PubMed2000

The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients.

Growing teratoma syndrome (GTS) is defined as an increase in tumour size during or after chemotherapy for germ cell tumour (GCT), and only mature teratoma at histological analysis of the resected tumour specimen. Between 1985 and 1997, 30 male patients fulfilling GTS criteria were included in the present study. 3 female patients were also included but analysed separately. A mature teratoma component was found in 86% of the primary GCT. 3 male patients (10%) had a complication at diagnosis of GTS. One male patient (4%) having undergone complete resection (n=24) had a recurrent GTS, compared with all but 1 patient (83%) in whom resection was partial (n=6) (P<0.001). 2 (8%) and 3 (50%) male patients treated with complete and partial resection subsequently developed a malignant NSGCT respectively (P=0.01). 2 female patients treated with partial resection presented a recurrent GTS. One of them died of this recurrent GTS. GTS is an entity in its own right with respect to complications and the natural history of the disease. Complete surgical resection is the treatment of choice for GTS.

Adolescent↗
PubMed2000

Chemotherapy in advanced androgen-independent prostate cancer 1990-1999: a decade of progress?

BACKGROUND AND PURPOSE: A great number of clinical research studies have been reported in the field of chemotherapy for advanced androgen-independent prostate cancer during the last ten years. The aims of the present review were to assess their impact on management of the disease and on survival of patients. METHODS: The review of full published reports was facilited by the use of a MEDLINE computer search. RESULTS: Clinical research studies have focused on defining guidelines for eligibility criteria and accurate endpoints for patients to be enrolled onto clinical trials and developing new agents or combination of drugs including estramustine phosphate. Any combination of current chemotherapy has no impact on overall survival of patients. Among drugs in development, only the promising activity observed with docetaxel deserves randomized trials to assess its impact on survival. The major innovative advance of the 90s is the demonstration of the impact of chemotherapy (mitoxantrone + prednisone) on quality of life as compared to prednisone alone. A greater and longer-lasting improvement in quality of life along with a concomitant decrease in costs was observed. CONCLUSIONS: At the present time, chemotherapy should be considered as a palliative treatment in patients with symptomatic androgen-independent disease. The enrollment of patients into clinical trials dealing with quality of life as primary endpoint is strongly solicited. A standard methodology should be used in phase II trials with a primary goal of selection of agents which should progress to randomized trials using survival as an endpoint. Hopefully new specific strategies targeted to reverse the molecular changes that underlie prostate tumorigenesis should rapidly impact the multimodality management of AIPC in the third millenium.

Antineoplastic Agents, Hormonal↗
PubMed2000

Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups.

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P<0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P< or =0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs.

Adult↗
PubMed2000

Peritoneal carcinomatosis in germ-cell tumor: relations with retroperitoneal lymph node dissection.

Peritoneal carcinomatosis from germ-cell tumor has rarely been described, and thus remains largely unknown. We report here five cases involving this entity. All five patients had embryonal carcinoma in their primary germ-cell tumor. Four of them had undergone retroperitoneal lymph node dissection (RPLND), and viable malignant cells were found. RPLND was performed for relapses (n = 3) and as primary therapy for stage II disease (n = 1). The peritoneum was the only site of relapse in three patients, and was associated with pleural effusion in one. The time to relapse after RPLND ranged from 6 to 14 months. One patient sustained injury to lymph nodes during RPLND, and another patient had a peritoneal xanthelasma. The only three patients already described in the literature underwent RPLND or surgical biopsy. All these observations suggest a striking relation between RPLND and occurrence of subsequent peritoneal carcinomatosis.

Adult↗
PubMed2000

Comparative tolerability of chemotherapy regimens for germ cell cancer.

Germ cell tumours, even at an advanced stage, represent a unique model of malignant curable disease since >80% of patients are expected to be cured after appropriate therapy: surgery and radiotherapy in early stages, and chemotherapy and surgery in advanced stages. In advanced stages, serum tumour marker levels as well as extrapulmonary (brain, liver and bone) visceral metastases are the most important prognostic factors that affect treatment modalities. 'Gold standard' regimens for germ cell cancer currently include etoposide plus cisplatin with (BEP) or without (EP) bleomycin. In patients with good risk disease (90% cure rate), the optimal regimen of chemotherapy should combine the best efficacy and the least toxicity. As a result of randomised trials, 3 regimens can be currently recommended: (i) 4 cycles of EP; (ii) 4 cycles of BEP (with etoposide 350 mg/m2 per cycle); or (iii) 3 cycles of BEP (with etoposide 500 mg/m2 per cycle). In patients with poor risk disease, 4 cycles of BEP (with etoposide 500 mg/m2 per cycle) allow a disappointing cure rate of 50%. The long term toxicity of these regimens (gonadal toxicity and secondary malignancies) appears to be negligible and clearly does not challenge current standard strategies.

Animals↗
PubMed2000

A phase I and pharmacokinetic study of melphalan using a 24-hour continuous infusion in patients with advanced malignancies.

The objectives of the present study were to determine the following: (a) the maximum tolerated dose (MTD) of melphalan using a 24-h continuous infusion; (b) the clinical toxicity; and (c) the pharmacokinetic characteristics of melphalan at each dose level. Twenty-one patients with refractory solid tumors were enrolled in the study. Melphalan, packaged in 3% sodium chloride, was administered i.v. over a 24-h period. Patients were assigned to one of three escalating dose levels of melphalan: (a) 20 mg/m2 (n = 5); (b) 30 mg/m2 (n = 7); and (c) 40 mg/m2 (n = 6). Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Melphalan concentrations in plasma were determined by high-performance liquid chromatography. Toxicity was evaluated after each course of chemotherapy. All of the patients were assessable for toxicity and pharmacokinetics, and 20 patients were assessable for response analysis. A total of 50 courses of melphalan was studied. The MTD was 30 mg/m2. The dose-limiting toxicity was neutropenia and thrombocytopenia. Hematotoxicity was reversible (nadir, 14-15 days; recovery, 3.5 and 12.5 days for 30 and 40 mg/m2, respectively), cumulative, and related to the administered dose and to the history of previous therapy. There were six episodes of neutropenic sepsis. Individual pharmacokinetic parameters were estimated using a Bayesian approach and linear elimination kinetics. Data were compatible with a one-compartment model. Relationships have been found between the area under the plasma concentration-time curve and doses and between Css and doses. Moreover, clearance, t1/2 elimination, and volume of distribution did not change statistically with dose, which suggests linear kinetics. Two partial responses were observed in patients with ovarian carcinoma or adenocarcinoma of unknown primary origin, and another patient had stabilization disease. In conclusion, melphalan MTD was determined to be 30 mg/m2 when administered as a 24-h infusion. Hematological toxicity was the dose-limiting toxicity. The most important nonhematological toxicity encountered was nausea and vomiting. The recommended dose for Phase II studies was 30 mg/m2.

Adolescent↗
PubMed2000

Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer.

The objective of the present study was to determine the pharmacokinetic profile of vinorelbine in patients 65 years or older with metastatic cancer in progression. Twelve patients were enrolled in this study. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m2 through a central venous catheter. Chemotherapy was repeated weekly. A total of 46 courses of vinorelbine was studied. Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Toxicity evaluation was carried out before each course of chemotherapy. Plasma vinorelbine determinations were performed by high-performance liquid chromatography with spectrofluorometric detection. A Bayesian estimation of individual pharmacokinetic parameters was carried out using the nonlinear mixed-effect modeling approach as implemented in the NONMEM computer program. An open three-compartment pharmacokinetic model with a zero order input rate was used to describe the kinetics of vinorelbine. Area under the plasma-concentration time curve (AUC) normalized to a 30 mg/m2 administered dose averaged 0.89 mg/liter x h (coefficient of variation = 23.7%). The total plasma clearance averaged 0.93 liter/h/kg (0.61-1.83 liter/h/kg; coefficient of variation = 38.6%). The elimination half-life was 38.1 +/- 5.8 h. A high correlation was found between patient age and total clearance (r = -0.8; P < 0.001). The main hematological toxicity observed was anemia in 11 patients. Neutropenia occurred in 50% of patients. Significant correlations were found between AUC and the decrease in the hemoglobin level (r = 0.60) and between AUC and the decrease in the neutrophil count (r = 0.66). Thrombocytopenia was observed in only one patient. In conclusion, the age-related decrease in clearance found in this study supports the design of a Phase I study of vinorelbine in patients older than 65 years or perhaps 70 years.

Age Factors↗
PubMed2000

[Gemcitabine and urothelial tumours].

Since 1985, standard chemotherapy of metastatic urothelial tumours has been based on a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC protocol). Two major lessons have been learned from the use of M-VAC, namely, clear evidence of chemo-sensitivity, and an absence of chemo-curability associated with notable toxicity. Three phase II studies using gemcitabine monotherapy have demonstrated promising efficacy with an objective response rate of 22-28%, and a satisfactory toxicity profile. Three further phase II studies have confirmed the efficacy of gemcitabine in association with cisplatine (GC protocol), with a response rate of 42-66%, of which 18-28% were complete responses. The main adverse effects were haematological, including neutropenia, or grade 3 or 4 thrombocytopenia without any symptoms of fever or significant haemorrhage. Current research with gemcitabine in the treatment of urothelial tumours is aimed at optimising administration of the GC protocol, investigating the use of gemcitabine in association with other cytotoxic agents such as taxanes, or expanding the use of this drug as adjuvant therapy. The results of a phase III study to compare the efficacy and toxicity of the M-VAC and GC protocols are eagerly awaited.

Animals↗
PubMed1999

Treatment outcome of patients with brain metastases from malignant germ cell tumors.

BACKGROUND: Multiinstitutional experience with the management of cerebral metastases from malignant germ cell tumors (MGCT) is presented. METHODS: Clinical data regarding brain metastases from MGCT at diagnosis (Group 1 [56 patients]) or after cisplatin-based chemotherapy (Group 2 [83 patients]) were collected retrospectively. All patients in Group 1 received "conventional" cisplatin-based chemotherapy supplemented by cerebral radiotherapy (36 patients) and/or neurosurgery (10 patients). In the patients in Group 2 cerebral metastases were detected a median of 9 months after the initiation of chemotherapy. Thirty-five patients received chemotherapy, 59 patients received radiotherapy, and 25 patients underwent neurosurgery. RESULTS: The 5-year cause specific survival rate in Group 1 was 45% (95% confidence interval [CI], 31-59%). Neurosurgery and the absence of extracerebral, nonpulmonary visceral disease, but not cerebral radiotherapy, were independent predictors of good prognosis. The 5-year cause specific survival rate in Group 2 was 12% (95% CI, 4-20%), but was 39% among patients with an isolated brain recurrence (24 patients). Radiotherapy, but not chemotherapy, represented an independent predictor of good prognosis together with brain metastases at first recurrence and the absence of extracerebral recurrence. CONCLUSIONS: Among patients with brain metastases at the time of diagnosis of an MGCT, cisplatin-based chemotherapy resulted in a 5-year cause specific survival rate of 45%, with cerebral radiotherapy having limited impact. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but increased to 39% in patients with an isolated brain recurrence. Cerebral radiotherapy (and neurosurgery) represent essential treatment modalities for patients in whom brain metastases are diagnosed after induction chemotherapy.

Adolescent↗