Prognostic Significance of Marker Half-life during Chemotherapy in Non-seminomatous Germ Cell Testicular Tumors

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life 7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis.     

Tumor marker kinetics predict outcome in patients with relapsed disseminated non-seminomatous germ-cell tumors

BackgroundAn early serum tumor marker (TM) decline during chemotherapy was shown to independently predict survival in patients with poor-prognosis disseminated non-seminomatous germ-cell tumors (NSGCTs). The aim of this study was to assess whether a TM decline (TMD) also correlates with the outcome in the salvage setting.Patients and methodsData regarding 400 patients with progressive or relapsed disseminated NSGCTs after first-line chemotherapy prospectively accrued onto two phase III clinical trials were obtained. Serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG) were assessed at baseline and after 6 weeks of chemotherapy. A total of 297 patients, 185 and 112 in the training and validation sets, with initially abnormal TMs for whom a change from baseline could be established were used for this analysis.ResultsAn unfavorable decline in either AFP or hCG was predictive of progression-free survival (PFS) [hazard ratio, HR = 2.15, (95% CI 1.48–3.11); P < 0.001; 2-year PFS rate: 50% versus 26%] as was the Lorch prognostic score (LPS). In the multivariate analysis, an unfavorable TMD, stratified based on the LPS, was an independent adverse prognostic factor for PFS and OS.ConclusionAn unfavorable TMD during the first 6 weeks after chemotherapy is associated with a poorer outcome in patients with relapsed disseminated NSGCTs.     

Tumour marker concentration at the start of chemotherapy is a stronger predictor of treatment failure than marker half-life: a study in patients with disseminated non-seminomatous testicular cancer.

We investigated the prognostic value of the serum half-life of human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP) during induction chemotherapy and the relative prognostic importance of initial marker concentrations and marker half-life. Marker half-lives were calculated using two abnormal values observed between day 8 and day 22 of the first chemotherapy cycle. Moreover, analyses were carried out using day 43 as the second measurement point. Treatment failure at any time was chosen as the end point. The relative prognostic influence of marker half-lives and initial marker concentrations was tested in univariate and multivariate analyses. Half-lives were considered to be prolonged if > 3 days for HCG and > 6 days for AFP. In addition, we separated patients into those with half-lives > 6 days for HCG and those with half-lives > 10 days for AFP to examine whether these long half-lives were associated with a poor prognosis. A group of 669 patients treated with cisplatin combination chemotherapy was studied. Forty-two per cent of the patients had normal HCG and 37% had normal AFP at the start of chemotherapy. At day 22, HCG was still elevated in 138 patients and AFP in 211. At day 43, the numbers of these patients were 35 and 80 respectively. Based on the measurements obtained on day 8 and day 22, a half-life of HCG > 3 days or > 6 days and/or a half-life AFP > 6 days or > 10 days did not accurately predict treatment failure (P=0.413 and P=0.851, respectively; values obtained using tests for trend). However, initial marker concentrations of HCG and/or AFP > 1000 IU l(-1) were highly significant prognosticators for treatment failure (P=0.001 and P < 0.001 respectively), independent of half-life values. Half-lives calculated with the values obtained on day 43 did not contribute to the accuracy of the prediction of treatment failure. We conclude that half-lives of HCG and AFP during induction chemotherapy are inaccurate parameters for the prediction of treatment failure. In contrast, initial serum concentrations of HCG and AFP are highly significant in the prediction of unfavourable treatment outcome.     

Brain metastases in malignant teratoma: a review of four years' experience and an assessment of the role of tumour markers.

Between 1973 and 1977, 247 patients with malignant teratoma have been treated in two units in London. Seventeen have developed brain metastases, an overall incidence of 6.2%. The median survival from diagnosis of cerebral metastases is 6 weeks and all patients except one have died. The survivor is disease-free 12 months after completing treatment, which included extensive use of chemotherapy, surgery and radiotherapy. Serum gonadotrophin (HCG) and alpha-foetoprotein (AFP) estimations have been performed in 264 patients as a means of monitoring the effects of therapy. In 42 patients (37 of whom had Stage IV disease) the peak HCG level was greater than 10(4) iu/l, and the incidence of brain metastases in this group was 26%, significantly higher than in the group with HCG levels below 10(4) iu/l, for which the incidence of cerebral deposits was 1.8% (P less than 0.0001). No significant correlation was seen between peak AFP levels and the incidence of brain metastasis. With the aim of improving results by earlier diagnosis, cerebrospinal fluid (CSF) specimens have been examined for HCG and AFP levels in 56 subjects, 9 of whom had brain metastases. A serum: CSF HCG ratio less than 40 is an accurate indication of the presence of brain metastases, and may have considerable predictive value. However, false-negative serum: CSF HCG rations (greater than 40) frequently occur in patients with proven brain deposits. Estimation of AFP in spinal fluid has not contributed to the early diagnosis of brain metastases in malignant teratoma.     

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

PURPOSE: The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. PATIENTS AND METHODS: Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. RESULTS: The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. CONCLUSION: Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.     

Prognostic factors in advanced nonseminomatous testicular cancer. A multivariate logistic regression analysis

In order to define prognostic factors for advanced stage of nonseminomatous germ cell tumors (NSGCT) of the testis, the authors reviewed 84 patients treated from 1978 through 1985. The survival rate was 51% at 3 years. Patients with elevated seric levels of human chorionic gonadotropin (HCG) and/or alpha-fetoprotein (AFP), or the presence of an abdominal mass had significantly worse survival. Only HCG and AFP levels retained their significance when multivariate Cox analysis was performed. The probability that a patient achieves a complete remission (CR) was assessed by a function of certain patient characteristics using a multivariate logistic regression analysis. The significant variables were a function of HCG and AFP values. Since both variables are related to the CR rate and survival the authors define the obtention of a CR as a unique outcome of interest. The probability of a CR greater than 70% adequately separates the patients into two prognostic subgroups. This model currently is being used to enrole NSGCT patients in a prospective modulated clinical trial according to these prognostic factors.     

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.     

Correlation of serum tumor markers in advanced germ cell tumors with responses to chemotherapy and surgery

Remission rates induced by chemotherapy alone or by combined chemotherapy and surgery were analyzed in relation to specific serum tumor marker abnormalities immediately before treatment in 103 patients with Stage III or bulky Stage II nonseminomatous germ cell tumors. Complete remission occurred in 92% (12 of 13) of patients with normal levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), in 26% (6/23) with elevated AFP only, in 46% (13/28) with elevated HCG only, and in 39% (13/36) with abnormalities of both AFP and HCG. Patients with elevated AFP less frequently had a complete remission (CR) to chemotherapy (CR, 34% versus 61% with normal AFP), but benefitted from adjunct surgery (CR, up to 59%). Patients with very high (greater than 1000 ng/ml) serum AFP or HCG responded poorly to chemotherapy (CR, 17%) but especially large tumor burdens may have contributed to these unfavorable responses. Patients with both minimal and advanced metastatic disease had higher CR rates if they had serum tumor marker levels below rather than above 1000 ng/ml. Adjunct surgery eliminated the correlation between the "poor prognostic factors" associated with specific marker abnormality and an incomplete response to chemotherapy by rendering a significant number of such patients free of disease through resection of residual metastatic deposits.     

Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy.

PURPOSE: The prognostic significance of the rate of decline of the serum tumor marker alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) during the first two cycles of chemotherapy in germ cell tumor (GCT) patients was initially reported by us, but its value has been debated. We re-examined this issue in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification system and investigated the role of including in the analysis patients whose markers normalized early. PATIENTS AND METHODS: One hundred eighty-nine GCT patients with elevated AFP/HCG marker values treated with platinum-based chemotherapy between 1986 and 1998 were included in this analysis. Patients were classified as good, intermediate, or poor risk by the IGCCCG criteria and as having satisfactory or unsatisfactory marker decline. Risk and marker decline were correlated with response, event-free survival, and overall survival. RESULTS: Satisfactory marker decline predicted improved complete response (CR) proportion and event-free and overall survival (P <.0001). The CR proportion, 2-year event-free, and 2-year overall survival rates for patients with a satisfactory and unsatisfactory marker decline were 92% versus 62%, 91% versus 69%, and 95% versus 72%, respectively. Marker decline remained a significant variable for all three end points when adjusted for risk (P <.01) with the outcome differences most pronounced in the poor-risk group. CONCLUSION: The rate of marker decline during chemotherapy has prognostic value independent of risk and may play a significant role in the management of poor-risk patients. It is appropriate to include patients whose markers normalized early.     

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.     

Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers

BACKGROUND: A standard concept for the integration of surgery into the chemotherapy-based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers. METHODS: The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin-based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow-up of 74 months (range, 24-207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753-64.553; P = 0.043 and P = 0.016, respectively; log-rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log-rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516-fold (95% CI, 1.786-87.781) and 9.311-fold (95% CI, 1.796-48.256), respectively. CONCLUSIONS: Salvage surgery in patients with high serum tumors markers resulted in long-term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long-term disease free status.     

Prognostic and clinical significance of subcellular CDC27 for patients with rectal adenocarcinoma treated with adjuvant chemotherapy

Rectal adenocarcinoma (READ) constitutes one-third of newly diagnosed colorectal cancer cases. Surgery, chemotherapy and concurrent chemoradiotherapy are the main treatments to improve patient outcomes for READ. However, patients with READ receiving these treatments eventually relapse, leading to a poor survival outcome. The present study collected surgical specimens from patients with READ and determined that cytoplasmic cell division cycle 27 (CDC27) expression was associated with the risk of lymph node metastasis and distant metastasis. Nuclear CDC27 expression was negatively associated with 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates. Multivariate Cox proportional regression analysis showed that nuclear CDC27 was an independent prognostic factor in the patients with READ, especially in those treated with adjuvant chemotherapy. High nuclear CDC27 expression was significantly associated with poorer 5-year DFS (HR, 2.106; 95% CI, 1.275-3.570; P=0.003) and 5-year OS (HR, 2.369; 95% CI, 1.270-4.6810; P=0.005) rates. The data indicated that cytoplasmic CDC27 expression could affect tumor progression and that it plays an important role in metastasis. Nuclear CDC27 expression was markedly associated with poorer survival outcomes and was an independent prognostic factor in patients with postoperative adjuvant chemotherapy-treated READ. Thus, CDC27 expression serves as a potential prognostic marker for rectal tumor progression and chemotherapy treatment.     

Prognostic Significance of the Peripheral Blood Absolute Monocyte Count in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma Receiving Systemic Chemotherapy

Background: The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy. Materials and Methods: Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS). Results: A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was 0.38 x109/L. Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009). Conclusions: Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy.     

Salvage radiotherapy in recurrent Hodgkin's disease.

Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year.     

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

Prognosis after resection of residual masses following chemotherapy for metastatic nonseminomatous testicular cancer: a multivariate analysis.

Following chemotherapy for metastatic nonseminomatous testicular cancer, 86 patients with normal serum markers AFP and HCG underwent resection of residual tumour masses (63 laparotomy, 11 thoracotomy, 12 both). Prognostic factors for relapse and survival were analysed with Kaplan-Meier curves and Cox regression analysis. Putative prognostic factors included age, the primary histology, prechemotherapy level of the tumour markers AFP and HCG, the extent of disease (lymph nodes, lung and hepatic metastases) before and after chemotherapy, the histology of the resected material and the completeness of the surgical procedure. Eleven patients relapsed during follow-up (median 47 months), accounting for a 5 year relapse free percentage of 87.4%. Adverse prognostic factors were (1) prechemotherapy level of HCG (> or = 10,000 IU l-1; (2) incomplete resection; and (3) the extent of disease, especially of lung metastases (prechemotherapy number < or = 3,4-19, > or = 20; or size after chemotherapy > 1 cm; or presence of any residual lung metastasis after chemotherapy without residual abdominal metastases). The histology found at resection was not associated with the risk of relapse, which might be explained by the effectiveness of postresection chemotherapy, which in the majority of these patients was a salvage regimen rather than two further cycles of the initial cytostatics. A good and a poor risk group were formed, based on HCG level and completeness of resection. The effect of salvage chemotherapy after resection of viable cancer cells needs further investigation.     

Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma.

One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM) seen between 1986 and 1999 at the authors' Institution were reviewed. Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%) and mixed in 12 (10%). Ninety-one patients received a treatment (38 palliative pleurectomy and no further therapy, 16 palliative pleurectomy followed by chemotherapy, 37 chemotherapy alone), while 30 were referred to supportive care only. Median survival of the whole population was 10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%, respectively. Univariate analysis of subgroups showed that poor performance status (PS), non-epithelial histotype, Butchart stage>I and International Mesothelioma Interest Group (IMIG) stage>I were individually associated with lower survival. Patients receiving any therapy survived longer than patients treated with supportive care only (P=0.0004). Treatment modality had an independent prognostic value (P=0.00005), with a survival advantage for patients receiving surgery and adjuvant chemotherapy. Multivariate analysis confirmed the independent prognostic value of PS (P=0.001; HR=2.48) and treatment modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and treatment modality (P=0.01) was confirmed in the subset of patients with epithelial histology. On the contrary, therapy had no impact on survival in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of a retrospective non-randomized evaluation of treatment-related factors, patients with good PS and epithelial histology seemed to have a survival benefit from surgery or multimodality therapy, as opposite to patients with poor PS or non-epithelial histotype. However, these results must be confirmed in a larger prospective trial with uniform treatment.     

Neutrophil‐lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: results of a large multicenter study involving 990 patients

Several studies have demonstrated the prognostic value of neutrophil‐lymphocyte ratio (NLR) in patients with solid tumors and non–Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)‐cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression‐free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression‐free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS‐cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS‐cHL patients.     

Prognostic factors in patients with gemcitabine-refractory pancreatic cancer

OBJECTIVE: The purpose of this study was to identify prognostic factors in patients with gemcitabine-refractory pancreatic cancer and to determine criteria for selecting candidates for second-line treatment. METHODS: The records of 74 patients who were treated with gemcitabine (GEM) and followed up until disease progression were reviewed retrospectively. Sixteen clinical variables at the time of disease progression after GEM chemotherapy were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULTS: At the time of analysis, 71 patients had died because of tumor progression. The overall median survival time was 5.1 months after first-line chemotherapy with GEM was initiated. Median survival time after disease progression was 2.0 months. Three factors, performance status, peritoneal dissemination and C-reactive protein level, were identified as independent prognostic factors in multivariate analysis. Median survival time in the good prognosis group (patients with performance status 0 or 1, no peritoneal dissemination and C-reactive protein <5.0 mg/dl) was 3.4 months. CONCLUSIONS: Performance status, serum level of C-reactive protein and peritoneal dissemination were identified as important prognostic factors in patients with GEM-refractory pancreatic cancer. These factors should be considered in determining the treatment following first-line chemotherapy in patients with advanced pancreatic cancer.     

联合铂类化疗改善晚期胰腺癌预后

目的探讨治疗晚期胰腺癌的有效药物。方法选择病理诊断明确的Ⅲ～Ⅳ期胰腺癌患者,至少接受2周期以上吉西他滨、氟尿嘧啶及铂类化疗,电话回访生存期,分析不同药物治疗后生存期变化。结果 95例晚期胰腺癌患者中位生存期7.1月,1年生存率30.5%,2年生存率8.4%,3年生存率3.2%。Cox单因素生存模型分析显示,Ⅳ期患者较Ⅲ期患者生存期短（P=0.002,HR：2.09,95%CI：1.31～3.35）,联合铂类化疗方案治疗患者较未联合患者生存期长（P=0.011,HR：0.56,95%CI：0.35～0.88）,胰体尾癌较胰头颈部癌患者生存期有缩短趋势,但差异无统计学意义（P=0.062,HR：1.53,95%CI：0.98～2.38）。Cox多因素生存模型分析显示,Ⅳ期患者较Ⅲ期患者死亡风险增加（P=0.026,HR：1.83,95%CI：1.08～3.10）,联合铂类化疗能降低晚期胰腺癌死亡风险（P=0.026,HR：0.59,95%CI：0.38～0.94）。结论Ⅳ期胰腺癌患者较Ⅲ期患者预后差,联合铂类化疗可能延长晚期胰腺癌生存期。