Prognostic factors in patients with hepatocellular carcinoma submitted to chemoembolization

The prognosis of unresectable hepatocellular carcinoma is poor. Encouraging response rates have been reported with chemoembolization, but no survival advantage has been demonstrated. Assessment of the impact of the treatment modality on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 16 variables in 63 patients submitted to chemoembolization. Patients were treated with epirubicin (50 mg) plus ethiodized oil and gelatin sponge (22 cases) or with a new program combining i.a, chemotherapy with chemoembolization (41 cases) as follows: L-leucovorin, 100 mg/m(2) i.v.; fluorouracil, 800 mg/m(2) i.a.; carboplatin, 250 mg/m(2) i.a. Chemoembolization with mitoxantrone, 10 mg/m(2), plus ethiodized oil and gelatine sponge was performed immediately after. Median survival for the whole group of patients was 294 days. A multivariate analysis showed a highly significant influence on survival for Child's status (p=0.002) and for TNM stage (p=0.01). Median survival for patients with Child's A disease was 13.9 months and for patients with TNM stage I-II disease 19 months. In conclusion, our data suggest that patients with limited disease and adequate liver function have a longer survival after chemoembolization.     

120例恶性胸膜间皮瘤的临床特征及诊断分析

目的:回顾性分析胸膜间皮瘤患者的临床资料,包括病史、症状、淋巴结及远处脏器转移的规律,并分析不同分期、病理类型及治疗方式的患者生存情况,为该疾病的诊断和治疗提供思路。方法:分析空军军医大学唐都医院2009年4月-2016年9月收治的120例胸膜间皮瘤患者资料,基于第8版TNM分期标准进行肿瘤分期。对不同临床分期、病理类型及治疗方式的患者生存期进行统计分析,应用Kaplan-Meier法进行生存分析。结果:120例患者中有职业暴露史3例(占2.5%)。发病部位为左侧胸膜56例(占46.7%),右侧胸膜63例(占52.5%),双侧胸膜1例。总体的误诊率为30%(36/120),其中误诊为结核32例(26.7%)。以胸痛症状发病55例(占45.8%),胸腔积液107例(占89.2%),两者合并为49例(占40.8%)。确诊方法包括胸膜穿刺诊断53例(占44.2%),胸腔镜诊断41例(占34.2%),开胸探查诊断26例(占21.6%)。所有患者中淋巴结转移(N1~N2)共43例(占35.8%),涉及54个淋巴区;纵隔淋巴结转移42例(占77.8%),纵隔外淋巴区转移12例(占22.2%)。成功随访78例患者,总体中位生存期为15.0个月,1、2、3及5年生存率分别为67.9%、27.7%、16.0%及4.2%。Ⅰ/Ⅱ期患者中位生存期为17.0个月,明显长于Ⅲ/Ⅳ期患者的13.0个月(P<0.05)。上皮型肿瘤患者的中位生存期为17.0个月,与混合型及肉瘤型患者比较有生存优势(P值均<0.05)。手术联合化疗组的患者中位生存期为30.0个月,优于单纯手术、单纯化疗及支持治疗的患者(P值均<0.05)。结论:胸膜间皮瘤的误诊率高,其中大多被误诊为肺结核。恶性胸膜间皮瘤患者主要以胸腔积液症状发病,而且淋巴结转移规律与肺癌有所不同。所以在胸膜间皮瘤的诊断和治疗中,应高度重视这些临床特征,尽量减少误诊,以提高治疗效果。另外,临床分期较早及上皮型病理类型的患者预后相对较好,而且采用手术联合化疗的综合治疗模式可以使胸膜间皮瘤患者获得相对较长的生存期。     

Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure

The effects on long-term post-operative quality of life (QoL) and disease-control in malignant pleural mesothelioma (MPM) of extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are compared. Seventy-seven patients affected by early-stage MPM received EPP (40) or P/D (37) associated with multimodal treatment between 1998 and 2009 at our institution. The last consecutive 39 (19 EPP and 20 P/D) were asked to answer the EORTC-QLQ-C30 questionnaire at baseline and at 6- and 12-months after treatment completion to evaluate the impact on QoL of both procedures. QoL evaluation was stopped at recurrence demonstration. Twenty-five (62%) EPP vs 9 (24%) P/D patients (p = 0.002) had in-hospital major complications, and 2/40 (5%) EPP vs no one P/D patients died after surgery. Both procedures caused a significant impairment of all the considered variables of the EORTC-QLQ-C30 questionnaire after treatment completion; only P/D patients returned at baseline levels after 12 months. EPP patients had a worse long-term post-operative QoL when compared with P/D. Median post-operative disease-free period was longer for EPP patients (14 vs 11 months) whereas the residual life to death period after recurrence detection was significantly longer for P/D patients (13 vs 9 months) (p = 0.01). Median long-term survival was longer, even not significant, for P/D patients (25 vs 20 months). MPM patients submitted to EPP had a higher post-operative complication rate, a worse long-term QoL, a shorter residual life time after recurrent disease, despite a similar long-term survival when compared to P/D.     

Relationship Between Prognosis and Neutrophil: Lymphocyte and Platelet:Lymphocyte Ratios in Patients with Malignant Pleural Mesotheliomas

Background: It has been demonstrated that neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR)ratios are associated with prognosis in cancer patients. The aim of this study was to investigate whetherpretreatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, basophil and eosinophil counts,LDH level, NLR and PLR are associated with prognosis in patients with malignant pleural mesothelioma (MPM).Materials and Methods: We retrospectively reviewed files of 50 patients who were managed with a diagnosis ofMPM between 2005 and 2010. Demographic and clinical characteristics, treatments, response to treatment andprognostic factors were evaluated, along with relationships between pretreatment blood parameters and prognosis.Results: Overall, 38 men and 12 women were included to the study. Mean age was 61.5±9.4 years (range: 39-83years). There was advanced disease in 86% (n=43) and the histological type was epithelial mesothelioma in themajority (82%). Of the cases, 17 (34%) received radiotherapy, while 42 cases underwent first- and second-linechemotherapy, with cisplatin plus pemetrexed as the most commonly used regimen. In the assessment aftertherapy, it was found that there was complete response in 4 cases (8%), partial response in 10 cases (20%),stable disease in 17 cases (34%) and progression in 19 cases (38%). Median follow-up was 10 months (range: 10day-30 months). Median overall survival was found to be 20.7 months while median progression-free survivalas 10 months. In univariate and multivariate analyses, it was found that factors significantly affecting overallsurvival included stage (p=0.030), response to treatment (p=0.026) and monocyte count (p=0.004), while factorsaffecting disease-free survival included NLR (p=0.018), response to treatment (p=0.001), and PLR score (p=0.003).Conclusions: Overall and disease-free survival was found to be better in cases with a WBC count<8.000, plateletcount<300,000, and low NLR and PLR scores in malignant pleural mesothelioma.     

High-dose methotrexate in combination with interferons in the treatment of malignant pleural mesothelioma.

Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-alpha (3 MIU days 2-10) and recombinant IFN-gamma1b (50 microg m(-2) on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-alpha and IFN-gamma is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.     

8cm以上肝癌术后残癌的肝动脉栓塞化疗预后因素分析

目的：了解肝动脉栓塞化疗对直径大于8cm肝癌术后残癌的疗效和影响预后的因素。方法：肝癌切除术后2个月内经超声和动脉造影证实有残癌的肝癌患者，行肝动脉栓塞化疗；采用COX模型研究影响疗效的因素。结果：治疗后1，2，3，4年生存率为74.9%，44.2%，36.8%，18.4%。肝癌切除术后残癌的TNM分期是影响疗效的独立因素（P=0.003)。而原发癌的肿瘤分期，手术方式（局部切除或肝叶切除），肝动脉栓塞化疗的次数，不是影响预后的独立因素。结论：肝癌术后行肝动脉栓塞化疗是可行的，术后残癌的分期是影响肝动脉栓塞化疗效果的主要因素，大体积肿瘤术后尽早行肝动脉栓塞化疗是必要的。     

Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients

Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.     

Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.     

Prognostic factors for patients with stage IV epithelial ovarian cancer receiving intraperitoneal chemotherapy after second-look assessment: results of long-term follow-up

BACKGROUND: The aim was to determine the long-term outcome for patients with FIGO stage IV epithelial ovarian carcinoma (EOC) treated with intraperitoneal (IP) chemotherapy after second-look assessment. METHODS: By using data from a retrospective cohort of 433 patients who received IP therapy after second-look assessment after primary surgery and initial systemic therapy for EOC between 1984 and 1998 at our institution, all FIGO stage IIIC and IV patients were identified. Standard statistical methods were used. RESULTS: Overall, 297 patients met study criteria (246 stage IIIC; 51 stage IV). The median survival for patients with stage IV disease was 34 months compared with 42 months for patients with stage IIIC disease (P=.02). The only significant predictor of overall survival in patients with stage IV disease was the presence of gross residual disease at initiation of IP therapy (P=.027). When comparing stage IV patients with and without pleural effusions to all stage IIIC patients, there was a significant trend toward improved survival in the patients with pleural effusions only compared with other stage IV patients (P=.01). CONCLUSIONS: Prolonged overall survival was observed in patients with no gross residual disease at the time of IP chemotherapy initiation. When compared with similarly treated stage IIIC patients, stage IV patients with malignant pleural effusions appear to have a better outcome than those with other sites of metastasis. Future prospective trials should evaluate the use of IP therapy for patients with stage IV EOC by virtue of malignant pleural effusions only who responded to initial systemic therapy.     

Natural history of stage IV epithelial ovarian cancer.

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV-defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV-defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.     

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.     

Adenocarcinoma of the stomach: univariate and multivariate analysis of factors associated with survival

Gastric cancer is the most frequent tumor of the digestive tract in Mexico. Most patients are diagnosed at advanced stages, and fatal outcome is expected. One hundred fifty patient charts were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic and treatment variables on survival. Most patients (75%) were at advanced stages, harboring poorly differentiated tumors. Surgery, mostly palliative, was performed on 114 patients. Chemotherapy was administered to 47 patients. On univariate analysis, significant prognostic factors were TNM stage, chemotherapy, surgical attempt, performance status, histology, and tumor site (p < 0.001). On multivariate analysis, independent prognostic factors were TNM stage, histology, tumor site, surgical attempt, and chemotherapy (p < 0.01). Median survival for patients with palliative or adjuvant chemotherapy was 11.4 and 10.4 months, respectively, compared with +/- 3 months for patients with no chemotherapy (p < 0.03). Nonsurgical patients receiving chemotherapy survived 5.4 months versus 1.1 months for those without chemotherapy. The favorable influence of chemotherapy persisted after a stratified analysis of subgroups eliminating potential biases. We identified prognostic factors for survival. Chemotherapy should be considered even for advanced-stage patients with either adjuvant or palliative attempts, because we consistently found a favorable impact on the median survival time. However, phase III prospective randomized trials are awaited.     

Long term results of cyclophosphamide, adriamycin and platinum chemotherapy in advanced epithelial ovarian cancer

Between January 1980 and December 1983, 57 consecutive patients with advanced epithelial ovarian cancer (FIGO Stage IIc n = 5; III n = 45; IV n = 7) were treated with 6 cycles of cyclophosphamide 600 mg/m2, adriamycin 30-45 mg/m2 and platinum 50 mg/m2 (CAP) at 3 weekly intervals. Pathological complete remission (CR) was documented in 10 (18%) and 4 with no residual disease after primary cytoreductive surgery were free from progression (FFP). There were 19 partial remissions (PR) giving a 51% overall response rate. The median duration of CR was 33 months from second look surgery. Median survival (MS) for all patients was 22 months. Multivariate analysis indicated that response to chemotherapy was the most important prognostic factor, with MS for CR of 53 months, PR 23 months and stable or progressive disease 11 months (p = 0.001). Most CR (8 of 10) occurred in patients with minimal residual disease (no single lesion greater than 2.0 cm), but extent of disease, though significant in univariate analysis of prognostic factors was not an independent predictor of survival. Six patients (11%) are alive and tumour free with a minimum follow-up of 7 years. All had FIGO Stage III disease at presentation and four had no residual tumour after primary surgery.     

Gastric Carcinoma: 5 Year Experience of a Single Institute

Puropse: Gastric cancer (GC) is the most common cause of cancer death registered in cancer institute. Background ‍clinical information is important for cancer prevention and therefore we here present characteristics and outcome ‍of GC patients, more than half coming from northern parts of Iran. ‍Materials and Methods: we retrospectively studied records patients with pathologic diagnosis of GC referred to ‍the Medical Oncology Department of the Cancer Institute from 1998 to 2003. ‍Results: Four hundred and thirteen patients were registered with GC with the average age of 58 and a male to ‍female ratio of 3/1. Tumor stage based on AJCC was stage 2(12.5%),stage 3(22%),stage 4(63%) and 2% unknown. ‍Most common site of involvement was cardia (43%). Median survival time of all patients (with or without treatment) ‍was 10 months overall. Gastrectomy was performed for 214 patients(39% with positive surgical margins), and 175 ‍of the gastrectomised patients received chemotherapy. Median survival with surgery only was 7 months but 20 ‍months with both surgery and chemotherapy. Only 21 patients received neoadjuvant chemotherapy. Median survival ‍of patients who had response to preoperative chemotherapy was 30 months. By multivariate analysis lower extent of ‍disease (p=0.0024), free surgical margin (p=0.0017), and chemotherapy (p=0.001) were associated with better ‍prognosis. ‍Conclusions: Only curative resection with free margins was associated with a survival benefit in this study. More ‍than 80% of patients were diagnosed in locally advanced or metastatic stage of disease and even with neoadjuvant ‍chemotherapy and salvage surgery the outcome was poor. Clearly more efforts need to be given to early detection of ‍lesions to allow a better cure rate.     

Safety and efficacy of trimodality therapy in patients undergoing extrapleural pneumonectomy

Malignant pleural mesothelioma (MPM) is a rare but rapidly deadly disease (1).Macroscopic complete resection (MCR) is the goal of surgery (2).MCR seems to have the most significant impact on survival in patients undergoing multimodality treatment for MPM.The role of surgical resection in the management of MPM remains controversial.The selection criterion to perform either extrapleural pneumonectomy (EPP) or extended/radical pleurectomy/decortication (PD) rely not only on the cardio-pulmonary status of the patient,tumor stage and intraoperative findings but is strongly dependent also on surgeons' decision and philosophy.This is reflected by a recent survey of opinions and beliefs among 802 thoracic surgeons,in which EPP was believed to be more effective than PD (3).Nonetheless,either surgery might achieve MCR.     

Multicentric study on malignant pleural mesothelioma in Turkey: clinicopathologic and survival characteristics of 282 patients

Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study retrospectively evaluated the data pertinent to 282 patients who were examined and treated in 11 different medical oncology centers in Turkey. There were 161 males (57.1?%) and 121 females (42.9?%), with a mean age of 56.38?±?12.07?years. Surgery was used in 74 patients, 21 patients (28.4?%) received only chemotherapy and 28 patients (37.8?%) received chemoradiotherapy after surgery. The median survival in patients who were administered adjuvant therapy after surgery was 24?months, while the median survival in patients who had only surgery was 6?months (p?=?0.029). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. Median survival, 1- and 2-year survival rates in patients who received platinum analogues and pemetrexed or gemcitabine combinations were found statistically similar (p?=?0.15). The median survival for all patients with MPM in our study was 18?months. The main factors influencing the overall survival were stage of the disease (p?=?0.020), performance status (p?<?0.001), asbestos exposure (p?=?0.030) and mesothelioma histological subtypes (p?<?0.001). Results of our study suggest that multi-modality treatment regimens consisting of surgery, radiotherapy and chemotherapy prolong overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.     

Evaluation of the role of surgery in 25 patients with metastatic neuroblastoma

The role of surgery was evaluated using a recently proposed TNM staging system in metastatic neuroblastomas. Of twenty-five patients, twenty-four were over 1 year, 1 case was 3 months old, nine were boys, sixteen were girls, and all were stage IV using Evans-D'Angio staging system (excluding IV-s). They were retrospectively assigned a TNM clinical stage (CS) preoperatively and a pathologic stage (PS) postoperatively. All twenty-five patients were CS 4 using this TNM staging system. The role of surgery was evaluated by analyzing survival according to the postoperative PS. PS 1-2-3A were regarded as satisfactory resections, since all macroscopic tumor was removed, while PS 3B-3C-4-5 were regarded as unsatisfactory resections. With Kaplan-Meier analysis, there was a slight survival advantage when satisfactory resection of the primary tumor was achieved in the cases with any evidence of metastasis at the time of operation. However, in the cases with no evidence of metastasis at operation, there was a survival advantage when satisfactory resection of the primary tumor was done (p = 0.05). If metastatic disease is controlled prior to operation, total resection improves prognosis of metastatic neuroblastoma.     

Early postoperative intraperitoneal chemotherapy with mitomycin C, 5-fluorouracil and cisplatin for advanced gastric cancer

OBJECTIVE: The long-term survival of patients who undergo surgery for stage IV gastric cancer is poor, due to metastatic spread of the tumor. Intraperitoneal chemotherapy (IPT) as a possible treatment for peritoneal dissemination has been investigated in a number of different tumors. The aim of this study was to investigate the toxicity and impact of early postoperative IPT on the survival of patients with advanced gastric cancer. METHODS: Between 1993 and 1997, a total of 91 patients with stage IV gastric cancer who underwent potentially curative or palliative resection received intraperitoneal mitomycin C before closure of the abdominal wound. 5-Fluorouracil and cisplatin were administered intraperitoneally on postoperative days 1-4, and this was repeated at 4-week intervals. RESULTS: All patients received a median of 3 IPT perfusions. There were 24 (26.4%) postoperative complications and 1 (1.1%) mortality. The most frequent hematologic toxicity (grade 3-4) was leukopenia. The major nonhematologic toxicities (grade 3-4) were emesis and nephrotoxicity. After a median follow-up period of 26 months, 14 patients remain alive without evidence of recurrence, whereas 75 patients died due to recurrence or progression of disease. The median survival period for all 91 patients was 15.4 months. When survival according to the residual tumor was analyzed, median survival was 36.0 months in the R0 (curative resection) group, 20.6 months in the R1 group (margins of resected specimens showing microscopic residual tumor or diameter of each residual tumor less than 3 mm) and 9.0 months in the R2 group (macroscopic residual tumor larger than 3 mm) (p < 0.001). CONCLUSIONS: IPT was found to be safe, and it appears to improve the prognosis in patients with minimal residual tumors. However, complete cytoreductive surgery is mandatory for achieving the beneficial effect of IPT.     

The treatment of malignant mesothelioma of the pleura: review of a 5-year experience, with special reference to radiotherapy.

Thirty-eight patients with malignant mesothelioma of the pleura were seen at Peter MacCallum Cancer Institute between 1981 and 1985. In 35 patients presenting with disease confined to one hemithorax, the following treatments were given: radical surgery, 13 patients: radical radiotherapy, 12 patients; palliative radiotherapy, 20 patients; chemotherapy, 9 patients; observation only, 2 patients. Median survival from time of diagnosis for all 38 patients was 9 months, with an estimated 2-year survival rate of 16%. Treatment did not significantly affect survival, although there was an indication that patients having radical surgery did better (median survival 17 months) than those who did not (median survival 9 months) (p = 0.13). Fifteen patients were given radiotherapy with radical intent but only 12 completed treatment (50 Gy). The median survival of the 12 patients completing radiotherapy was 17 months, with an estimated 2-year survival rate of 17%. Two patient deaths were attributable to radical radiotherapy (one radiation hepatitis, one radiation myelopathy). Twenty-one patients received 31 courses of palliative radiotherapy for various symptoms, predominantly pain. The results were assessable for 26 courses, with 17 (65%) being at least partly successful. In conclusion, radiotherapy appears to be ineffective in prolonging survival in malignant mesothelioma of the pleura, but has a useful role in palliation.     

Malignant pleural mesothelioma

Opinion statement Despite innumerable trials of surgery, radiotherapy, and countless chemotherapeutic drugs, it is unclear whether any intervention has had a significant impact on more than a few highly selected patients with malignant pleural mesothelioma. Because most patients die of respiratory failure from extensive disease progression in the thorax, treatment usually includes attempts at local control. Unfortunately, radiotherapy is associated with significant complications in pleural mesothelioma, and surgery is feasible in only a small percentage of patients. Although there have been several single-institution reports of combined-modality therapy with extrapleural pneumonectomy, postoperative radiation, and chemotherapy in which prolonged survival has been observed, most patients with malignant pleural mesothelioma have locally advanced disease, advanced age, or comorbid medical illnesses that preclude aggressive surgery. Therefore, the use of a systemic anticancer agent is the only treatment option for most patients with malignant pleural mesothelioma. Evaluation of effective chemotherapy regimens for this disease has been hampered by many factors. Because mesothelioma is an uncommon malignancy, most studies have enrolled small numbers of patients, and few trials have been randomized. The disease is heterogenous, yet until recently there was no single staging system that could reliably predict survival, nor is there a universally accepted set of prognostic criteria for selecting a uniform group of patients. Response assessment has been limited by the inherent difficulties of reproducibly measuring pleural-based disease. The real impact of systemic chemotherapy on the natural history of malignant mesothelioma is still uncertain because phase III trials comparing chemotherapy with best supportive care have not yet been completed. Although nearly every class of cytotoxic agent has been evaluated in mesothelioma, response rates of greater than 20% have not been consistently demonstrated for any drug. The most active drug classes are the antifolates, the anthracyclines, and the platinums. Doxorubicin has historically been considered the gold-standard chemotherapy, although its true response rate is likely only 15%. The most active commercially available drug for mesothelioma so far appears to be gemcitabine. Although gemcitabine has a limited role as a single agent, it is quite active in combination with a platinating agent. The impressive 48% response rate reported for the combination of gemcitabine with cisplatin in a single phase II study has made this regimen the new standard of care for off-protocol treatment of this disease, although this trial still requires validation. With the recent introduction of several new agents with definite activity in this disease, the therapeutic nihilism previously associated with malignant pleural mesothelioma is gradually being replaced by a cautious optimism. Early trials of angiogenesis inhibitors, gene therapy, and vaccines offer additional avenues for treatment. As we begin to incorporate these active new drugs with each other and in adjuvant and neoadjuvant treatment regimens, there is reason to believe that superior results for patients with malignant pleural mesothelioma can be achieved in the near future.