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Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common recurrence diseases, which affects the patient's prognosis. The aim of this report is to evaluate recurrence risk after primary treatment by the combination study with the clinical features and immunohistological findings. METHODS: 153 removable HCCs were examined by immunohistochemical study of the proliferating cell nuclear antigen (PCNA), p53, or Bax. The relationships of these factors with histological grades, the presence of intra-hepatic metastasis (IM), tumor size, value of serum alpha-fetoprotein (AFP), and prognosis were studied. PCNA labeling index (LI) was calculated to count positive nuclei in 1,000 cells. RESULTS: PCNALI was significantly higher in cancer and correlated with tumor size. PCNALI and the tumor diameter in themselves could be a good predictor for patient prognosis and the combination study of them was an even stronger indicator. The value of AFP was significantly higher in positive p53 cases. The incidence of p53 was associated with histological types. The presence of IM was found in negative Bax cases of main tumors. The appearance of Bax was not correlated with histological types. The incidence of p53 or Bax was indicated to distinguish the patient prognosis of the lower grade histological cases, in which differences could not be found by the routine histological study. CONCLUSIONS: The combination study of the immunohistochemical findings and the clinical features could be one of the most important aids in interpreting the status of HCC.

Aged↗

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis.

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7 +/- 17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7 +/- 14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (> or = 44) and AgNOR count (> or = 6) had a significantly poorer prognosis than the remaining 22 (P = 0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.

Adult↗

[Morphology and prognosis of follicular thyroid cancer--a clinico-pathologic and DNA cytometric study of 95 tumors].

A retrospective study of 95 follicular thyroid carcinomas was conducted to evaluate the prognostic value of different morphological and clinical features. The biological behaviour of these tumours was primarily influenced by presence or absence of a capsule type of confinement: the frequency of lethal outcome among widely invasive carcinomas was six times higher than among encapsulated neoplasms. Furthermore, dismal prognosis could be demonstrated for tumours occurring in older patients (with a sharp break in the prognosis at the age of 52 years) and for those lesions which displayed oxyphilic metaplasia. The same effect was shown for presence of lymph node metastasis, tumour invasion of the cervical soft tissue and, for the case of encapsulated carcinomas, distant haematogenous spread. Conversely, the degree of differentiation and the patients' sex proved to have no significant influence on prognosis. In 22 carcinomas, cytophotometric and flow-cytometric determinations of DNA values were performed. These procedures revealed to have only limited diagnostic value, since for the majority of the tumours, benignancy or malignancy could not be judged from the DNA histograms. However, DNA measurements proved to contribute valuable information for the prognosis in individual cases of widely invasive follicular carcinomas. The discussion focuses on the diagnostic, therapeutic and prognostic relevance of these findings and on their impact on subclassification of follicular thyroid carcinomas.

Adenocarcinoma↗

Radiologic assessment of resectability and prognosis in esophageal carcinoma.

Utilizing double-contrast technique it is possible to detect the earliest malignant lesions of the esophagus even when the carcinoma is confined to the mucosa. In patients with carcinoma, it is also important to attempt to grade and classify the lesion in order to predict its resectability and prognosis. The resectability of a lesion is determined by the depth of invasion and by the presence or absence of lymph node metastases. The significant factors are the length of the lesion, its gross morphology, the character of its margins, and the depth of ulceration. Unfortunately, the depth of invasion is not necessarily directly related to the prognosis. In some carcinomas confined to the submucosa, lymph node metastases are already present, and these patients have a poor prognosis. The presence of lymph node metastases in early carcinoma can be suggested by the gross morphology of the lesion, its length, irregularity of the surface, and the presence of a complex lesion. Careful analysis of the radiographic features of the carcinoma can be valuable for the assessment of resectability and prognosis.

Carcinoma↗

[The prognosis of autologous tooth transplants in orthodontic treatment planning].

Autogenous tooth transplantation is an alternative treatment for preserving continuity of the dental arch following early loss of teeth. The prognosis of transplants determines the indication as compared with other methods of space closure. Transplanted buds of upper premolars as well as of lower third molars continue their root growth. The clinical and roentgenological analysis of 81 autogenously transplanted upper canines, following different operative procedures, indicates, that 50% of the transplants remain in situ for five years and only 25% remain in situ longer than six years. The statistical chances of survival of vitally transplanted, apicoectomied teeth are more favourable. Short-term prognosis is determined by inflammatory bone and/or tooth resorption due to odontogenic infection or occlusal trauma. Long-time prognosis is determined by different forms of tooth resorption. Regular radiographic examination as reveal early odontogenic infections which can then be treated endodontically. The doubtful prognosis necessitates strict indications.

Adolescent↗

Predictive role of serum procollagen III peptide and Knodell's index in survival prognosis of patients with hepatitis B virus liver cirrhosis.

OBJECTIVE: The objective of the study was to improve the accuracy of survival prognosis in patients with liver cirrhosis using procollagen III peptide (PIIIP), as a marker of inflammation and fibrogenesis, and Knodell's histologic activity index (KI) in addition to previously used prognostic factors. PATIENTS AND METHODS: Five-year survival was followed in a group of 75 patients with hepatitis B virus (HBV) liver cirrhosis (patients testing anti-HBe positive and HBV-DNA negative). There were 31 patients with compensated cirrhosis and 44 with decompensated cirrhosis. The diagnostic procedure included clinical, laboratory, ultrasound and pathohistologic examination. We combined PIIIP and KI with other significant variables to achieve the highest possible sensitivity, specificity and accuracy for survival prognosis in HBV liver cirrhosis. The models were compared using ROC analysis. RESULTS: At the end of the five-year period of survival follow-up, there were 39 survivors and 36 patients had died (only three died from an extrahepatic cause). In the quantitative model, the discriminant canonical function (DCF) identified PIIIP, bilirubin, prothrombin time, ascites and KI as statistically significant parameters in the prognosis of five-year survival. Calculation of the score based on DCF yielded an accuracy of 89.3%. In the semiquantitative model, the analysis of variance identified PIIIP, bilirubin, albumin, pro-thrombin time, alkaline phosphatase, ascites and KI as significant variables. When PIIIP was added to the clinicohistologic diagnosis, Child-Pugh score and KI, the level of accuracy improved by 12% (from 78% to 90%), 11% (from 79% to 90%) and 10.6% (from 80% to 90.6%), respectively. When calculated with the three biochemical parameters (alkaline phosphatase, PIIIP and bilirubin) and KI identified by DCF, the accuracy was 90.6%. CONCLUSION: Combining PIIIP and KI with other prognostic parameters is useful in achieving a better precision of survival prognosis in patients with HBV liver cirrhosis.

Adult↗

[Manifestations of atherosclerosis in various vascular regions. Similarities and differences regarding epidemiology, etiology and prognosis].

Pathologic studies have demonstrated that atherosclerosis involves the whole arterial vessel tree. In the Framingham study, cardiovascular risk factors could be defined with different prognostic value for the development of atherosclerosis in various vascular regions. The prognosis of patients with atherosclerosis in coronary, carotid or leg arteries is worse compared to a normal population. Moreover, patients with symptomatic lesions in one vascular bed often have additional asymptomatic atherosclerotic lesions in other vascular regions. Patients with atherosclerosis in multiple vascular regions have a worse prognosis than patients with atherosclerosis in one vascular bed only. In a study of 804 patients, we could show a significantly higher incidence of cardiovascular events (death, myocardial infarction, stroke) in patients with coronary artery disease (CAD) and additional lesions in peripheral arteries (leg, carotid) during a 3.2-year follow-up compared to those with CAD only. Local and systemic inflammatory processes in the arterial vessel wall are considered to play an important role with regard to plaque instability. It has been suggested, that besides the symptomatic atherosclerotic lesion, multiple stable or unstable lesions are present in the whole arterial vessel tree predicting the patient's prognosis. Chronic infections with multiple pathogens ("concept of infectious burden") probably play an important role by triggering these inflammatory processes. Therefore, systemic therapeutic regimes are necessary for the treatment of patients with atherosclerosis. The platelet aggregation inhibitors improve the prognosis of patients with atherosclerosis in all vascular areas. Another important therapeutic regime is the use of statins, which seem to be not only effective in lipid lowering but also in plaque stabilization.

Arterial Occlusive Diseases↗

[Prognosis of malignant melanoma following dissection regional lymph node metastases].

BACKGROUND: Malignant melanomas usually metastasize in the regional lymph nodes. This generally leads to a worsening of prognosis. Survival probability after extirpation of the tumorous regions is conditioned by various factors. Until now, the basis for differentiated therapy has been the precise understanding of the TNM classification. Clinical parameters are also relevant to therapy and of decisive importance to the further course of disease. QUESTION: Which clinical parameters are important to the prognosis of patients with regional melanoma and lymph node disease? PATIENTS AND METHODS: This study is a retrospective analysis of patients at the Clinic and Polyclinic of General Surgery of the University Hospital in Münster,Germany, together with a review of the literature. Included were 137 patients who received curative resection of lymph node metastases from malignant melanomas between 1974 and 1996. From the literature, 6,694 cases were found which allowed the establishment of 13 different prognosis parameters following lymph node metastasis resection These parameters were compared with our own results concerning established, relevant parameters. RESULTS: The cumulative 5-year survival rate for patients studied was 50.7%. The 5-year survival rates relating to characteristics varied between 12.9% and 80.0%. Of the 13 variables from the literature relevant to prognosis that were included in this analysis, four were found to be significant: Breslow penetration depth, standardized age and age at primary tumor diagnosis, recurrence, and location of the primary tumor. Considering these significant characteristics, one can arrive at a detailed prognostic classification of patient and history. This is indispensable for correctly tailoring therapy to disease stage.

Adult↗

HLA class I and class II frequencies in patients with cutaneous malignant melanoma from southeastern Spain: the role of HLA-C in disease prognosis.

Available data have led to a controversy on the relationship between human leukocyte antigen (HLA) and cutaneous malignant melanoma susceptibility or prognosis. Moreover, the influence of HLA-C on melanoma has not yet been well established. Therefore, the aim of the current study was to analyze the possible influence of the HLA system on melanoma susceptibility and prognosis in the Spanish population. For this purpose, HLA-A and HLA-B serotyping and HLA-C, HLA-DRB1, and HLA-DQB1 genotyping by polymerase chain reactions using sequence-specific oligonucleotide (PCR-SSO) and sequence-specific primer (PCR-SSP) were performed in 174 melanoma patients and 227 ethnically matched controls. The number of controls was increased up to 356 for HLA-C typing. Patients were stratified according to the histological subtypes of melanoma, sentinel lymph node status, tumor thickness, and ulceration of primary lesion. No HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 relationship with melanoma was observed for susceptibility or disease prognosis. However, the analysis of HLA-C locus showed that individuals homozygous for HLA-C(Lys80) were significantly more frequent within the patient than the control group. Remarkably, individuals homozygous for group 2 HLA-C alleles (HLA-C(Lys80)) seem to be associated with metastatic progression of melanoma. In contrast, we found a negative association between group 1 HLA-C alleles (HLA-C(Asn80)) and disease susceptibility or metastasis development. In conclusion, although an association with HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 was not demonstrated, the study of the HLA-C locus revealed that the analysis of the dimorphism at position 80 in the alpha1 helix may help to evaluate the risk and prognosis of melanoma in our population.

Case-Control Studies↗

Cytogenetic and Southern blot analysis to demonstrate clonality and to estimate prognosis in patients with myelodysplastic syndromes.

We examined the bone marrow of 109 patients with myelodysplastic syndrome (MDS) at the time of diagnosis and during the course of the disease by means of Southern blot analysis and/or cytogenetic studies to detect and evaluate clonal markers, their implications for the prognosis of the disease, and the response to treatment. The patients either were enrolled in an EORTC study and received low-dose Ara-C with (n=31) or without (n=21) growth factors, according to the study protocol, or were treated supportively (only one patient received regular chemotherapy for concomitant lymphoma). Full or at least partial remission was achieved by 34% of the treated patients (n=54). In 57% (53 of 93) of all patients a clonal marker of either kind was detected by Southern blot analysis and/or cytogenetic examination. Clonal chromosomal aberrations were found in 45% (35 of 77) of the cases examined at diagnosis, with solitary del(5q) aberrations occurring in 10% of the cases and complex aberrations in 18%, trisomy 8 or monosomy 7 being a frequent finding. Of all patients, 49% (28 of 57) were characterized by one or more gene rearrangements (e.g., Ig-JH, TcR-beta, M-bcr, GM-CSF, G-CSF, or IL-3) at diagnosis. In five of 21 cases (24%) studied in hematological remission of the disease chromosomal aberrations were still detectable, and in seven of 23 (30%) a gene rearrangement persisted. We also found six cases with multiple clones exhibiting different susceptibilities to treatment and thereby indicating the oligoclonal character of this disease. Clinical evaluation revealed that the prognosis of the respective patients was directly related to the particular clonal markers detected at diagnosis: Risk groups were subdivided according to the karyotypes, with a solitary del(5q) aberration meaning a favorable, a normal karyotype an intermediate, solitary aberrations without del(5q) a poor, and complex karyotypes a very poor prognosis. We showed that densitometry helps to increase the sensitivity of Southern blot analysis by quantifying the amount of altered DNA, which often increases shortly before or at progression of MDS. Overall, there was a high level of concordance of both clonality examinations with the clinical course of the disease and the response rate. Therefore, we recommend cytogenetic studies and Southern blot analysis to detect clonal markers at diagnosis of MDS, to detect oligoclonality and clonal evolution, or to quantify the amount of clonal DNA, which appears to be a sensitive tool for evaluating the prognosis and response to therapy in MDS.

Aged↗

[Influence of impaired fasting glucose on the incidence and prognosis of atherosclerosis in various vascular regions].

UNLABELLED: Patients with cardiovascular disease have a poorer diagnosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions. METHODS: In a prospective study we included 906 patients (72.5% men, mean age 62 +/- 9 years) preceding heart catheterization. All patients were evaluated for the presence of peripheral stenosis by carotid duplex sonography (pathologic: stenosis >50%) and evaluation of the ankle-brachial index (pathologic <0.9). Blood samples were drawn from each subject after an overnight fasting period and serum glucose was evaluated. RESULTS: Patients were compared with regard to the presence of DM (known DMor fasting glucose > or =126 mg/dL, N = 283, 31.2%) or IFG (fasting glucose >110 and <126 mg/dL, N = 89, 9.8%). Patients with IFG and DM had a higher prevalence of atherosclerotic manifestations in the coronary, carotid and peripheral vessels. Diabetics had the highest prevalence of atherosclerotic manifestations in multiple vascular regions (=advanced atherosclerosis). Cardiovascular events (death, myocardial infarction and stroke) after a median follow-up of 4.1 years were evaluated in 901 patients (99.4%). Presence of IFG and DM significantly increased the incidence of cardiovascular events (event rate: no DM 10.9%, IFG 13.6%, DM 23.4%, P < 0.0001). Moreover, patients with advanced atherosclerosis suffered significantly more often from cardiovascular events (event rate: no stenosis 4.1%, coronary artery disease without peripheral stenosis 9.7%, advanced atherosclerosis 23.9%). Prognosis was worst in patients with DM and advanced atherosclerosis with an event rate of 35%.Patients with cardiovascular disease have a poorer prognosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions.

Aged↗

Clinical characteristics and long term prognosis in early onset multiple sclerosis.

The clinical features, disease course and long term prognosis of early onset multiple sclerosis (EOMS) are variable. A preponderance of female sex, a high incidence of visual and brainstem symptoms at onset and a relapsing-remitting disease course with slower progression rate all have been considered relatively frequent in this subgroup of MS patients. Unfortunately, follow-up in previous studies has usually been limited to less than 10 years, precluding general statements on the long term evolution and prognosis in EOMS. In this retrospective study of EOMS with a substantially longer follow-up of 20.8 years, clinical characteristics, disease course and long term prognosis are described in 49 EOMS patients. In a representative subgroup of 28 patients disability was scored using Kurtzke's Functional System (FS) and Expanded Disability Status Scale (EDSS). The mean period of follow- up for these patients was 28.7 years. The present study confirms that several specific clinical characteristics can be identified in EOMS patients, such as a mainly relapsing-remitting disease onset and frequent presentation with brainstem- cerebellar dysfunction (28.6 %), pyramidal symptoms (18.4 %) and optic neuritis (14.3%). However, after a long period of follow-up the overall disease course and prognosis do not seem to differ from that in adult onset MS. By consequence a young age at onset in MS cannot be considered a favourable prognostic factor.

Adolescent↗

Prognosis of antenatally diagnosed oligohydramnios of renal origin.

Although clinical outcome data on fetuses with oligohydramnios of renal origin are scarce, prognosis is regarded as poor due to a high risk of renal dysfunction and pulmonary hypoplasia. This review aims to summarize the current knowledge and clinical experience with patients presenting antenatally with renal oligohydramnios. By reviewing the underlying mechanisms, complications, and outcome data, we hope to further improve antenatal counseling and postnatal care. We conclude that prognosis of ROH has changed in recent years. While early data before the introduction of sophisticated neonatal intensive care and renal replacement therapy indicated a poor prognosis, nowadays, a much more optimistic prognosis of children after renal oligohydramnios can be expected from the recent publications in the literature.

Female↗

Long-term prognosis of gallbladder cancer diagnosed after laparoscopic cholecystectomy.

BACKGROUND: Several clinical and laboratory studies concerning port-site recurrence have raised the concern that laparoscopic procedures might worsen the prognosis of malignant disease. However, the long-term prognosis of patients with malignancy who undergo laparoscopic surgery is still unknown. The purpose of this study was to examine the long-term prognosis of patients with unexpected gallbladder cancer diagnosed after laparoscopic cholecystectomy (LC). METHODS: A clinicopathologic study was performed on 41 patients with postoperatively diagnosed gallbladder cancer from among 5,027 patients undergoing LC at 24 institutions. The cumulative survival rate was compared with that reported for gallbladder cancer diagnosed after open cholecystectomy (OC). RESULTS: Of 26 patients with early gallbladder cancer (pTis or pT1), 23 were simply followed up, and 9 of 15 patients with advanced cancer (pT2 or pT3) had additional resection after the diagnosis of gallbladder cancer. Port-site recurrence occurred in four patients, and two of them died of the cancer. However, at this writing, the other two are still alive after abdominal wall resection or radiation therapy, having survived for 31 and 71 months, respectively. The 5-year survival rate was 92% for early cancer and 59% for advanced cancer. These results were comparable with 5-year survival rates for gallbladder cancer diagnosed after OC. CONCLUSIONS: Although port-site recurrence occurred in four patients with advanced gallbladder cancer, the long-term prognosis of patients with undiagnosed gallbladder cancer who underwent LC was not worsened by the laparoscopic procedure. We conclude that surgeons can perform LC with reasonable confidence, even if the lesion is possibly malignant.

Adenocarcinoma↗

Cytoplasmic, but not nuclear, p16 expression may signal poor prognosis in high-grade astrocytomas.

BACKGROUND: The negative consequences of the cytoplasmic localization of p16 in patients with high-grade astrocytomas, on their prognosis, was investigated. METHODS: p16 Expression was examined in 20 anaplastic astrocytoma and 42 glioblastoma patients by immunohistochemical analysis, and the relationship between both cytoplasmic and nuclear p16 expression and prognosis analyzed. RESULTS: The cytoplasmic expression of p16 statistically correlated with poor prognosis. On the other hand, no correlation was observed between p16 nuclear expression and patient survival. CONCLUSION: The cytoplasmic immunoreactivity of p16 appears to be an unfavorable prognostic indicator in high-grade astrocytoma patients. The localization of p16 expression should be determined when evaluating the prognosis of these patients.

Adolescent↗

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. PATIENTS AND METHODS: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. RESULTS: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. CONCLUSION: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

AIDS-Related Opportunistic Infections↗

Comparative accuracy of clinical tests for diagnosis and prognosis of coronary artery disease.

The discriminant accuracy of 14 variables derived from clinical evaluation, cardiac fluoroscopy, exercise electrocardiography, thallium scintigraphy and radionuclide angiography was assessed with respect to the diagnosis of angiographic coronary artery disease (CAD) among 607 patients undergoing coronary angiography, and with respect to the prognosis of subsequent cardiac death or nonfatal infarction among 4,104 patients followed for 1 year after testing. Discriminant accuracy (quantified in terms of the area under a receiver-operating characteristic curve for each variable) ranged from 50 to 73% for diagnosis, and from 54 to 77% for prognosis. Although there was a great deal of variability from test to test, variables representing direct or indirect manifestations of myocardial ischemia tended to correlate better with prognosis. Thus, variables derived from radionuclide angiography and thallium scintigraphy tended to have more prognostic accuracy than diagnostic accuracy, while fluoroscopy tended to have more diagnostic accuracy than prognostic accuracy. The pattern associated with clinical evaluation and exercise electrocardiography was less discernable. Accordingly, the accuracy of noninvasive tests with respect to diagnosis and prognosis of CAD should be separately determined based on individual empiric observation.

Adult↗

Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.

BACKGROUND: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. METHODS: Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.m-2.day-2), 5 fluorouracil (1,000 mg.m-2.day-2), and etoposide (75 mg.m-2.day-2) concurrent with accelerated fractionation radiation therapy (1.5 Gy twice a day, to a dose of 27 Gy). Induction was followed in 4 weeks by resection. Postoperatively, a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. RESULTS: Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%), and 2 patients (5%) had no residual carcinoma at operation. There were 11 postoperative complications (31%) and 4 postoperative deaths (11%). Thirteen patients (31%) are alive and disease-free, 24 (57%) have persistent disease or have recurred (15 distant, 5 locoregional, 4 both), and 9 patients are alive with disease. The median survival is 21 months and the 2-year Kaplan-Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients (p = 0.63). CONCLUSIONS: We conclude that accelerated induction therapy and resection in poor prognosis stage III non-small cell lung cancer (1) is toxic, with a 12% treatment mortality; (2) is effective with a 79% resection rate and 40% pathologic downstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IIIA patients.

Adult↗