Disease Stage Groups Research Articles

Survival trends in mantle cell lymphoma in the United States over 16 years, 1992-2007.

e18530 Background: Mantle cell lymphoma is a subtype of Non-Hodgkin’s lymphoma and constitutes six percent of cases. Prognosis is poor with median overall survival approximately 3-5 years. Several new treatment protocols have emerged over the last decade. The purpose of this study is to determine if newer protocols and regimens have translated into an overall survival benefit in the United States. Methods: Retrospective cohort analysis was done using the Surveillance, Epidemiology, and End-Results (SEER) database of the national cancer institute. A total of 5367 cases of mantle cell lymphoma were identified from 1992-2007 using the SEER database. Cases were split into three different cohorts. Group 1 included all cases of mantle cell lymphoma from 1992- 1999, Group 2 included cases from 2000-2003 and Group 3 was from 2004-2007. Overall Survival was analyzed using a Cox proportional hazards model to adjust for age, gender and disease stage and summarized using ANOVA. Results: The proportion of advanced cases compared to localized has increased over the years (Fisher’s exact test p= 0.0012). In a survival model, increased age (4.6%, p< 0.001) and male sex (19.2 %, p< 0.001) were both associated with a higher mortality. Compared to the cohort from 1992-1999 (group1), mortality was reduced in 2000-2003(group 2) by 9.5% (p=0.03) and in 2004-2007 (group 3) by 14.6% (p=0.0036). Patients with localized disease had a 38.8% better survival than those with advanced disease (p < 0.001), but there was no difference between the groups in survival in patients with localized disease. For patients with advanced disease, there is a 14.1% reduction in mortality in group 2 (p=0.0064) compared to group 1. Mortality in group 3 was 22.8 % lower than group 1 (p<0.001), and 8.7% lower than group 2. Conclusions: The survival for patients with mantle cell lymphoma with advanced stage has improved in the United States over the last sixteen years. However, the overall survival remains unchanged. This is most likely due to a significant increase in the proportion of patients with poor prognostic features- advanced age, male sex and advanced stage of disease. In a survival model predicted by disease stage,age, sex and year group, a significantly better survival was noted in women.

Treatment outcomes in children with Burkitt lymphoma and L3 acute lymphoblastic leukemia treated using the lymphoma malignancy B protocol at a single institution

BackgroundWe compared the outcomes of patients with Burkitt lymphoma and French-American-British (FAB) L3 acute lymphoblastic leukemia treated using Lymphoma Malignancy B (LMB) or other treatment protocols.MethodsThirty-eight patients diagnosed between July 1996 and December 2007 were treated using LMB 96, and 22 patients diagnosed between January 1991 and May 1998 (defined as the early period) were treated using the D-COMP or CCG-106B protocols. We retrospectively reviewed their medical records and analyzed cumulative survival according to the treatment period by using Kaplan-Meier analysis.ResultsThere were no intergroup differences in the distribution of age, disease stage, or risk group. The median follow-up period of the 33 live patients in the LMB group was 72 months (range, 36-170 months). Overall survival (OS) and event-free survival (EFS) of patients treated using LMB 96 were 86.8%±5.5% and 81.6%±6.3%, respectively, whereas OS and EFS of patients treated in the early period were 72.7%±9.6% and 68.2%±9.9%, respectively. In the LMB 96 group, OS of cases showing non-complete response (N=8) was 62.5%±17.1%, and OS of relapsed or primary refractory cases (N=6) was 33.3%±19.3%. Central nervous system (CNS) disease, high lactate dehydrogenase levels at diagnosis, and treatment response were significant prognostic factors.ConclusionSurvival outcome has drastically improved over the last 2 decades with short-term, dose-intensive chemotherapy. However, CNS involvement or poor response to chemotherapy was worse prognostic factors; therefore, future studies addressing this therapeutic challenge are warranted.

Comprehensive out-patient pulmonary rehabilitation: Treatment outcomes in early and late stages of chronic obstructive pulmonary disease

BACKGROUND:The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) and to establish whether in early disease stage PR is as effective as in late stages of disease.METHODS:A total of 55 stable COPD patients, 28 with early and 27 with late disease stages, were assessed. Patients underwent a comprehensive out-patient PR program for 8 weeks. To eluciate the effects of PR and compare the level of improvement; lung function, dyspnea sensation [Medical Research Council (MRC)], body composition [body mass index (BMI), fat free mass (FFM), fat free mass index (FFMI)], exercise capacity [incremental shuttle walking test, endurance shuttle walking test], health related quality of life (HRQoL) with St. George Respiratory Disease Questionnaire, psycohological status (Hospital anxiety–depression (HAD) scale) were evaluated before and after PR.RESULTS:At the end of PR in the early disease stage group, the improvement in forced vital capacity (FVC) reached a statistically significant level (P < 0.05). In both disease stages, there were no significant differences in BMI, FFM, and FFMI. The decrease in exertional dyspnea for the two groups evaluated with the modified BORG scale were not found statistically significant, though the dyspnea scores evaluated with MRC showed significant improvements (P < 0.001). HRQoL and exercise capacity were significantly improved for the two groups (P < 0.001). Psychological status evaluated with the HAD scale improved after PR (P < 0.001) both in early and late stages. Gainings in the study parameters did not differ in the early and the late disease stages.CONCLUSIONS:These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Even patients with earlier stage of disease should be referred and encouraged to participate in a PR program.

Expression of the Retinoblastoma-related Gene Rb2/p130 in the Pathogenesis of Serous Carcinoma of the Ovary

The purpose of this study was to evaluate the immunohistochemical Rb2/p130 expression in a series of benign, borderline, and malignant ovarian tumors. Seventy-six operative specimens were analyzed. Frequencies and percents were calculated for variables by each of the 5 disease stage groups in increasing severity and again for the disease stage groups collapsed into benign (serous cystadenoma or endosalpingosis), low-grade [serous borderline tumors (SBT) or low-grade serous carcinoma (LGSC)] and high-grade serous carcinoma. There was no loss of expression in benign serous cystadenomas (0/18). Ten percent of SBT's (2/20), 47% of LGSC's (9/19), and 16% of HGSC's (3/16) had loss of expression. There was a significant difference in the expression during the progression from cystadenoma to SBT to LGSC. Loss of Rb2/p130 expression is a rare event in benign cystadenoma. The progression to LGSC is associated with a decrease in gene expression.

Quality of Life Correlates After Surgery for Laryngeal Carcinoma

To assess the correlation of operation mode, postoperative radiotherapy, and disease stage factors with the health-related quality of life (HRQL) measures after surgery for laryngeal carcinoma. Reanalysis of data of two multi-institutional cross-sectional studies. We interviewed 218 laryngectomees and 153 partial laryngectomy patients in and near Leipzig, Germany, in two cross-sectional studies, using the general and the head- and neck-specific quality of life questionnaires of the European Organization for the Research and Treatment of Cancer (EORTC QLQ-C30 and EORTC QLQ-H&N35). Multifactorial univariate and multivariate models were calculated, with laryngectomy vs. partial laryngectomy, radiotherapy (irradiated or not), and disease stage (International Union Against Cancer [UICC] stages I/II vs. III/IV) as influencing factors and the HRQL scales and items as dependent variables. Analyses were adjusted for the patient's age and the time elapsed since the operation. Laryngectomees were more affected in their sense of smell (P < or = .000). Among irradiated patients, functioning levels and many symptom scales showed worse results (P < or = .05). Both operation mode and postoperative radiotherapy were independently associated with head- and neck-specific HRQL in multivariate analysis. Differences between disease stage groups, however, were not significant. Patient's age was an influencing factor on HRQL, but time since operation was not. : Postoperative radiotherapy seems to have the greatest impact on patients' HRQL independent of other clinical factors following surgery for laryngeal carcinoma. Aftercare of irradiated laryngeal carcinoma patients should focus more on the patient's quality of life.

Psychopathology in Verified Huntington’s Disease Gene Carriers

Huntington's disease is characterized by motor, cognitive, and neuropsychiatric symptoms. This study reviews original research on psychopathology in Huntington's disease that uses standardized instruments in verified gene carriers. Frequently reported neuropsychiatric symptoms are depressed mood, anxiety, irritability, and apathy, with prevalences of 33% to 76%. Obsessive-compulsive symptoms and psychosis occur less often with prevalences of 10% to 52% and 3% to 11%, respectively. Available research provides little insight into the true prevalences of psychopathology in Huntington's disease due to small sample sizes, use of different methodologies, and lack of comparison groups. Future research requires larger cohorts stratified to disease stage, consistent methodologies, and adequate comparison groups.

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes

The American Joint Committee on Cancer (AJCC) TNM classification for breast carcinoma had not been changed for 15 years, since the publication of the third edition in 1987. However, in the sixth edition, published in 2002, significant modifications were made with regard to the number of metastatic axillary lymph nodes. The authors investigated whether the sixth edition of the TNM classification provided more reliable prognostic information compared with the third edition. The records of 1230 patients who underwent surgery for invasive breast carcinoma between 1993 and 1999 were reviewed. Each patient was assigned to axillary lymph node and disease stage groups according to the 1987 and 2002 AJCC TNM classifications. Disease-free survival (DFS) curves were calculated and plotted using the Kaplan-Meier method and the two-sided log-rank test was used to compare the survival curves of the patient groups. Of the 1067 patients who were classified as having Stages II and III disease according to the 1987 classification, 411 (38.5%) were shifted to higher disease stages using the 2002 classification. Among the 1987 Stage IIA, Stage IIB, and Stage IIIA patients, the DFS rates of the patients who were shifted to higher stages of disease were significantly worse than those of the patients for whom the stage of disease was not changed. Among those patients classified as having T4anyNM0 (Stage IIIB) disease according to the 1987 classification, there was no survival difference noted between those patients with T4N0,1,2M0 disease (who formed the Stage IIIB group) and those with T4N3M0 disease (who formed the Stage IIIC group) according to the new staging system. Of the 221 patients who formed the new Stage IIIC group, 12.2% were classified as having Stage IIA disease, 42.1% as having Stage IIB disease, 38.9% as having Stage IIIA disease, and 6.8% as having Stage IIIB disease according to the 1987 classification. The survival rates of these Stage IIA, Stage IIB, and Stage IIIA patients were not found to be significantly different; however, the survival of patients in the Stage IIIB group was found to be significantly worse than the survival of the patients in the other disease stage groupings, and the patients in the Stage IIIC group were not a prognostically homogeneous group. On the basis of these results, the authors placed patients with T4anyNM0 disease in the same group (Stage IIIB). When the 2002 classification was rearranged in this manner, patients with Stage IIIC disease formed a homogeneous group; the 5-year DFS rate of patients with Stage IIIB disease was found to be significantly worse than that for patients with Stage IIIC disease (P = 0.0011). In the 2002 TNM classification for breast carcinoma, patients with T4anyNM0 disease should form a distinct stage grouping and this stage grouping (Stage IIIC) should be placed before Stage IV, and Stage IIIB disease groupings should include patients with T1,2,3N3M0 disease. In this way, the authors hope that the 2002 AJCC TNM classification, which provides more reliable prognostic information than the 1987 classification, will become more refined.

The effect of anaemia on efficacy and normal tissue toxicity following radiotherapy for locally advanced squamous cell carcinoma of the head and neck

Purpose: The aims of this analysis were to determine the effect of anaemia on loco-regional control, relapse-free survival, cause-specific survival, overall survival, and acute and late radiation therapy toxicity in patients with Stage III and IV squamous cell carcinoma of the head and neck treated with radiotherapy. Patients and methods: Between 1991 and 1998, 350 patients were randomly assigned to either conventional radiotherapy, (70 Gy in 35 fractions in 49 days) or to accelerated radiotherapy (59.4 Gy in 33 fractions in 24 days). Patients were divided into two groups according to their haemoglobin level: a normal haemoglobin group (≥13 g/dl in males, ≥12 g/dl in females) and a low haemoglobin group (<13 g/dl in males, <12 g/dl in females). The influence of anaemia on cause-specific survival and the development of confluent mucositis independent of other variables was tested using Cox proportional hazards model. Results: Of 350 patients recruited to the trial, 238 had haemoglobin measurements and were eligible for inclusion in this secondary analysis. One hundred and ninety-three were considered to have normal haemoglobin, and 45 patients were considered to be anaemic. There were significant differences between the groups in loco-regional control, relapse-free survival, cause-specific survival and overall survival, with hazards ratios of 0.56 (95% confidence interval (CI) 0.34–0.94), 0.57 (95% CI 0.35–0.92), 0.49 (95% CI 0.29–0.85) and 0.43 (95% CI 0.26–0.70) in favour of the normal haemoglobin group. Using Cox proportional hazards modelling, haemoglobin level was a significant predictor of cause-specific survival in addition to disease site, stage, and Eastern Cooperative Oncology Group status. There were no statistically significant differences between the groups in the development of acute or late reactions. Conclusion: Significant reductions in loco-regional control, disease-free survival, cause-specific survival and overall survival occur in the presence of anaemia. No significant differences in normal tissue toxicity have been identified in this analysis.

Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1–2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15–53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529–50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944–1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20– 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457–82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which incorporate a parameter for a statistically cured fraction of patients CSLN, CTCR and CACC, but because of the long follow-up range of 20–44 years, also by complete life analysis. The survival experience of those who did not die of their original cancer of the larynx was compared to the expected survival experience of a population with the same age, birth cohort and sex structure. To date it has been generally assumed for early stage disease that although for some 5–10 years after treatment the survival experience of this patient subgroup might be no different from that expected in the matched group, thereafter the death rate of this subgroup becomes lower than that of the matched group. This implies that surviving cancer patients cured of their disease tend to die of other conditions at a higher than normal rate as they become older, and therefore cancer is never totally cured. Our conclusion is that at least for cancer of the glottic larynx, the answer to the question: ‘Can cancer totally be cured?’ is ‘Yes to at least 15-years post-treatment and also probably to 25 years.’

Evaluating health-related wellbeing outcomes among outpatient adults with human immunodeficiency virus infection in the HAART era.

Quality of life (QoL) changes among 56 adult patients living with HIV/AID (PHA) were assessed following two years of care in which most had received highly active antiretroviral therapy (HAART). The sample was stratified by initial disease stage; subjects were classified 'asymptomatic' if they had no HIV-related constitutional symptoms, 'symptomatic' if they had at least one symptom, and 'AIDS' if symptomatic with a history of opportunistic infections and/or CD4 count less than 200 cells/ micro L. For the overall group, changes in mean QoL (Medical Outcomes Study Short-Form-36 [SF-36]) ratings were non-significant, irrespective of initial disease stage or prior HAART exposure. Although overall there were health status improvements over the two-year period, clinical changes were generally unrelated to changes in QoL ratings. Patients with better immunologic/virologic outcomes showed slight improvements in mean QoL ratings, while those with poorer clinical outcomes showed slight deterioration. These within-group changes over time were statistically non-significant. The corresponding between-group differences in changes in SF-36 social and psychological dimensions were significant. Statistically significant differences among the three disease stage groups on a number of subscales at baseline (Physical Function, Body Pain, Vitality, Role Limitations due to Physical Problems) became non-significant (i.e. nullified) at follow-up. Significant increases in mean number of symptoms for the asymptomatic and symptomatic groups were not associated with two-year changes in QoL ratings. Overall, wellbeing was moderately stable over the two-year follow-up period, although somewhat affected by symptom changes and immunologic/virologic outcome. The study results contrast with pre-HAART longitudinal research, in which deterioration in all areas of QoL occurred.

Using two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing adaptation to breast cancer.

The validity and reliability of two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing coping style was assessed by examining the relationship between the subscales, psychological distress, and quality of life (QOL) among Stage II and Stage IV breast cancer patients in four phases. First, MANOVAs assessed differences in coping, distress, and QOL across disease stages. Second, for each MAC factor structure, canonical correlation analyses assessed the relationship between coping styles, distress, and QOL, for each disease-stage group separately. Third, structural equation modeling (SEM) assessed the relationship among coping styles, distress, and QOL for all participants. Finally, the internal consistency of both MAC factor structures was assessed using Chronbach's alpha. The results were as follows: (1) significant differences across disease stages were found for coping styles using either the Watson or the Schwartz MAC subscales, but there were no differences in levels of distress or QOL; (2) for both MAC factor structures, coping style was found to be highly related to emotional distress and QOL, however, the strengths of the correlations between individual coping styles and distress/QOL indicators varied across disease stages; (3) SEM indicated that coping style was significantly related to distress and QOL when stage of disease was not considered, and that coping style and indicators of distress/QOL are separate, but highly correlated factors, as opposed to a single latent construct; and, (4) the Watson MAC subscales showed slightly better internal consistency than the Schwartz MAC subscales. Taken together, these findings highlight: (i) the validity of both MAC factor structures for clinical and research use with American breast cancer patients; (ii) the role of coping style as a mediator between disease stage and psychological distress and QOL; and, (iii) the need for refinement of certain Watson and Schwartz subscales.

Disease stage of chronic hepatitis C assessed by both peritoneoscopic and histologic findings and its relationship with response to interferon therapy

Background:Disease stage in patients with chronic hepatitis C was assessed by both peritoneoscopy and histology and correlated with responses to interferon therapy. Methods:The subjects were 105 patients with chronic hepatitis C treated with interferon who were classified into 28 sustained responders, 34 transient responders, and 43 nonresponders according to alanine aminotransferase normalization. The influence of various patient's characteristics on responses to interferon therapy was investigated by multivariate analysis. Results:Patients were categorized into 21 patients who exhibited a “smooth liver” on peritoneoscopy and did not demonstrate histologic bridging fibrosis (group I) and 84 patients who exhibited a “granular” or “nodular liver” on peritoneoscopy and/or had histologic bridging fibrosis (group II). Multivariate analysis showed that genotype 2a/2b ( p = .0002), low viremia ( p = .0048), and early disease stage (group I) ( p = .0290) were significant independent factors contributing to sustained response, and that early disease stage (group I) ( p = .0010) and genotype 2a/2b ( p = .0085) were those contributing to sustained or transient response. Neither peritoneoscopic nor histologic findings alone were a significant factor influencing responses to interferon therapy. Conclusion:Disease stage assessed by both peritoneoscopic and histologic findings may serve as a reliable marker for predicting responses to interferon therapy in chronic hepatitis C. (Gastrointest Endosc 1997;45:168-75.)