Long-term Survival Of Cancer Patients Research Articles

FRI0532 Effect of rheumatic diseases on long-term survival of cancer patients.

BackgroundPatients with rheumatic diseases (RD) have underlying immune dysregulation and receive long-term immunosuppressive mediations which might negatively affect the outcome of a cancer in those patients. Conversely, autoimmune cells might...

Can mouse models of cancer reliably improve clinical trial outcome?

One of the major threats humankind faces today is cancer. Incidences of neoplasia worldwide are estimated to translate to 13 million cancer deaths by 2030. Despite promising response rates through treatment modalities such as surgical resection as well as chemo- and radiation therapy in a few cancer entities, we still lack sufficient therapeutics that provide long-term survival in cancer patients, especially in patients with advanced disease. Hence, accelerated translation of highly encouraging in vitro and in vivo preclinical therapeutic findings is urgently needed to meet the demand for novel cancer drugs to combat cancer mortality successfully. Genetically engineered mouse models recapitulating characteristics of human disease have become an indispensable tool in cancer research to predict clinical outcome. This commentary highlights current benefits and limitations of developing novel mouse models of cancer to subsequently improve clinical trial outcome in humans.

Health-related quality of life supersedes other psychosocial predictors of long-term survival in cancer patients undergoing radiotherapy

Background. To investigate the prognostic value of several psychosocial factors for long-term survival in cancer patients. Material and methods. Baseline data were gathered in routine radiotherapy practice during 44 months. The analysis is based on 938 patients for whom follow-up data were available. Baseline psychosocial distress, depression, health-related quality of life (HRQOL), and life satisfaction were assessed using Questionnaire on Stress in Cancer Patients (QSC-R23), Self-Rating Depression Scale (SDS), Functional Assessment of Therapy – General (FACT-G) questionnaire, and Questions on Life Satisfaction (FLZM). Patients were followed up for 7 to 10 years. Kaplan-Meier plots and Cox proportional hazards models were used to investigate associations between sociodemographic, clinical, psychosocial factors and overall survival (OS). Results. Patients’ median survival time was 35 months (95% CI 28.9–41.1). Significant multivariate predictors of OS were age, health insurance type, Karnofsky performance status, cancer site, and cancer stage. Controlling for these variables, HRQOL was the only psychosocial predictor of survival (hazard ratio 0.988, 95% CI 0.979–0.997, p =0.009). The physical well-being and the functional well-being subscales of the FACT-G emerged as the relevant HRQOL facets predictive of survival. Conclusion. HRQOL has incremental predictive value for long-term survival in cancer patients.

Mixture cure models in credit scoring: If and when borrowers default

Mixture cure models were originally proposed in medical statistics to model long-term survival of cancer patients in terms of two distinct subpopulations – those that are cured of the event of interest and will never relapse, along with those that are uncured and are susceptible to the event. In the present paper, we introduce mixture cure models to the area of credit scoring, where, similarly to the medical setting, a large proportion of the dataset may not experience the event of interest during the loan term, i.e. default. We estimate a mixture cure model predicting (time to) default on a UK personal loan portfolio, and compare its performance to the Cox proportional hazards method and standard logistic regression. Results for credit scoring at an account level and prediction of the number of defaults at a portfolio level are presented; model performance is evaluated through cross validation on discrimination and calibration measures. Discrimination performance for all three approaches was found to be high and competitive. Calibration performance for the survival approaches was found to be superior to logistic regression for intermediate time intervals and useful for fixed 12 month time horizon estimates, reinforcing the flexibility of survival analysis as both a risk ranking tool and for providing robust estimates of probability of default over time. Furthermore, the mixture cure model’s ability to distinguish between two subpopulations can offer additional insights by estimating the parameters that determine susceptibility to default in addition to parameters that influence time to default of a borrower.

Eight primary malignancies: case report and review of literature

The incidence of multiple primary malignancies has increased over the past years secondary to the long-term survival of cancer patients due to improvements in the early detection and adequate treatment of cancer. We present a patient with eight primary malignant tumors and review the relevant literature. Our patient was a 59-year-old female with Crohn disease with an otherwise non-contributory medical history. Risk factors for multiple primary tumors were not detected in our patient. At a follow-up of 108 months from the time of diagnosis of the first malignancy, our patient was still alive. Similar long-term survival has been reported in the literature. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

Chronische Fatigue bei Krebspatienten*

Due to improvements in long-term survival in cancer patients, emphasis is increasingly placed on chronic symptoms such as cancer-related fatigue in patients after completion of cancer treatment. Fatigue prevalence in these patients ranges from 17% to 56%. However, there is a lack of complex treatments that take the multifactorial character of fatigue causation into account. Based on a needs analysis, a patient education program was developed and evaluated. The study aimed at cancer patients after completion of the cancer treatment who suffer from chronic fatigue. The self-management program FIBS consists of six modules. Information about fatigue and behavioural therapy orientated strategies and exercises are included. Patients who attended the program were highly satisfied. They were satisfied with the selected topics at an average of 84.0%, and with the conditions at 84.25%. 95.8% of the patients achieved a subjectively perceived personal benefit, on average 8.14 of 12 possible points. The overall patient education satisfaction scored 78.72%. The newly developed self-management program closes a gap in health care of cancer patients with chronic fatigue for whom there are hardly any intervention options to date. The program is characterised by target group-specific contents and methods and a high satisfaction of the patients.

Optimization of protocols for human ovarian tissue cryopreservation with sucrose, 1,2-propanediol and human serum

Chemotherapy and/or radiotherapy protocols have improved the long-term survival of cancer patients. Frequent consequences of antiblastic treatments, used to eradicate malignancies, are the partial loss of ovarian function, which in children and young women can result in permanent sterility. Ovarian tissue cryopreservation implemented before the beginning of treatment may potentially restore fertility. However, the physical effects of cryopreservation can damage oocyte survival and decrease follicular cell integrity and stromal preservation. The aim of this study was to examine the effects of different concentrations of 1,2-propanediol (PROH) and sucrose as cryoprotectants and human serum as protein support. Particular concentrations tested were 1.26, 1.5 and 1.08 mol/l PROH, 0.175, 0.2, 0.224 and 0.3 mol/l of sucrose and 20%, 30% and 40% human serum in the freezing solutions and normal or raised sucrose concentrations in the dilution solutions. Ovarian cortical slices from 13 patients, aged 5-38 years, were cryopreserved using slow freezing-rapid thawing. Tests were conducted using light and transmission electron microscopy. Cryo-damage occurred predominantly in the stromal and follicular cells. The best preservation of morphological characteristics was obtained using the freeze-thaw protocol in which concentrations of cryoprotectants were among the lowest (1.26 mol/l PROH+0.175 mol/l sucrose) with 30% human serum.

Long-term survival of cancer patients compared to heart failure and stroke: a systematic review.

BackgroundCancer, heart failure and stroke are among the most common causes of death worldwide. Investigation of the prognostic impact of each disease is important, especially for a better understanding of competing risks. Aim of this study is to provide an overview of long term survival of cancer, heart failure and stroke patients based on the results of large population- and hospital-based studies.MethodsRecords for our study were identified by searches of Medline via Pubmed. We focused on observed and relative age- and sex-adjusted 5-year survival rates for cancer in general and for the four most common malignancies in developed countries, i.e. lung, breast, prostate and colorectal cancer, as well as for heart failure and stroke.ResultsTwenty studies were identified and included for analysis. Five-year observed survival was about 43% for all cancer entities, 40-68% for stroke and 26-52% for heart failure. Five-year age and sex adjusted relative survival was 50-57% for all cancer entities, about 50% for stroke and about 62% for heart failure. In regard to the four most common malignancies in developed countries 5-year relative survival was 12-18% for lung cancer, 73-89% for breast cancer, 50-99% for prostate cancer and about 43-63% for colorectal cancer. Trend analysis revealed a survival improvement over the last decades.ConclusionsThe results indicate that long term survival and prognosis of cancer is not necessarily worse than that of heart failure and stroke. However, a comparison of the prognostic impact of the different diseases is limited, corroborating the necessity for further systematic investigation of competing risks.

From cancer patients to cancer survivors: The issue of Cardioncology – A biological perspective

Long-term survival of cancer patients can be worsened by cardiovascular morbidity and mortality due to anticancer treatments based on cardiotoxic or antiangiogenic regimens. Growing scientific evidences support a role for circulating endothelial progenitor cells (EPCs) both in cancer pathogenesis and in cardiovascular diseases. High frequency of circulating EPCs seems to play a role in cancer growth and dissemination by favouring tumor angiogenesis and estabilishment of sites of metastasis. On the other hand, high level of circulating EPCs seems to be associated with a lower risk of developing cardiovascular diseases and with improved vascular regeneration after cardiovascular damage. Here, the possibile opposing roles of circulating EPCs in cancer patients suffering from therapy related-cardiovascular diseases are discussed, under the light of the potential modulation of their levels for therapeutic purposes. This can become a relevant issue in the field of cardioncology, the discipline that deals with the managing and treatment of cancer patients suffering from concomitant cardiovascular diseases or who are exposed to an increased risk to develop therapy related-cardiovascular complications.

Abstract A229: Novel in vivo imaging of chemotherapy-induced gonadotoxicity

Abstract Introduction: Advances in cancer therapy have improved the long-term survival of cancer patients who may then face infertility and premature gonadal failure due to chemotherapy. It has been demonstrated that the chemotherapeutic agent doxorubicin (DXR) induces apoptosis in germ cells, though its role in inflicting potential gonadal failure remains obscure. We had previously shown ovarian damage in mice following DXR treatment, manifested by reduced ovarian size and weight and by apoptosis. We aimed at establishing a real-time in vivo molecular imaging platform in mice designated to evaluate chemotherapy-induced toxicity and to assess potential vascular insult in both ovaries and testes. Methods: The volume of both ovaries and testes was measured in vivo by ultrasound biomicroscopy (Vevo2100) and by high resolution MRI, over a period of one month after adminstration of 10mg/kg intraperitoneal DXR. Ovaries were imaged by ultrasound using microbubbles as a contrast agent for evaluating the effect of DXR on ovarian blood flow. Results: We have established a platform of visualizing the gonads by innovative high resolution ultrasound biomicroscopy and MRI that enabled in vivo detection of chemotherapy-induced effects in the same individuals over time. We observed a constant, significant reduction in gonadal volume, evident by both MRI and ultrasound. The ovary volume was reduced to 52% (N=10, p<0.05) of baseline values over one month. A similar trend was observed in the testes (reduced to 38% of baseline values over one month; N=6 p<0.05)). The use of bubbles as contrast media depicted a 30% reduction in ovarian blood flow already 15 min after DXR administration. Conclusions: Using high resolution, state of the art imaging modules enabled us to trace chemotherapy-induce gonadotoxicity by in vivo imaging of the same individuals throughout an extended period of time. The acute reduction of ovarian blood flow following chemotherapy treatment may suggest a role for vascular injury in inflicting ovarian damage. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A229.

Trends in Long-term Cancer Survival in Singapore: 1968-2002

The life expectancy of cancer patients has increased in recent decades due to better diagnostic and screening tools as well as better treatment modalities. Hence, it becomes increasingly important to study trends in long-term cancer patient survival in order to document that medical progress has conveyed benefit at the population level. In this paper, we assessed the long-term survival experience of all incident cancer patients in Singapore. The study population consisted of patients diagnosed with single primary invasive cancer from 1 January 1968 to 31 December 2002, and passively followed up to 31 December 2005. The data was derived from the Singapore Cancer Registry, which has been in existence since 1968. Relative survival via the period approach was used to provide a more up-to-date estimate by looking at recent cohorts of patients. Sex- and stage-specific survival was compared for each cancer. The overall age-standardised 10-year relative survival ratios for the calendar years of 1998 to 2002 were 30.5% in males and 44.2% in females. A steady improvement in overall long-term cancer survival was observed over the study period. This upward trend in survival was observed in localised tumours and cancers with a favourable prognosis such as breast, cervical and colorectal cancers. In contrast, survival of cancers with poor prognosis such as lung, liver and pancreas remained low. Although factors such as changes in diagnostic criteria could influence the trend in survival, we believed that the improvement in survival predominantly reflected real progress in cancer control in Singapore.

A Radiation-Derived Gene Expression Signature Predicts Clinical Outcome for Breast Cancer Patients

Activation of the DNA damage response pathway is a hallmark for early tumorigenesis, while loss of pathway activity is associated with disease progression. Thus we hypothesized that a gene expression signature associated with the DNA damage response may serve as a prognostic signature for outcome in cancer patients. We identified ionizing radiation-responsive transcripts in human lymphoblast cells derived from 12 individuals and used this signature to screen a panel of cancer data sets for the ability to predict long-term survival of cancer patients. We demonstrate that gene sets induced or repressed by ionizing radiation can predict clinical outcome in two independent breast cancer data sets, and we compare the radiation signature to previously described gene expression-based outcome predictors. While genes repressed in response to radiation likely represent the well-characterized proliferation signature predictive of breast cancer outcome, genes induced by radiation likely encode additional information representing other deregulated biological properties of tumors such as checkpoint or apoptotic responses.

Health-related quality of life: Return to baseline after major and minor liver resection

Assessment of quality of life (QOL) after a major operation has become increasingly pertinent to patient care and may be as important as long-term survival in cancer patients. No current study has evaluated the long-term quality-of-life effects or the time to return to baseline quality of life in oncology patients undergoing hepatic resection for cancer. Thus, the aim of our study was to evaluate that the time to return to baseline QOL after major and minor hepatectomy is similar to other major abdominal operations. A prospective study of 32 patients with malignant liver tumors completed the FACT-Hep, FACT-FHSI-8, EORTC QLQ-C30, Profile of Mood States, EORTC QLQ-Pan26, and Global Rating Scale at the time of consent, discharge, first postoperative visit, 6 weeks, 3 months, 6 months, and 12 months. Twenty-four patients underwent major (>2 segments) and 8 minor hepatectomy. Patients who underwent major hepatectomy demonstrated a significant loss in FACT-physical and functional scores at first postoperative visit and 6 weeks (P = .04) with return to baseline at 3 months. Similar nadir in all quality-of-life assessment scores were observed for POMS, EORTC QLQ-C30, FHSI-8, and certain global rating scales at 6 weeks, with a return to baseline at 3 months. For minor hepatectomy, the nadir for most quality-of-life scores occurred at the first postoperative visit with a return to baseline at 6 weeks. Patients undergoing major hepatectomy return to their baseline quality of life at 3 months with a progressive and sustained increase in physical, emotional, and global rating scale at 6 months. This study is the first one to demonstrate that major hepatectomy can be performed with short-term adverse QOL effects and long-term improvements in overall QOL.

Recent Major Progress in Long-Term Cancer Patient Survival Disclosed by Modeled Period Analysis

To disclose most recent trends in long-term cancer patient survival. We estimated trends in 5- and 10-year relative survival of cancer patients in the United States in 1998 to 2003 from the 1973 to 2003 database of the Surveillance, Epidemiology, and End Results Program using recently introduced period-analysis modeling techniques that provide the most up-to-date and precise survival estimates. Statistically significant and partly very substantial improvement in 5- and 10-year relative survival in the 1998 to 2003 period was seen for 14 of 24 of the assessed common forms of cancer, including breast and colorectal cancer. For example, by 2003, 5-year relative survival exceeded 90% for patients with breast cancer and reached levels of about two thirds for patients with colorectal cancer and kidney cancer and patients with non-Hodgkin's lymphoma. Unfortunately, 5-year relative survival remained essentially unchanged at approximately 16% for lung cancer patients, and, despite statistically significant improvement, as low as 7% for pancreatic cancer patients. Overall, improvement was most pronounced for patients with regional tumor spread and somewhat less so for patients with localized tumors, whereas hardly any improvement was achieved for patients with distant tumor spread. Our analysis discloses further major improvement in prognosis for most, but not all forms of cancer in recent years. The largest contribution to this improvement comes from improved prognosis of patients with regional tumor spread.

Fertility preservation in female cancer survivors

SummaryThe advancement of cancer therapies over the last few decades has significantly improved long-term survival of cancer patients, especially children and adolescents. As many of the therapeutic agents used are highly cytotoxic, cancer survivors have to pay the price of enduring various immediate and long-term side-effects. Unfortunately, gonadal failure and infertility are among the most common long-term side-effects, resulting in distress, lowered self-esteem and quality of life. Three modalities of fertility preservation can be offered to female patients prior to commencing their cancer treatment: embryo, oocyte and ovarian tissue cryopreservation. This paper reviews the outcomes for female patients who underwent fertility preservation in University College Hospital between 1995 and 2005, and post-therapeutic use of their frozen specimens. In addition, the effects of cytotoxic agents on fertility and ovarian function, and the range of fertility preservation available for female cancer sufferers are also discussed.

Long-term survival of cancer patients in Germany achieved by the beginning of the third millenium

Background:: Over the last decades, long-term survival rates have substantially increased for many forms of cancer. However, these improvements have often been detected with substantial delay by traditional methods of survival analyses.Patients and methods:: Using data of the population-based Saarland Cancer Registry, 5- and 10-year relative survival rates were derived for patients with 24 common forms of cancer in Saarland/Germany for the years 2000–2002 by period analysis and compared with conventional cohort estimates of 5- and 10-year relative survival rates pertaining to patients diagnosed in 1990–1992.Results:: For many forms of cancer, the 2000–2002 period survival estimates were substantially higher than the corresponding estimates for the cohorts of patients diagnosed in 1990–1992. For example, 10-year relative survival rates achieved in 2000–2002 were close to 100% for patients with testis and thyroid cancer, >85% for patients with melanomas of the skin, ∼80% for patients with endometrial cancer and prostate cancer, close to 70% for patients with breast cancer and kidney cancer, and close to 60% for patients with colon cancer and lymphomas.Conclusions:: Survival expectations of patients diagnosed with cancer at the beginning of the third millenium are substantially higher than previously available survival statistics have suggested.

Thoracotomy Is Associated With Significantly More Profound Suppression in Lymphocytes and Natural Killer Cells Than Video-Assisted Thoracic Surgery Following Major Lung Resections for Cancer

Major surgery is immunosuppressive, and this could have an impact on postoperative tumor immunosurveillance and, therefore, long-term survival in cancer patients. Video-assisted thoracic surgery (VATS) lung resection is a new alternative surgical approach to thoracotomy for patients with early lung cancer. This is a pilot study to examine the postoperative changes in leukocytes, lymphocyte subsets, B cells, T cells, and natural killer (NK) cells in non-small-cell lung cancer (NSCLC) patients undergoing lung resection with VATS versus thoracotomy approaches. Twenty-one consecutive patients with resectable primary NSCLC were assigned to VATS or thoracotomy approach over a 3-month period. Blood samples were collected preoperatively and at postoperative days (POD) 1, 3, and 7 for flow cytometry determination of total leucocytes, B cells, NK cells, lymphocytes, total T cells, and T4 and T8 cell numbers. There were no demographic differences between the two groups. Compared with the preoperative values, significantly increased total white cell numbers were detected at POD 1, 3, and 7 in all patients. At POD 1, although T8 cells and NK cells were reduced in both groups, total T cell, T4 cell, and lymphocyte numbers were significantly reduced only in the thoracotomy group. At POD 7, NK cell numbers were significantly lower in the thoracotomy group than that in the VATS group. No significant intra- or intergroup differences were seen with B cells. No significant differences in survival or disease-free survival were found between the two groups. Thus, VATS major lung resection for NSCLC is associated with less, as well as quicker recovery from, postoperative immunosuppression compared with the thoracotomy approach. The clinical relevance of better preserved cellular immunity in the early postoperative period warrants confirmation from large randomized trials.

Recent increase in cancer survival according to age: higher survival in all age groups, but widening age gradient

A major increase in long-term survival of cancer patients in the 1990s has recently been demonstrated. It is unclear, however, to what extent this increase has been shared by cancer patients at various ages. Using the 1973-2000 data base of the Surveillance, Epidemiology, and End Results programme, recent increase in 10-year relative survival of cancer patients in the US was assessed for 4 major age groups and 15 major cancer sites by comparing results of a period analysis for the 1996-2000 period with results of a cohort analysis for patients diagnosed in 1986-1990. Period estimates of 10-year relative survival for all forms of cancer combined in 1996-2000 were 66.1%, 58.8%, 56.3% and 47.1% for age groups 15-54, 55-64, 65-74 and > or = 75 years, respectively. They were 7.4%, 10.4%, 7.8% and 3.0% units higher than the respective 1986-1990 cohort estimates for these age groups. The increase in 10-year relative survival strongly varied by cancer site, but it was generally less pronounced in older than in younger patients. We conclude that long-term survival expectations of cancer patients have increased in all age groups in the 1990s. However, for most common forms of cancer, the age gradient in survival has either persisted or widened.

Up-to-date long-term survival of cancer patients: an evaluation of period analysis on Swedish Cancer Registry data

The natural development of cancers as well as the measures to fight the disease are often long processes that require decades of follow up. Available information on long-term survival will thus often appear outdated and irrelevant. A few years ago, period-survival analysis was proposed as a means to obtain more up-to-date information on long-term cancer survival. This article assesses period and conventional cohort-based survival analyses on their ability to predict future survival. Based on historical data from the nationwide Swedish Cancer Registry 5-, 10- and 15-year relative survival actually observed for patients diagnosed at one particular point in time are compared to the most recent period and cohort-based survival estimates available at that point in time. The study shows that period analysis can, in most cases, be used to provide more up-to-date long-term estimates of cancer survival. Period analysis reduces the time lag of the survival estimates by some 5–10 years for all cancers combined and especially affects the survival estimates for small intestine carcinoids, meningioma and intracranial neurinoma of the brain, non-seminoma testicular cancer, chronic lymphocytic leukaemia and Hodgkin's lymphoma.

Combining cohort and period methods for retrospective time trend analyses of long-term cancer patient survival rates.

Assessing trends in long-term cancer patient survival is an essential component of monitoring progress against cancer by cancer registries. Traditional assessment of long-term survival (‘cohort analysis’) is very useful to disclose trends in long-term survival rates of patients diagnosed many years ago, but it does not allow the disclosure of recent trends in long-term survival rates. The latter can be achieved by an alternative method of survival analysis (‘period analysis’), which has been proposed a few years ago. On the other hand, unlike cohort analysis, period analysis does not provide estimates of long-term survival rates for patients diagnosed in the early years after initiation of cancer registration. In this paper, a method of retrospective analysis of time trends in long-term survival rates is introduced, which combines the advantages of both cohort and period analysis (‘mixed analysis’). This method thereby allows for a comprehensive monitoring of trends in long-term survival over an extended time span from the earliest to the most recent years of cancer registration. The use of the method is illustrated for retrospective time trend analyses of long-term survival of cancer patients in the United States with the 1973–1999 database of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.