Paul W. Dickman

Vaginal Changes and Sexuality in Women with a History of Cervical Cancer

BACKGROUND In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known. METHODS In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function. RESULTS We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes. CONCLUSIONS Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.

Reasons for increasing trends in large for gestational age births

OBJECTIVE: To describe the magnitude of change in the proportion of term and postterm (37 completed weeks or more) large for gestational age (LGA) infants between 1992–2001 in Sweden and to examine whether time trends in prevalence of LGA births can be explained by changes in maternal risk factors. METHODS: Using the population-based Swedish Birth Register, we analyzed data from 1992 through 2001 on births of women who delivered live, singleton, term infants without malformations (N = 874,163). Unconditional logistic regression was used to model the odds of LGA birth. RESULTS: Mean birth weight and proportions of LGA births and births 4,500 g or more rose during the period 1992 to 2001. An unadjusted analysis estimated that the risk of LGA birth increased by 23% over 10 years. However, the prevalence of overweight and obesity (body mass index of 25 or greater) increased from 25% to 36%, and the prevalence of smoking decreased from 23% to 11% during the same period. After adjusting trends in all covariates simultaneously, the association between risk of LGA birth and calendar year disappeared. CONCLUSION: The increasing proportions of LGA births over time is explained by concurrent increases in maternal body mass index and decreases in maternal smoking. With the increasing prevalence of overweight among adolescents and young women, the prevalence of LGA infants and associated risks may increase over time. LEVEL OF EVIDENCE II-2

Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study

BACKGROUND Heterocyclic amines formed in cooked meat and fish are carcinogenic in animal models and form DNA adducts in human beings. We undertook a study to assess whether these substances are related to the risks of cancer in the large bowel and urinary tract. METHODS In a population-based case-control study, cases were identified from the Swedish cancer registry. Controls were randomly selected from the population register. Information on intake of various foods and nutrients was assessed by questionnaire, with photographs of foods cooked at various temperatures. We measured the content of heterocyclic amines in foods cooked under these conditions. FINDINGS Information was retrieved from 553 controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for controls and 70% for cases. The estimated daily median intake of heterocyclic amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95% CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no controls, had an estimated daily intake of heterocyclic amines above 1900 ng. INTERPRETATION Intake of heterocyclic amines, within the usual dietary range in this study population, is unlikely to increase the incidence of cancer in the colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are consistent with human carcinogenicity, but the precision was extremely low.

Patterns of Survival in Multiple Myeloma: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2003

PURPOSE To define patterns of survival among all multiple myeloma (MM) patients diagnosed in Sweden during a 30-year period. PATIENTS AND METHODS A total of 14,381 MM patients (7,643 males; 6,738 females) were diagnosed in Sweden from 1973 to 2003 (median age, 69.9 years; range 19 to 101 years). Patients were categorized into six age categories and four calendar periods (1973 to 1979, 1980 to 1986, 1987 to 1993, and 1994 to 2003). We computed relative survival ratios (RSRs) as measures of patient survival. RESULTS One-year survival improved (P < .001) over time in all age groups and RSRs were 0.73, 0.78, 0.80, and 0.82 for the four calendar periods; however, improvement in 5-year (P < .001) and 10-year (P < .001) RSR was restricted to patients younger than 70 years and younger than 60 years, respectively. For the first time, in analyses restricted to MM patients diagnosed at age younger than 60 years, we found a 29% (P < .001) reduced 10-year mortality in the last calendar period (1994 to 2003) compared with the preceding calendar period (1987 to 1993). Females with MM had a 3% (P = .024) lower excess mortality than males. CONCLUSION One-year MM survival has increased for all age groups during the last decades; 5-year and 10-year MM survival has increased in younger patients (younger than 60 to 70 years). High-dose melphalan with subsequent autologous stem-cell transplantation, thalidomide, and a continuous improvement in supportive care measures are probably the most important factors contributing to this finding. New effective agents with a more favorable toxicity profile are needed to improve survival further, particularly in the elderly.

Dietary acrylamide and cancer of the large bowel, kidney, and bladder: Absence of an association in a population-based study in Sweden

Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case–control study encompassing cases with cancer of the large bowel (N=591), bladder (N=263) and kidney (N=133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300–1200 μg kg−1) or moderate (range 30–299 μg kg−1) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied.

Interpreting trends in cancer patient survival

Data on cancer patient survival are an invaluable tool in the evaluation of therapeutic progress against cancer as well as other lethal diseases. As with all quantitative information routinely used in evidence‐based clinical management – including diagnostic tests, prognostic markers and comparisons of therapeutic interventions – data on patient survival require evaluation based on an understanding of the underlying statistical methodology, methods of data collection and classification, and, most notably, clinical and biologic insight. This article contains an introduction to the methods used for estimating cancer patient survival, including cause‐specific survival, relative survival and period analysis. The methods, and their interpretation, are illustrated through presentation of trends in incidence, mortality and patient survival for a range of different cancers. Our aim was to lay out the strengths and limitations of survival analysis as a tool in the evaluation of progress in the diagnosis and treatment of cancer.

Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study

PURPOSE The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. METHODS Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. RESULTS Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. CONCLUSION Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Feasibility of using web-based questionnaires in large population-based epidemiological studies

To date, few large web-based epidemiological studies have been performed in a population-based setting. Sweden has optimal prerequisites for web-based studies with more than 80% of the general population having access to the Internet. Our aim was to investigate (I) response rates in an epidemiological study using primarily the web as a tool for data collection and (II) whether socio-demographic patterns vary between responders to a web and a paper questionnaire. In 2003, we invited 47,859 women to complete a web questionnaire. Two reminders were sent to non-responders; in the first a random sample received a paper questionnaire and in the second the majority received a paper questionnaire. All other non-responders received web questionnaires. Differences in response rates between responders to web and paper questionnaires with regard to socio-demographic and other variables were analyzed, and estimates of the bias introduced by these differences were estimated. In total, 41% of the women responded to the web questionnaire and 31% to the paper questionnaire (overall response rate 72%). The web-, paper- and non-responders respectively did not differ significantly in age, physical activity levels, and body mass index. Women answering web or paper questionnaires had a higher level of education and income and a lower level of smoking than non-responders. The bias associated with collecting information using web questionnaires was not greater than that caused by paper questionnaires. We conclude that web-based questionnaires are a feasible tool for data collection in large population based epidemiological studies in Sweden.

Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008

PURPOSE Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. PATIENTS AND METHODS Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3173; 1796 males and 1377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. RESULTS Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. CONCLUSION This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.

Survival of Cancer Patients in Finland 1955-1994

INTRODUCTION The study of survival of cancer patients is essential for monitoring the effectiveness of cancer control. The previous monograph describing cancer patient survival in Finland was published by the Finnish Cancer Registry in 1981 and covered patients diagnosed in 1953-1974. This new supplement assesses cancer patient survival up to the year 1995. MATERIAL AND METHODS The study includes over 560000 tumours registered at the Finnish Cancer Registry with a date of diagnosis between 1955 and 1994. Patients were followed up to the end of 1995. Trends in relative survival rates are studied over four 10-year diagnostic periods from 1955 to 1994. In addition, detailed results are presented for patients diagnosed during 1985-1994, including relative survival rates tabulated by stage, sex, and age. Additional sections describe differences in cancer patient survival according to social class and region of residence and a comparison of cancer patient survival in Finland to other European countries. RESULTS Patient survival improved over time for almost all anatomical sites. The main exception is in cancer of the cervix uteri, where patient survival has decreased slightly from 1965-1974 to 1985-1994 due to the selective prevention of less aggressive tumours through cytologic screening. Very few differences in patient survival are observed between males and females. A substantial improvement in survival can be seen for childhood cancers. CONCLUSION The increasing survival rates reflect improvements that have taken place in various areas of cancer control, from health education and early diagnosis to treatment and aftercare. This study provides valuable reference information for both clinicians and health administrators, as well as a baseline for more detailed studies of patient survival for individual anatomical sites.