Fractures among long‐term survivors of childhood cancer

BACKGROUND:

Although reductions in bone mineral density are well documented among children during treatment for cancer and among childhood cancer survivors, little is known about the long‐term risk of fracture. The objective of this study was to ascertain the prevalence of and risk factors for fractures among individuals participating in the Childhood Cancer Survivor Study (CCSS).

METHODS:

Analyses included 7414 ≥5‐year survivors of childhood cancer diagnosed between 1970 and 1986 who completed the 2007 CCSS follow‐up questionnaire and a comparison group of 2374 siblings. Generalized linear models stratified by sex were used to compare the prevalence of reported fractures between survivors and siblings.

RESULTS:

The median ages at follow‐up among survivors and siblings were 36.2 years (range, 21.2‐58.8 years) and 38.1 years (range, 18.4‐62.6 years), respectively, with a median 22.7 years of follow‐up after cancer diagnosis for survivors. Approximately 35% of survivors and 39% of siblings reported ≥1 fracture during their lifetime. The prevalence of fractures was lower among survivors than among siblings, both in males (prevalence ratio, 0.87; 95% confidence interval, 0.81‐0.94; P < .001) and females (prevalence ratio, 0.94; 95% confidence interval, 0.86‐1.04; P = .22). In multivariable analyses, increasing age at follow‐up, white race, methotrexate treatment, and balance difficulties were associated with increased prevalence of fractures among female survivors (P = .015). Among males, only smoking history and white race were associated with an increased prevalence of fracture (P < .001).

CONCLUSIONS:

Findings from this study indicated that the prevalence of fractures among adult survivors did not increase compared with that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted. Cancer 2012. © 2012 American Cancer Society.     

Health‐related quality of life in long‐term breast cancer survivors

BACKGROUND:

The Survivor's Health and Reaction (SHARE) study examined health‐related quality of life (HRQL) in breast cancer patients who had participated in Cancer and Leukemia Group B Trial 8541 from 1985 to 1991.

METHODS:

In total, 245 survivors (78% of eligible patients) who were 9.4 to 16.5 years postdiagnosis (mean, 12.5 years postdiagnosis) completed HRQL surveys relating to 5 domains. Analyses examined HRQL domains according to 3 different chemotherapy dose levels that were administered in the original treatment trial: low‐dose cyclophosphamide, doxorubicin, and fluorouracil (CAF) at 300 mg/m², 30 mg/m², and 300×2 mg/m², respectively, over 4 cycles; standard‐dose CAF at 400 mg/m², 40 mg/m², and 400×2 mg/m², respectively, over 6 cycles; and high‐dose CAF at 600 mg/m², 60 mg/m² and 600×2 mg/m², respectively, over 4 cycles.

RESULTS:

In univariate analyses, a statistically significant difference was observed on the Medical Outcomes Study 36‐item short form Physical Role Functioning subscale by treatment group, with lower mean scores in the standard treatment arm (mean, 65.05) compared with mean scores in the low‐dose arm (mean, 74.66) and the high‐dose arm (mean, 84.94; P.0001). However, multivariate analysis revealed that treatment arm no longer was statistically significant, whereas the following factors were associated with decreased physical role functioning: age ≥60 years (odds ratio [OR], 3.55; P = .006), increased comorbidity interference total score (OR, 1.64; P = .005), lower vitality (OR, 1.05; P = .0002), and increased menopausal symptoms (OR, 1.04 P = .02).

CONCLUSIONS:

At 9.4‐16.5 years after their original diagnosis, differences in physical role functioning among breast cancer survivors who had received 3 different dose levels of chemotherapy were explained by clinical and demographic variables, such as age, fatigue, menopausal symptoms, and comorbidities. Prospective studies are needed to further assess the role of these factors in explaining HRQL and physical role functioning among long‐term survivors. Cancer 2009. © 2009 American Cancer Society.     

Measuring social activities and social function in long‐term cancer survivors who received hematopoietic stem cell transplantation

Objective: Cancer survivors report deficits in social functioning even years after completing treatment. Commonly used measures of social functioning provide incomplete understanding of survivors' social behavior. This study describes social activities of survivors and evaluates the psychometric properties of the Social Activity Log (SAL) in a cohort of long‐term survivors of hematopoietic stem cell transplantation (HSCT) for cancer. Methods: One hundred and two (5–20 year) survivors completed the SAL, Short‐Form‐36 Health Survey (SF‐36), and other patient‐reported outcomes. Principal components analysis determined the factor structure of the SAL along with correlations and regressions to establish validity. Results: Principal component analysis yielded three factors in the SAL: ‘non‐contact events’ (e.g. telephone calls), ‘regular events’ (e.g. played cards), and ‘special events’ (e.g. concerts), which explained 59% of the total variance. The SAL possessed good internal consistency (Cronbach's α=0.82). SF‐36 social function and SAL were moderately correlated (r=0.31). In linear regressions, physical function and depression explained 16% of the variance in the SAL (P<0.001), while physical function, depression, and fatigue predicted 55% of the variance in SF‐36 social function (P<0.001). Conclusions: Results support the use of the SAL as a measure of social activity in cancer survivors who received HSCT. Although the SAL is designed to measure social behaviors, SF‐36 social function assesses subjective experience and is more strongly associated with depression and fatigue. The SAL appears to be a promising tool to understand the behavioral social deficits reported by long‐term survivors of cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Prospective assessment of quality of life in long‐term ovarian cancer survivors

The objective of our study was to compare prospectively the QoL in long‐term ovarian cancer survivors with short‐term survivors and to explore discriminating variables between short‐term and long‐term survival. Thirty‐three patients were included, 22 died within 5 years post diagnosis and 11 survived beyond 10 years. QoL data were collected pre‐treatment (baseline), 1‐year post diagnoses and for long‐term survivors 10 years post‐treatment using the EORTC QLQ‐C30. At baseline, there was no difference in terms of FIGO stage, residual tumor and adjuvant chemotherapy. Significantly, more short‐term survivors (96%) had intra operative ascites as compared to long‐term survivors (55%) (p=0.01). Before treatment, short‐term survivors had clinically significantly lower QoL scores on the physical functioning (mean 75.45) and role functioning scale (mean 68.94) compared to long‐term survivors (mean 68.94 and 84.85, respectively). They also reported higher levels of symptoms. One year post‐diagnosis, QoL scores were comparable in most domains. Long‐term survivors had a significantly better global QoL but more insomnia. Emotional functioning and global QoL/health status improved significantly from baseline to 1‐year post‐diagnosis and remained relatively stable at the 10‐year follow‐up. The presence of intra operative ascites and a supporting social network were identified as significant variables that discriminated between short‐term and long‐term survival. Compared to a reference sample, long‐term survivors showed similar QoL scores but more dyspnoea. Although ovarian cancer patients do not belong to the most prevalent survivor populations, we found that long‐term survivors have QoL scores similar to females without a history of cancer.     

Fear of recurrence in long-term testicular cancer survivors

Objective: To explore fear of recurrence (FoR) in long‐term testicular cancer survivors (TCSs) since FoR hardly has been examined in TCSs. Methods: In a cross‐sectional questionnaire study, 1336 TCSs at a mean of 11.4 years (SD 4.2) after diagnosis gave information about their medical and social situation, and completed measures on mental distress, fatigue, quality of life, coping, self‐esteem and neuroticism. FoR during the last week was explored with one question, with the response categories rated on a 4‐point Likert scale. Nine percent of the TCSs had a structured psychiatric interview. Results: Twenty‐four percent of the TCSs reported ‘quite a bit’ FoR and 7% reported ‘very much’ FoR during the last week. The FoR question showed moderate correlations (0.22–0.51) with established psychological measures. The level of FoR was significantly positively correlated with mental distress, fatigue and neuroticism and significantly negatively correlated with quality of life, self‐esteem and coping. In univariate analyses, neurotoxic side effects and somatic symptoms, but not treatment modality, were significantly associated with level of FoR. In a multivariate analysis, a medium educational level, increasing levels of traumatic cancer‐related stress symptoms and of neuroticism were significantly associated with rising FoR. Among those who had a psychiatric interview, the presence of at least one current mental disorder was significantly associated with FoR. Conclusions: High levels of FoR in long‐term TCSs are not uncommon. Levels of mental and somatic problems are associated with the levels of FoR. Clinical consequences of these findings for TCSs are discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

Fertility, gonadal and sexual function in survivors of testicular cancer

Modern treatments cure most testicular cancer patients, so an important goal is to minimise toxicity. Fertility and sexual functioning are key issues for patients. We have evaluated these outcomes in a cross-sectional study of long-term survivors of testicular cancer. In total, 680 patients treated between 1982 and 1992 completed the EORTC Qly-C-30(qc30) questionnaire, the associated testicular cancer specific module and a general health and fertility questionnaire. Patients have been subdivided according to treatment received: orchidectomy either alone (surveillance, S n = 169), with chemotherapy (C, n = 272), radiotherapy (R, n = 158), or both chemotherapy and radiotherapy (C/RT n = 81). In the surveillance group, 6% of patients had an elevated LH, 41% an elevated FSH and 11% a low (< 10 nmol l(-1)) testosterone. Hormonal function deteriorated with additional treatment, but the effect in general was small. Low testosterone was more common in the C/RT group (37% P = 0.006), FSH abnormalities were more common after chemotherapy (C 49%, C/RT 71% both P < 0.005) and LH abnormalities after radiotherapy (11% P < 0.01) and chemotherapy (10%, P < 0.001). Baseline hormone data were available for 367 patients. After treatment, compared to baseline, patients receiving chemotherapy had significantly greater elevations of FSH (median rise of 6 (IQR 3-9.25) iu l(-1) compared to 3 (IQR 1-5) iu l(-1) for S; P < 0.001) and a fall (compared to a rise in the surveillance group) in median testosterone levels (-2 (IQR -8.0 to -1.5) vs 1.0. (IQR -4.0-4.0) P < 0.001). Patients with low testosterone (but not elevated FSH) had lower quality of life scores related to sexual functioning on the testicular cancer specific module and lower physical, social and role functioning on the EORTC Qly C-30. Patients with a low testosterone also had higher body mass index and blood pressure. Treatment was associated with reduction in sexual activity and patients receiving chemotherapy had more concerns about fathering children. In total, 207 (30%) patients reported attempting conception of whom 159 (77%) were successful and a further 10 patients were successful after infertility treatment with an overall success rate of 82%. There was a lower overall success rate after chemotherapy (C 71%; CRT 67% compared to S 85% (P = 0.028)). Elevated FSH levels were associated with reduced fertility (normal FSH 91% vs elevated 68% P < 0.001). In summary, gonadal dysfunction is common in patients with a history of testicular cancer even when managed by orchidectomy alone. Treatment with chemotherapy in particular can result in additional impairment. Gonadal dysfunction reduces quality of life and has an adverse effect on patient health. Most patients retain their fertility, but the risk of infertility is likely to be increased by chemotherapy. Screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors.     

Long‐term neurologic and peripheral vascular toxicity after chemotherapy treatment of testicular cancer

BACKGROUND:

Testicular cancer is curable in the majority of men, and persisting treatment toxicity is a concern. The authors report a cross‐sectional study of the long‐term effects of chemotherapy (C) on neurologic function and development of Raynaud phenomenon.

METHODS:

Seven hundred thirty‐nine patients who were treated between 1982 and 1992 gave consent to enter the study. Patients were classified according to the receipt of C (n = 384) or no C (n = 355). Patients completed a general health questionnaire and a quality‐of‐life form (the European Organization for Research and Treatment of Cancer Quality‐of‐Life C30 questionnaire with testicular module). Symptom scores of 3 or 4 were considered clinically significant. Patients were assessed in the clinic, and clinical history was used to diagnose Raynaud phenomenon (RP) and tinnitus. Examinations included peripheral nerve function testing for light touch and vibration sense. Five hundred seventy‐seven patients underwent audiometry.

RESULTS:

On physician assessment, peripheral neuropathy and RP were more common after C (21.7% vs 9.1% [P<.001] and 20.3% vs 1.7% [P<.001], respectively). Similar results were obtained for symptom scores (12.5% vs 5.5% [P = .002] and 9.7% vs 3.7% [P<.001], respectively). On multivariate analysis, for peripheral neuropathy, the significant predictors were cisplatin dose, carboplatin dose, and age. For RP, the significant predictor was bleomycin. Significant differences in hearing thresholds were noted at 8000 hertz only and, on multivariate analysis, were related to age, cisplatin dose, and vincristine dose. Auditory symptom scores did not differ between groups.

CONCLUSIONS:

With long‐term follow‐up, peripheral neuropathy and RP remained detectable in approximately 20% of patients and caused significant symptoms in 10% of patients. Detectable effects on high frequency remained but caused little symptomatic problem. These effects persisted and were related to the cumulative chemotherapy dose. Cancer 2010. © 2010 American Cancer Society.     

Comparison of lasting life changes after cancer and BMT: perspectives of long‐term survivors and spouses

Objective: This qualitative follow up of long‐term (>5 years) cancer survivor and spouse participants from a large, previous study of quality of life after blood and marrow transplantation (BMT) was designed to gain a deeper understanding of lasting life changes they experienced. Methods: Thirty spouse–survivor pairs, an average of 13 years post‐BMT, were individually interviewed to identify lasting life changes. Participants were asked about their most significant long‐lasting change since cancer/BMT, most significant positive change and negative change, and whether the experience had affected them and their spouse differently. Results: Spouses and survivors spontaneously identified both positive and negative changes. Spouses reported a higher proportion of negative changes (24%) than did survivors (15%), and survivors a higher proportion of positive changes (85%) than spouses (76%). For both groups, the most frequent positive change was in ‘perspective/outlook on life’ and negative change was ‘lingering health effects,’ although survivors mentioned the latter twice as often as did spouses. Spouses were more likely to talk about changes in the first‐person plural (we, us) that were largely emotional or in relation to the survivor, whereas survivors spoke of changes in the first‐person singular (I, me) that occurred to them directly and were largely physical. Conclusions: Although both spouses and survivors described similar negative and positive long‐lasting changes that continued an average of 13 years post‐BMT, they reported differences in the ways they were impacted by the experience, which was reflected in the language they used. Implications for future studies, family education, and couples‐based interventions are discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Life is precious and I'm making the best of it: coping strategies of long‐term cancer survivors

Objective: Coping strategies mediate the relationship between challenging situations and their impact on psychosocial outcomes. Many long‐term cancer survivors continue to face a range of challenges in their daily lives, yet little is known about how this population copes. The study explored the prevalence and predictors of cancer‐specific coping strategies among a heterogeneous sample of long‐term cancer survivors. Methods: A population‐based cross‐sectional sample of 863 adult cancer survivors 5–6 years post‐diagnosis completed a pen‐and‐paper survey. Cancer‐specific coping was assessed via the Mini‐Mental Adjustment to Cancer (mini‐MAC) Scale. Potential predictor variables included patient, disease and treatment characteristics and social support. Results: The most commonly used coping strategies were fatalism and fighting spirit. Of those survivors that used any of the coping strategies assessed, 53% used at least two strategies. Maladaptive coping was commonly predicted by low social support (OR=1.77 to 2.49) and being a disability pensioner, whereas having ever received chemotherapy widely predicted greater use of all types of coping. A weekly household income of over $1000 a week uniquely predicted not using any mini‐MAC coping strategies. Conclusions: Survivors continue to engage in cancer‐specific coping strategies many years after diagnosis, albeit to a lesser extent than recent survivor populations. A number of predictors were identified that can alert health workers to long‐term survivors at increased risk of maladaptive coping. Given that low social support consistently predicted maladaptive coping responses, interventions aimed at promoting positive coping responses should include strategies to increase access to social support. Copyright © 2010 John Wiley & Sons, Ltd.     

Care of long‐term cancer survivors

BACKGROUND:

Studies have shown that follow‐up care for cancer patients differs by physician specialty, and that coordination between specialists and generalists results in better care. Little is known, however, regarding which specialties of physicians provide care to long‐term cancer survivors.

METHODS:

The authors used Surveillance, Epidemiology, and End Results data from 1992 through 1997 that were linked to 1997‐2003 Medicare data to identify persons diagnosed >5 years earlier with bladder, female breast, colorectal, prostate, or uterine cancer. Physician specialties were assigned by combining Medicare data with the American Medical Association Masterfile and the Unique Physician Identification Number Registry. The percentage of long‐term survivors who visited physicians of interest was determined by analyzing Medicare outpatient claims submitted 6 to 12 years after initial diagnosis.

RESULTS:

Over the entire study period, 46% of female breast cancer survivors, 26% of colorectal cancer survivors, and 14% of prostate cancer survivors saw hematologists/oncologists. Radiation oncologists were seen by 11%, 2%, and 14% of breast, colorectal, and prostate cancer survivors, respectively. Survivors also sought care from specialists related to their cancer: 19% of breast cancer survivors had a cancer‐coded visit with a surgeon, 26% of colorectal cancer survivors visited a gastroenterologist, and 68% of prostate cancer survivors visited a urologist. The percentage of survivors who visited cancer and cancer‐related physicians declined each year. In contrast, nearly 75% of female breast, colorectal, and prostate cancer survivors saw primary care providers, and these percentages did not decrease annually.

CONCLUSIONS:

The findings of the current study underscore the need to include both primary care providers and cancer‐related specialists in education and guidelines regarding cancer survivorship. Cancer 2009. © 2009 American Cancer Society.     

Health-related quality of life in long-term breast cancer survivors: nationwide survey in Denmark

Aim To investigate health-related quality of life (HRQOL) in a nationally representative sample of long-term breast cancer survivors (BCS) in Denmark. Participants and methods An age-stratified random sample of 2,000 female BCS ≥ 5 years after primary surgery without recurrence was drawn from the Danish Breast Cancer Cooperative Group register, which is representative regarding long-term BCS in Denmark, and compared with 3,104 women of the nationally representative Danish Health and Morbidity Survey 2000. The Short Form-36 questionnaire assessed HRQOL and its association with BCS’ sociodemography, type of surgery, systemic therapy, radiotherapy, time since operation, receptor status, and low/high risk protocol. Results The response rate was 79%. BCS tended to rate HRQOL better than the general female population. BCS reported significantly less “bodily pain” (P < 0.0001), better “general health” (P < 0.0001), but worse “mental health” (P < 0.0001). Age interacted significantly with four other subscales (P < 0.05): Younger BCS reported worse HRQOL than equally aged women of the general population, while older BCS reported better HRQOL. Poor HRQOL was significantly associated with being single (all subscales: P < 0.05), short education (all subscales: P < 0.05, except “social function”), and high body mass index (“physical function”, “role physical”: P < 0.05). Breast cancer (low/high risk, receptor status) and treatment did not affect HRQOL. Conclusion HRQOL was similar between BCS and women of the general population. Potential long-term effects of breast cancer (low/high risk, receptor status) and treatment did not seem to impact HRQOL. However, predictors for worse HRQOL in BCS were being single, and having a short education.