The influence of chemotherapy-induced neurotoxicity on psychological distress and sleep disturbance in cancer patients

Purpose

In the present study, we aimed to investigate the effects of chemotherapy-induced peripheral neurotoxicity (cipn) on psychological distress and sleep quality in cancer patients.

Methods

A total of 706 cancer patients were interviewed for the study. In the 4th week of treatment, patient cipn was measured using the Patient Neurotoxicity Questionnaire (pnq). The sleep quality and psychological distress of patients were measured using the Pittsburgh Sleep Quality Index (psqi), the Distress Thermometer (dt), and the Hospital Anxiety and Depression Scale (hads). Multiple logistic regression was applied to determine the independent effects of cipn on psychological distress and sleep disturbance in the patients.

Results

These correlation coefficients were obtained: 0.387 (p < 0.0001) between the pnq total score and the dt score, 0.386 (p < 0.0001) between the pnq total score and the hads Depression score, 0.379 (p < 0.0001) between the pnq total score and the hads Anxiety score, and 0.399 (p < 0.0001) between the pnq total score and the psqi global score. The prevalence rates of distress, depression, anxiety, and poor sleep quality in the five pnq grades were statistically significantly different (p < 0.0001). After controlling for age, sex, education level, social supports, fatigue, disease stage, and tumour site, the pnq grades were found to be associated with depression (p < 0.0001), anxiety (p < 0.0001), and poor sleep quality (p < 0.0001).

Conclusions

Chemotherapy-induced peripheral neurotoxicity negatively affects psychological distress and sleep quality in cancer patients treated with chemotherapy. High pnq grades were significantly associated with poor psychological status and sleep quality. Our results emphasize the importance of assessing peripheral neuropathies during chemotherapy and of adjusting treatment plans based on assessment results.     

Factors associated with publication of randomized phase iii cancer trials in journals with a high impact factor

Background

Impact factor (if) is often used as a measure of journal quality. The purpose of the present study was to determine whether trials with positive outcomes are more likely to be published in journals with higher ifs.

Methods

We reviewed 476 randomized phase iii cancer trials published in 13 journals between 1995 and 2005. Multivariate logistic regression models were used to investigate predictors of publication in journals with high ifs (compared with low and medium ifs).

Results

A positive outcome had the strongest association with publication in high-if journals [odds ratio (or): 4.13; 95% confidence interval (ci): 2.67 to 6.37; p < 0.001]. Other associated factors were a larger sample size (or: 1.06; 95% ci: 1.02 to 1.10; p = 0.001), intention-to-treat analysis (or: 2.53; 95% ci: 1.56 to 4.10; p < 0.001), North American authors (or for European authors: 0.36; 95% ci: 0.23 to 0.58; or for international authors: 0.41; 95% ci: 0.20 to 0.82; p < 0.001), adjuvant therapy trial (or: 2.58; 95% ci: 1.61 to 4.15; p < 0.001), shorter time to publication (or: 0.84; 95% ci: 0.77 to 0.92; p < 0.001), uncommon tumour type (or: 1.39; 95% ci: 0.90 to 2.13; p = 0.012), and hematologic malignancy (or: 3.15; 95% ci: 1.41 to 7.03; p = 0.012).

Conclusions

Cancer trials with positive outcomes are more likely to be published in journals with high ifs. Readers of medical literature should be aware of this “impact factor bias,” and investigators should be encouraged to submit reports of trials of high methodologic quality to journals with high ifs regardless of study outcomes.     

Clinical manifestations in patients with alpha-fetoprotein–producing gastric cancer

Background

Patients with alpha-fetoprotein (afp)–producing gastric cancer have a high incidence of liver metastasis and poor prognosis. There is some controversy about clinical manifestations in these patients.

Methods

Our study enrolled patients who, before surgery, had gastric cancer with serum afp exceeding 20 ng/mL [afp>20 (n = 58)] and with serum afp 20 ng/mL or less [afp≤20 (n = 1236)]. Clinical manifestations were compared between the groups.

Results

Early gastric cancer was more frequent (30.1% vs. 4%) and advanced gastric cancer was less frequent (69.9% vs. 96%) in the afp≤20 group than the afp>20 group (p < 0.001). Liver and lymph node metastasis occurred less frequently in the afp≤20 group (4.4% vs. 27.6%, p < 0.001, and 60.7% vs. 91.4%, p < 0.001, respectively). The 1-, 3-, 5-, and 10-year survival rates of afp≤20 patients were 75.2%, 53.4%, 45.8%, and 34.6% respectively. The 1-, 3-, 5-, and 10-year survival rates of patients with afp greater than 20 ng/mL, but 300 ng/mL or less, were 46.7%, 28.9%, 17.8%, and 13.3% respectively. The 1-, 3-, and 5-year survival rates of patients with serum afp greater than 300 ng/mL were 15.4%, 7.7%, and 0% respectively. The independent predictors for survival time were afp concentration, age, peritoneal seeding, liver metastasis, lymph node metastasis, vascular invasion, TNM stage, curative surgery, serosal invasion, and Lauren classification.

Conclusions

Patients with high serum afp had a high frequency of liver and lymph node metastasis and very poor prognosis. More aggressive management with multimodal therapy (for example, chemotherapy, radiotherapy) might be needed when treating such patients.     

Prognostic value of pretreatment circulating neutrophils,monocytes, and lymphocytes on outcomes in lung stereotactic body radiotherapy

PurposeIn the present study, we determined the association of pretreatment circulating neutrophils, monocytes, and lymphocytes with clinical outcomes after lung stereotactic body radiotherapy (sbrt).MethodsAll patients with primary lung cancer and with a complete blood count within 3 months of lung sbrt from 2005 to 2012 were included. Overall survival (os) was calculated using the Kaplan–Meier method. Factors associated with os were investigated using univariable and multivariable Cox proportional hazards regression. Fine–Gray competing risk regression was performed to test the association of the neutrophil:lymphocyte (nlr) and monocyte:lymphocyte (mlr) ratios with two types of failure: disease-related failure and death, and death unrelated to disease.ResultsOf the 299 sbrt patients identified, 122 were eligible for analysis. The median and range of the nlr and mlr were 3.0 (0.3–22.0) and 0.4 (0.1–1.9) respectively. On multivariable analysis, sex (p = 0.02), T stage (p = 0.04), and nlr (p < 0.01) were associated with os. On multivariable analysis, T stage (p < 0.01) and mlr (p < 0.01) were associated with disease-related failure; mlr (p = 0.03), nlr (p < 0.01), and sbrt dose of 48 Gy in 4 fractions (p = 0.03) and 54 Gy or 60 Gy in 3 fractions (p = 0.02) were associated with disease-unrelated death. Median survival was 4.3 years in the nlr≤3 group (95% confidence interval: 3.5 to not reached) and 2.5 years in the nlr>3 group (95% confidence interval: 1.7 to 4.8; p < 0.01).ConclusionsIn lung sbrt patients, nlr and mlr are independently associated with os and disease-unrelated death. If validated, nlr and mlr could help to identify patients who would benefit most from sbrt.     

Risk factors for locoregional recurrence after postmastectomy radiotherapy in breast cancer patients with four or more positive axillary lymph nodes

Background

We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt).

Methods

Medical records (1998–2007) were retrospectively reviewed for the population of interest. The Kaplan–Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr.

Results

The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis–free survival (dmfs), and breast cancer–specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001).Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs.

Conclusions

In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs.     

Age at diagnosis predicts local recurrence in women treated with breast-conserving surgery and postoperative radiation therapy for ductal carcinoma in situ: a population-based outcomes analysis

Purpose

The main goal of treating ductal carcinoma in situ (dcis) is to prevent the development of invasive breast cancer. Most women are treated with breast-conserving surgery (bcs) and radiotherapy. Age at diagnosis may be a risk factor for recurrence, leading to concerns that additional treatment may be necessary for younger women. We report a population-based study of women with dcis treated with bcs and radiotherapy and an evaluation of the effect of age on local recurrence (lr).

Methods

All women diagnosed with dcis in Ontario from 1994 to 2003 were identified. Treatments and outcomes were collected through administrative databases and validated by chart review. Women treated with bcs and radiotherapy were included. Survival analyses were performed to evaluate the effect of age on outcomes.

Results

We identified 5752 cases of dcis; 1607 women received bcs and radiotherapy. The median follow-up was 10.0 years. The 10-year cumulative lr rate was 27% for women younger than 45 years, 14% for women 45–50 years, and 11% for women more than 50 years of age (p < 0.0001). The 10-year cumulative invasive lr rate was 22% for women younger than 45 years, 10% for women 45–50 years, and 7% for women more than 50 years of age (p < 0.0001). On multivariate analyses, young age (<45 years) was significantly associated with lr and invasive lr [hazard ratio (hr) for lr: 2.6; 95% confidence interval (ci): 1.9 to 3.7; p < 0.0001; hr for invasive lr: 3.0; 95% ci: 2.0 to 4.4; p < 0.0001]. An age of 45–50 years was also significantly associated with invasive lr (hr: 1.6; 95% ci: 1.0 to 2.4; p = 0.04).

Conclusions

Age at diagnosis is a strong predictor of lr in women with dcis after treatment with bcs and radiotherapy.     

Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience

Background

Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)–positive, her2-negative, T1–2, N0 disease. Our objectives were to

• □ estimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.
• □ compare the indices preferred by oncologists with the indices available to them.
• □ correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.
• □ assess interobserver variation.

Methods

All of the er-positive, her2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test.

Results

During 2007–2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%).

Conclusions

Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.     

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population

Background

Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada.

Methods

Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993–1999, 2000–2005, and 2006–2011.

Results

Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993–1999 to 2006–2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993–1999 vs. 84% in 2006–2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome.

Interpretation

The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.     

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma

Background

Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy.

Methods

In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child–Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt.

Results

Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8–8.5 cm), which decreased with tace to 5.0 cm (range: 3.3–7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival.

Conclusions

The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.     

Sensitivity and specificity of the Distress Thermometer in screening for distress in long-term nasopharyngeal cancer survivors

Background

The Distress Thermometer (dt) is a screening tool recommended to quickly identify cancer patients with distress. Our study aimed to examine the sensitivity and specificity of the dt in detecting psychological distress in long-term Chinese nasopharyngeal cancer (npc) survivors.

Methods

Data for the 442 participating npc survivors were collected through a self-administered questionnaire based on the dt and the Hospital Anxiety and Depression Scale (hads). The hads was used to define cases of psychological distress. Positive and negative groups were defined based on 4 hads criteria (Anxiety, Depression, Anxiety or Depression, and overall score). Receiver operating characteristic (roc) curves were used to examine the ability of all possible cut-off values of the dt to detect positive and negative cases. For each roc curve, the area under the curve (auc) was used as an indicator of the overall accuracy of the dt to identify positive cases of distress.

Results

The positive auc values [with 95% confidence intervals (ci)] for the 4 hads criteria were 0.715 (95% ci: 0.667 to 0.764), 0.714 (95% ci: 0.661 to 0.768), 0.724 (95% ci: 0.677 to 0.771), and 0.724 (95% ci: 0.664 to 0.775) respectively. At a cut-off score of 4, the sensitivity of the dt to the four hads criteria was, respectively, 0.366 (95% ci: 0.296 to 0.436), 0.448 (95% ci: 0.364 to 0.532), 0.362 (95% ci: 0.299 to 0.425), and 0.421 (95% ci: 0.339 to 0.502), and the specificity of the dt to the 4 hads criteria was, respectively, 0.860 (95% ci: 0.818 to 0.902), 0.860 (95% ci: 0.821 to 0.899), 0.854 (95% ci: 0.814 to 0.894), and 0.854 (95% ci: 0.814 to 0.894). At a cut-off score of 5, the corresponding sensitivities were lower than those at the cut-off score of 4. All potential cut-off scores showed poor sensitivity (<0.90).

Conclusions

The roc analysis showed poor discrimination. No potential dt cut-off score had an acceptable sensitivity. The dt showed poor sensitivity in npc survivors. Thus, the dt might not be a valid scale for psychological distress screening in long-term Chinese npc survivors.     

Weathering storms: a cohort study of how participation in a mindfulness-based stress reduction program benefits women after breast cancer treatment

Introduction

A growing number of psychosocial interventions are being offered to cancer patients during and after their medical treatment. Here, we examined whether Mindfulness-Based Stress Reduction (mbsr), a stress management course, helps women to cope better with stress and illness once their breast cancer treatment is completed. Our aim was to understand how mbsr may benefit those who participate in the course.

Methods

Our cohort study enrolled 59 women in an 8-week mbsr program. They completed “before and after” questionnaires pertaining to outcomes (stress, depression, medical symptoms) and process variables (mindfulness, coping with illness, sense of coherence). Paired t-tests examined changes from before to after the mbsr course. Changes in mindfulness were correlated with changes in post-mbsr variables, and a regression analysis examined which variables contributed to a reduction in stress after program participation.

Results

Adherence to the program was 91%. Participants reported significant reductions in stress (p < 0.0001), depression (p < 0.0001), and medical symptoms (p < 0.0001), and significant improvements in mindfulness (p < 0.0001), coping with illness (p < 0.0001), and sense of coherence (p < 0.0001). Changes in mindfulness were significantly related to changes in depression, stress, emotional coping, and sense of coherence. Increases in mindfulness and sense of coherence predicted reductions in stress.

Conclusions

It appears that learning how to be mindful is beneficial for women after their treatment for breast cancer.     

Quality of life of nasopharyngeal cancer survivors in China

Purpose

We assessed the quality of life (qol) of nasopharyngeal carcinoma (npc) survivors with a survival time of more than 2 years in Fujian, China, and we analyzed factors influencing qol.

Methods

We calculated the prevalence of psychological distress and radiotherapy (rt)–induced symptoms in 216 npc survivors who participated in a cross-sectional survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (version 3.0) was used to assess the qol of npc survivors. Multiple linear regression was applied to analyze the factors influencing qol.

Results

The prevalence rates of rt-induced symptoms and psychological problems were 11.58% (95% ci: 7.21% to 15.58%) for difficulty in swallowing, 17.59% (95% ci: 12.51% to 22.67%) for mouth dryness or sores, 13.89% (95% ci: 9.28% to 18.50%) for nasal dryness or congestion, 18.52% (95% ci: 13.34% to 23.70%) for fatigue, 11.11% (95% ci: 6.92% to 15.30%) for frequent dizziness, 18.06% (95% ci: 12.93% to 23.19%) for decline in hearing, 14.81% (95% ci: 10.07% to 19.55%) for poor sleep quality, 18.52% (95% ci: 13.34% to 23.70%) for worry about disease recurrence, 18.98% (95% ci: 13.75% to 24.21%) for anxiety, and 25.00% (95% ci: 19.23% to 30.77%) for depression. Mean survival times were 4.32 ± 2.63 years in patients with mouth dryness or sores, 4.26 ± 2.90 years in patients with fatigue, and 5.60 ± 2.94 years in patients with a decline in hearing. The mean global qol score was 74.21 (95% ci: 72.22 to 76.20). At a significance level of α = 0.05, the factors influencing qol were age (p = 0.032), education level (p = 0.001), anxiety score (p < 0.001), depression score (p < 0.001), mouth dryness or sores (p < 0.001), fatigue (p = 0.027), and disease stage (p = 0.044).

Conclusions

The prevalence rates of mouth dryness or sores, fatigue, decline in hearing, depression, and anxiety were high in npc survivors with a survival time of more than 2 years. These rt-induced symptoms and psychological problems can last for many years after rt. The qol of the npc survivors was good. Factors influencing qol were age, education level, anxiety, depression, mouth dryness or sores, fatigue, and disease stage. Our results suggest that during clinical treatment, doctors should minimize the radiation dose to the ears of patients. In addition, our results emphasize the importance of providing oral and ear nursing and psychological care to npc survivors.     

Hepcidin and ferroportin expression in breast cancer tissue and serum and their relationship with anemia

ObjectiveOur correlation study investigated the relationships of the expression of hepcidin and ferroportin (fpn) in tissues and serum from breast cancer (bca) patients and the relationships of hepcidin and fpn with anemia.MethodsWe used elisa and immunohistochemistry to detect the expression of hepcidin and fpn in tissue and serum from 62 individuals with bca, and we analyzed correlations between hepcidin and fpn expression in tissue and in serum. At the same time, we evaluated the relationships between hepcidin, fpn, and anemia.ResultsMean serum hepcidin was 8.18 ± 3.75 μg/L in bca patients with anemia and 4.53 ± 2.07μg/L in those without anemia, a statistically significant difference (t = 3.7090, p < 0.01). Mean serum fpn was obviously lower in the anemia group than in the non-anemia group (1.77 ± 0.51 μg/L vs. 2.46 ± 0.52 μg/L, t = 3.5115, p < 0.01). Serum hepcidin and hemoglobin were negatively correlated (r = −0.502, p < 0.01); however, serum fpn was positively correlated with hemoglobin, and serum hepcidin was negatively correlated with fpn. The rates of hepcidin and fpn expression in bca tissues were 50.0% and 61.2% respectively, but no association with anemia was observed. We also observed no relationship between expression of hepcidin and fpn in serum and in tissue.ConclusionsIn bca patients, expression of hepcidin in serum was high, but expression of fpn was low, suggesting that serum hepcidin plays a major role in anemia in those patients. Expression of hepcidin and fpn in bca tissue showed no correlation with their expression in serum and no clear relationship with anemia.     

One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer: analysis of outcomes and toxicity

Background

Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment.

Methods

Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed.

Results

Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001).

Conclusions

In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.     

Factors associated with breast cancer mortality after local recurrence

Purpose

We aimed to identify risk factors for mortality after local recurrence in women treated for invasive breast cancer with breast-conserving surgery.

Experimental Design

Our prospective cohort study included 267 women who were treated with breast-conserving surgery at Women’s College Hospital from 1987 to 1997 and who later developed local recurrence. Clinical information and tumour receptor status were abstracted from medical records and pathology reports. Patients were followed from the date of local recurrence until death or last follow-up. Survival analysis used a Cox proportional hazards model.

Results

Among the 267 women with a local recurrence, 97 (36.3%) died of breast cancer within 10 years (on average 2.6 years after the local recurrence). The actuarial risk of death was 46.1% at 10 years from recurrence. In a multivariable model, predictors of death included short time from diagnosis to recurrence [hazard ratio (hr) for <5 years compared with ≥10 years: 3.40; 95% confidence interval (ci): 1.04 to 11.1; p = 0.04], progesterone receptor positivity (hr: 0.35; 95% ci: 0.23 to 0.54; p < 0.001), lymph node positivity (hr: 2.1; 95% ci: 1.4 to 3.3; p = 0.001), and age at local recurrence (hr for age >45 compared with age ≤45 years: 0.61; 95% ci: 0.38 to 0.95; p = 0.03).

Conclusions

The risk of death after local recurrence varies widely. Risk factors for death after local recurrence include node positivity, progesterone receptor negativity, young age at recurrence, and short time from diagnosis to recurrence.     

Predicting the risk of cardiovascular comorbidities in adult cancer survivors

Objectives

Data on how to identify cancer survivors (css) at the greatest risk for cardiovascular conditions are limited. We aimed to characterize the clinical factors associated with ischemic heart disease (ihd) and congestive heart failure (chf) in css and to develop a stratification schema for predicting the risk of cardiovascular comorbidities in css.

Methods

Cancer survivors and non-cancer controls (nccs) were identified from the U.S. National Health and Nutrition Examination Survey. Independent factors associated with increased relative risk (rr) for cardiovascular conditions were determined. A risk stratification schema was devised that correlated risk score with the prevalence of cardiovascular comorbidities in cs.

Results

Baseline characteristics were similar for the 1869 css and 24,337 nccs included in the study. Compared with nccs, css were more likely to report ihd (13.7% vs. 5.2%), chf (7.9% vs. 2.1%), or both (4.2% vs. 1.2%; all p < 0.01). Based on multivariate analyses, risk factors for cardiovascular problems included ages 40–60 years (rr: 3.66; 95% ci: 1.87 to 7.17), 60–80 years (rr: 14.18; 95% ci: 7.65 to 26.30), and 80 years or older (rr: 25.34; 95% ci: 13.16 to 48.78); male sex (rr: 2.25; 95% ci: 1.72 to 2.94); U.S. citizenship (rr: 2.10; 95% ci: 1.08 to 4.08); annual incomes of $20,000–$45,000 (rr: 1.81; 95% ci: 1.21 to 2.70) and less than $20,000 (rr: 3.05; 95% ci: 1.81 to 5.14); comorbid diabetes mellitus (rr: 2.97; 95% ci: 2.05 to 4.32); and physical inactivity (rr: 1.98; 95% ci: 1.41 to 2.79).

Conclusions

Independent risk factors for ihd and chf in css were identified. The risk stratification schema presented here may be helpful in developing a risk-based approach to preventive cardiovascular strategies for css.     

Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study

Background

Patients with cancer are often treated with glucocorticoids (gcs) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting.

Methods

Adult patients taking gc as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with random glucometer measurements taken at least 3 hours after the last dose gcs.

Results

We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25–82 years); mean body mass index (bmi): 26.4 kg/m² (range: 15.8–45.3 kg/m²)] receiving gc as part of cancer treatment. Mean total daily gc dose in the group was 238.5 mg (range: 30–1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (dm)–range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3–20 hours). Presence of hyperglycemia did not correlate with traditional dm risk factors such as age, sex, bmi, and personal or family history of dm. A longer interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups.

Conclusions

Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for dm. We recommend that all cancer patients receiving gc be screened for hyperglycemia at least 4–6 hours after gc administration.     

Axillary lymph node status,adjusted for pathologic complete response in breast and axilla after neoadjuvant chemotherapy,predicts differential disease-free survival in breast cancer

Background

Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pcr) information into axillary lymph node restaging after neoadjuvant chemotherapy (nac) adds significance to its prognostic values.

Methods

Patients included in the analysis had stage ii or iii disease, with post-nac axillary lymph node dissection (alnd), without sentinel lymph node biopsy before completion of nac, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pcr in both breast and axilla into ypN0(pcr) and ypN0(non-pcr). Univariate and multivariate survival analyses were performed.

Results

Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (hr+) and negative for the human epidermal growth factor receptor (her2–), 101 had tumours that were positive for her2 (her2+), and 55 had tumours that were triple-negative. The rate of pcr in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pcr patients, the pcr patients had better disease-free survival (dfs) and overall survival (os): p = 0.002 for dfs and p = 0.011 for os. In non-pcr patients, dfs and os were similar in the ypN0(non-pcr) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pcr) (n = 75), ypN0– 1(non-pcr) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year dfs was 98%, 91%, and 56%, and the 3-year os was 100%, 91%, and 82% respectively. The differences in dfs and os between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pcr were the only two independent factors predicting dfs.

Conclusions

Axillary lymph node status after nac, adjusted for pcr in breast and axilla, predicts differential dfs in patients without prior sentinel lymph node biopsy.     

Genitourinary small-cell carcinoma: a single-institution experience

Background

Small-cell carcinomas (sccs) of the genitourinary (gu) tract are rare systemic diseases, and there is no standard treatment strategy for patients with this malignancy. The objectives of the present study were to report the management and outcome of patients with scc of the gu tract treated at a tertiary-care institution from 1982 to 2009.

Methods

In a chart review of all patients diagnosed with scc of the gu tract between 1982 and 2009, data on demographics, clinical and pathologic characteristics, treatment, and patient outcomes were collected.

Results

The 58 patients identified had scc in the following primary sites: urinary bladder (n = 35), prostate (n = 17), and upper urinary tract (n = 6). In 38 patients (66%), the scc was of pure histology; in the remainder, histology was mixed. Overall, 28 patients had limited-stage disease; 24 had extensive-stage disease; and staging was unknown in 6 patients. Median survival for the entire cohort was 7.5 months, with extensive-stage disease being identified as a poor prognostic factor (survival was 22.0 months for limited-stage patients and 4.1 months for extensive-stage patients, p < 0.001). Based on site, prostate patients fared worst, with a median survival of only 5.1 months. Compared with best supportive care, treatment was associated with better outcomes (median survival: 12.3 months vs. 2.3 months, p < 0.0001).

Conclusions

Small-cell cancer of the gu tract is an aggressive cancer, with a poor prognosis overall. Although there is no standard of care, patients should be treated using a multimodality approach analogous to that used in the treatment of small-cell lung cancer.     

Irradiation after surgery for breast cancer patients with primary tumours and one to three positive axillary lymph nodes: yes or no?

Objective and Methods

We retrospectively analyzed clinicopathologic features and survival in breast cancer patients who had T1 or T2 primary tumours and 1–3 histologically involved axillary lymph nodes and who were treated with modified radical mastectomy without adjuvant radiotherapy (rt). We also explored prognosis to find the high- and low-risk groups.

Results

From May 2001 to April 2005, 368 patients treated at Tianjin Tumor Hospital met the study criteria. The 5- and 8-year rates were 7.2% and 10.7% for locoregional recurrence (lrr), 85.1% and 77.7% for disease-free survival (dfs), and 92.8% and 89.3% for overall survival (os). Multivariate Cox regression analysis showed that age, tumour size, estrogen receptor (er) status, and lymphovascular invasion (lvi) were independent prognostic factors for lrr and dfs. Based on 4 patient-related factors that indicate poor prognosis (age < 40 years, tumour > 3 cm, er negativity, and lvi), the high-risk group (patients with 3 or 4 factors, accounting for 12.5% of the cohort) had 5- and 8-year rates of 24.3% and 36.9% for lrr, 57.2% and 39.2% for dfs, and 74.8% and 43.8% for os compared with 5.0% and 7.1% for lrr, 88.9% and 83.1% for dfs, 91.6% and 83.4% for os in the low-risk group (patients with 0–2 factors, accounting for 87.5% of the cohort; p < 0.001).

Conclusions

Our study identified several risk factors that correlated independently with a greater incidence of lrr and distant metastasis in patients with T1 and T2 breast cancer and 1–3 positive nodes. Patients with 0–2 risk factors may not be likely to benefit from post-mastectomy rt, but patients with 3–4 risk factors may need rt to optimize locoregional control and improve survival.