Factors influencing the quality of local management of ductal carcinoma in situ: a cohort study

Background

Guidelines recommend radiotherapy (rt) after breast-conserving surgery (bcs) for optimal control of ductal carcinoma in situ (dcis). The aim of the present study was to characterize the rates of rt consideration and administration, and to identify factors influencing those rates in a cohort of women diagnosed between 1998 and 2005 in Quebec.

Methods

Quebec’s medical service claims and discharge abstract database were used. Using consultation for rt as an indicator for rt consideration, odds ratios (ors) and 95% confidence intervals (cis) were estimated using a generalized estimating equations regression model.

Results

Of 4139 women analyzed (mean age: 58 years), 3435 (83%) received a consultation for rt, and 3057 of them (89%) proceeded with treatment. The rate of rt consideration increased by 7.1% over the study period, with notable differences in the various age groups. Relative to women 50–69 years of age, the ors for being considered for rt were, respectively, 0.89 (95% ci: 0.71 to 1.12), 0.71 (95% ci: 0.55 to 0.92), and 0.20 (95% ci: 0.14 to 0.31) for women younger than 50, 70–79, and 80 years of age and older. Distance to a designated breast care centre lowered the probability of rt consideration, but the presence of comorbidities did not. A surgeon’s volume of bcss increased the probability of being considered for rt by 7% for every 10 such procedures performed (or: 1.07; 95% ci: 1.04 to 1.11).

Conclusions

Consideration for rt has increased over time. However, older women (despite being in good health) and those living far from a designated breast care centre or having a low-case-volume surgeon were less likely to be considered for rt.     

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.     

Helicobacter pylori infection predicts favorable outcome in patients with gastric cancer

Background

Recent studies have suggested a controversial role of Helicobacter pylori infection in gastric cancer prognosis. The aim of the present study was to investigate the potential impact of H. pylori status on the prognosis of patients with gastric cancer in a Chinese prospective cohort.

Methods

Between 2007 and 2009, 261 patients with curatively resected gastric cancer were enrolled in the study. H. pylori status was defined by means of immunohistochemical staining in tumour and non-neoplastic tissues. Treatment prognosis was measured in terms of cancer-specific survival and disease-free survival (dfs). Univariate and multivariate Cox regression models were used to assess the association between H. pylori status and patient prognosis.

Results

Positivity for H. pylori infection was observed in 188 of the 261 patients (72.0%). In patients positive for H. pylori, mean cancer-specific survival was 55.2 months [95% confidence interval (ci): 53.4 to 56.9 months] and mean dfs was 53.9 months (95% ci: 51.8 to 56.0 months); the same survivals were, respectively, 45.1 months (95% ci: 42.2 to 47.9 months) and 43.7 months (95% ci: 40.4 to 47.0 months) in patients negative for H. pylori. In univariate analysis, positive H. pylori status was associated with better cancer-specific survival [hazard ratio (hr): 0.486; 95% ci: 0.271 to 0.870; p = 0.015] and dfs (hr: 0.540; 95% ci: 0.307 to 0.950; p = 0.033). In multivariate analysis, H. pylori was an independent prognostic factor for cancer-specific survival (hr: 0.485; 95% ci: 0.265 to 0.889; p = 0.019).

Conclusions

Our study demonstrates that positive H. pylori status is a beneficial prognostic indicator in patients with gastric cancer and might suggest possible therapeutic approaches for gastric cancer. Further research is required to better understand inflammation mechanisms and cancer progression.     

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.     

Ductal carcinoma in situ in a 25-year-old man presenting with apparent unilateral gynecomastia

Ductal carcinoma in situ (dcis) in a young man is rarely reported. Our patient, a 25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He has a strong history of cancer on both the maternal and paternal sides of his family, including breast and lung (maternal) and melanoma, colon, and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on paternal genetic testing.The patient was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gynecomastia and dcis were discovered. To date, only 4 cases of gynecomastia and dcis have been described in younger male patients. Because only 30%–50% of patients with dcis eventually develop invasive cancer in the subsequent 10–20 years, dcis prevalence in the general population may be higher than predicted. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be, and physicians must remain cautious of cancer in young men with gynecomastia.     

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.     

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.     

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.     

A comparison of the risks of in-breast recurrence after a diagnosis of dcis or early invasive breast cancer

Background

It is controversial whether ductal carcinoma in situ (dcis) is a preinvasive marker of breast cancer or if it is part of a spectrum of small cancers with malignant potential. Comparing clinical outcomes in women with invasive and noninvasive breast lesions might help to resolve the issue.

Methods

From a database of 2641 patients with breast cancer, we selected women who had been treated with breast-conserving surgery for a cancer that was 2.0 cm or less in size, node-negative, and nonpalpable. No subject received chemotherapy. Cancers were categorized as noninvasive (stage 0, n = 172) or invasive (stage 1, n = 401) based on a review of the pathology records. We compared the actuarial risks of in-breast recurrence after invasive and noninvasive breast lesions before and after adjusting for tamoxifen and radiotherapy.

Results

The 18-year cumulative risk of in-breast recurrence was 35.2% for patients with dcis and 12.8% for patients with small invasive cancers (hazard ratio: 2.4; 95% confidence interval: 1.5 to 3.8; p < 0.0003). After adjustment for radiotherapy and tamoxifen treatment, the difference was small and nonsignificant (hazard ratio: 1.4; 95% confidence interval: 0.9 to 2.4; p = 0.22).

Conclusions

For women with small, nonpalpable, node-negative breast cancers, the likelihood of experiencing an in-breast recurrence was associated with radiotherapy and with tamoxifen, but not with the presence of cancer cells invading beyond the basement membrane.     

Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: a single-centre experience

BackgroundMetastatic colorectal cancer (mcrc) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012.MethodsThis single-centre retrospective analysis estimated overall survival (os) and progression-free survival (pfs) using the Kaplan–Meier method. Multivariate analysis was used to adjust for age, sex, Eastern Cooperative Oncology Group performance status, score on the Charlson comorbidity index, dependency in activities of daily living, and exposure to 1 or more chemotherapy doublets, capecitabine alone, or best supportive care (bsc).ResultsOf 109 patients identified, 29 elected bsc, and 80 received chemotherapy. In multivariate analysis, age was not associated with os [hazard ratio (hr): 0.99; 95% confidence interval (ci): 0.92 to 1.05], but a performance status of 2 or higher was associated with a decreased likelihood of survival (hr: 3.12; 95% ci: 1.87 to 5.76), and exposure to 1 or more doublets was associated with improved survival (hr: 0.33; 95% ci: 0.17 to 0.66). In univariate analysis, a trend toward improved os was observed for first-line doublet chemotherapy compared with capecitabine (hr: 0.66; 95% ci: 0.41 to 1.07), and pfs was superior (hr: 0.46; 95% ci: 0.26 to 0.84). Compared with exposure to 1 doublet, exposure to the 3 potential cytotoxic chemotherapies was not associated with improved os (hr: 0.77; 95% ci: 0.41 to 1.43). The incidence of neutropenia with first-line folfiri was 40%; the incidences of bevacizumab-related arterial and venous thrombosis were both 8%.ConclusionsExposure to 1 or more doublet chemotherapies for mcrc was associated with better outcomes in non-trial patients 70 years of age and older. Elderly patients treated with palliative chemotherapy and bevacizumab should be monitored carefully for arterial and venous thrombotic events.     

A population-based study of ethnicity and breast cancer stage at diagnosis in Ontario

Background

Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario.

Methods

We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005–2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii–iv compared with stage i.

Results

The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii–iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii–iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82).

Conclusions

Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.     

Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell lung cancer

Purpose

Outcomes after treatment with accelerated hypofractionated radiotherapy in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were determined.

Methods

Our single-institution retrospective review looked at medically inoperable patients with T1–2N0M0 nsclc treated with accelerated hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients were staged mainly by computed tomography imaging of chest and abdomen, bone scan, and computed tomography/magnetic resonance imaging of brain. Positron-emission tomography (pet) staging was performed in 6 patients. Medical charts were reviewed to determine demographics, radiotherapy details, sites of failure, toxicity (as defined by the Common Terminology Criteria for Adverse Events, version 3.0) and vital status. The cumulative incidence of local and distant failure was calculated. Overall (os) and cause-specific (css) survival were estimated by the Kaplan–Meier method.

Result

In the 60 patients treated during the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in 20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions (n = 4). All patients were treated once daily. The median follow-up was 27 months (range: 4–94 months). The os rates at 2 and 5 years were 61% [95% confidence interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%) respectively. The cumulative incidence of local failure was 20% at 5 years. The cumulative incidence of distant failure was 28% at 5 years. No patients experienced grade 3 or greater pneumonitis or esophagitis.

Conclusions

Accelerated hypofractionated regimens are well tolerated and provide good local control in medically inoperable patients with stage i nsclc. Such regimens may be a reasonable treatment alternative when stereotactic body radiation therapy is not feasible.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone for the treatment of locally advanced nasopharyngeal carcinoma: a retrospective controlled study

Objective

We evaluated the survival benefit of providing concurrent chemoradiotherapy (ccrt) plus adjuvant chemotherapy compared with ccrt alone to patients with locally advanced nasopharyngeal carcinoma.

Methods

This retrospective study included 130 patients with nasopharyngeal carcinoma treated with ccrt plus adjuvant chemotherapy from June 2005 to December 2010. Another 130 patients treated with ccrt alone during the same period were matched on age, sex, World Health Organization histology, T stage, N stage, and technology used for radiotherapy. The endpoints included overall survival, locoregional failure-free survival, distant metastasis failure-free survival, and failure-free survival.

Results

At a mean follow-up of 42.1 months (range: 8–85 months), the observed hazard ratios for the group receiving ccrt plus adjuvant chemotherapy compared with the group receiving ccrt alone were: for overall survival, 0.77 [95% confidence interval (ci): 0.37 to 1.57]; for locoregional failure-free survival, 1.00 (95% ci: 0.37 to 2.71); for distant metastasis failure-free survival, 1.15 (95% ci: 0.56 to 2.37); and for failure-free survival, 1.26 (95% ci: 0.69 to 2.28). There were no significant differences in survival between the groups. After stratification by disease stage, ccrt plus adjuvant chemotherapy provided a borderline significant benefit for patients with N2–3 disease (hazard ratio: 0.35; 95% ci: 0.11 to 1.06; p = 0.052). Multivariate analyses indicated that only tumour stage was a prognostic factor for overall survival.

Conclusions

Patients with locally advanced nasopharyngeal carcinoma received no significant survival benefit from the addition of adjuvant chemotherapy to ccrt. However, patients with N2–3 disease might benefit from the addition of adjuvant chemotherapy to ccrt.     

Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis

Purpose

Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment.

Methods

We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines.

Results

We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43.

Conclusions

Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology.     

Genetic polymorphisms of insulin-like growth factor 1 and insulin-like growth factor binding protein 3, xenoestrogen,phytoestrogen, and premenopausal breast cancer

BackgroundPrevious studies suggest a combined effect of insulin-like growth factor 1 (igf-1) and igf binding protein 3 (igfbp-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the igf-1 signalling pathway and serum concentrations in the igf system, which are associated with premenopausal breast cancer (bca) risk.MethodsBetween 2010 and 2012, our study recruited 140 premenopausal bca patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (oc) use, dietary habits, and other bca risk factors. TaqMan assays were used to determine igf-1 rs1520220 and igfbp-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (easis) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ors) and 95% confidence intervals (cis) of the igf-1 rs1520220 and igfbp-3 rs2854744 genotypes, oc use, and intake of easis. Stratified analyses were performed to detect the gene–environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (iors) by the multiplicative model, with 95% cis. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (reri), attributable proportions of interaction (apis)] and 95% cis.ResultsThe igf-1 and igfbp-3 genotypes, oc use, and easis were not found to be associated with bca risk (p > 0.05). Stratified analysis showed that the risk of bca was markedly increased in women carrying the igfbp-3C allele and using ocs compared with women either carrying the igfbp-3C allele or using ocs (or: 3.02; 95% ci: 1.04 to 8.79). The interaction coefficients ior, reri, and api were 4.89 (95% ci: 1.09 to 21.90), 2.42 (95% ci: −0.76 to 5.61), and 0.80 (95% ci: 0.46 to 1.67) respectively.ConclusionsThe igfbp-3 rs2854744 polymorphism and oc use might synergistically increase premenopausal bca risk.     

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.     

Bortezomib in multiple myeloma: systematic review and clinical considerations

We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We searched medline, embase, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult mm patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects.Twenty-six unique studies met the inclusion criteria. For patients with previously untreated mm and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (hr): 0.48, p < 0.001; and hr: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (hr compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016).In relapsed or refractory mm, overall survival (p = 0.03), time to progression (hr: 1.82; p = 0.000004), and progression-free survival (hr: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (hr: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001).In previously untreated or in relapsed or refractory mm patients, bortezomib-based therapy has improved disease control and, in some patients, overall survival.     

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.     

Multimodality breast cancer screening in women with a familial or genetic predisposition

Background

Women with a predisposition for breast cancer require a tailored screening program for early cancer detection. We evaluated the performance of mammography (mg), ultrasonography (us), and magnetic resonance imaging (mri) screening in these women.

Patients and Methods

In asymptomatic women either confirmed as BRCA1/2 carriers, or having a greater than 30% probability of being so as estimated by brcapro [Berry D, Parmigiani G. Duke spore (Specialized Program of Research Excellence) in Breast Cancer. 1999], we conducted a prospective comparative trial consisting of annual mri and mg, and biannual us and clinical breast examination. All evaluations were done within 30 days of one another. For each screening round, imaging tests were independently interpreted by three radiologists.

Results

The study enrolled 184 women, and 387 screening rounds were performed, detecting 12 cancers (9 infiltrating, 3 in situ), for an overall cancer yield of 6.5%. At diagnosis, 7 infiltrating cancers were smaller than 2 cm (T1); only 1 woman presented with axillary nodal metastases. All tumours were negative for the human epidermal growth factor receptor 2. Of the 12 cancers, mri detected 10, and mg, 7; us did not identify any additional cancers. The overall recall rate after mri was 21.8%, as compared with 11.4% for us and 16.1% for mg. Recall rates declined with successive screening rounds. In total, 45 biopsies were performed: 21 as a result of an us abnormality; 17, because of an mri lesion; and 7, because of a mg anomaly.

Interpretation

In high-risk women, mri offers the best sensitivity for breast cancer screening. The combination of yearly mri and mg reached a negative predictive value of 100%. The recall rate is greatest with mri, but declines for all modalities with successive screening rounds.