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.     

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.     

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.     

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.     

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.     

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.     

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 single-centre chart review exploring the adjusted association between breast cancer phenotype and prognosis

Purpose and Methods

Using a retrospective chart review, we investigated the differences in survival and prognostic factors between patients with triple-negative breast cancer (tnbc) and those with non-tnbc. The review included 1018 breast cancer patients who were diagnosed between 2000 and 2005 in Essex, Kent, and Lambton counties in Ontario, Canada.

Results

Our findings indicate that, although the unadjusted results suggested that patients with tnbc were more likely than patients with non-tnbc to die [hazard ratio (hr): 2.29; 95% confidence interval (ci): 1.33 to 2.93], an adjusted survival analysis revealed no significant difference in overall survival between the groups (hr: 1.22; 95% ci: 0.63 to 2.39). The significant predictors of survival in the adjusted analysis were age, stage of cancer, and size of cancer.

Conclusions

Our findings support those of earlier reports, which suggest that presenting tumour size is the most important prognostic factor in tnbc. Investigations into unique screening methods to identify these tumours at an earlier stage and to prevent advanced-stage cancer in this patient subpopulation are necessary.     

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.     

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.     

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.     

Rash rates with egfr inhibitors: meta-analysis

Introduction

Currently marketed epidermal growth factor receptor inhibitors (egfris) have been associated with high rates of dermatologic toxicity.

Methods

We formally reviewed the literature at medline and embase. Additional searches were conducted using Internet search engines. Studies were eligible if they were randomized controlled clinical trials of egfris, specifically cetuximab and panitumumab, in which at least one arm consisted of a non-egfri treatment and rash safety data were reported. The random effects method was used to pool differences in incident rash rates. Results are summarized as differences in incident rash (egfri therapy rate minus the non-egfri therapy rate) with corresponding 95% confidence intervals (cis) for all severity grades of rash and for grades 3 and 4 rash.

Results

Sixteen studies met the initial inclusion criteria of randomized controlled trials comparing egfri with non-egfri therapy. Seven publications that provided information on all severity grades of rash were found to have an overall difference in incident rash rate of 0.74 (95% ci: 0.68 to 0.81; p < 0.01). Thirteen studies that reported the incidence of grades 3 and 4 rash showed an overall difference in the incident rash rate of 0.12 (95% ci: 0.09 to 0.14; p < 0.01) between egfri and non-egfri therapy. Sensitivity analyses showed that the results were generally robust, but sensitive to small samples.

Conclusions

Results quantify the difference in rash rates between egfri and non-egfri therapy.     

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.     

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.     

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.     

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.     

Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer

Question

What are the benefits associated with the use of anti–epidermal growth factor receptor (anti-egfr) therapies in squamous cell carcinoma of the head and neck (hnscc)? Anti-egfr therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab.

Perspectives

Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, hnscc is the sixth most common neoplasm, and despite advances in therapy, long-term survival in hnscc patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages iii–ivb) hnscc; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years.Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced hnscc and as monotherapy for patients with recurrent or metastatic (stage ivc) hnscc who have progressed on platinum-based therapy.Given the interest in anti-egfr agents in advanced hnscc, the Head and Neck Cancer Disease Site Group (dsg) of Cancer Care Ontario’s Program in Evidence-Based Care (pebc) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment.

Outcomes

Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-egfr therapies.

Methodology

The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to locate primary articles and practice guidelines. The reference lists from relevant review articles were searched for additional trials. All evidence was reviewed, and that evidence informed the development of the clinical practice guideline. The resulting recommendations were approved by the Report Approval Panel of the pebc, and by the Head and Neck Cancer dsg. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline.

Results

The electronic search identified seventy-four references that were reviewed for inclusion. Only four phase iii trials met the inclusion criteria for the present guideline. No practice guidelines, systematic reviews, or meta-analyses were found during the course of the literature search.The randomized controlled trials (rcts) involved three distinct patient populations: those with locally advanced hnscc being treated for cure, those with incurable advanced recurrent or metastatic hnscc being treated with first-line platinum-based chemotherapy, and those with incurable advanced recurrent or metastatic hnscc who had disease progression despite, or who were unsuitable for, first-line platinum-based chemotherapy.

Practice Guideline

These recommendations apply to adult patients with locally advanced (nonmetastatic stages iii–ivb) or recurrent or metastatic (stage ivc) hnscc.

• Platinum-based chemoradiation remains the current standard of care for treatment of locally advanced hnscc.
• In patients with locally advanced hnscc who are medically unsuitable for concurrent platinumbased chemotherapy or who are over the age of 70 years (because concurrent chemotherapy does not appear to improve overall survival in this patient population), the addition of cetuximab to radical radiotherapy should be considered to improve overall survival, progression-free survival, and time to local recurrence.Cetuximab in combination with platinum-based combination chemotherapy is superior to chemotherapy alone in patients with recurrent or metastatic hnscc, and is recommended to improve overall survival, progression-free survival, and response rate.
• The role of anti-egfr therapies in the treatment of locally advanced hnscc is currently under study in large randomized trials, and patients with hnscc should continue to be offered clinical trials of novel agents aimed at improving outcomes.

Qualifying Statements

Chemoradiation is the current standard of care for patients with locally advanced hnscc, and to date, there is no evidence that compares cetuximab plus radiotherapy with chemoradiation, or that examines whether the addition of cetuximab to chemoradiation is of benefit in these patients. However, five ongoing trials are investigating the effect of the addition of egfr inhibitors concurrently with, before, or after chemoradiotherapy; those trials should provide direction about the best integration of cetuximab into standard treatment.In patients with recurrent or metastatic hnscc who experience progressive disease despite, or who are unsuitable for, first-line platinum-based chemotherapy, gefitinib at doses of 250 mg or 500 mg daily, compared with weekly methotrexate, did not increase median overall survival [hazard ratio (hr): 1.22; 96% confidence interval (ci): 0.95 to 1.57; p = 0.12 (for 250 mg daily vs. weekly methotrexate); hr: 1.12; 95% ci: 0.87 to 1.43; p = 0.39 (for 500 mg daily vs. weekly methotrexate)] or objective response rate (2.7% for 250 mg and 7.6% for 500 mg daily vs. 3.9% for weekly methotrexate, p > 0.05). As compared with methotrexate, gefitinib was associated with an increased incidence of tumour hemorrhage (8.9% for 250 mg and 11.4% for 500 mg daily vs. 1.9% for weekly methotrexate).     

Prospective evaluation of unmet needs of rural and aboriginal cancer survivors in Northern British Columbia

Background

The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities.

Methods

We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing “no unmet need” and 4 representing “very high unmet need.” A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results.

Results

We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss.

Conclusions

First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations.     

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.