Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice

Introduction

Randomized controlled trials (rcts) are the “gold standard” for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to

• □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and
• □ compare the effectiveness of ppdc in routine practice with its efficacy in rcts.

Methods

Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario’s regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient’s symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas “well-being” item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts.

Results

We identified 906 patients with pre-ppdc esas records. Median survival was 31 weeks compared with 28–48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%–63% who had improved or stable qol in rcts.

Conclusions

The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.     

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.     

Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients

Breast cancer is heterogenous, with variable expression of the estrogen receptor (er), progesterone receptor (pr), and human epidermal growth factor receptor 2 (her2). Overexpression of her2 is generally considered a negative prognostic feature, but whether outcomes for her2-positive early breast cancer remain different from those for other subtypes in the era of trastuzumab-based adjuvant therapy is unknown.

Methods

Using a retrospective chart review, we compared overall survival (os) and relapse-free survival (rfs) in 3 groups of patients with early-stage breast cancer: er-positive or pr-positive (or both) and her2-negative [“hormone receptor–positive” (hr+)]; her2-positive (her2+); and er-negative, pr-negative, and her2-negative [“triple-negative” (tn)].

Results

In the 503 charts analyzed (332 hr+, 94 her2+, 77 tn), the 5-year os and rfs were, respectively, 94.2% and 87.2% for hr+ patients, 88.6% and 74.9% for her2+ patients, and 85.4% and 76.2% for tn patients. On multivariate analysis, the os for the her2+ subtype was similar to that for the hr+ subtype (hazard ratio:1.07; 95% confidence interval: 0.31 to 3.67 with hr+ as reference), but os was significantly worse for tn patients than for hr+ patients (hazard ratio: 4.37; 95% confidence interval: 1.56 to 12.24). In her2+ patients, the 5-year os and rfs trended better for patients with er+ or pr+ disease than for patients with er-negative and pr-negative disease (5-year os: 92.1% vs. 86.9%; 5-year rfs: 79.8% vs. 71.4%). Of her2+ patients, just 80.9% received trastuzumab, including 33.3% of her2+ patients with sub-centimetre tumours.

Conclusions

In the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort.     

Testing for her2 in breast cancer: current pathology challenges faced in Canada

This review is designed to highlight several key challenges in the diagnosis of human epidermal growth factor receptor 2 (her2)–positive breast cancer currently faced by pathologists in Canada:

• Pre-analysis issues affecting the accuracy of her2 testing in non-excision sample types: core-needle biopsies, effusion samples, fine-needle aspirates, and bone metastases
• her2 testing of core-needle biopsies compared with surgical specimens
• Criteria for retesting her2 status upon disease recurrence

Literature searches for each topic were carried out using the medline, Embase, International Pharmaceutical Abstracts, and biosis databases. In addition, the congress databases of the American Society of Clinical Oncology (2005–2011) and the San Antonio Breast Cancer Symposium (2007–2011) were searched for relevant abstracts.All authors are expert breast pathologists with extensive experience of her2 testing, and several participated in the development of Canadian her2 testing guidelines. For each topic, the authors present an evaluation of the current data available for the guidance of pathology practice, with recommendations for the optimization or improvement of her2 testing practice.     

Cost-effectiveness of lapatinib plus letrozole in her2-positive,hormone receptor–positive metastatic breast cancer in Canada

Background

The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor–positive (hr+), human epidermal growth factor receptor 2–positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.

Methods

A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib–letrozole, letrozole, anastrozole, or trastuzumab–anastrozole as first-line treatment. Clinical inputs for lapatinib–letrozole and letrozole were taken from the EGF30008 trial ({"type":"clinical-trial","attrs":{"text":"NCT00073528","term_id":"NCT00073528"}}NCT00073528). Clinical inputs for anastrozole and trastuzumab–anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer’s price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan’s Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.

Results

Quality-adjusted life years gained with lapatinib–letrozole were 0.236 compared with trastuzumab–anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib–letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab–anastrozole. Results from the societal perspective were similar.

Conclusions

In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib–letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab–anastrozole.     

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.     

Concurrent chemoradiotherapy for locally advanced breast cancer—time for a new paradigm?

Background

In cases of locally advanced breast cancer (labc), preoperative (“neoadjuvant”) therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor–positive and her2-negative. A new paradigm for labc patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (ccrt) is routinely used in neoadjuvant and adjuvant treatment protocols alike.

Results

The literature suggests that ccrt in labc patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone.

Conclusions

Ongoing trials in this field are eagerly awaited to determine if ccrt should become the new paradigm.     

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.     

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.     

After radiotherapy,do bone metastases from gastrointestinal cancers show response rates similar to those of bone metastases from other primary cancers?

Purpose

Reports investigating whether the response rates to palliative radiation therapy (rt) for painful bone metastases from gastrointestinal (gi) cancers are similar to rates for bone metastases from other primary cancer sites have been limited. The present study evaluated response rates for symptomatic bone metastases from gi cancers after palliative outpatient rt in the Rapid Response Radiotherapy Program (rrrp).

Patients and Methods

We identified 69 patients with bone metastases from gi primaries who received palliative rt in the rrrp clinic during 1999–2006. We extracted records for 31 of these patients during 1999–2003 from an rrrp database that used the Edmonton Symptom Assessment Scale (esas). Record for the remaining 38 patients during 2003–2006 were extracted from an rrrp database that used the Brief Pain Inventory (bpi). Eligibility criteria for encryption in the two rrrp databases and for collection of patient demographic information (age, sex, primary cancer site, and Karnofsky performance status) were identical.Response rates for this cohort of metastatic gi patients were then compared to rates for 479 patients receiving palliative rt for bone metastases from other primary cancer sites. Pain scores from the esas and bpi and data on analgesic consumption were collected at baseline and by telephone follow-up at 4, 8, and 12 weeks after rt for all patients. Complete (cr), partial (pr), and overall (cr+pr) responses were evaluated according to International Consensus Endpoints.

Results

Assessment of the 69 patients with metastatic gi cancers revealed cr, pr, and cr+pr rates of 18%, 42%, and 61% at 4 weeks; 22%, 35%, and 57% at 8 weeks; and 50%, 21%, and 71% at 12 weeks for evaluable patients. The 479 evaluable patients with metastatic cancer from other primary cancer sites had cr, pr, and cr+pr rates of 25%, 27%, and 51% at 4 weeks; 26%, 22%, and 48% at 8 weeks; and 22%, 29%, and 51% at 12 weeks. No statistically significant differences were observed in rt response rates for bone metastases from gi cancers than from other primary cancer sites.

Conclusions

After palliative rt, bone metastases from gi cancers demonstrate response rates that are similar to rates for metastases from other primary cancer sites. Patients with symptomatic bone metastases from gi malignancies should be referred for palliative rt as readily as patients with osseous metastases from other primary cancer sites.     

Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Background

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Methods

We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.

Results

During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.

Conclusions

Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.     

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.     

Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline

Questions

1. In limb salvage surgery for extremity soft-tissue sarcoma (sts), what is an adequate surgical margin?
2. What is the appropriate number of samples to take from the margins of a surgical resection specimen?
3. What is the appropriate handling of surgical resection specimens?

Background

Surgery is the primary treatment for extremity sts. The combination of radiotherapy with surgery allows for limb salvage by using radiation to biologically “sterilize” microscopic extensions of tumour and to spare neurovascular and osseous structures. Adjuvant chemotherapy in sts—except for rhabdomyosarcoma and Ewing sarcoma—continues to be controversial.

Methods

The medline and embase databases (1975 to June 2011) and the Cochrane Library were searched for pertinent studies. The Web sites of the main guideline organizations and the American Society of Clinical Oncology conference proceedings (2007–2010) were also searched.

Results and Conclusions

Thirty-three papers, including four guidelines, one protocol, and one abstract, were eligible for inclusion.The data suggest that patients with clear margins have a better prognosis, but no prospective studies have indicated how wide margins should be. In limb-salvage surgery for extremity sts, the procedure should be planned to achieve a clear margin. However, to preserve functionality, surgery may result in a very close (<1 cm) or even microscopically positive margin. In this circumstance, the use of preoperative or postoperative radiation should be considered.No studies described the optimal number of tissue sections required to assess adequacy of excision nor the appropriate handling of surgical resection specimens. The Sarcoma Disease Site Group made its recommendations based on expert opinion and consensus.     

Economic evaluation of hormonal therapies for postmenopausal women with estrogen receptor–positive early breast cancer in Canada

Background

Aromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)–positive early breast cancer.

Methods

The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with er-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs.

Results

The sequential tam–ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai–tam strategy, ai–tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis.

Conclusions

In postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost.     

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.     

Are two-centimeter breast cancers large or small?

Background

Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage ii, and smaller cancers, as stage i. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage i or a stage ii breast cancer.

Methods

Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1–1.9 cm, exactly 2.0 cm, and 2.1–2.9 cm.

Results

In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1–3.0 cm). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.2% for women with 21-mm to 29-mm tumours.

Conclusions

For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis.     

The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer

Background

Accurate prediction of outcome in advanced non-small-cell lung cancer (nsclc) remains challenging. Even within the same stage and treatment group, survival and response to treatment vary. We set out to determine the predictive value of inflammatory markers C-reactive protein (crp) and white blood cells (wbcs) in patients with advanced nsclc.

Patients and Methods

Patients were assigned a prognostic index (pi):

• 0 for crp 10 mg/L or less and wbcs 11×10⁹/L or less,
• 1 if one of the two markers was elevated, and
• 2 if both markers were elevated.

We then used chest computed tomography (ct) imaging to evaluate response after 2 cycles of chemotherapy treatment.

Results

Of 134 patients, 46 had a pi of 0; 60, a pi of 1; and 28, a pi of 2. Disease progressed in 41 patients. Progression was significantly more frequent among patients with a pi of 2 (p = 0.008). Median survival was 20.0 months for the pi 0 group, 10.4 months for the pi 1 group, and 7.9 months for the pi 2 group (p < 0.001). The pi was the only significant prognostic factor for survival even after adjustment for performance status, smoking, and weight loss (hazard ratio: 1.57; 95% confidence interval: 1.2 to 2.14; p = 0.004).

Conclusions

Inflammatory state correlates significantly with both chemotherapy response and survival in stage iv nsclc. The pi may provide additional guidance for therapeutic decision-making.     

Systemic therapy for advanced gastric cancer: a clinical practice guideline

Question

What is the optimal chemotherapy regimen in advanced gastric cancer?

Perspectives

Gastric cancer is the second leading cause of cancer mortality worldwide. Despite low incidence rates for gastric cancer in Ontario, the overall prognosis is bleak, with 5-year survival rates of approximately 23% in Canada. Even with the considerable body of research available on chemotherapy for advanced gastric cancer, uncertainty remains. There is no recognized standard treatment, and there appears to be geographic variation in practice.

Outcomes

Outcomes of interest were overall survival, objective response rate (complete plus partial responses), time to disease progression, adverse effects, and quality of life.

Methodology

After a systematic review, a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted. The practice guideline was reviewed and approved by the Gastrointestinal Disease Site Group (gi dsg) and the Report Approval Panel of the Program in Evidence-Based Care. External review by Ontario practitioners was obtained through a survey, the results of which were incorporated into the practice guideline.

Practice Guideline

The gi dsg makes the following recommendations:

• To improve survival, a platinum agent should be included in any combination chemotherapy regimen.
• Within a combination chemotherapy regimen, oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)—that is, epirubicin–cisplatin–capecitabine is preferred over the prior standard regimen, epirubicin–cisplatin–5fu (ecf).
• Epirubicin–oxaliplatin–capecitabine (eox) is a reasonable alternative to ecf. The choice between ecf and eox should be based on patient preference.
• Trastuzumab in combination with cisplatin and a fluoropyrimidine (5fu or oral capecitabine) is recommended for advanced gastric cancer positive for the human epidermal growth factor receptor 2 (her2/neu).

     

Treatment and follow-up strategies in desmoid tumours: a practice guideline

Objectives

We set out to

• determine the optimal treatment options—surgery, radiation therapy (rt), systemic therapy, or any combinations thereof—for patients with desmoid tumours once the decision to undergo active treatment has been made (that is, monitoring and observation have been determined to be inadequate).
• provide clinical-expert consensus opinions on follow-up strategies in patients with desmoid tumours after primary interventional management.

Methods

This guideline was developed by Cancer Care Ontario’s Program in Evidence-Based Care and the Sarcoma Disease Site Group. The medline, embase, and Cochrane Library databases, main guideline Web sites, and abstracts of relevant annual meetings (1990 to September 2012) were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Sarcoma Disease Site Group.

Recommendations

Treatments

• Surgery with or without rt can be a reasonable treatment option for patients with desmoid tumours whose surgical morbidity is deemed to be low.
• The decision about whether rt should be offered in conjunction with surgery should be made by clinicians and patients after weighing the potential benefit of improved local control against the potential harms and toxicity associated with rt.
• Depending on individual patient preferences, systemic therapy alone or rt alone might also be reasonable treatment options, regardless of whether the desmoid umours are deemed to be resectable.

Follow-Up Strategies

• Undergo evaluation for rehabilitation (occupational therapy or physical therapy, or both).
• Continue with rehabilitation until maximal function is achieved.
• Undergo history and physical examinations with appropriate imaging every 3–6 months for 2–3 years, and then annually.