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.     

Treatment outcomes for male breast cancer: a single-centre retrospective case–control study

Background

Male breast cancer (bc) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female bc. The objective of the present study was to compare disease-free (dfs) and overall survival (os) for men compared with women having early-stage bc.

Methods

This retrospective case–control study compared men and women treated for stage 0–iiib bc at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan–Meier analysis was used to calculate os and dfs.

Results

For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean dfs was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both dfs and os was stage at diagnosis.

Conclusions

This case–control study is one of the largest to report treatment outcomes in early-stage male bc patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and dfs. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.     

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

Objective and Methods

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

Results

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

Conclusions

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

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

Background

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

Methods

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

Results

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

Conclusions

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

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience

Background and Purpose

Extended-volume external-beam radiation therapy (rt) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume rt treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy.

Patients and Methods

From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume rt. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3–4, N0–1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous rt were excluded. All 15 study patients received 4 cycles of 5-fluorouracil–based chemotherapy. External-beam rt was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The rt was delivered concurrently with the third cycle of chemotherapy. The study outcomes—disease-free survival (dfs) and overall survival (os)—were calculated by the Kaplan–Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute’s Common Toxicity Criteria.

Results

The study accrued 10 men and 5 women of median age 64 years (range: 48–80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5–53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median dfs was 23 months, and the median os was 21 months.

Conclusions

Extended-volume external-beam rt encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3–4, N0–1 esophageal cancer patients after esophagectomy.     

An exploratory comparative analysis of tyrosine kinase inhibitors or docetaxel in second-line treatment of EGFR wild-type non-small-cell lung cancer: a retrospective real-world practice review at a single tertiary care centre

Background

Treatment for advanced non-small-cell lung cancer (nsclc), especially in patients with wild-type EGFR, remains limited. Recently, erlotinib, a tyrosine kinase inhibitor (tki) targeting EGFR mutation, was approved as second-line treatment in EGFR wild-type nsclc. Despite evidence of better overall survival (os) with chemotherapy than with tki in second-line treatment, data on the use of tki in the real-life clinical setting remain limited. The present practice review of tki use for second- and third-line treatment in EGFR wild-type nsclc also compares clinical outcomes for tki and single-agent docetaxel as second-line treatment.

Methods

Our retrospective cohort study included patients with EGFR wild-type nsclc treated at the Jewish General Hospital (Montreal, QC) between 2003 and 2013. Patients received a tki (erlotinib or gefitinib) in the second and third line or docetaxel in the second line. For each group, we determined os, disease control rate, progression-free survival (pfs), and event-free survival (efs).

Results

The tki group included 145 patients, with 92 receiving second-line treatment. In the control group, 53 patients received docetaxel as second-line therapy. In the tki group, os was 6.0 months; pfs, 2.7 months; and efs, 3.0 months. Comparing second-line treatments, os was 5.3 and 5.0 months respectively (p = 0.88), pfs was 2.5 and 1.8 months respectively (p = 0.041), and efs was 3.0 and 1.7 months respectively (p = 0.009).

Conclusions

In our study cohort, second-line therapy for EGFR wild-type nsclc with tki (compared with docetaxel) was associated with statistically better pfs and efs and noninferior os. Those findings raise the question of whether efs should also be considered when choosing second-line treatment in this patient population.     

Alignment of practice guidelines with targeted-therapy drug funding policies in Ontario

Background

We evaluated clinical practice guideline (cpg) recommendations from Cancer Care Ontario’s Program in Evidence-Based Care (pebc) for molecularly targeted systemic treatments (tts) and subsequent funding decisions from the Ontario Ministry of Health and Long-Term Care.

Methods

We identified pebc cpgs on tt published before June 1, 2010, and extracted information regarding the key evidence cited in support of cpg recommendations and the effect size associated with each tt. Those variables were compared with mohltc funding decisions as of June 2011.

Results

From 23 guidelines related to 17 tts, we identified 43 recommendations, among which 38 (88%) endorsed tt use. Among all the recommendations, 38 (88%) were based on published key evidence, with 82% (31 of 38) being supported by meta-analyses or phase iii trials. For the 38 recommendations endorsing tts, funding was approved in 28 (74%; odds ratio related to cpg recommendation: 29.9; p = 0.003). We were unable to demonstrate that recommendations associated with statistically significant improvements in overall survival [os: 14 of 16 (88%) vs. 8 of 14 (57%); p = 0.10] or disease- (dfs) or progression-free survival [pfs: 16 of 21 (76%) vs. 3 of 5 (60%); p = 0.59] were more likely to be funded than those with no significant difference. Moreover, we did not observe significant associations between funding approvals and absolute improvements of 3 months or more in os [6 of 6 (100%) vs. 3 of 6 (50%), p = 0.18] or pfs [6 of 8 (75%) vs. 10 of 12 (83%), p = 1.00].

Conclusions

For use of tts, most recommendations in pebc cpgs are based on meta-analyses or phase iii data, and funding decisions were strongly associated with those recommendations. Our data suggest a trend toward increased rates of funding for therapies with statistically significant improvements in os.     

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma

Objective

We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc).

Methods

The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test.

Results

Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan–Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non–clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001).

Conclusions

Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.     

Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis

Background

The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll).

Methods

The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation).

Results

Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting.

Conclusions

Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting.     

Cost–utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

Background

Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost–utility (cu) of this therapy could help to determine its role in clinical practice.

Methods

Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters.

Results

Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained.

Conclusions

Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.     

Adenoid cystic carcinoma of head and neck: clinical predictors of outcome from a Canadian centre

ObjectivesAdenoid cystic carcinoma (acc) is often treated with surgery, with or without adjuvant radiation therapy (rt). We evaluated disease characteristics, treatments, and potentially prognostic variables in patients with acc.MethodsOur retrospective analysis considered consecutive cases of acc presenting at a tertiary care hospital between 2000 and 2014. Factors predictive of overall survival (os) and disease-free survival (dfs) were identified by univariate analysis.ResultsThe 60 patients analyzed had a mean age of 58 years (range: 22–88 years), with a 2:1 female:male ratio. Tumour locations included the major salivary glands (40% parotid, 17% submandibular and sublingual), the oro-nasopharyngeal cavity (27%), and other locations (16%). Of the 60 patients, 35 (58%) received surgery with adjuvant rt; 12 (20%), rt only; 13 (22%), surgery only. Of 18 patients (30%) who experienced a recurrence within 5 years, 3 (5%) developed local recurrence only, and the remaining 15 (25%), distant metastasis. The 5-year os and dfs were 64.5% [95% confidence interval (ci): 45.9% to 78.1%] and 46.2% (95% ci: 29.7% to 61.2%) respectively. In patients without recurrence, 5-year os was 77% (95% ci: 52.8% to 89.9%), and in patients with recurrence, it was 42.7% (95% ci: 15.8% to 67.6%). Patients treated with rt only had a 5-year os of 9.2%. Predictors of 5-year dfs were TNM stage, T stage, nodal status, treatment received, and margin status; age, nodal status, treatment received, and margin status predicted 5-year os.ConclusionsDespite surgery and rt, one third of patients with acc experience distant recurrence. Patients whose tumours are not amenable to surgery have a poor prognosis, indicating a need for alternative approaches to improve outcomes.     

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 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.     

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.     

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.     

Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009

Background

Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (crc) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort.

Methods

All patients (n = 196) had metastatic crc, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (aes), time to disease progression (ttp), and overall survival (os) from diagnosis.

Results

Median follow-up was 36.0 months. Median ttp was 8.0 months [95% confidence interval (ci): 7.0 to 9.0 months). Median os was 41.0 months (95% ci: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumab-related aes experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3).

Conclusions

In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.     

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.     

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador

Background

In 2005, bevacizumab was approved by Health Canada for patients with metastatic colorectal cancer (mcrc). Newfoundland and Labrador was one of the first Canadian provinces to fund this agent in combination with folfiri (irinotecan, 5-fluorouracil, leucovorin) chemotherapy. In this analysis, the entire provincial bevacizumab sample for the first 2 years was assessed for overall safety and efficacy.

Methods

The medical records of 43 patients with mcrc who had received folfiri with bevacizumab were identified and reviewed. The longitudinal data collection format that was adopted assessed occurrences of adverse events after each cycle of treatment. Toxicity outcomes such as gastrointestinal (gi) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (vtes) were collected and graded using the U.S. National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 3.0. Time to treatment failure (ttf) and overall survival (os) were determined using the Kaplan–Meier method.

Results

Overall, the 43 study patients received 398 cycles of anticancer therapy (median: 6 cycles; range: 1–24 cycles). No gi perforations were identified. However, 4 bleeding events occurred (9.3%), 3 requiring permanent discontinuation of bevacizumab. Also, 6 grade 3 or 4 vtes occurred (14.0%), 3 of which required a hospital admission. In addition, grades 3 and 4 diarrhea, febrile neutropenia, and proteinuria showed cumulative incidences of 11.6%, 2.3%, and 2.3% respectively. Median ttf was 6.3 months; median os was 24.4 months.

Conclusions

Bevacizumab in combination with folfiri appears to be well tolerated, and efficacy is consistent with trial reports. However, patients should be closely monitored to avoid potentially serious events such as bleeding and vtes.     

Cost-effectiveness of zoledronic acid compared with clodronate in multiple myeloma

Background

In the U.K. Medical Research Council Myeloma IX trial (mmix), zoledronic acid 4 mg once every 3–4 weeks, compared with clodronate 1600 mg daily, reduced the incidence of skeletal related events (sres), increased progression-free survival (pfs), and prolonged overall survival (os) in 1970 patients with newly-diagnosed multiple myeloma. The incidence of confirmed osteonecrosis of the jaw was higher with zoledronic acid than with clodronate. The objective of the present study was to evaluate, based on the findings in mmix, the cost-effectiveness of zoledronic acid compared with clodronate in patients with newly-diagnosed multiple myeloma.

Methods

An economic model was used to project pfs, os, the incidence of sres and adverse events, and expected lifetime health care costs for patients with newly diagnosed multiple myeloma who are alternatively assumed to receive zoledronic acid or clodronate. The incremental cost-effectiveness ratio (icer) of zoledronic acid compared with clodronate was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (qalys). Model inputs were based on results of mmix and published sources. Results were generated under different assumptions regarding the beneficial effects of zoledronic acid on os beyond 5 years after treatment initiation.

Results

Assuming lifetime treatment effects of zoledronic acid, treatment with zoledronic acid (compared with clodronate) increased qalys by 0.27 at an additional cost of CA$13,407, yielding an icer of CA$49,829 per qaly gained. If the threshold icer is CA$100,000 per qaly, the estimated probability that zoledronic acid is cost-effective is 80%. Assuming that the benefits of zoledronic acid on pfs and os diminish over 5 years beginning at the end of year 5, the icer is CAN$63,027 per qaly gained. If the benefits of zoledronic acid on pfs and os are assumed to persist for 5 years only, the icer is CAN$76,948 per qaly gained.

Conclusions

Compared with clodronate, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.     

Panitumumab monotherapy compared with cetuximab and irinotecan combination therapy in patients with previously treated KRAS wild-type metastatic colorectal cancer

Background

The survival benefit for single-agent anti–epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan.

Methods

The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database.

Results

Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01).

Conclusions

Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc.