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.     

Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis

Background

Given the use of tamoxifen as standard treatment for hormone receptor–positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor–positive breast cancer in premenopausal women.

Methods

Premenopausal patients with hormone receptor– positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints.

Results

Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025).

Conclusions

In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor–positive breast cancer in premenopausal women were similar.     

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.     

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.     

Capecitabine or infusional 5-fluorouracil for gastroesophageal cancer: a cost-consequence analysis

Background

In patients with advanced gastroesophageal cancer, the phase iii Randomized ECF for Advanced and Locally Advanced Esophagogastric Cancer 2 (real-2) trial demonstrated equivalent clinical efficacy when capecitabine (x) was substituted for 5-fluorouracil (5fu) in the epirubicin–cisplatin–5fu (ecf) regimen. The present analysis compares the direct medical costs associated with both regimens.

Methods

This cost–consequence analysis of direct medical costs took resource utilization data from the real-2 trial where available. Direct medical costs were derived from the perspective of the Canadian public health care system in 2008 Canadian dollars. Mean cost per patient on each treatment arm was calculated.

Results

Drug costs from start of treatment until first progression, including pre- and post-chemotherapy medications and administration costs, totalled $5,344 for ecx as compared with $3,187 for ecf. Costs for treatment of adverse events were estimated at $2,621 for ecx as compared with $3,397 for ecf. An additional cost of $873 was associated with insertion of an implanted venous access. Total incremental cost of ecx over ecf was $508.

Conclusions

In advanced gastroesophageal cancer, capecitabine is an attractive alternative to 5fu. Although the drug cost per se is greater, use of capecitabine is associated with decreased consumption of hospital resources. Not only does capecitabine fit with patient preference for oral therapy, it also avoids the inconvenience and complications of central venous access.     

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.     

Role of oxaliplatin combined with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer

Question

What is the role of oxaliplatin combined with 5-fluorouracil (5-fu) and folinic acid (fa) in the first- and second-line treatment of advanced (unresectable locally advanced or metastatic) colorectal cancer?

Perspectives

Evidence was selected and reviewed by two members of the Gastrointestinal Cancer Disease Site Group (gi dsg) of Cancer Care Ontario’s Program in Evidence-Based Care (pebc) and by a methodologist. The resulting practice guideline report has been reviewed and approved by the gi dsg, which comprises medical and radiation oncologists, surgeons, a pathologist, and patient representatives.External review by Ontario practitioners was obtained through a mailed survey. Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee.

Outcomes

Outcomes of interest were 1-year survival, response rates, and quality of life.

Methodology

The medline, cancerlit, embase, Guidelines International Network, and Cochrane Library databases were systematically searched for relevant studies. Recommendations were formed based on the evidence reviewed. Through a survey, these recommendations were appraised by Ontario clinicians; the recommendations were then revised by the gi dsg. The systematic review and modified recommendations were approved by a review body within pebc.

Results

The literature review found twenty-one randomized controlled trials and two meta-analyses. Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival and tumour response, with lower incidences of most adverse effects except peripheral neuropathy. For second-line treatment after fluoropyrimidine monotherapy, folfox is a reasonable alternative for patients with contraindications to second-line irinotecan. After progression on infusional 5-fu/fa/irinotecan (folfiri), folfox is the preferred therapy. Evidence from a single randomized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment.

Practice Guideline

These recommendations apply to adult patients with advanced colorectal cancer who have high performance status (Eastern Cooperative Oncology Group score 0–2).Refer to Appendix A for available treatment options and to Appendix b for recommended dosages and schedules.The folfox regimen is an important component of therapy for advanced colorectal cancer.

First-line Therapy

In one trial, folfox was shown to be superior to ifl. The folfox regimen has superior rates of median survival and tumour response. Compared with ifl, folfox has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy.Short-term infusional 5-fu/fa in combination with either oxaliplatin (folfox) or irinotecan (folfiri) are both acceptable alternatives for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences—for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin.

Second-line Therapy

After progression on first-line anti-thymidylate synthase monotherapy (for example, 5-fu/fa, capecitabine), irinotecan is standard second-line therapy. The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan.After progression on both irinotecan and an anti-thymidylate synthase agent, folfox is the preferred therapy. Recent trials suggest that, as compared with folfox alone, folfox combined with bevacizumab provides additional survival benefits.

Qualifying Statements

The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer is not addressed in this guideline.Use of chronomodulated regimens is a topic that intersects with the use of oxaliplatin/5-fu combinations, particularly chronomodulation of 5-fu in these combinations. Chronomodulation of oxaliplatin has not been extensively studied, and the topic of chronomodulation is beyond the scope of this guideline and is not addressed.Although data exist to support the use of bevacizumab in combination with folfox in second-line treatment, no first-line treatment data are available on which to make a recommendation.     

Cost-effectiveness of oxaliplatin in the adjuvant treatment of colon cancer in Canada

Objective

The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5fu/lv)—the folfox regimen—was compared with that of 5fu/lv alone as adjuvant therapy for patients with stage iii colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the mosaic (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the folfox regimen significantly improved disease-free survival. The mosaic trial formed the basis of the present analysis.

Methodology

Extrapolated patient-level data from the mosaic trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the mosaic trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature.

Results

Lifetime incremental cost-effectiveness ratios for folfox compared with 5fu/lv were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (qaly) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed.

Conclusions

With an incremental cost of CA$24,104 per qaly gained, folfox is a cost-effective adjuvant treatment for stage iii colon cancer. Compared with 5fu/lv alone, this regimen offers better clinical outcomes and provides good value for money.     

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.     

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).

     

The BC Cancer Agency Compassionate Access Program: outcome analysis of patients with esophagogastric cancer

Background

The BC Cancer Agency Gastro-intestinal Tumor Group supports one standard of care (soc) chemotherapy regimen for metastatic esophagogastric adenocarcinoma—specifically, weekly cisplatin and 5-fluorouracil (5fu) infusion. All other regimens require Compassionate Access Program (cap) approval for public funding.

Objectives

We examined response, toxicity, and survival after first-line cap chemotherapy (cap1), or soc and second-line cap chemotherapy (cap2).

Patients and Methods

We searched cap records for December 1999 to April 2006, abstracted charts, constructed a database, and undertook survival analyses. Treatment response, serious toxicities, and hospitalizations were recorded.

Results

We identified 32 esophageal (10 gastroesophageal junction) and 53 gastric cancer (62%) patients, 55 of whom were stage M1 at diagnosis. Prior therapy consisted of chemoradiotherapy (n = 14), adjuvant chemotherapy (n = 3), and radical surgery (n = 34). Of these 85 patients, 50 received cap1, and 35 received soc, then cap2. Docetaxel and irinotecan regimens accounted for 34% and 36%, 5% and 55%, 16% and 32% respectively of first-, second-, and third-line cap requests. Partial responses were documented with soc (11/35, 31%) and cap1 (6/50, 12%). Grade 3+ toxicity rates were 19/50 (38%) and 6/35 (17%) with cap1 and soc chemotherapy. With cap chemotherapy, 20 hospitalizations occurred, and with soc chemotherapy, 2 hospitalizations. For all patients, median follow-up and survival times were 8.9 months and 9.7 months respectively.

Limitations

This is a retrospective analysis of patients deemed suitable to receive non-soc chemotherapy regimens or unsuitable to receive soc chemotherapy.

Conclusions

Toxicities in cap chemotherapy regimens were substantial. Survival times were consistent with results of international phase ii and iii trials in esophagogastric cancer.     

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.     

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.     

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.     

Diagnostic value of preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 in colorectal cancer

Background

Since the first introduction of tumour markers, their usefulness for diagnosis has been a challenging question. The aim of the present prospective study was to investigate, in colorectal cancer patients, the relationship between preoperative tumour marker concentrations and various clinical variables.

Methods

The study prospectively enrolled 131 consecutive patients with a confirmed diagnosis of colorectal carcinoma and 131 age- and sex-matched control subjects with no malignancy. The relationships of the tumour markers carcinoembryonic antigen (cea) and carbohydrate antigen (ca) 19-9 with disease stage, tumour differentiation (grade), mucus production, liver function tests, T stage, N stage, M stage were investigated.

Results

Serum concentrations of cea were significantly higher in the patient group than in the control group (p = 0.001); they were also significantly higher in stage iii (p = 0.018) and iv disease (p = 0.001) than in stage i. Serum concentrations of cea were significantly elevated in the presence of spread to lymph nodes (p = 0.005) in the patient group. Levels of both tumour markers were significantly elevated in the presence of distant metastasis in the patient group (p = 0.005 for cea; p = 0.004 for ca 19-9).

Conclusions

Preoperative levels of cea and ca 19-9 might provide an estimate of lymph node invasion and distant metastasis in colorectal cancer patients.     

Distribution and clinical significance of tumour-associated macrophages in pancreatic ductal adenocarcinoma: a retrospective analysis in China

Background

We aimed to characterize the localization and prognostic significance of tumour-associated macrophages (tams) in pancreatic ductal adenocarcinoma (pdac).

Methods

Tumour specimens from 70 patients with pdac and inflammatory specimens from 13 patients with chronic pancreatitis were collected and analyzed for tam and M2 macrophage counts by immunohistochemistry. Correlations between tam distributions and clinicopathologic features were determined.

Results

Immunohistochemical analysis showed that tam and M2 macrophage counts were higher in tissues from pdac than from chronic pancreatitis. The tams and M2 macrophages both infiltrated more into peritumour. Both macrophage types were positively associated with lymph node metastasis (p = 0.041 for tams in peritumour, p = 0.013 for M2 macrophages in introtumour, p = 0.006 for M2 macrophage in peritumour). In addition, abdominal pain was significantly more frequent in pdac patients with a greater tams count. The survival rate was much lower in patients having high infiltration by M2 macrophages than in those having low infiltration.

Conclusions

The tam count might be associated with neural invasion in pdac, and M2 macrophages might play an important role in lymph node metastasis. Higher counts of either macrophage type were associated with increased risk of lymph node metastasis, and the M2 macrophage count could potentially be a marker for evaluating prognosis.     

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

Background

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

Methods

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

Results

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

Conclusions

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

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.     

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.