Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma

Background

Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy.

Methods

In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child–Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt.

Results

Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8–8.5 cm), which decreased with tace to 5.0 cm (range: 3.3–7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival.

Conclusions

The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.     

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.     

18F-Fluorodeoxyglucose positron-emission tomography could have a prognostic role in patients with advanced hepatocellular carcinoma

Introduction

We set out to evaluate the prognostic value of ¹⁸F-fluorodeoxyglucose positron-emission tomography (pet) in patients with advanced (non-transplant-eligible) hepatocellular carcinoma (hcc) and to evaluate the correlation between standardized uptake values (suvs) and survival outcomes.

Methods

We identified patients with hcc who, from 2005 to 2013, underwent pet imaging before any treatment. This retrospective study from our hcc database obtained complete follow-up data for the 63 identified patients.

Results

Of the 63 patients, 10 underwent surgical resection, and 59 underwent locoregional therapy. In this cohort, 28 patients were pet-positive (defined as any lesion with a suv ≥ 4.0) before any therapy was given, and 35 patients were pet negative (all lesions with a suv < 4.0). On survival analysis, median survival was greater for the pet-negative than for the pet-positive patients: 29 months (range: 16.3–41.1 months) versus 12 months (range: 4.0–22.1 months) respectively, p = 0.0241. The pet-positive patients more often had large tumours (≥5 cm), poor differentiation, and extrahepatic disease, reflecting more aggressive tumours. On multivariate analysis, only pet positivity was associated with poor survival (p = 0.049).

Conclusions

Compared with pet-positive patients, pet-negative patients with hcc experienced longer survival. Imaging by pet can be of value in early prognostication for patients with hcc, especially patients receiving locoregional therapy for whom pathologic tumour differentiation is rarely available. This potential role for pet requires further validation in a prospective study.     

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.     

Selected abstracts submitted to the 2nd International Cancer Fatigue Symposium: Putting the Pieces Together: Hyatt Regency,Montreal, Quebec; October 3–4, 2010

Objectives:

In this study, we used the European Organisation for Research and Treatment of Cancer (eortc) Quality of Life Questionnaire-30 (qlq-C30) to investigate cancer-related fatigue symptoms in digestive cancer patients.

Methods:

Between June 2007 and June 2009, the study enrolled 262 inpatients with cancer of digestive system from 4 Guangzhou hospitals: 50 patients with pancreatic cancer (pc), 60 with liver cancer (lc), 50 with esophageal cancer (ec), 50 with gastric cancer (gc), and 52 with colorectal cancer (cc). Fatigue in these patients was evaluated using 3 items from the eortc qlq-C30 assessing fatigue symptoms (total possible score: 3–12).

Results:

Fatigue scores were significantly higher in female patients than in male patients (6.34 ± 2.72 vs. 5.56 ± 2.47, p = 0.022). Patients staged iii or iv by TNM experienced more severe fatigue than did those staged i or ii (6.39 ± 2.70 vs. 5.24 ± 2.34, p = 0.001). Fatigue symptoms were more severe in patients who received chemotherapy than in those who underwent surgery (6.92 ± 2.75 vs. 5.13 ± 2.15, p = 0.000). In each digestive cancer group, scores by TNM stage and treatment were similarly significantly different, but the differences between male and female patients were nonsignificant. Fatigue scores were sharply higher in the pc group (9.74 ± 2.28) than in the other 4 groups (lc: 6.03 ± 1.62; ec: 4.12 ± 1.32; gc: 4.76 ± 1.30, cc: 4.44 ± 1.29; all p = 0.000). In addition, scores were higher in the lc group than in the ec group, the gc group, and the cc group (all p = 0.000). Differences between the ec group, the gc group, and the cc group were nonsignificant (all p > 0.05).

Conclusions:

Symptoms of fatigue are an obstacle for digestive cancer patients, especially at advanced stages or when being treated with chemotherapy. Pancreatic cancer patients experience more severe fatigue.

• Curr Oncol. 2010 Oct; 17(5): 78–83.
»
• P002 Liver Cancer–Related Fatigue: Its Correlations with Quality of Life and Social Support of Patients

Curr Oncol. 2010 Oct; 17(5): 78.

P002 Liver Cancer–Related Fatigue: Its Correlations with Quality of Life and Social Support of Patients

L. Jia,^*† S.M. Jiang,^*† and Y.H. Liu^*†

L. Jia

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by L. Jia

S.M. Jiang

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by S.M. Jiang

Y.H. Liu

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by Y.H. LiuAuthor information Copyright and License information Disclaimer^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaCopyright 2010 Multimed Inc.     

Patient preferences for timing and access to radiation therapy

Purpose

Patient preferences for radiation therapy (rt) access were investigated.

Methods

Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded.

Results

Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%–15% preferred 07h30–08h00 or 16h30–17h00; 10% preferred 17h00–18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively.

Conclusions

An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%–20% of rt capacity on weekends and during 07h30–08h00 and 16h30–18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.     

Management of renal collecting duct carcinoma: a systematic review and the McMaster experience

Introduction

Collecting duct carcinoma (cdc) is a rare, aggressive form of renal carcinoma that presents at an advanced stage and has a poor prognosis. Little is known concerning the optimal management of cdc. We present the results of a systematic review addressing the management of cdc and the McMaster University cdc series.

Methods

The medline, Cochrane Library, and embase databases and conference proceedings were searched to identify studies relating to the management of cdc. Included studies reported on a minimum of 10 subjects receiving a single intervention. Series in which an evaluation of therapeutic effectiveness was not possible were excluded. The McMaster University (Hamilton, Ontario) series of 6 cases of cdc were retrospectively reviewed.

Results

We identified 3 studies relevant to the management of cdc that included a total of 72 patients. A gemcitabine–cisplatin or –carboplatin regimen resulted in a 26% objective response rate in 23 patients with metastatic cdc. Two additional studies indicated that 49 patients treated with immunotherapy achieved no response. In the McMaster series, cytoreductive nephrectomy was performed in 4 of 6 patients. In 2 patients, mvac therapy (methotrexate–vinblastine–doxorubicin–cisplatin) achieved no response. No significant therapeutic complications occurred, but survival was poor (median: 11 months; range: 10–33 months).

Conclusions

Our review and clinical experience suggest that the current standard of care for metastatic cdc is a gemcitabine–cisplatin regimen.     

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.     

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.     

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.     

Age at diagnosis predicts local recurrence in women treated with breast-conserving surgery and postoperative radiation therapy for ductal carcinoma in situ: a population-based outcomes analysis

Purpose

The main goal of treating ductal carcinoma in situ (dcis) is to prevent the development of invasive breast cancer. Most women are treated with breast-conserving surgery (bcs) and radiotherapy. Age at diagnosis may be a risk factor for recurrence, leading to concerns that additional treatment may be necessary for younger women. We report a population-based study of women with dcis treated with bcs and radiotherapy and an evaluation of the effect of age on local recurrence (lr).

Methods

All women diagnosed with dcis in Ontario from 1994 to 2003 were identified. Treatments and outcomes were collected through administrative databases and validated by chart review. Women treated with bcs and radiotherapy were included. Survival analyses were performed to evaluate the effect of age on outcomes.

Results

We identified 5752 cases of dcis; 1607 women received bcs and radiotherapy. The median follow-up was 10.0 years. The 10-year cumulative lr rate was 27% for women younger than 45 years, 14% for women 45–50 years, and 11% for women more than 50 years of age (p < 0.0001). The 10-year cumulative invasive lr rate was 22% for women younger than 45 years, 10% for women 45–50 years, and 7% for women more than 50 years of age (p < 0.0001). On multivariate analyses, young age (<45 years) was significantly associated with lr and invasive lr [hazard ratio (hr) for lr: 2.6; 95% confidence interval (ci): 1.9 to 3.7; p < 0.0001; hr for invasive lr: 3.0; 95% ci: 2.0 to 4.4; p < 0.0001]. An age of 45–50 years was also significantly associated with invasive lr (hr: 1.6; 95% ci: 1.0 to 2.4; p = 0.04).

Conclusions

Age at diagnosis is a strong predictor of lr in women with dcis after treatment with bcs and radiotherapy.     

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

Objective

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

Methods

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

Results

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

Conclusions

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

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.     

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.     

Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience

Background

Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)–positive, her2-negative, T1–2, N0 disease. Our objectives were to

• □ estimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.
• □ compare the indices preferred by oncologists with the indices available to them.
• □ correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.
• □ assess interobserver variation.

Methods

All of the er-positive, her2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test.

Results

During 2007–2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%).

Conclusions

Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.     

Superficial parotid lobe–sparing delineation approach: a better method of dose optimization to protect the parotid gland in intensity-modulated radiotherapy for nasopharyngeal carcinoma

Purpose

We used a superficial parotid lobe–sparing delineation approach for dose optimization with better protection for the parotid glands in intensity-modulated radiotherapy (imrt) for nasopharyngeal carcinoma (npc) patients.

Methods

Compared with traditional contouring of the entire parotid glands as organs at risk (oars) in imrt for npc, we used a superficial parotid lobe–sparing delineation approach of contouring the superficial parotid lobes as oars. Changes in dose to the parotid glands, the targets, and other oars were evaluated.

Results

The mean dose to the parotid glands overall decreased by more than 4 Gy in the test plans. Impressively, the mean dose to the superficial parotid lobes in the test plans was not more than 30 Gy, regardless of clinical stage. In T1–3 npc patients, the dose distributions for targets were not significantly different in the control plans and the test plans. However, for some T4 patients, the dose distributions for targets and brainstem in the test plans could not meet clinical requirements.

Conclusions

The superficial parotid lobe–sparing delineation approach can significantly lower the mean dose to the entire parotid and to the superficial parotid lobe in T1–3 npc patients, which would be expected to result in less xerostomia and better quality of life for those patients.     

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.     

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.     

Clinical analysis of osteosarcoma patients treated with high-dose methotrexate-free neoadjuvant chemotherapy

Objective

High-dose methotrexate (hdmtx) is a common therapeutic agent in the treatment of osteosarcoma. However, hdmtx is highly toxic and requires complex pharmacokinetic monitoring and leucovorin rescue. Thus, alternative therapeutic strategies are necessary. Here, we analyzed the clinical efficacy of a dia regimen (cisplatin–ifosfamide–doxorubicin) to evaluate its potential as an alternative to hdmtx–based therapy.

Methods

Patients received 12 cycles of chemotherapy administered over 2 years (2 preoperative cycles and 10 postoperative cycles). Cumulative dose was the same in all cycles: cisplatin 120 mg/m² on day 1 of week 1, followed by ifosfamide 2.0 g/m² days 1–5 of week 2, and doxorubicin 20 mg/m² days 1–3 of week 2.

Results

Between January 2004 and October 2008, 39 eligible patients (median age: 16 years) were enrolled, with 36 being evaluable for the study. Of those 36 patients, 20 (55.6%) had a good histologic response to preoperative chemotherapy (>90% tumour necrosis). The estimated 5-year rates of event-free survival (efs) and overall survival were 54.8% and 61.5% respectively.

Conclusions

The results of our study suggest that, in osteosarcoma patients, the dia regimen produces an efs rate and survival outcomes comparable to those attained with hdmtx–containing regimens, with fewer adverse reactions. The dia regimen is well tolerated, and we observed a high level of patient compliance. Our results demonstrate that hdmtx-free osteosarcoma treatment regimens can be effective, warranting further investigation.     

Has the practice of radiation oncology for locally advanced and metastatic non-small-cell lung cancer changed in Canada?

Aim

Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (nsclc) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic nsclc among Canadian radiation oncologists.

Materials and Methods

An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate. The survey consisted of three scenarios focusing on areas of nsclc treatment in which the radiotherapy (rt) regimen that provides the best therapeutic ratio is unclear.

Results

Replies from 41 respondents were analyzed. For an asymptomatic patient with stage iiib nsclc unsuitable for radical treatment, 22% recommended immediate rt, and 78% recommended rt only if the patient were to become symptomatic. Those who believed that immediate rt prolongs survival were more likely to recommend it (p = 0.028). For a patient with a bulky stage iiib tumour and good performance status, 39% recommended palliative treatment, and 61% recommended radical treatment (84% concurrent vs. 16% sequential chemoradiation at 60–66 Gy in 30–33 fractions). Those who believed that chemoradiation has a greater impact on survival were more likely to recommend it (p < 0.001). For a symptomatic patient with stage iv nsclc, 54% recommended external-beam rt (ebrt) alone, 41% recommended other modalities (brachytherapy, endobronchial therapy, or chemotherapy) with or without ebrt, and 5% recommended best supportive care. A majority (76%) prescribed 20 Gy in 5 fractions for ebrt.

Conclusions

Compared with previous surveys, more radiation oncologists now offer radical treatment for locally advanced nsclc. Management of nsclc in Canada may be evidence-based, but perception by radiation oncologists of the treatment’s impact on survival also influences treatment decisions.