Outcomes for a large series of radical cystectomies for bladder cancer

Aims

We present the characteristics and outcomes of a large Chinese series of patients treated with radical cystectomy and pelvic lymphadenectomy for invasive cancer of the bladder. Our aim is to determine the significant independent prognostic factors that determine this outcome.

Methods

The records of 356 patients with invasive bladder cancer, operated at three Chinese medical institutes between 1995 and 2004, were reviewed. Of the 356 patients, 324 (91.0%) were TCC, 24 (6.7%) were adenocarcinoma, eight (2.3%) were squamous carcinoma. The incidence of pelvic lymph node involvement was 22.8%. The mean (SD, range) follow-up of the 356 patients was 54.89 (31.66, 3–137) months. Multivariate analysis was used to assess the clinical and pathological variables affecting disease-free survival (DFS).

Results

The 1-, 2- and 5-year DFS rates were 87%, 75% and 48%, respectively. In multivariate analysis, tumor configuration (RR = 1.62, p = 0.012), multiplicity (RR = 1.41, p = 0.036), histological subtype (RR = 2.17, p < 0.001), tumor stage (RR = 2.50, p < 0.001), tumor grade (RR = 2.40, p < 0.001), node status (RR = 2.51, p < 0.001), neoadjuvant chemotherapy (RR = 0.46, p = 0.016) had independent significance for survival on multivariate analysis.

Conclusions

The results of this series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and DFS in patients with invasive bladder cancer. Multivariates affect the prognosis after radical cystectomy for invasive bladder cancer. The treatment of invasive bladder cancer in China is still in need of improvement and normalization.     

Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults

Objectives

The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC).

Methods

From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS).

Results

At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p = 0.032), for DFS, margins after surgery (p = 0.007), for DSS, regional or distant metastasis at diagnosis (p = 0.002), initial AJCC and MSKCC stage (p = 0.018 and p = 0.048) and margins after surgery (p = 0.042). On multivariate analysis, margins remained statistically significant for DFS (p = 0.039) when there was a trend with the initial AJCC stage (p = 0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system.

Conclusions

Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

Sentinel node biopsy for high-risk cutaneous squamous cell carcinoma

Aim

The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC.

Materials and methods

Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method.

Results

Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis (p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively (p = 0.016).

Conclusions

SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.     

Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: Results from a retrospective analysis

Background

Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS).

Methods

Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure.

Results

From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n = 231 (36.0%), ANS n = 410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p < 0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p = 0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p = 0.002), despite similar baseline characteristics in both groups.

Conclusion

Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample.     

Recombinant human thyrotropin-aided versus thyroid hormone withdrawal-aided radioiodine treatment for differentiated thyroid cancer after total thyroidectomy: A meta-analysis

Background and purpose

We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) on thyrotropin stimulation prior to remnant ablation of differentiated thyroid cancer (DTC).

Material and methods

A comprehensive search was conducted for articles discussing rhTSH and THW prior to December 2012. After applying the inclusion criteria, all the available data were summarized to analyze the efficacy of rhTSH and THW for stimulating TSH.

Results

Seven RCTs that involved a total of 1535 patients, were included in the analysis. The ablation rates of the rhTSH group and the THW group were not significantly different (RR = 0.97, 95% CI: 0.94–1.01, p = 0.1). Patients in the rhTSH group had a better quality of life (QoL) than those in the THW group on the day of ablation (RR = 3.92, 95% CI: 3.44–5.40, p < 0.00001). However, there was no difference in the QoL 3 months after ablation (RR = −0.9, 95% CI: −2.20–0.39, p = 0.17). Additionally, there were no significant differences in serum thyroglobulin (Tg) levels measured just before radioiodine remnant ablation (preablation thyroglobulin levels) (RR = −0.14, 95% CI: −0.73–0.45, p = 0.65), or in days of hospital isolation (RR = −10.51, 95% CI: −32.79–11.73, p = 0.35)

Conclusions

Our findings indicate that the administration of rhTSH had resulted in an ablation rate similar to that of THW for DTC patients, but rhTSH provided a better QoL at the time of ablation.     

Equivalent survival in patients with advanced stage IB–II and III–IVA cervical cancer treated by adjuvant surgery following chemoradiotherapy

Objectives

To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy.

Methods

One hundred and forty-four patients with biopsy-proven stage IB–IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status.

Results

Tumour FIGO stages were IB–II in 91 cases and III–IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB–II and III–IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1–67.5] and 65% [95% CI: 56.2–75]. OS was significantly affected by the type of surgery (p < 2.10⁻¹⁶), the presence of tumoural residue (p = 0.002) and the pelvic lymphatic status (p < 0.001). DFS was affected by the pelvic (p = 0.02) and para-aortic lymphatic status (p = 0.009). No significant difference was observed between OS and DFS in stage IB–II and III–IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p = 0.022).

Conclusion

Survival rates were equivalent between patients with IB–II and III–IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.     

Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: Results from IALT,JBR.10 and ANITA

Introduction

CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.002) and overall survival (OS; HR = 1.9, p = 0.004).

Methods

To validate these results, mucin staining was performed on primary tumor specimens from 780 patients treated on IALT, 351 on JBR.10 and 150 on ANITA. The histochemical technique using mucicarmine was performed. The prognostic value of mucin for DFS and OS was tested in a Cox model stratified by trial and adjusted for clinical and pathological factors. A pooled analysis of all 4 trials was performed for the predictive value of mucin for benefit from adjuvant chemotherapy.

Results

The cross-validation group had 48% squamous, 37% adenocarcinoma and 15% other NSCLC compared with 29%, 56%, and 15%, respectively in CALGB. Among 1262 patients with assessable results, mucin was positive in IALT 24%, JBR.10 30%, ANITA 22% compared with 45% in CALGB. Histology was the only significant covariate (p < 0.0001) in multivariate analysis with mucin seen more commonly in adenocarcinoma (56%) compared with squamous (5%) and other NSCLC (15%). Mucin was a borderline negative prognostic factor for DFS (HR = 1.2 [1.0–1.5], p = 0.06) but not significantly so for OS (HR = 1.1 [0.9–1.4], p = 0.25). Prognostic value did not vary according to histology: HR = 1.3 [1.0–1.6] in adenocarcinoma vs. 1.6 [1.2–2.2] for DFS in other histology (interaction p = 0.69). Mucin status was not predictive for benefit from adjuvant chemotherapy (test of interaction: DFS p = 0.27; OS p = 0.49).

Conclusions

Mucin was less frequent in the cross-validation group due to its higher percentage of squamous cell carcinomas. The negative impact of mucin was confirmed for DFS but not for OS. Mucin expression was not predictive of overall survival benefit from adjuvant chemotherapy.     

Long-term follow-up reveals that ulceration and sentinel lymph node status are the strongest predictors for survival in patients with primary cutaneous melanoma

Purpose

To assess the long-term outcome after sentinel lymph node biopsy (SLNB) in melanoma patients.

Methods

Between 1995-2009 450 melanoma patients underwent SLNB in a single center. Survival and prognostic factors were analyzed for 429 patients.

Results

Median age was 53 (range 11-84) years. Median Breslow thickness was 2.4 (range 1-20) mm and 36% were ulcerated melanomas. Median follow-up time was 64.8 (range 2-174) months. A tumor-positive SLN was present in 140 patients (31%). Completion lymph node dissection (CLND) was performed in 119 patients and these patients were analyzed for recurrence and survival.124 Patients (29%) relapsed during follow-up; 55 in the node-positive group who underwent CLND (55/119; 46%) and 69 in the node-negative group (69/310; 22%; p < 0.001). In the node-negative group 17 patients developed recurrence in the regional node field; false-negative rate 11%.On multivariate analysis strongest prognostic factors for disease free survival (DFS) were primary melanoma ulceration and SLN positivity (Hazard Ratio (HR) of 2.2 and 2.3; p < 0.001). For disease specific survival (DSS) the same was found to be true with an HR of 2.1 for ulceration and 2.0 for SLN positivity (p = 0.001 and p = 0.002 respectively). 10-Year DFS was 71% for node-negative patients compared with 48% for node-positive patients (p < 0.001). 10-Year DSS was 77% for node-negative patients compared to 60% for node-positive patients (p < 0.001).

Conclusions

This study shows a remarkably high percentage of tumor-positive SLN. The long-term follow-up data confirm that tumor-positive SLN patients have a worse DFS and DSS than tumor-negative SLN patients. Ulceration and SLN status proved to be the strongest prognostic factors for long-term DFS and DSS.     

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

Hürthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003

Introduction

Previous studies have included Hürthle cell carcinoma (HCC) as a variant of follicular thyroid carcinoma in analysis of clinical outcome and others have failed to adequately distinguish between benign and malignant Hürthle cell neoplasms. The aim of this study was to report our experience of histologically confirmed malignant HCC, identifying patient, tumour and treatment factors that predict outcome.

Methods

A retrospective review was undertaken of all patients treated with HCC between 1946 and 2003. Study end-points were disease-free survival (DFS) and cause-specific survival (CSS). Demographic, pathological and treatment-related factors were all correlated with the study end-points.

Results

Sixty-two patients were followed up for a median (range) of 58 months (2–629). On multivariate analysis, only extent of surgery (p < 0.001) was an independent factor affecting CSS. Lymph node status (p = 0.008), presence of metastases at diagnosis (p = 0.005) and tumour stage (p = 0.009) were independent predictors of DFS.

Conclusions

HCC appears to be a separate entity from follicular thyroid carcinoma (FTC), with a more aggressive disease profile. Lymph node status, tumour stage, and the presence of metastases are independent predictors of DFS. Radical surgery may improve outcome in HCC.     

Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer

Introduction

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

Patients and Methods

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3–6 cycles of epirubicin + docetaxel, AdC comprised EC ± taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

Results

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p = 0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p = 0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p = 0.008), loco-regional and distant recurrence-rates (HR 3.0, p = 0.03 and HR 2.0, p = 0.02).

Discussion

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.     

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

Background and purpose

Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions.

Materials and methods

This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose–volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain.

Results

Prone treatment resulted in: improved dose coverage (p < 0.001); better homogeneity (p < 0.001); less volumes of over-dosage (p = 0.001); reduced acute skin desquamation (p < 0.001); a 3-fold decrease of moist desquamation p = 0.04 (chi-square), p = 0.07 (Fisher’s exact test)); lower incidence of dermatitis (p < 0.001), edema (p = 0.005), pruritus (p = 0.06) and pain (p = 0.06); 2- to 4-fold reduction of grades 2–3 toxicity; lower ipsilateral lung (p < 0.001) and mean LAD (p = 0.007) dose; lower, though statistically non-significant heart and maximum LAD.

Conclusions

This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.     

Lymph node micrometastasis in node negative early gastric cancer

Aims

The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC).

Methods

We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000.

Results

Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion (p = 0.012), venous invasion (p = 0.026) and larger tumor (p = 0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion (p = 0.004, RR = 22.915, 95% CI = 2.709 ∼ 193.828) and tumor size (p = 0.029, RR = 1.493, 95% CI = 1.042 ∼ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ∼ 147 months), there was no death from a cancer recurrence.

Conclusions

The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.     

Quality of care indicators and their related outcomes: A population-based study in prostate cancer patients treated with radiotherapy

Background and purpose

We describe variations across the regional cancer centres in Ontario, Canada for five prostate cancer radiotherapy (RT) quality indicators: incomplete pre-treatment assessment, follow-up care, leg immobilization, bladder filling, and portal film target localization. Along with cancer centre volume, we examined each indicator’s association with relevant outcomes: long-term cause-specific survival, urinary incontinence, and gastrointestinal and genitourinary late morbidities.

Materials and methods

We conducted a population-based retrospective cohort study of 924 prostate cancer patients diagnosed between 1990 and 1998 who received RT within 9 months of diagnosis. Data sources included treating charts and registry and administrative data. The associations between indicators and outcomes were analysed using regression techniques to control for potential confounders.

Results

Practice patterns varied across the regional cancer centres for all indicators (p < 0.0001). Incomplete pre-treatment assessment was associated with worse cause-specific survival although this result was not significant when adjusted for confounding (adjusted RR = 1.78, 95% CI = 0.79–3.98). Treatment without leg immobilization (adjusted RR = 1.72, 95% CI = 1.16–2.56) and with an empty bladder (adjusted RR = 1.98, 95% CI = 1.08–3.63) was associated with genitourinary late morbidities. Treatment without leg immobilization was also associated with urinary incontinence (adjusted RR = 2.18, 95% CI = 1.23–3.87).

Conclusions

We documented wide variations in practice patterns. We demonstrated that measures of quality of care can be shown to be associated with clinically relevant outcomes in a population-based sample of prostate cancer patients.     

Improving staging accuracy in colon and rectal cancer by sentinel lymph node mapping: A comparative study

Aim

To compare the predictive value of sentinel lymph node (SN) mapping between patients with colon and rectal cancer.

Patients and methods

An ex vivo SN procedure was performed in 100 patients with colon and 32 patients with rectal cancer. If the sentinel node was negative, immunohistochemical analyses using two different antibodies against cytokeratins (Cam5.2 and CK 20) and one antibody against BerEp-4 were performed to detect occult tumour cells. Isolated tumour cells (<0.2 mm) were discriminated from micrometastases (0.2–2 mm).

Results

An SN was identified in 117 patients (89%), and accurately predicted nodal status in 106 patients (accuracy 91%). Both sensitivity and negative predictive value were higher in colon carcinomas than in rectal carcinomas (83% versus 57%, p = 0.06 and 93% versus 65%, p = 0.002 respectively). In patients with extensive lymph node metastases the SN procedures were less successful. Eleven of the 13 unsuccessful SN procedures were performed in patients with rectal cancer who had pre-operative radiotherapy. After immunohistochemical analysis 21 of the 73 N0 patients had occult tumour cells in their SN; eight patients had micrometastases and 13 patients had isolated tumour cells.

Conclusion

SN mapping accurately predicts nodal status in patients with colonic cancer. Immunohistochemical analysis demonstrates micrometastatic disease in eight out of 73 N0 patients, with a true upstaging rate of 11%. SN mapping is less reliable in patients with rectal cancer after pre-operative radiotherapy.     

Referral bias in thyroid cancer surgery: Direction and magnitude

Aim

This study was conducted to clarify the impact of referral bias in thyroid cancer surgery.

Methods

Analysis of 1419 consecutive patients with papillary (n = 653), follicular (n = 248), and medullary thyroid cancer (n = 518) referred to a specialist center for initial surgery or reoperation.

Results

With increasing travel distance (successive postal code areas), mean age decreased among patients referred for initial surgery (from 53 to 35 years for papillary cancer, 65 to 49 years for sporadic medullary cancer, and 40 to 23 years for hereditary medullary cancer, all p ≤ 0.001; and from 65 to 54 years for follicular cancer, p = 0.26). The significant decline in mean age continued among patients reoperated on for papillary cancer (from 53 to 43 years, p < 0.001), but was lost among patients reoperated on for medullary cancers.For patients with differentiated, but not medullary cancers, greater travel distance was associated with higher frequencies of extrathyroidal extension at initial surgery (from 17% to 63% for follicular cancer, p = 0.003) and reoperation (from 18% to 47% for papillary, and 5% to 44% for follicular cancer, all p < 0.001), and higher frequencies of lymph node metastasis at initial surgery (from 23% to 58% for papillary, and 17% to 50% for follicular cancer, p ≤ 0.008) and reoperation (from 27% to 77% for papillary, and 0% to 35% for follicular cancer, all p < 0.001).

Conclusion

Referral bias in thyroid cancer surgery can include two components working in opposite directions: age and extent of disease. Controlling for these components should reduce the impact of referral bias on thyroid cancer research.     

Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis

Background

Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment.

Methods

We searched PubMed and Web of Science (January 1966-July 2009) and American Society of Clinical Oncology conferences held (January 2000-July 2009) for relevant articles and abstracts. Summary incidence rates, relative risks (RRs), and 95% confident intervals (CIs) were calculated using a fixed-effects or random-effects model.

Results

11,882 patients from 10 RCTs were included for analysis. The incidences of LVEF decrease and congestive heart failure (CHF) were 7.5% (95% CI 4.2-13.1) and 1.9% (95% CI 1.0-3.8) among patients receiving trastuzumab. Trastuzumab significantly increased the risk of LVEF decrease (RR = 2.13, 95% CI, 1.31-3.49; p = 0.003). In addition, it significantly increased the risk of CHF (RR = 4.19, 95% CI 2.73-6.42; p < 0.00001). The increased risk of CHF was observed in patients with early stage (RR = 4.05, 95% CI 2.49-6.58; p < 0.00001) as well as metastatic disease (RR = 4.75, 95% CI 1.93-11.71; p = 0.0007). Furthermore, trastuzumab significantly increased the risk of CHF (RR = 4.27, 95% CI 2.75-6.61, p < 0.00001) in patients receiving anthracycline-based chemotherapy, but not in patients receiving non-anthracycline chemotherapy (RR = 2.42, 95% CI 0.36-16.19, p = 0.36).

Conclusion

The addition of trastuzumab to anthracycline-based chemotherapy significantly increase the risk of cardiac dysfunction in breast cancer patients. Further studies are recommended for non-anthracycline chemotherapy.     

Positive prognostic impact of miR-210 in non-small cell lung cancer

Objectives

miR-210 is an important regulator of the cellular response to hypoxia. Therefore, we aimed to explore the prognostic significance of miR-210 in non-small cell lung cancer (NSCLC) patients with stage I-IIIA disease.

Materials and methods

In addition to clinicopathological and demograpic information, tumor tissues were collected and tissue micro arrays (TMAs) were constructed from 335 patients with stage I-IIIA NSCLC. Expression of miR-210 in cancer cells and stromal cells of the tumor was assessed by in situ hybridization.

Results

In univariate analyses, high cancer cell (p = 0.039) and high stromal cell expression (p = 0.008) of miR-210 were both significantly associated with an improved disease-spesific survival (DSS). High co-expression of miR-210 in cancer and stromal cells was also a positive prognostic factor for DSS (p = 0.010). In multivariate analysis, miR-210 in stromal cells (p = 0.011), and miR-210 co-expressed in cancer and stromal cells was an independent prognosticator for DSS (p = 0.011).

Conclusions

We show that miR-210 in stromal cells, and co-expressed in cancer cells and stromal cells mediates an independent prognostic impact. It is a candidate marker for prognostic stratification in NSCLC.