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.     

Combined management of retroperitoneal sarcoma with dose intensification radiotherapy and resection: Long-term results of a prospective trial

Background

Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS.

Methods

From June 1996 to October 2000, eligible patients with resectable RPS were entered onto a phase II trial of preoperative XRT (45–50 Gray) plus postoperative BT (20–25 Gray). Kaplan Meier survival curves were constructed and compared by log rank analysis (SPSS 21.0).

Results

All 40 patients had preoperative XRT and total gross resection as part of the prospective trial, nineteen received BT (48%). Median follow-up was 106 months. For the entire cohort, OS at 5 and 10 years was 70% and 64%, respectively; RFS at 5 and 10 years was 69% and 63%. RFS was significantly reduced in high versus low grade RPS at 5 years (53% vs. 88%, p = 0.016), but not at 10 years (53% vs. 75%, p = 0.079). RFS and OS at 10 years were reduced in patients who presented with recurrent compared to primary disease (RFS 30% vs. 74%, p = 0.015; OS 36% vs. 76%, p = 0.036). At 10 years, neither RFS nor OS was improved in patients who received BT compared to those who did not (RFS 56% vs. 69%, p = 0.54; OS 52% vs.76%, p = 0.23).

Conclusions

In this prospective trial with mature follow-up, long-term OS and RFS in patients who underwent combined preoperative XRT plus resection of RPS compare favourably with those reported in retrospective institutional and population-based series. Postoperative BT was associated with unacceptable toxicity and did not contribute to disease control.

Condensed abstract

In a prospective trial with mature follow-up, preoperative radiation combined with complete resection of retroperitoneal sarcoma resulted in favourable long-term RFS and OS compared to historical controls. Dose escalation with postoperative brachytherapy was not associated with better disease control.     

The clinical outcome and prognostic factors after multi-visceral resection for advanced colon cancer

Aim

The value of multi-visceral resection (MVR) for treating primary advanced colon cancer infiltrating into the neighboring organs had been debated because of the high mortality.

Methods

We reviewed 1288 patients who underwent curative resection for pT3–4 colon cancer without distant metastasis from 1994 to 2004.

Results

Eighty four patients (6.5%) with colon cancer infiltrating into the neighboring organs (cT4) underwent MVR. The accuracy of the intra-operative decision for true invasion (pT4) was 35.7%. Major surgical morbidity occurred in 11 patients of the standard resection group (0.9%) and in 2 patients of the MVR group (2.3%) (p = 0.206). Most of the recurrence was distant metastasis (20 patients, 23.8%). Local recurrence was occurred in five patients (6.0%). The prognostic factors for recurrence and survival were pathologic tumor invasion (p = 0.033 and p = 0.016, respectively) and lymph node metastasis (p = 0.010 and p < 0.001, respectively).

Conclusion

Multi-visceral resection was a safe and curative procedure as compared with standard resection for patients with advanced colon cancer. The cause of a poor prognosis in MVR was not local recurrence but distant metastasis. Pathologic tumor invasion and lymph node metastasis were the potential prognostic factors.     

Comparison of chemoradiation with radiation as postoperative adjuvant therapy in cervical cancer patients with intermediate-risk factors

Aims

In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We retrospectively compared the treatment outcome of chemoradiation with that of radiation.

Methods

From 1997 to 2005, 79 consecutive cervical cancer patients received postoperative adjuvant therapy indicated by intermediate-risk factors. Fifty-five women received chemoradiation and 24 women received radiation. Risk factors, recurrence-free survival (RFS), adverse events, and recurrence pattern were investigated and were compared between the chemoradiation and radiation groups. RFS was calculated by the Kaplan–Meier method and was compared by the log-rank test.

Results

Risk factors were well-balanced between the two groups. Four patients recurred in the chemoradiation group and eight patients recurred in the radiation group. RFS rate of the chemoradiation group was significantly higher than that of the radiation group (P = 0.01). Hematologic toxicity was more common in the chemoradiation group than in the radiation group (P < 0.01). However, non-hematologic toxicity was similar between the two groups and most of the patients (97%) completed postoperative adjuvant therapy. Recurrence pattern was similar between the two groups.

Conclusion

In cervical cancer patients with intermediate-risk factors, chemoradiation was well-tolerated and more effective than radiation as a postoperative adjuvant therapy.     

Treatment outcomes and unfavorable prognostic factors in patients with occult breast cancer

Aims

The purpose of this study was to evaluate the treatment outcomes and prognostic factors in patients with occult breast cancer (OBC).

Methods

We retrospectively analyzed 95 patients with OBC who were treated at our facility between January 1998 and June 2010. Of the 95 patients, 64 underwent mastectomy plus axillary lymph node dissection (ALND) with or without post-mastectomy radiation (Mast + ALND group), 13 underwent ALND followed by ipsilateral breast radiotherapy (BR + ALND group) and the remaining 18 were treated with ALND (ALND group).

Results

Patients who underwent Mast + ALND or BR + ALND had significantly improved rates of locoregional recurrence-free survival (LRFS) and recurrence/metastasis-free survival (RFS) than patients who only underwent ALND (p < 0.05). There were no significant differences in the LRFS (p = 0.718), RFS (p = 0.935) and breast cancer-specific survival (BCSS) (p = 0.991) rates between the patients who underwent Mast + ALND compared with those who received BR + ALND. Multivariate analysis revealed that patients with four or more involved lymph nodes had significantly worse outcomes (p = 0.042, HR = 4.63, 95% CI = 1.66–32.47 for BCSS and p = 0.038, HR = 3.62, 95% CI = 1.08–20.77 for RFS).

Conclusions

Patients with OBC who received ALND and subsequent breast radiotherapy had similar outcomes to patients who underwent mastectomy. The presence of four or more involved lymph nodes may independently predict poor outcomes of OBC.     

Patterns of lymph node spread and its influence on outcome in resectable parotid cancer

Aim

To assess the metastatic topography of intraparotideal and neck lymph nodes in parotid cancer and its influence on tumour recurrence and survival.

Methods

The lymph node spread of 142 patients with primary parotid carcinoma treated from 1986 to 2006 was analysed. Disease-free survival (DFS) and overall survival (OS) were calculated. The role of the metastatic pattern as prognostic factors were univariately and multivariately analysed.

Results

A lateral, total or radical parotidectomy was performed in 19, 80 and 43 patients, respectively. A radical/radical-modified or selective neck dissection was performed in 68 and 74 patients, respectively. Eighty-seven neck dissection specimens were negative (pN0). Twelve patients had intraparotideal and cervical lymph node involvement (pPar+/pN+). In 24 patients only intraparotideal metastases were detected (pPar+/pN0). 19 patients only had cervical nodal involvement (pPar−/pN+). Twenty-five patients had occult locoregional lymph metastases (cN0/pN+). The median follow-up was 24.4 months. The disease-free survival rate was 81% at 5 years, and 62% at 10 years. By univariate analysis, R+ (p = 0.001), pT (p = 0.019), lymphangiosis carcinomatosa (p = 0.019), pN+ (p = 0.042), and extracapsular spread (p = 0.046) were prognostic for disease-free survival. Multivariate analysis revealed R+ as independent risk factor (p = 0.046). In pN+ patients, involvement of parotid lymph nodes (p = 0.013), nodes in neck level I (p < 0.0001) and IV (p = 0.005) were univariate risk factors. Multivariate analysis showed lymph node metastases in level I as independent risk factor (p = 0.022).

Conclusion

Total parotidectomy and radical-modified neck dissection is recommended as surgical treatment of parotid cancer and should be analysed in a prospective trial.     

Improved survival after resectable non-cardia gastric cancer in the Netherlands: The importance of surgical training and quality control

Background

In the Netherlands, standardised limited D1 and extended D2 lymph node dissections in the treatment of resectable gastric cancer were introduced nationwide within the framework of the Dutch D1–D2 Gastric Cancer Trial between 1989 and 1993. In a population-based study, we evaluated whether the survival of patients with resectable gastric cancer improved over time on a regional level.

Methods

We compared 5-year overall and relative survival of patients with curatively resected non-cardia gastric cancer in the regional cancer registry of the Comprehensive Cancer Centre West in the Netherlands before the Dutch D1–D2 trial (1986 to mid 1989; n = 273), during the trial period (mid 1989 to mid 1993; n = 255), and after the trial (mid 1993 to 1999; n = 219), adjusting for prognostic variables.

Results

Unadjusted survival was highest in the post-trial period: 5-year overall and relative survival were 42% and 52%, respectively, compared to 34% and 41% in the pre-trial period, and 39% and 46% in the trial period (p = 0.31 and p = 0.06, respectively). After adjustment for age, gender, tumour site, pT-stage, nodal status and hospital volume, the effect of period on survival was more apparent (p = 0.009). Compared to the pre-trial period, the hazard ratio was 0.83 (95% confidence interval, 0.68–1.02) for the trial period, and 0.72 (0.58–0.89) after the trial. Less than 1% of the patients received adjuvant therapy.

Conclusion

Survival of patients with curatively resected non-cardia gastric cancer has improved. Standardisation and surgical training in D1 and D2 lymph node dissection are the most likely explanation for this improvement.     

Postoperative adjuvant transcatheter arterial chemoembolisation improves survival of intrahepatic cholangiocarcinoma patients with poor prognostic factors: Results of a large monocentric series

Background

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is currently unsatisfactory. The aims of this study were to identify prognostic factors after curative ICC resection, and to evaluate the effects of postoperative transcatheter arterial chemoembolisation (TACE).

Methods

A retrospective analysis was conducted of 114 ICC patients who underwent curative resection from January 2005 to December 2006. Relationships between survival and clinicopathological factors were evaluated using univariate and multivariate analyses. The benefits of adjuvant TACE were investigated separately.

Results

The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%, respectively. Multivariate analysis revealed that tumour size ≥5 cm (hazard ratio [HR] 1.875, 95% CI 1.139–3.088, P = 0.013) and advanced TNM stage (stage III or IV) (HR 1.681, 95% CI 1.035–2.732, P = 0.036) were independently associated with poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with poor prognostic factors, TACE improved the survival rate (P < 0.001). However, in patients without poor prognostic factors, TACE did not significantly change the survival rate (P = 0.724).

Conclusions

Postoperative adjuvant TACE can prolong survival in ICC patients with tumour size ≥5 cm or advanced TNM stage.     

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.     

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.     

Pattern of CAIX expression is prognostic for outcome and predicts response to ARCON in patients with laryngeal cancer treated in a phase III randomized trial

Background and purpose

In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated.

Material and methods

261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival.

Results

Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p < 0.01 and MFS 92% vs 69%, p = 0.06).Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (65% vs 84%, p = 0.01, 70% vs 96%, p < 0.01 and 42% vs 71%, p < 0.01 respectively), and this could not be improved with ARCON. After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival.

Conclusions

ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression. The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value.     

Outcome of distal gastric cancer with pyloric stenosis after curative resection

Aims

Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without.

Methods

A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated.

Results

The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT₁, RR of pT₂ 3.1, p = 0.009; pT₃ 6.1, p < 0.001; pT₄ 16.5, p < 0.001), and more lymph node metastasis (RR 3.6; p = 0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p = 0.001).

Conclusions

Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.     

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients

Objective

The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96–98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND).

Methods

Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, pN0/pN_SN0) were assessed from our prospective database. Patients underwent either ALND (n = 178) in 1990–1997 or SLN biopsy (n = 177) in 1998–2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen.

Results

The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p = 0.008) and overall survival (p = 0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10–0.73, p = 0.009) and overall survival (HR: 0.34, 95% CI: 0.14–0.84, p = 0.019).

Conclusions

This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.     

Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer

Background

Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer.

Patients and methods

TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors.

Results

High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10).

Conclusion

TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer.     

Sentinel node status predicts survival in thick melanomas: The Oxford perspective

Aims

To determine the prognostic value of SLNB in patients with thick melanoma in terms of overall survival (OS) and recurrence-free survival (RFS).

Methods

136 patients with primary tumours (Breslow thickness ≥4.0 mm) underwent SLNB. OS and RFS were calculated and a multivariate Cox regression model used to determine the important prognostic factors for predicting OS and RFS.

Results

Median Breslow thickness was 5.5 mm and 60% were ulcerated. Median follow up was 4 years (95% CI = 4–5) with 54 patients having died at the time of analysis. 5-year OS for SLNB positive patients was 32%, compared to 78% for negative patients. The significant predictors of poorer OS were increasing age (p = 0.03), increasing Breslow thickness (p = 0.03) and SLNB positivity (p < 0.0001). 5 year RFS was significantly worse in the SLNB positive population compared to the negative patients (p < 0.0001); 27% versus 66% respectively.

Conclusions

Patients with a thick melanoma and a positive SLNB have a significantly worse RFS and OS compared to those with a negative SLNB. Over three-quarters of patients with a negative SLNB survived five years. These findings have implications for the subpopulations included in adjuvant therapy trials and we advocate SLNB be recommended in patients with thick melanomas.     

Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes

Purpose

To examine use of and outcomes from adjuvant locoregional radiotherapy (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1-3 positive nodes (1-3 N+) before and after the 1997 publication of randomised trial evidence of a survival advantage from post-mastectomy LRRT.

Methods

Data were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1-3 N+, treated with BCS and RT. LRRT use was analysed over time. Ten-year Kaplan-Meier locoregional control (LRC), breast cancer-specific survival (BCSS) and overall survival (OS) curves were compared using the log-rank test. Cox regression modeling of LRC and BCSS were performed.

Results

LRRT use in patients with 1-3 N+ increased from 23% before 1997 to 57% after 1997. LRRT was associated with significant improvements in LRC, but not in DRFS, BCSS, or OS. 10--year LRC was 89% with local RT alone and 93% with LRRT (p = 0.006). On multivariable analysis, LRRT was associated with improved LRC compared to local RT alone (HR 0.55, 95% CI: 0.40-0.77), but not with significant BCSS differences. Margin status, grade, % positive nodes, and hormonal therapy were significant predictors for LRC, while tumour size, grade, % positive nodes, and hormonal therapy significantly affected BCSS.

Conclusion

Post-BCS LRRT use in British Columbia increased almost threefold in patients with 1-3 N+ after 1997. Adjuvant LRRT was associated with improved LRC, but not with improved BCSS compared to breast RT alone.     

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.     

Prognostic value of parapharyngeal extension in nasopharyngeal carcinoma treated with intensity modulated radiotherapy

Background and purpose

The development of improved diagnostic and therapeutic techniques has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study is to revaluate the prognostic value of parapharyngeal extension in NPC in the IMRT era.

Material and methods

We retrospectively reviewed data from 749 biopsy-proven non-metastatic NPC patients. All patients were examined with magnetic resonance imaging (MRI) and received intensity-modulated radiotherapy (IMRT) as the primary treatment.

Results

The incidence of parapharyngeal extension was 72.1%. A significant difference was observed in the disease-free survival (DFS; 70.3% vs. 89.1%, P < 0.001), distant metastasis-free survival (DMFS; 79.3% vs. 92.0%, P < 0.001), and local relapse-free survival (LRFS; 92.8% vs. 99.0%, P = 0.002) of patients with and without parapharyngeal extension. Parapharyngeal extension was an independent prognostic factor for DFS and DMFS in multivariate analysis (P = 0.001 and P = 0.015, respectively), but not LRFS. The difference between DMFS in patients with or without parapharyngeal space extension was statistically significant in patients with cervical lymph node metastasis (P < 0.001).

Conclusions

In the IMRT era, parapharyngeal extension remains a poor prognosticator for DMFS in NPC, especially in patients with positive lymph node metastasis. Additional therapeutic improvements are required to achieve a favorable distant control in NPC with parapharyngeal extension.     

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.     

Prognostic influence of immunohistochemically detected lymph node micrometastasis and histological subtype in pN0 oesophageal cancer

Introduction

Differences in frequency and clinical impact of lymph node micrometastasis between histological subtypes of oesophageal cancer have not been determined.

Methods

1204 lymph nodes from 32 squamous cell carcinomas and 54 adenocarcinomas with complete resection and pN0 status were re-evaluated using a serial sectioning protocol including immunohistochemistry. Intra-nodal tumour cells were classified as micrometastases (0.2–2 mm) or isolated tumour cells (<0.2 mm).

Results

There was no significant difference in the frequency of micrometastases between adenocarcinoma and squamous cell carcinoma (11.3% vs. 3.1%, p = n.s.). In the squamous cell carcinoma group, Kaplan–Meier curves showed a significantly prolonged 5-year survival (p = 0.02) and disease free interval (p < 0.01) for immunohistochemically node negative versus node positive patients. In patients with adenocarcinoma, no such difference (p = n.s. and p = n.s., respectively) was seen. In patients who did not undergo pre-treatment, those with adenocarcinoma had a significant 5-year survival (65% vs. 53%; p = 0.03) and disease free interval (83% vs. 58%; p < 0.05) advantage over those with squamous cell carcinoma. After pre-treatment, no difference between the histological subtypes was detected.Regression analysis did not reveal any factors that significantly affected overall survival in node negative patients. However, four factors did significantly influence disease free interval: pre-treatment (HR 3.3 [95% CI 1.2–9.1], p = 0.02); micrometastasis (HR 5.3 [95% CI 1.4–19.7], p = 0.01); UICC stage II vs. 0/I (HR 2.2 [95% CI 1.1–4.4], p = 0.03); and adenocarcinoma (HR 0.3 [95% CI 0.1–0.9], p = 0.03).

Conclusion

The difference in frequency and clinical impact of immunohistochemically detected micrometastasis may indicate that adenocarcinoma and squamous cell carcinoma should not be treated as one entity.