A study of lymph node ratio as a prognostic marker in colon cancer

Aim

The aim of this study was to evaluate and describe the lymph node ratio (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic involvement is the key, focus was set at stage III disease. Interest was directed at the possibility of identifying high-risk groups and the clinical implementation and consequence.

Method

The study was retrospective using a database of clinical data of all cancer patients treated at our unit. It has been continuous in registration, inclusion and update since 1999 including survival and clinical features. All patients (n = 265) diagnosed with stage III colon cancer during 1999–2003 were included for the study. LNR was calculated and quartile groups were created. LNR and associated parameters were analysed towards 3-year disease-free survival (DFS). Basic patient data as well as surgery, pathology and postoperative treatment were taken into consideration.

Results

Significant differences in disease-free survival were found for TNM N-status, tumour differentiation grade and LNR quartile group. There was a difference in 3-year DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results were of prognostic interest both independently and in interaction with each other. High-risk groups could be identified and in the worst prognosis LNR group we also found a tendency towards more side effects with adjuvant chemotherapy.

Conclusion

The lymph node ratio, the quota between the number of lymph node metastasis and assessed lymph nodes, is a highly significant (p < 0.001) prognostic factor in stage III colon cancer. It can be an aid in identifying risk groups that could benefit from a more intense postoperative surveillance and possibly bring changes in adjuvant treatment strategy. More studies of clinical data, genetic and biochemical markers are needed in this patient group to understand the possible difference in tumour behaviour and tailor the treatment.     

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.     

Lymph Node Ratio is an Independent Prognostic Factor in Node Positive Rectal Cancer Patients Treated with Preoperative Chemoradiotherapy Followed by Curative Resection

Background: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection. Materials and Methods: A total of 131 consecutive rectal cancer patients who underwentneoadjuvant CRT and total mesorectal excision were included in this study. Patients were divided into two groups according to the LNR (≤0.2 [n=86], >0.2 [n=45]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). Results: The median number of retrieved and metastatic lymph node (LN) was 14 (range 1-48) and 2 (range 1-10), respectively. The median LNR was 0.154 (range 0.04-1.0). In multivariate analysis, LNR was shown to be an independent prognostic factor for both overall survival (hazard ratio[HR]=3.778; 95% confidence interval [CI] 1.741-8.198; p=0.001) and disease-free survival (HR=3.637; 95%CI 1.838-7.195; p<0.001). Increased LNR was significantly associated with worse OS and DFS in patients with <12 harvested LNs, and as well as in those ≥12 harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). Conclusions: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those≥12 harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.     

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Aim

To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS).

Materials and methods

Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan–Meier were performed.

Results

Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p < 0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR = 5.6, p < 0.001), positive SN (RR = 5.0, p < 0.001) and male sex (RR = 2.9, p = 0.001). The presence of a metastatic SN (RR = 8.4, p < 0.001), male sex (RR = 6.1, p < 0.001), Breslow thickness (RR = 3.2, p = 0.013) and ulceration (RR = 2.6, p = 0.015) were significantly associated with a poorer DSS.

Conclusion

SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure.     

Metastatic lymph node ratio in stage III rectal cancer; prognostic significance in addition to the 7th edition of the TNM classification

Aims

Optimal staging in rectal cancer is indispensable for the decision on further treatment and estimation of prognosis. This study assesses the prognostic capacity of the metastatic lymph node ratio (LNR) in addition to the new TNM classification.

Methods

LNR was determined, in stage III patients from the Dutch TME-trial. Six year median follow up data from the trial database were used to analyse the relation of LNR to overall survival (OS) and local recurrence (LR). The relation of LNR to lymph node yield was assessed and appropriate cut off values of LNR for clinical use were determined.

Results

605 patients were analyzed. 278 underwent pre-operative radiotherapy. 82 patients developed a local recurrence and 289 distant metastases. LNR was an independent risk factor for OS, hazard ratio (HR) 2.10 (95% CI 1.35–3.27) (in addition to age >= 65 years, involved circumferential resection margin (CRM) and new TNM stage) and LR, HR 2.25 (95% CI 1.02–4.56) (in addition to pre-operative radiotherapy and involved CRM). LNR is predictive of OS and LR from a lymph node yield of more than one and more than five respectively. A LNR value of 0.60 offers the best cut off to identify high risk patients (5-years OS was 61 vs. 32%, HR 2.45 (95% CI 1.96–3.08) and 5-years LR rate 12.6 versus 16.3%, HR 1.65 (95% CI 1.03–2.64)).

Conclusions

LNR is an independent risk factor for OS and LR in addition to the 7th edition of the TNM classification. It can aid in predicting prognosis and identifying patients that should be considered for adjuvant treatment.     

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 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.     

A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: A meta-analysis of 1909 patients

Aim

To compare outcomes between pancreaticoduodenectomy (PD) and extended pancreaticoduodenectomy (EPD) from all published comparative studies in the literature.

Methods

Using meta-analytical techniques the present study compared operative details, post-operative adverse events and survival following PD and EPD. Comparative studies published between 1988 and 2005 of PD versus EPD were included. End points were classified into peri-operative details, post-operative complications including 30 day mortality, and survival as measured during follow up. A random effect model was employed.

Results

Sixteen comparative studies comprising 1909 patients (865 PD and 1044 EPD), including 3 randomized controlled trials with 454 patients (226 PD and 228 EPD) were identified. Tumour size was comparable between the groups (weighted mean difference (WMD) −0.16 cm, p = 0.76). Significantly more lymph nodes were harvested from those patients undergoing EPD (WMD p = 14 nodes, p ≤ 0.001). Operative time was longer in EPD (WMD −48.9 min, p < 0.001) and there was a trend towards fewer positive resection margins (odds ratio (OR) 1.78, p = 0.080). Peri-operative adverse events were similar between the groups with only delayed gastric emptying (OR 0.59, p = 0.030) occurring less frequently in the PD group. Peri-operative mortality (OR 1.48, p = 0.180) and long-term survival (hazard ratio 0.77, p = 0.100) showed a non-significant trend favouring EPD.

Conclusions

EPD is associated with a greater nodal harvest and fewer positive resection margins than PD. However, the risk of delayed gastric emptying is increased and no significant survival benefit has been shown. Better designed, adequately powered studies are required to settle this question.     

Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: A prospective,hypothesis driven study on patients with locally advanced rectal cancer

Purpose/objective

Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer.

Material/methods

295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages).

Results

276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response.

Conclusion

CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of earlier developed prediction models using clinical variables and PET-information. The new model could help to an early adaptation of treatment in rectal cancer patients.     

Prediction of rectal lymph node metastasis by pelvic computed tomography measurement

Aim

Rectal cancer staging represents a crucial step to select the best treatment for this tumour. Particularly after neo-adjuvant chemoradiotherapy (CRT), it may influence the surgical procedure (e.g. radical resection vs. local excision). The aim of this study was to determine the best lymph node size cut-off at computed tomography (CT) to predict nodal metastasis in rectal cancer patients with and without preoperative CRT.

Methods

A consecutive series of patients operated on for primary mid–low rectal adenocarcinoma, all staged with pelvic CT scan, were subdivided as follows: those who underwent surgery alone treatment without CRT (Group A) and those who underwent preoperative CRT (Group B). All CT scans were re-viewed by a single radiologist and, based on the lymph node size, findings were compared with pathologic lymph node status (pN). At each lymph node size cut-off value, the following were calculated: accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The best cut-off value was defined as having an accuracy ≥70% with the highest NPV.

Results

The study population consisted of 162 patients: Group A (n = 52) and Group B (n = 110). Patients classified as pN-positive (n = 45) had a higher number of and larger sized lymph nodes by CT scan than patients classified as pN-negative (n = 117). The cut-off values with an accuracy ≥70% ranged between 7 and 11 mm in Group A and between 9 and 14 mm in Group B. The cut-off with the best NPV was 7 mm for Group A and 10 mm for Group B.

Conclusions

Acknowledging the limitations of the dimensional criterion, lymph node size cut-off values found in our study may be useful for planning rectal cancer treatment using CT scan.     

Clinical outcomes in older or younger patients with papillary thyroid carcinoma: Impact of lymphadenopathy and patient age

Aims

To examine lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC) according to clinicopathological features and outcomes associated with the nodal status.

Methods

We reviewed 231 patients with PTC (≥1.0 cm) who underwent initial thyroidectomy with modified neck dissection. LNM was examined in the central and lateral compartment and risk factors for disease-free survival (DFS) were evaluated. Nodal status and outcomes were further evaluated in four subgroups, 19 older patients (≥45 years old) with palpable lymphadenopathy (PLA) and 134 without PLA, and 11 younger patients (<45 years old) with PLA and 67 without PLA, because multivariate analysis revealed that age (p < 0.05, Hazard ratio (HR) 3.51) and PLA (p < 0.0001, HR 14.9) were risk factors for DFS.

Results

Central and lateral LNM were found in 176 and 151 patients. Seventeen exhibited skip metastasis. Recurrence and disease death occurred in 23 and 5. In analysis of the four subgroups, recurrence was significantly frequent in older patients with PLA than in younger patients with PLA or older patients without PLA (8/19 vs. 3/11 or 12/134). Younger patients without PLA did not exhibit recurrence.

Conclusions

Prognosis is worse in older patients with PLA. Such patients should be treated carefully with a considerable treatment strategy.     

Improvements in breast cancer survival over time,related to adjuvant treatment and node status

Background

There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups.

Methods

A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan–Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis.

Results

The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p = 0.99. Within the node negative group, patients with tumours ≥ 2 cm had an improved RFS from 80% to 88%, p = 0.02.

Conclusion

The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.     

Comparison of concomitant boost radiotherapy against concurrent chemoradiation in locally advanced oropharyngeal cancers: A phase III randomised trial

Purpose

To test the toxicity and efficacy of concomitant boost radiotherapy alone against concurrent chemoradiation (conventional fractionation) in locally advanced oropharyngeal cancer in our patient population.

Methods and materials

In this open-label, randomised trial, 216 patients with histologically proven Stage III–IVA oropharyngeal cancer were randomly assigned between June 2006 and December 2010 to receive either chemoradiation (CRT) to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (100 mg/m² on days 1, 22 and 43) or accelerated radiotherapy with concomitant boost (CBRT) to a dose of 67.5 Gy in 40 fractions over 5 weeks. The compliance, toxicity and quality of life were investigated. Disease-free survival (DFS) and overall survival (OS) curves were estimated with the Kaplan–Meier method and compared using log rank test.

Results

The compliance to radiotherapy was superior in concomitant boost with lesser treatment interruptions (p = 0.004). Expected acute toxicities were significantly higher in CRT, except for grade 3/4 mucositis which was seen more in CBRT arm (39% and 55% in CRT and CBRT, respectively; p = 0.02). Late toxicities like Grade 3 xerostomia were significantly high in CRT arm than CBRT arm (33% versus 18%; p < 0.0001). The quality of life was significantly poor in CRT arm at all follow up visits (p < 0.0001). The rates of 2 year disease-free survival were similar with 56% in the chemoradiotherapy group and 61% in CBRT group (p = 0.2; HR-0.81, 95%CI-0.53–1.2). Subgroup analysis revealed that patients with nodal size >2 cm had significantly better DFS with CRT (p = 0.05; HR-1.59, 95%CI-0.93–2.7).

Conclusion

In selected patients of locally advanced oropharyngeal cancer, concomitant boost offers a better compliance, toxicity profile and quality of life with similar disease control, than chemoradiation.     

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.     

Prognostic value of lymph node metastases and lymph node ratio in esophageal squamous cell carcinoma

Aims

Although the positive lymph node (LN) metastasis in patients with thoracic esophageal squamous cell carcinoma carcinoma (SCC) has been reported to be a risk factor to reduce long-term survival, only a few studies have so far evaluated the lymph node metastasis among this group of patients. The purpose of this study was to evaluate the impact of lymph node positivity and ratio on survival of esophageal SCC.

Methods

All patients undergoing esophagectomy at the Forth Hospital of Hebei Medical University between January 1986 and December 2002 were reviewed. Survival curves were estimated using the Kaplan-Meier method.

Results

Of 1325 patients with invasive cancer, had squamous cell cancer of the esophagus. Median overall survival (OS) of the entire group was 36.7 months and 5-year OS was 39.3%. The most significant prognostic factor for overall survival was the presence of positive LN (P < 0.01). Additionally, patients with zero involved LN had a 5-year survival of 49.1%, while patients with 1–3 positive LN and >3 positive LN had 5-year survival of 19.5% and 11.0%, respectively (P < 0.01). Finally, an increasing ratio of positive to examined LN was linearly associated with a worsening 5-year survival, patients with <25%, 25%–50% and >50% positive LN had 5-year survival of 47.53%, 14.6% and 8.9%, respectively (P < 0.01).

Conclusion

Increasing number of positive LN in patients with esophageal cancer and increasing ratio of metastatic to examine LN portend a poor prognosis. These factors should play an important role in predicting prognosis of patients.     

Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: Long-term results focused on topographic pattern of locoregional relapse

Background

Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT.

Methods

A total of 335 patients with LARC [?cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed.

Results

Median follow-up was 72.6 months (range, 4–205). In multivariate analysis distal margin distance ?10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1–2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC.

Conclusions

Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.     

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.     

Does the count after inguinofemoral lymphadenectomy in vulvar cancer correlate with outcome?

Background

Inguinal lymph node (LN) metastasis is an important prognostic factor in vulvar cancer. Our aim was to determine the prognostic value of the number of resected LNs in inguinofemoral lymphadenectomy.

Methods

A retrospective analysis was performed in a series of 158 individuals who underwent bilateral inguinofemoral lymphadenectomy for vulvar squamous cell carcinoma from January 1980 to February 2010.

Results

The mean age was 67 years (range: 15–90). Median tumor size was 5 cm (range: 1–18). A median of 22.5 inguinal LNs (range: 2–57) was resected. Thirteen (8.2%) patients had <12 LNs resected, and 145 (91.8%) had ≥12 LNs resected. Eighty (50.6%) patients had LN metastasis, with a median of 2 positive LNs (range: 1–16). Of those with positive LNs, 19 (23.8%), 23 (28.8%), and 38 (47.5%) patients had 1, 2, and 3 or more positive LNs, respectively. Thirty-three (41.2%) patients had bilateral LN metastasis. For patients without LN involvement, we failed to observe any significant difference between patients with <12 LNs and ≥12 LNs that were resected with regard to risk of recurrence (p = 0.97) and death from cancer (p = 0.43) in 5 years. However, resection of <12 LNs in patients with positive LNs negatively impacted the risk of recurrence (p = 0.003) and death from cancer (p = 0.043).

Conclusions

Resection of fewer than 12 LNs in vulvar cancer has a negative impact on outcome for patients with positive inguinal LNs.     

Markers of tumour angiogenesis and tumour cells in bone marrow in gastric cancer patients

Aims

Vascular endothelial growth factors VEGF-A, VEGF-C and VEGF-D are considered to be potentially angiogenetic and lymphangiogenetic. “Minimal residual disease” is responsible for cancer progression and recurrence. In this study, we investigated the relation between expressions of VEGF-A, VEGF-C and VEGF-D in gastric cancer tissue and the presence of tumour cells in bone marrow.

Methods

A total of 50 resected primary gastric adenocarcinomas, 44 non-cancerous gastric mucosa and 36 lymph node metastases were analyzed by immunohistochemistry for VEGF-A, VEGF-C and VEGF-D. The specimens used were drawn from a previous study cohort, where the presence of ITC in bone marrow was confirmed with immunohistochemical assay with cytokeratin (CK)-18.

Results

The levels of expression of VEGF-A, VEGF-C and VEGF-D were highest in tumour (p < 0.001), and the level in lymph node metastases was significantly higher (p < 0.01) than in mucosa. The expression of VEGF-A was correlated significantly with venous tumour invasion (p < 0.05) and the presence of tumour cells in bone marrow (p < 0.05). Tumours expressing high levels of VEGF-D showed significantly advanced stages of tumour infiltration (p < 0.05) and lymph node metastasis (p < 0.01).

Conclusions

VEGF-A is a significant marker for the presence of tumour cells in the bone marrow of gastric cancer patients. Our results confirm VEGF-D as a predictor for the lymphatic spread of tumour cells. Therefore, the route of metastatic spread of gastric cancer could be determined, at least in part, by the profile of VEGF family members expressed in the primary tumour of gastric cancer patients.     

Prognosis Impact of the Lymph Node Ratio in Patients with Colon Adenocarcinoma: a Single-Centre Experience

Purpose

Recently, the positive lymph node ratio (LNR) is considered a new prognostic parameter on survival and time to progression for patients with colon cancer. The aim of this study was to determine the prognostic impact of the LNR as an independent factor for overall survival (OS) and disease-free survival (DFS) in patients with colon cancer regardless of their clinical stage.

Methods

We retrospectively identified 85 consecutive patients diagnosed with colon adenocarcinoma treated in our centre during 2010. We categorized patients according to a LNR cutoff of 0.25. Three-year OS and DFS were determined according to the Kaplan–Meier method. A Cox proportional model was used to assess the influence of other prognostic variables on each outcome.

Results

After median follow-up of 34.8 months, neither median OS nor DFS has been reached by any of the subgroups. Nevertheless, patients with a LNR?≥?0.25 exhibited a higher risk of death (hazard ratio, 3.10; 95 % confidence interval (CI), 1.38–7.01; log-rank test: p?=?0.006) and a shorter interval without progression (hazard ratio, 6.59; 95 % CI, 1.96–22.15; log-rank test: p?=?0.002.) than patients with LNR?<?0.25. After adjusting for prespecifed variables, the impact of a LNR?≥?0.25 was independently associated with OS (hazard ratio, 2.8; 95 % CI, 1.01–7.73; p?=?0.04) and DFS (hazard ratio, 7.07; 95 % CI, 1.23–40.45; p?=?0.03).

Conclusions

LNR was independently associated with OS and DFS in patients with colon adenocarcinoma regardless of its clinical stage.