F-FDG PET bio-metabolic monitoring of neoadjuvant therapy effects in rectal cancer: Focus on nodal disease characteristics

Objective

To evaluate efficacy of ¹⁸F-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy.

Patients and methods

Patients with confirmed diagnosis of rectal cancer (T2-4 or N+) were prospectively studied with ¹⁸F-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4-6 weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference in SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI).

Results

A total of 64 patients were enrolled for pathological and bio-metabolic response assessment. Compared to cN0, cN+ patients had a higher SUV₁ mean value (6.5 vs. 7.6, p = 0.04) and ypN+ patients had higher SUV₂ mean values (2.4 vs 3.5, p = 0.06). difSUV values of ?4 was the most efficient diagnostic parameter (sensitivity = 45.8%, specificity = 86.2%, positive predictive value (PPV) = 73.3%, negative predictive value(NPV) = 65.7%). With an RI of 66.6%, the sensitivity was 38.5%, specificity = 81.5%, PPV = 66.6%, and NPV = 57.8%. Patients who experienced disease progression had an RI ? 66% and a difSUV ? 4.

Conclusion

¹⁸F-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnostic imaging techniques.     

Intensified neoadjuvant chemoradiotherapy in locally advanced rectal cancer – impact on long-term quality of life

Aims

In spite of advances in rectal cancer surgery and the use of preoperative 5-fluorouracil-(5-FU) based chemoradiotherapy (CRT) in stage II and III disease distant metastases still occur in about 35–40% of the patients. Intensified preoperative CRT (ICRT) using other drugs in conjunction with 5-FU has been investigated in order to improve the pathological complete remission (pCR) rate and thereby prognosis of patients with locally advanced rectal cancer. However, acute toxicity, especially diarrhea, was reported to be high and no improvement in pCR rates has been observed in randomized trials. Long-term results of these trials are pending. In the present analysis we investigated the impact of ICRT on health related quality of life and long term toxicity.

Methods

The present study included 119 patients with locally advanced rectal cancer who underwent neoadjuvant CRT followed by surgery within controlled clinical trials. Patients received ICRT (n = 83) or standard CRT (n = 36). Evaluation of HRQoL was performed using EORTC QLQ-C30 and QLQ-CR29 questionnaires.

Results

The overall rating of global health status/QLQ scale of the EORTC QLQ-C30 questionnaire was identical in both patient groups but patients in the CRT group showed better results in four out of nine function scales. Concerning symptom scales, patients in the CRT arm exhibited significantly less diarrhea (p = 0.028) and less disorders with taste (0.042).

Conclusions

This data suggests that higher gastrointestinal acute toxicity caused by ICRT might lead to a higher risk of long-term deterioration of “gastrointestinal QoL”. Future results of randomized trials investigating ICRT versus CRT should be discussed in the light of long-term QoL data.     

Optimal Interval for 18F-FDG-PET After Chemoradiotherapy for Rectal Cancer

Introduction

Although ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been increasingly used to evaluate the response to preoperative chemoradiotherapy (CRT) in patients with rectal cancer, the optimal intervals between completion of CRT, PET, and surgery have not been fully investigated.

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.     

Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: Preliminary results of a monoinstitutional prospective study

Purpose

To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant chemoradiotherapy (CRT).

Methods and materials

A total of 28 patients with LARC underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor volume (TV) was calculated on T2-weighted MRI scans as well as the apparent diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. Post-treatment difference ADC (%ΔADC) and TV (%ΔTV) changes at 8 weeks were compared complete response (CR; TRG1) and non-complete response tumors (non-CR; TRG2–5).

Results

The mean % ADC increase of CR group was significantly higher compared to non-CR group (77.2 ± 54.63% vs. 36.0 ± 29.44%; p = 0.05). Conversely, the mean % TV reduction did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p = 0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to discriminate CR from non-CR group was significantly higher than that of the mean % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative correlation between mean % ADC increase and TRG was recorded (r = −0.69; p = 0.006).

Conclusion

The mean % ADC increase appears to be a reliable tool to differentiate CR from non-CR after CRT in patients with LARC.     

Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment – A pilot study

Aim

In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

Patients and methods

Fifty-three (n = 53) patients with locally advanced rectal cancers treated with neoadjuvant CRT followed by surgery were identified from the pathology databases of 2 tertiary referral centres over a 4-year period. Immunohistochemical staining of treatment specimens was carried out using the 5-Methylcytidine (Eurogentec, Seraing, Belgium) antibody. Quantitative analysis of staining was performed using an automated image analysis platform. The modified tumour regression grading system was used to assess tumour response to neoadjuvant therapy.

Results

Seven (13%) patients showed complete pathological response while 46 (87%) patients were partial responders to neoadjuvant treatment. In 38 (72%) patients, significant reduction in methylation was observed in post-treatment resection specimens compared to pre-treatment specimens (171.5 vs 152.7, p = 0.01); in 15 (28%) patients, methylation was increased. Pre-treatment methylation correlated significantly with tumour regression (p < 0.001), T-stage (p = 0.005), and was able to predict complete and partial pathological responders (p = 0.01).

Conclusion

Neoadjuvant CRT appears to alter the rectal cancer epigenome. The significant correlation between pre-treatment DNA methylation with tumour response suggests a potential role for methylation as a biomarker of response.     

Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: A near pathologic complete response does not translate into good clinical outcome

Background

After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum.

Aim

The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients.

Methods

Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6–8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators.

Results

The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators.

Conclusion

The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that “watch-and-wait” in LARC patients should be applied with care.     

Can complete tumor resection be predicted in advanced primary epithelial ovarian cancer? A systematic evaluation of 360 consecutive patients

Background

Postoperative tumor-residual-mass is the most important prognostic factor in epithelial ovarian cancer (EOC). Aim of our study was to define risk factors for incomplete tumor resection in advanced primary EOC.

Patients & methods

A validated intraoperative documentation tool (“Intraoperative-Mapping of Ovarian-Cancer” = “IMO”) was applied to systematically evaluate intraabdominal tumor dissemination pattern, maximal tumor load, tumor residuals and operative morbidity for all EOC-patients who underwent primary surgery in our institution during 09/2000–08/2009. Univariate- and multivariate analysis were performed to identify independent risk factors of incomplete tumor resection and operative complications.

Results

We evaluated 360 consecutive EOC-patients of FIGO-stage-III/IV. In 221(61%) patients a complete tumor resection could be obtained. In 50(14%) patients tumor residuals were <0.5 cm. Sixty (17%) patients developed a major (14%) complication. Multivariate analysis identified intestinal resection (OR:2.0; 95%CI:1.14–3.4; p = 0.01) and macroscopical tumor residuals (OR:0.5; 95%CI:0.2–1.2; p = 0.05) as independent predictors of major operative morbidity. Tumor dissemination pattern and maximal tumor load were significantly different between tumor-free and not-tumor-free operated patients, with less extrapelvic tumor involvement in the tumor-free group (p < 0.001). More than 4 IMO-fields of tumor involvement (OR:3.3; 95%CI:1.5–7.0; p = 0.002) were identified to be of predictive significance for incomplete tumor resection. FIGO-stage, histology, age, CA125-levels, bowel resection and ascites did not affect optimal tumor resectability.

Conclusions

Tumor expanding in multiple (>4) abdominal quadrants was the major negative predictors for complete tumor resection in primary EOC-patients. Bowel resection and macroscopical tumor residuals were of predictive value for a higher operative major morbidity. Identifying high-risk patients for suboptimal tumor resection and operative complications may improve surgical outcome in advanced primary EOC.     

The metabolic response using F-fluorodeoxyglucose-positron emission tomography/computed tomography and the change in the carcinoembryonic antigen level for predicting response to pre-operative chemoradiotherapy in patients with rectal cancer

Background and purpose

To predict tumor regression in pre-operative chemoradiotherapy (CRT) using ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and serum carcinoembryonic antigen (CEA) in patients with rectal cancer.

Materials and methods

The metabolic response of the tumor was assessed by determining the maximal standardized uptake value (SUV_max), absolute difference (ΔSUV_max), and SUV reduction ratio (SRR) on pre- and post-CRT PET/CT scans. The serum CEA, absolute difference (ΔCEA), and the CEA reduction ratio (CRR) were also determined. A receiver-operating characteristic (ROC) curve was generated.

Results

Of all seventy two patients, mean pre- and post-CRT SUV_max was 14.9 and 5.8, respectively. The mean pre- and post-CRT CEA level was 15.5 ng/ml and 5.4 ng/ml, respectively. Forty-three patients (59.8%) were classified as responders (Dworak’s tumor regression grade 3-4) and 36 patients (50%) achieved tumor down-staging. ROC analysis showed that both post-CRT SUV_max and SRR were predictive factors for responders (p = 0.03 and p = 0.02, respectively). A threshold of post-CRT SUV_max was 5.4 and that of SRR was 53.1%. Pre-CRT SUV_max, ΔSUV_max, and all parameters in regard to CEA were not significant in ROC analysis.

Conclusions

The post-CRT SUV_max and SRR are potential factors for predicting tumor response in pre-operative CRT. The patients with lower post-CRT SUV_max and higher SRR could be expected to achieve maximum tumor regression after pre-operative CRT in this study.     

Integrated models for the prediction of late genitourinary complaints after high-dose intensity modulated radiotherapy for prostate cancer: Making informed decisions

Background and purpose

To develop predictive models for late radiation-induced hematuria and nocturia allowing a patient individualized estimation of pre-treatment risk.

Materials and methods

We studied 262 PCa patients treated with curative intensity modulated radiotherapy to the intact prostate or prostate bed. A total of 372 variables were used for prediction modeling, among which 343 genetic variations. Toxicity was scored using an in-house developed toxicity scale. Predictor selection is achieved by the EMLasso procedure, a penalized logistic regression method with an EM algorithm handling missing data and crossvalidation avoiding overfit. Model performance was expressed by the area under the curve (AUC) and by sensitivity and specificity.

Results

Variables of the model predicting late hematuria (36/262) are bladder volume receiving ?75 Gy, prostatic transurethral resection and four polymorphisms. (AUC = 0.80, sensitivity = 83.3%, specificity = 61.5%). The AUC drops to 0.67 when the genetic markers are left out. The model that predicts for late nocturia (29/262) contains the minimal clinical target volume (CTV) dose, the CTV volume and three polymorphisms (AUC = 0.76, sensitivity = 75.9%, specify = 67.4%). This model is a better predictor for nocturia compared to the nongenetic model (AUC of 0.60).

Conclusions

We were able to develop models that predict for the occurrence of late radiation-induced hematuria and nocturia, including genetic factors which might improve the prediction of late urinary toxicity.     

Impaired continence function five years after intensified chemoradiation in patients with locally advanced rectal cancer

Aims

While the influence on survival is only seen in patients with complete regression after neoadjuvant treatment in locally advanced rectal cancer the impairment of the continence capacity weighs even more for patients with little oncological benefit.

Methods

Patients treated with intensified preoperative radiochemotherapy patients treated only by TME surgery were asked five years after treatment to complete the Wexner and SF-12 quality of life questionnaire.

Results

25 after neoadjuvant treatment had a median Wexner score of 14 [3–20] after 63 [42–78] months. Histopathological stage or grade of regression did not influence the Wexner score (p = 0.76, resp. p = 0.9). 12% describe themselves as being permanently continent; 40% are stool incontinent “always” or “most of the time”. 68% are always wearing pads.29 patients after TME only showed a median Wexner score of 5 [range 0–17] after 66 months [26–133].SF-12 showed significantly lower values in physical (p = 0.02) as well as mental summary scales (p = 0.015) in patients after RCTX while patients after radical surgery showed no difference to the norm population.

Conclusion

This study shows that continence is significantly worse five years after neoadjuvant treatment. Moreover, patients after neoadjuvant treatment and surgery have impaired quality of life compared to norm population. These results may contribute to the discussion of only applying neoadjuvant chemoradiation selectively in patients with advanced rectal cancer.     

Predictors of axillary lymph node metastasis in breast cancer: A systematic review

Aims

To review the established and emerging techniques in axillary lymph node prediction and explore their potential impact on clinical practice. To reliably identify patients in whom axillary lymph node surgery, including SLNB, can be safely omitted.

Methods

Searches of PubMed were made using the search terms “axilla” (or “axillary”), “lymph”, “node” and “predictor” (or “prediction”). Articles from abstracts and reports from meetings were included only when they related directly to previously published work.

Findings

There are numerous studies in which the predictive utility of biomarkers as determinants of axillary lymph node status have been investigated. Few of these have specifically addressed the attributes of the primary tumour which could offer much potential for the prediction of tumour metastasis to the axillary lymph nodes.

Conclusions

Currently, no single marker is sufficiently accurate to obviate the need for formal axillary staging using SLNB or axillary clearance.     

Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells,involving miRNAs-320a, -224, -132 and let7g

Background and purpose

Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity.

Material and methods

Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies.

Results

Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7g was associated with a good prognosis in rectal cancer patients (P = 0.03).

Conclusions

This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker.     

Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer

Background:

Foxp3⁺ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown.

Methods:

Foxp3⁺, CD3⁺, CD4⁺, CD8⁺ and IL-17⁺ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated.

Results:

Stromal Foxp3⁺ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3⁺ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3⁺ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade.

Conclusions:

Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer.     

Tumor response after long interval comparing 5x5Gy radiation therapy with chemoradiation therapy in rectal cancer patients

Background

In the era of organ preserving strategies in rectal cancer, insight into the efficacy of preoperative therapies is crucial. The goal of the current study was to evaluate and compare tumor response in rectal cancer patients according to their type of preoperative therapy.

Utility or futility of prognostic scoring systems for colorectal liver metastases in an era of advanced multimodal therapy

Objectives

To assess the general applicability of prognostic scores for colorectal liver metastases (CRLM).

Methods

Review of English language studies from 1980 to 2008 (Medline and Embase). Search keywords included “Colorectal neoplasms”, “liver metastases”, “liver resection”, “prognostic scoring system”.

Results

Six scoring systems and fourteen prognostic factors within these studies were identified. No prognostic factor was common in all scoring methods. Five scores retained the number of metastases as a prognostic factor. Size of metastases and time between the onset of the primary tumor and the discovery of metastases were present in four scores. Three scores predicted 5-year survival using carcinoembryonic antigen (CEA) and R1 resection. Only two scores were assessed preoperatively. Successive scoring methods had improved predictive accuracy compared to earlier systems. However, their applicability in general populations remains debatable. An evaluation of the scores applicability to different patient populations demonstrated that the models were minimally effective in predicting disease-specific survival and recurrence, suggesting that stratification of patients by clinical and pathologic factors alone, may be clinically unreliable and not applicable for selection of patients for surgery.

Conclusion

The utility of prognostic models on general populations is inconsistent. Current clinicopathologic factors may be inadequate to determine disease prognosis in CRLM. Future attempts to develop prognostic scores should include additional biologic and clinical variables, and be validated in larger populations.     

Local recurrence in rectal cancer can be predicted by histopathological factors

Aim

The main cause of local recurrence (LR) in rectal cancer is involvement of the circumferential resection margin (CRM). However, patients with a negative CRM can also develop LR, suggesting that additional factors are important for LR. The aim of this study was to identify histopathological factors predictive for the development of LR after primary rectal cancer treatment.

Methods

T × N × M0 patients treated for locally recurrent rectal cancer at the Catharina hospital from 1994 to 2006 (n = 92) were matched with a control group of patients who did not develop LR after primary rectal cancer treatment for at least 2 years (n = 185) based on the type of neoadjuvant treatment in a 1:2 ratio. The pathology of all primary rectal cancers was reviewed. Patient, treatment and histopathological characteristics were studied in relation to the development of LR with logistic regression.

Results

Logistic regression indicated the presence of lymphovascular invasion (LVI, OR 4.66, P < 0.001), extramural venous invasion (EMVI, OR 4.54, P < 0.001), positive CRM (OR 2.56, P = 0.032), serosal involvement (OR 6.74, P = 0.035) and poor differentiation (OR 2.59, P = 0.012) as factors with an increased risk to develop LR. Older age was a protective factor (OR 0.95, CI 0.93–0.98, P = 0.001).

Conclusion

Apart from a positive CRM and serosal involvement, LVI, EMVI and poor differentiation are important independent predictive factors for the development of LR. Adjuvant therapy may be considered in the presence of these features in order to decrease the risk of a local recurrence.     

Quantitation of sentinel node metastatic burden and Her-2/neu over-expression accurately predicts residual axillary nodal involvement and extranodal disease in breast cancer

Background data

Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established.

Aims

To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases.

Methods

84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors.

Results

Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm² was an independent predictor for NSLN metastases and extranodal disease.

Conclusion

Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.     

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.