Magnetic resonance for assessment of axillary lymph node status in early breast cancer: A systematic review and meta-analysis

Introduction

Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients.

Methods

Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard.

Results

Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%).

Conclusions

USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.     

Accuracy of sentinel lymph node biopsy in large and multifocal/multicentric breast carcinoma—A systematic review

Background

While sentinel lymph node biopsy (SLNB) is established in the management of small unifocal breast cancer its role in management of multifocal (MF), multicentric (MC) and larger tumors is still evolving.

Methods

Medline was searched; studies meeting pre-determined criteria were included. Data were extracted and entered into evidence tables.

Results

Twenty six studies met inclusion criteria and reported data on accuracy; no randomized trials were identified. For MF cancers (n = 314 cases), success rate for identification of an SLN was 86-94%, SLN positivity rate 42-59%, false negative rate (FNR) 0-33% and overall accuracy 78-100%. For MC (n = 294 cases): success rate 92-100%, SLN positivity rate 25-61%, FNR 4-8% and accuracy 96-100%. For ‘multiple breast cancer’ (studies combining MF/MC cases; n = 996 cases): success rate 92-100%, SLN positivity rate 12-63%, FNR 0-25%, and accuracy 82-100%. For larger tumors (n = 1912 cases): success rate 86-100%, SLN positivity rate 49-77%, FNR 3-18% and accuracy 85-98%. For MC/MF and larger cancers overall non-SLN positivity rates were up to 82%; axillary recurrence rates were low but seldom reported.

Conclusion

There are no randomized trials evaluating the safety of SLNB in MF/MC and larger breast cancers. Based on limited evidence, success rate and FNR appear to be similar to those for small unifocal cancers, however node positivity rates are higher and rates of non-SLN positivity are very high. Awareness of these issues is essential when recommending SLNB based axillary management for these higher-risk tumors.     

Cost-effectiveness of MRI and PET imaging for the evaluation of axillary lymph node metastases in early stage breast cancer

Background

UK guidelines for breast cancer recommend axillary nodal assessment via surgical methods such as sentinel lymph node biopsy (SLNB). However, these procedures are associated with adverse effects such as lymphoedema. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are non-invasive imaging techniques. The aim of this study is to evaluate the cost-effectiveness of MRI and PET compared with SLNB for assessment of axillary lymph node metastases in newly-diagnosed early stage breast cancer patients in the UK.

Methods

An individual patient discrete-event simulation model was developed in SIMUL8^® to estimate the lifetime costs and benefits of replacing SLNB with MRI or PET, or adding MRI or PET before SLNB. Effectiveness outcomes were derived from a recent systematic review; patient utilities and resource use data were sourced from the literature.

Results

Based on our analysis the baseline SLNB strategy is dominated by the strategies of replacing SLNB with either MRI or PET. The strategy of replacing SLNB with MRI has the highest total quality-adjusted life years (QALYs) and lowest total costs. However, clinical evidence for MRI is based on a limited number of small studies and replacing SLNB with MRI or PET leads to more false-positive and false-negative cases. The strategy of adding MRI before SLNB is cost-effective, but subject to greater uncertainty.

Conclusions

Based on this analysis the most cost-effective strategy is to replace SLNB with MRI. However, further large studies using up-to-date techniques are required to obtain more accurate data on the sensitivity and specificity of MRI.     

The value of 18-FDG PET/CT in early-stage breast cancer compared to traditional diagnostic modalities with an emphasis on changes in disease stage designation and treatment plan

Background

Proper preoperative staging is vital in the treatment of breast cancer patients. The aim of our study was to assess the value of the diagnostic information provided by PET/CT in surgical practice in breast cancer cases considered early-stage by conventional diagnostic modalities.

Methods

Whole-body 18-FDG PET/CT was performed on 115 breast cancer patients in whom traditional diagnostic modalities showed no signs of distant metastases or extensive axillary and/or extra-axillary lymphatic spreading, and the size of the primary tumor was <4 cm.

Results

The sensitivity of PET/CT in the detection of the primary tumor was 93%. The sensitivity of the traditional diagnostic modalities in the detection of multifocality was 43.8% while that of PET/CT was 100% (p < 0.001). In the assessment of axillary lymph nodes, ultrasound had a sensitivity of 30% and a specificity of 95%. The corresponding estimates for PET/CT were 72% and 96%, respectively. PET/CT detected distant metastases in 8 patients. TNM classification was modified after PET/CT scanning in 54 patients (47%). PET/CT data changed the treatment plan established upon the results of traditional imaging modalities in 18 patients (15.6%).

Conclusions

PET/CT is able to assess primary tumor size and axillary lymphatic status more accurately than traditional diagnostic methods. It can detect distant metastases in 7-8% of those patients who were declared free of metastasis by clinical investigations. PET/CT scan modifies the disease stage determined by traditional diagnostic modalities in almost half of the patients and leads to a change in the treatment plan in every 6th patient.     

The Comparative Study of Ultrasonography,Contrast-Enhanced MRI,and 18F-FDG PET/CT for Detecting Axillary Lymph Node Metastasis in T1 Breast Cancer

Purpose

A more noninvasive evaluation of axillary lymph node in breast cancer is one of the principal challenges of breast cancer treatment. To detect axillary lymph node metastasis (ALNM) in T1 breast cancer, we have compared the axillary ultrasonography (AUS), contrast-enhanced magnetic resonance imaging (cMRI), and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) to determine the most adequate test or a combination of tests.

Methods

Retrospectively, 349 T1 breast cancer patients who were preoperatively examined using AUS, cMRI, and PET/CT between 2008 and 2011 and whom underwent pathological evaluations of axillary lymph nodes were reviewed and analyzed.

Results

In total, 26.4% (92/349) of patients exhibited ALNM. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of AUS for determining ALNM were 44.6%, 88.7%, 58.6%, 81.7%, and 77.1%, respectively. cMRI was similar to AUS. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT were 44.5%, 94.2%, 73.2%, 82.6%, and 81.1%, respectively. The combination including cMRI and PET/CT was the most accurate with sensitivity, specificity, PPV, NPV, and accuracy values of 39.1%, 98.8%, 92.3%, 81.9%, and 83.1%, respectively. The mean number (3.5±4.2) of ALNMs in the patients who were positive based on cMRI and PET/CT and also pathologically proven to exhibit ALNM was significantly larger than the number (2.16±2.26) in other patients who exhibited ALNM (p=0.035).

Conclusion

There are no definitive modalities for detecting ALNM in T1 breast cancers to replace sentinel lymph node biopsy (SLNB). If ALNM is suspected based on cMRI and PET/CT, the axillary dissection without SLNB might be a better option because it is related to high possibilities of ALNM and large axillary metastatic volumes.     

Sentinel lymph node biopsy after previous axillary surgery: A review

Background

The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers.

Methods

We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND).

Results

There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up.

Conclusion

SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery.     

Axillary nodal yields: A comparison between primary clearance and completion clearance after sentinel lymph node biopsy in the management of breast cancer

Aims

Axillary nodal status is the most important prognostic indicator which in turn influences adjuvant therapy and long term outcomes. The aim of this study was to compare total nodal yields from primary axillary lymph node dissection (pALND) with completion ALND after a cancer positive SLNB: either concurrently (cALND) following intra-operative assessment (IOA) of the SLN’s or as a delayed procedure (dALND) when the SLN was found to be cancer positive on post-operative histological examination.

Methods

All axillary procedures performed between May 2006 and September 2009 were identified from a prospective database and categorised into four groups: SLNB with no further axillary surgery, pALND, cALND and dALND. Total nodal yield was the sum of SLN/s and ALND yields.

Results

Of 1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%) underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were 15.0, 16.0 and 14.5 respectively (p = 0.3).

Conclusion

Total nodal yields for primary, concurrent and delayed ALND were comparable suggesting completion dALND performed as a second operation does not compromise axillary staging.     

Perioperative diagnosis of the positive axilla in breast cancer: A safe, time efficient algorithm

Background

This study evaluates the combined role of axillary ultrasound (Ax US), fine needle aspiration (FNAC) and intraoperative frozen section analysis of the sentinel node (FS SN) in a practical, time efficient algorithm to reduce the requirement for reoperation for axillary clearance in breast cancer in a busy tertiary unit.

Methods

Between October 2007 and June 2009 188 women underwent Ax US as a first investigation for nodal status. Suspicious nodes were biopsied, negative axillae proceeded to FS SN at time of primary breast surgery. All confirmed positive cases proceeded to immediate axillary clearance.

Results

93 women had positive axillary nodes at final histology. Ax US + FNAC identified 59 positive axillae and had a sensitivity of 63.4% and specificity of 100%. FS SN identified a further 26 cases with a sensitivity of 76.5% and specificity of 100%. Overall, only 8 women required reoperation for axillary clearance. Sensitivity for the combined procedures was 91.4%. Commencement of adjuvant therapy was significantly less in those women identified earlier compared to those requiring a second operation (23.3 days vs 49.0 days, p < 0.005).

Conclusion

95.7% of cases were diagnosed accurately in the perioperative period, preventing delay to triage to definitive oncological care and reducing requirement for costly reoperation.     

The efficacy of portal vein embolization prior to right extended hemihepatectomy for hilar cholangiocellular carcinoma: A retrospective cohort study

Background/Purpose

Preoperative portal vein embolization was introduced to minimize complications after extended hepatectomy. This retrospective cohort study was conducted to compare outcomes with and without portal vein embolization before hepatectomy for hilar cholangiocellular carcinoma.

Methods

This study was conducted with 35 patients who underwent right extended hemihepatectomy for hilar cholangiocellular carcinoma from 2001 to 2008. Preoperative portal vein embolization was performed in 14 patients (embolization group) and not performed in 21 patients (non-embolization group).

Results

The groups did not differ in terms of sex, age, operative time, transfusion, postoperative serum bilirubin level, prothrombin time, and length of intensive care unit (ICU) stay. Although blood loss was higher in the embolization group than in the non-embolization group (P = .009), no major complications were observed between embolization and resection. At presentation, future liver remnant was smaller in the embolization group (19.8%, range 16-35%) than in non-embolization group (28.3%, 15-47%; P = .001). After embolization, the volume of the future liver remnant increased significantly to 27.2% (range, 23-42%; P = .001). Future liver remnants just before operation were similar in both groups (P > .99). There was no significant difference in terms of the rate of morbidity and in-hospital mortality. No statistically significant differences were observed in disease-free survival (P = .52) and overall survival (P = .30).

Conclusions

Portal vein embolizations do not increase the rate of morbidity, in-hospital mortality, local recurrence and system metastasis. Therefore it can be considered safe and effective for patients with small future liver remnants. Embolization can lessen postoperative liver failure and widen the indication of the surgical resection, especially in patients with marginal future liver remnants.     

Persistent pain,sensory disturbances and functional impairment after immediate or delayed axillary lymph node dissection

Background

Patients treated with 2-step axillary lymph node dissection (ALND) may be at increased risk of nerve damage due to more challenging surgery than an ALND immediately after a sentinel lymph node biopsy (SLNB), and thus more at risk for persistent pain after breast cancer treatment (PPBCT). The aim of this study was to examine PPBCT, sensory disturbances and functional impairment in patients treated with a 2-step ALND compared to patients with an SLNB followed by an immediate ALND, and patients with ALND without a prior SLNB.

Methods

The study is a cross-sectional questionnaire study, comparing 2847 women treated with ALND in Denmark in 2005–2008. 196 patients treated with a 2-step ALND were compared with 1558 patients treated with an ALND after SLNB and 1093 with an ALND without a prior SLNB.

Results

Overall prevalence of PPBCT and sensory disturbances was high, with about 55% reporting PPBCT and 77% reporting sensory disturbances in all groups. No differences were found between the groups on prevalence and intensity of PPBCT (p = 0.92), sensory disturbances (p = 0.32), and functional consequences (p = 0.35).

Conclusions

A 2-step ALND does not modify the risk of developing PPBCT compared to an immediate ALND.     

The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast

Aim

Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM.

Methods

A review of 51 patients with a diagnosis of DCIS (n = 45) or DCISM (n = 6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed.

Results

In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (<2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (>2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found.

Conclusions

In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear.     

Clinical Significance of the Axillary Arch in Sentinel Lymph Node Biopsy

Purpose

The axillary arch is an anomalous muscle that is not infrequently encountered during axillary sentinel lymph node biopsy (SLNB) of breast cancer patients. In this study, we aimed to investigate how often the axillary arch is found during SLNB and whether it affects the intraoperative sentinel lymph node (SLN) identification rate.

Methods

We retrospectively analyzed the correlation between the presence of the axillary arch and the SLN sampling failure rate during SLNB in 1,069 patients who underwent axillary SLNB for invasive breast cancer.

Results

Of 1,069 patients who underwent SLNB, 79 patients (7.4%) had the axillary arch present. The SLNB failure rate was high when the patient''s body mass index was ≥25 (p=0.026), when a single SLN mapping technique was used (p=0.012), and when the axillary arch was present (p<0.001). These three factors were also found to be statistically significant by multivariate analysis, and of these three factors, presence of the axillary arch most significantly increased the SLNB failure rate (hazard ratio, 10.96; 95% confidence interval, 4.42-27.21; p<0.001). Additionally, if the axillary arch was present, the mean operative time of SLNB was 20.8 minutes, compared to 12.5 minutes when the axillary arch was not present (p<0.001). If the axillary arch was present, the SLN was often located in a high axillary region (67%) rather than in a general low axillary location.

Conclusion

The axillary arch was found to be a significant factor affecting intraoperative SLN failure rate. It is necessary to keep in mind that carefully checking the high axillar region during SLNB in breast cancer patients with the axillary arch is important for reducing SLN sampling failure.     

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.     

A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study

Background

Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines.

Patients and methods

In part I, we used a 3 + 3 dose-escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1-14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD.

Results

Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20 mg/m² plus capecitabine 1000 mg/m² was the MTD. Pharmacokinetic analysis showed no apparent drug-drug interaction. In all patients, the main grade 3-4 toxicities were asthenia (n = 5), hand-foot syndrome (n = 5), neutropenia (n = 21), neutropenic infection (n = 1), and neutropenic colitis (n = 1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2-47.2%). The median response duration was 3.1 months (95% CI: 2.1-8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months.

Conclusions

Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC.     

Surgical complications related to hematopoietic stem cell transplantation

Background

Surgical complications in recipients of hematopoietic stem cell transplantation (HSCT) are common. However, this issue is infrequently reported in the literature.

Methods

The records of 165 patients who underwent hematopoietic stem cell transplantation at King Hussein Cancer Center between January 2007 and December 2008 were retrospectively reviewed. All surgical complications were included and were classified into gastrointestinal (GI), catheter-related, ear, nose and throat (ENT), peri anal, musculoskeletal, neurological and urological complications.

Results

There were 279 surgical complications in the studied patients. Gastrointestinal (n = 122) and catheter-related (n = 78) complications were the most frequent. The frequency and the percentage of patients needing surgical intervention for the 5 most common complications were as follows: Gastrointestinal (n = 122, 4.5% needed surgical intervention), catheter-related (n = 78, 46.2%), ear, nose and throat (n = 31, 9.7%), perianal disease (n = 21, 19%) and urinary complications (n = 17, 5.9%). Surgical consultation was sought for 116 surgical complications. Surgical interventions were necessary for 55 patients. All the patients who underwent surgery did not have an intervention-related mortality except for one patient who died from surgical intervention post-gastrointestinal complication.

Conclusion

The majority of surgical complications after HSCT do not require surgical intervention. However, these conditions may overlap with the more common reasons for surgical consultation and must be identi?able by the surgeon. Extra vigilance is necessary when dealing with both GI and catheter-related complications as they are the most frequent. The early involvement of surgeons and proper timing of surgical management may circumvent detrimental outcomes.     

The post ACOSOG Z0011 era: Does our new understanding of breast cancer really change clinical practice?

Background

The ACOSOG Z0011 trial (Z0011) expanded our thinking about breast cancer (BC) and showed that limited metastatic disease left behind in the axilla did not compromise oncological safety in a selected group of patients. The aim of the current study was to assess the potential impact of Z0011 on clinical practice by testing the applicability of its criteria to a European patient population.

Methods

We reviewed a consecutive series of 389 sentinel lymph node biopsies (SLNB) performed for invasive BC at the University Hospital Basel between 2003 and 2009 (65.6% of all surgically treated patients, n = 593).

Results

When compared to the axillary lymph node dissection (ALND) arm of Z0011, our patients had significantly less advanced LN involvement (≥3 LN: 8.5% vs. 21.0%, p = 0.048). Thirty-five patients (9.0%) met the Z0011 inclusion criteria and had 1-2 SLNs with macrometastases (5.9% of all surgically treated BC patients). If the inclusion criteria of Z0011 had been applied, a considerable number of LNs would have been missed in two cases (0.5% of all SLNBs).

Conclusions

The application of the Z0011 led to the omission of completion ALND in less than 10% of all SLNB procedures (<6% of all surgically treated BC patients); therefore, we do not think that the perception of Z0011 as “practice changing” is justified. On the other side, skeptics of the routine implementation of the Z0011 protocol may overestimate its potential hazards. When performing a thorough preoperative clinical axillary staging, the number of patients who would have been undertreated is minimal.     

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.     

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

Purpose

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

Methods

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

Results

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

Conclusions

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

Early prediction of response by F-FDG PET/CT during preoperative therapy in locally advanced rectal cancer: A systematic review

Aim

To assess the predictive value of fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in early assessing response during neo-adjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer.

Materials and methods

A systematic review was performed by search of MEDLINE Library for the following terms: “rectal carcinoma OR rectal cancer”, “predictive OR prediction OR response assessment OR response OR assessment”, “early OR ad interim”, “therapy”, “FDG OR ¹⁸F-FDG”, “PET OR PET/CT”. Articles performed by the use of stand-alone PET scanners were excluded.

Results

10 studies met the inclusion criteria, including 302 patients. PET/CT demonstrated a good early predictive value in the global cohort (mean sensitivity = 79%; mean specificity = 78%). SUV and its percentage decrease (response index = RI) were calculated in all studies. A higher accuracy was demonstrated for RI (mean sensitivity = 82%; pooled specificity = 85%) with a mean cut-off of 42%. The mean time point to perform PET scan during CRT resulted to be at 1.85 weeks. Some PET parameters resulted to be both predictive and not statistical predictive of response, maybe due to the small population and few studies bias.

Conclusion

PET showed high accuracy in early prediction response during preoperative CRT, increased with the use of RI as parameter. In the era of tailored treatment, the precocious assessment of non-responder patients allows modification of the subsequent strategy especially the timing and the type of surgical approach.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.