The association between active tumor volume, total lesion glycolysis and levels of S-100B and LDH in stage IV melanoma patients.

INTRODUCTION: The Standardized Uptake Value (SUV) in single lesions on 18F-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUVmean/max, metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for follow-up. METHODS: In 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed. RESULTS: S-100B was elevated (>0.15 µg/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R2 = 0.19). S-100B was correlated to both MATV (R2 = 0.375) and TLG (R2 = 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p < 0.001) and also in patients with elevated LDH (>250 U/l) (p < 0.001). There was no association between the biomarkers and SUVmean/max. Survival analysis indicated that LDH was the only predictor of melanoma-specific survival. CONCLUSION: In newly diagnosed stage IV melanoma patients S-100B correlates with 18F-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis.

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

Pelvic lymph node dissection in metastatic melanoma to the groin should not be abandoned yet.

BACKGROUND: In recent years there has been a plea to abandon the pelvic lymph node dissection in the treatment of patients with metastatic melanoma to the groin. A trend towards a conservative surgical treatment is already evolving in several European countries. The purpose of this study is to identify factors associated with pelvic nodal involvement, in order to improve selection of patients whom might benefit from a pelvic nodal dissection. METHODS: A retrospective analysis was performed on prospectively collected data concerning patients who underwent an inguinal lymph node dissection (ILND) with pelvic lymph node dissection for metastatic melanoma at the University Medical Center Groningen. Multivariable logistic regression analysis was performed to determine factors associated with pelvic nodal involvement. Diagnostic accuracy was calculated for 18F-FDG PET + contrast enhanced CT-scan and 18F-FDG PET + low dose CT-scan. RESULTS: Two-hundred-and-twenty-six ILND's were performed in 223 patients. The most common histologic subtype was superficial spreading melanoma (42.6%). In patients with micrometastatic disease, 15.7% had pelvic nodal involvement vs 28.2% in patients with macrometastatic disease (p: 0.030). None of the characteristics known prior to the ILND, were associated with pelvic nodal involvement. Imaging methods were unable to accurately predict pelvic nodal involvement. Negative predictive value was 78% for 18F-FDG PET + low dose CT-scan and 86% for an 18F-FDG PET + contrast enhanced CT-scan. CONCLUSION: There are no patient- or tumor characteristics available that can predict pelvic nodal involvement in patients with melanoma metastasis to the groin. As no imaging technique is able to predict pelvic nodal involvement it seems unjust to abandon the pelvic lymph node dissection.

Fractures after multimodality treatment of soft tissue sarcomas with isolated limb perfusion and radiation; likely to occur and hard to heal.

OBJECTIVES: Treatment associated fractures (TAFs) are known severe side effects after surgery and radiotherapy for soft tissue sarcoma (STS). There is no literature about TAF after multimodality treatment with isolated limb perfusion (ILP) for locally advanced STS. This study aimed to analyze predictive factors, treatment and outcome for TAF after multimodality treatment with ILP. METHOD: Out of 126 consecutive patients undergoing ILP after 1991 till now, 25 patients were excluded due to no surgery or direct amputation at initial surgery. Therefore, 101 patients were at risk and 12 developed a TAF (12%). RESULTS: The majority of tumors was located at the upper leg and knee (N = 60), and 11 patients developed a TAF (18%) after median 28 (5-237) months. Twenty-five tumors were located at the lower leg, and 1 patient developed a TAF after 12 months (4%). No patients with a tumor at the upper extremities (N = 16) developed a TAF. Ten out of 12 patients with a fracture received adjuvant RT with a dose of 50 Gy, and a median boost dose of 18 (10-20) Gy. Predictive factors were periosteal stripping, age over 65 years at time of treatment and tumor size after ILP ≥10 cm. Multivariate analysis showed periosteal stripping and tumor size after ILP ≥10 cm as significant predictive factors. The majority of the fractures were treated with intramedullary nailing. Only one of 12 patients without radiotherapy reached bone union (8%). The median survival after developing TAF was 18 (1-195) months. CONCLUSION: The overall risk of TAF after multimodality treatment with ILP was relatively high with 15% at ten years. The incidence of TAF for patients with tumors located at the thigh and knee after resection with periosteal stripping and radiotherapy was even >50%. The treatment of these fractures is challenging due to the high non-union rate, requiring an extensive orthopedic oncological TAF experience.

Practice variation in Sentinel Lymph Node Biopsy for melanoma patients in different geographical regions in the Netherlands.

BACKGROUND: Due to the lack of solid evidence for treatment benefit of Sentinel Lymph Node Biopsy (SLNB) as part of loco-regional surgical treatment of non-distant metastatic melanoma, there might be variation in surgical treatment strategies in the Netherlands. The objective of the current study was to assess differences in the performance of SLNB, in geographical regions in the Netherlands, of non-distant metastatic melanoma patients (American Joint Committee on Cancer (AJCC) stage I-III). MATERIALS AND METHODS: A total of 28 550 melanoma patients, diagnosed between 2005 and 2013, were included in this population based retrospective study. Data were retrieved from the Netherlands Cancer Registry (NCR). Treatment strategies in 8 regions of the Netherlands were compared according to stage, excluding patients with distant metastasis (AJCC stage IV). RESULTS: Throughout the Netherlands, there was substantial practice variation across the regions. The performance of SLNB in patients with clinically unsuspected lymph nodes and Breslow thickness >1.0 mm was significantly different between the regions. In a post hoc analysis, we observed that patients aged over 60 years, female patients and patients with a melanoma located in head and neck have lower odds to receive a SLNB. CONCLUSION: There is considerable loco-regional practice variation which cannot completely be explained by the patient and tumor characteristics, in the surgical treatment of non-distant metastatic melanoma patients in the Netherlands. Although national guidelines recommend considering SLNB in all patients with a melanoma thicker than 1 mm, only half of the patients received a SLNB. Future research should assess whether this practice variation leads to unwanted variations in clinical outcome.

A prediction tool incorporating the biomarker S-100B for patient selection for completion lymph node dissection in stage III melanoma.

INTRODUCTION: Completion lymph node dissection (CLND) in sentinel node (SN)-positive melanoma patients is accompanied with morbidity, while about 80% yield no additional metastases in non-sentinel nodes (NSNs). A prediction tool for NSN involvement could be of assistance in patient selection for CLND. This study investigated which parameters predict NSN-positivity, and whether the biomarker S-100B improves the accuracy of a prediction model. METHODS: Recorded clinicopathologic factors were tested for their association with NSN-positivity in 110 SN-positive patients who underwent CLND. A prediction model was developed with multivariable logistic regression, incorporating all predictive factors. Five models were compared for their predictive power by calculating the Area Under the Curve (AUC). A weighted risk score, 'S-100B Non-Sentinel Node Risk Score' (SN-SNORS), was derived for the model with the highest AUC. Besides, a nomogram was developed as visual representation. RESULTS: NSN-positivity was present in 24 (21.8%) patients. Sex, ulceration, number of harvested SNs, number of positive SNs, and S-100B value were independently associated with NSN-positivity. The AUC for the model including all these factors was 0.78 (95%CI 0.69-0.88). SN-SNORS was the sum of scores for the five parameters. Scores of ≤9.5, 10-11.5, and ≥12 were associated with low (0%), intermediate (21.0%) and high (43.2%) risk of NSN involvement. CONCLUSIONS: A prediction tool based on five parameters, including the biomarker S-100B, showed accurate risk stratification for NSN-involvement in SN-positive melanoma patients. If validated in future studies, this tool could help to identify patients with low risk for NSN-involvement.

Melanoma patients' disease-specific knowledge, information preference, and appreciation of educational YouTube videos for self-inspection.

BACKGROUND: Informing and educating melanoma patients is important for early detection of a recurrence or second primary. This study aimed to investigate Dutch melanoma patients' disease-specific knowledge, and their opinions on information provision and the value of e-Health videos. METHODS: All AJCC stage I-II melanoma patients in follow-up between March 2015 and March 2016 at a single melanoma center were invited to complete 19 online questions, addressing respondents' characteristics, knowledge on melanoma, and opinions on melanoma-specific information received and the educational YouTube videos. RESULTS: In total, 100 patients completed the survey (response = 52%); median age was 60 years and 51% were female. Breslow tumor thickness was unknown by 34% and incorrectly indicated by 19%, for presence of ulceration this was 33% and 11%, for mitosis 65% and 14%, and for AJCC stage 52% and 23%, respectively. Only 5% correctly reproduced all four tumor characteristics. Orally delivered information regarding warning signs, severity, treatment possibilities, and importance of self-inspection was clearest for patients, compared to information in the melanoma brochure. According to 77% of patients, YouTube videos regarding self-inspection of the skin and regional lymph nodes had additional value. Altogether, 63% preferred receiving information in multiple ways; 92% orally by their physician, 62% through videos, and 43% through brochures. CONCLUSIONS: Patients' melanoma-specific knowledge appears to be limited. There is an urgent need for further improvement of providing information and patient education. In addition to oral and written information, e-Health videos seem to be a convenient supplemental and easy accessible method for patient education.

Patient, tumour and treatment factors affect complication rates in soft tissue sarcoma flap reconstruction in a synergistic manner.

INTRODUCTION: Flap reconstruction plays an essential role in the management of soft tissue sarcoma, facilitating wide resection while maximizing preservation of function. The addition of reconstruction increases the complexity of the surgery and identification of patients who are at high risk for post-operative complications is an important part of the preoperative assessment. This study examines predictors of complications in these patients. METHODS: 294 patients undergoing flap reconstruction following sarcoma resection were evaluated. Data on patient, tumour and treatment variables as well as post-operative complications were collected. Bivariate and multivariate regression analysis was performed to identify independent predictors of complications. Analysis of synergistic interaction between key patient and tumour risk factors was subsequently performed. RESULTS: A history of cerebrovascular events or cardiac disease were found to be the strongest independent predictors of post-operative complications (OR 14.84, p = 0.003 and OR 5.71, p = 0.001, respectively). Further strong independent tumour and treatment-related predictors were high grade tumours (OR 1.91, p = 0.038) and the need for additional reconstructive procedures (OR 2.78, p = 0.001). Obesity had significant synergistic interaction with tumour resection diameter (RERI 1.1, SI 1.99, p = 0.02) and high tumour grade (RERI 0.86, SI 1.5, p = 0.01). Comorbidities showed significant synergistic interaction with large tumour resections (RERI 0.91, SI 1.83, p = 0.02). CONCLUSION: Patient, tumour and treatment-related variables contribute to complications following flap reconstruction of sarcoma defects. This study highlights the importance of considering the combined effect of multiple risk factors when evaluating and counselling patients as significant synergistic interaction between variables can further increase the risk of complications.

No difference in clinical outcome between patient-matched positioning guides and conventional instrumented total knee arthroplasty two years post-operatively: a multicentre, double-blind, randomised controlled trial.

AIMS: We wished to compare the clinical outcome, as assessed by questionnaires and the rate of complications, in total knee arthroplasty (TKA) undertaken with patient-matched positioning guides (PMPGs) or conventional instruments. PATIENTS AND METHODS: A total of 180 patients (74 men, 106 women; mean age 67 years) were included in a multicentre, adequately powered, double-blind, randomised controlled trial. The mean follow-up was 44 months (24 to 57). RESULTS: There were no significant or clinically relevant differences between the two groups for all outcome measures (Knee Society Score, p = 0.807; Oxford Knee Score, p = 0.304; Western Ontario and McMaster osteoarthritis index, p = 0.753; visual analogue scale for pain, p = 0.227; EuroQol-5D-3L index score, p = 0.610; EuroQol-5D-3L VAS health, p = 0.968.) There was no difference in the rate of complications (p = 0.291). CONCLUSION: PMPGs are already in relatively common use and their short-term clinical results are equal to conventional instrumented TKA. Cite this article: Bone Joint J 2016;98-B:939-44.

The interval between primary melanoma excision and sentinel node biopsy is not associated with survival in sentinel node positive patients - An EORTC Melanoma Group study.

BACKGROUND: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. AIM: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. METHODS: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. RESULTS: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. CONCLUSIONS: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.

Is there a relation between type of primary melanoma treatment and the development of intralymphatic metastasis? A review of the literature.

BACKGROUND: Intralymphatic metastases (ILM) originate from tumor cell emboli entrapped in dermal lymphatics between primary tumor and regional lymph node basin. Because of this origin, sentinel lymph node biopsy (SLNB) might increase ILM by restricting lymph flow. METHODS: Pubmed, Embase, Cochrane and Medline were searched for articles on ILM between 1980 and September 2014. ILM Incidences were calculated after wide local excision (WLE), excision with elective lymph node dissection (ELND) or therapeutic lymph node dissection (TLND), WLE with SLNB with or without completion lymph node dissection (CLND) and delayed lymph node dissection (DLND) for patients developing nodal metastasis during follow-up. RESULTS: In 36 studies, 14,729 patients underwent WLE, 1682 patients WLE/ELND, 362 patients WLE/DLND and 11,201 patients WLE/SLNB. On meta-analysis, ILM occurrence was 3.4% (95% CI 2.8-4.2%). ILM occurred most frequently in the WLE/DLND group (5.5%, 95% CI 3.5-8.7%), followed by WLE/ELND (4.7%, 95% CI 3.1-7.0%), WLE/SLNB (4.5%, 95% CI 3.5-5.7%) and WLE alone (1.9%, 95% CI 1.4-2.7%). 1330 SLNB+ patients were identified and 5783 SLNB- patients. For these groups, on meta-analysis, ILM recurrence was 13.2% (95% CI 10.8-16.2%) and 3.4% (95% CI 2.5-4.5%), respectively (p=0.01). CONCLUSION: In this review SLNB is associated with an increase of ILM with an incidence of 1.9% for WLE vs. 3.4% for SNLB-. Selection bias in this review cannot be excluded. However, ILM occur four times more frequently after SLNB+ than SLNB- procedures and more often after SLNB+/CLND than WLE/DLND or WLE/ELND. ILM should therefore be viewed as a bio-marker of aggressive primary disease. SYNOPSIS: Sentinel lymph node biopsy is thought to increase intralymphatic metastasis by restricting lymph flow. This review demonstrates that there is an increase in metastasis, but this result has to be interpreted with caution due to possible selection bias. Aggressive tumor characteristics are likely the cause of this increase.

A systematic review and meta-analyses of sentinel lymph node identification in breast cancer and melanoma, a plea for tracer mapping.

PURPOSE: Sentinel lymph node biopsy (SLNB) has become a widely accepted staging procedure for both breast carcinoma and melanoma. The aim of our study was to systematically review different SLNB techniques and perform a meta-analysis for corresponding identification and false-negative rates. METHODS: A systematic review of the literature on SLNB in patients with early stage breast carcinoma and melanoma was performed. Only original study groups were included. The SLN identification rate and false negative rate were pooled for patients with breast carcinoma or melanoma according to radiocolloid tracer, blue dye, indocyanine green (ICG), or a combination of a radiocolloid tracer with blue dye or ICG. RESULTS: Between 1992 and 2012, a total of 154 studies (88 breast carcinoma and 66 melanoma) were reported that met our eligibility criteria. These studies included a total of 44,172 patients. The pooled SLN identification rate in breast carcinoma and melanoma patients using solely blue dye was 85% (range: 65-100%) and 84% (range: 59-100%), while for radiocolloid alone it was 94% (range: 67-100%) and 99% (range: 83-100%), respectively. Using a combination of radiocolloid and blue, identification rates were 95% (range 94-95%) and 98% (range: 98-98%). CONCLUSIONS: The current meta-analysis provides data that favors the use of radiocolloid or radiocolloid combined with a blue dye for SLN identification. Performing SLNB with radiocolloid alone is the technique of choice for experienced surgeons, since blue dye has multiple disadvantages. SLNB using ICG as a fluorescent dye seems a promising technique for the near future.

The predictive power of serum S-100B for non-sentinel node positivity in melanoma patients.

BACKGROUND: Completion lymph node dissection (CLND) in sentinel node (SN) positive melanoma patients leads to substantial morbidity and costs, while only approximately 20% have a metastasis in non-sentinel nodes (NSNs). The aim of this study was to investigate if the biomarkers S-100B and Lactate Dehydrogenase (LDH) are associated with NSN positivity, to identify patients in whom CLND could safely be omitted. METHODS: All SN positive patients who underwent CLND at the University Medical Centre Groningen between January 2004 and January 2015 were analysed. Patient and tumor characteristics, and serum S-100B and LDH values measured the day before CLND were statistically tested for their association with NSN positivity. RESULTS: NSN positivity was found in 20.6% of the 107 patients undergoing CLND. Univariate analysis revealed male gender (p = 0.02), melanoma of the lower extremity (p = 0.05), Breslow thickness (p = 0.004), ulceration (p = 0.04), proportion of involved SNs (p = 0.045) and S-100B value (p = 0.01) to be associated with NSN positivity. LDH level was not significantly associated with positive NSNs (p = 0.39). In multivariable analysis, S-100B showed to have the strongest association with NSN positivity, within its reference interval of 0.20 µg/l (p = 0.02, odds ratio 5.71, 95% confidence interval 1.37-23.87). CONCLUSION: In this study, the preoperatively measured S-100B value is the strongest predictor for NSN positivity in patients planned for CLND. Fluctuations of the S-100B level within the reference interval might give important clues about residual tumor load. Although further validation will be needed, this new closer look of S-100B could be of value in patient selection for CLND in the future.

Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized? : A Retrospective, Multicenter Cohort Study.

BACKGROUND: Patients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient. AIM: The aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future. METHODS: This study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992-2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET - low-dose CT). RESULTS: Median age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11-46 months). Median Breslow thickness was 2.10 mm (IQR 1.40-3.40 mm), and 26 % of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35 % of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1-2] vs. 3 [IQR 1-4] for positive deep pelvic nodes; p < 0.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10-0.25) vs. 0.33 (IQR 0.14-0.54); p < 0.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84 % of patients. CONCLUSIONS: Patients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

Tumor mitotic rate added to the equation: melanoma prognostic factors changed? : a single-institution database study on the prognostic value of tumor mitotic rate for sentinel lymph node status and survival of cutaneous melanoma patients.

BACKGROUND: This study aimed to investigate the predictive value of the tumor mitotic rate per mm(2) (TMR) for sentinel lymph node (SLN) status and survival in intermediate and thick cutaneous melanoma. METHODS: Patients treated for stage I and II melanoma with wide local excision and SLN biopsy between May 1995 and May 2013 were analyzed. In case of insufficient data regarding TMR, pathology slides were reanalyzed. Prognostic factors for SLN status and survival were analyzed with the emphasis on TMR, which was analyzed as a continuous variable, dichotomized (median value) and categorized by two methods. RESULTS: The study analyzed 453 patients with complete TMR data. The median Breslow thickness was 2.20 mm, and 31.8 % of patients had tumor-positive sentinel lymph node biopsies (SLNBs). In the univariate analysis, TMR was associated with tumor-positive SLNB. This association was not significant in the multivariate analysis. Breslow thickness, primary tumor location on trunk and legs, and younger age were associated with tumor-positive SNLB. At a median follow-up of 47 months, 119 patients (26.3 %) had recurrent disease, and 92 (20.3 %) had died of melanoma. In the univariate analysis, TMR could be established as a significant prognostic factor for disease-free and disease-specific survival, but not in the multivariate analyses. Breslow thickness, ulcerated melanoma, and tumor-positive SLNB were significant prognostic factors for survival. CONCLUSION: The study was unable to establish TMR as an independent prognostic factor associated with the presence of SLN metastasis. Regarding survival, increasing TMR showed a strong association with decreased survival in the univariate analysis, but this association was rendered nonsignificant by the importance of Breslow thickness and ulceration status in the multivariate model.

Mortality in emergency surgical oncology.

PURPOSE: Cancer patients can experience problems related to their disease or treatment. This study evaluated reasons for presentation at the emergency room (ER) and outcome of surgical oncology patients. METHODS: A retrospective chart review for all surgical oncology patients who presented at the ER of the UMCG for surgical consultation between October 1, 2012, and March 31, 2013. RESULTS: A total of 200 cancer patients visited the ER for surgical consultation: 53.5 % with complications of (previous) cancer treatment, 25.5 % with symptoms caused by malignant disease, and 21.0 % with symptoms not related to cancer or cancer treatment. The 30-day mortality rate for patients with progressive disease was 25.5 %, and overall mortality rate was 62.8 %. The most frequent reason for ER presentation was intestinal obstruction (26.5 %), of which 41.5 % was malignant. Most cancer patients (59.5 %) did not undergo surgery during follow-up. The 30-day mortality for these patients was 14.3 % and overall mortality was 37.8 %. Most patients who died within the first 30 days after ER presentation had not undergone any surgery after presentation (89.5 %). CONCLUSIONS: There is great variation in mortality rates for cancer patients presenting at the ER for surgical consultation. The mortality in this study was greatest for patients with progressive disease (30-day mortality 25.5 % and overall mortality 62.8 %), and the majority of patients who died within 30 days (89.5 %) had not undergone surgery after ER presentation. Surgery should only be performed in the acute setting when essential and when the expected outcome is favorable for the patient.

Radiofrequency ablation in the treatment of cartilaginous lesions in the long bones: results of a pilot study.

Atypical cartilaginous tumours are usually treated by curettage. The purpose of this study was to show that radiofrequency ablation was an effective alternative treatment. We enrolled 20 patients (two male, 18 female, mean age 56 years (36 to 72) in a proof-of-principle study. After inclusion, biopsy and radiofrequency ablation were performed, followed three months later by curettage and adjuvant phenolisation. The primary endpoint was the proportional necrosis in the retrieved material. Secondary endpoints were correlation with the findings on gadolinium enhanced MRI, functional outcome and complications. Our results show that 95% to 100% necrosis was obtained in 14 of the 20 patients. MRI had a 91% sensitivity and 67% specificity for detecting residual tumour after curettage. The mean functional outcome (MSTS) score six weeks after radiofrequency ablation was 27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p < 0.001). No complications occurred after ablation, while two patients developed a pathological fracture after curettage. We have shown that radiofrequency ablation is capable of completely eradicating cartilaginous tumour cells in selective cases. MRI has a 91% sensitivity for detecting any residual tumour. Radiofrequency ablation can be performed on an outpatient basis allowing a rapid return to normal activities. If it can be made more effective, it has the potential to provide better local control, while improving functional outcome.

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials.

BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

Key roles for MYC, KIT and RET signaling in secondary angiosarcomas.

BACKGROUND: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas. METHODS: Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set. RESULTS: In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas. CONCLUSIONS: Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.

Surgical emergencies in oncology.

An oncologic emergency is defined as an acute, potentially life threatening condition in a cancer patient that has developed as a result of the malignant disease or its treatment. Many oncologic emergencies are signs of advanced, end-stage malignant disease. Oncologic emergencies can be divided into medical or surgical. The literature was reviewed to construct a summary of potential surgical emergencies in oncology that any surgeon can be confronted with in daily practice, and to offer insight into the current approach for these wide ranged emergencies. Cancer patients can experience symptoms of obstruction of different structures and various causes. Obstruction of the gastrointestinal tract is the most frequent condition seen in surgical practice. Further surgical emergencies include infections due to immune deficiency, perforation of the gastrointestinal tract, bleeding events, and pathological fractures. For the institution of the appropriate treatment for any emergency, it is important to determine the underlying cause, since emergencies can be either benign or malignant of origin. Some emergencies are well managed with conservative or non-invasive treatment, whereas others require emergency surgery. The patient's performance status, cancer stage and prognosis, type and severity of the emergency, and the patient's wishes regarding invasiveness of treatment are essential during the decision making process for optimal management.