Radiomics Biomarkers Correlate with CD8 Expression and Predict Immune Signatures in Melanoma Patients.

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers. PET/CT scans from 52 patients with stage III/IV melanoma were assessed and CT image parameters were evaluated as prognostic biomarkers. Analysis indicated patients with high standard deviation or high mean of positive pixels (MPP) had worse progression-free survival (P = 0.00047 and P = 0.0014, respectively) and worse overall survival (P = 0.0223 and P = 0.0465, respectively). Whole-exome sequencing showed high MPP was associated with BRAF mutation status (P = 0.0389). RNA-sequencing indicated patients with immune "cold" signatures had worse survival, which was associated with CT biomarker, MPP4 (P = 0.0284). Multiplex immunofluorescence confirmed a correlation between CD8 expression and image biomarkers (P = 0.0028). IMPLICATIONS: CT parameters have the potential to be cost-effective biomarkers of survival in melanoma, and reflect the tumor immune-microenvironment. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/950/F1.large.jpg.

Primary cutaneous melanoma of the scalp: Patterns of recurrence.

INTRODUCTION: Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. METHODS: A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. RESULTS: A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). DISCUSSION: Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma.

Assessment of morbidity following regional nodal dissection in the axilla and groin for metastatic melanoma.

BACKGROUND: This study assessed and compared the morbidity of nodal dissection in the axilla and groin including sentinel lymph node biopsy (SLNB), completion lymph node dissection for a positive SLNB (CLND) and therapeutic lymph node dissection (TLND) with and without adjuvant radiotherapy (RT). METHODS: Patients who had nodal dissection in the axilla or groin for cutaneous melanoma over an 18-year period (1995-2013) were prospectively documented on a database. The median follow-up was nearly 3 years. Early complications and clinically relevant lymphoedema were retrospectively analysed to assess the incidence and differences between the region and type of nodal surgery. RESULTS: Included were 1521 patients following nodal dissection in the axilla (916 patients) and groin (605 patients). Less early complications occurred following SLNB in the axilla compared with the groin (5% versus 14%, P = 0.0001). Early complications were similar for CLND and TLND in the groin (49% versus 43%, P = 0.879) and axilla (28% versus 33%, P = 0.607). Moderate to severe lymphoedema rates were similar following axillary SLNB and CLND (6% versus 8%, P = 0.407). The lymphoedema rate for groin SLNB was lower than CLND (10% versus 20%, P = 0.063). No significant difference in lymphoedema rates followed CLND and TLND in each region. Following TLND, RT increased lymphoedema rates. CONCLUSIONS: Morbidity may occur following SLNB with the groin having a higher rate of early complications and lymphoedema compared with the axilla. The morbidity following CLND and TLND were similar. Lymphoedema rates were increased following RT.

Prospective study of patterns of surgical management in adults with primary cutaneous melanoma at high risk of spread, in Queensland, Australia.

BACKGROUND: Knowledge of variation in diagnosis and surgery in high-risk primary melanoma patients is limited. We assessed frequency and determinants of diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy (SLNB). METHODS: People in Queensland newly diagnosed with melanoma, clinical stage 1b or 2, were recruited prospectively. Patient information was collected from questionnaires and pathology records. Differences in surgical procedures in relation to host and tumor characteristics were assessed. RESULTS: In 787 participants, primary melanoma was diagnosed by surgical excision (74%), shave (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs) diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health sector, treating doctor's specialty and melanoma site and thickness. 766 patients had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were ≤ 1 mm at diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261 (33%) patients. SLNB was more common in those under 50, in remoter locations or treated by GP initially, and less common with head and neck melanoma. CONCLUSION: Diagnostic and surgical procedures for primary melanoma vary substantially and partial biopsy can influence initial tumor microstaging. Patient, tumor and doctor characteristics influence SLNB practice.

Patterns of Recurrence in Patients with Stage IIIB/C Cutaneous Melanoma of the Head and Neck Following Surgery With and Without Adjuvant Radiation Therapy: Is Isolated Regional Recurrence Salvageable?

BACKGROUND: Understanding recurrence patterns is vital for guiding treatment. This study describes recurrence patterns for patients with stage IIIB/C head and neck melanoma (HNM) after therapeutic lymph node dissection (TLND) ± adjuvant radiation therapy (RT). We also report outcomes for salvage therapy for patients with isolated regional relapse. METHODS AND MATERIALS: A single-institution prospective database of 173 patients with American Joint Committee on Cancer (AJCC) stage IIIB/C HNM undergoing TLND between 1997 and 2012 was retrospectively reviewed. Timing and patterns of recurrence were reviewed. Univariable and multivariable analyses were undertaken using the Kaplan-Meier and Cox regression methods to determine factors predictive of recurrence. Median follow-up was 32 months. RESULTS: Adjuvant RT was administered to 66/173 (38 %) patients. Patients selected for RT had a higher AJCC stage and had more extracapsular invasion. The 5-year distant, cervical nodal and in-transit recurrence rates were 38, 10, and 13 %, respectively, following surgery alone compared with 60, 17, and 31 %, respectively, for the adjuvant RT group. The head and neck regional 5-year recurrence rate (combining in-basin nodal and in-transit) was 23 % for the entire cohort. Isolated cervical recurrence occurred in 19 patients: 17/19 underwent salvage surgery (10/17 patients received RT after salvage surgery) and 2/19 had RT alone. However, distant recurrence occurred in 12/19 salvage patients, with most occurring within 12 months, while 4/19 were disease free. CONCLUSIONS: Using a selective approach for adjuvant RT, isolated cervical recurrence after TLND is uncommon. Isolated cervical recurrence can be salvaged effectively with further local therapy; however, distant disease frequently follows.

Supportive care needs, anxiety, depression and quality of life amongst newly diagnosed patients with localised invasive cutaneous melanoma in Queensland, Australia.

OBJECTIVE: The aim of this paper is to determine levels of supportive care needs, anxiety, depression and symptoms amongst patients newly diagnosed with localised invasive primary melanoma and if these varied amongst patients who had a sentinel lymph node biopsy (SLNB). We also considered quality of life compared with general population norms. METHODS: Patients newly diagnosed with clinical stage IB-II invasive melanoma were ascertained through Queensland hospitals, specialist clinics and pathology laboratories. Validated surveys measured 46 need items (Supportive Care Needs Survey-Short Form + melanoma subscale), anxiety and depression (Hospital Anxiety and Depression Scale) and quality of life and symptoms (Functional Assessment of Cancer Therapy-Melanoma). Regression models compared outcomes according to whether or not participants had a SLNB. RESULTS: We surveyed 386 patients, 155 before and 231 after wide local excision, of whom 46% reported ≥1 moderate-level or high-level unmet need. The three highest needs were for help with fears about cancer spreading (17%), information about risk of recurrence (17%) and outcomes when spread occurred (16%). Those who had a SLNB were more likely to report a moderate or high unmet need for help with uncertainty about the future or with lymphoedema (p < 0.05). Overall, 32% of participants had anxiety and 15% had depression regardless of performance of SLNB. Melanoma-specific symptoms were worse in SLNB patients (p = 0.03). Compared with the general population, emotional well-being was lower amongst melanoma patients. CONCLUSIONS: A substantial proportion of newly diagnosed patients with localised invasive melanoma need further melanoma-specific information and support with psychological concerns. Patients who have a SLNB clear of disease may need help with symptoms after surgery.

Nomograms to predict recurrence and survival in stage IIIB and IIIC melanoma after therapeutic lymphadenectomy.

BACKGROUND: Current staging algorithms in melanoma patients undergoing therapeutic lymph node dissection (LND) fail to accurately distinguish long-term survivors from those at risk of rapid relapse. Our goal was to establish and validate nomograms for predicting both recurrence and survival after LND. METHODS: A prospective cohort of stage IIIB and IIIC melanoma patients was ascertained from a tertiary hospital in Brisbane, Australia. Failure-time multivariate analysis identified key factors that, in adjusted combinations, generated nomograms to predict 2-year recurrence and 5-year melanoma-specific survival. The predictive value of these nomograms was further validated in a patient cohort from Rotterdam, The Netherlands. RESULTS: In 494 Australian patients, number of positive lymph nodes, extra-capsular extension and nodular histopathological subtype were the main independent predictors of 2-year recurrence while age, number of positive nodes and extra-capsular extension were the independent predictors of survival. Predictive value was confirmed in The Netherlands cohort of 331 patients. The nomograms were able to classify patients according to their 2-year recurrence and 5-year survival rates even within each stage III sub-class. CONCLUSIONS: Models that include extra-capsular extension predict outcomes in patients with clinically involved lymph nodes. This tool may help tailor treatment and monitoring of this group of patients.

An innovative approach for locally advanced stage III cutaneous melanoma: radiotherapy, followed by nodal dissection.

Patients with advanced nodal melanoma are typically managed with a regional nodal dissection; however, they have a high rate of distant relapse after surgery. This study assesses the role of preoperative radiotherapy to assist with the regional control in this subset of patients. Patients who had histologically confirmed stage III malignant melanoma and were treated with preoperative radiotherapy between 2004 and 2011 were eligible. All patients were staged with computer tomography and most with [F]-fluorodeoxyglucose (FDG) PET. Patients received preoperative radiotherapy, followed by a planned regional dissection at 12-14 weeks from completion with assessment of clinical, radiological and pathological responses. The primary outcome measure was the 1-year actuarial in-field control. There were 12 patients, with nine having disease of the axilla. All patients received radiotherapy up to a median dose of 48 Gy in 20 fractions, with seven patients achieving a partial clinical response. Ten patients proceeded to surgery, with four patients developing minor wound complications. The FDG-PET response did not appear to correlate with the pathological response. The 1-year in-field control rate was 92% (95% confidence interval 54-99) and the 1-year relapse-free survival was 54% (95% confidence interval 21-78). For selected patients with high-volume regional disease, we have successfully used preoperative radiotherapy, followed by a nodal dissection. Whether this type of protocol is of value in a more general group of patients with high-volume regional disease is currently under investigation.

Microsurgical hepatic artery reconstruction in paediatric liver transplantation.

BACKGROUND/AIMS: Hepatic artery thrombosis is a serious complication of paediatric liver transplantation often leading to retransplantation. It is also associated with decreased patient survival rates. In 1999 microsurgical hepatic artery reconstruction by Plastic and Reconstructive Surgeons was introduced to the Queensland Liver Transplant Service at the Royal Children's Hospital, Brisbane, in an attempt to decrease hepatic artery complications. METHODOLOGY: A review of the computerised database of the Queensland Liver Transplant Service was undertaken. Between March 1985 and December 2005, 252 transplants were performed without microsurgery. Since December 1999, 23 transplants were performed with microsurgical hepatic artery reconstruction by Plastic and Reconstructive Surgeons using the operating microscope. RESULTS: There were a total of 28 cases of hepatic artery thrombosis in 275 transplants. Survival for patients with hepatic artery thrombosis was significantly worse than for patients without (one year survival rate 61.5% versus 83.6%, p = 0.0065). The microsurgery group had a lower incidence of hepatic artery thrombosis (4.3% versus 10.7%, p = 0.29), a lower retransplantation rate (4.3% versus 9.1%, p = 0.38) and increased one year patient survival (91.3% versus 79.7%, p = 0.31). CONCLUSIONS: Microsurgical hepatic artery reconstruction in paediatric liver transplantation may decrease hepatic artery thrombosis rates, decrease retransplantation rates and improve survival.

Desmoplastic melanoma: the role of radiotherapy in improving local control.

BACKGROUND: Desmoplastic melanoma (DM) is a rare subtype of cutaneous malignant melanoma reported to have a high local recurrence rate with surgical excision alone. The incidence of regional and distant metastasis is considered to be lower than traditional cutaneous melanoma, warranting more aggressive treatment of local disease. We conducted a retrospective analysis of patients with DM treated through the Princess Alexandra Hospital Melanoma Clinic to address the role of radiotherapy in the local control of this tumour. METHODS: A review of a clinical database identified 24 patients between January 1997 and March 2006 with histopathologically confirmed DM who had received surgical excision as initial treatment followed by postoperative radiotherapy. All histopathology reports and radiotherapy treatment plans were reviewed. The primary outcome measure was 3-year in-field relapse-free survival. RESULTS: There were 24 patients with 22 having a DM in the head and neck region. The median tumour thickness was 5.2 mm. The histopathological margin was less than 10 mm in 17 (71%) of patients. The 3-year in-field relapse-free survival was 91% (95% confidence interval 68.1-97.6%), the 3-year relapse-free survival was 86% (95% confidence interval 63.2-95.4%) with a 3-year overall survival of 83% (95% confidence interval 54.9-94.3%). CONCLUSION: In a selected series of patients with DM with a high risk of local recurrence, adjuvant radiotherapy may have been effective in reducing the rate of local recurrence after surgical resection. A randomized trial is currently being developed to confirm this possible benefit.