Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma.

BACKGROUND: Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report 5-year outcomes from the phase II NeoCombi trial. PATIENTS AND METHODS: NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial. Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, American Joint Committee on Cancer seventh edition clinical stage IIIB-C BRAF V600E/K-mutant melanoma and Eastern Cooperative Oncology Group performance status ≤1. Patients received 52 weeks of treatment with dabrafenib 150 mg (orally twice per day) plus trametinib 2 mg (orally once per day), with complete resection of the pre-therapy tumour bed at week 12. RESULTS: Between 20 August 2014 and 19 April 2017, 35 patients were enrolled. At data cut-off (17 August 2021), the median follow-up was 60 months [95% confidence interval (CI) 56-72 months]. Overall, 21 of 35 (60%) patients recurred, including 12 (57%) with first recurrence in locoregional sites (followed by later distant recurrence in 6) and 9 (43%) with first recurrence in distant sites, including 3 in the brain. Most recurrences occurred within 2 years, with no recurrences beyond 3 years. At 5 years, recurrence-free survival (RFS) was 40% (95% CI 27% to 60%), distant metastasis-free survival (DMFS) was 57% (95% CI 42% to 76%), and overall survival was 80% (95% CI 67% to 94%). Five-year survival outcomes were stratified by pathological response: RFS was 53% with pathological complete response (pCR) versus 28% with non-pCR (P = 0.087), DMFS was 59% versus 55% (P = 0.647), and overall survival was 88% versus 71% (P = 0.205), respectively. CONCLUSIONS: Neoadjuvant dabrafenib plus trametinib has high pathological response rates in clinical stage III melanoma, but low rates of RFS, similar to those achieved with adjuvant targeted therapy alone. Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare.

Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma.

BACKGROUND: Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS. PATIENTS AND METHODS: Clinicopathological characteristics of lymph node dissection specimens of 83 patients enrolled in the OpACIN-neo clinical trial were evaluated. Two methods of assessing histological features of immunotherapeutic response were evaluated: the previously described immune-related pathologic response (irPR) score and our novel immunotherapeutic response score (ITRS). For a subset of cases (n = 29), cellular composition of the tumour bed was analysed by flow cytometry. RESULTS: There was strong interobserver reproducibility in assessment of pathological response (κ = 0.879) and percentage residual viable melanoma (intraclass correlation coefficient = 0.965). The immunotherapeutic response subtype with high fibrosis had the strongest association with lack of recurrence (P = 0.008) and prolonged RFS (P = 0.019). Amongst patients with criteria for pathological non-response (pNR, >50% viable tumour), all who recurred had ≥70% viable melanoma. Higher ITRS and irPR scores correlated with lack of recurrence in the entire cohort (P = 0.002 and P ≤ 0.0001). The number of B lymphocytes was significantly increased in patients with a high fibrosis subtype of treatment response (P = 0.046). CONCLUSIONS: There is strong reproducibility for assessment of pathological response using INMC criteria. Immunotherapeutic response of fibrosis subtype correlated with improved RFS, and may represent a biomarker. Potential B-cell contribution to fibrosis development warrants further study. Reclassification of pNR to a threshold of ≥70% viable melanoma and incorporating additional criteria of <10% fibrosis subtype of response may identify those at highest risk of recurrence, but requires validation.

Histopathological features of complete pathological response predict recurrence-free survival following neoadjuvant targeted therapy for metastatic melanoma.

BACKGROUND: Recent clinical trials demonstrated the safety and efficacy of neoadjuvant dabrafenib and trametinib (DT) among patients with surgically resectable clinical stage III BRAFV600E/K mutant melanoma. Although patients achieving a complete pathological response (pCR) exhibited superior recurrence-free survival (RFS) versus those who did not, 30% of pCR patients relapsed. We sought to identify whether histopathological features of the pathological response further delineated risk of relapse. METHODS: Surgical resection specimens from DT-treated patients in two phase 2 clinical trials were reviewed. Histopathological features, including relative amounts of viable tumour, necrosis, melanosis, and fibrosis (hyalinized or immature/proliferative) were assessed for associations with patient outcomes. RESULTS: Fifty-nine patients underwent surgical resection following neoadjuvant DT. Patients achieving pCR (49%) had longer RFS compared with patients who did not (P = 0.005). Patients whose treated tumour showed any hyalinized fibrosis had longer RFS versus those without (P = 0.014), whereas necrosis (P = 0.012) and/or immature/proliferative fibrosis (P = 0.026) correlated with shorter RFS. Multivariable analyses showed absence of pCR or presence of immature fibrosis independently predicted shorter RFS. Among pCR patients, mature/hyalinized-type fibrosis correlated with improved RFS (P = 0.035). CONCLUSIONS: The extent and composition of the pathological response following neoadjuvant DT in BRAFV600E/K mutant melanoma correlates with RFS, including pCR patients. These findings support the need for detailed histological analysis of specimens collected after neoadjuvant therapy.

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

BACKGROUND: The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma. PATIENTS AND METHODS: ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS). RESULTS: The detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma. CONCLUSION: Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.

Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma.

Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines. Results: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated. Conclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.

Survivorship care plans in cancer: a systematic review of care plan outcomes.

BACKGROUND: Eight years after the Institute of Medicine recommended survivorship care plans (SCPs) for all cancer survivors, this study systematically reviewed the evidence for their use. METHODS: Studies evaluating outcomes after implementation of SCPs for cancer survivors were identified by searching databases (MEDLINE, EMBASE and Cochrane). Data were extracted and summarised. RESULTS: Ten prospective studies (2286 survivors) met inclusion criteria (5 randomised controlled trials (RCTs)). Study populations included survivors of breast, gynaecological, colorectal and childhood cancer. Several models of SCP were evaluated (paper based/on-line, oncologist/nurse/primary-care physician-delivered and different templates). No significant effect of SCPs was found on survivor distress, satisfaction with care, cancer-care coordination or oncological outcomes in RCTs. Breast cancer survivors with SCPs were better able to correctly identify the clinician responsible for their follow-up care. One study suggested a positive impact on reducing unmet needs. Levels of survivor satisfaction with, and self-reported understanding of, their SCP were very high. Feasibility was raised by health professionals as a significant barrier, as SCPs took 1-4 h of their time to develop. CONCLUSIONS: Emerging evidence shows very few measurable benefits of SCPs. Survivors reported high levels of satisfaction with SCPs. Resource issues were identified as a significant barrier to implementation.

The management of cervical lymph nodes in patients with cutaneous melanoma.

BACKGROUND: The aim of this study was to review the management of cervical lymph nodes in patients with cutaneous melanoma and to analyze factors influencing prognosis. METHODS: This was a retrospective cohort study of patients who had cervical node surgery at the Sydney Melanoma Unit from 1990 to 2004. RESULTS: Of 716 patients who met the study criteria, 339 had a sentinel node biopsy (SNB) and 396 had a neck dissection. Locoregional recurrence occurred in 27.6 % of those undergoing therapeutic neck dissection and 60 % eventually developed distant metastases. Radiotherapy was given as adjuvant treatment in 110 of the patients who had a therapeutic neck dissection (41 %), but this was not associated with improved regional control (p = .322). Multivariate analysis showed that nodal positivity (p < .001) and primary tumor ulceration (p = < .027) were the most important predictors of locoregional recurrence and that primary tumor Breslow thickness (p = .009) and node positivity (p = .046) were the most important factors predicting survival. SNB-positive patients who underwent immediate completion lymphadenectomy had a 5-year survival advantage over those who had a therapeutic neck dissection for macroscopic disease (54 % vs 47 %, p = .028). CONCLUSIONS: Nodal status was the most important factor predicting disease-free and overall survival in patients with melanoma of the head and neck. Adjuvant radiotherapy was not associated with better locoregional control in the non-randomized cohorts of patients in this study.

Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB; patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma.

High-resolution lymphoscintigraphy is essential for recognition of the significance of internal mammary nodes in breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) of internal mammary nodes (IMNs) in breast cancer is controversial. Most centers rarely identify IMN on lymphoscintigraphy but others report up to 45% of cases. Controversy relates to the technique of lymphatic mapping, safety of IMN SNB, the significance of positive IMN, and potential to impact survival. METHODS: Assessment of drainage rates from two unrelated nuclear medicine departments' databases. Review of related literature. RESULTS: High-resolution lymphoscintigraphy results in IMN drainage in one-third of breast cancers. There is a learning curve for the technique. In 1754 consecutive cases, internal mammary drainage occurred in 53% of medial tumors, 37% midline tumors and 24% of lateral tumors (overall 34%). Extended radical mastectomy series also demonstrate the (approximately) 1/3 ratio when comparing IMN positivity rates to axillary node positivity rates (18.8% : 48.3%) and in node-positive patients (31% : 100%). The management altering potential of IMN assessment and potential survival impact are discussed. CONCLUSIONS: IMN mapping gives information that alters management in up to one-third of cases. These rates of IMN drainage are reproducible and reflect lymphatic density and anatomy of the breast. A priority need exists to establish a collaborative clinical trial to clarify the value of IMN assessment.

Regional variation in immediate breast reconstruction in Australia.

BACKGROUND: Breast reconstruction following mastectomy has proven benefits and is the standard of care in many high-income countries. This audit documented regional variation in immediate breast reconstruction rates across Australia. METHODS: The Breast Surgeons of Australia and New Zealand (BreastSurgANZ) Quality Audit database and geospatial software were used to model the distribution of breast reconstructions performed on women having mastectomy in Australia in 2013. Geospatial mapping identified the distribution of these procedures in relation to the Greater Capital City Statistical Areas (GCCSAs) of the five largest states. Data were analysed using χ2 tests of independence and an independent-samples t test. RESULTS: Of 3786 patients having a mastectomy, 692 underwent breast reconstruction of which 679 (98·1 per cent) were immediate reconstructions. Rates of reconstruction differed significantly between jurisdictions (χ2 = 164·90), and were significantly higher in GCCSAs (χ2 = 144·60) and private hospitals (χ2 = 50·72) (all P < 0·001). Immediate breast reconstruction was not reported for 43·8 per cent of hospitals where mastectomy was conducted by members of BreastSurgANZ, including 29·8 per cent of hospitals within GCCSAs. A wider age range of women appeared to have had immediate reconstructions at hospitals within GCCSAs, although the difference in mean age between regions was not significant. Immediate breast reconstruction was considerably less likely to be performed in women who lived in areas of lower to mid socioeconomic status. CONCLUSION: Variations in the rate of immediate breast reconstruction may not be purely resource-driven.

Measuring the quality of melanoma surgery - Highlighting issues with standardization and quality assurance of care in surgical oncology.

In an attempt to ensure high standards of cancer care, there is increasing interest in determining and monitoring the quality of interventions in surgical oncology. In recent years, this has been particularly the case for melanoma surgery. The vast majority of patients with melanoma undergo surgery. Usually, this is with combinations of wide excision, sentinel lymph node biopsy and lymphadenectomy. The indications for these procedures evolved during a time when no effective systemic adjuvant therapy was available, and whilst the rationale has been sound, the justification for differences in extent and thoroughness has generally been supported by inadequate or low-level evidence. This has led to a substantial variation among melanoma centres or even among surgeons within a centre in how these procedures are done. With recent rapid progress in the efficacy of systemic treatments that are impacting on overall survival, the prospect of long-term survival in these previously high risk patients means that more than ever long-term locoregional control of melanoma is imperative. Furthermore, the understanding of effects of systemic therapy on locoregional disease will only be interpretable if surgeons use standardized, high quality techniques. This article focuses on standardization and evolution of quality indicators for melanoma surgery and how these might have a positive impact on patient care.

Patterns and outcomes of breast reconstruction in older women - A systematic review of the literature.

PURPOSE: Older age is associated with lower rates of breast reconstruction (BR) for women requiring mastectomy. The purpose was to assess the available evidence on uptake, outcome and quality of life (QoL) after BR in older women. METHODS: A systematic literature review was performed via Medline, Embase and Cochrane databases using the search terms breast reconstruction, breast cancer, and mastectomy. Eligible studies reported rates of BR, rates of different reconstructive techniques, complication rates, and/or patient reported outcome measures (PROMs) of BR in women aged 60 years or older undergoing mastectomy for ductal carcinoma in situ or invasive carcinoma. RESULTS: A total of 42 eligible studies were included, with 32 of these reporting BR rates, 10 reporting rates of different reconstructive techniques, 10 reporting rates of complications, and four reporting PROMs. The studies reported 24,746 cases of BR in 407,570 mastectomy patients aged 60 years or older from 1987 to 2012. Implant based BR was more common than autologous techniques. Mostly, complication rates were not higher in older women, and QoL outcomes were similar to younger women. CONCLUSIONS: This review confirms that BR rates are lower in older women despite recent studies demonstrating its efficacy. The perception among some surgeons and women requiring mastectomy that the potential risks of BR in older women outweigh the benefits needs to be revisited. Education of consumers and surgeons along with public advocacy for offering BR to all clinically eligible women are the most promising means of changing practice.

Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment.

PURPOSE: Synovial sarcoma (SS) is a common soft tissue sarcoma (STS) with a propensity for young adults and notable sensitivity to chemotherapy (CT). This study provides a current clinicopathologic, staging, and prognostic assessment for SS. The problems with the current American Joint Committee for Cancer (AJCC) Staging System in relation to SS are discussed. METHODS: Review of a prospective database supplemented by retrospective data. RESULTS: One hundred fifty patients were assessed; median age was 30 years and median follow-up was 52 months. Overall actuarial 5-year survival rate was 57%. Size trend, but not a cutoff of less than 5 cm versus > or = 5 cm, was a prognostic indicator (P <.001). The current AJCC/International Union Against Cancer Staging System differentiated prognosis less well than the recently proposed Royal Marsden Hospital Staging System. Age greater than 20 years at diagnosis implied worse prognosis. A local recurrence event was associated with a worse survival (P <.001). Therapeutic CT was administered to 55 patients. Eleven of 19 patients had an objective response to a combination of ifosfamide and doxorubicin. Four cases had complete response after CT. Twenty-one patients had pulmonary metastasectomy, with an actuarial 5-year survival rate of 23%. CONCLUSION: SS tends to affect young people. In this subtype of STS, size trend is the most significant influence on stage and hence survival; however, smaller SSs have an unexpectedly poor prognosis. Adequate local control may affect survival. SS is often chemosensitive, and given its poor prognosis, multicenter trials of adjuvant therapy are warranted.

Extra-axillary sentinel node biopsy in the management of early breast cancer.

AIM: To document of our experience with EAS SNB and evaluate its impact on the staging, management and the associated morbidities of patients with early breast cancer. METHOD: A review of two prospective breast cancer databases identifying all SNB procedures performed at two affiliated breast units from 1998 to 2003. RESULTS: A series of 979 patients underwent lymphatic mapping. Sentinel nodes were successfully identified in 903 patients. There were 142 cases in which lymphoscintigraphy identified EAS. In 17 cases extraaxillary sentinel nodes were identified with lymphoscintigraphy but could not be removed. There were 138 cases where internal mammary nodes (IMN) were removed. Of those IMN removed 25 were positive for metastases and in six of these cases only the IMN was positive. Of the 21 cases where other EAS were identified there was one case in which a supraclavicular sentinel node was positive. Twenty-five of the 26 positive sentinel nodes in EAS were macrometastases and one was a micrometastasis. No significant morbidity resulted from biopsy of EAS SNB. During IMN SNB there were eight pleural breeches, which did not result in pneumothoraces, and one case in which bleeding was difficult to control. CONCLUSION: EAS SNB is technically feasible in the majority of cases. Minimal morbidity occurs after an initial learning phase. IMN SNB was shown to have significant impact on the staging and management in 18% of patients when IMNs were identified with lymphoscintigraphy. The impact of other extraaxillary lymph nodes is more difficult to assess due to small numbers. As there is little morbidity and valuable information is gained in a significant percentage of cases we strongly advocate EAS SNB.

Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node positivity.

AIMS: This study evaluates the breast cancer nomogram (BCN), an online tool developed by Memorial Sloan-Kettering Cancer Center to determine the rate of non-SLN positivity, in an independent cohort of SLN positive patients. MATERIAL AND METHODS: Available data between 02/2000 and 06/2004 in two prospective databases, 749 cases had successful SLN biopsy including 149 axillary-SLN metastases study cases. These cases had accurately graded tumours up to 9 cm in size and CAD with a minimum total 10 nodes removed. Histopathological assessment of nodes included hematoxylin and eosin staining and/or immunohistochemistry. Computerized BCN was used to estimate probability of non-SLN positivity and compared with actual probability after grouping into deciles. RESULTS: The trend of actual probability in various decile groups was comparable to the predicted probability. An area under the receiver operating characteristic curve was 0.75 as compared to 0.76 in the original study. CONCLUSION: Although this study is small, the results are encouraging and suggest the nomogram is a useful tool to estimate the likelihood of positive axillary non-SLN. However, variations in pathological assessment between centres are the major impediment to widespread application of BCN. If SLN positive patients decline the standard recommendation of CAD or entry into clinical trials evaluating the significance of CAD then the BCN could help in decision making.

Quality assurance in melanoma surgery: The evolving experience at a large tertiary referral centre.

BACKGROUND: The quality of melanoma surgery needs to be assessed by oncological outcome and complication rates. There is no published consensus on complication rates for common melanoma surgeries, namely wide excision (WE), sentinel node biopsy (SNB) and regional lymph node dissection (RLND). Consequently there are no agreed standards by which surgeons can audit their practices. METHODS: Surgical standards were proposed in 2008 following review of the literature and from expert opinion. Melanoma Institute Australia (MIA) self-reported audit data from 2011 and 2012 were compared with these standards. To quality check the self-reported audit, RLND data were extracted from the MIA database. RESULTS: Six surgeons performed a mean of 568 surgeries each quarter; with a mean of 106 major procedures. Following WE with primary closure or flap repair, wound infection or dehiscence occurred in <1% of cases. When skin grafting was required non-take of >20% of the grafted area was observed in 5.9% of cases. Following SNB wound infection and significant seroma occurred in 1.8% of cases. RLND node counts were below the 90% standard in 4 of 409 procedures. In comparison, data extraction identified 405 RLNDs, with node counts below the 90% standard in eight procedures. Two of these patients had previously undergone surgery removing nodes from the field and two had gross coalescing disease with extensive extra-nodal spread. CONCLUSION: The quality standards proposed in 2008 have been validated long-term by high volume caseloads. The data presented provide standards by which melanoma surgeons can audit their surgical performance.

Clinical significance of intramammary lymph nodes.

Intramammary lymph nodes (IMLN) are present in up to 47% of breasts and may be involved in metastatic disease in up to 9.8 % of operable breast cancer cases. IMLN are likely to be increasingly recognized with wider acceptance of high quality screening mammography and the use of ultrasound assessment of breast disease. The aim of this study is to demonstrate how IMLN can have an impact on management of breast cancer patients by presenting a case series of three patients. We conclude that IMLN metastases from breast cancer alters the prognosis and hence the management of patients. This will need to be addressed more frequently as sentinel node biopsy is more widely utilized.