Melanoma with unknown primary: report and analysis of 24 patients

In the literature, there are some papers reporting on patients with metastatic melanoma from an unknown primary lesion (MUP). The pathogenesis of this phenomenon and the prognosis of these patients are still debatable. Therefore, we reviewed our casistics on MUP patients. We identified 24 MUP patients out of all patients registered into a melanoma database from June 1996 to June 2011. The incidence was 1.4?%. We compared the survival rate of all patients with MUP stage III-IV with all patients with metastatic melanoma known primary (MMKP) stage III-IV observing a clear survival improvement for MUP patients in front of MMKP patients (p?相似文献   

Patients undergoing lymphadenectomy for stage III melanomas of known or unknown primary site do not differ in outcome

The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma‐specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five‐year adjusted melanoma‐specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.     

An evidence-based staging system for cutaneous melanoma

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.     

The effect of locoregional recurrence on survival and distant metastasis after conservative treatment for invasive breast carcinoma

AimsPatients with invasive breast cancer submitted to conservative treatment must be followed for a long period of time to study locoregional control. In this study, we analysed the outcome and relationships between locoregional recurrence (LRR), distant metastases and survival.Materials and methodsA 15-year study, including 470 women with early breast cancer, stage I and II, who underwent breast conservative treatment. Tumour size, nodal status, age, menopausal status, histological grade and LRR were analysed for their ability to predict overall survival, disease-specific survival and distant disease-free survival.ResultsWith a median follow-up time of 6.6 years (3 months to 19.1 years), there were 19 LRR at their first site of recurrence and 53 distant metastases. Tumour size greater than 2 cm, positive lymph nodes and histological grade III were significantly related to lower overall and distant metastases-free survival. On multivariate analysis, nodal status, histological grade III and LRR (coded as a time-dependent variable) were significantly related to overall, specific and distant metastases-free survival, whereas tumour size had only a borderline effect on specific and distant disease-free survival. Landmark analysis showed that women who presented an LRR within 2 years after surgery had significantly lower distant disease-free survival (hazard ratio [HR]: 8.39; 95% CI 2.56–27.47; P < 0.001), specific survival (HR: 8.19; 95% CI 2.45–27.41; P < 0.001) and overall survival (HR: 6.02; 95% CI 2.25–16.11; P < 0.005).ConclusionsLRR seems to be a significant predictor of distant metastases and survival, and patients who sustain early LRR tend to display a more aggressive clinical course.     

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients

BackgroundWe examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites.Patients and methodsClinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites.ResultsThe anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%,P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%,P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively.ConclusionsThe largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.     

Conditional survival of malignant melanoma in The Netherlands: 1994–2008

BackgroundCutaneous malignant melanoma causes the majority of skin cancer related deaths and features increasing incidence and mortality rates in the Netherlands. Conditional survival analysis is performed on patients who survived the preceding year(s).MethodsPatients with invasive melanoma, as recorded in the population-based Netherlands Cancer Registry, were included. To assess prognosis of melanoma survivors according to gender and Breslow thickness, conditional five-year relative survival was calculated for lymph node negative melanoma patients and conditional one-year relative survival was analysed for melanoma patients with and without nodal involvement.FindingsBetween 1994 and 2008, 40,050 patients developed a melanoma (stage I–III, of whom 6% with nodal involvement). Six to 8 years after diagnosis, survival of patients with a 1–2 mm (T2) thick melanoma equalised the general population. Conditional five-year relative survival for patients with >4 mm thick (T4) melanomas increased from about 60% at diagnosis to 90% at 7 years after diagnosis. Largest improvements were found in patients with thick melanomas and female patients with nodal involvement.InterpretationThe prognosis for melanoma survivors improved with each additional year of survival after diagnosis, except for patients with a ⩽1 mm thick melanoma, who never had any excess mortality during follow-up. Conditional survival of melanoma was better amongst females, amongst those with lower Breslow thickness and nodal stage.     

Metastatic melanoma to lymph nodes in patients with unknown primary sites

BACKGROUND: The natural history of metastatic melanoma in lymph nodes in the absence of a known primary site (MUP) has been defined poorly; thus, treatment guidelines for patients with MUP are not clear-cut. METHODS: The authors conducted a retrospective analysis of consecutive patients with melanoma (from 1990 to 2001) who underwent surgical resection for melanoma metastatic to regional lymph nodes. Among those patients, 71 patients with MUP and 466 control patients who had regional lymph node metastases of similar stage with a known primary site were identified. Associations between clinicopathologic factors and survival were estimated by using the Cox proportional hazards model. RESULTS: After they underwent lymph node dissection, patients with MUP were classified with N1b disease (47%), N2b disease (14%), or N3 disease (39%). With a median follow-up of 7.7 years, the 5-year and 10-year overall survival rates were 55% and 44%, respectively, for patients with MUP, compared with 42% and 32%, respectively, for the control group (P = .04). In multivariate analyses, age 50 years or older, male gender, and N2b or N3 disease status were identified as adverse prognostic factors, and MUP was identified as a favorable prognostic factor (hazard ratio, 0.61; 95% confidence interval, 0.42-0.86; P = .006) for overall survival. CONCLUSIONS: The relatively favorable long-term survival of patients with MUP in the current study suggested that patients with MUP have a natural history that is similar to (if not better than) the survival of many patients with Stage III disease. Therefore, patients with MUP should be treated with an aggressive surgical approach with curative intent and should be considered for Stage III adjuvant therapy protocols. Cancer 2006. (c) 2006 American Cancer Society.     

The revised American Joint Committee on Cancer staging system for melanoma

Substantial progress has been made in identifying the most significant clinical and pathologic characteristics of melanoma that predict for metastasis and survival. The American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma was recently revised to include these prognostic variables. Major changes in the staging include: (1) melanoma thickness and ulceration but not level of invasion will be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, "microscopic") versus clinically apparent (ie, "macroscopic") nodal metastases will be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactate dehydrogenase (LDH) will be used in the M category; (4) all patients with stage I, II, or III disease will be upstaged when a primary melanoma is ulcerated; (5) satellite metastases around a primary melanoma and in-transit metastases will be merged into a single staging entity that is grouped into stage III disease; and (6) distinct definitions for clinical and pathologic staging will take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.     

A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III)

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.     

Cutaneous melanoma: prognosis and treatment results worldwide.

This first metanalysis of melanoma from treatment centers worldwide consisted of 15,798 patients with localized melanoma (stages I and II) and 2,116 stage II melanoma patients with nodal metastases. Comparisons of dominant prognostic variables showed consistent results from center to center, despite the heterogeneity of the patient population. Six of eight centers that performed a multivariate analysis ranked ulceration among the first three most dominant prognostic factors. Men had a higher proportion of ulcerated lesions than did women. There was a positive correlation between ulceration and thickness. Patients with melanoma of the scalp had a worse prognosis than did those with lesions of the face and neck; those with melanomas on the hands had a significantly worse prognosis than did those with lesions on the arms or legs. In this study, women had a statistically significant survival advantage over men. Their melanomas arose in more favorable sites, were thinner, and less ulcerative and had a lower stage of disease at presentation. Stage III melanomas were more common in males, thicker, and more ulcerated and had a nodular growth pattern. Patients with clinically occult nodal metastases detected by pathological examination and those with a single metastatic node fared the best. Five of six centers identified the number of metastatic nodes to be the most significant prognostic factor. Distant metastases (stage IV were analysed at only two centers, which found that the number and site of metastases appeared to be the dominant prognostic features of stage IV melanoma. When all factors were analyzed in a Cox regression analysis, the dominant factors for stage IV melanoma patients were (1) the number of metastatic sites, and (2) the remission duration. There were no histologic criteria of the primary melanomas that predicted the patient's clinical course once distant metastases had developed.     

Complete metastasectomy in patients with stage IV metastatic melanoma

Patients with stage IV melanoma have traditionally been managed with various systemic treatments; however, overall survival with this approach has been disappointing. Findings of many retrospective, single-institution, and multicentre studies suggest that participants treated with complete metastasectomy for stage IV metastases have enhanced overall 5-year survival. Complete surgical resection of metastatic disease to stage IV sites-including skin, soft tissue, distant lymph nodes, lungs, or other non-CNS visceral regions-offers the best chance for prolonged survival. This Review will present data lending support to the idea that if complete surgical metastasectomy is technically feasible, then surgery should be the first option for properly selected patients with stage IV melanoma.     

Intermediate- and high-risk melanoma

Opinion statement Intermediate and high risk for recurrence melanoma comprise a unique subset of patients with surgically treatable melanoma for whom cure is possible but relapse and distant metastases likely. Strategies to improve the prognosis for such patients with effective adjuvant therapies are critical. In recent randomized trials conducted by the cooperative groups in the United States of patients at high risk for recurrence (patients with thick primary melanomas and those with regional lymph node metastases) administered adjuvant therapy with high-dose interferon alfa-2b (HDI), relapse-free survival and overall survival rates improved significantly. Research efforts in this area continue to assess the role of intermediate-dose interferon, but there is no convincing evidence of success of the lower-dose regimens, despite the reduction in toxicity. For a subset of patients at highest risk (two or more involved lymph nodes), a regimen of therapy for metastatic stage IV melanoma (interleukin-2 based biochemotherapy) is being compared with HDI in an ongoing phase III trial. For intermediate-risk melanoma, no effective adjuvant therapy is available. For such patients, enrollment in ongoing clinical trials assessing the role of shorter courses of HDI or vaccines should be encouraged.     

Metastatic melanoma of unknown primary resembles the genotype of cutaneous melanomas

BackgroundAlthough 90% of all melanomas are of cutaneous origin, some patients present with melanoma metastases of unknown origin (MUP). Commonly, in these patients an extensive search for the primary tumor is carried out. In the past, genetic analyses have shown substantial differences in pathogenetic mutations among cutaneous, acral and mucosal melanomas. The aim of this study was to assess the mutational status of MUP in order to better characterize the putative origin of the primary tumor and to evaluate potential prognostic factors.Patients and methodsThe medical records of 44 patients with MUP were analyzed and a survival analysis was conducted. In total, 66 paraffin samples of 44 patients were analyzed, and in 15 patients multiple metastases were tested. Mutational analysis of the BRAF, NRAS and KIT genes was carried out.ResultsTwenty-three patients (52.3%) had a mutation in the BRAF gene and 12 patients (23.8%) had a mutation in the NRAS gene. There were neither mutations in the KIT gene. In patients with multiple samples, there was 100% consistency regarding mutational status among the different metastases. The median overall survival (OS) was 86.4 months (39–134). The American Joint Committee on Cancer stage at first diagnosis of metastatic melanoma (stage III versus IV) was significantly associated with OS (P < 0.001), BRAF or NRAS mutation status had no significant prognostic impact on clinical outcomes.ConclusionsMUP resembles the genotype of cutaneous melanoma and not that of mucosal melanomas.     

The role of sentinel lymph node biopsy for melanoma

Regional lymph nodes are a common site of melanoma metastases, and the presence or absence of melanoma in regional lymph nodes is the single most important prognostic factor for predicting survival. Furthermore, identification of metastatic melanoma in lymph nodes and excision of these nodes may enhance survival in a subgroup of patients whose melanoma has metastasized only to their regional lymph nodes and not to distant sites. Sentinel lymph node (SLN) biopsy was developed as a low morbidity technique to stage the lymphatic basin without the potential morbidity of lymphedema and nerve injury. The presence or absence of metastatic melanoma in the SLN accurately predicts the presence or absence of metastatic melanoma in that lymph node basin. When performed by experienced centers, the false-negative rate of SLN biopsy is very low. As such, the nodal basin that contains a negative SLN will usually be free of microscopic disease. Since occult micrometastatic disease affects only 12% to 15% of patients with melanoma, selective SLN dissection allows up to 85% of patients with melanoma to be spared a formal lymph node dissection, thus avoiding the complications usually associated with that procedure. While standard pathologic evaluation of lymph nodes may miss metastatic melanoma cells, more sensitive techniques are developing which may identify micrometastases more accurately. The clinical significance of these micrometastases remains unknown and is the subject of active investigations.     

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

BackgroundThe 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 methodsctDNA 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).ResultsThe 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.ConclusionPre-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.     

Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: Correlation with clinical parameters and outcome

PurposeThe presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3, may play a pivotal role in the promotion of metastasis to regional lymph nodes. This study was designed to detect and evaluate whether the expression of VEGFR-3 or its soluble form plays a role in metastatic malignant melanoma and to determine the relationship with clinicopathological parameters and patients outcome.Experimental designVEGFR-3 expression on melanoma tumour was evaluated by immunohistochemical study. Using a sensitive enzyme-linked immunosorbent assay, sVEGFR-3 was measured in sera of 60 metastatic melanoma patients in comparison with 30 healthy controls.ResultsImmunohistochemical study demonstrated a high expression of VEGFR-3 in melanoma cells. Median level of pre-treatment sVEGFR-3 was significantly higher (p = 0.00001) in melanoma patients as compared to healthy donors. No association was noted between VEGFR-3 in situ or in sera and gender, age or LDH level. Median serum VEGFR-3 levels were significantly higher in patients with high tumour burden as compared to those with low tumour burden (p = 0.013) as well as in non-responding patients (n = 33) as compared to responding ones (n = 27). Finally, low level of VEGFR-3 was also related positively to disease free survival (X² = 3.85, p = 0.022).ConclusionThese results suggest that the expression and high pre-treatment sVEGFR-3 level are significantly correlated to poorer prognosis, and may be promising targets for new therapeutic strategies in melanoma disease.     

Survival of patients with metastatic melanoma and brain metastases in the era of MAP-kinase inhibitors and immunologic checkpoint blockade antibodies: A systematic review

BackgroundThe incidence of brain metastases (BM) in melanoma patients is common and associated with poor prognosis. MAP-kinase inhibitors and immunologic checkpoint blockade antibodies led to improved survival of metastatic melanoma patients; however, patients with BM are under-represented or excluded from the majority of clinical trials and the impact of new drugs on their survival is less clear. With the present systematic review, we aimed to analyze outcomes of patients with melanoma BM treated with the new drugs, both in the setting of phase I–II–III clinical trials and in the “real world”.MethodsAn electronic search was performed to identify studies reporting survival outcomes of patients with melanoma BM treated with MAP-kinase inhibitors and/or immunologic checkpoint blockade antibodies, regardless of study design.ResultsTwenty-two studies were included for a total of 2153 patients. Median OS was 7.9 months in phase I–II–III trials and 7.7 months in “real world” studies. In clinical trials, median OS was 7.0 months for patients treated with immunotherapy and 7.9 months for patients treated with BRAF inhibitors. In “real world” studies, median OS was 4.3 months and 7.7 months for patients treated with immunotherapy and BRAF inhibitors, respectively. Evidence of clinical activity exists for both immunotherapy and MAP-kinase inhibitors.ConclusionsMAP-kinase inhibitors and immunologic checkpoint blockade antibodies have clinical activity and may achieve improved OS in patients with metastatic melanoma and BM. These results support the inclusion of patients with BM in investigations of new agents and new treatment regimens for metastatic melanoma.     

Male breast cancer: A retrospective analysis

BackgroundTo evaluate our results in the treatment of male breast cancer patients with respect to local control (LC), overall survival (OS) and possible prognosis factors for survival.Patients and methodsThirty-nine patients with male breast cancer have been retrospectively studied with the trial aim to evaluate the results of our practice. Among them, 94.8% had invasive ductal carcinoma (IDC), 2.6% invasive papillary carcinoma (IPC) and 2.6% invasive lobular carcinoma (ILC) and the distribution according to stage was found to be 12.8, 46.2, 30.7 and 10.3% in Stages I, II, III and IV, respectively. Among the patients, 7.7% received radiotherapy (RT) and hormonotherapy (HT), 22.8% received chemotherapy (CT), 61.8% received chemoradiotherapy (CRT) and HT and 7.7% received HT in addition to surgery.ResultsThe distant metastases rate was 36% and the local recurrence rate was 5%. All the local recurrences and the distant metastases had occurred after the first two years. The five-year disease free survival (DFS) and OS rates were 65.8 and 80.1% respectively. In our series, univariate analysis for OS demonstrated statistical significance for lymph node metastases (p = 0.00001), stage (p = 0.0098) and age (p = 0.03); while RT in the treatment modality (p = 0.6849), and tumor size (p = 0.4439) demonstrated no significance. The presence of lymph node metastases significantly impairs OS (p = 0.004) and DFS (p = 0.014) in multivariate analysis.ConclusionPostoperative radiotherapy was important in the management of male breast cancer to improve LC resulting in one local failure, but did not improve OS and DFS in our analysis. The presence of lymph node metastases significantly impaired OS and DFS.     

Efficacy and safety of ipilimumab 3 mg/kg in patients with pretreated,metastatic, mucosal melanoma

BackgroundMucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma.MethodsIpilimumab was available upon physician request for patients aged ⩾16 years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12 using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4 days of each scheduled visit.ResultsOf 855 patients participating in the EAP in Italy, 71 (8%) had metastatic, mucosal melanoma. With a median follow-up of 21.8 months, the response rate was 12% and the immune-related disease control rate was 36%. Median progression-free survival and overall survival were 4.3 and 6.4 months, respectively. In total, 34% of patients reported treatment-related AEs of any grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable as per protocol-specific guidelines.Conclusion/interpretationIpilimumab may be a feasible treatment option in pretreated patients with metastatic mucosal melanoma, and warrants further investigation in prospective clinical trials.