Cutaneous Malignant Melanoma Stage Research Articles

TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma

BackgroundThe incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only.MethodsThe TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/− whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.DiscussionThis is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.ResultsThe first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.Trial registrationClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412

Efficacy of positron emission tomography and computed tomography in clinical staging of cutaneous malignant melanoma.

Accurate staging is very important for determining the prognosis and appropriate treatment for malignant melanoma (MM). The aim of this study is to determine the effectiveness of positron emission tomography and computed tomography (PET/CT) imaging in staging MM. Patients diagnosed with MM who then underwent PET/CT metastasis before treatment were assessed retrospectively. For each patient, the following variables were recorded: Breslow thickness, Clark's level, number of mitoses, the presence of ulceration detected in the pathology report, and the presence of lymph nodes and/or distant metastases detected by PET/CT. The pathology and PET/CT reports of 139 patients (79 female and 60 male) were retrospectively evaluated for staging after MM diagnosis. Patients with a Breslow thickness greater than 3.4 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with regional lymph node metastasis after PET/CT scans. Patients with Breslow thickness greater than 2.85 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with distant metastasis after PET/CT scan. The results of our study suggest that PET/CT imaging for metastasis scanning, starting with T2 patients, may be used in MM staging to reduce the need for sentinel lymph node (SLN) biopsy and lymph node dissection.

Diagnostic Accuracy and Impact of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Preoperative Staging of Cutaneous Malignant Melanoma: Results of a Prospective Study in Indian Population.

The aim of the study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) in staging patients with primary cutaneous malignant melanoma (CMM). We further compared the performance of PET/CT with conventional imaging (CI) (CT and ultrasonography [USG]) and assessed the impact of PET/CT on disease management. This was a single institution, prospective, double-blinded study, recruiting a total of 70 treatment naïve patients. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT for N staging were 86%, 96%, 80%, and 97%, respectively. The sensitivity, specificity, NPV, and PPV of PET/CT for M staging were 87%, 100%, 93%, and 100%, respectively. The diagnostic accuracy of the PET/CT was superior to CI for N staging (90% vs. 84% for CT and 80% for USG) and M staging (95% vs. 90% for CT). No statistically significant difference was noted between PET/CT and CI for N staging (PET/CT vs. CT, P = 0.125; PET/CT vs. USG, P-0.063) or M staging (PET/CT vs. CT, P = 0.125). PET/CT upstaged 23% of patients with clinically localized disease and 58% of patients with clinically palpable regional nodes. To conclude, fluorodeoxyglucose PET/CT is a highly sensitive and specific imaging modality for preoperative staging of primary CMMs. PET/CT impacts disease management in significant number of patients and should be especially recommended in all patients with clinically palpable regional nodes.

Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality

Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis and outcome.Material and methods All patients with primary invasive CMM diagnosed in 2004–2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality.Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage-specific incidence of CMM. The incidence of stage I–II tumors was higher in the western health care region, whereas the incidence of stage III–IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level. The geographic disparities in CMM stage influenced relative survival with an excess five-year mortality ratio in the southern region versus the western region of 1.49 (95% confidence interval 1.22–1.82). The excess mortality ratio for patients with low versus high educational level was 1.81 (1.37–2.40).Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM.

Diagnostic accuracy of contrast-enhanced FDG-PET/CT in primary staging of cutaneous malignant melanoma

To evaluate the diagnostic accuracy of contrast-enhanced FDG-PET/CT (ce-PET/CT), PET-only, and CT-only in patients with newly diagnosed and resected cutaneous malignant melanoma. A final group of 56 patients (mean age 62 years, range 23-86 years; 29 women, 27 men) were staged with ce-PET/CT after resection of the primary tumour. Histopathology as well as clinical follow-up (mean 780 days, range 102-1,390 days) served as the standards of reference. Differences between the staging modalities were tested for statistical significance with McNemar's test. All imaging procedures provided low sensitivities in the detection of lymph nodes (sensitivity N-stage: PET/CT and PET-only 38.5%; CT-only 23.1%) and distant metastases (sensitivity M-stage: PET/CT 41.7%, PET-only 33.3%, CT-only 25.0%) in initial staging after resection of the primary tumour. No statistically significant differences were detected between the imaging procedures (p > 0.05). PET/CT resulted in an alteration in further treatment in two patients compared to PET-only and in four patients compared to CT-only. All imaging modalities had a low sensitivity on initial staging of patients with malignant melanoma. Thus, close patient follow-up must be considered mandatory.

Role of PET in the Initial Staging of Cutaneous Malignant Melanoma: Systematic Review

To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC1.

Reliability and accuracy of sentinel node biopsy in cutaneous malignant melanoma.

The aims of this study were 1) to investigate whether sentinel lymph node (SLN) biopsy could become the method of choice for the early detection of metastatic disease in patients with malignant melanoma and 2) to identify those patients with lymph node metastases who could benefit from regional lymphadenectomy. Our study started in March 1998 and involved 110 patients with primary cutaneous malignant melanoma stage I or II (AJCC) in whom the primary lesion had been surgically removed no more than 90 days previously. On the day of lymph node dissection patients were given an intradermal injection of colloid particles of human serum albumin labeled with technetium-99m and an injection of isosulfan blue. The surgical procedure was usually performed with local anesthesia but in some cases locoregional or general anesthesia was preferred. Contralateral and ipsilateral lymphatic areas were scanned with a hand-held gamma camera (Scintiprobe MR 100) to measure the background and identify the hot point indicating the location of the sentinel node to direct the incision. The combined use of lymphoscintigraphy, isosulfan blue and gamma probe allowed us to identify sentinel nodes in 108 of 110 patients (98.18%) while the SLN was blue in only 90 cases (81.81%). The SLN was positive for metastases in 13 of the 108 patients (12.03%) and regional and distal lymphadenectomy was performed in all of them. The distribution of positive SLNs by primary lesion thickness was as follows: 0.76-1.5 mm: one positive SLN/44 patients (2.27%); 1.51-4 mm: six positive SLNs/51 patients (11.7%); > 4 mm: six positive SLNs/15 patients (40%). Only four of 12 patients with ulcerated cutaneous melanoma had positive SLNs. The patients in our study underwent follow-up visits every four months. The median follow-up was 481 days (range, 97-1271 days). In patients with primary cutaneous melanoma the histological status of the SLN accurately reflects the presence or absence of metastatic disease in the relevant regional lymph node basin. Complete lymph node dissection should only be performed in patients with positive SLNs. Patients with lesions > 4 mm are likely to develop recurrences and to die of systemic disease, so in these patients the usefulness of SLN biopsy is questionable. In conclusion, sentinel node mapping is a rational approach for the selection of patients who might benefit from early lymph node dissection of the affected basin.

Diagnosis, detection, and staging of cutaneous malignant melanoma

Diagnosis, detection, and staging of cutaneous malignant melanoma