Anne Brecht Francken

The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up.

AbstractBackground: The late Dr. Vincent McGovern (1915 to 1983) was an international authority on melanoma pathology and one of the first to suggest that assessment of tumor mitotic rate (TMR) might provide useful prognostic information. Data for a large cohort of patients, now with extended follow-up, whose tumors had been assessed by Dr. McGovern were analyzed to reassess the independent prognostic value of TMR in primary localized, cutaneous melanoma. Methods: Information was extracted from the Sydney Melanoma Unit database for 1317 patients treated between 1957 and 1982 for whom there was complete clinical information and whose primary lesion pathology, which included tumor thickness, ulcerative state, and TMR, had been assessed by Dr. McGovern. All these assessments were made according to the recommendations of the Eighth International Pigment Cell Conference, held in Sydney in 1972 under the auspices of the International Union Against Cancer. Factors predicting melanoma-specific survival were analyzed with the Cox proportional hazards regression model. Results: Stage, according to the recently revised American Joint Committee on Cancer Staging System (which is based on tumor thickness and ulceration) was the most predictive factor for survival (P < .0001). This was followed by primary lesion site (P < .0001), patient age (P = .0005), and TMR (P = .008). Conclusions: TMR was confirmed to be an important independent predictor of survival of patients with primary cutaneous melanoma. However, its predictive value was less than it was when assessed according to the 1982 revisions of the 1972 TMR recommendations.

Optimizing the Frequency of Follow-Up Visits for Patients Treated for Localized Primary Cutaneous Melanoma

PURPOSE To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma. METHODS We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence. RESULTS For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary. CONCLUSION By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma.

Follow-up schedules after treatment for malignant melanoma

Existing follow‐up guidelines after treatment for melanoma are based largely on dated literature and historical precedent. This study aimed to calculate recurrence rates and establish prognostic factors for recurrence to help redesign a follow‐up schedule.

Breslow thickness in the Netherlands: a population-based study of 40 880 patients comparing young and elderly patients

Background:Melanoma incidence has increased rapidly in the last decades, and predictions show a continuing increase in the years to come. The aim of this study was to assess trends in melanoma incidence, Breslow thickness (BT), and melanoma survival among young and elderly patients in the Netherlands.Methods:Patients diagnosed with invasive melanoma between 1994 and 2008 were selected from the Netherlands Cancer Registry. Incidence (per 100 000) over time was calculated for young (<65 years) and elderly patients (⩾65 years). Distribution of BT for young and elderly males and females was assessed. Regression analysis of the log-transformed BT was used to assess changes over time. Relative survival was calculated as the ratio of observed survival to expected survival.Results:Overall, 40 880 patients were included (42.3% male and 57.7% female). Melanoma incidence increased more rapidly among the elderly (5.4% estimated annual percentage change (EAPC), P<0.0001) than among younger patients (3.9% EAPC, P<0.0001). The overall BT declined significantly over time (P<0.001). Among younger patients, BT decreased for almost all locations. Among elderly males, BT decreased for melanomas in the head and neck region (P=0.001) and trunk (P<0.001), but did not decrease significantly for the other regions. Among elderly females, BT only decreased for melanomas at the trunk (P=0.01). The relative survival of elderly patients was worse compared with that of younger patients (P<0.001).Conclusion:Melanoma incidence increases more rapidly for elderly than for younger patients and the decline in BT is less prominent among elderly patients than among young patients. Campaigns in the Netherlands should focus more on early melanoma detection in the elderly.

Follow-Up of Melanoma Patients: The Need for Evidence-Based Protocols

Over the past decade it has become clear that sensible, safe, evidence-based guidelines are required for the followup of cancer patients. Patient expectations for high-quality care have increased, although ever-increasing restrictions are being imposed on expensive health care resources. Therefore the need for constructive, cost-effective, highquality guidelines for patients with a range of cancer types has now become urgent. For patients who have had a melanoma frequent clinical consultation and regular imaging studies are still common practice in many centres, despite a lack of evidence regarding their influence on overall survival, disease-free survival or quality of life. Why is this so? In the first place we cling to historical precedent. It is well known that this form of cancer is unpredictable, and the assumption has therefore been made that it should be monitored frequently and carefully. Secondly, it seems appropriate to detect recurrence at an early stage, since effective treatment of local, in-transit and regional node metastases offers the possibility of cure, and long-term survival can also follow complete resection of systemic metastases. Third, patient satisfaction and patient reassurance are provided by frequent clinical consultation. In this and a recent issue of Annals of Surgical Oncology two interesting studies are reported. The study of Meyer et al. is a retrospective report of 118 American Joint Committee on Cancer (AJCC) stage II and III melanoma patients who underwent regular structural imaging with a minimum follow-up of 2 years. Recurrence occurred in 35% (n = 43), of which 43% (n = 15) were distant metastases. However, only 7% (n = 3) of these patients were asymptomatic and had their recurrence detected by routine imaging. Another 26% (n = 11) were detected by routine clinical follow-up, including medical history and physical examination. This study is consistent with previous reports that found two-thirds of melanoma recurrences were patient detected. The study of Morton et al. evaluated 108 patients with AJCC stage IIIA and IIIB melanoma who were prospectively enrolled in a monitoring schedule of 6-monthly chest X-rays (CXR) in addition to clinical follow-up. They found metastases in 21% (n = 23) of the patients, which were detected in 48% (n = 11) by surveillance CXR. The other pulmonary metastases were not detected by CXR surveillance. The authors found sensitivity and specificity for surveillance CXR was 48% [95% confidence interval (CI) 0.27–0.68] and 78% (95%CI 0.77–0.79), respectively. In only 13% (n = 3) was metastasectomy considered appropriate. Moreover, 19 patients had a false-positive result for melanoma metastasis, 10 of whom underwent a pulmonary biopsy. This study confirms earlier results of retrospective studies: routine CXR does not seem to contribute to an improvement in survival of melanoma patients, nor is it cost effective. The results of these two valuable studies underscore the limited value of routine imaging in the follow-up of melanoma patients. However, both studies have their shortcomings. First the retrospective nature by the study of Meyer et al. and the lack of a control group in the study by Morton et al. reduce the level of evidence according to standard methodology. Second, the low number of patients in both studies makes them underpowered due to the low rate of events. Nevertheless, this type of clinical report is of great importance since large-scale prospective studies and appropriately designed randomised studies are extremely difficult to perform in this particular field; they might even be a waste of time and money based on current knowledge. The Author(s) 2009. This article is published with open access at Springerlink.comOver the past decade it has become clear that sensible, safe, evidence-based guidelines are required for the followup of cancer patients. Patient expectations for high-quality care have increased, although ever-increasing restrictions are being imposed on expensive health care resources. Therefore the need for constructive, cost-effective, highquality guidelines for patients with a range of cancer types has now become urgent. For patients who have had a melanoma frequent clinical consultation and regular imaging studies are still common practice in many centres, despite a lack of evidence regarding their influence on overall survival, disease-free survival or quality of life. Why is this so? In the first place we cling to historical precedent. It is well known that this form of cancer is unpredictable, and the assumption has therefore been made that it should be monitored frequently and carefully. Secondly, it seems appropriate to detect recurrence at an early stage, since effective treatment of local, in-transit and regional node metastases offers the possibility of cure, and long-term survival can also follow complete resection of systemic metastases. Third, patient satisfaction and patient reassurance are provided by frequent clinical consultation. In this and a recent issue of Annals of Surgical Oncology two interesting studies are reported. The study of Meyer et al. is a retrospective report of 118 American Joint Committee on Cancer (AJCC) stage II and III melanoma patients who underwent regular structural imaging with a minimum follow-up of 2 years. Recurrence occurred in 35% (n = 43), of which 43% (n = 15) were distant metastases. However, only 7% (n = 3) of these patients were asymptomatic and had their recurrence detected by routine imaging. Another 26% (n = 11) were detected by routine clinical follow-up, including medical history and physical examination. This study is consistent with previous reports that found two-thirds of melanoma recurrences were patient detected. The study of Morton et al. evaluated 108 patients with AJCC stage IIIA and IIIB melanoma who were prospectively enrolled in a monitoring schedule of 6-monthly chest X-rays (CXR) in addition to clinical follow-up. They found metastases in 21% (n = 23) of the patients, which were detected in 48% (n = 11) by surveillance CXR. The other pulmonary metastases were not detected by CXR surveillance. The authors found sensitivity and specificity for surveillance CXR was 48% [95% confidence interval (CI) 0.27–0.68] and 78% (95%CI 0.77–0.79), respectively. In only 13% (n = 3) was metastasectomy considered appropriate. Moreover, 19 patients had a false-positive result for melanoma metastasis, 10 of whom underwent a pulmonary biopsy. This study confirms earlier results of retrospective studies: routine CXR does not seem to contribute to an improvement in survival of melanoma patients, nor is it cost effective. The results of these two valuable studies underscore the limited value of routine imaging in the follow-up of melanoma patients. However, both studies have their shortcomings. First the retrospective nature by the study of Meyer et al. and the lack of a control group in the study by Morton et al. reduce the level of evidence according to standard methodology. Second, the low number of patients in both studies makes them underpowered due to the low rate of events. Nevertheless, this type of clinical report is of great importance since large-scale prospective studies and appropriately designed randomised studies are extremely difficult to perform in this particular field; they might even be a waste of time and money based on current knowledge. The Author(s) 2009. This article is published with open access at Springerlink.com

Radioactive seed localization is the preferred technique in nonpalpable breast cancer compared with wire-guided localization and radioguided occult lesion localization

Objectives Three commonly used techniques for localization of nonpalpable breast cancer are radioactive seed localization (RSL), wire-guided localization (WGL) and radioguided occult lesion localization (ROLL). In this study, we analysed the surgical margins of these three techniques. Methods Women diagnosed with nonpalpable breast cancer undergoing breast-conserving surgery with one of the above-mentioned techniques were retrospectively included. The primary outcome parameter was tumour-free margin rate. Secondary outcomes were re-excision rate, recurrence of disease and volume of removed tissue. Results In total, 272 women were included in whom RSL (n=69), WGL (n=76) or ROLL (n=137) was performed. RSL showed a higher tumour-free margin rate [64 (92.8%)] compared with WGL [51 (67.1%)] and ROLL [113 (82.5%)] (P=0.001). In our multivariable analysis, RSL showed a higher tumour-free margin rate as well compared with WGL (P=0.036) and ROLL (P=0.049). Also, fewer re-excisions were encountered using RSL [5 (7.2%)] compared with WGL [13 (17.1%)] and ROLL [15 (10.9%)] (P=0.171). In 11 patients (WGL n=2, ROLL n=9), recurrence of disease occurred, despite a radical excision. The mean resection volumes were comparable within the three groups. Conclusion RSL results in a higher tumour-free margin rate in nonpalpable breast tumours compared with WGL and ROLL. Therefore, we prefer using RSL in nonpalpable breast tumours.