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Implementation of the 7th edition AJCC staging system: effects on staging and survival for pT1 melanoma. A Dutch population based study
Poster Session, Saturday 28 January 2017 Conclusions: Age >50, Breslow thickness >2 mm and N2 versus N1 are prognostic for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and help select the appropriate population for adjuvant therapy (trials). No conflict of interest. 1204A POSTER Implementation of the 7th edition AJCC staging system: effects on staging and survival for pT1 melanoma. A Dutch population based study 1 C. Oude Ophuis1 , M. Louwman2 , D. Grunhagen ¨ , C. Verhoef1 , A. Van Akkooi3 . 1 Erasmus MC − Cancer Institute, Surgical Oncology, Rotterdam, Netherlands; 2 Netherlands Comprehensive Cancer Organization IKNL, Department of Research, Utrecht, Netherlands; 3 Netherlands Cancer Institute - Antoni van Leeuwenhoek, Surgical Oncology, Amsterdam, Netherlands
Background: In the 7th edition of the AJCC staging system the mitotic rate criterion replaced Clark level to increase correct classification of high risk thin melanoma patients (pT1B). Additionally, sentinel node biopsy (SNB) was recommended for nodal staging for pT1B melanomas. Aim: To evaluate the effects on pT1 substaging and clinical implications in the national pT1 melanoma population. Material and Methods: All pT1 melanomas diagnosed in the Netherlands between 2003 and 2014 were selected from the Netherlands Cancer Registry (IKNL). Patients were stratified by cohort: according to AJCC edition: (1) 2003−2009 (6th ) and (2) 2010−2014 (7th ). Relative survival was calculated to estimate melanoma specific survival. Results: A total of 29,546 pT1 melanoma patients were included. The pT1b proportion increased from 10.1% in cohort 1, to 21.5% in cohort 2. The proportion of performed SNBs per cohort increased: for pT1b melanomas alone from 4.5% to 13.0%. SNB positivity rate decreased from 10.5% to 8.8% for the entire pT1 population, and for pT1b melanomas from 11.3% to 8.6%. Conclusions: At 5 years, the relative survival rate was similar for pT1a and pT1b in both cohorts, namely pT1a 100% vs pT1b 97% (cohort 1), and pT1a 100% vs. pT1b 98% (cohort 2). The 7th edition of the AJCC staging system has caused an increased number of patients to undergo SNB, without an increase in SNB positivity rate. Survival between pT1 subgroups remains similar. The mitotic rate criterion for pT1b classification and the recommendation to perform SNB for pT1b melanomas should be reconsidered. No conflict of interest. 1205 POSTER SPOTLIGHT PET/CT surveillance detects asymptomatic recurrences in stage IIIB and IIIC melanoma patients: a prospective cohort study M. Madu1 , P. Timmerman1 , M. Wouters1 , B. Van der Hiel2 , J. Van der Hage1 , A. Van Akkooi1 . 1 The Netherlands Cancer Institute, Surgical Oncology, Amsterdam, Netherlands; 2 The Netherlands Cancer Institute, Nuclear Medicine, Amsterdam, Netherlands Background: AJCC stage IIIB and IIIC melanoma patients are at risk for disease relapse or progression. The advent of effective systemic therapies has made curative treatment of progressive disease a possibility. Since resection of oligometastatic disease can confer a survival benefit and immunotherapy is possibly most effective in a low tumor load setting, there is a likely benefit to early detection of progression. The aim of this pilot study was to evaluate a PET/CT surveillance schedule for resected stage IIIB and IIIC melanoma. Study design: From 1-2015, stage IIIB and IIIC melanoma patients at our institution underwent 6-monthly surveillance with PET/CT, together with 3-monthly S100B assessment. When symptoms or elevated S100B were detected, an additional PET/CT was performed. Descriptive statistics were used to evaluate outcomes for this surveillance schedule. Results: Twenty-five patients were included. Fourteen patients (56%) were suspected of relapse on PET/CT. Relapses were confirmed in 11 patients. Recurrences were mostly regional in stage IIIB patients (2 out of 3) and mostly distant in stage IIIC cases (5 out of 9). Three cases were false positive. There were no false negative cases. Six out of 11 recurrences detected by PET/CT were asymptomatic at that time, with a normal range S100B. Nine patients received curative treatment after diagnosis of relapse. Conclusions: Surveillance imaging with S100B in combination with PET/CT seems an effective strategy to detect asymptomatic recurrence in stage IIIB and IIIC melanoma patients in the first months after complete surgical resection. No conflict of interest.
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1205A POSTER Positive sentinel node in the groin area: Extent of completion lymphadenectomy and prognosis for melanoma patients C. Oude Ophuis1 , M. Madu2 , D. Verver1 , B. Van Leeuwen3 , M. Faut3 , J. De Wilt4 , J. Bonenkamp4 , D. Grunhagen1 , A. Van Akkooi2 , C. Verhoef1 . 1 Erasmus MC Cancer Institute, Surgical Oncology, Rotterdam, Netherlands; 2 Netherlands Cancer Institute - Antoni van Leeuwenhoek, Surgery, Amsterdam, Netherlands; 3 Groningen University Medical Center, Surgical Oncology, Groningen, Netherlands; 4 Radboud University Medical Center, Surgical Oncology, Nijmegen, Netherlands Background: The therapeutic effect of completion lymphadenectomy (CLND) after a positive sentinel node biopsy (SNB) is still being investigated. The optimal surgical extent of a groin CLND, i.e. superficial groin dissection (SGD) or combined superficial and deep groin dissection (CGD) including additional removal of pelvic nodes, is a highly controversial topic. The aim of the present study is to investigate whether the extent of groin CLND after a positive inguinal SNB is associated with better survival outcome. Methods: Data of all sentinel node (SN) positive patients who underwent a groin CLND at four tertiary melanoma referral centers were retrieved retrospectively. Inclusion was based on complete CLND details and absence of positive SNs outside the groin area. Baseline, patient and tumor characteristics were collected for descriptive statistics, survival analyses and Cox proportional hazards regression analyses. Recurrence pattern, disease free survival (DFS), distant metastasis free survival (DMFS), and melanoma specific survival (MSS) were analyzed across both treatment groups. Results: A total of 255 patients were included, of which 125 (49%) were men. Median age was 51 years [interquartile range (IQR) 39−62 years], median follow-up was 51 months [IQR 26−99 months]. Median Breslow thickness was 2.90 mm [IQR 1.80–4.55 mm], and 108 (42%) patients had ulcerated primaries. One-hundred-thirty-seven (54%) patients underwent SGD, and 118 (46%) CGD. The overall non-SN metastasis rate was 19%, the inguinal non-SN metastasis rate was 16% and the pelvic non-SN metastasis rate was 10%. The inguinal non-SN metastasis rate after CGD was significantly higher than after SGD (21% vs. 11%, P = 0.025), but the median number of excised inguinal nodes was similar (8 [IQR 5−10] vs. 8 [IQR 5−11], P = 0.417). Recurrence pattern, 5-year MSS, DFS and DMFS were similar between SGD and CGD. In a MSS Cox-proportional hazards model CLND type was not significant univariate nor after adjustment for known risk factors. Conclusions: CGD compared to SGD was not associated with better outcome in patients with a positive SNB. The risk of pelvic nodal involvement in these patients was low (10%). These results illustrate that SGD may be a safe first approach as CLND in most patients with micrometastatic disease. No conflict of interest. 1206 POSTER A possibility for therapy of metastatic cutaneous melanoma with cationic peptides A. Lushnikova1 , D. Ponkratova1 , S. Andreev2 , I. Tsyganova1 , I. Abramov3 , R. Khaitov2 . 1 N.N. Blokhin Cancer Research Center, Carcinogenesis Institute, Moscow, Russian Federation; 2 National Research Center “Institute of Immunology”, Laboratory of Peptid Immunogenes, Moscow, Russian Federation; 3 N.N. Blokhin Cancer Research Center, Clinical Oncology Institute, Moscow, Russian Federation Introduction: Cutaneous melanoma (CM) is the most aggressive form of skin cancer in human. Metastatic dissemination is responsible for the majority of melanoma-related mortalities. Nucleophosmin/NPM1 and nucleolin/NCL are multifunctional nucleolar phosphoproteins, which play a key role in cell cycle regulation, ribosome biogenesis, transcription and translation, molecular transport and signaling. As a rule, high levels of NPM1/NCL expression in tumors is correlated with poor clinical outcome. Highly expressed NPM1/NCL in tumor cells are considered as a possible targets for anticancer treatment. Cationic peptides (CP) are promising as a low-toxic and resistant to intercellular degradation molecule, which can penetrate cells and induce tumor cell death. Material and Methods: A group of CP with different molecular structure, including linear and dendritic ones, has been tested in vitro. The dynamics of cell proliferation and toxicity of CP was studied on CM cell lines mH745 and mIS223 and human fibroblast line H1036 as a control. Structure and expression of NPM/NCL genes were analyzed by PCR, subsequent PAAGE, RT PCR and western-blotting, using p53 and NCLspecific antibodies. The BRAF/NRAS oncogene and TP53 gene mutations were analyzed by PCR followed by direct sequencing. Peptide toxicity was determined by standard MTT assay.
Background: In the 7th edition of the AJCC staging system the mitotic rate criterion replaced Clark level to increase correct classification of high risk thin melanoma patients (pT1B). Additionally, sentinel node biopsy (SNB) was recommended for nodal staging for pT1B melanomas. Aim: To evaluate the effects on pT1 substaging and clinical implications in the national pT1 melanoma population. Material and Methods: All pT1 melanomas diagnosed in the Netherlands between 2003 and 2014 were selected from the Netherlands Cancer Registry (IKNL). Patients were stratified by cohort: according to AJCC edition: (1) 2003−2009 (6th ) and (2) 2010−2014 (7th ). Relative survival was calculated to estimate melanoma specific survival. Results: A total of 29,546 pT1 melanoma patients were included. The pT1b proportion increased from 10.1% in cohort 1, to 21.5% in cohort 2. The proportion of performed SNBs per cohort increased: for pT1b melanomas alone from 4.5% to 13.0%. SNB positivity rate decreased from 10.5% to 8.8% for the entire pT1 population, and for pT1b melanomas from 11.3% to 8.6%. Conclusions: At 5 years, the relative survival rate was similar for pT1a and pT1b in both cohorts, namely pT1a 100% vs pT1b 97% (cohort 1), and pT1a 100% vs. pT1b 98% (cohort 2). The 7th edition of the AJCC staging system has caused an increased number of patients to undergo SNB, without an increase in SNB positivity rate. Survival between pT1 subgroups remains similar. The mitotic rate criterion for pT1b classification and the recommendation to perform SNB for pT1b melanomas should be reconsidered. No conflict of interest. 1205 POSTER SPOTLIGHT PET/CT surveillance detects asymptomatic recurrences in stage IIIB and IIIC melanoma patients: a prospective cohort study M. Madu1 , P. Timmerman1 , M. Wouters1 , B. Van der Hiel2 , J. Van der Hage1 , A. Van Akkooi1 . 1 The Netherlands Cancer Institute, Surgical Oncology, Amsterdam, Netherlands; 2 The Netherlands Cancer Institute, Nuclear Medicine, Amsterdam, Netherlands Background: AJCC stage IIIB and IIIC melanoma patients are at risk for disease relapse or progression. The advent of effective systemic therapies has made curative treatment of progressive disease a possibility. Since resection of oligometastatic disease can confer a survival benefit and immunotherapy is possibly most effective in a low tumor load setting, there is a likely benefit to early detection of progression. The aim of this pilot study was to evaluate a PET/CT surveillance schedule for resected stage IIIB and IIIC melanoma. Study design: From 1-2015, stage IIIB and IIIC melanoma patients at our institution underwent 6-monthly surveillance with PET/CT, together with 3-monthly S100B assessment. When symptoms or elevated S100B were detected, an additional PET/CT was performed. Descriptive statistics were used to evaluate outcomes for this surveillance schedule. Results: Twenty-five patients were included. Fourteen patients (56%) were suspected of relapse on PET/CT. Relapses were confirmed in 11 patients. Recurrences were mostly regional in stage IIIB patients (2 out of 3) and mostly distant in stage IIIC cases (5 out of 9). Three cases were false positive. There were no false negative cases. Six out of 11 recurrences detected by PET/CT were asymptomatic at that time, with a normal range S100B. Nine patients received curative treatment after diagnosis of relapse. Conclusions: Surveillance imaging with S100B in combination with PET/CT seems an effective strategy to detect asymptomatic recurrence in stage IIIB and IIIC melanoma patients in the first months after complete surgical resection. No conflict of interest.
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1205A POSTER Positive sentinel node in the groin area: Extent of completion lymphadenectomy and prognosis for melanoma patients C. Oude Ophuis1 , M. Madu2 , D. Verver1 , B. Van Leeuwen3 , M. Faut3 , J. De Wilt4 , J. Bonenkamp4 , D. Grunhagen1 , A. Van Akkooi2 , C. Verhoef1 . 1 Erasmus MC Cancer Institute, Surgical Oncology, Rotterdam, Netherlands; 2 Netherlands Cancer Institute - Antoni van Leeuwenhoek, Surgery, Amsterdam, Netherlands; 3 Groningen University Medical Center, Surgical Oncology, Groningen, Netherlands; 4 Radboud University Medical Center, Surgical Oncology, Nijmegen, Netherlands Background: The therapeutic effect of completion lymphadenectomy (CLND) after a positive sentinel node biopsy (SNB) is still being investigated. The optimal surgical extent of a groin CLND, i.e. superficial groin dissection (SGD) or combined superficial and deep groin dissection (CGD) including additional removal of pelvic nodes, is a highly controversial topic. The aim of the present study is to investigate whether the extent of groin CLND after a positive inguinal SNB is associated with better survival outcome. Methods: Data of all sentinel node (SN) positive patients who underwent a groin CLND at four tertiary melanoma referral centers were retrieved retrospectively. Inclusion was based on complete CLND details and absence of positive SNs outside the groin area. Baseline, patient and tumor characteristics were collected for descriptive statistics, survival analyses and Cox proportional hazards regression analyses. Recurrence pattern, disease free survival (DFS), distant metastasis free survival (DMFS), and melanoma specific survival (MSS) were analyzed across both treatment groups. Results: A total of 255 patients were included, of which 125 (49%) were men. Median age was 51 years [interquartile range (IQR) 39−62 years], median follow-up was 51 months [IQR 26−99 months]. Median Breslow thickness was 2.90 mm [IQR 1.80–4.55 mm], and 108 (42%) patients had ulcerated primaries. One-hundred-thirty-seven (54%) patients underwent SGD, and 118 (46%) CGD. The overall non-SN metastasis rate was 19%, the inguinal non-SN metastasis rate was 16% and the pelvic non-SN metastasis rate was 10%. The inguinal non-SN metastasis rate after CGD was significantly higher than after SGD (21% vs. 11%, P = 0.025), but the median number of excised inguinal nodes was similar (8 [IQR 5−10] vs. 8 [IQR 5−11], P = 0.417). Recurrence pattern, 5-year MSS, DFS and DMFS were similar between SGD and CGD. In a MSS Cox-proportional hazards model CLND type was not significant univariate nor after adjustment for known risk factors. Conclusions: CGD compared to SGD was not associated with better outcome in patients with a positive SNB. The risk of pelvic nodal involvement in these patients was low (10%). These results illustrate that SGD may be a safe first approach as CLND in most patients with micrometastatic disease. No conflict of interest. 1206 POSTER A possibility for therapy of metastatic cutaneous melanoma with cationic peptides A. Lushnikova1 , D. Ponkratova1 , S. Andreev2 , I. Tsyganova1 , I. Abramov3 , R. Khaitov2 . 1 N.N. Blokhin Cancer Research Center, Carcinogenesis Institute, Moscow, Russian Federation; 2 National Research Center “Institute of Immunology”, Laboratory of Peptid Immunogenes, Moscow, Russian Federation; 3 N.N. Blokhin Cancer Research Center, Clinical Oncology Institute, Moscow, Russian Federation Introduction: Cutaneous melanoma (CM) is the most aggressive form of skin cancer in human. Metastatic dissemination is responsible for the majority of melanoma-related mortalities. Nucleophosmin/NPM1 and nucleolin/NCL are multifunctional nucleolar phosphoproteins, which play a key role in cell cycle regulation, ribosome biogenesis, transcription and translation, molecular transport and signaling. As a rule, high levels of NPM1/NCL expression in tumors is correlated with poor clinical outcome. Highly expressed NPM1/NCL in tumor cells are considered as a possible targets for anticancer treatment. Cationic peptides (CP) are promising as a low-toxic and resistant to intercellular degradation molecule, which can penetrate cells and induce tumor cell death. Material and Methods: A group of CP with different molecular structure, including linear and dendritic ones, has been tested in vitro. The dynamics of cell proliferation and toxicity of CP was studied on CM cell lines mH745 and mIS223 and human fibroblast line H1036 as a control. Structure and expression of NPM/NCL genes were analyzed by PCR, subsequent PAAGE, RT PCR and western-blotting, using p53 and NCLspecific antibodies. The BRAF/NRAS oncogene and TP53 gene mutations were analyzed by PCR followed by direct sequencing. Peptide toxicity was determined by standard MTT assay.