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Predictive factors of Mohs micrographic surgery stages in nonmelanoma skin cancer in Indonesian population
4620
5459
Predicting return of chronic idiopathic urticaria symptoms following omalizumab treatment discontinuation: Exploratory analysis of phase III data Ana Gim enez-Arnau, MD, Hospital del Mar-Parc de Salut Mar; Marta Ferrer, MD, Clinica Universidad de Navarra; Diego Saldana, Novartis Pharma AG; Nico Janssens, Novartis Pharma AG; Maria-Magdalena Balp, Novartis Pharma AG; Sam Khalil, Novartis Pharma AG Introduction: Factors that influence urticaria symptom return are poorly understood in chronic idiopathic urticaria (CIU) patients who discontinue omalizumab treatment. This analysis explored potential predictors of rapid symptom return following omalizumab discontinuation in CIU patients. Methods: Variables predicting symptom return over the 16-week follow-up period were identified using a least absolute shrinkage and selection operator (LASSO) regularization regression model. The analysis used pooled Phase III randomized controlled trial (RCT) data from ASTERIA I (n ¼ 319; 6x4-weekly injections of omalizumab 75, 150, 300 mg or placebo) and ASTERIA II (n ¼ 323; 3x4-weekly injections of omalizumab 75, 150, 300 mg or placebo), or pooled omalizumab 300 mg data only. Probability of rapid symptom return was assessed using linear regression with prediction intervals, and relapse probability was represented using heat map visualizations. Accuracy of the omalizumab 300 mg-based model was tested using data from GLACIAL Phase III RCT (n ¼ 336; 6x4-weekly injections of omalizumab 300 mg or placebo).
Predictive factors of Mohs micrographic surgery stages in nonmelanoma skin cancer in Indonesian population Adhimukti T. Sampurna, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Amanda N. Wardani, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Inadia P. Chairista, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Riva A. Pradita, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia Introduction: Nonmelanoma skin cancer (NMSC) as the most common type of skin cancer are rarely metastasize to distant site. Despite the low metastasis rate, these cancers can result into a substantial local destruction and extend to surrounding areas. Therefore sufficient complete tumor tissue removal should always be the aim of surgery. On this wise, Mohs micrographic surgery (MMS) is the recommended therapeutic approach. However, in Asian countries especially Indonesia, MMS is still considered as a novel technique. In our national tertiary referral hospital, MMS has been performed in 56 cases from June 2014 to August 2016. Our study aims to evaluate the characteristic of NMSC treated with MMS and to identify the predictive factors of MMS stages required.
Results: Of 2,677 variables assessed, 2 were shown by the models to have a statistically significant impact as predictors of symptom return. The variables were baseline UAS7 (weekly urticaria activity score) and early area above the curve (AAC e determined by plotting the UAS7 scores from baseline to week 4). Results suggest high baseline UAS7 and low AAC (representing slow decrease of symptoms, as measured by the UAS7 score, in the 4 weeks after start of the treatment) indicate higher probability of rapid symptom return. Predictive accuracy was higher when the model included pooled dose data vs omalizumab 300 mg data only. Conclusions: Findings suggest that in CIU patients who discontinue treatment with omalizumab, probability of rapid symptom return can be estimated based on baseline UAS7 and early AAC. Influence of early AAC decreases and that of baseline UAS7 increases when the model is based on omalizumab 300 mg alone. Commercial support: ASTERIA I, ASTERIA II and GLACIAL studies were funded by Genentech Inc., South San Francisco, CA, USA, and Novartis Pharma AG, Basel, Switzerland.
Methods: All patients with NMSC who visited the dermatology and venereology outpatient clinic of Dr Cipto Mangunkusumo National Hospital and treated with MMS, were recruited. Patients with incomplete data, presented with other genetic diseases, and of Fitzpatrick skin type I - III were excluded. Fifty three cases of NMSC were reviewed in this study. Socio-demographic data, tumor size, anatomic location, number of MMS stages, and histopathologic subtype were collected from the medical records. We divided histopathologic subtype of BCC into aggressive and non-aggressive according to National Comprehensive Cancer Network (NCCN) guidelines version 2.2016. Results: The mean age was 64.89 and 31 (58.5%) of the patients were female. The mean tumor size was 25.89 mm (620.136). Seventy nine percent of these tumors were BCC. Overall, 43.4% tumors required two or more MMS stages, with nose as the most common site. In tumors smaller than 2 mm, 17 (63%) required only one stage of excision, compared with 13 (50%) in tumors larger than 2 mm. In BCC subgroup, the aggressive histopathologic subtype was a significant predictor of more MMS stages required (P ¼ .002; OR 10.5; 95% CI 2.475 e 44.545). Conclusion: To conclude our study, aggressive histopathologic subtype of BCC is a predictor of more MMS stages required. Identifying other factors, such as tumor size, location, and histopathologic type of non-BCC tumor, provide some important insight of which NMSC tumors that may require more MMS stages to clear. Therefore, such MMS patient candidates can be adequately prepared given the possibility of a more extensive surgery. Commercial support: None identified.
5225
5312 Predictive factors associated with eyebrow lifting by botulinum toxin type A Supitcha Kamolratanakul, MD, Division of Dermatology, Department of Medicine, Chulalongkorn University; Marisa Pongprutthipan, MD, Division of Dermatology, Department of Medicine, Chulalongkorn University Background: Eyebrow lifting improves the appearance of eyelid hooding and widens the eyes. Botulinum toxin A(BTx-A) injection to lift the eyebrows has been used with highly satisfaction but variable outcomes. Objectives: To identify factors associated with eyebrow lifting effect at 2nd, 6th and 12th weeks. Materials and Methods: 24 participants were enrolled in the study. Periorbital muscle power, skin laxity (graded by snap test), intercanthal distance and 5-point eyebrow height on each side were assessed. Six units of BTx-A (BotoxTM, Allergen, USA, 100 units diluted with 2.5 mL) were intramuscularly injected to three injection points on each eyebrow as follows: 3 units on medial brow, 1 unit on the lower margin of brow at the imaginary vertical lateral limbus line, and 2 units on lateral brow. Follow-up evaluations were performed at 2nd, 6th, and 12th weeks. Results: Mean age of participants was 40.91 6 11.25. At week 2, all 10-point measurements of eyebrow height (5 points on each side) were increased (mean 0.95 6 1.66 mm). The highest brow elevation was shown at the lateral brow followed by the lateral limbus line and medial brow which corresponded with the injection areas (mean 1.57 mm, 1.04 mm and 0.94 mm respectively with statistical significance (P \.05)). The mean intercanthal distance is statistically increase at week 2 with mean 1.27 6 2.25 mm (P ¼.012). The eyebrow lifting effect at all points disappeared at 12 weeks but the intercanthal distance was still statistically significant (P ¼ .004) shown different from baseline. Skin laxity and only upper lid crow’s feet pattern were shown to be the only factors which affected the eyebrow elevation (P\.05). The overall satisfaction was high in 62% of the subjects. No serious complications were found. These effects were decreased at 12 weeks. Conclusion: BTx-A treatment for brow lift and reshape has been achieved with high satisfaction with the technique applied in this study without any serious complication. Commercial support: None identified.
AB202
J AM ACAD DERMATOL
Predictors of response to 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of actinic keratosis: A post hoc analysis of a phase III, randomized, vehicle-controlled trial Eggert Stockfleth, St. Josef-Hospital; John Ryan, Alverton Practice; Meritxell Falques, Almirall S.A.; Nathalie Ivanoff, Almirall S.A.; Rosario Rodriguez Azeredo, Almirall S.A.; David Vilardell, Almirall S.A. Introduction: Field- and lesion-directed treatment of actinic keratosis (AK) lesions with 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) is efficacious in terms of complete clinical clearance (CCC) rate; however, the role of patient- or lesionrelated factors in predicting response to treatment has not yet been established. Objectives: This post-hoc analysis of a phase III, multicenter, randomized, doubleblind, vehicle-controlled trial (NCT02289768) examined the influence of patient- and lesion-related factors on response to 5-FU/SA in the field-directed treatment of AK. Methods: Adults with a 25 cm(2) area of skin on their face, bald scalp, or forehead covering 4e10 clinically confirmed AK lesions (Grade I/II) were randomized 2:1 to 5-FU/SA (n ¼ 111) or vehicle (n ¼ 55) applied topically once daily for 12 weeks. Data were analyzed to identify factors predictive of response to 5-FU/SA (defined as CCC of AK lesions in the treatment field 8 weeks after the end of treatment). Of the 111 patients randomized to 5-FU/SA treatment, 105 were included in the responder analysis (52 responders, 53 non-responders). Results: Response rate was significantly higher for 5-FU/SA than vehicle (52/105 [49.5%] vs 10/55 [18.2%], respectively; odds ratio 3.9 [95% CI: 1.7, 8.7]; P ¼.0006). In the 5-FU/SA group, no significant differences were found between responders and non-responders in terms of patient demographics apart from body weight (responders vs non-responders mean weight (SD) 80.7 (12.2) and 85.8 (13.4), respectively): body mass index, number of AK lesions or subclinical lesions, baseline lesion location or lesion severity; baseline lesion or subclinical lesion characteristics (assessed by reflectance confocal microscopy); AK history; Fitzpatrick skin type; prior medication use; Physician Global Assessment at each treatment visit; or change from baseline in the total score and individual domains of the Dermatology Life Quality Index questionnaire. Furthermore, no qualitative clinical differences were observed between responders and non-responders in terms of medical history or physical examination findings. Conclusions: Response to 5-FU/SA in the field-directed treatment of AK was not predicted by any of the patient- or lesion-related factors included in our exploratory analysis. We conclude that 5-FU/SA is an effective treatment in this clinical setting and that its efficacy is not influenced by factors such as lesion grade or location. Funding: Almirall S.A. Commercial support: This sub-analysis and its parent study were funded by Almirall S.A. (Barcelona, Spain), the manufacturer of Actikerall (5-fluorouracil 0.5%/salicylic acid 10% solution).
JUNE 2017
5459
Predicting return of chronic idiopathic urticaria symptoms following omalizumab treatment discontinuation: Exploratory analysis of phase III data Ana Gim enez-Arnau, MD, Hospital del Mar-Parc de Salut Mar; Marta Ferrer, MD, Clinica Universidad de Navarra; Diego Saldana, Novartis Pharma AG; Nico Janssens, Novartis Pharma AG; Maria-Magdalena Balp, Novartis Pharma AG; Sam Khalil, Novartis Pharma AG Introduction: Factors that influence urticaria symptom return are poorly understood in chronic idiopathic urticaria (CIU) patients who discontinue omalizumab treatment. This analysis explored potential predictors of rapid symptom return following omalizumab discontinuation in CIU patients. Methods: Variables predicting symptom return over the 16-week follow-up period were identified using a least absolute shrinkage and selection operator (LASSO) regularization regression model. The analysis used pooled Phase III randomized controlled trial (RCT) data from ASTERIA I (n ¼ 319; 6x4-weekly injections of omalizumab 75, 150, 300 mg or placebo) and ASTERIA II (n ¼ 323; 3x4-weekly injections of omalizumab 75, 150, 300 mg or placebo), or pooled omalizumab 300 mg data only. Probability of rapid symptom return was assessed using linear regression with prediction intervals, and relapse probability was represented using heat map visualizations. Accuracy of the omalizumab 300 mg-based model was tested using data from GLACIAL Phase III RCT (n ¼ 336; 6x4-weekly injections of omalizumab 300 mg or placebo).
Predictive factors of Mohs micrographic surgery stages in nonmelanoma skin cancer in Indonesian population Adhimukti T. Sampurna, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Amanda N. Wardani, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Inadia P. Chairista, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia; Riva A. Pradita, MD, Department of Dermatology and Venereology, Dr Cipto Mangunkusumo Hospital, Universitas Indonesia Introduction: Nonmelanoma skin cancer (NMSC) as the most common type of skin cancer are rarely metastasize to distant site. Despite the low metastasis rate, these cancers can result into a substantial local destruction and extend to surrounding areas. Therefore sufficient complete tumor tissue removal should always be the aim of surgery. On this wise, Mohs micrographic surgery (MMS) is the recommended therapeutic approach. However, in Asian countries especially Indonesia, MMS is still considered as a novel technique. In our national tertiary referral hospital, MMS has been performed in 56 cases from June 2014 to August 2016. Our study aims to evaluate the characteristic of NMSC treated with MMS and to identify the predictive factors of MMS stages required.
Results: Of 2,677 variables assessed, 2 were shown by the models to have a statistically significant impact as predictors of symptom return. The variables were baseline UAS7 (weekly urticaria activity score) and early area above the curve (AAC e determined by plotting the UAS7 scores from baseline to week 4). Results suggest high baseline UAS7 and low AAC (representing slow decrease of symptoms, as measured by the UAS7 score, in the 4 weeks after start of the treatment) indicate higher probability of rapid symptom return. Predictive accuracy was higher when the model included pooled dose data vs omalizumab 300 mg data only. Conclusions: Findings suggest that in CIU patients who discontinue treatment with omalizumab, probability of rapid symptom return can be estimated based on baseline UAS7 and early AAC. Influence of early AAC decreases and that of baseline UAS7 increases when the model is based on omalizumab 300 mg alone. Commercial support: ASTERIA I, ASTERIA II and GLACIAL studies were funded by Genentech Inc., South San Francisco, CA, USA, and Novartis Pharma AG, Basel, Switzerland.
Methods: All patients with NMSC who visited the dermatology and venereology outpatient clinic of Dr Cipto Mangunkusumo National Hospital and treated with MMS, were recruited. Patients with incomplete data, presented with other genetic diseases, and of Fitzpatrick skin type I - III were excluded. Fifty three cases of NMSC were reviewed in this study. Socio-demographic data, tumor size, anatomic location, number of MMS stages, and histopathologic subtype were collected from the medical records. We divided histopathologic subtype of BCC into aggressive and non-aggressive according to National Comprehensive Cancer Network (NCCN) guidelines version 2.2016. Results: The mean age was 64.89 and 31 (58.5%) of the patients were female. The mean tumor size was 25.89 mm (620.136). Seventy nine percent of these tumors were BCC. Overall, 43.4% tumors required two or more MMS stages, with nose as the most common site. In tumors smaller than 2 mm, 17 (63%) required only one stage of excision, compared with 13 (50%) in tumors larger than 2 mm. In BCC subgroup, the aggressive histopathologic subtype was a significant predictor of more MMS stages required (P ¼ .002; OR 10.5; 95% CI 2.475 e 44.545). Conclusion: To conclude our study, aggressive histopathologic subtype of BCC is a predictor of more MMS stages required. Identifying other factors, such as tumor size, location, and histopathologic type of non-BCC tumor, provide some important insight of which NMSC tumors that may require more MMS stages to clear. Therefore, such MMS patient candidates can be adequately prepared given the possibility of a more extensive surgery. Commercial support: None identified.
5225
5312 Predictive factors associated with eyebrow lifting by botulinum toxin type A Supitcha Kamolratanakul, MD, Division of Dermatology, Department of Medicine, Chulalongkorn University; Marisa Pongprutthipan, MD, Division of Dermatology, Department of Medicine, Chulalongkorn University Background: Eyebrow lifting improves the appearance of eyelid hooding and widens the eyes. Botulinum toxin A(BTx-A) injection to lift the eyebrows has been used with highly satisfaction but variable outcomes. Objectives: To identify factors associated with eyebrow lifting effect at 2nd, 6th and 12th weeks. Materials and Methods: 24 participants were enrolled in the study. Periorbital muscle power, skin laxity (graded by snap test), intercanthal distance and 5-point eyebrow height on each side were assessed. Six units of BTx-A (BotoxTM, Allergen, USA, 100 units diluted with 2.5 mL) were intramuscularly injected to three injection points on each eyebrow as follows: 3 units on medial brow, 1 unit on the lower margin of brow at the imaginary vertical lateral limbus line, and 2 units on lateral brow. Follow-up evaluations were performed at 2nd, 6th, and 12th weeks. Results: Mean age of participants was 40.91 6 11.25. At week 2, all 10-point measurements of eyebrow height (5 points on each side) were increased (mean 0.95 6 1.66 mm). The highest brow elevation was shown at the lateral brow followed by the lateral limbus line and medial brow which corresponded with the injection areas (mean 1.57 mm, 1.04 mm and 0.94 mm respectively with statistical significance (P \.05)). The mean intercanthal distance is statistically increase at week 2 with mean 1.27 6 2.25 mm (P ¼.012). The eyebrow lifting effect at all points disappeared at 12 weeks but the intercanthal distance was still statistically significant (P ¼ .004) shown different from baseline. Skin laxity and only upper lid crow’s feet pattern were shown to be the only factors which affected the eyebrow elevation (P\.05). The overall satisfaction was high in 62% of the subjects. No serious complications were found. These effects were decreased at 12 weeks. Conclusion: BTx-A treatment for brow lift and reshape has been achieved with high satisfaction with the technique applied in this study without any serious complication. Commercial support: None identified.
AB202
J AM ACAD DERMATOL
Predictors of response to 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of actinic keratosis: A post hoc analysis of a phase III, randomized, vehicle-controlled trial Eggert Stockfleth, St. Josef-Hospital; John Ryan, Alverton Practice; Meritxell Falques, Almirall S.A.; Nathalie Ivanoff, Almirall S.A.; Rosario Rodriguez Azeredo, Almirall S.A.; David Vilardell, Almirall S.A. Introduction: Field- and lesion-directed treatment of actinic keratosis (AK) lesions with 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) is efficacious in terms of complete clinical clearance (CCC) rate; however, the role of patient- or lesionrelated factors in predicting response to treatment has not yet been established. Objectives: This post-hoc analysis of a phase III, multicenter, randomized, doubleblind, vehicle-controlled trial (NCT02289768) examined the influence of patient- and lesion-related factors on response to 5-FU/SA in the field-directed treatment of AK. Methods: Adults with a 25 cm(2) area of skin on their face, bald scalp, or forehead covering 4e10 clinically confirmed AK lesions (Grade I/II) were randomized 2:1 to 5-FU/SA (n ¼ 111) or vehicle (n ¼ 55) applied topically once daily for 12 weeks. Data were analyzed to identify factors predictive of response to 5-FU/SA (defined as CCC of AK lesions in the treatment field 8 weeks after the end of treatment). Of the 111 patients randomized to 5-FU/SA treatment, 105 were included in the responder analysis (52 responders, 53 non-responders). Results: Response rate was significantly higher for 5-FU/SA than vehicle (52/105 [49.5%] vs 10/55 [18.2%], respectively; odds ratio 3.9 [95% CI: 1.7, 8.7]; P ¼.0006). In the 5-FU/SA group, no significant differences were found between responders and non-responders in terms of patient demographics apart from body weight (responders vs non-responders mean weight (SD) 80.7 (12.2) and 85.8 (13.4), respectively): body mass index, number of AK lesions or subclinical lesions, baseline lesion location or lesion severity; baseline lesion or subclinical lesion characteristics (assessed by reflectance confocal microscopy); AK history; Fitzpatrick skin type; prior medication use; Physician Global Assessment at each treatment visit; or change from baseline in the total score and individual domains of the Dermatology Life Quality Index questionnaire. Furthermore, no qualitative clinical differences were observed between responders and non-responders in terms of medical history or physical examination findings. Conclusions: Response to 5-FU/SA in the field-directed treatment of AK was not predicted by any of the patient- or lesion-related factors included in our exploratory analysis. We conclude that 5-FU/SA is an effective treatment in this clinical setting and that its efficacy is not influenced by factors such as lesion grade or location. Funding: Almirall S.A. Commercial support: This sub-analysis and its parent study were funded by Almirall S.A. (Barcelona, Spain), the manufacturer of Actikerall (5-fluorouracil 0.5%/salicylic acid 10% solution).
JUNE 2017