TWENTY-THIRD ISSUE
DECEMBER 21, 2022
Association Between Tumor-infiltrating Lymphocyte Classification and Disease Progression in Metastatic Melanomas Receiving Checkpoint Inhibitor Therapy
JAMA Dermatology
JAMA Dermatology
Checkmate, melanoma!
Only about 40% of patients respond to checkpoint inhibitor therapy (CIT) for advanced melanoma. Though revolutionary, CITs are associated with adverse effects, which underscores the importance of predicting treatment response. Tumor infiltrating lymphocytes (TILs) are a type of CD8+ T-cell found in melanomas with elevated tumor mutational burden. The role between TILs and response to CIT in patients with metastatic disease is unclear.
This cohort study examined the dermatopathology reports of 142 patients diagnosed with stage IV melanoma who were treated with CIT. Patients were stratified by disease status (progressive or nonprogressive) and level of TILs (absent; present, non-brisk; present, brisk). Uni- and multivariable logistic regressions were performed to find the best-fit model when considering age, sex, and presence of TILs with progressive disease (PD).
Of 142 patients, 72 (50.7%) had PD. Patients with absent TILs had significantly increased rates of PD versus those with present TILs (OR, 2.10; 95% CI, 1.07-4.11; P=0.03). Of patients with PD, 30 (65.2%) had absent TILs, 34 (42.5%) had non-brisk TILs, and 8 (50%) had brisk TILs. On multivariable analysis, the best fit model for predicting PD included both sex (male: OR, 2.23; 95% CI, 1.05-4.73) and TILs (absent: OR, 2.60; 95% CI, 1.23-5.50).
Limitations: This cohort had a small number of patients with brisk TILs.
Main Takeaways: Overall, the absence of primary tumor infiltrating lymphocytes was associated with melanoma disease progression in patients receiving checkpoint inhibitors. The presence of TILs, in conjunction with sex, may be useful in predicting response to checkpoint inhibition therapy in patients with metastatic melanoma.
Only about 40% of patients respond to checkpoint inhibitor therapy (CIT) for advanced melanoma. Though revolutionary, CITs are associated with adverse effects, which underscores the importance of predicting treatment response. Tumor infiltrating lymphocytes (TILs) are a type of CD8+ T-cell found in melanomas with elevated tumor mutational burden. The role between TILs and response to CIT in patients with metastatic disease is unclear.
This cohort study examined the dermatopathology reports of 142 patients diagnosed with stage IV melanoma who were treated with CIT. Patients were stratified by disease status (progressive or nonprogressive) and level of TILs (absent; present, non-brisk; present, brisk). Uni- and multivariable logistic regressions were performed to find the best-fit model when considering age, sex, and presence of TILs with progressive disease (PD).
Of 142 patients, 72 (50.7%) had PD. Patients with absent TILs had significantly increased rates of PD versus those with present TILs (OR, 2.10; 95% CI, 1.07-4.11; P=0.03). Of patients with PD, 30 (65.2%) had absent TILs, 34 (42.5%) had non-brisk TILs, and 8 (50%) had brisk TILs. On multivariable analysis, the best fit model for predicting PD included both sex (male: OR, 2.23; 95% CI, 1.05-4.73) and TILs (absent: OR, 2.60; 95% CI, 1.23-5.50).
Limitations: This cohort had a small number of patients with brisk TILs.
Main Takeaways: Overall, the absence of primary tumor infiltrating lymphocytes was associated with melanoma disease progression in patients receiving checkpoint inhibitors. The presence of TILs, in conjunction with sex, may be useful in predicting response to checkpoint inhibition therapy in patients with metastatic melanoma.
Mohs surgery is associated with better survival outcomes in the treatment of high-risk cutaneous SCC vs traditional wide excision
Journal of The American Academy of Dermatology
What has the Mohs-t success in treating skin cancer??
The incidence of cutaneous squamous cell carcinoma (cSCC) continues to increase. While most cSCC are successfully treated, high-risk tumors (stage ≥ T2b or T3 depending on staging scale) are at increased risk of local recurrence (LR), nodal metastases (NM), distant metastases (DM), and disease-specific death (DSD).
In this retrospective study, researchers sought to compare clinical outcomes such as LR, NM, DM, and DSD in 581 high-risk cSCC tumors treated with Mohs surgery (MS). They compared these outcomes to established metrics of wide local excision published in the literature. Patients with LR, NM, or DM at the initial visit were excluded. Patients were followed up every two to three months for the first two to three years after surgery, then every six months after that, with a follow-up rate of 99.7%. Analysis of follow-up data showed the 5-year DSD to be 95.7%. NM rate was 6.2% compared to 15-23% for wide excision reported in the literature. The 5-year LR-free survival was 96.9% and the 5-year DM-free survival was 97.3% for MS, superior to reported outcomes for wide excision.
Limitations: Retrospective study design and use of two different inclusion criteria for tumor staging.
Main Takeaway: Treatment of high-risk cSCC with Mohs surgery shows excellent clinical outcomes compared to traditional wide excision.
The incidence of cutaneous squamous cell carcinoma (cSCC) continues to increase. While most cSCC are successfully treated, high-risk tumors (stage ≥ T2b or T3 depending on staging scale) are at increased risk of local recurrence (LR), nodal metastases (NM), distant metastases (DM), and disease-specific death (DSD).
In this retrospective study, researchers sought to compare clinical outcomes such as LR, NM, DM, and DSD in 581 high-risk cSCC tumors treated with Mohs surgery (MS). They compared these outcomes to established metrics of wide local excision published in the literature. Patients with LR, NM, or DM at the initial visit were excluded. Patients were followed up every two to three months for the first two to three years after surgery, then every six months after that, with a follow-up rate of 99.7%. Analysis of follow-up data showed the 5-year DSD to be 95.7%. NM rate was 6.2% compared to 15-23% for wide excision reported in the literature. The 5-year LR-free survival was 96.9% and the 5-year DM-free survival was 97.3% for MS, superior to reported outcomes for wide excision.
Limitations: Retrospective study design and use of two different inclusion criteria for tumor staging.
Main Takeaway: Treatment of high-risk cSCC with Mohs surgery shows excellent clinical outcomes compared to traditional wide excision.
Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa
Journal of Investigative Dermatology
What did the antibody go to the Halloween party as?
– an immuno-goblin!
Hidradenitis suppurativa (HS) is a painful, chronic, inflammatory skin disease featuring recurrent nodules and abscesses, most commonly found in areas with increased friction (such as the axilla, groin, etc). Although we know that the mechanism of HS likely involves the immune system, we still do not know exactly how HS occurs. Because HS has been associated with inflammasome components (a part of the innate immune system), people have thought that HS is mostly an autoinflammatory disease (compared to an autoimmune disease, which involves the adaptive immune system). However, recent studies suggest that HS also features dysregulation of the adaptive immune system, involving T cells, B cells, and plasma cells. One common feature of autoimmune disorders is the presence of autoantibodies—think lupus and rheumatoid arthritis. In this study, Macchiarella et al. identified new autoantibodies in blood from patients with HS that were directed against N-carboxyethyl lysine (CEL), which is a glycation end-product. They also found anti-CEL producing plasmablasts in skin from patients with HS. Interestingly, the autoantibodies correlated with HS disease severity and duration. These data suggest an issue with the methylglyoxal pathway in HS and supports an autoimmune component to HS.
Main Takeaways: The authors found anti-carboxyethyl lysine autoantibodies in patients with HS correlate with disease severity. Additional studies are required to see whether these autoantibodies cause disease or are a byproduct of disease.
– an immuno-goblin!
Hidradenitis suppurativa (HS) is a painful, chronic, inflammatory skin disease featuring recurrent nodules and abscesses, most commonly found in areas with increased friction (such as the axilla, groin, etc). Although we know that the mechanism of HS likely involves the immune system, we still do not know exactly how HS occurs. Because HS has been associated with inflammasome components (a part of the innate immune system), people have thought that HS is mostly an autoinflammatory disease (compared to an autoimmune disease, which involves the adaptive immune system). However, recent studies suggest that HS also features dysregulation of the adaptive immune system, involving T cells, B cells, and plasma cells. One common feature of autoimmune disorders is the presence of autoantibodies—think lupus and rheumatoid arthritis. In this study, Macchiarella et al. identified new autoantibodies in blood from patients with HS that were directed against N-carboxyethyl lysine (CEL), which is a glycation end-product. They also found anti-CEL producing plasmablasts in skin from patients with HS. Interestingly, the autoantibodies correlated with HS disease severity and duration. These data suggest an issue with the methylglyoxal pathway in HS and supports an autoimmune component to HS.
Main Takeaways: The authors found anti-carboxyethyl lysine autoantibodies in patients with HS correlate with disease severity. Additional studies are required to see whether these autoantibodies cause disease or are a byproduct of disease.
G-tubes are a feasible intervention for nutritional support in patients with epidermolysis bullosa and gastrointestinal involvement
Journal of Pediatric Dermatology
Journal of Pediatric Dermatology
Need nutritional support? Never fear, G-tubes are here!
Epidermolysis bullosa (EB) is a group of inherited genetic disorders that causes skin and mucosal blistering after minor trauma. Impaired wound healing and chronic inflammation associated with severe EB leads to high metabolic demand. However, patients with EB who suffer from mucosal blisters, dysphagia, and esophageal strictures may experience limited caloric intake, leading to chronic malnutrition. Gastrostomy tubes (G-tubes) are a practical intervention for nutritional support to minimize growth failure. Some caregivers have expressed hesitations to proceed with G-tube placement given the associated risks, including incisional hernia, leakage, bleeding, and infection, along with cultural and social difficulties integrating G-tube feeding. To date, few studies have investigated the efficacy and side effects of G-tube usage in EB patients.
The researchers conducted a questionnaire survey of adult caregivers of 20 patients with EB and active G-tubes over an 8-week study period. All caregivers were parents. The average patient age of G-tube placement was 2.7 years (SD: 2.1, range 0-8) and duration of G-tube utilization was an average of 12.0 years (SD: 7.8, range 1-25). Represented EB subtypes included dystrophic (75%), junctional (15%), and simplex (10%). 50% of patients underwent prior esophageal dilations: 70% had over 10 dilations and 30% had 3-6 dilations. The most common reasons for initial placement of a G-tube included nutritional supplementation (75%), esophageal strictures (50%), and oral blistering (50%). 75% of patients experienced G-tube complications, including leakage (50%), infection (35%), and gastric reflux (25%). Almost all caregivers (90%) reported high levels of satisfaction with G-tube management, and over half of caregivers (60%) reported that they would have adopted G-tubes earlier. Caregivers rated mealtimes as more enjoyable and easier for both themselves and their child with EB post-G-tube placement.
Limitations: Given the small sample size of this study and short study period, larger prospective studies are needed to better understand G-tube satisfaction in caregivers and patients with EB.
Main Takeaway: This study found a high rate of satisfaction for G-tube use among caregivers of patients with epidermolysis bullosa across varying ages and household settings.
Epidermolysis bullosa (EB) is a group of inherited genetic disorders that causes skin and mucosal blistering after minor trauma. Impaired wound healing and chronic inflammation associated with severe EB leads to high metabolic demand. However, patients with EB who suffer from mucosal blisters, dysphagia, and esophageal strictures may experience limited caloric intake, leading to chronic malnutrition. Gastrostomy tubes (G-tubes) are a practical intervention for nutritional support to minimize growth failure. Some caregivers have expressed hesitations to proceed with G-tube placement given the associated risks, including incisional hernia, leakage, bleeding, and infection, along with cultural and social difficulties integrating G-tube feeding. To date, few studies have investigated the efficacy and side effects of G-tube usage in EB patients.
The researchers conducted a questionnaire survey of adult caregivers of 20 patients with EB and active G-tubes over an 8-week study period. All caregivers were parents. The average patient age of G-tube placement was 2.7 years (SD: 2.1, range 0-8) and duration of G-tube utilization was an average of 12.0 years (SD: 7.8, range 1-25). Represented EB subtypes included dystrophic (75%), junctional (15%), and simplex (10%). 50% of patients underwent prior esophageal dilations: 70% had over 10 dilations and 30% had 3-6 dilations. The most common reasons for initial placement of a G-tube included nutritional supplementation (75%), esophageal strictures (50%), and oral blistering (50%). 75% of patients experienced G-tube complications, including leakage (50%), infection (35%), and gastric reflux (25%). Almost all caregivers (90%) reported high levels of satisfaction with G-tube management, and over half of caregivers (60%) reported that they would have adopted G-tubes earlier. Caregivers rated mealtimes as more enjoyable and easier for both themselves and their child with EB post-G-tube placement.
Limitations: Given the small sample size of this study and short study period, larger prospective studies are needed to better understand G-tube satisfaction in caregivers and patients with EB.
Main Takeaway: This study found a high rate of satisfaction for G-tube use among caregivers of patients with epidermolysis bullosa across varying ages and household settings.