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2.
Cancer ; 128(5): 975-983, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724197

RESUMO

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.


Assuntos
Imunoterapia , Melanoma , Dermatopatias/induzido quimicamente , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados , Humanos , Imunoterapia/efeitos adversos , Incidência , Ipilimumab , Melanoma/patologia , Nivolumabe , Neoplasias Cutâneas/patologia
3.
Support Care Cancer ; 30(2): 989-994, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34519869

RESUMO

PURPOSE: Treatment options for corticosteroid-refractory and/or high-grade checkpoint inhibitor (CPI)-induced cutaneous adverse events (CAEs) are limited; however, anecdotal reports of biologic therapies have been successful. We aim to characterize the appropriate treatment scenarios and safety and efficacy profiles of biologics used to treat patients with CPI-induced CAEs at a single institution. METHODS: This is a retrospective case series of patients from January 1st, 2015 to October 20th, 2020, with CPI-induced CAEs who were treated with biologics at a single cancer center. Patients were identified using institutional electronic medical record who underwent CPI therapy with subsequent CAEs that necessitated biologic therapy. Diagnostic criteria utilized for CAEs were based on documentation by four board-certified dermatologists, in combination with detailed chart reviews and pathology findings. Primary study outcome measurements include CAE response, tumor response, and adverse events during biologics treatment. RESULTS: We identified 17 patients who fit study criteria. Sixteen patients experienced some degree of CAE improvement on biologics, with 10 of 10 patients reaching CAE resolution at 6 months post biologics. Eight patients needed new systemic treatment post biologics treatment, while 9 patients received no further treatment or stayed on the CPI. Thirteen patients tolerated biologics well with no significant adverse events or blood abnormalities, with only 2 patients experiencing biologic dose delays. CONCLUSION: In our cohort, biologics appear to be extremely efficacious in the treatment of severe-grade and/or steroid refractory CAEs. They also appeared to be well-tolerated without overtly negative effects on tumor response. In patients with limited cancer treatment options and good tumor response to CPIs, biologics should be considered for severe-grade and/or refractory CAEs.


Assuntos
Neoplasias , Dermatopatias , Terapia Biológica , Humanos , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Pele
4.
In Vivo ; 35(4): 2275-2281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182506

RESUMO

BACKGROUND: Distal femur and proximal tibia replacements as limb-salvage procedures with good outcome parameters for patients with tumours have been broadly described. However, the overall midterm outcome in a mixed, heterogeneous patient collective is still unclear. PATIENTS AND METHODS: We retrospectively analysed 59 consecutive patients (33 for primary and 26 for revision surgery) between 1998 and 2017. Indication for implantation was tumour (n=16), periprosthetic fracture (n=14), traumatic fracture (n=14), infection (n=10), aseptic loosening (n=3), and pathological fracture (n=2). The mean follow-up duration was 3 years. Clinical functions were evaluated by Toronto Extremity Salvage Score and Knee Society Score. Knee extension and flexion force were measured. RESULTS: The overall survival rate of arthroplasties was 59% (n=35). Major complications were observed in 36 (61%) patients. During the follow-up period, 14 (24%) patients died. We recorded periprosthetic joint infection in 21 (36%) patients, recurrence of tumour in two (3%), and aseptic implant failure in three (5%). The mean Toronto Extremity Salvage Score was 66±33, and the mean Knee Society Score was 49±30. The mean extension force on the operated side was significantly reduced at 60° and 180° compared to the healthy side (p=0.0151 and p=0.0411, respectively). CONCLUSION: Distal femur and proximal tibia replacements showed limited clinical function in a heterogeneous patient collective. Indication for implantation should be considered carefully.


Assuntos
Artroplastia do Joelho , Neoplasias , Artroplastia do Joelho/efeitos adversos , Fêmur/cirurgia , Humanos , Reoperação , Estudos Retrospectivos , Tíbia/cirurgia , Resultado do Tratamento
5.
Dermatol Surg ; 47(6): 775-779, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029250

RESUMO

BACKGROUND: Paronychia is a common toxicity associated with targeted anticancer therapies. Antibiotics and steroids are the standard treatments for severe paronychia, yet they are often inadequate, prolonging the patient's suffering and resulting in changes to effective cancer therapy. OBJECTIVE: This article describes the clinical course of drug-induced paronychia and attempts to identify circumstances under which nail surgery may be beneficial. MATERIALS AND METHODS: This is a retrospective case series from a single institution's electronic medical record for patients on paronychia-inducing anticancer therapies with nail disease visit diagnosis codes. RESULTS: The authors identified 36 nail procedures performed on 12 patients, all of whom were managed with conservative steroid and antibiotic therapy with varying degrees of improvement; however, no further improvement was seen after 90 days. Partial matricectomy, nail avulsion, debridement/clipping, and incision and drainage were performed with resolution rates of 100% (11/11), 38.5% (5/13), 12.5% (1/8), and 0% (0/4), respectively. The average time to surgical intervention was 196 days, and the average time to resolution was 268 days. CONCLUSION: This series highlights the prolonged course of severe drug-induced paronychia and the importance of surgical intervention to reduce pain and impact on cancer treatment. Partial matricectomy should be considered for paronychia unresponsive to conservative therapy by 3 months.


Assuntos
Antineoplásicos/efeitos adversos , Drenagem/métodos , Neoplasias/tratamento farmacológico , Paroniquia/cirurgia , Adulto , Idoso , Antibacterianos/administração & dosagem , Terapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Unhas/efeitos dos fármacos , Unhas/imunologia , Unhas/patologia , Paroniquia/induzido quimicamente , Paroniquia/diagnóstico , Paroniquia/imunologia , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Resultado do Tratamento
6.
Adv Exp Med Biol ; 1342: 319-330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972971

RESUMO

Due to the novelty of immune checkpoint inhibitors, their cutaneous adverse events (AEs) have only been recently characterized. This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat cutaneous AEs. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Incidence varies between 35 and 60% for cutaneous AEs among the seven FDA-approved drugs used as monotherapy or combination therapy. Although only 2% are reported as grade 3 or 4 events with monotherapy, the incidence can be as high as 6-9% for combination therapy and the impact on quality of life can be significant for these patients. Of ipilimumab patients, 43.5% have a cutaneous AE, and, at our institution, 20% of them had a dose interruption as a result. This means potentially 9% of patients have dose interruption of ipilimumab because of their cutaneous AEs. In the following chapter, we review the categories of these drugs, common cutaneous effects, their grading, and management options.


Assuntos
Exantema , Inibidores de Checkpoint Imunológico , Exantema/induzido quimicamente , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/efeitos adversos , Qualidade de Vida
9.
Adv Exp Med Biol ; 1244: 235-246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301018

RESUMO

Due to the novelty of immune checkpoint inhibitors, their cutaneous adverse events (AEs) have only been recently characterized. This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat cutaneous AEs. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Incidence varies between 35 and 50% for cutaneous AEs among the eight FDA-approved drugs. Although only 2% are reported as grade 3 or 4 events, the impact on quality of life can be significant for these patients and is best described and most severe in ipilimumab trials. Of ipilimumab patients, 43.5% have a cutaneous AE and, at our institution, 20% of them had a dose interruption as a result. This means potentially 9% of patients have dose interruption of ipilimumab because of their cutaneous AEs. In the following chapter, we review the categories of these drugs, common cutaneous effects, their grading, and management options.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Exantema/induzido quimicamente , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias/terapia , Prurido/induzido quimicamente , Exantema/diagnóstico , Exantema/terapia , Humanos , Neoplasias/imunologia , Prurido/diagnóstico , Prurido/terapia , Qualidade de Vida
10.
J Immunother Precis Oncol ; 3(4): 141-146, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35665373

RESUMO

Introduction: Phosphoinositide 3-kinase (PI3K) inhibitors are a new class of cancer therapeutics that inhibits one or more enzymes in the PI3K/AKT/mTOR tumor growth pathway. As compared to other tyrosine kinase inhibitors, there is evidence that PI3K inhibitors have a higher incidence of severe cutaneous adverse events (CAEs) ranging from 2-21%. There is a lack of further characterization of clinical trials and management options for these CAEs. Methods: A retrospective chart review of our institution's records between January 2015 and May 2019 was conducted; electronic medical records were queried by using a pharmacy database and ICD-10 codes for patients receiving PI3K inhibitor who experienced CAEs during therapy. These CAEs were characterized by two board-certified dermatologists at a major cancer center. Results: Eleven patients were identified as having 12 cumulative CAEs. Average time to rash onset was 4 weeks, and the most common identified rashes were eczematous (25%) and morbilliform (17%). Four patients experienced a dose delay, and one patient immediately discontinued their PI3K inhibitor. Conclusion: Although most CAEs caused by PI3K inhibitors in this study were limited to grade 1-2 and were controlled with topical corticosteroids and oral antihistamines, a number of patients experienced dose impact. This highlights the dermatologist's role in managing and minimizing interruption of therapy while maintaining quality of life.

12.
Adv Exp Med Biol ; 995: 117-129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30539508

RESUMO

The novelty of immune checkpoint inhibitors has only recently led to the characterization of cutaneous adverse events (AEs). This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Incidence varies between 35 and 50% for cutaneous AEs among the three FDA-approved drugs. Although only 2% are reported as grade 3 or 4 events, the quality of life impact can be significant for these patients and is best described in ipilimumab trials. 43.5% of ipilimumab patients have a cutaneous AE and, at our institution, 20% of them had a dose interruption as a result. This means potentially 9% of patients having dose interruption of ipilimumab because of their cutaneous AEs. In the following chapter, we will review the categories of these drugs, common cutaneous effects, their grading, and management options.


Assuntos
Antineoplásicos/efeitos adversos , Exantema/induzido quimicamente , Imunoterapia/efeitos adversos , Ipilimumab/efeitos adversos , Prurido/induzido quimicamente , Anticorpos Monoclonais , Antineoplásicos/uso terapêutico , Humanos , Ipilimumab/uso terapêutico , Qualidade de Vida
13.
J Cutan Pathol ; 45(10): 764-773, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29943453

RESUMO

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.


Assuntos
Acantólise/induzido quimicamente , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Erupção por Droga/etiologia , Erupção por Droga/patologia , Idoso , Humanos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias da Língua/tratamento farmacológico
14.
Adv Exp Med Biol ; 995: 175-184, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28321818

RESUMO

The novelty of immune checkpoint inhibitors has only recently led to the characterization of cutaneous adverse events (AEs). This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat. In the following chapter, we will review the categories of these drugs, common cutaneous effects, their grading, and management options.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/antagonistas & inibidores , Erupção por Droga/etiologia , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Erupção por Droga/diagnóstico , Erupção por Droga/terapia , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
15.
Dermatol Clin ; 31(2): 317-26, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23557658

RESUMO

Photosensitivity disorders in childhood are rare, with the notable exception of overexposure as sunburn, and therefore require a more circumspect approach. Practitioners who treat children are key players in identifying and managing the many photosensitivity disorders that rarely present in childhood. A classic photodistribution of skin findings may suggest photosensitivity, but a correct diagnosis depends on a detailed history correlated with clinical findings.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Transtornos de Fotossensibilidade/diagnóstico , Protetores Solares/uso terapêutico , Criança , Pré-Escolar , Dermatologia/métodos , Dispositivos de Proteção dos Olhos/estatística & dados numéricos , Humanos , Transtornos de Fotossensibilidade/tratamento farmacológico , Transtornos de Fotossensibilidade/imunologia , Roupa de Proteção , Luz Solar/efeitos adversos
16.
Brachytherapy ; 12(2): 114-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22884255

RESUMO

PURPOSE: Most institutions model breast epidermis with a surface contour and record the maximum dose on the external surface of the patient. The objective of this study was to compare the external surface contour (ext) model of the skin with our current volumetric model for skin for radiation treatment planning in accelerated partial breast irradiation brachytherapy. METHODS AND MATERIALS: A literature search was conducted to identify studies measuring breast epidermal thickness. Clinical plans were performed with a 2-mm contraction of the external surface contour. This 2-mm contraction of the external surface contour was used to approximate breast epidermis thickness. Then, the external surface contour was expanded 5mm outside the external contour of the patient for the second skin model. Maximum doses from the two models were recorded and compared. RESULTS: The average breast epidermal thickness from five studies was 1.68mm. Mean percent difference between skin and ext+5mm for balloon plans, strut plans, and all plans was 10.1%, 14.5%, and 12.5%, respectively. Differences in doses between the two skin models were statistically significant (p<0.0001). CONCLUSIONS: The volumetric skin model was validated because the average breast epidermal thickness was 1.68mm. The surface model for skin may underestimate the dose delivered to the epidermis by as much as 23.8%. The external surface contour method does not accurately represent the dermatologic skin thickness of the breast as the skin is modeled as a surface rather than a volume. These discrepancies may skew correlations of dose to skin and toxicity determinations.


Assuntos
Algoritmos , Modelos Biológicos , Doses de Radiação , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Fenômenos Fisiológicos da Pele , Simulação por Computador , Humanos , Especificidade de Órgãos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Pediatr Dermatol ; 30(6): e283-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22471737

RESUMO

Ecthyma gangrenosum is the cutaneous manifestation of pseudomonas infection in patients with sepsis. A previously healthy 7-month-old girl who developed ecthyma gangrenosum without apparent inciting factors became neutropenic secondary to autoimmune neutropenia 2 months after initial presentation. She was treated with appropriate surgical and medical intervention and was discharged in stable condition only to die suddenly 2 days after discharge.


Assuntos
Ectima/imunologia , Gangrena/imunologia , Neutropenia/imunologia , Infecções por Pseudomonas/imunologia , Sepse/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Ectima/microbiologia , Evolução Fatal , Feminino , Gangrena/microbiologia , Humanos , Lactente , Neutropenia/microbiologia , Infecções por Pseudomonas/patologia , Sepse/microbiologia
18.
Clin Nephrol ; 78(2): 164-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22790462

RESUMO

Retroperitoneal sarcoma is a rare tumor accounting for 10 - 15% of all soft tissue malignancies with an incidence of 2.5 per million. Of those, liposarcoma is the most common type of retroperitoneal sarcoma accounting for 41% of cases. It usually presents late with vague symptoms such as abdominal discomfort or palpable mass. Vascular invasion is seen in 18% of retroperitoneal sarcomas but acute renal failure secondary to bilateral renal artery invasion/stenosis by these tumors has never been described yet. In this report, we describe the first case, to our knowledge, in the medical literature and discuss epidemiology, diagnosis, and management. Treatment is primarily surgical and the ability to completely resect the tumor is the most important predictor of survival. Active clinical trials are currently testing the use of adjunct chemotherapy and radiotherapy to improve morbidity and mortality.


Assuntos
Injúria Renal Aguda/etiologia , Artéria Renal , Neoplasias Retroperitoneais/complicações , Sarcoma/complicações , Neoplasias Vasculares/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia
19.
J Drugs Dermatol ; 11(7): 826-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22777223

RESUMO

Infantile hemangiomas are benign vascular neoplasms of childhood that often have implications on development, cosmesis, and comfort. Traditional therapy has involved either observation or corticosteroids, depending on location and size. Recent studies have reported the successful use of beta-adrenergic antagonists in treating infantile hemangiomas. This succinct review discusses the properties and current applications of beta-adrenergic antagonists as well as the established treatments for infantile hemangioma.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Antagonistas Adrenérgicos beta/farmacologia , Hemangioma/patologia , Humanos , Lactente , Receptores Adrenérgicos beta/metabolismo , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-22690129

RESUMO

Advances in current understanding of the pathophysiology of atopic dermatitis have led to improved targeting of the structural deficiencies in atopic skin. Ceramide deficiency appears to be one of the major alterations in atopic dermatitis and the replenishment of this epidermal component through topically applied ceramide based emollients appears to be safe, well tolerated, and effective. Recently a ceramide hyaluronic acid foam has become commercially available and increasing evidence supports its safety and efficacy in patients who suffer from atopic dermatitis.

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