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BACKGROUND: Limited data on immune checkpoint inhibitor (ICI)-induced pruritus per se and efficacy of different therapeutic modalities in its management exist. OBJECTIVE: To study the quantitative and qualitative characteristics of ICI-induced pruritus per se and to assess the efficacy of the therapeutic modalities usually applied. METHODS: We retrospectively reviewed the records of 91 patients who were under treatment with ICIs for any kind of neoplasia and developed pruritus during treatment. RESULTS: Twenty out of 91 individuals (22.0%) with ICI-induced pruritus had pruritus as the only symptom, while 71/91 (78.0%) presented with pruritus coexisting with an additional cutaneous toxicity. Pruritus was treated with antihistamines (18/20, 90.0%) and/or topical regimens, as first-line choice. In resistant cases, as a second therapeutic intervention, narrow-band UVB (NBUVB), oral steroids and GABA analogs were added (70.0%). Statistical analysis revealed a significant difference in mean pruritus Numerical Rating Scale (NRS) scores between baseline and sequential visits. Moreover, subgroup analysis revealed a significant reduction in mean NRS scores in those treated with phototherapy. LIMITATIONS: Retrospective design, low number of patients and survivorship bias. CONCLUSION: Pruritus per se was present in a substantial portion of our cohort (22.0%). Our study confirms the efficacy of current treatment strategies and suggests NBUVB as a potential steroid-sparing therapeutic alternative.
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Terapia Ultravioleta , Humanos , Estudos Retrospectivos , Prurido/induzido quimicamente , Fototerapia , Raios UltravioletaRESUMO
Despite brodalumad demonstrated efficacy in clinical trials, real-world data reflecting clinical benefits in unselected patient populations treated in routine clinical practice are limited. Thus, we performed a longitudinal, retrospective, real-world analysis assessing the long-term clinical benefits of patients with moderate-to-severe psoriasis treated with brodalumab in Greece in the long term (up to 24 months). Main efficacy assessments included changes from baseline in the psoriasis area and severity index (PASI) and proportions of patients achieving at least 50%, 75%, 90% and 100% reduction from baseline in PASI scores (PASI50, PASI75, PASI90 and PASI100) at different timepoints up to 24 months. Other endpoints included changes in the dermatology life quality index (DLQI) and body surface area (BSA) involvement. Data from medical records of 180 patients with moderate-to-severe psoriasis treated with brodalumab for up to 24 months were assessed. Following treatment, mean [standard deviation (SD)] PASI scores were decreased across all visits compared to baseline (p < 0.001). The proportion of patients achieving PASI50, PASI75, PASI90 or PASI100 were high as early as at month 1 and consistently tended to increase over time, mainly during the first 6 months. Improvements on disease severity were further reflected by reductions from baseline on BSA scores across all visits (p < 0.001). Concurrent improvements on DLQI scores were observed across all visits (p < 0.001). This retrospective analysis provides real-world evidence supporting the long-term efficacy profile of brodalumab in Greek patients with moderate-to-severe psoriasis treated in standard clinical practice, which is characterized by a rapid onset of action generally sustained over time.
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Psoríase , Anticorpos Monoclonais Humanizados , Grécia , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51-20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84-27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021-1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53-10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.
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Transtornos de Deglutição , Neoplasias Orofaríngeas , Humanos , Idoso , Transtornos de Deglutição/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , BocaRESUMO
INTRODUCTION: Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy. OBJECTIVES: We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management. METHODS: Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The internet was searched for relevant studies. RESULTS: A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation. CONCLUSION: Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients' quality of life.
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Introduction: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking. Methods: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models. Results: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03). Conclusions: EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.
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Purpose: In this study we sought to investigate factors associated to dysphagia and subsequent need for percutaneous gastrostomy (PEG) usage, in patients with head and neck cancer receiving radiation therapy. Methods: The records of 123 patients with non-metastatic, stage I-IV head and neck cancer who were submitted to radiation therapy were retrospectively reviewed. Logistic regression models were used to investigate for associations between the outcomes of interest (grade ≥2 dysphagia and need for [PEG] usage) and potential predictive factors. Results: Mean dose to pharyngeal constrictor muscles (OR=1.08, p=.002), concurrent chemotherapy (OR=3.78, p=0.015) and upper aerodigestive tract malignancies (OR=3.27, p=0.044) were associated with dysphagia grade≥2. A threshold of constrictors mean dose for dysphagia manifestation was also identified at 43 Gy (OR=4.51, p=0.002). Need for PEG use was correlated with definitive treatment (OR=7.03, p=.022), nasopharyngeal (OR=12.62, p=0.003), upper aerodigestive tract (OR=9.12, p=0.007) or occult primary malignancies (OR=10.78, p=0.016). Conclusion: Patients suffering from upper aerodigestive tract malignancies, those with calculated constrictors mean dose >43 Gy, or planned to receive concurrent chemotherapy-radiotherapy should be closely monitored during treatment for dysphagia manifestation. Prophylactic PEG could be considered for patients receiving definitive therapy of the nasopharynx, upper aerodigestive tract or occult primary malignancies.