217 research outputs found
The more the better? An appraisal of combination therapies for actinic keratosis
Actinic keratoses (AK) are common precancerous lesions of the skin. Numerous interventions exist for the treatment of AK, including lesionâ and fieldâdirected approaches. In daily practice, different treatment modalities are often combined to maximize clearance rates. However, whether a combination therapy is preferable to monotherapy in terms of efficacy and safety has been subject of intense debate. In this review, we summarize the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK. Combination approaches of cryosurgery followed by photodynamic therapy (PDT), laserâassisted PDT, PDT in combination with topical interventions and microneedlingâassisted PDT have shown slightly better efficacy results with similar tolerability compared to the respective monotherapy. However, the individual usage of combination therapies should be checked on a caseâbyâcase basis and take into account individual patientâ and lesionâspecific aspects as more resources are needed and because the individual monotherapies are already highly effective
Outcome and treatment-related adverse events of combined immune checkpoint inhibition with flipped dosing in a real-world cohort of 79 patients with metastasized melanoma
IntroductionCombined immune checkpoint inhibition (ICI) with ipilimumab and nivolumab is a widely used treatment regimen for metastatic melanoma with non-resectable metastases. Nevertheless, the standard dose of ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw is associated with a high rate of treatment-related adverse events (trAEs) (59% grade 3â4). In the CheckMate 511 study, it could be shown that flipped dosing with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw resulted in a significant reduction of trAE.MethodsWe have also used this regimen in the clinical setting and report the trAE, progression-free survival, and overall survival for 79 patients with metastatic melanoma who started combined ICI in the flipped dosing between March 2019 and April 2020.Resultsin total, 40 patients started first-line, 50% of whom had an elevated lactate dehydrogenase level at baseline. The disease control rate of these patients was 50%. The 2-year overall survival rate 67%. Moreover, 33% of the patients suffered grade 3 or 4 treatment related adverse events. DiscussionThe results of our study correspond very well to the results of the CheckMate 511 study (2-year OS: 65%, grade 3-4 immune-related side effects: 35%). Combined ICI with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw seems to be an equally effective but better-tolerated therapy regimen for metastasized melanoma patients, also in a real-world cohort
Cost-effectiveness analysis in melanoma detection: a transition model applied to dermoscopy
Abstract Aim: The main aim of this study is to demonstrate how our melanoma disease model (MDM) can be used for cost-effectiveness analyses (CEAs) in the melanoma detection field. In particular, we used the data of two cohorts of Belgian melanoma patients to investigate the cost-effectiveness of dermoscopy. Methods: A MDM, previously constructed to calculate the melanoma burden, was slightly modified to be suitable for CEAs. Two cohorts of patients entered into the model to calculate morbidity, mortality and costs. These cohorts were constituted by melanoma patients diagnosed by dermatologists adequately, or not adequately, trained in dermoscopy. Effectiveness and costs were calculated for each cohort and compared. Effectiveness was expressed in quality-adjusted life years (QALYs), a composite measure depending on melanoma-related morbidity and mortality. Costs included costs of treatment and follow-up as well as costs of detection in non-melanoma patients and costs of excision and pathology of benign lesions excised to rule out melanoma. Results: The result of our analysis concluded that melanoma diagnosis by dermatologists adequately trained in dermoscopy resulted in both a gain of QALYs (less morbidity and/or mortality) and a reduction in costs. Conclusion: This study demonstrates how our MDM can be used in CEAs in the melanoma detection field. The model and the methodology suggested in this paper were applied to two cohorts of Belgian melanoma patients. Their analysis concluded that adequate dermoscopy training is cost-effective. The results should be confirmed by a large-scale randomised study
Reinduction of Hedgehog Inhibitors after Checkpoint Inhibition in Advanced Basal Cell Carcinoma : A Series of 12 Patients
For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog
inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i
failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced
(n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received
HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration
was 20.8 (2â64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or
patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a
partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1
(0.8â16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient
request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial
response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1â29)
months. Response duration in the four responding patients was 2â29+ months. Thus, a subgroup
of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this
sequential treatment represents a feasible treatment option
Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma
BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment
The EORTC-DeCOG nomogram adequately predicts outcomes of patients with sentinel node-positive melanoma without the need for completion lymph node dissection
Purpose: Based on recent advances in the management of patients with sentinel node (SN)âpositive melanoma, we aimed to develop prediction models for recurrence, distant metastasis (DM) and overall mortality (OM). Methods: The derivation cohort consisted of 1080 patients with SN-positive melanoma from nine European Organization for Research and Treatment of Cancer (EORTC) centres. Prognostic factors for recurrence, DM and OM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across centres. The models were externally validated using a prospective cohort consisting of 705 German patients with SN-positive: 473 trial participants of the German Dermatologic Cooperative Oncology Group study (DeCOG-SLT) and 232 screened patients. A nomogram was developed for graphical presentation. Results: The final model for recurrence and the calibrated models for DM and OM included ulceration, age, SN tumour burden and Breslow thickness. The models showed reasonable calibration. The c-index for the recurrence, DM and OM model was 0.68, 0.70 and 0.70, respectively, and 0.70, 0.72 and 0.74, respectively, in external validation. The EORTC-DeCOG model identified a robust low-risk group, with all identified low-risk patients (approximately 4% of the entire population) having a 5-year recurrence probability of <25% and an overall 5-year recurrence rate of 13%. A model including information on completion lymph node dissection (CLND) showed only marginal improvement in model performance. Conclusions: The EORTC-DeCOG nomogram provides an adequate prognostic tool for patients with SN-positive melanoma, without the need for CLND. It showed consistent results across validation. The nomogram could be used for patient counselling and might aid in adjuvant therapy decision-making
Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial
Patient-centered motives and expectations of the treatment of actinic keratoses (AK) have received little attention until now. Hence, we aimed to profile and cluster treatment motivations and expectations among patients with AK in a nationwide multicenter, cross-sectional study including patients from 14 German skin cancer centers. Patients were asked to complete a self-administered questionnaire. Treatment motives and expectations towards AK management were measured on a visual analogue scale from 1â10. Specific patient profiles were investigated with subgroup and correlation analysis. Overall, 403 patients were included. The highest motivation values were obtained for the items âavoid transition to invasive squamous cell carcinomaâ (mean ± standard deviation; 8.98 ± 1.46), âAK are considered precancerous lesionsâ (8.72 ± 1.34) and âtreating physician recommends treatmentâ (8.10 ± 2.37; p < 0.0001). The highest expectation values were observed for the items âeffective lesion clearanceâ (8.36 ± 1.99), âsafetyâ (8.20 ± 2.03) and âtreatment-related costs are covered by health insuranceâ (8.00 ± 2.41; p < 0.0001). Patients aged â„77 years and those with â„7 lesions were identified at high risk of not undergoing any treatment due to intrinsic and extrinsic motivation deficits. Heat mapping of correlation analysis revealed four clusters with distinct motivation and expectation profiles. This study provides a patient-based heuristic tool for a personalized treatment decision in patients with AK
Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic MelanomaâA Retrospective Multicenter ADOReg Study
The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progressionfree (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma.
Long-term survivors have been identified particularly among patients with a complete response
(CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who
achieved a CR maintain a durable response and whether treatment cessation might be a safe option
in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical
course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with
BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi
therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg.
Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP)
and response to second-line treatments were collected and analyzed. Of 461 patients who received
BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%)
mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT
(n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP
compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients
who received TT for more than 16 months and who discontinued TT for other reasons than TP or
toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates
to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint
inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable
number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary realworld cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to
ongoing TT but was also found in patients who discontinued TT
The EORTC-DeCOG nomogram adequately predicts outcomes of patients with sentinel nodeâpositive melanoma without the need for completion lymph node dissection
Purpose: Based on recent advances in the management of patients with sentinel node (SN)âpositive melanoma, we aimed to develop prediction models for recurrence, distant metastasis (DM) and overall mortality (OM). Methods: The derivation cohort consisted of 1080 patients with SN-positive melanoma from nine European Organization for Research and Treatment of Cancer (EORTC) centres. Prognostic factors for recurrence, DM and OM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across centres. The models were externally validated using a prospective cohort consisting of 705 German patients with SN-positive: 473 trial participants of the German Dermatologic Cooperative Oncology Group study (DeCOG-SLT) and 232 screened patients. A nomogram was developed for graphical presentation. Results: The final model for recurrence and the calibrated models for DM and OM included ulceration, age, SN tumour burden and Breslow thickness. The models showed reasonable calibration. The c-index for the recurrence, DM and OM model was 0.68, 0.70 and 0.70, respectively, and 0.70, 0.72 and 0.74, respectively, in external validation. The EORTC-DeCOG model identified a robust low-risk group, with all identified low-risk patients (approximately 4% of the entire population) having a 5-year recurrence probability of <25% and an overall 5-year recurrence rate of 13%. A model including information on completion lymph node dissection (CLND) showed only marginal improvement in model performance. Conclusions: The EORTC-DeCOG nomogram provides an adequate prognostic tool for patients with SN-positive melanoma, without the need for CLND. It showed consistent results across validation. The nomogram could be used for patient counselling and might aid in adjuvant therapy decision-making
Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany
Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated
advanced melanoma patients in Germany and on the value of different real-world endpoints as
surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with
advanced melanoma from the German registry ADOReg was used. We examined OS, real-world
progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time
on treatment (rwToT). Spearmanâs rank and iterative multiple imputation (IMI)-based correlation
coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the
first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0â35.4) months, the
rwPFS was 3.9 months (95%CI 3.5â4.9), the rwTtNT was 10.7 months (95%CI 9.0â12.9), and the rwToT
was 6.2 months (95%CI 5.1â6.8). The rwTtNT showed the highest correlation with the OS based on
the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and
rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were
similar for the overall sample and those in first-line therapy. The median OS was higher compared to
recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice.
The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with
the OS among the investigated real-world endpoints
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