The semiparametric Cox regression model is often fitted in the modeling of survival data. One of its main advantages is the ease of interpretation, as long as the hazards rates for two individuals do ...not vary over time. In practice the proportionality assumption of the hazards may not be true in some situations. In addition, in several survival data is common a proportion of units not susceptible to the event of interest, even if, accompanied by a sufficiently large time, which is so-called immune, “cured,” or not susceptible to the event of interest. In this context, several cure rate models are available to deal with in the long term. Here, we consider the generalized time-dependent logistic (GTDL) model with a power variance function (PVF) frailty term introduced in the hazard function to control for unobservable heterogeneity in patient populations. It allows for non-proportional hazards, as well as survival data with long-term survivors. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation was conducted to evaluate the performance of the models. Its practice relevance is illustrated in a real medical dataset from a population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil.
Management of In-Transit Metastases Queiroz, Marcello Moro; Bertolli, Eduardo; Belfort, Francisco Aparecido ...
Current oncology reports,
05/2022, Letnik:
24, Številka:
5
Journal Article
Recenzirano
Purpose of Review
The purpose of this study is to discuss the current knowledge and future perspectives regarding the treatment options for in-transit metastases (ITM), along with the optimal ...algorithms for patients presenting with this adverse manifestation of melanoma.
Recent Findings
In addition to procedures historically accepted for the management of ITM, encompassing surgery and regional techniques, novel medications in the form of immune checkpoint inhibitors (ICI) and targeted therapies now represent standard options, allowing for the possibility of combined approaches, with an expanding role of systemic therapies.
Summary
Melanoma in-transit metastases consist of intralymphatic neoplastic implants distributed between the primary site and the regional nodal basin, within the subepidermal and dermal lymphatics. Distinct risk factors may influence the development of ITM, and the clinical presentation can be highly heterogeneous, enhancing the complexity of the management of ITM. Surgical resection, when feasible, continues to represent a standard approach for patients with curative intent. Patients with extensive or unresectable disease may also benefit from regional approaches that include isolated limb perfusion or infusion, electrochemotherapy, and a wide variety of intralesional therapies. Over the past decade, regimens with ICI and BRAF/MEK inhibitors dramatically expanded the benefit of systemic treatments for patients with melanoma, both in the adjuvant setting and for those with advanced disease, and the combination of these modalities with regional treatments, as well as neoadjuvant approaches, may represent the future for the treatment of patients with ITM.
Background
Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors ...regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario.
Methods
This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS.
Results
From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38–50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76–103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS).
Conclusions
SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.
Background
No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small ...cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC.
Methods
A prospective cohort of MCC patients was analyzed using Kaplan–Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy.
Results
Eighty-four patients were included 47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis with 565 NSE samples (median 15; interquartile range 12.6–22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease (
P
= 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy (
N
= 23; 248 NSE values), all complete responders (
N
= 10) had a normalized NSE (< 18.2 ng/ml), all partial responders (
N
= 5) had a decreasing NSE. In nonresponders (
N
= 8), all NSE levels remained elevated.
Conclusions
NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.
Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure ...disease-free margins. The intraoperative “en face” freezing technique evaluates all peripheral and deep margins.
To report the results of the “en face” freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination.
Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil.
This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative “en face” frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions.
Not having a minimum follow-up time of 5 years for all patients.
The “en face” freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.
This 5-year prospective single-center follow-up study of multiple primary melanomas in two first-degree relatives with MC1R R/R genotype is an eye opener for the need of strict melanocytic lesions ...monitoring in high-risk patients, combining clinical expertise and different, yet synergic, skin imaging technologies. Our cohort of 60 cutaneous melanomas present in only two individuals show a high percentage (83.3%). Second primary melanomas, alas 16.7% of our cases were invasive melanomas with Breslow’s thickness up to 1.5 mm. This proportion of potentially aggressive melanomas cannot be disregarded. We bring awareness to all medical specialties, government health managers, and health care insurances for the need of rigorous monitoring of high-risk patients and their families, allowing better chances of earlier cutaneous melanoma diagnosis and longer survivals.
The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients.
To evaluate patients with T1 ...melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems.
This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution.
Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023).
Unicentric study.
The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.
Introduction: Scalp reconstruction after cancer resection remains a challenge for surgeons, especially considering the increasing incidence of skin cancer among elderly patients. Dermal matrix (DM) ...is a heterogeneous group of wound covering materials that aid in wound closure and replace some of the skins functions, either temporarily or permanently. Patients at higher surgical risk can benefit from the use of DM, which help to generate a new dermis, offering great improvements in coverage of complex and extensive defects Methods: It is a retrospective study with analysis of medical records and report of two cases of patients at the A.C.Camargo Cancer Center-SP, Brazil. Results: We report two cases of complex and extensive scalp defects at a single center using DM associated with skin grafting and negative pressure therapy (NPT) in reconstructive surgery after resection of malignant skin neoplasm with satisfactory functional and esthetic results. Conclusions: Extensive lesions of the scalp are a challenge in clinical practice and a multidisciplinary treatment is essential. The results obtained indicate that DM associated with partial skin grafting and NPT have enormous potential to increase the therapeutic options available to the surgeon and possibly benefit patients, especially those who do not have the clinical conditions for extensive coverage surgery with microsurgical flap.
Diphencyprone has been reported as a local immunotherapy for cutaneous melanoma metastases. We aim to report cases of melanoma patients treated with diphencyprone in a single Brazilian institution ...and highlight their outcomes. Since 2012, we have treated 16 melanoma patients with cutaneous metastases with topical diphencyprone. To date, we have had 37.5% of complete response, 25% of partial responses, and 31.25% patients without any response. Treatment was well tolerated and local toxicity was easily controlled. We believe topical diphencyprone is a feasible treatment that can be another option for treating melanoma patients, especially in cases of in-transit or extensive disease.
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