Background
This study aimed to improve the understanding of the prognostic value of tumor mitotic rate (TMR) in cutaneous melanoma and assessed its significance as a predictor for overall, ...melanoma‐specific, and recurrence‐free survival.
Patients and Methods
This is a retrospective multicenter Italian cohort study of 13,016 patients diagnosed with and treated for invasive primary melanoma between 2005 and 2020 with median follow‐up of 5.5 years. The survival probability was assessed by Kaplan–Meier method, hazard ratios (HRs), and corresponding 95% confidence interval (CI) of all‐cause mortality and recurrence/death by multivariable Cox proportional hazards models.
Results
Higher dermal mitoses number was associated with decreased overall survival. Among patients with TMR 0/mm2, 1/mm2, 2/mm2–3/mm2, 4/mm2–10/mm2, and >10/mm2, 5‐year overall survival (OS) was 97.3%, 93.6%, 88.3%, 73.0%, and 60.9%, respectively. In multivariate analyses, compared to TMR of 0/mm2, HRs for all‐cause mortality were 1.35 (95% CI, 1.08–1.68), 1.70 (95% CI, 1.40–2.07), 2.04 (95% CI, 1.67–2.49), and 2.39 (95% CI, 1.90–3.00) for 1 mitoses/mm2, 2 mitoses/mm2–3 mitoses/mm2, 4 mitoses/mm2–10 mitoses/mm2, and >10 mitoses/mm2, respectively. A similar increase in risks was observed in melanoma‐specific survival (MSS) and recurrence‐free survival (RFS). The HRs for MSS and RFS for the highest compared to the lowest TMR category were 3.01 (95% CI, 2.20–4.11) and 2.26 (95% CI, 1.88–2.73), respectively. Sentinel lymph‐node biopsy positivity was significantly associated with TMR increase even with adjustment for several potential confounders.
Conclusions
A clear association was demonstrated between an increasing TMR and decreased OS, MSS, and RFS, suggesting a reconsideration of TMR prognostic role for future inclusion in the melanoma staging system.
Plain Language Summary
The 8th American Joint Committee on Cancer for melanoma staging removed tumor mitotic rate (TMR) from the staging criteria for T1 melanomas, giving way to ulceration and tumor thickness as stronger prognostic predictors.
However, it is still recommended that TMR should be assessed and recorded in all primary invasive melanomas.
In a large retrospective multicenter study on primary invasive melanomas, we investigated the prognostic value of TMR to assess its significance as survival predictor.
Our results showed a clear association between increasing TMR and decreased patients' survival, suggesting that TMR should be considered for inclusion in the melanoma staging system.
Increasing tumor mitotic rate (TMR) is clearly associated with decreased overall, melanoma‐specific, and recurrence‐free survival. Our results suggest that the prognostic role of TMR should be reconsidered, and dermal mitotic rate should be assessed and recorded for all primary melanomas.
Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have ...addressed the quality of care and the costs for adolescents and young adults (AYA) population.
To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category.
This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method.
In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004).
In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.
The Buschke-Lowenstein tumor (BLT), also known as giant condyloma acuminatum, is a rare sexually transmitted disease often associated with human papillomavirus types 6 and 11. There are no specific ...guidelines for treating BLT. Surgery is the preferred treatment, although it can have profound consequences on a patient's quality of life. A 41-year old male, who was HIV-positive and a kidney transplant recipient treated with cyclosporine, was referred to the Veneto Institute of Oncology (Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit) after a two-year history of perianal warts that always relapsed after surgical treatment. A multidisciplinary evaluation was conducted to assess an individually tailored treatment plan. Tailored bleomycin-based electrochemotherapy (ECT) was proposed in order to achieve local disease control and preserve kidney function. A total of three cycles of ECT with a 25%-reduced dose of intravenous bleomycin (11,250 IU/m.sup.2) were administered, and a complete response was achieved 20 months after the final ECT session.
Aim of the study
Skeletal muscle metastases (SMM) are a rare entity, mainly detected at autopsy. Nevertheless, radiological and nuclear medicine imaging can contribute to the diagnosis with a ...significant impact on the treatment and prognosis of neoplastic patients. This study aimed to systematically review the features of SMM at imaging considering the primary tumors and the sites of occurrence.
Materials and methods
We conducted a systematic search of three electronic database (i.e., PubMed, Science Direct, and Web of Science) up to May 2019, without any language or time interval restriction. Two reviewers performed the search and selection process, data extraction, and synthesis. We resolved disagreements by consensus and/or involving a third reviewer. The included studies have been classified according to the Oxford Centre for Evidence Based Medicine (CEBM) grading system.
Results
Out of 8598 and 1077 articles respectively for radiological and hybrid imaging, 29 papers were included. According to CEBM, twelve were level 4. Computed tomography (CT) is mainly applied and, despite the existence of CT and magnetic resonance–based classifications, these are rarely used. Positron emission tomography/CT allowed the detection of small and subtle lesion also in the extremities. Muscles of the trunk were mostly affected and mainly respiratory tumors are associated with this type of metastatic spread.
Conclusion
Radiological and hybrid imaging allow a precise characterization of SMM. However, a more systematic approach, including also the application of available classification systems, may increase the diagnostic accuracy for this rare type of metastases.
Key Points
• Skeletal muscle metastases have heterogeneous characteristics at imaging but mostly abscess-like features and high metabolic activity are described.
• Skeletal muscle metastases mainly affect the muscles of the trunk.
• Pulmonary, urological, and gastrointestinal cancers are the most frequent cause of skeletal muscle metastases.
Interpatient clinical variability in soft-tissue sarcomas (STS) highlights the need for novel prognostic markers supporting patient risk stratification. As sarcomas might exhibit a more mesenchymal ...or a more epithelial state, we focused on epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) for prognostic clues, and selected three histotypes with variable aggressiveness.
The expression of EMT/MET-related factors was measured by qRT-PCR in 55 tumor samples from patients with leiomyosarcoma, myxofibrosarcoma, or undifferentiated pleomorphic sarcoma. The identified marker was further evaluated by IHC in 31 leiomyosarcomas and by measuring its circulating levels in 67 patients. The prognostic value of a sarcoma-tailored EMT score was analyzed. Epirubicin chemosensitivity and migration were studied in primary STS cultures. Associations with overall survival (OS) were assessed using Kaplan-Meier and Cox regression methods.
High expression of periostin, a mesenchymal matricellular protein, in sarcoma tissues (
= 0.0024), its high stromal accumulation in leiomyosarcomas (
= 0.0075), and increased circulation (>20 ng/mL,
= 0.0008) were associated with reduced OS. High periostin expression HR 2.9; 95% confidence interval (CI), 1.3-6.9;
= 0.0134 and circulation (HR 2.6; 95% CI, 1.3-5.1;
= 0.0086), and a mesenchymal EMT score (mesenchymal vs. transitioning; HR, 5.2; 95% CI, 2.1-13.0,
= 0.0005) were associated with increased risk in multivariable models. An intrinsic or induced mesenchymal state enhanced chemoresistance and migration in sarcoma cell lines.
Although limited to a pilot study, these findings suggest that periostin might contribute prognostic information in the three studied STS histotypes. Moreover, a transitioning EMT score measured in the tumor might predict a less active and a more chemosensitive disease.
Retroperitoneal soft-tissue sarcomas (RPS) are rare forms of mesenchymal tumors that account for ~0.15% of all malignancies. The purpose of the present study was to determine the differences between ...RPS and non-RPS anatomopathological and clinical features and to analyze whether the hazard ratio for short-term mortality differs between patients with RPS and non-RPS, after adjusting for differences in base-line anatomopathological and clinical features. The Veneto Cancer Registry, a high-resolution population-based dataset spanning the regional population, was used as a data source for the analysis. The current analysis focuses on all incident cases of soft-tissue sarcoma recorded by the Registry from January 1, 2017 to December 31, 2018. A bivariate analysis was carried out to compare demographic and clinical characteristics in RPS and non-RPS. Short-term mortality risk was analyzed by primary tumor site. The significance of variations in survival by site group was determined using Kaplan-Meier curves and the Log-rank test. Finally, Cox regression was used to assess the hazard ratio for survival by sarcoma group. RPS accounted for 22.8% of the total sample (92 out of 404 cases). The mean age at diagnosis was 67.6 years for RPS vs. 63.4 for non-RPS; 41.3% of RPS were >150 mm vs. 5.5% for non-RPS. Stages III and IV were more prevalent in RPS (53.2 vs. 35.6%), despite the fact that, in both groups, advanced stages are the most common onset at diagnosis. Regarding surgical margins, the present study showed that R0 is the most prevalent in non-RPS (48.7%), while R1-R2 is the most frequent in patients with RPS (39.1%). The 3-year mortality rate for retroperitoneum was 42.9 vs. 25.7%. Comparing RPS and non-RPS, the multivariable Cox model showed a hazard ratio of 1.58 after adjusting for all other prognostic factors. RPS clinical and anatomopathological characteristics differ from those of non-RPS. Overall, despite adjusting for other prognostic factors, the retroperitoneum site was an independent prognostic factor associated with a worse overall survival in sarcoma patients compared with other sites.
Cutaneous melanoma, the most aggressive type of skin cancer, remains one the most represented forms of cancer in the United States and European countries, representing, in Australia, the primary ...cause of cancer-related deaths. Recently, many studies have shown that sex disparities previously observed in most cancers are particularly accentuated in melanoma, where male sex is consistently associated with an increased risk of disease progression and a higher mortality rate. The causes of these sex differences rely on biological mechanisms related to sex hormones, immune homeostasis and oxidative processes. The development of newer therapies, such as immune checkpoint inhibitors (ICIs) (i.e., anti-PD-1 and anti-CTLA-4 monoclonal antibodies) has dramatically changed the treatment landscape of metastatic melanoma patients, though ICIs can interfere with the immune response and lead to inflammatory immune-related adverse events (irAEs). Recently, some studies have shown a potential adverse influence of this immunotherapy treatment also on male fertility and testicular function. However, while many anticancer drugs are known to cause defects in spermatogenesis, the effects of ICIs therapy remain largely unknown. Notwithstanding the scarce and conflicting information available on this topic, the American Society of Clinical Oncology guidelines recommend sperm cryopreservation in males undergoing ICIs. As investigations regarding the long-term outcomes of anticancer immunotherapy on the male reproductive system are still in their infancy, this review aims to support and spur future research in order to understand a potential gonadotoxic effect of ICIs on testicular function, spermatogenesis and male fertility.
A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is ...associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation ...(UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth's surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the "coast-plain-hill gradient" could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control.
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