Treatment Of Primary Melanoma Research Articles

Assisted reproductive technology, pregnancy and recurrent disease in melanoma patients: a 30-year single institution experience.

Objectives The aim of this study is to assess differences in melanoma recurrence between patients conceiving spontaneously versus those undergoing assisted reproductive technology (ART), to determine use of ART in post-melanoma patients and to examine the impact of counseling of this specific patient group. Design This study is a 30-year analysis including data from a single center questionnaire and a retrospective cohort study. Participants/Materials Women of childbearing age with a history of melanoma were requested to participate in our study. We selected patients who underwent either primary melanoma treatment or treatment of local / distant recurrence at our institute between 1994 and 2021. Each participant received a questionnaire and informed consent form. The questions concerned general health, primary tumor characteristics, utilization of ART, subsequent pregnancies and development of recurrent melanoma. Additional information was collected from the medical files. Setting The research was conducted in a dedicated oncology center and tertiary referral center for melanoma in The Netherlands. Methods Participants received the questionnaires by mail. Six weeks later a reminder was sent to non-responders. Analysis was performed using descriptive statistics. For comparisons between groups Chi-square tests were used. P-value was considered significant when below 0.05. A clinically relevant difference in recurrence rate was defined as a 10% difference. Results A total of 498 questionnaires were available for analyses, 449 from living patients and 49 from relatives of diseased patients. One hundred and seventy-nine patients (36%) with a history of melanoma became pregnant following their diagnosis. In this group, 28 patients (16%) attempted to conceive using ART, and eight of them experienced disease recurrence. There was no difference in the recurrence rate between patients who became pregnant after the diagnosis of melanoma and those who never subsequently conceived (37% vs 35%, p=0.609). Limitations The main limitations of the study are its size, observational design and questionnaire methodology. Conclusions Pregnancy did not increase the risk of recurrent melanoma. The group of patients conceiving after ART was small and therefore it is difficult to confidently conclude that the recurrence risk is comparable to the other groups. Prospective international registration of these patients, their oncologic follow-up and possible use of assisted reproduction, will provide valuable information to determine any potential association between ART and risk of recurrent melanoma. This would enable health professionals to develop surveillance strategies and pre-conception counselling of patients wishing to conceive.

Changes in Health Care Costs, Survival, and Time Toxicity in the Era of Immunotherapy and Targeted Systemic Therapy for Melanoma

Melanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice. To examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma. This cohort study assessed a longitudinal, propensity score (PS)-matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023. Era of melanoma diagnosis (2007-2012 vs 2018-2019). The primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts. A PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20). This cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system-wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.

Plasma Methylated DNA Markers for Melanoma Surveillance.

Surveillance after primary melanoma treatment aims to detect early signs of low-volume systemic disease. The current standard of care, surveillance imaging, is costly and difficult to access. We therefore sought to develop methylated DNA markers (MDMs) as promising alternatives for disease surveillance. We used reduced representation bisulfite sequencing (RRBS) to identify MDMs in DNA samples obtained from metastatic melanoma, benign nevi, and normal skin tissues. The identified MDMs underwent validation in an independent cohort of tissue and buffy coat DNA samples. Subsequently, we tested the validated MDMs in the plasma DNA of patients with metastatic melanoma undergoing surveillance with total body imaging and compared them with cancer-free controls. To estimate the overall predictive accuracy of the MDMs, we used random forest modeling with bootstrap cross-validation. Forty MDMs demonstrated discrimination between melanoma cases and controls consisting of benign nevi and normal skin. Nine MDMs passing biological validation in tissue were run on 77 plasma samples from individuals with a history of metastatic melanoma, 49 of whom had evidence of disease detected by imaging at the time of blood draw, and 100 cancer-free controls. The cross-validated sensitivity of the panel for imaging-positive disease was 80% with a specificity of 100% in cancer-free controls, resulting in an overall AUC of 0.88 (95% CI, 0.81 to 0.96). The survival estimates for patients with melanoma who tested positive for the panel at 6 months and 1 year were 67% and 56%, respectively, while those who tested negative had survival rates of 100% and 92%. MDMs identified by RRBS demonstrate a high degree of concordance with imaging results in the plasma of patients with metastatic melanoma. Further prospective studies in larger intended use cohorts are needed to confirm these findings.

Study of the skin-penetration promoting effect and mechanism of combined system of curcumin liposomes prepared by microfluidic chip and skin penetrating peptides TD-1 for topical treatment of primary melanoma

The transdermal drug delivery system (TDDS) is an effective strategy for the treatment of melanoma with fewer side effects and good biocompatible, but the skin penetration of drugs should be further promoted. Here, we proposed a new system that combined curcumin liposomes (Cur-Lips) with skin-penetrating peptides to promote skin penetration ability. However, the preparation of Cur-Lips has drawbacks of instability and low entrapment efficiency by the traditional methods. We thus innovatively designed and applied a microfluidic chip to optimize the preparation of Cur-Lips. Cur-Lips exhibited a particle size of 106.22 ± 4.94 nm with a low polydispersity index (＜0.3) and high entrapment efficiency of 99.33 ± 1.05 %, which were prepared by the microfluidic chip. The Cur-Lips increased the skin penetration capability of Cur by 2.76 times compared to its solution in vitro skin penetration experiment. With the help of skin-penetrating peptide TD-1, the combined system further promoted the skin penetration capability by 4.48 times. The (TD-1 + Cur-Lips) system also exhibited a superior inhibition effect of the tumor to B16F10 in vitro. Furthermore, the topical application of (TD-1 + Cur-Lips) gel suppressed melanoma growth in vivo, and induced tumor cell apoptosis in tumor tissues. The skin-penetration promotion mechanism of the system was investigated. It was proved that the system could interact with the lipids and keratin on the stratum corneum to promote the Cur distribute into the stratum corneum through hair follicles and sweat glands. We proved that the microfluidic chips had unique advantages for the preparation of liposomes. The innovative combined system of liposomes and biological transdermal enhancers can effectively promote the skin penetration effect of drugs and have great potential for the prevention and treatment of melanoma.

Melanoma surgery-An update.

Cutaneous melanoma is the major cause of mortality from all skin cancers. The treatment has been revolutionized in recent years by introduction of immunotherapy and targeted therapy for melanoma patients Stages III and IV. Therefore, the role of surgery in melanoma treatment needs to be redefined. In this narrative review, we will focus on surgery for diagnosis, treatment of primary tumor, and metastases in the era of new and effective medical treatment options. Neoadjuvant therapy is currently investigated in several trials. Surgery for treatment-resistant metastases is another field of interest. In conclusion, surgery remains a cornerstone for diagnosis and treatment of primary melanoma. Therapeutic lymphadenectomy has lost importance while surgery in sentinel lymph node diagnostics and metastasectomy are useful in a tailored individual approach of combined treatments. There is a trend to less invasive surgical procedures.

S1801: A randomized trial of adjuvant versus neoadjuvant pembrolizumab for melanoma.

TPS9585 Background: Although long term outcomes for most patients with early-stage melanoma is excellent following surgery, patients who have high-risk features such as lymph node involvement have poorer outcomes. Adjuvant therapy (AT) is currently considered for patients with stage III melanoma and selected patients with resected stage IV melanoma. Currently, AT for melanoma is anti-PD-1 or targeted therapy in the presence of a BRAF mutation. At this time, we are not able to predict which patients will derive benefit from AT and experience cure. While curative intent is the goal of treatment for primary melanoma, patients with bulky nodal involvement are at high risk of local or distant recurrence despite upfront surgery. Neoadjuvant treatment (NAT) offers the benefit of an early on-treatment pathological sample that can be profiled for biomarkers and correlated with response and survival. Treating with anti-PD1 while tumor remains visible in the body may generate a stronger immune response against in vivo tumor antigens compared to the traditional adjuvant setting where antigen is presented by microscopic residual tumor burden. Pilot studies of NAT with anti-PD-1 therapy have been initiated in melanoma. Multidisciplinary coordination in these cases is paramount. In these studies, an improvement in relapse-free survival and overall survival has been observed; additionally, pathologic response rates to NAT have been estimated in small studies. Methods: S1801 is a randomized phase II study of AT versus NAT with pembrolizumab (PEM, NCT03698019). Patients with measurable, clinically detectable and resectable cutaneous, acral, and mucosal melanomas without brain metastasis are eligible. Patients with Stage IIIB to oligometastatic, resectable Stage IV are randomized 1:1 to AT or NAT. Patients getting AT undergo surgery first followed by 18 doses of PEM 200 mg IV every 3 weeks. Patients getting NAT receive 3 doses of pre-operative PEM followed by surgery and then 15 doses of adjuvant PEM. Radiation may be given on either arm after surgery, at the investigator’s discretion. Primary endpoint is event-free survival measured from the date of randomization to the date of first documented progression that renders the patient unable to receive planned protocol surgery, failure to begin adjuvant therapy within 84 days of surgery, relapse after surgery, or death due to any cause. Secondary endpoints include RECIST and iRECIST response rates, as well as a number of surgical outcomes. Safety monitoring is conducted with disease progression and toxicity thresholds. The key Translational Medicine objective of this trial is to determine the pathologic response rate to NAT after 3 doses of PEM. Surgical pathology grossing instructions to ensure readout for pathologic response are provided in the form of training slides. Enrollment is at 40% of a planned 500 patients. Clinical trial information: NCT03698019.

Primary malignant melanoma of the esophagus successfully treated with nivolumab: a case report

IntroductionPrimary malignant melanoma of the esophagus is a rare and aggressive disease that tends to have a poor response to chemotherapies. Previous studies have indicated that currently available treatment for primary malignant melanoma of the esophagus is insufficient. Here, we describe a case of recurrent primary malignant melanoma of the esophagus successfully treated with the immune checkpoint inhibitor nivolumab.Case presentationAn 81-year-old Japanese female presented with a 3-month history of dysphagia. She was medicated for hypertension and sarcoidosis. The patient had no past history of cutaneous, ocular, or other-site melanomas. An esophagoscopy identified a 30-mm giant tumor in the lower esophagus, at a site 30 cm from the incisors. Enhanced computed tomography revealed wall thickening measuring 30 mm in size at the middle-third of the intrathoracic esophagus, with no significant lymph node infiltration or distant metastasis. Esophageal biopsy showed proliferation of large round tumor cells and melanophages. On the basis of these findings, the patient was diagnosed with esophageal malignant melanoma and underwent esophagectomy and lymph node dissection with gastric tube reconstruction. Although the pathological diagnosis was primary malignant melanoma of the esophagus, the patient presented with multiple lymph node and bone metastases 4 months after surgery. Subsequently, treatment with nivolumab 240 mg every 2 weeks was administered as the first-line treatment. Diffusion-weighted imaging with background body signal suppression following eight courses of nivolumab revealed that the multiple lymph node and bone metastases were markedly reduced. The patient received 30 courses of nivolumab and has maintained the partial response. No severe adverse events related to the immunotherapy were recorded.ConclusionThe current study suggests that nivolumab may be a viable option for patients with metastatic primary malignant melanoma of the esophagus. Additional evidence from future clinical trials and research is necessary to fully validate these findings.

A Malignant Melanoma of the Penile : A Very Rare Case Report and Literature Review

Background: Malignant melanoma of the penis is very rare, accounting for approximately 1.4% of all primary penile carcinomas. With a small prevalence of penile melanoma, there is lack of data about quality of the therapy. The primary treatment of melanoma of the penile is surgical, although there is a lack of consensus regarding the extent of treatment that is indicated.&#x0D; Case Report: A 60-year-old Caucasian man came to Division of Urology, Department of Surgery, Dr. Kariadi General Hospital Semarang with chief complaint painless and fast growing lesions on his penile. His general condition was fine, and has a normal vital signs. On the physical examination of penile region, there were found lesions on the ventral of the glans and penile foreskin and covered with blood and pus, with bilateral inguinal lymph nodes and lung metastasis from Multi Slice Computed Tomography. We already performed partial penectomy and bilateral inguinal lymph nodes dissection with histopathological results a malignant melanoma Clark IV. The final stage of penile melanoma was pT2N1M1. We follow-up the patient until 1 year after procedure, and there wasn’t any recurrence.&#x0D; Conclusion: Malignant melanoma of the penis is rare. Penile melanoma is highly treatable with surgical excision in its early stages because of resistant to both chemotherapy and radiotherapy. Delay in diagnosed and surgical treatment can lead to an adverse prognosis. The anamnesis, physical examination, and imaging studies must be done appropriately to improve the survival.

Can we reduce excision margins for head and neck melanoma? A 12-year retrospective study

Although wide local excision is the standard treatment for primary melanoma, the surgical margin remains controversial. Melanomas of the head and neck exhibit higher recurrence rates and worse prognosis than lesions in other body locations, and their close proximity to critical anatomical and functional structures means that wide excision margins are often not feasible. Surgeons must therefore achieve a balance of oncological safety and functional and aesthetic needs. The aim of this study was to retrospectively analyse melanoma data over a 12-year period at a large skin surgery unit to identify potential differences in outcomes in patients who had reduced wide local excision margins for primary head and neck melanoma. The study would provide further evidence for the need for large randomised prospective trials to reduce excision margins for head and neck melanoma. Local cancer network data were retrospectively analysed over a period of 12 years (2008-2019). Data included site, initial stage, multidisciplinary team (MDT) meeting recommendations for excision margins and the actual wide local excision margin taken, recurrence rate, and disease-specific and absolute survival. A total of 222/305 patients (73%) had the recommended excision margin, while in 27% margins were reduced due to anatomical or functional considerations. Recurrence rates were similar (recommended 11.7% vs narrow 13.3% excision margins) (p = 0.64). The mean follow-up time for all patients was 48.5 months. In aesthetically and functionally sensitive areas of the head and neck, wide local excision margins need to be carefully considered after MDT discussion and discussion with the patient. This study suggests the need for further multicentre trials to address the uniqueness of head and neck melanoma.

Potential predictive value of SCN4A mutation status for immune checkpoint inhibitors in melanoma

Melanoma refers to a pigmented nevus with malignant changes. The preferred treatment for primary melanoma is surgical excision and postoperative radiotherapy, but the prognosis is poor. Immune checkpoint inhibitors (ICIs) have been remarkably successful in different types of cancers, but not all cancer patients can benefit from it. Therefore, it is essential to find predictable biomarkers and improve the accuracy of treatment. In this study, we used survival analysis, gene panorama analysis, immune cell enrichment analysis, TMB analysis, and GSEA to demonstrate that SCN4A gene mutations may be used as one of the indicators to predict the prognosis of melanoma patients undergoing ICI treatment. The research further indicates that SCN4A gene mutations improve the prognosis of ICI treatment. It is hoped that the effect of SCN4A on immunogenicity and tumor immunity can be demonstrated to further suggest the effect of this gene on the efficacy of ICIs.

Reconstruction after Mohs Surgery for Digit Melanoma: Description of Techniques and Postoperative Limb Function

IntroductionMohs surgery and reconstruction has enabled tissue-preserving resection of cutaneous malignancies. The goal of our case series evaluation is to present reconstructive techniques and functional outcomes in patients undergoing digit-sparing treatment for primary melanoma. Materials and MethodsA chart review was performed to identify consecutive patients undergoing Mohs surgery and reconstruction for melanoma of the digits. Quality of life (QOL) survey was performed to assess function after the procedure. ResultsThirty-two patients (13 hand, 19 foot, Age: 65.03 +/–17.78 years) who were undergoing Mohs surgery were identified. No recurrence was identified with an average follow-up of 16.1 months (1–95 months). The average defect size was 5.79 +/–4.54 cm2. Reconstruction was performed 0–4 days after resection. The most common techniques included full-thickness skin graft (FTSG) (N = 7), collagen matrix + FTSG (N = 4), and volar advancement flap (N = 7). The reconstructive technique choice appears correlated with defect size (p = 0.0125). Neuro-QOL upper extremity survey results showed a difference that approached statistical significance between patients who underwent digit-sparing treatment (n = 7) versus direct to amputation controls (n = 5) (p = 0.072). No survey differences between digit-sparing treatment (n = 10) and amputation (n = 8) were identified in the lower extremity (p = 0.61). ConclusionOur results show digit-sparing treatment can confirm clear surgical margins and a trend toward improvement in upper extremity function compared with immediate amputation.

S1801: A randomized phase II trial of adjuvant versus neoadjuvant pembrolizumab (PEM) for melanoma.

TPS10090 Background: Although long term outcomes for most patients with early-stage melanoma is excellent following surgery, patients who have high-risk features such as lymph node involvement have poorer outcomes. Adjuvant therapy (AT) is currently considered for patients with stage III melanoma and selected patients with resected stage IV melanoma. Currently, AT for melanoma is anti-PD-1 or targeted therapy in the presence of a BRAF mutation. At this time we are not able to predict which patients will derive benefit from AT and experience cure. While curative surgery is the goal of early treatment of primary melanoma, some cases with bulky nodal involvement are at high risk of local or distant recurrence despite upfront surgery. Neoadjuvant treatment (NAT) offers the benefit of an early on-treatment pathological sample that can be profiled for biomarkers and correlated with survival. Treating with anti-PD1 while tumor transiently remains in the body may generate a stronger immune response from tumor-infiltrating lymphocytes against in vivo tumor antigens compared to the traditional adjuvant setting where antigen is presented by microscopic residual tumor burden. Pilot studies using NAT with have been initiated in melanoma. Multidisciplinary coordination in these cases is paramount. In these studies, an improvement in relapse-free survival and overall survival has been observed; additionally, pathologic response rates to NAT have been estimated in small studies. Methods: S1801 is a randomized phase II study of AT versus NAT with PEM (NCT03698019). Patients with measurable, clinically detectable and resectable cutaneous, acral, and mucosal melanomas without brain metastasis are eligible. Patients are randomized 1:1 to the AT or the NAT. Patients getting AT receive surgery first followed by 18 doses of PEM 200 mg IV every 3 weeks. Patients getting NAT receive 3 doses of pre-operative PEM followed by surgery and then 15 doses of adjuvant PEM. Radiation may be given on either arm after surgery, at the investigator’s discretion. Primary endpoint is event-free survival measured from the date of randomization to the date of first documented progression that renders the patient unable to receive planned protocol surgery, failure to begin AT within 84 days of surgery, relapse after surgery, or death due to any cause. Safety monitoring is conducted with disease progression and toxicity thresholds. The key Translational Medicine objective of this trial is to determine the pathologic response rate to NAT with 3 doses of PEM. Enrollment is at 94 of a planned 500 patients. Clinical trial information: NCT03698019.

Results of surgical treatment for primary malignant melanoma of the esophagus: A multicenter retrospective study

ObjectiveFew large-sample research data sets exist on long-term survival and prognostic factors among patients with primary malignant melanoma of the esophagus (PMME), a rare malignancy associated with poor outcomes. We sought to investigate postoperative survival and prognostic factors in patients with PMME. MethodsWe retrospectively analyzed long-term follow-up results for patients with PMME who underwent surgery at 10 Chinese centers between January 1998 and January 2018. We performed uni- and multivariate analyses to investigate clinicopathologic factors associated with survival. ResultsMedian overall survival for the entire group (N = 70 patients) was 13.5 months. Female sex (hazard ratio [HR], 0.352; 95% confidence interval [CI], 0.138-0.900; P = .029), ≥12 lymph nodes dissected (HR, 0.274; 95% CI, 0.133-0.563; P < .001), absence of lymph node metastasis (HR, 0.195; 95% CI, 0.084-0.451; P < .001), and postoperative adjuvant therapy (HR, 0.474; 95% CI, 0.249-0.901; P = .023) were factors of favorable prognosis. Preoperative pathologic diagnosis of PMME was as low as 47.1%. A high proportion of patients had lymph node metastasis, including those with early-stage tumors. Rates of lymph node metastasis were 54.2% (13/24) for pT1, 44.4% (12/27) for pT2, 57.1% (8/14) for pT3, and 100% (5/5) for pT4. Regional lymph node recurrence (N = 43 [61.4%]) was the predominant postoperative pattern of recurrence or metastasis. ConclusionsFemale sex, pN0, increased number of lymph nodes dissected, and postoperative adjuvant therapy were associated with better outcomes among patients with PMME. Preoperative pathologic diagnosis of PMME was low, patients had lymph node metastasis (even those with early-stage tumors), and regional lymph node recurrence was common.

A plasma microRNA biomarker of melanoma as a personalised assessment of treatment response.

New tools for monitoring response to primary melanoma treatment are needed to reduce recurrence rates and patient anxiety. A previously developed plasma-based microRNA signature (MEL38) was measured in four melanoma patient samples obtained before and 12-14 days after treatment (i.e. surgical excision), as well as in two nonmelanoma controls. The value of the MEL38 score and selected individual genes were compared between the time points. The MEL38 scores of the four patients with melanoma became more 'normal like' after tumour excision, with a statistically significant 15% mean reduction. MicroRNAs involved in tumour suppression were upregulated in the postexcision samples and those involved in facilitating treatment resistance and tumour invasion were downregulated. Based on these limited preliminary data, the MEL38 signature may have clinical utility in assessing an individual patient's response to the most common form of melanoma treatment. Additional studies are needed on larger, clinically diverse patient cohorts, sampled over longer periods of time.

Itraconazole treatment of primary malignant melanoma of the vagina evaluated using positron emission tomography and tissue cDNA microarray: a case report

BackgroundPrimary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial.Case presentationA 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)–computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET–CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months.ConclusionThe findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.

The value of metastasectomy in stageIV cutaneous melanoma.

Cutaneous melanoma is an aggressive neoplasia of melanocytes. Prognosis is dependent on tumor stage. StageIV melanoma is characterized by the occurrence of distant metastases. Response of metastases to classical chemotherapy is limited and toxicity of treatment is high. In recent years, new developments in immunotherapy and targeted therapies improved prognosis of stageIV melanoma patients with better tolerability of treatment. There is no dispute about surgical treatment of primary melanoma. But what is the value of metastasectomy in the era of new systemic treatments? This review aims to discuss available data for surgical removal of distant metastases for several organs and tissues. The available evidence suggests that for selected patients with possible complete resection of all tumor metastases, metastasectomy remains an effective treatment option with abenefit in overall survival.

High Number of Circulating Tumor Cells Predicts Poor Survival of Cutaneous Melanoma Patients in China.

BackgroundMelanoma is an aggressive cancer with complex etiology and poor prognosis. Surgical resection is still the primary treatment of melanoma, but shows limited efficacy in late-stage patients. Additionally, reliable prognostic markers of skin melanoma patients are still lacking. Circulating tumor cells (CTCs) have shown promise in predicting prognosis of multiple cancers.Evaluating the prognostic value of CTC number in melanoma patients.Material/MethodsCTCs were isolated by immunomagnetic capture from 7.5-mL samples of blood from 100 patients with cutaneous melanoma. Baseline CTC number (pre-treatment) and post-treatment CTC number were measured. Baseline CTC number and CTC number alteration were correlated with clinicopathological features and survival.ResultsForty-three (43%) patients had more than 6 CTCs, whereas 57 (57%) had 6 cells or less. High baseline CTC count was associated with deep local invasion, lymph node metastasis, and distance metastasis, with P value of 0.003, 0.047, and 0.034, respectively. High baseline CTC count was also correlated with short overall survival time and was considered as an independent prognostic factor (P value=0.012, hazard ratio=2.262). CTC cell alteration was associated with progression-free survival and disease-specific survival (with P values of 0.012 and 0.009, respectively).ConclusionsBaseline CTC count was correlated with adverse pathological features and was predictive of survival in melanoma patients. Alteration of CTC count before and after treatment was an indicator of therapy response and prognosis. Measuring the baseline and post-treatment CTC counts is a powerful tool in monitoring melanoma progression, drug response, and survival.

Is there a relation between type of primary melanoma treatment and the development of intralymphatic metastasis? A review of the literature.

Intralymphatic metastases (ILM) originate from tumor cell emboli entrapped in dermal lymphatics between primary tumor and regional lymph node basin. Because of this origin, sentinel lymph node biopsy (SLNB) might increase ILM by restricting lymph flow. Pubmed, Embase, Cochrane and Medline were searched for articles on ILM between 1980 and September 2014. ILM Incidences were calculated after wide local excision (WLE), excision with elective lymph node dissection (ELND) or therapeutic lymph node dissection (TLND), WLE with SLNB with or without completion lymph node dissection (CLND) and delayed lymph node dissection (DLND) for patients developing nodal metastasis during follow-up. In 36 studies, 14,729 patients underwent WLE, 1682 patients WLE/ELND, 362 patients WLE/DLND and 11,201 patients WLE/SLNB. On meta-analysis, ILM occurrence was 3.4% (95% CI 2.8-4.2%). ILM occurred most frequently in the WLE/DLND group (5.5%, 95% CI 3.5-8.7%), followed by WLE/ELND (4.7%, 95% CI 3.1-7.0%), WLE/SLNB (4.5%, 95% CI 3.5-5.7%) and WLE alone (1.9%, 95% CI 1.4-2.7%). 1330 SLNB+ patients were identified and 5783 SLNB- patients. For these groups, on meta-analysis, ILM recurrence was 13.2% (95% CI 10.8-16.2%) and 3.4% (95% CI 2.5-4.5%), respectively (p=0.01). In this review SLNB is associated with an increase of ILM with an incidence of 1.9% for WLE vs. 3.4% for SNLB-. Selection bias in this review cannot be excluded. However, ILM occur four times more frequently after SLNB+ than SLNB- procedures and more often after SLNB+/CLND than WLE/DLND or WLE/ELND. ILM should therefore be viewed as a bio-marker of aggressive primary disease. Sentinel lymph node biopsy is thought to increase intralymphatic metastasis by restricting lymph flow. This review demonstrates that there is an increase in metastasis, but this result has to be interpreted with caution due to possible selection bias. Aggressive tumor characteristics are likely the cause of this increase.

Prediction of the engendering mechanism and specific genes of primary melanoma by bioinformatics analysis

Abstract Objective Our aim was to explore the engendering mechanism and gene targets for melanoma. Methods The microarray data of GSE46517 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between primary melanoma samples and normal controls were analyzed using the GEO2R online tool. The screened DEGs were mapped to a protein–protein interaction network based on the Search Tool for the Retrieval of Interacting Genes database. The functions and pathways involved with DEGs were analyzed using the Database for Annotation Visualization and Integrated Discovery software) online tools. Then, the DEGs were further annotated via the TRANSFAC, Tumor-Suppressor Gene, and Tumor-Associated Gene databases. Results A total of 1095 DEGs including 511 upregulated genes and 584 down-regulated ones were screened out. The nodes of CCL5 , ISG15 , CDKN2A , EGFR , and ERBB2 showed a high connectivity degree in protein–protein interaction networks and were mainly enriched in Biological Process GO terms such as the regulation of catalytic activity and cell adhesion, as well as the pathways of cytochrome P450. The DEGs were classified into 31 transcription factors and 43 downregulated tumor associated genes. Conclusion Catalytic activity, cell adhesion, and the cytochrome P450 associated pathways are dysregulated in the melanoma formation. The significant nodes such as ISG15 , IRF4 , ERBB2 and EGFP may be potential targets for primary melanoma treatment.

Analysis of recurrence patterns in acral versus nonacral melanoma: should histologic subtype influence treatment guidelines?

Current surgical treatment of primary melanoma is uniform for all histosubtypes, although certain types of melanoma, such as acral lentiginous melanoma (ALM), have a worse prognosis. No study has explored the effectiveness of standard melanoma treatment guidelines for managing ALM compared with nonacral melanoma (NAM). Study subjects were identified from a prospectively enrolled database of patients with primary melanoma at New York University. Patients with ALM were matched to those with NAM (1:3) by gender and melanoma stage, including substage (ALM, 61; NAM, 183). All patients received standard-of-care treatment. Recurrence and survival outcomes in both cohorts were compared. ALM histologic subtype was an independent negative predictor of recurrence-free survival (hazard ratio [HR], 2.24; P=.001) and melanoma-specific survival (HR, 2.58; P=.001) compared with NAM. Recurrence was significantly more common in patients with ALM than in those with NAM (49% vs 30%; P=.007). For tumors less than 2 mm in thickness, a significantly higher recurrence rate was seen with ALM versus NAM (P=.048). No significant difference was seen in recurrence for tumors greater than 2 mm (P=.12). Notably, the rate of locoregional recurrence was nearly double for ALM compared with NAM (P=.001). The data presented herein reveal a high rate of locoregional failure in ALM compared with NAM when controlling for AJCC stage. These results raise the question of whether ALM may require more aggressive surgical treatment than nonacral cutaneous melanomas of equal thickness, particularly in tumors less than 2 mm thick. Larger multicenter trials are necessary for further conclusions.