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The National Cancer Data Base report on cutaneous and noncutaneous melanoma
Abstract
BACKGROUND
This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U. S. within the last decade.METHODS
Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated.RESULTSThe percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment.CONCLUSIONS
Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival. Cancer 1998;83:1664-1678. © 1998 American Cancer Society.
... While the majority of malignant melanoma cases arise from the skin (cutaneous), there are other subtypes of melanoma that arise from mucosal membranes and from the ocular region. 2 These subtypes are known to be less responsive to commonly used immunotherapy in comparison to cutaneous melanoma (CM) and therefore there is still an unmet need for improved treatment regimens for these histological subtypes. [3][4][5] Of particular interest are Melanomas arising from the ocular region, with uveal melanoma (UM) being the most common subtype of ocular Melanoma. ...
... 6 Despite the fact that UM is the most common subtype of ocular Melanoma, it is still a rare disease with an incidence of 1.3-8.6 cases per million per year. 2 The main risk factors for UM include older age, fair skin, light eye color and inability to tan. 7 While UM can sometimes arise in the iris or ciliary body, the vast majority (90%) of cases arise from the choroid region. 2 It has been previously established that this anatomic location is associated with a higher risk to metastasize leading to a poorer prognosis. 8,9 Choice of local therapy for early stage disease is dependent on tumor location, extent, size and visual acuity. ...
... 6 Despite the fact that UM is the most common subtype of ocular Melanoma, it is still a rare disease with an incidence of 1.3-8.6 cases per million per year. 2 The main risk factors for UM include older age, fair skin, light eye color and inability to tan. 7 While UM can sometimes arise in the iris or ciliary body, the vast majority (90%) of cases arise from the choroid region. 2 It has been previously established that this anatomic location is associated with a higher risk to metastasize leading to a poorer prognosis. 8,9 Choice of local therapy for early stage disease is dependent on tumor location, extent, size and visual acuity. ...
Introduction
Uveal melanoma (UM) is a subtype of melanoma arising from the ocular region. Despite various local therapies available, a significant portion of patients develop distant metastases, primarily to the liver. While cutaneous melanoma is very sensitive to immunotherapy, UM is known to be less responsive and patients were excluded from pivotal clinical trials. To date, there is no standard first line therapy for metastatic UM and clinical trial participation is encouraged. While UM is considered a radio-resistant tumor, there is a role for radiotherapy (RT) as palliative treatment and possibly for immune sensitization. This a retrospective analysis aimed at addressing the role of combination checkpoint inhibitors (ICI) with RT as a synergistic treatment in metastatic UM patient. We hypothesized that concurrent RT would improve the clinical response to immunotherapy.
Methods
Retrospective chart review of patients with metastatic UM treated with ICI at Ella Lemelbaum Institute between 2015 and 2021. Patients’ electronic medical records were analyzed for baseline characteristics, response rate and survival data. Patients were grouped according to receipt of concomitant RT. Study was approved by local IRB and statistical analyses done using Stata V.17
Results
Thirty-nine patients were treated with immunotherapy. Fifty percent were treated with anti-programmed cell death (PD)-1 and 50% with anti-PD1– anti CTLA4 combination therapy. Nine patients were treated concomitantly with immunotherapy and external beam RT or with stereotactic body RT (group A) and 29 patients were treated with immunotherapy alone (group B). Overall response rate was significantly higher in group A (44% versus 10%, p = 0.004). Median progression-free survival was longer for patients in group A (22 months versus 3 m, Hazard Ratio (HR) = 0.37, p = 0.036). Median overall survival was also longer for group A (26 months versus 7.5 m, HR = 0.34, p = 0.03). Toxicity was comparable between the groups.
Conclusions
RT may improve response to immunotherapy with ICI in metastatic UM patients and may confer an advantage in survival. Further prospective, larger studies are warranted.
... 5 6 The 5-year survival rate for patients with metastatic MM is only 16%. 6 The therapeutic efficacy of programmed death 1 (PD-1) monoclonal antibodies for patients with malignant MM was limited. A post-hoc analysis of the KEYNOTE-001, 002, 006 trials indicated that patients with MM treated with pembrolizumab had an objective response rate (ORR) of 19%, median progression-free survival (PFS) of 2.8 months, and median overall survival (OS) of 11.3 months. ...
Background
Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.
Methods
We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).
Results
Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.
Conclusion
Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.
Trial registration number
Chinese Clinical Trial Registry, ChiCTR1900023277.
... (1,2) Melanomas commonly occur during the sixth decade of life, with an increasing incidence as age progresses. (3,4) The differential diagnosis includes numerous conditions of retinal origin, retinal pigment epithelial origin, and choroidal origin. Atypical presentations of the tumour have been reported to occur. ...
Pseudomelanoma may refer to lesions that clinically simulate choroidal or ciliary body melanoma. These include certain benign and malignant conditions of retinal and choroidal origin like hamartomas of the sensory retina, hyperplasia of the retinal pigmentary epithelium (RPE), melanocytomas, hemorrhagic retinal detachment and melanocytic nevi, making the diagnosis of a choroidal melanoma a formidable task. If not taken care of, this diagnostic conundrum may lead to radical procedures such as enucleation. We report a case of a 70-year-old male who was clinically diagnosed with choroidal melanoma based on characteristic appearance with radiological evaluation and underwent an enucleation procedure. However, the subsequent histopathological examination of the enucleated eye revealed a hemorrhagic choroidal and retinal detachment with vitreous haemorrhage.
... Even though the National Comprehensive Cancer Network (NCCN) guideline recommends treatment of the nodal basin only in the patients with significant clinical and imaging findings, a 5-year survival of node positive patients was less than 20% while node negative patients were 40% [21]. The result shows the potential significance of performing sentinel lymph node biopsy in patients who were treated for a mucosal melanoma [22]. ...
Background: Primary mucosal melanoma of the larynx is an extremely rare entity. Our case represents the seventeenth case reported to date globally, and the first Canadian case to be reported. Case presentation: We present the case of a 70-year-old male who was referred for hoarseness and found to have a T3N0M0 glottic mucosal melanoma involving the left true vocal cord. The laryngeal tumour was resected via a transoral laser microsurgery approach with a CO2 laser, wherein an extended partial laryngectomy with negative margins was achieved. There were no regional or distant metastases. Mucosal melanoma is a rare, but an aggressive malignancy as it is generally discovered at an advanced stage. Herein we present our diagnostic, treatment, and post-operative follow-up approaches. Conclusion: Owing to the rarity of mucosal melanoma, especially of the larynx, we believe additional reported cases to the literature will contribute to better understanding of this malignancy and improve treatment strategies.
... The 5-year overall survival rate for MM is about 25% with a significantly poorer survival compared to other subtypes of melanoma (4). This may be related to a more advanced disease at diagnosis and the challenges of achieving definitive local control at presentation due to anatomic constraints. ...
Background
Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.
Method
Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities.
Results
We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients.
Conclusion
Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.
... Metastasis from unknown primary sites constitutes around 2% of melanoma. 3 Among the mucosal melanoma of the gastrointestinal (GI) tract, the most common sites are the anorectum, oropharynx and oesophagus. 4 Primary gastric melanoma (PGM) is a rare entity and is usually a diagnosis of exclusion. ...
Primary gastric melanoma is a rare clinical finding. It presents with upper gastrointestinal symptoms like abdominal pain, weight loss and melaena. It is often difficult to differentiate a primary gastric melanoma from primary cutaneous melanoma with gastric metastasis. Upper gastrointestinal endoscopy and biopsy of the lesion for histopathology and immunohistochemistry help to reach a definite diagnosis. We report a case of primary gastric melanoma with metastases to the liver and bone. The patient was treated with palliative radiotherapy, palliative chemotherapy and a bone-stabilising agent.
Immune checkpoint inhibitor therapy can provide significant clinical benefit in patients with certain cancer types including melanoma; however, objective responses are only observed for a subset of patients. Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and, compared with cutaneous melanoma, is significantly less responsive to immune checkpoint inhibitors. Spontaneous canine tumours have emerged as valuable models to inform human cancer studies. In contrast to human melanoma, most canine melanomas are mucosal—an incidence that may be leveraged to better understand the subtype in humans. However, a more comprehensive understanding of the immune landscape of the canine disease is required. Here, we quantify tumour infiltrative T and myeloid cells in canine mucosal ( n = 13) and cutaneous ( n = 5) melanomas using immunohistochemical analysis of CD3 and MAC387 expression, respectively. Gene expression analysis using the Canine IO NanoString panel was also performed to identify genes and pathways associated with immune cell infiltration. T and myeloid cell densities were variable with geometric means of 158.7 cells/mm ² and 166.7 cells/mm ² , respectively. Elevated T cell infiltration was associated with increased expression of cytolytic genes as well as genes encoding the coinhibitory checkpoint molecules PD‐1, CTLA‐4, TIM‐3 and TIGIT; whereas increased myeloid cell infiltration was associated with elevated expression of protumourigenic cytokines. These data provide a basic characterization of the tumour microenvironment of canine malignant melanoma and suggest that, like human melanoma, inherent variability in anti‐tumour T cell responses exists and that a subset of canine melanomas may respond better to immunomodulation.
Introdução: Embora seja causa importante de óbitos por neoplasia no Brasil, o perfil de sobrevida dos pacientes com melanoma cutâneo primário em locais considerados de baixa incidência necessita de descrição mais recente. Objetivo: Descrever o perfil de sobrevida do paciente com melanoma cutâneo primário na cidade de Goiânia entre os anos de 2003 e 2016. Método: Estudo de base populacional realizado com dados do Registro de Câncer de Base Populacional de Goiânia (RCBP-GO). Foram incluídos casos novos de melanoma cutâneo diagnosticados no período. Os dados foram coletados e analisados segundo sexo, faixa etária, cor da pele, profissão, CID-10, data do diagnóstico, status vital, localização da lesão primária, metástase e tipo histológico. A análise estatística foi realizada com o pacote SPSS. A distribuição segundo o status vital foi testada pelo teste qui-quadrado. As curvas de sobrevida foram realizadas e testadas por meio do teste de log rank. O nível de significância adotado foi de 5%. Resultados: Foram registrados 653 novos casos de melanoma cutâneo em Goiânia no período. Os fatores relacionados à menor sobrevida dos pacientes foram: sexo masculino, idade igual ou superior a 60 anos, cor parda, atividades externas e metástase. Conclusão: O perfil de sobrevida encontrado reforça a necessidade de estratégias que incentivem homens de cor parda com idade superior a 60 anos a realizarem o diagnóstico precoce.
Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations. One of the promising approaches is using liquid biopsies, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), for detecting and monitoring the disease at the early stages. These non-invasive methods can help us identify the most effective treatment strategies for each patient. Single-cellular is a brand-new analysis platform that gives treasured insights into diagnosis, prognosis, and remedy. The incorporation of this data with known clinical and genomics information will give a better understanding of the complicated molecular mechanisms that UM diseases exploit. In this review, we focused on the heterogeneity and molecular panorama of UM, and to achieve this goal, the authors conducted an exhaustive literature evaluation spanning 1998 to 2023, using keywords like "uveal melanoma, “heterogeneity”. “Targeted therapies”," "CTCs," and "single-cellular analysis".
Background
Full-body skin examination (FSE) is fundamental to the diagnosis of cutaneous malignancy but may not always include concealed site examination (CSE).
Objectives
To determine the approach of international dermatologists to CSE during FSE and examine influencing factors, barriers and attitudes toward CSE.
Methods
Members of the International Dermoscopy Society were surveyed using an online 12-question survey disseminated via email.
Results
There were 706 completed responses among 1249 unique clicks to the survey, representing a completion rate of 56.5%. Fifty-four percent of respondents reported always examining the breasts, while 52.8%, 18.8%, and 11.8% always examined the scalp, oral, and anogenital mucosa, respectively. The most frequent reason for examining concealed sites was patient concern, whilst common reasons for not examining concealed sites included low incidence of pathology and concern regarding allegations of sexual misconduct.
Conclusions
Our findings allude to the need for international consensus guidelines regarding the conduct and inclusion of concealed or sensitive sites in routine FSE. This is essential to define clinician responsibilities, inform patient expectations of care, and thereby mitigate potential medicolegal repercussions.
The vulva can be involved as apart of more generalised dermatological disease but there are specific disorders that affect the genital skin. This chapter discusses the dermatoses, infections, premalignant and malignant disease and pain that affect the female genital skin.
b> Introduction: Malignant melanoma most commonly occurs in the skin. Primary malignant melanoma of endometrium is quite rare. Its diagnosis depends on clinical characteristics and pathological examination. It usually exhibits high degree of tumor histology, early onset of distant metastases, and unfavorable prognoses. Case Presentation: In this paper, we report a case of a 73-year-old woman with primary malignant melanoma of endometrium. This patient denied a history of nevus removal or any family medical history of cancer. She was admitted to the hospital for irregular vaginal bleeding after menopause and performed an endometrial biopsy. Pathological of the scrapings suggested malignant melanoma. She subsequently underwent a radical surgery. The final pathology diagnosis was primary malignant melanoma of endometrium, and BRAF gene mutation was detected. The tumor staged as IVB according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Thus, she then started adjuvant chemotherapy. This patient is currently on oral targeted therapy and is still being followed up. Conclusion: Mucosal melanoma is infrequent, and primary malignant melanoma of endometrial is a rare subtype. To the best of our knowledge, malignant melanoma originating from endometrium has never been reported before. It has a high degree of malignancy and is prone to early metastasis. Further investigations are warranted to explore its underlying pathogenesis, management, and outcomes.
Purpose
In a population‐based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies.
Method
A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies.
Results
After more than 20 years of follow‐up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different.
Conclusion
Patients with UM may be diagnosed with non‐ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow‐up of the UM patients seems necessary. The UM is not always the main problem.
Cancer is one of the major public health challenges in China. Rare cancers collectively account for a considerable proportion of all malignancies. The lack of awareness of rare cancers among healthcare professionals and the general public, the typically complex and delayed diagnosis, and limited access to clinical trials are key challenges. Recent years have witnessed an increase in funding for research related to rare cancers in China. In this review, we provide a comprehensive overview of rare cancers and summarize the status of research on rare cancers in China and overseas, including the trends of funding and publications. We also highlight the challenges and perspectives regarding rare cancers in China.
Anorectal melanoma (ARM) is an exceedingly rare and very aggressive malignancy. It originates from the melanocytic cells in the anorectal mucosa, which produces melanin. Other mucosal melanomas commonly found in the mucosa of the oral cavity, vulvovaginal, pharynx and urinary tract. Patients usually present with bleeding per rectum, perianal pain and difficulty in defaecation. Distinction of primary anorectal melanoma from other tumours of this region is difficult because of the lack of common imaging features. MRI is the modality of choice for its better tissue characterisation and resolution. There is no standard treatment protocol available mainly due to scarcity of data. Surgery is the mainstay therapy. Herein we present a case of a male patient in his 30s who presented with rectal bleeding and perianal pain. Haematological analysis revealed normocytic normochromic anaemia. MRI detected a mass lesion in the anorectal region. Contrast enhanced CT revealed multiple metastases in the liver, lungs, periportal, mesorectal and inguinal lymph nodes. The diagnosis of the ulcerated anorectal melanoma was established on histopathological examination. The patient underwent abdominoperineal resection (APR) followed by chemotherapy. Afterward the patient presented to the emergency room with respiratory distress for which he was on ventilator support. Sadly, the patient died after four days.
Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation. Other immunotherapy strategies, such as oncolytic virotherapy for injectable cutaneous melanoma and bispecific T-cell engager therapy for HLA-A*02:01 genotype-positive uveal melanoma, are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous melanoma, traditional immunotherapy biomarkers (ie, programmed death-ligand 1 expression, tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using immunotherapy to treat melanoma, with topics including therapy selection in the advanced and perioperative settings, intratumoral immunotherapy, when to use immunotherapy for patients with BRAF V600-mutated disease, management of patients with brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.
Objective
This study aimed to construct prognostic models to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary gastrointestinal melanoma (PGIM).
Design
An observational and retrospective study.
Setting
Data were obtained from the Surveillance, Epidemiology and End Results (SEER) programme database, encompassing a broad geographical and demographic spectrum of patients across the USA.
Participants
A total of 991 patients diagnosed with PGIM were included in this study.
Methods
A total of 991 patients with PGIM were selected from the SEER database. They were further divided into a training cohort and a validation cohort. Independent prognostic factors were identified by Cox regression analysis. Two prognostic models were constructed based on the results of multivariable Cox regression analysis. The concordance index (C-index) and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the discriminative ability. Calibration curves were plotted to evaluate the agreement between the probability as predicted by the models and the actual probability. Risk stratification was developed given the model.
Results
By the multivariable Cox regression analysis, we identified four independent risk factors (age, stage, lymph node density and surgery) for OS, and three independent risk factors (stage, lymph node density and surgery) for CSS, which were used to construct prognostic models. C-index, time-dependent AUC, calibration curves and Kaplan-Meier curves of risk stratification indicated that these two models had good discriminative ability, predictive ability as well as clinical value.
Conclusions
The prognostic models of OS and CSS had satisfactory accuracy and were of clinical value in evaluating the prognosis of patients with PGIM.
The budding yeast, Saccharomyces cerevisiae , has been used for decades as a powerful genetic tool to study a broad spectrum of biological topics. With its ease of use, economic utility, well‐studied genome, and a highly conserved proteome across eukaryotes, it has become one of the most used model organisms. Due to these advantages, it has been used to study an array of complex human diseases. From broad, complex pathological conditions such as aging and neurodegenerative disease to newer uses such as SARS‐CoV‐2, yeast continues to offer new insights into how cellular processes are affected by disease and how affected pathways might be targeted in therapeutic settings. At the same time, the roles of RNA and RNA‐based processes have become increasingly prominent in the pathology of many of these same human diseases, and yeast has been utilized to investigate these mechanisms, from aberrant RNA‐binding proteins in amyotrophic lateral sclerosis to translation regulation in cancer. Here we review some of the important insights that yeast models have yielded into the molecular pathology of complex, RNA‐based human diseases.
This article is categorized under: RNA in Disease and Development > RNA in Disease
Mucosal melanoma is a rare subtype of melanoma distinct from the cutaneous type in its clinical and biological aspects, requiring different therapeutical management. Anorectal melanomas represent less than 1% of anorectal cancers and 0.3% of malignant melanomas, and they are by far the most studied type. Proctologic examination, colonoscopy, and biopsy can establish a correct diagnosis. Imaging techniques, especially MRI can show some characteristic features, but it is essentially performed for extension assessment. We report the case of a 63-year-old man who consulted for rectal bleeding. The proctological examination found a brownish ulcerative-vegetating tumor of 3 cm in diameter located 3 cm from the anal rim. The endoscopic examination revealed a predominance of ulcerative budding lesions and the biopsy specimen confirmed a rectal melanoma. The extension assessment, based on a computed tomography scan and MRI did not show locoregional or distant metastases. Radiotherapy and abdominoperineal resection with pelvic node dissection was the treatment of choice with good evolution.
Background:
Around 1.2 to 3.1% of thyroid malignancies are due to metastasis. Among them, cutaneous malignant melanomas constitute 4% of malignancy metastasized to the thyroid. Uveal melanoma is uncommon, and its metastasis to the thyroid has only rarely been reported. Hereby, we describe an unusual case of uveal melanoma metastasized to the thyroid and discuss the concept of correct diagnosis. Case Report. During a routine ophthalmological examination, an 86-year-old Caucasian female was found to have retinal detachment secondary to choroidal melanoma. She was treated with gamma knife which resulted in reduction of tumor size. Three months later, she was noted to have a goiter on physical examination. Follow-up thyroid ultrasonography demonstrated numerous vascularized nodules in both lobes. The fine needle aspiration (FNA) of the left dominant nodule was indeterminate the first time and nondiagnostic the second time. FNA of the right dominant nodule was nondiagnostic twice but showed malignant cells the third time. Subsequent immunohistochemistry staining of the FNA sample from the right thyroid nodule confirmed a profile consistent with malignant melanoma.
Conclusion:
It should be kept in mind that a thyroid nodule detected in a patient with a diagnosis of uveal melanoma can be metastasis and that uveal melanoma diagnosis should be taken into account for the examination of the thyroid tumors of these patients. It is important to employ immunohistochemical staining FNA examination of the patient with such tumors for markers associated with a patient's known malignancy to facilitate diagnosis.
In brachytherapy (BT), or internal radiation therapy, cancer is treated by radioactive implants. For instance, episcleral plaques (EPs) for the treatment of uveal melanoma, are designed according to generic population approximations. However, more personalized implants can enhance treatment precision through better adjustment of dose profiles to the contours of cancerous tissues. An original approach integrating biomedical imaging, 3D printing, radioactivity painting, and biomedical imaging, is developed as a workflow for the development of tumor shape‐specific BT implants. First, computer‐aided design plans of EP are prepared according to guidelines prescribed by the Collaborative Ocular Melanoma Study protocol. Polyetheretherketone (PEEK), a high‐performance polymer suitable for permanent implants, is used to 3D‐print plaques and the geometrical accuracy of the printed design is evaluated by imaging. The possibility to modulate the dose distribution in a tridimensional manner is demonstrated by painting the inner surfaces of the EPs with radioactive 103Pd, followed by dose profile measurements. The possibility to modulate dose distributions generated by these 3D‐printed plaques through radioactivity painting is therefore confirmed. Ex vivo surgical tests on human eyeballs are performed as an assessment of manipulation ease. Overall, this work provides a solution for the fabrication of tumor‐specific radioactive implants requiring higher dose precision.
Background
Carbon‐ion radiotherapy (C‐ion RT) is effective for head and neck mucosal melanoma (HN‐MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN‐MM are insufficient.
Aims
To analyze the efficacy and safety of ICI salvage therapy in patients with HN‐MM recurrence after C‐ion RT.
Methods and Results
This retrospective study analyzed the medical records of 52 patients with HN‐MM treated with C‐ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3‐year overall survival (OS) rate. The median follow‐up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3‐year OS rate in the ICI group (n = 16) and best supportive care group (n = 13) were 53.8% and 0.0%, respectively (p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C‐ion RT were related to or exacerbated by ICI.
Conclusion
ICI salvage therapy is effective and safe for patients with HN‐MM recurrence after C‐ion RT.
We present a case of malignant melanoma in the middle ear in a 63-year-old woman who presented with severe pain on the right side of her face and head, tinnitus, photophobia, and hemorrhagic discharge from the right ear, as well as right facial nerve paralysis. After more than two years of conservative treatment for otitis media and sclerotic mastoiditis, a pathologically enlarged lymph node on the right side of the neck appears. It is removed, and the histopathological examination reveals that it is metastatic malignant melanoma. Imaging examinations reveal a tumoral lesion in the middle ear with bone infiltration. The right middle ear is operated on, and the tissue sent for testing reveals melanoma. The patient was treated with Nivolumab after the operation and is now in sustainably good condition.
Purpose:
The purpose of this study is to explore the frequency of additional primary malignancies in uveal melanoma (UM) patients and cause-specific mortality, to help guide surveillance strategies after UM.
Methods:
All patients diagnosed with UM at Oslo University Hospital during 1990-2017 were eligible for inclusion. Linkage to the Cancer Registry of Norway obtained information on additional malignancies and cause of death throughout 2019. UM patients were categorized according to timing of additional malignancy (prior/simultaneously or after UM) or no additional cancer, and by UM stage at diagnosis. Age-adjusted mortality rates were presented per 1000 person-years with 95% confidence intervals (CI).
Results:
The study population included 960 UM patients: 77% were diagnosed in stage and I/II and 56% were men. Mean age at diagnosis was 63 years. Additional malignancies were observed in 152 patients prior/simultaneous to UM, and in 120 patients >1 year after UM. Overall, mortality per 1000 person-years was 3.5 (95% CI 3.1-3.9) for UM and 3.0 (2.6-3.4) for other causes. Lowest UM mortality [1.3 (0.60-2.1)] was seen in patients with a second malignancy after UM, regardless of stage. Highest UM mortality was seen for UM patients in stage III/IV, both without [16.1 (13.2-19.1)] and with any additional malignancy [16.9 (6.6-27.3)].
Conclusion:
Our results support that UM patients frequently have additional malignancies, both before and after UM. Low-UM mortality in patients with a primary malignancy after UM, might indicate less aggressive UM. The cumulative UM mortality flattens about 10 years after diagnosis and annual follow-up of patients for 10 years seems adequate.
Neck swelling due to lymph node (LN) metastasis is one of the initial symptoms of head and neck cancer, and in some cases, the primary tumor is not clinically evident. The purpose of imaging for LN metastasis from an unknown primary site is to identify the primary tumor or detect its absence, which leads to the correct diagnosis and optimal treatment. The authors discuss diagnostic imaging approaches for identifying the primary tumor in cases of unknown primary cervical LN metastases. The distribution and characteristics of LN metastases may help locate the primary site. Unknown primary LN metastasis often occurs at nodal levels II and III, and in recent reports, these were mostly related to human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx. Another characteristic imaging finding suggestive of metastasis from HPV-associated oropharyngeal cancer is a cystic change in LN metastases. Other characteristic imaging findings such as calcification may help predict the histologic type and locate the primary site. In cases of LN metastases at nodal levels IV and VB, a primary lesion located outside the head and neck region must also be considered. One clue for detecting the primary lesion at imaging is the disruption of anatomic structures, which can help in identifying small mucosal lesions or submucosal tumors at each subsite. Additionally, fluorine 18 fluorodeoxyglucose PET/CT may help identify a primary tumor. These imaging approaches for identifying primary tumors enable prompt identification of the primary site and assist clinicians in making the correct diagnosis. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.
Primary spinal cord melanoma (PSCM) and primary pleural melanoma (PPM) are extremely rare entities with scarce cases reported in the literature. We present a case of a 54-year-old male diagnosed with possible primary pleural melanoma and primary spinal melanoma, managed with partial surgical resection, postoperative radiotherapy, and chemotherapy consisting of Ipilimumab, nivolumab, and temozolomide. This leads to decreased symptoms and improved quality of life of the patient. In this case report, we review the literature on PSCM and PPM in detail, addressing the pertinent clinical aspects as well as current and upcoming therapeutic options.
Uveal melanoma (UM) is a rare type of melanoma with distinct features from cutaneous melanoma, low response rates to immune checkpoint inhibition, and poor survival rates. Tebentafusp, a bispecific antibody engaging T cells with gp 100 on HLA-A*02:01, was recently approved by the FDA as the first drug of its class and the first treatment approved by the FDA to treat UM. In this review, we summarize the preclinical and clinical data on tebentafusp for UM. We additionally discuss patient selection and the relevant challenges. For the literature search, PubMed search and relevant articles presented at international conferences were used.
Objective:
To evaluate differences in treatment outcomes for head and neck mucosal melanoma (HNMM) patients seen at academic versus nonacademic centers and high versus low volume facilities.
Study design:
Retrospective cohort study.
Setting:
National Cancer Database.
Methods:
Differences in treatment course and overall survival (OS) by facility type and volume were assessed for 2772 HNMM cases reported by the 2004 to 2017 National Cancer Database. A subgroup analysis was performed with a smaller cohort containing staging data. The analysis employed Kaplan-Meier and Cox proportional hazards models.
Results:
A higher proportion of patients treated at academic centers within the HNMM cohort waited longer for surgery after diagnosis (p < .001), had negative surgical margins (p < .001), and were readmitted to the hospital within 30 days of surgery (p = .001); these relationships remained significant when controlling for cancer stage. Kaplan-Meier analysis demonstrated higher 5-year OS for patients treated at academic versus nonacademic facilities within the main cohort (32.5% ± 1.3% vs 27.3% ± 1.5%; p = .006) and within the stage-controlled subgroup (34.8% ± 2.1% vs 27.2% ± 2.6%; p = .003). Treatment at high volume versus low volume facilities was associated with improved 5-year OS for main cohort patients (33.5% ± 1.7% vs 28.8% ± 1.2%; p = .016) but not for subgroup patients (35.3% ± 2.7% vs 30.1% ± 2.1%; p = .100). Upon multivariate analysis controlling for demographic and oncologic factors, there was no significant difference in OS by facility type (main cohort: odds ratio [OR] = 1.07, 95% confidence interval [CI] = 1.01-1.21; subgroup: OR = 1.13, 95% CI = 0.97-1.32).
Conclusion:
Neither facility type nor surgical volume predicts overall survival in HNMM.
Background:
Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe) squamous carcinoma (SCC) is now well established but melanoma (MM) has only rarely been reported complicating GLSc.
Methods:
We have performed a systematic literature review of GLSc in patients with genital melanoma (GMM). Only articles that mentioned both GMM and LSc affecting either the penis or vulva were included.
Results:
Twelve studies with a total of 20 patients were included. Our review shows that an association of GLSc with GMM has been more frequently reported in women and female children than men viz, 17 cases compared with three. It is notable that five of the cases (27.8%) concerned female children aged under twelve.
Discussion:
These data suggest a rare association between GLSc and GMM. If proven, there arise intriguing questions about pathogenesis and consequences for counselling of patients and follow-up.
Acral melanoma (AM) and mucosal melanomas (MM) are rare clinical subtypes of melanoma. AM and MM are etiologically, biologically, and molecularly distinct from cutaneous melanoma (CM). Despite the recent development of immune checkpoint inhibitors (ICIs) for the treatment of advanced CMs, the true therapeutic efficacy of ICIs for these rare subtypes remains unclear. Since these subtypes are rare, especially in the Caucasian population, their biological features and corresponding novel therapies are underexplored than those of CM. Even in the larger phase III clinical trials for ICIs, the sample size of patients with AM and MM is limited. Consequently, establishment of standard of care for advanced AM and MM has been challenging. This review covers current update and overview on clinical efficacy of ICIs and ICI‐based therapy for advanced AM and MM, based mainly on the reported clinical trials, prospective observational studies, and retrospective studies, to provide a better understanding of the current landscape of this field. In addition, we discuss the future direction of treatment for those rare clinical subtypes, focusing on issues relevant to dermatology and medical oncology.
Melanoma is the most aggressive type of skin cancer, with few effective treatments. Indocyanine green nanoemulsion for photothermal therapy was first time investigated and showed significant reduction of the pigmented tumors.
Silverberg's Principles and Practice of Surgical Pathology and Cytopathology is one of the most durable reference texts in pathology. Thoroughly revised and updated, this state-of-the-art new edition encompasses the entire fields of surgical pathology and cytopathology in a single source. Its practice-oriented format uniquely integrates these disciplines to present all the relevant features of a particular lesion, side by side. Over 4000 color images depict clinical features, morphological attributes, histochemical and immunohistochemical findings, and molecular characteristics of all lesions included. This edition features new highly experienced and academically accomplished editors, while chapters are written by the leading experts in the field (several new to this edition, bringing a fresh approach). Dr Steven Silverberg's practical approach to problem solving has been carefully preserved. The print book is packaged with access to a secure, electronic copy of the book, providing quick and easy access to its wealth of text and images.
Cutaneous melanoma is a relatively common neoplasm, with fairly well understood pathogenesis, risk factors, prognosis and therapeutic protocols. The incidence of this disease is increasing every year. The situation is different for rare malignancies such as vulvar melanomas and for the even rarer vaginal melanomas. The risk factors for vulvovaginal tumors are not fully understood. The basis of treatment in both cases is surgical resection; however, other types of treatments such as immunotherapy are available. This paper focuses on comparing the pathogenesis and risk factors associated with these neoplasms as well as the efficacy of two groups of drugs—anti-PD-L1 and anti-CTLA4 inhibitors—against both cutaneous melanoma and melanoma of the lower genital tract (vulva and vagina). In the case of cutaneous melanoma, the situation looks more optimistic than for vulvovaginal melanoma, which has a much worse prognosis and, as it turns out, shows a poorer response to immune therapy.
Orbital masses include a broad spectrum of benign and malignant entities. Often these masses are asymptomatic or show a slow growth rate, so that emergence of clinical symptoms is prolonged. In this context, cross-sectional imaging plays an elementary role in the characterization of these lesions. Aside from the characterization of the underlying entity, an evaluation of the involved compartments is possible by sufficient imaging, which also facilitates optimal treatment and surgery planning. The purpose of this review is to explore different benign and malignant orbital tumors and their typical appearance in imaging together with histopathologic findings.
Melanoma is a tumor arising from uncontrolled proliferation of melanocytes, neural crest derived cells responsible for production of pigment in the basal layer of the epidermis. While the prevalence of melanoma is greatest in fair-skinned populations, racial and ethnic minority populations disproportionately experience lower rates of survival when diagnosed with melanoma. Recent studies indicate that, among minority populations, melanoma tends to present at a more advanced stage with more aggressive melanoma subtypes, increased and atypical distributions over the body, and increased tumor depths. Populations of color are also shown to carry unique mutations in BRCA genes that may predispose them to developing melanoma and account for increased mortality rates. Socioeconomic status has also been linked to melanoma disparities, where limited access to quality healthcare including skin exams, insurance, and education may result in decreased melanoma survival rates. The aim of this article is to review the relationship between melanoma and underserved communities as well as discuss the current explanations behind these observations.
Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5–1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract—primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T‐cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.
This all‐case postmarketing surveillance (PMS) survey (101 centers; February 15, 2017, to March 3, 2020) captured factors that impact the safety and effectiveness of newly initiated pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan. Eligible patients were enrolled both retrospectively and prospectively, and followed up at 1, 3, 6, and 12 months. Safety assessments included treatment‐related adverse events (TRAEs), adverse events of special interest (AEOSIs) from the Japanese Risk Management Plan (J‐AEOSIs), and J‐AEOSIs related to pembrolizumab. Effectiveness assessments included objective response rate (ORR; complete response/partial response) and disease control rate (DCR) according to the RECIST criteria. Overall, 294 and 236 patients comprised the safety and effectiveness (RECIST) assessment sets, respectively. Median (range) age of the patients was 70 (22–94) years, and the majority (60.4%) received pembrolizumab as first‐line therapy. The most common type of melanoma was cutaneous (41.5%), followed by mucosal (29.3%), acral (24.8%), and unknown (4.4%). Overall, 45.2% and 24.8% of patients experienced TRAEs and AEOSIs, respectively. In total, 24.8% and 9.2% of patients experienced any‐grade and grade ≥3 pembrolizumab‐related AEOSIs, respectively. The most common grade ≥3 pembrolizumab‐related AEOSIs were endocrine disorders and liver dysfunction (2.4% each), followed by colitis/severe diarrhea (2.0%), interstitial lung disease (1%), and type 1 diabetes (0.7%). No grade 5 J‐AEOSIs were observed. ORR was 16.5% at the 1‐year follow‐up: mucosal melanoma (20%), acral melanoma (10%), and cutaneous melanoma (17.5%). ORR was higher among patients who did not receive versus those who did receive previous systemic therapy across all three melanoma types. DCR was 52.1% at the 1‐year follow‐up: cutaneous melanoma (57.3%), acral melanoma (51.7%), and mucosal melanoma (43.1%). This all‐case PMS survey confirmed the real‐world safety and effectiveness of pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan.
Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients’ chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.
Background
Acral and mucosal melanomas are aggressive subtypes of melanoma, which have a significantly lower burden of somatic mutations than cutaneous melanomas, but more frequent copy number variations, focused gene amplifications, and structural alterations. The landscapes of their genomic alterations remain to be fully characterized.
Methods
We compiled sequencing data of 240 human acral and mucosal melanoma samples from 11 previously published studies and applied a uniform pipeline to call tumor cell content, ploidy, somatic and germline mutations, as well as CNVs, LOH, and SVs. We identified genes that are significantly mutated or recurrently affected by CNVs and implicated in oncogenesis. We further examined the difference in the frequency of recurrent pathogenic alterations between the two melanoma subtypes, correlation between pathogenic alterations, and their association with clinical features.
Results
We nominated PTPRJ , mutated and homozygously deleted in 3.8% (9/240) and 0.8% (2/240) of samples, respectively, as a probable tumor suppressor gene, and FER and SKP2 , amplified in 3.8% and 11.7% of samples, respectively, as probable oncogenes. We further identified a long tail of infrequent pathogenic alterations, involving genes such as CIC and LZTR1 . Pathogenic germline mutations were observed on MITF , PTEN , ATM , and PRKN . We found BRAF V600E mutations in acral melanomas with fewer structural variations, suggesting that they are distinct and related to cutaneous melanomas. Amplifications of PAK1 and GAB2 were more commonly observed in acral melanomas, whereas SF3B1 R625 codon mutations were unique to mucosal melanomas (12.9%). Amplifications at 11q13-14 were frequently accompanied by fusion to a region on chromosome 6q12, revealing a recurrent novel structural rearrangement whose role remains to be elucidated.
Conclusions
Our meta-analysis expands the catalog of driver mutations in acral and mucosal melanomas, sheds new light on their pathogenesis and broadens the catalog of therapeutic targets for these difficult-to-treat cancers.
Objectives:
Mucosal melanoma (MM) is a rare malignancy that can present in the head and neck (H&N). The Oral cavity is the second most common primary site in the H&N after sinonasal mucosa. This study investigates the impact of demographic and clinical factors on survival in oral cavity MM. Further, it investigates the outcomes and utility of elective neck dissections (END) in the management of oral MM.
Methods:
The National Cancer Database was used to evaluate 432 patients with oral cavity MM from 2004 to 2016. Kaplan-Meir and Cox regression analyses were used to determine variables associated with survival.
Results:
The mean age was 64.0 ± 16.0 years. Most patients were white (85.1%) and male (60.0%). Gingiva (37.6%) and hard palate (36.1%) were the most common primary subsites in the oral cavity. Five-year overall survival was 31.0%. Age (Hazards Ratio [95% Confidence Interval], 1.03 [1.01-1.06]), N-stage (1.94 [1.10-3.42]), M-stage (10.13 [3.33-30.86]), male sex (1.79 [1.06-3.03]), and African-American race (2.63 [1.14-6.11]) were significantly associated with worse survival. 199 patients (46.9%) underwent neck dissection including 118 with lymph node yield (LNY) ≥ 18. The rate of occult nodal positivity was 45.4% for LNY ≥ 18 and 28.3% for LNY ≥ 1. ENDs were not associated with improved outcomes. However, occult lymph node involvement was associated with worse overall survival (p = 0.004).
Conclusions:
Oral cavity MM has a poor prognosis. Lymph node involvement, distant metastasis, age, race, and male sex are associated with worse outcomes. Performing an END did not improve survival. However, END may have a prognostic role and help select patients for treatment intensification.
Level of evidence:
4 Laryngoscope, 2022.
Objective:
Anorectal melanoma (AM) is a rare but aggressive tumour with limited information in the existing literature. This study aimed to assess the effect of surgical treatment for AM and predict the prognosis of affected patients.
Design:
A retrospective cohort study.
Setting:
Data of patients diagnosed with AM between 1975 and 2016 in the USA were collected from the Surveillance, Epidemiology, and End Results (SEER) database.
Participants:
This study enrolled a total of 795 patients with AM from the SEER database and the validation cohort comprised 40 patients with AM enrolled from Chinese institutes.
Primary and secondary outcome measures:
Overall survival (OS) and AM-specific survival (AM-SS).
Results:
A total of 795 patients with AM diagnosed between 1975 and 2016 were enrolled in this study. Data over the past four decades showed a trend of increase in incidence rate. A nomogram based on a multivariate Cox regression model was generated to predict AM-SS. The C-index of the nomogram was 0.74 (95% CI 0.71 to 0.77) on internal verification. In the validation cohort, the C-index of the nomogram was 0.72 (95% CI 0.68 to 0.76). The results of propensity score matching (PSM) analysis showed that patients who underwent surgical treatment achieved significant survival (OS: log-rank=17.41, p<0.001; AM-SS: log-rank=14.55, p<0.001). Patients who underwent surgery were stratified into local and extended surgery subgroups. AM-SS and OS were also compared after PSM, but the results were not significantly different between the two surgery subgroups (all p>0.05).
Conclusions:
The nomogram based on the analysis of SEER data showed good performance in predicting OS and AM-SS. Patients with AM can benefit from surgery; however, extensive surgery and appendectomy may not improve AM-SS or OS.
Background:
Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in Caucasians and remain poorly characterized in other ethnic groups, such as East-Asians/Hispanics/Africans.
Methods:
Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 was collected retrospectively from five independent institutions in the US, Australia and China. Tumor response, survival, and immune-related adverse events (irAEs) were compared by ethnicity (Caucasian versus East-Asian/Hispanic/African) across different melanoma subtypes (non-acral-cutaneous[NAC]/unknown primary[UP] and acral/mucosal/uveal).
Results:
In total 1,135 patients were included. Caucasians had significantly higher ORR (54% [95% CI 50-57%] versus 20% [95% CI 13-28%], adjusted P=2*10-12 ) and longer PFS (14.2 [95% CI 10.7-20.3] versus 5.4 months [95% CI 4.5-7.0], adjusted P=2*10-9 ) than East-Asians/Hispanics/Africans in NAC/UP subtypes. Caucasian ethnicity remained independently associated with higher ORR (OR 4.10, 95% CI 2.48-6.81, adjusted P=2*10-7 ) and longer PFS (HR 0.58, 95% CI 0.46-0.74, adjusted P=4*10-5 ) in multivariate analyses after adjustment for age, sex, primary anatomic location, M stage, baseline lactate dehydrogenase (LDH) level, mutational status, and prior systemic treatment. Whereas Caucasians and East-Asian/Hispanics/Africans shared similar ORR/PFS in acral/mucosal/uveal melanomas. Similar melanoma-subtype-specific ethnic discrepancies were observed in complete response rate and overall survival. Caucasians had higher rates of GI but lower rates of endocrine/liver/other-rare-types of irAEs. These differences in irAEs by ethnicity were not attributable to varying melanoma subtypes.
Conclusions:
Ethinic discrepancy in clinical benefit is melanoma subtype-specific, East-Asians/Hispanics/Africans with NAC/UP melanomas have poorer clinical benefits than previously recognized. Ethinic discrepancy in toxicity observed across different melanoma subtypes warrants an ethinicity-based irAE surveillance strategy. More research is needed to elucidate the molecular and immunologic determinants of these differences.
Malignant biliary obstruction generally results from primary malignancies of the pancreatic head, bile duct, gallbladder, liver, and ampulla of Vater. Metastatic lesions from other primaries to these organs or nearby lymph nodes are rarer causes of biliary obstruction. The most common primaries include renal cancer, lung cancer, gastric cancer, colorectal cancer, breast cancer, lymphoma, and melanoma. They may be difficult to differentiate from primary hepato-pancreato-biliary cancer based on imaging studies, or even on biopsy. There is also no consensus on the optimal method of treatment, including the feasibility and effectiveness of endoscopic intervention or surgery. A thorough review of the literature on pancreato-biliary metastases and malignant biliary obstruction due to metastatic non-hepato-pancreato-biliary cancer is presented. The diagnostic modality and clinical characteristics may differ significantly depending on the type of primary cancer. Different primaries also cause malignant biliary obstruction in different ways, including direct invasion, pancreatic or biliary metastasis, hilar lymph node metastasis, liver metastasis, and peritoneal carcinomatosis. Metastasectomy may hold promise for some types of pancreato-biliary metastases. This review aims to elucidate the current knowledge in this area, which has received sparse attention in the past. The aging population, advances in diagnostic imaging, and improved treatment options may lead to an increase in these rare occurrences going forward.
Objective:
To evaluate the clinicopathologic characteristics of metastatic cutaneous melanoma to the eye and identify potential distinguishing characteristics from the more common primary uveal melanoma; particularly, tumor location within the eye, cytomorphology and immunohistochemical/specific molecular genetic features.
Methods:
A retrospective observational case series using surgical enucleation and diagnostic vitrectomy cytologic specimens from seven patients with suspected intraocular melanoma, eventually diagnosed as metastatic melanoma, was conducted. Hematoxylin and eosin-stained sections of tumor and immunohistochemical (IHC) stains for BRAFV600E and Ki-67 were critically reviewed; BAP1 IHC was also evaluated in cases where additional tissue was available. Clinical imaging studies and medical records were reviewed.
Results:
The majority of patients (86%) with metastatic melanoma have primary vitreoretinal (not uveal) involvement and epithelioid, highly malignant cytomorphology (100%); many (50%) harbor BRAFV600E mutations, a finding not seen in large cohorts of primary uveal melanoma.
Conclusions:
Characteristics favoring or defining metastatic intraocular melanoma over primary uveal melanoma include high-grade epithelioid cytology, predominant involvement of the vitreous cavity and/or retina, and presence of positive immunostaining for BRAFV600E.
We report a man in his 80s who presents with epigastric abdominal pain and fatigue for 2 weeks. His medical history was significant for left toe acral melanoma (excised 6 years prior) and a lung mass, further workup for which was declined at the time by the patient. On presentation, he had iron deficiency anaemia and esophagogastroduodenoscopy revealed a gastric mass. Histopathological analysis of gastric and subsequently, pulmonary, lesions were consistent with metastatic melanoma. This case demonstrates the unique slow progression of untreated pulmonary metastasis in metastatic melanoma.
Background
Accurate forecasting of the risk of death is crucial for people living with head and neck mucosal melanoma (HNMM). We aimed to establish and validate an effective prognostic nomogram for HNMM.
Methods
Patients with HNMM who underwent surgery between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database for model construction. After eliminating invalid and missing clinical information, 288 patients were ultimately identified and randomly divided into a training cohort (199 cases) and a validation cohort (54 cases). Univariate and multivariate Cox proportional hazards regression analyses were performed in the training cohort to identify prognostic variables. Independent influencing factors were used to build the model. Through internal verification (training cohort) and external verification (validation cohort), the concordance indexes (C-indexes) and calibration curves were used to evaluate the predictive value of the nomogram.
Results
For the training cohort, five independent risk predictors, namely age, location, T stage, N stage, and surgery, were selected, and nomograms with estimated 1- and 3-year overall survival (OS) and cancer-specific survival (CSS) were established. The C-index showed that the predictive performance of the nomogram was better than that of the TNM staging system and was internally verified (through the training queue: OS: 0.764 vs 0.683, CSS: 0.783 vs 0.705) and externally verified (through the verification queue: OS: 0.808 vs 0.644, CSS: 0.823 vs 0.648). The calibration curves also showed good agreement between the prediction based on the nomogram and the observed survival rate.
Conclusion
The nomogram prediction model can more accurately predict the prognosis of HNMM patients than the traditional TNM staging system and may be beneficial for guiding clinical treatment.
The cloning of the genes encoding cancer antigens has opened new possibilities for the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies.
We used the lesional steps in tumor progression and multivariable logistic regression to develop a prognostic model for primary, clinical stage I cutaneous melanoma. This model is 89% accurate in predicting survival. Using histologic criteria, we assigned melanomas to tumor progression steps by ascertaining their particular growth phase. These phases were the in situ and invasive radial growth phase and the vertical growth phase (the focal formation of a dermal tumor nodule or dermal tumor plaque within the radial growth phase or such dermal growth without an evident radial growth phase). After a minimum follow-up of 100.6 months and a median follow-up of 150.2 months, 122 invasive radial-growth-phase tumors were found to be without metastases. Eight-year survival among the 264 patients whose tumors had entered the vertical growth phase was 71.2%. Survival prediction in these patients was enhanced by the use of a multivariable logistic regression model. Twenty-three attributes were tested for entry into this model. Six had independently predictive prognostic information: (a) mitotic rate per square millimeter, (b) tumor-infiltrating lymphocytes, (c) tumor thickness, (d) anatomic site of primary melanoma, (e) sex of the patient, and (f) histologic regression. When mitotic rate per square millimeter, tumor-infiltrating lymphocytes, primary site, sex, and histologic regression are added to a logistic regression model containing tumor thickness alone, they are independent predictors of 8-year survival (P less than .0005).
The incidence of melanoma is increasing at a rate faster than that for any other cancer in the United States and worldwide. Several factors show that this increase in incidence is real and not due to artifact. The rapid increase is not attributable to better overall counting of the cases of cancer (because the incidence of other cancers is decreasing). Furthermore, it is not due to changes in histologic criteria. Finally, the mortality rate from melanoma continues to increase at a time when survival rates are also increasing. This apparent paradox can be true only if the actual incidence is increasing at an even faster rate than the death rate. This dramatic increase in the incidence of melanoma highlights the need for improved methods of prevention, diagnosis, and treatment as melanoma becomes increasingly important as a public health issue.
PURPOSE
Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.
METHODS
A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients.
RESULTS
A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy.
CONCLUSION
IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.
THE INCIDENCE of melanoma of the skin appears to be rapidly rising. The increased incidence may be partially attributable to increased detection resulting from screening. In 1992, approximately 32000 newly diagnosed cases and 6700 deaths are expected in the United States. Melanoma tends to occur in adults in the prime of their family and professional lives. Detection and surgical treatment of the early stages of this malignancy are usually curative. In contrast, diagnosis and treatment in late stages often have dismal results.Traits associated with an increased risk of developing melanoma include multiple typical moles, atypical moles, freckling, history of severe sunburn, ease of burning, inability to tan, and light hair with blue eyes. Other factors include the presence of familial atypical mole and melanoma syndrome, disorders of DNA repair, and excessive sun exposure.Efforts to increase public awareness of melanoma and its treatment without causing unnecessary fear present a
Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1993) data are described here.
Five calls for data have yielded a total of 3,700,000 cases for the years 1985 through 1993, including 477,679 cases for 1988, and 608,593 cases for 1993, from hospital cancer registries across the U.S.
The most recent call for data for 1993 comprised 52% of the estimated new cases of cancer in the U.S. The country was comprised of 6 regions, with the Mountain and Southeast regions having the highest regional reporting of new cases of cancer (69% and 55%, respectively) and the Northeast and Pacific regions having the lowest (47% each). Approximately 96% of patients received their treatment at the reporting hospital. The 4 most common carcinomas were breast (15.7%), lung (14.6%), prostate (14.2%), and colon (7.5%) and comprised the majority of new cases. Trends in patterns of care for breast carcinoma were analyzed for possible bias in the 1988 and 1993 periods. When hospitals reporting only in 1988 or in 1993 were compared with hospitals reporting at both time points, the only differences were small differences in ethnic participation. These differences were less than 1.5% in the proportion of African Americans reported in the different time periods. There were no significant differences in the downstaging of breast carcinoma, or the role of conservative surgery or adjuvant radiation therapy.
The NCDB is a cancer management and outcomes data base for health care organizations that presently comprises 52% of the estimated new cases in the U.S. This will increase to 80% as the approved hospitals of the Commission on Cancer are required to report to the NCDB. Comparison of breast carcinoma findings at two time periods appeared similar regardless of hospital reporting set (i.e., set of hospitals reporting for one period versus both periods).
The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention including the National Center for Health Statistics (NCHS) agreed to produce together an annual "Report Card" to the nation on progress related to cancer prevention and control in the U.S.
This report provides average annual percent changes in incidence and mortality during 1973-1990 and 1990-1995, plus age-adjusted cancer incidence and death rates for whites, blacks, Asians and Pacific Islanders, and Hispanics. Information on newly diagnosed cancer cases is based on data collected by NCI, and information on cancer deaths is based on underlying causes of death as reported to NCHS.
For all sites combined, cancer incidence rates decreased on average 0.7% per year during 1990-1995 (P > 0.05), in contrast to an increasing trend in earlier years. Among the ten leading cancer incidence sites, a similar reversal in trends was apparent for the cancers of the lung, prostate, colon/rectum, urinary bladder, and leukemia; female breast cancer incidence rates increased significantly during 1973-1990 but were level during 1990-1995. Cancer death rates for all sites combined decreased on average 0.5% per year during 1990-1995 (P < 0.05) after significantly increasing 0.4% per year during 1973-1990. Death rates for the four major cancers (lung, female breast, prostate, and colon/rectum) decreased significantly during 1990-1995.
These apparent successes are encouraging and signal the need to maximize cancer control efforts in the future so that even greater in-roads in reducing the cancer burden in the population are achieved.
The American College of Surgeons performed a patient care and evaluation study of melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. Melanomas of the skin, eye, mucous membrane, metastases with unknown primary site and miscellaneous sites were included. Details concerning 5,004 patients from 681 hospitals in the study in 1981 and 6,900 patients from 844 hospitals in the study in 1987 were obtained--most melanomas were located in the skin; a decline in symptoms occurred at initial diagnosis; an increase in age at first diagnosis was reported; most melanomas were in Caucasian patients; slightly more melanomas occurred in men than women; more melanomas occurred in men on the head and neck and trunk, and more in the lower extremity in women; most tumors were not large in diameter; a significant shift was reported to lower levels of Clark's invasion, and a significant amount of unknowns existed in the Breslow's thickness of invasion. The large number of unknowns makes analysis difficult, but there seems to be some shift toward thinner levels of Breslow's in tumors in which it was known, from 1981 to 1987. Only a small proportion of patients in the current series was known to have node involvement or known distant metastases. An overall decline in diagnostic studies occurred between 1981 and 1987.
• To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.
(Arch Surg 1987;122:1380-1383)
Melanoma is an especially important malignant disease for surgeons to know about, since it can be cured with surgical treatment if diagnosed at an early stage. In the American College of Surgeons Melanoma Survey of 4,545 melanoma patients diagnosed during 1980, the typical melanoma was relatively thin (less than 1.5 millimeters), not ulcerated (except in 9 per cent) and did not invade into the reticular dermis or beyond (level IV or V). The melanomas were most commonly located on the trunk in men and on the lower extremities in women. Eighty-eight per cent of the patients had no clinical evidence of metastases to regional nodes or to distant sites at the time of initial diagnosis. Only a small proportion (1 per cent) of patients in the survey were black and in most of these patients, their melanoma were located on the feet or hands. The treatment of melanoma was surgical in 92.5 per cent of the patients, with the majority of patients undergoing a wide excision of the melanoma as the initial form of treatment. Only one-fifth of the patients underwent elective regional node dissection for suspected micrometastases, and most of these patients had a tumor thickness exceeding 1.5 millimeters or a lesion invading to the reticular dermis (level III, IV or V). While the Breslow Microstaging Method is now recognized as the most important parameter that predicts the clinical course of the patient, this parameter was reported in only 45 per cent of the patients in the survey. The natural history of melanoma is changing, since the disease is increasing in frequency and becoming more curable. Surgical treatment should be tailored to the biologic aggressiveness of each individual patient's melanoma. This can be estimated by integrating such prognostic factors as the melanoma thickness, the presence or absence of ulceration, the level of invasion, the anatomic site and the gender of the patient.
Previous Commission on Cancer Studies have examined time trends in stage of disease and treatment patterns for melanoma. Reported herein are the most current National Cancer Data Base (NCDB) data for melanoma.
Two calls for data have yielded 20,165 melanoma cases for 1985, 1988, and 1990 from hospital cancer registries across the country.
There was a marked increase in Stage 0 (in situ) tumors between 1985 and 1990. NCDB data confirm a trend for more conservative surgical excision of skin melanoma. Use of multimodality therapy was infrequent.
Survival data confirmed an excellent correlation between stage of disease and outcome. Early skin melanoma is highly curable.
To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction.
One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy).
GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance.
(1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.
Previous malignant melanoma studies regarding prognostic factors have often selected their patients from hospitals. Unfortunately, most of these studies have had small numbers of patients, consisted of short-term data sets, omitted important factors, did not optimize histopathologic classification, had too short or inadequate follow-up, and did not test their predictive models.
Our study goals were to identify independent clinical and histopathologic determinants of survival in malignant melanoma, to analyze changes in prognostic value over follow-up time, and, finally to construct a prognostic index.
A random sample from the Swedish Cancer Registry of the records of 498 (246 men and 252 women) patients defined by gender, five 5-year time periods of diagnosis from 1960 through 1984, and five anatomic sites formed the cohort on whom data were analyzed by univariate analyses. Multivariate analyses were based on data on 476 patients with complete information about all variables. All patients in the cohort had complete follow-up through December 31, 1989. Clinical information was abstracted and recorded as: date of diagnosis, stage at diagnosis, sex, age, anatomic site of primary tumor, date of death, and cause of death. Histopathologic slides were re-examined and classified with regard to histogenetic type, level of invasion, tumor thickness, ulceration, vascular invasion, regression, lymphocytic reaction, pre-existing nevus, and cell type.
All variables, except pre-existing nevus and cell type, were significant predictors of survival. In the multivariate analyses including all variables, women still had a significant, 33% lower relative hazard than men. The prognosis was poor in the youngest age group. Patients with external ear, scalp-neck, and trunk-located melanoma had increasing relative hazard when all variables were included. Regional metastases and tumor thickness remained independent prognostic factors. No significant association between histogenetic type or level of invasion persisted. Patients whose tumors showed ulceration or vascular invasion had lower relative hazard when all variables were included. Level of invasion, tumor thickness, ulceration, and vascular invasion were significantly associated with the prognosis during both short- and long-term follow-up. The patients were subgrouped according to percentage fractions of their score on the prognostic index. Survival curves for these groups of patients were well separated, thus identifying patients with a low or high risk of death from malignant melanoma.
The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site.
Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.
A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients.
A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy.
IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.
Among women, cancers of the lung and bronchus, breast, and colon and rectum are expected to account for more than half of all cancer deaths in 1998 (Fig. 2). In 1987, lung cancer surpassed breast cancer as the leading cause of cancer death in women, and it is expected to account for 25% of all cancer deaths in women in 1998. Although lung cancer mortality in men is leveling off, the mortality rate and the number of deaths from lung cancer in women are steadily increasing. Between 1990 and 1994, the lung cancer mortality rate in women increased about 1.7% per year.3 Conversely, the numbers of deaths of women from breast and colorectal cancers appear to be leveling off and may be beginning to decline. These sites account for 16% and 11%, respectively, of cancer deaths in women (Fig. 2). Between 1990 and 1994, mortality rates in women decreased about 1.8% per year for breast cancer and 1.5% per year for colorectal cancers.3
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