Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

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Late Recurrence and Second Primary Malignancy among 139 Patients with Germ Cell Tumors: Long-term Outcome of the Disease in a Single-center Experience

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyp142 ◽

2009 ◽

Vol 40 (2) ◽

pp. 157-162 ◽

Cited By ~ 3

Author(s):

S. Sato ◽

T. Tanaka ◽

A. Takahashi ◽

M. Sasai ◽

H. Kitamura ◽

...

Keyword(s):

Germ Cell Tumors ◽

Late Recurrence ◽

Second Primary ◽

Single Center ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Term Outcome ◽

Long Term Outcome ◽

Single Center Experience

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Thyroid carcinoma associated with other primary neoplasms, a single center study

Medicine and Pharmacy Reports ◽

10.15386/mpr-2346 ◽

2021 ◽

Author(s):

Katalin Gabora ◽

Ovidiu Bălăcescu ◽

Adrian Trifa ◽

Ana Maria Morariu ◽

Bogdan Pop ◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Survival Rates ◽

Braf V600e Mutation ◽

Braf V600e ◽

Second Primary ◽

Time Interval ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Primary Neoplasms

Background and aims. Thyroid carcinoma is the most frequent endocrine malignancy. It develops following a complex interaction of environmental and genetic factors. Its incidence is on the rise mostly due to the frequent diagnosis of microcarcinomas (tumor<1 cm ). In most cases, it has very good prognosis and survival rates. The incidence of a second primary malignancy in thyroid cancer patients is higher than in the general population. In this article, we focus on the role of BRAF V600E mutation in the development of other primary neoplasms associated with thyroid carcinoma. Methods. This study was conducted in the department of Nuclear Medicine and Genetics of the "Prof. Dr. Ion Chiricuță” Institute of Oncology of Cluj-Napoca. We evaluated patients with thyroid carcinoma, who were diagnosed and treated for other malignancies such as breast, colorectal, lung cancer and malignant melanoma. In addition, we tested for the BRAF V600E mutation using paraffin samples of patients. Results. We identified 17 patients that had thyroid carcinoma associated with other primary malignancies. Two of the patients included in the study had three associated primary cancers. The time interval between the diagnoses of two primary neoplasms in the same patient was 6.15 years, with a standard deviation (SD) of 5.39 years. The most common primary tumor associated with thyroid carcinoma in this study was breast cancer. We applied genetic testing for the BRAF V600E mutation in 12 patients. The BRAF V600E mutation positivity rate was 26.9% and most of the cancer associations were metachronous (occurring at least 6 months after thyroid cancer). Conclusions. The BRAF V600E mutation is an important prognostic factor in the neoplasms included in this study, but its presence is not a predictive factor for the appearance of a metachronous or synchronous associated primary neoplasm to thyroid cancer.

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Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Hormone and Metabolic Research ◽

10.1055/a-0851-3275 ◽

2019 ◽

Vol 51 (07) ◽

pp. 451-457 ◽

Cited By ~ 5

Author(s):

Lin Mei ◽

Arushi Khurana ◽

Taha Al-Juhaishi ◽

Anthony Faber ◽

Francesco Celi ◽

...

Keyword(s):

Prognostic Factors ◽

Surgical Resection ◽

Pathogenic Mutation ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Carotid Bodies ◽

Younger Age ◽

Second Primary Malignancies ◽

Distant Spread

AbstractPheochromocytoma (PCC) and paraganglioma (PGL) are rare malignancies while pathogenesis is strongly influenced by genetics. The prognostic factors of these patients remain poorly defined. We aim to study the epidemiology and survival pattern by analyzing the combination of SEER and Cancer Genome Atlas (TCGA) database. Primary outcome was overall survival (OS) and disease specific survival (DSS). Between 1973 and 2013, a total of 1014 patients with PGL or PCC were analyzed. Younger age and female were associated with better outcomes. The incidence of second primary malignancy in PGL/PCC patients was about 14.6%. This population had a significant longer DSS. Other factors, including surgical resection and origin from of aortic/carotid bodies, conferred remarkable survival advantage. In contrast, distant spread portended worse prognosis. Laterality, race, positive serum catecholamine marker did not demonstrate a significant association with OS and DSS. By analyzing TCGA database with total 184 patients were identified. Eighty out of 184 patients (43.5%) had at least one pathogenic mutation. Female had higher ratio of pathogenic mutations than male (58.7% vs. 41.3%) and NF1 mutation was associated with elderly population. SHDB mutation had higher percentage in male. Twenty-nine patients (15.8%) had 2 or more primary. ATRX was the most common oncogenic mutations in metastatic cohort. In conclusion, younger age, female sex, origin from aortic/carotid bodies, complete surgical resection, regional disease, as well as concomitant second primary malignancies were associated with better prognosis. The prognostic value of radiotherapy and oncogenomics warrants further investigation.

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Systemic Mastocytosis in United States: A Population Based Study

Blood ◽

10.1182/blood-2018-99-120192 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1830-1830

Author(s):

Amir Bista ◽

Dipesh Uprety ◽

Yazhini Vallatharasu ◽

Lubina Arjyal ◽

Subash Ghimire ◽

...

Keyword(s):

Multivariate Analysis ◽

African American ◽

General Population ◽

Systemic Mastocytosis ◽

Relative Survival ◽

Population Based ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Population Based Study

Abstract Introduction: Systemic mastocytosis (SM) is a rare hematological disorder characterized by clonal proliferation and activation of abnormal mast cells. It can vary from an indolent form to an aggressive form including progression to leukemia. There is limited data on epidemiology, clinical characteristics and outcome of this disease in population based setting. Till date, a retrospective study by Lim, Ken-Hong, et.al which included 342 patients diagnosed with systemic mastocytosis in Mayo clinic, is the largest series of patient published so far. This study reports the clinical presentation and outcome of patients with SM but there are no population based study in United States so far. We therefore conducted this population based study to determine epidemiology, survival pattern and incidence of second primary malignancy among patients with SM. Methods: We used SEER 18 database (2000-2014) to select all adult patients with age 20 or above with SM. Patient population was divided into various cohorts based on age (20-59, 60-79 and 80+ years), sex, race (Caucasians, African American and Others), area of residence (rural, urban and metropolitan) and annual household income (<$25000, $25000-<$50000 and ≥$50000). Age adjusted incidence rate was calculated using 2000 US standard population using SEER stat rate session. 5-year relative survival (RS) rate was calculated using SEER stat and compared using Z test. Cox proportional hazard model was used for multivariate analysis of factors associated with relative survival using Cansurv software. MP-SIR session in SEER stat was used to calculate the risk of second primary malignancy. Result: The incidence was found to be 0.046 per 10000 among general population. Incidence was found to be higher among Caucasians compared to African American (0.056 vs. 0.018 per 100000). Median age at diagnosis was 55 years. Of the total 425 patients, majority were Caucasians (92.5%), age <60 years (59.3%) and from metropolitan area (84.7%) but there was equal distribution among male and females. 10 year overall survival was found to be 61.5±3.1% by KM curve. 5-year RS was found to be 74.0±2.7% for the whole population. Females had significantly better survival compared to males, 5-year RS of 84.7±3.1% vs. 62.3±4.3%, P <0.0001. Survival trended to be better for Caucasians compared to African American but didn't reach clinical significance, 74.6±2.8 vs. 50±14.8, p 0.08. Patients <60 years had significant better survival compared to 60 to 79 and 80+ years ( 5-year RS of 88.6±2.4 vs. 58.4±5.2 and 16.0±11.2 respectively with P <0.0001 for both comparison). In multivariate analysis, younger age group, female sex and Caucasian race were found to be independent predictor of better 5 year relative survival with P<0.0001 compared to their counterparts. Patients with systemic mastocytosis were found to have higher risk of developing both solid organ as well as hematological malignancy within 5 years of diagnosis (as shown in table 1). After that the risk decreased and was comparable to general population. Conclusion: Our study shows that systemic mastocytosis is rare disease in general population and survival is better among specific subgroup of patients including females, younger patient and Caucasians. As the majority deaths occurred in first 5 years after diagnosis and as incidence of second primary malignancy is higher in the first 5 years, we recommend close follow up for first five years after diagnosis. Disclosures No relevant conflicts of interest to declare.

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Occurrence of second primary malignancy in medullary thyroid cancer (MTC) patients

Endocrine Abstracts ◽

10.1530/endoabs.67.o2 ◽

2019 ◽

Author(s):

George Simeakis ◽

Katerina Saltiki ◽

Evangelia Zapanti ◽

Evanthia Kassis ◽

Maria Alevizaki

Keyword(s):

Thyroid Cancer ◽

Medullary Thyroid Cancer ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Medullary Thyroid

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Prognostic Significance of Metabolic Parameters by 18F-FDG PET/CT in Thymic Epithelial Tumors

Cancers ◽

10.3390/cancers13040712 ◽

2021 ◽

Vol 13 (4) ◽

pp. 712

Author(s):

Joohee Lee ◽

Young Seok Cho ◽

Jhingook Kim ◽

Young Mog Shim ◽

Kyung-Han Lee ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Fdg Pet ◽

Univariate Analysis ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Masaoka Stage ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.

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Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01912-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Shunqiao Feng ◽

Lin Han ◽

Mei Yue ◽

Dixiao Zhong ◽

Jing Cao ◽

...

Keyword(s):

Next Generation Sequencing ◽

Langerhans Cell Histiocytosis ◽

Mutation Screening ◽

Langerhans Cell ◽

Braf V600e ◽

P Value ◽

Type I ◽

Next Generation ◽

Mutation Status ◽

Generation Sequencing

Abstract Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

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PROGNOSTIC FACTORS OF RENAL TUMOR RECURRENCE AFTER RADICAL NEPHRECTOMY

British Journal of Surgery ◽

10.1093/bjs/znab160.044 ◽

2021 ◽

Vol 108 (Supplement_3) ◽

Author(s):

G Martínez Izquierdo ◽

A R Arnaiz Pérez ◽

E Escolano Fernández ◽

M Merayo Álvarez ◽

B Carrasco Aguilera ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Radical Nephrectomy ◽

Univariate Analysis ◽

Malignant Neoplasms ◽

Histopathological Analysis ◽

Chi Square ◽

Renal Sinus ◽

Chi Square Test

Abstract INTRODUCTION Renal cell carcinoma (RCC) represents 3% of overall malignant neoplasms in adults. However, its aetiology has not been clearly established. Although surgery represents the cornerstone in treatment, recurrence postoperative rates are around 20-30%, what implies prognostic factors search must be mandatory in order to help to plan de follow-up and the different adjuvant therapy possibilities available in case they were necessary. MATERIAL AND METHODS A retrospective observational study was carried out in 110 patients who underwent radical nephrectomy between 2004 and 2018, with the aim of identifying possible prognostic factors of recurrence of RCC after these surgeries. Preoperative data (epidemiological, comorbidities and laboratory tests), surgical, pathological and variables related to follow-up were taken into account. A univariate and multivariate analysis were performed, using chi-square test and logistic regression, respectively. RESULTS The median follow-up time was 53.5 months (SD = 35.8), time in which 19 patients had a recurrence of RCC after radical nephrectomy (17.2%). Histopathological items such as the surgical piece size, the nodal and microvascular invasion, the renal sinus invasion and the presence of necrosis in the surgical piece were associated with RCC recurrence in the univariate analysis, while only the presence of necrosis in the surgical piece showed a significant result in the multivariate analysis (p = 0.004). CONCLUSIONS Histopathological analysis, highlighting the presence of necrosis in the histological sample, was proved to be the main risk factor of RCC recurrence.

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