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JAMA Oncology Jun 2024The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake.
IMPORTANCE
The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake.
OBJECTIVE
To evaluate the outcomes of SABR in patients with oligometastatic and oligoprogressive gynecologic cancers.
DESIGN, SETTING, AND PARTICIPANTS
In this retrospective pooled analysis, patients with oligometastatic and oligoprogressive gynecologic cancers receiving SABR at 5 institutions from Canada and the US were studied. Data were collected from January 2011 to December 2020, and data were analyzed from January to December 2023.
EXPOSURE
Stereotactic ablative radiotherapy.
MAIN OUTCOMES AND MEASURES
Cumulative incidence of local and distant recurrence, chemotherapy-free survival (CFS), and overall survival (OS) probabilities after SABR were calculated using Kaplan-Meier methods. Univariable and multivariable analysis was conducted using Cox regression methods.
RESULTS
A total of 215 patients with 320 lesions meeting criteria were included in the analysis; the median (range) age at primary diagnosis was 59 (23-86) years. The median (range) follow-up from SABR was 18.5 (0.1-124.5) months. The primary site included the endometrium (n = 107), ovary (n = 64), cervix (n = 30), and vulva or vagina (n = 14). Local cumulative incidence of recurrence was 13.7% (95% CI, 9.4-18.9) and 18.5% (95% CI, 13.2-24.5) at 1 and 5 years, respectively. Distant cumulative incidence of recurrence was 48.5% (95% CI, 41.4-55.1) and 73.1% (95% CI, 66.0-79.0) at 1 and 5 years, respectively. OS was 75.7% (95% CI, 69.2-81.1) and 33.1% (95% CI, 25.3-41.1) at 1 and 5 years, respectively. The median CFS was 21.7 months (95% CI, 15.4-29.9). On multivariable analysis, local recurrence was significantly associated with nodal metastasis, lesion size, biologically effective dose, treatment indication, institution, and primary disease type. Distant progression-free survival was associated with nodal targets and lesion size. OS and CFS were significantly associated with lesion size.
CONCLUSIONS AND RELEVANCE
In this study, SABR appeared to have excellent local control with minimal toxic effects in this large patient group, and certain patients may achieve durable distant control and OS as well. It may be possible to delay time to chemotherapy in select patient subtypes and therefore reduce associated toxic effects. Prospective multicenter trials will be critical to establish which characteristics procure the greatest benefit from SABR use and to define the ideal time to implement SABR with other oncologic treatments.
PubMed: 38869888
DOI: 10.1001/jamaoncol.2024.1796 -
Journal of Family & Reproductive Health Mar 2024Aggressive Angiomyxoma (AA) of the vulva is a slow-growing mesenchymal tumour with a tendency to local invasion and recurrence.
OBJECTIVE
Aggressive Angiomyxoma (AA) of the vulva is a slow-growing mesenchymal tumour with a tendency to local invasion and recurrence.
CASE REPORT
We report two cases of vulvoperineal masses that were diagnosed to be Aggressive Angiomyxomas after surgical excision. Both patients presented to the Gynaecology OPD of All India Institute of Medical Sciences, Bathinda, Punjab, India, in 2020 and 2022 with complaints of a mass coming out of introitus of three years duration and 14 years duration, respectively. The first patient was managed by surgical excision of the mass via abdominoperineal approach, while the second patient underwent vaginal hysterectomy along with the removal of the mass. Both patients were given GnRH analogues after the surgery to avoid any further recurrences and have been in remission on follow-ups so far.
CONCLUSION
Due to its rare occurrence, clinicians should consider the possibility of AA while encountering patients with vulvovaginal masses to avoid misdiagnosis and delayed management.
PubMed: 38863840
DOI: 10.18502/jfrh.v18i1.15442 -
Parasitology Research Jun 2024Mastophorus muris (Gmelin, 1790) is a globally distributed parasitic nematode of broad range mammals. The taxonomy within the genus Mastophorus and the cryptic diversity...
Mastophorus muris (Gmelin, 1790) is a globally distributed parasitic nematode of broad range mammals. The taxonomy within the genus Mastophorus and the cryptic diversity among the genus are controversial among taxonomists. This study provides a detailed morphological description of M. muris from Mus musculus combined with a molecular phylogenetic approach. Moreover, descriptions and molecular data of M. muris from non-Mus rodents and wildcats complement our findings and together provide new insights into their taxonomy. The analysis of M. muris was based on light microscopy and scanning electron microscopy. The morphological description focused on the dentition pattern of the two trilobed pseudolabia. Additionally, we described the position of the vulva, arrangement of caudal pairs of papillae, spicules and measured specimens from both sexes and the eggs. For the molecular phylogenetic approach, we amplified the small subunit ribosomal RNA gene and the internal transcribed spacer, and the cytochrome c oxidase subunit 1. Mastophorus morphotypes based on dentition patterns and phylogenetic clustering indicate a subdivision of the genus in agreement with their host. We recognize two groups without a change to formal taxonomy: One group including those specimens infecting Mus musculus, and the second group including organisms infecting non-Mus rodents. Our genetic and morphological data shed light into the cryptic diversity within the genus Mastopohorus. We identified two host-associated groups of M. muris. The described morphotypes and genotypes of M. muris allow a consistent distinction between host-associated parasites.
Topics: Animals; Phylogeny; Female; Male; Mice; Microscopy, Electron, Scanning; Spiruroidea; Electron Transport Complex IV; Genetic Variation; Sequence Analysis, DNA; Microscopy; DNA, Helminth; DNA, Ribosomal; DNA, Ribosomal Spacer; Cluster Analysis; Molecular Sequence Data
PubMed: 38856825
DOI: 10.1007/s00436-024-08259-1 -
European Journal of Surgical Oncology :... Jul 2024Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of...
INTRODUCTION
Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC).
METHODS
This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC.
RESULTS
We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.
Topics: Humans; Female; Vulvar Neoplasms; Carcinoma, Squamous Cell; Retrospective Studies; Aged; Neoplasm Recurrence, Local; Middle Aged; Tertiary Care Centers; Prognosis; Neoplasm Staging; Lymphatic Metastasis; Survival Rate; Papillomavirus Infections; Aged, 80 and over; Adult; Neoplasm Grading; Margins of Excision; Neoplasm Invasiveness
PubMed: 38843661
DOI: 10.1016/j.ejso.2024.108447 -
BMC Public Health Jun 2024Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.
METHODS
The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention.
DISCUSSION
Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden.
TRIAL REGISTRATION
NCT05057312.
Topics: Humans; Texas; Young Adult; Papillomavirus Vaccines; Papillomavirus Infections; Adolescent; Adult; Female; Male; Health Promotion; Vaccination
PubMed: 38840086
DOI: 10.1186/s12889-024-18828-9 -
Orphanet Journal of Rare Diseases Jun 2024Extramammary Paget's disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration...
BACKGROUND
Extramammary Paget's disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape.
METHODS
Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed.
RESULTS
Notable copy number gains (logFC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (logFC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event.
CONCLUSION
Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.
Topics: Humans; Paget Disease, Extramammary; Whole Genome Sequencing; Male; Receptor, ErbB-2; Aged; DNA Copy Number Variations
PubMed: 38831459
DOI: 10.1186/s13023-024-03169-y -
Case Reports in Women's Health Jun 2024Angiomyofibroblastoma (AMFB) represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. It is usually diagnosed in middle-aged women....
Angiomyofibroblastoma (AMFB) represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. It is usually diagnosed in middle-aged women. Histopathology and immunohistochemical study remain the key to diagnosis. Like other benign mesenchymal vulval tumors, AMFB shows indolent behavior and rarely recurs after complete surgical excision. Herein, we present a case of vulvar AMFB in a 51-year-old woman to highlight the diagnostic difficulties when considering this rare entity.
PubMed: 38827183
DOI: 10.1016/j.crwh.2024.e00617 -
Anticancer Research Jun 2024Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation...
BACKGROUND/AIM
Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer.
PATIENTS AND METHODS
Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package.
RESULTS
In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001).
CONCLUSION
Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer.
Topics: Humans; Female; Vulvar Neoplasms; Aged; Lymphatic Metastasis; Magnetic Resonance Imaging; Aged, 80 and over; Middle Aged; Adult; Lymph Nodes; Carcinoma, Squamous Cell; Inguinal Canal
PubMed: 38821619
DOI: 10.21873/anticanres.17078 -
Experimental and Molecular Pathology Jun 2024Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS...
BACKGROUND
Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions.
METHODS
Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach.
RESULTS
Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq.
CONCLUSION
mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.
Topics: Humans; Female; DNA Copy Number Variations; Paraffin Embedding; High-Throughput Nucleotide Sequencing; Formaldehyde; Tissue Fixation; Whole Genome Sequencing; Vulvar Neoplasms; Papillomavirus Infections; Anus Neoplasms
PubMed: 38820761
DOI: 10.1016/j.yexmp.2024.104906 -
Archives of Dermatological Research May 2024
Topics: Humans; Dermoscopy; Retrospective Studies; Female; Skin Neoplasms; Male; Middle Aged; Carcinoma, Basal Cell; Aged; Adult; Aged, 80 and over
PubMed: 38819453
DOI: 10.1007/s00403-024-03068-z