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Mousavi SE, Ghasemi H, Najafi M, Nejadghaderi SA. Global Epidemiology and Socioeconomic Correlates of Salivary Gland Cancer From 2020 to 2040. Community Dent Oral Epidemiol 2025; 53:316-328. [PMID: 39979564 DOI: 10.1111/cdoe.13033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 01/18/2025] [Accepted: 02/07/2025] [Indexed: 02/22/2025]
Abstract
OBJECTIVES To report the epidemiology and socioeconomic correlates of salivary gland cancers (SGCs) at global, regional and national levels by age, sex and country. METHODS Data on the incidence and mortality of SGC for the year 2020 were extracted from the Global Cancer Observatory. The relationships between incidence and mortality rates with the human development index (HDI) and the ratio of current healthcare expenditure to gross domestic product were investigated using bivariate correlation tests. Also, projections for new cancer cases or mortalities in a specific nation or region between 2025 and 2040 were estimated by multiplying age-specific incidence or mortality rates, with the anticipated population for the years 2025-2040. RESULTS In 2020, the global crude incidence and mortality rates of SGC were 0.69 and 0.29, respectively. Among the World Health Organization regions, the Americas and Africa had the highest SGC age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR), respectively. By HDI classification, the very high HDI group had the highest SGC ASIR at 0.69, whereas the low HDI group had the highest SGC ASMR at 0.49. Among different age groups, those aged 70+ had the highest SGC incidence and mortality crude rates. Globally, males had higher SGC incidence and mortality crude rates than females. A strong negative correlation was found between HDI and SGC ASMR and the mortality-to-incidence ratio (p < 0.001). By 2040, the global incidence and mortality numbers of SGC are projected to increase by 50% and 60%, respectively. CONCLUSIONS These findings provide crucial insight into the global distribution and disparities in SGC care quality. Furthermore, this report has the potential to aid in the planning of SGC control initiatives.
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Affiliation(s)
- Seyed Ehsan Mousavi
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hoomaan Ghasemi
- Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Morvarid Najafi
- Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
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Girardi FM, Pesenatto GG, Fuchs LD, Maahs TP, Treister NS, Maahs GS. Navigating Treatment‐Induced Head and Neck Malignancies in Cancer Survivors. Oral Dis 2024. [DOI: 10.1111/odi.15213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 11/19/2024] [Indexed: 01/03/2025]
Abstract
ABSTRACTCancer presents a significant global health burden. Traditional treatment modalities, especially radiotherapy and chemotherapy, have improved survival, but they have long‐term consequences. Treatment‐induced malignancies, a growing concern, pose risks to survivors. Often with limited treatment options, these tumors tend to have a worse survival rate. A thorough understanding of the main risk groups is critical for lifelong follow‐up and personalized care strategies. This review provides an update on the knowledge of treatment‐induced malignancies of the head and neck in cancer survivors; specifically, it discusses the risks, histological considerations, diagnosis and treatment strategies, follow‐up recommendations, and future perspectives.
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Affiliation(s)
- Fábio Muradás Girardi
- Head and Neck Surgery Department Ana Nery Hospital Santa Cruz do Sul Rio Grande do Sul Brazil
| | - Gustavo Guthmann Pesenatto
- Postgraduate Program in Otorhinolaryngology Hospital São Lucas da PUCRS Porto Alegre Rio Grande do Sul Brazil
| | - Larissa Dill Fuchs
- School of Dentistry Universidade Federal do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Thomas Peter Maahs
- Otorhinolaryngology and Head and Neck Surgery Department Pontifícia Universidade Católica Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul Brazil
| | - Nathaniel S. Treister
- Division of Oral Medicine and Dentistry Brigham and Women's Hospital Boston Massachusetts USA
- Department of Oral Medicine, Infection and Immunity Harvard School of Dental Medicine Boston Massachusetts USA
| | - Gerson Schulz Maahs
- Otorhinolaryngology and Head and Neck Surgery Department Pontifícia Universidade Católica Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul Brazil
- Otorhinolaryngology and Head and Neck Surgery Department Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil
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Filippini DM, Carosi F, Querzoli G, Fermi M, Ricciotti I, Molteni G, Presutti L, Foschini MP, Locati LD. Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review. Diagnostics (Basel) 2024; 14:2365. [PMID: 39518333 PMCID: PMC11544949 DOI: 10.3390/diagnostics14212365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/14/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.
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Affiliation(s)
- Daria Maria Filippini
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi, 40138 Bologna, Italy;
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy;
| | - Francesca Carosi
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy;
| | - Giulia Querzoli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, 40138 Bologna, Italy;
- Pathology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy
| | - Matteo Fermi
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.F.); (G.M.); (L.P.)
| | - Ilaria Ricciotti
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi, 40138 Bologna, Italy;
| | - Gabriele Molteni
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.F.); (G.M.); (L.P.)
| | - Livio Presutti
- Department of Otorhinolaryngology—Head and Neck Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.F.); (G.M.); (L.P.)
| | - Maria Pia Foschini
- Unit of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bellaria Hospital, 40139 Bologna, Italy;
| | - Laura Deborah Locati
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy;
- Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
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Gillard DM, Farzal Z, Ryan WR. Update on the Treatment of Salivary Gland Carcinomas. Surg Oncol Clin N Am 2024; 33:747-760. [PMID: 39244292 DOI: 10.1016/j.soc.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/09/2024]
Abstract
Salivary gland carcinoma is a rare form of head and neck carcinoma, but it comprises a variety of subsites and histologic subtypes that each present with unique clinical courses and management challenges. Preoperative work-up generally consists of fine-needle aspiration cytology and MRI. However, because of the large variety of subtypes, there are often challenges obtaining a histologic diagnosis before surgery. Upfront surgery at the primary site leads to the greatest improvement in survival. Posttreatment surveillance of these patients is important. This article discusses some of the current controversies in the management of salivary gland carcinomas.
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Affiliation(s)
- Danielle M Gillard
- Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Zainab Farzal
- Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Otolaryngology Head and Neck Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9035, USA
| | - William R Ryan
- Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
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Mishra S, Mishra S, Regmi S, Gupta V. A comparative study of low voltage, low contrast cerebral computed tomography angiography with iterative reconstruction and conventional cerebral computed tomography angiography. Neuroradiol J 2024; 37:221-228. [PMID: 38148622 PMCID: PMC10973829 DOI: 10.1177/19714009231224412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2023] Open
Abstract
BACKGROUND Cerebral computed tomography angiography (CTA) has revolutionized the diagnosis of neurovascular emergencies. Strategies to reduce radiation, a concern for cancer, involve tube voltage and current reduction but with increased noise and inferior image quality. Hence, the objective of the study was to evaluate the quality of images obtained through low-dose radiation and low-contrast volume CTA with an iterative reconstruction (IR) technique versus standard CTA without IR. METHODS This prospective trial involved 100 adults requiring cerebral CTA for cerebrovascular diseases. They were split into two groups: one with 120 kVp tube voltage and 80 mL contrast using filtered back projection, and the other with 80 kVp and 30 mL contrast with IR. Evaluation criteria included attenuation values, signal-to-noise ratio, contrast-to-noise ratio, and subjective assessments. RESULTS Compared to 120 kVp, 80 kVp showed higher vessel attenuation in the internal (272.91 ± 30.59 vs 405.52 ± 53.08; p < .001) and middle cerebral artery (247.55 ± 29.84 vs 372.55 ± 49.02; p < .001) regions. Brain parenchymal attenuation at the centrum semiovale was lower with 80 kVp (29.12 ± 1.87 vs 24.78 ± 2.94; p < .001), accompanied by higher noise. Signal-to-noise ratio (p < .001) and contrast-to-noise ratio (p < .05) were lower at 80 kVp. Image quality didn't significantly differ, and radiation exposure reduced significantly by 70% in the 80 kVp group, suggesting its diagnostic feasibility. CONCLUSIONS The 80 kVp protocol for CTA of the cerebral vessels combined with lower contrast volume produces images with similar image quality with significant radiation effective dose and total iodine dose reduction. The 80 kVp protocol holds significant promise for replacing the standard 120 kVp protocol in cerebral CTA.
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Affiliation(s)
- Saurav Mishra
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, India
- Department of Radiodiagnosis and Imaging, Vayodha Hospital, Nepal
| | - Sandeep Mishra
- Department of Neurosurgery and Neuro-intervention, Neo Multispecialty Hospital, India
| | - Sabina Regmi
- Department of Anesthesia and Intensive care, Neo Multispecialty Hospital, India
| | - Vivek Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, India
- Department of Neuro-interventional Radiology, Fortis Hospital, India
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Ghaderi H, Kruger E, Ahmadvand S, Mohammadi Y, Khademi B, Ghaderi A. Epidemiological Profile of Salivary Gland Tumors in Southern Iranian Population: A Retrospective Study of 405 Cases. J Cancer Epidemiol 2023; 2023:8844535. [PMID: 38026266 PMCID: PMC10681769 DOI: 10.1155/2023/8844535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/07/2023] [Accepted: 10/24/2023] [Indexed: 12/01/2023] Open
Abstract
Aims Salivary gland tumors (SGTs) are a rare and diverse group of tumors that account for 3 to 10% of all head and neck malignancies. We aimed to conduct a comprehensive epidemiological analysis of SGTs in the south of Iran and compare the findings with previous reports from Iran and other parts of the world. Methods Using a retrospective study, 405 patients diagnosed with SGTs were observed over an eight-year period between April 2013 and October 2021 in Shiraz, Iran. Patients' demographic and clinicopathological features were obtained from patients' records. Quantitative and descriptive data analysis was performed using SPSS software. Results There were 302 benign (74.5%) and 103 (25.4%) malignant SGTs. Pleomorphic adenoma and Warthin's tumors were the most common benign SGTs (70.5% and 21.5%, respectively). The most common malignant SGTs were mucoepidermoid carcinoma and adenoid cystic carcinoma (26.2% and 22.3%, respectively). There was a statistically significant association between tumor origin and its malignancy status (p < 0.001). In addition, the results indicated that benign tumors were most commonly detected in the parotid gland (p < 0.05). The benign tumors were more frequently observed among the younger population (p = 0.006). Conclusion In summary, the findings of the current study were mainly consistent with the previous reports from Iran and the rest of the world. Benign tumors were the most prevalent type of SGTs, and the parotid gland was the most common site. While the majority of cases that developed from the major salivary glands were benign, all the minor SGTs were malignant. Older patients were more likely to develop malignant tumors compared to younger ones. This study provides insights into the prevalence, age-related incidence, gender distribution, and geographic variation of salivary gland tumors. This can be instrumental to develop a guideline for screening, diagnosis, and determining an optimal treatment.
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Affiliation(s)
- Hamid Ghaderi
- Faculty of Science, School of Human Science, University of Western Australia, Australia
- West Wimmera Health Service, Nhill, Victoria 3418, Australia
| | - Estie Kruger
- Faculty of Science, School of Human Science, University of Western Australia, Australia
| | - Simin Ahmadvand
- Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yousef Mohammadi
- Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bijan Khademi
- Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abbas Ghaderi
- Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
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7
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Twenty-seven years of primary salivary gland carcinoma in Wales: an analysis of histological subtype and associated risk factors. The Journal of Laryngology & Otology 2022; 136:167-172. [DOI: 10.1017/s002221512200007x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
AbstractObjectiveRisk factors for salivary gland carcinoma are poorly understood. Although links between background radiation, smoking and obesity have been previously suggested, no studies have so far established any significant results. This study aimed to establish correlations between common environmental and lifestyle risk factors and different subtypes of salivary gland carcinoma.MethodA study of population data in Wales spanning 27 years was conducted; 2 national databases were used to identify 356 cases of primary salivary gland carcinoma over this period. Histological subtype of cancer and geographical location of each case was recorded. Public health data was used to establish radon levels, smoking, obesity and activity levels of populations in each geographical location. A population matched multivariate analysis of variance analysis was performed using histological subtype and risk factor data for each geographical location.ResultsA significantly higher incidence of mucoepidermoid cancer in populations with higher background radon levels (p = 0.006), epithelial-myoepithelial cancer in populations with higher smoking levels (p = 0.029) and adenoid cystic cancer in populations with higher obesity levels (p = 0.028) was found.ConclusionTo the authors’ knowledge, this is the first study to establish significant links between background radiation, smoking and obesity with different subtypes of salivary gland carcinoma.
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Povlow MR, Streiff M, Madireddi S, Jaramillo C. A Primary Parotid Mucosa-Associated Lymphoid Tissue Non-Hodgkin Lymphoma in a Patient With Sjogren Syndrome. Cureus 2021; 13:e15679. [PMID: 34277270 PMCID: PMC8281787 DOI: 10.7759/cureus.15679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2021] [Indexed: 11/05/2022] Open
Abstract
The salivary gland tumors are rare entities and the majority of these are benign. However, there are some entities such as prior neck radiation, certain infections, and systemic diseases which should raise the clinical suspicion for a malignant lesion. Patients with Sjogren syndrome are at increased risk for a salivary gland neoplasm, specifically non-Hodgkin lymphoma. While clinical findings play an important role in the initial workup, imaging plays a critical role in the diagnosis and management. This case describes a patient with Sjogren syndrome who presented with a left face mass where imaging was able to confidently diagnose her with a suspicious parotid neoplasm with lymphoma as the favored diagnosis. After histological evaluation, she was diagnosed with primary parotid mucosa-associated lymphoid tissue (MALT) non-Hodgkin lymphoma after which she went on to non-operative management.
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Affiliation(s)
- Michael R Povlow
- Department of Radiology, Brooke Army Medical Center, San Antonio, USA
| | - Mitchell Streiff
- Department of Radiology, Ponce Health Sciences University, Ponce, USA
| | | | - Couger Jaramillo
- Department of Pathology, Brooke Army Medical Center, San Antonio, USA
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Khanna L, Prasad SR, Yedururi S, Parameswaran AM, Marcal LP, Sandrasegaran K, Tirumani SH, Menias CO, Katabathina VS. Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings. Radiographics 2021; 41:876-894. [PMID: 33891523 DOI: 10.1148/rg.2021200171] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management. An invited commentary by Shapiro is available online. ©RSNA, 2021.
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Affiliation(s)
- Lokesh Khanna
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Srinivasa R Prasad
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Sireesha Yedururi
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Anand M Parameswaran
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Leonardo P Marcal
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Kumar Sandrasegaran
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Sree Harsha Tirumani
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Christine O Menias
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Venkata S Katabathina
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
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Therapeutic challenges in radiation-induced salivary gland cancers. Curr Opin Otolaryngol Head Neck Surg 2021; 29:120-125. [PMID: 33394737 DOI: 10.1097/moo.0000000000000694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs). RECENT FINDINGS Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy. SUMMARY Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.
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Multidisciplinary Management of Radiation-Induced Salivary Gland Carcinomas in the Modern Radiotherapy Era. Cancers (Basel) 2020; 12:cancers12123769. [PMID: 33327563 PMCID: PMC7765068 DOI: 10.3390/cancers12123769] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 12/19/2022] Open
Abstract
Simple Summary Etiopathogenesis of salivary gland cancers [SGCs] is largely unknown, even if exposition to ionizing radiation is a recognized risk factor for SGCs development. To date, exhaustive data to guide clinicians in managing patients with radiation-induced [ri] SGCs are scarce and their treatment remains challenging. The purpose of this work is to describe and to analyze clinical and histopathological features, delivered treatments, and outcome of a series of patients with ri-SGCs treated at two Italian cancer referral sites. Given the rarity of ri-SGCs, this retrospective analysis conducted on a case series of 13 patients adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach. Abstract Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed 14 ri-SGCs (one patient had 2 synchronous ri-SCGs), after a median LT of 23 years (range 16–34). Parotid was the primary site in 8 cases (57%) and salivary duct carcinoma was the most frequent histotype (29%). Nine patients (69%) underwent surgery (Sx). Among them, 4 patients (31%) underwent Sx alone, 5 received post-operative treatments: 3 (23%) photon-based (X) reRT, one (8%) protons and carbon ions, one (8%) carbon ions only. One patient (8%) received definitive XRT. The remaining 3 patients (23%) received androgen deprivation therapy. With a median follow-up of 48 months (range 24–72), median OS and PFS were 74 and 24 months, respectively. In the subgroup of AR+ ri-SGCs, median PFS and OS were 12 and 74 months, respectively. Given the rarity of ri-SGCs, this work adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.
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Aegisdottir AL, Tryggvason G, Jonsdottir AM, Jonasson JG. Salivary gland tumours in Iceland 1986-2015: a nationwide epidemiological analysis over a 30-year time period. APMIS 2020; 129:55-60. [PMID: 33064861 DOI: 10.1111/apm.13090] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 10/13/2020] [Indexed: 02/03/2023]
Abstract
Salivary gland tumours (SGT) are a vast and heterogenous group of neoplasms. There is a relative lack of comprehensive nationwide epidemiological studies on the subject. The aim of this nationwide analysis was to gain insight into epidemiological traits, such as site, incidence and histological subtypes of SGT in general. Patients diagnosed with a primary SGT between 1986 and 2015 were identified from The Icelandic Cancer Registry and registries from all pathology departments in Iceland. Information on age, sex, tumour location and histology was retrieved from pathology reports. A total of 687 patients were diagnosed with a SGT, 609 (89%) were benign and 78 (11%) malignant. 9% of parotid gland tumours, 22% of submandibular gland tumours and 26% of minor SGT were malignant. The most common malignant tumours were mucoepidermoid carcinoma, acinic cell carcinoma and adenoid cystic carcinoma. The incidence of benign SGT was 4.9 per 100 000 among men and 7.0 per 100 000 among women. The incidence of malignant tumours was 0.59 per 100 000 for men and 0.79 per 100 000 for women. The proportion of malignant SGT is lower than most often reported. Only 10% of parotid gland tumours, 20% of submandibular gland tumours and 25% of minor salivary gland tumours are malignant.
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Affiliation(s)
| | - Geir Tryggvason
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland.,Department of Otorhinolaryngology, The National University Hospital of Iceland, Reykjavik, Iceland
| | | | - Jon Gunnlaugur Jonasson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland.,Department of Pathology, The National University Hospital of Iceland, Reykjavik, Iceland
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13
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Howell RM, Smith SA, Weathers RE, Kry SF, Stovall M. Adaptations to a Generalized Radiation Dose Reconstruction Methodology for Use in Epidemiologic Studies: An Update from the MD Anderson Late Effect Group. Radiat Res 2019; 192:169-188. [PMID: 31211642 PMCID: PMC8041091 DOI: 10.1667/rr15201.1] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Epidemiologic studies that include patients who underwent radiation therapy for the treatment of cancer aim to quantify the relationship between radiotherapy and the risk of subsequent late effects. Because of the long follow-up period required to observe late effects, these studies are conducted retrospectively. The studies routinely include patients treated across numerous institutions using a wide range of technologies and represent treatments over several decades. As a result, determining the dose throughout the patient's body is uniquely challenging. Therefore, estimating doses throughout the patient's body for epidemiologic studies requires special methodologies that are generally applied to a wide range of radiotherapy techniques. Over ten years ago, the MD Anderson Late Effects Group described various dose reconstruction methods for therapeutic and diagnostic radiation exposure for epidemiologic studies. Here we provide an update to the most widely used dose reconstruction methodology for epidemiologic studies, analytical model calculations combined with a 3D age-specific computational phantom. In particular, we describe the various adaptations (and enhancements) of that methodology, as well as how they have been used in radiation epidemiology studies and may be used in future studies.
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Affiliation(s)
- Rebecca M. Howell
- Department of Radiation Physics, The University of Texas at MD Anderson Cancer Center, Houston, Texas
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14
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Mantravadi AV, Moore MG, Rassekh CH. AHNS series: Do you know your guidelines? Diagnosis and management of salivary gland tumors. Head Neck 2018; 41:269-280. [PMID: 30548929 DOI: 10.1002/hed.25499] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 08/17/2018] [Indexed: 12/13/2022] Open
Abstract
This article is the next installment of the series "Do you know your guidelines" presented by the Education Committee of the American Head and Neck Society. Guidelines for the workup and management of tumors of the major and minor salivary glands are reviewed.
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Affiliation(s)
- Avinash V Mantravadi
- Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana
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15
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Radoï L, Barul C, Menvielle G, Carton M, Matrat M, Sanchez M, Pilorget C, Velten M, Stücker I, Luce D. Risk factors for salivary gland cancers in France: Results from a case-control study, the ICARE study. Oral Oncol 2018; 80:56-63. [PMID: 29706189 DOI: 10.1016/j.oraloncology.2018.03.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 03/14/2018] [Accepted: 03/30/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Epidemiological studies on the risk factors for salivary gland cancers (SGC) are rare, concern a small sample size, and show inconsistent results. The aim of the present work was to analyze several risk factors for SGC, using the data from the ICARE study, a multicenter, population-based case-control study. MATERIALS AND METHODS Data from 73 SGC cases and 3555 controls were collected using a standardized questionnaire on lifestyle habits, personal and family medical history, and lifetime occupational history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regressions. RESULTS Tobacco use and alcohol consumption were not associated with the risk of SGC. A history of head and neck cancer or that of cervicofacial radiotherapy was associated with a higher risk of SGC (OR = 17.06, 95% CI: 4.34-67.05, and OR = 31.74, 2.48-405.25, respectively). Significantly increased risks were observed for some occupations: waiter (OR = 2.94, 1.11-7.78), charworker (OR = 3.02, 1.38-6.60), electrical and electronic equipment assembler (OR = 7.16, 2.02-25.38), plumber (OR = 3.95, 1.33-11.67), electric arc welder (OR = 6.15, 1.76-21.48), sheet-metal worker (OR = 2.89, 1.01-8.32), building painter (OR = 3.42, 1.01-11.49), and material handling equipment operator (OR = 5.05, 1.71-14.84). Results for industries were consistent with those observed for occupations. CONCLUSION Our results showed that a history of head and neck cancer, cervicofacial radiotherapy, and several occupations and industries, were associated with an increased risk of SGC. Further studies with larger sample sizes are indicated to confirm our results.
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Affiliation(s)
- Loredana Radoï
- University Paris Sud, Paris Saclay University, UVSQ, CESP, INSERM, Environmental Epidemiology of Cancer Team, Villejuif, France; University Paris Descartes, Faculty of dental surgery, Oral surgery department, Paris, France.
| | - Christine Barul
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Pointe-à-Pitre, France
| | - Gwenn Menvielle
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France
| | - Matthieu Carton
- Institut Curie, PSL Research University, DRCI, Biométrie, Saint-Cloud, France
| | - Mireille Matrat
- Université Paris Est Créteil, Faculté de médecine, Créteil, France; Centre Hospitalier Intercommunal, Service des Pathologies Professionnelles et de l'Environnement, Créteil, France
| | - Marie Sanchez
- University Paris Sud, Paris Saclay University, UVSQ, CESP, INSERM, Environmental Epidemiology of Cancer Team, Villejuif, France
| | - Corinne Pilorget
- The French Public Health Agency, Department of Occupational Health, Saint Maurice, France; University Lyon, Claude Bernard Lyon1 University, Ifsttar, UMRESTTE, UMR T_9405, Lyon, France
| | | | - Isabelle Stücker
- University Paris Sud, Paris Saclay University, UVSQ, CESP, INSERM, Environmental Epidemiology of Cancer Team, Villejuif, France
| | - Danièle Luce
- Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Pointe-à-Pitre, France
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16
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Tseng YD, Cutter DJ, Plastaras JP, Parikh RR, Cahlon O, Chuong MD, Dedeckova K, Khan MK, Lin SY, McGee LA, Shen EYL, Terezakis SA, Badiyan SN, Kirova YM, Hoppe RT, Mendenhall NP, Pankuch M, Flampouri S, Ricardi U, Hoppe BS. Evidence-based Review on the Use of Proton Therapy in Lymphoma From the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee. Int J Radiat Oncol Biol Phys 2017; 99:825-842. [PMID: 28943076 DOI: 10.1016/j.ijrobp.2017.05.004] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/24/2017] [Accepted: 05/02/2017] [Indexed: 12/25/2022]
Affiliation(s)
- Yolanda D Tseng
- Department of Radiation Oncology, University of Washington, Seattle Cancer Care Alliance Proton Therapy Center, Seattle, Washington
| | - David J Cutter
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - John P Plastaras
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rahul R Parikh
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Oren Cahlon
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael D Chuong
- Miami Cancer Institute at Baptist Health South Florida, Miami, Florida
| | - Katerina Dedeckova
- Proton Therapy Department, Proton Therapy Center, Prague, Czech Republic
| | - Mohammad K Khan
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia
| | - Shinn-Yn Lin
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan
| | - Lisa A McGee
- Department of Radiation Oncology, Mayo Clinic Arizona, Scottsdale, Arizona
| | - Eric Yi-Liang Shen
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan
| | - Stephanie A Terezakis
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shahed N Badiyan
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Youlia M Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Richard T Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, California
| | - Nancy P Mendenhall
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida; University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Mark Pankuch
- Northwestern Medicine Chicago Proton Center, Warrenville, Illinois
| | - Stella Flampouri
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida; University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | | | - Bradford S Hoppe
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida; University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
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17
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Machado RA, Moubayed SP, Khorsandi A, Hernandez-Prera JC, Urken ML. Intermittent facial spasms as the presenting sign of a recurrent pleomorphic adenoma. World J Clin Oncol 2017; 8:86-90. [PMID: 28246588 PMCID: PMC5309717 DOI: 10.5306/wjco.v8.i1.86] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 12/17/2016] [Accepted: 01/03/2017] [Indexed: 02/06/2023] Open
Abstract
The intimate anatomical relationship of the facial nerve to the parotid parenchyma has a significant influence on the presenting signs and symptoms, diagnosis and treatment of parotid neoplasms. However, to our knowledge, hyperactivity of this nerve, presenting as facial spasm, has never been described as the presenting sign or symptom of a parotid malignancy. We report a case of carcinoma arising in a recurrent pleomorphic adenoma of the left parotid gland (i.e., carcinoma ex pleomorphic adenoma) that presented with hemifacial spasms. We outline the differential diagnosis of hemifacial spasm as well as a proposed pathophysiology. Facial paralysis, lymph node enlargement, skin involvement, and pain have all been associated with parotid malignancies. To date the development of facial spasm has not been reported with parotid malignancies. The most common etiologies for hemifacial spasm are vascular compression of the ipsilateral facial nerve at the cerebellopontine angle (termed primary or idiopathic) (62%), hereditary (2%), secondary to Bell’s palsy or facial nerve injury (17%), and hemifacial spasm mimickers (psychogenic, tics, dystonia, myoclonus, myokymia, myorthythmia, and hemimasticatory spasm) (17%). Hemifacial spasm has not been reported in association with a malignant parotid tumor but must be considered in the differential diagnosis of this presenting symptom.
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18
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Schlieve T, Heidel RE, Carlson ER. Second Primary Head and Neck Cancers After Non-Head and Neck Primary Cancers. J Oral Maxillofac Surg 2016; 74:2515-2520. [DOI: 10.1016/j.joms.2016.05.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 05/09/2016] [Accepted: 05/10/2016] [Indexed: 12/30/2022]
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19
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Trends in Use of Radiation Therapy for Hodgkin Lymphoma From 2000 to 2012 on the Basis of the National Cancer Data Base. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2016; 16:12-7. [DOI: 10.1016/j.clml.2015.11.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 11/12/2015] [Indexed: 11/21/2022]
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20
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Mann JM, Kellman RM, Hahn SS, de la Roza GL, Gajra A. Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma. Head Neck 2015; 37:E96-8. [PMID: 25242451 DOI: 10.1002/hed.23873] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. METHODS AND RESULTS We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. CONCLUSION Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.
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Affiliation(s)
- Justin M Mann
- Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, New York
| | - Robert M Kellman
- Department of Otolaryngology and Communication Sciences, SUNY Upstate Medical University, Syracuse, New York
| | - Seung S Hahn
- Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, New York
| | | | - Ajeet Gajra
- Department of Hematology/Oncology, SUNY Upstate Medical University, Syracuse, New York
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21
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Chowdhry AK, McHugh C, Fung C, Dhakal S, Constine LS, Milano MT. Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 2015; 121:1436-45. [PMID: 25572913 DOI: 10.1002/cncr.29231] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 11/24/2014] [Accepted: 11/25/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Survivors of Hodgkin lymphoma (HL) are at an increased risk of developing second malignancies. To the authors' knowledge, the risks of head and neck cancer (HNC) after HL and subsequent survival have not been thoroughly investigated. METHODS From the US population-based Surveillance, Epidemiology, and End Results (SEER) database for 1973 through 2011, survivors of HL who developed HNC as a second cancer were analyzed. Patients with a first primary HNC were used as a comparison group. Observed-to-expected ratios and summary statistics were performed on patients with HL with squamous cell carcinoma (HL-SCC) and salivary gland cancer (HL-SGC). The impact of HL history on overall survival was assessed using a multivariate Cox proportional hazards model. RESULTS The observed-to-expected ratio for SCC among patients with HL was 1.73 (95% confidence interval [95% CI], 1.36-2.16; P<.05), whereas it was 8.56 for SGC (95% CI, 5.82-12.15; P<.05). Using Cox proportional hazards modeling, a history of HL was found to be an adverse prognostic factor for overall survival for SCC (hazard ratio, 1.37; 95% CI, 1.08-1.73 [P = .009]) but not SGC (hazard ratio, 1.21; 95% CI, 0.82-1.79 [P = .34]). The inferior survival of the patients in the HL-SCC cohort appears to be attributable to more deaths from HL and other malignancies diagnosed after SCC. CONCLUSIONS There is a significantly increased risk of salivary and nonsalivary HNC after HL, and worse survival for patients with HL-SCC versus those with a first primary SCC. Clinicians should be aware of the risks of HNC after HL. In the absence of evidence-based criteria, the authors recommend that survivors of HL undergo periodic head and neck examination.
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Affiliation(s)
- Amit K Chowdhry
- Department of Biostatistics and Computational Biology, University of Rochester School of Medicine, Rochester, New York
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22
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de Ridder M, Balm AJM, Smeele LE, Wouters MWJM, van Dijk BAC. An epidemiological evaluation of salivary gland cancer in the Netherlands (1989-2010). Cancer Epidemiol 2014; 39:14-20. [PMID: 25454260 DOI: 10.1016/j.canep.2014.10.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Revised: 10/14/2014] [Accepted: 10/15/2014] [Indexed: 11/25/2022]
Abstract
BACKGROUND The relative 5-year survival rate of salivary gland cancer is moderate at best. This study was set up to evaluate whether the improvements in diagnosis and treatment in the last decades impacted the incidence, mortality and survival of salivary gland cancer. METHODS Data on patients with salivary gland cancer from 1989 through 2010 were extracted from the Netherlands Cancer Registry (NCR); we examined incidence, mortality and relative survival. Furthermore, information on sex, age, tumor stage, histology, and treatment was taken into account. RESULTS A total of 2737 patients were included. Fifty-three percent (53%) were males and 47% were females with a significant higher proportion of early stages in women. In 2010, the incidence rate (European Standardized Rate (ESR)) of salivary gland cancer was 0.9 per 100,000 per year. The estimated annual percentage change in incidence rate since 1989 equaled 0.6% (95%CI: -0.2-1.4). Mortality rates (ESR) decreased in men until 1997 and increased thereafter. Mortality in women remained stable at 1.5 per 100,000. Over time more patients were treated by surgery and radiotherapy (p<0.001). The relative five-year survival rate equaled 69% and did not change in time. CONCLUSION We observed no relevant changes in incidence or mortality rates in the last two decades. Despite the increased combined treatment by surgery and radiotherapy, survival did not improve. This implies an urgent need for the development of new effective treatment modalities.
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Affiliation(s)
- Mischa de Ridder
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands.
| | - Alfons J M Balm
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands
| | - Ludi E Smeele
- Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands; Department of Maxillo-facial Surgery, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Michel W J M Wouters
- Department of Surgical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands
| | - Boukje A C van Dijk
- Department of Research, Comprehensive Cancer Centre, Utrecht, The Netherlands; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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23
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Black A, Gibson TM, Shiels MS, Park Y, Robien K, Albanes D, Weinstein SJ, Freeman LEB, Andreotti G, Purdue MP, Fraumeni JF, Hartge P, Tucker MA, Hoover RN, Cerhan JR, Zeleniuch-Jacquotte A, Curtis RE, Elena J, Sampson JN, Berrington de Gonzalez A, Morton LM. Pooling prospective studies to investigate the etiology of second cancers. Cancer Epidemiol Biomarkers Prev 2014; 23:1598-608. [PMID: 24832874 PMCID: PMC4119533 DOI: 10.1158/1055-9965.epi-14-0191] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on nontreatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology. METHODS We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements. RESULTS Overall, 96,513 incident, first primary malignancies were diagnosed during 1985 to 2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). A total of 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers. CONCLUSIONS Pooling data from cohort studies to investigate nontreatment risk factors for second primary cancers seems feasible but there are important methodologic issues-some of which are barriers to specific research questions-that require special attention. IMPACT Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information.
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Affiliation(s)
| | | | | | | | - Kim Robien
- Department of Epidemiology and Biostatistics, George Washington University School of Public Health and Health Services, Washington, D.C
| | | | | | | | | | | | | | | | | | | | - James R Cerhan
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; and
| | - Anne Zeleniuch-Jacquotte
- Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York
| | | | - Joanne Elena
- Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, DHHS, Rockville, Maryland
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Sun C, Hu Z, Zhong Z, Jiang Y, Sun R, Fei J, Xi Y, Li X, Song M, Li W, Li Q. Clinical and prognostic analysis of second primary squamous cell carcinoma of the tongue after radiotherapy for nasopharyngeal carcinoma. Br J Oral Maxillofac Surg 2014; 52:715-20. [PMID: 25085271 DOI: 10.1016/j.bjoms.2014.06.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 06/24/2014] [Indexed: 11/24/2022]
Abstract
We have investigated the clinical characteristics and prognostic factors of squamous cell carcinoma (SCC) of the tongue after definitive radiotherapy for nasopharyngeal carcinoma, and evaluated the effect of common therapeutic regimens for these patients. We retrospectively reviewed follow-up data for patients whose nasopharyngeal carcinoma had been treated by radiotherapy, and selected the 68 who had then developed SCC of the tongue, in the border of the tongue in half, and in the dorsum in 25 (37%). Eight of the 68 patients had clinical lymph node metastasis (12%), and 45 presented with stage I-II disease at the time of the diagnosis of the SCC (66%). Resection or radiotherapy alone was an effective treatment for patients with stage I-II SCC of the tongue, but patients with stage III-IV disease had a poor prognosis, despite being given multidisciplinary treatment. Multivariate analysis showed that the risk factors that independently influenced the survival of these patients were use of alcohol, recurrence of their nasopharyngeal carcinoma, the latency period, and the clinical TNM stage. Tongue SCC after radiotherapy was generally at an early stage and commonly occurred on the border or the dorsum of the tongue, with few lymph node metastases. Resection or radiotherapy is an effective treatment, and the risk factors that independently influenced the survival of patients indicate that improving the technique of radiotherapy and close follow-up after nasopharyngeal cancer are vitally important.
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Affiliation(s)
- Chuanzheng Sun
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Zedong Hu
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Zhaoming Zhong
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Yue Jiang
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Ruimei Sun
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Jimin Fei
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Yan Xi
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Xiaojiang Li
- Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China
| | - Ming Song
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, China; State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou, China
| | - Wenhui Li
- Department of Radiotherapy, The Third Affiliated Hospital of Kunming Medical University, 519 Kunzhou Road, Kunming, China.
| | - Qiuli Li
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, China; State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou, China.
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25
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Patel NR, Sanghvi S, Khan MN, Husain Q, Baredes S, Eloy JA. Demographic trends and disease-specific survival in salivary acinic cell carcinoma: an analysis of 1129 cases. Laryngoscope 2013; 124:172-8. [PMID: 23754708 DOI: 10.1002/lary.24231] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 05/13/2013] [Accepted: 05/13/2013] [Indexed: 12/13/2022]
Abstract
OBJECTIVE/HYPOTHESIS Acinic cell carcinoma (AciCC) is a rare salivary gland malignancy that most commonly arises in the parotid gland. Characteristics of AciCC are slow growth and a long clinical course. As a rare tumor, population-based studies are limited. We analyzed the incidence and survival for AciCC using a national population-based database. STUDY DESIGN Retrospective analysis. METHODS The United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry was utilized to calculate incidence and disease-specific survival trends for AciCC between 1973 and 2009. Patient data were stratified according to age, gender, race, grade, and extent of disease. Incidence trends were studied across the last 30 years and long-term disease-specific survival outcomes were compared across the different demographic parameters. RESULTS A total of 1,129 cases of AciCC were identified, comprising of 672 (59.52%) females. Incidence trend analysis revealed significant changes in yearly incidence rates from 1973 to 2009 for male gender and white and "others" races. Overall 5-year survival was 97.15%, 10-year survival was 93.81%, and 20-year survival was 89.74%. Significant differences in survival outcomes were noted for extent of disease. Patients exhibiting distant metastasis displayed the worse long-term prognosis at 21.99% 20-year disease-specific survival. Hazard ratios demonstrated a significant increase in mortality in patients with poorly differentiated, undifferentiated, and metastatic disease. CONCLUSION Trends in incidence of AciCC are influenced by gender, race and age. Long-term survival of this rare malignant tumor is influenced by gender, grade, race, and extent of disease. Future studies need to be conducted to investigate these dynamic trends related to AciCC.
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Affiliation(s)
- Neal R Patel
- Department of Otolaryngology-Head & Neck Surgery, Neurological Institute of New Jersey, Newark, New Jersey, U.S.A
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Boukheris H, Stovall M, Gilbert ES, Stratton KL, Smith SA, Weathers R, Hammond S, Mertens AC, Donaldson SS, Armstrong GT, Robison LL, Neglia JP, Inskip PD. Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 2013; 85:776-83. [PMID: 22836059 PMCID: PMC3500417 DOI: 10.1016/j.ijrobp.2012.06.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Revised: 06/04/2012] [Accepted: 06/05/2012] [Indexed: 11/26/2022]
Abstract
PURPOSE To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). METHODS AND MATERIALS Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. RESULTS During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. CONCLUSION Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.
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Affiliation(s)
- Houda Boukheris
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Marilyn Stovall
- Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Ethel S. Gilbert
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Kayla L. Stratton
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Susan A. Smith
- Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Rita Weathers
- Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Sue Hammond
- Department of Pathology, Ohio State University School of Medicine, Columbus, OH
| | | | - Sarah. S. Donaldson
- Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA
| | - Gregory T. Armstrong
- Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN
| | - Leslie L. Robison
- Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN
| | - Joseph P. Neglia
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
| | - Peter D. Inskip
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
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Manninen AL, Isokangas JM, Karttunen A, Siniluoto T, Nieminen MT. A comparison of radiation exposure between diagnostic CTA and DSA examinations of cerebral and cervicocerebral vessels. AJNR Am J Neuroradiol 2012; 33:2038-42. [PMID: 22700752 PMCID: PMC7965573 DOI: 10.3174/ajnr.a3123] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2011] [Accepted: 02/25/2012] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE While the number of CTA examinations is continually increasing compared with DSA examinations, there is little comparative dose information about the different imaging techniques. We compared patient radiation exposure resulting from diagnostic CTA and DSA examinations for both cerebral and cervicocerebral vessels. MATERIALS AND METHODS An anthropomorphic phantom was irradiated by using typical diagnostic CTA and DSA setups and imaging parameters. For both imaging techniques, the imaging area of cerebral vessels included intracranial vessels only, while the imaging area of cervicocerebral vessels included both cervical and intracranial vessels from the aortic arch to the vertex. The effective dose was determined by using RPLDs. The DSA examination was simulated by using a biplane angiography system, and the CTA examination, by using a 64-row multidetector CT scanner. RESULTS For the imaging of cerebral vessels, the effective dose according to ICRP 103 was 0.67 mSv for CTA and 2.71 mSv for DSA. For the imaging of cervicocerebral vessels, the effective dose was 4.85 mSv for CTA and 3.60 mSv for DSA. The maximum absorbed dose (milligray) for skin, brain, salivary glands, and eyes was 166.2, 73.5, 35.6, and 21.8 mGy for DSA and 19.0, 16.9, 20.4, and 14.8 mGy for CTA, respectively. The conversion factors from DAP and DLP to effective dose were calculated. CONCLUSIONS The effective dose for CTA assessment of cerebral vessels was approximately one-fifth the dose compared with DSA. In the imaging of cervicocerebral vessels, the effective dose for CTA was approximately one-third higher compared with DSA.
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Affiliation(s)
- A-L Manninen
- Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
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Ettl T, Schwarz-Furlan S, Gosau M, Reichert TE. Salivary gland carcinomas. Oral Maxillofac Surg 2012; 16:267-283. [PMID: 22842859 DOI: 10.1007/s10006-012-0350-9] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Accepted: 07/18/2012] [Indexed: 06/01/2023]
Abstract
INTRODUCTION Salivary gland carcinomas are rare tumours of heterogeneous morphology that require distinctive surgical and adjuvant therapy. METHODS Relevant studies were electronically searched in PubMed and reviewed for innovative and important information. RESULTS Recent insights in genetic alterations like chromosomal aberrations, expression of receptor tyrosine kinases, malfunction of tumour suppressor genes or DNA promoter methylations increased the knowledge about aetiology and pathogenesis. New histological subtypes are recognised, and a three-tiered grading system seems reasonable. Ultrasound remains the basic diagnostic imaging procedure. New developments comprise the diffusion-weighed magnetic resonance imaging, while fluorodeoxyglucose positron emission tomography/computed tomography shows good diagnostic accuracy in detecting distant metastases and local recurrence. Fine-needle aspiration cytology helps in differentiating a neoplasia from a non-neoplastic lesion while being unreliable in recognising malignancy. In contrast, additional core needle biopsy and/or intraoperative frozen section diagnosis increase the accuracy in diagnosing a malignant lesion. Conservative parotid surgery with nerve monitoring remains state-of-the-art. Free flaps or musculoaponeurotic flaps are proposed for prevention of Frey's syndrome. As parotid cancer often shows skip metastases, complete ipsilateral neck dissection (level I-V) is indicated particularly in high-grade lesions. Adjuvant radio(chemo)therapy increases local tumour control, whereas overall survival is not necessarily improved. Current results of systemic chemotherapy or targeted therapy in advanced tumour stages are disappointing. CONCLUSION Despite several developments, salivary gland carcinomas remain a heterogeneous group of tumours challenging both pathologists and clinicians.
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Affiliation(s)
- Tobias Ettl
- Department of Oral and Maxillofacial Surgery, Regensburg University, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
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Oeffinger KC, van Leeuwen FE, Hodgson DC. Methods to assess adverse health-related outcomes in cancer survivors. Cancer Epidemiol Biomarkers Prev 2012; 20:2022-34. [PMID: 21980010 DOI: 10.1158/1055-9965.epi-11-0674] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Designing a study focused on adverse health-related outcomes among cancer survivors is complex. Similarly, reading and interpreting the findings of a survivorship-focused study requires an appreciation of the complexities of study design, potential biases, confounding factors, and other limitations. The topic areas are broad--study design, comparison populations, measures of risk, key health outcomes of interest, potential modifying factors to consider. With brevity, this article includes basic information to consider within these areas as well as examples and concepts intended to advance the science of survivorship research and encourage further reading and exploration.
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Affiliation(s)
- Kevin C Oeffinger
- Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
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Narendranathan T, Guiney AJ, Drummond KJ. Mixed, solid cystic mass in the right temporal lobe. J Clin Neurosci 2010. [DOI: 10.1016/j.jocn.2009.07.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Staege MS, Körholz D. New treatment strategies for Hodgkin's lymphoma. Leuk Res 2009; 33:886-8. [DOI: 10.1016/j.leukres.2009.01.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Revised: 01/11/2009] [Accepted: 01/12/2009] [Indexed: 01/01/2023]
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Abstract
Chromosomal translocations and fusion oncogenes serve as the ultimate biomarker for clinicians as they show specificity for distinct histopathologic malignancies while simultaneously encoding an etiologic mutation and a therapeutic target. Previously considered a minor mutational event in epithelial solid tumors, new methodologies that do not rely on the detection of macroscopic cytogenetic alterations, as well as access to large series of annotated clinical material, are expanding the inventory of recurrent fusion oncogenes in both common and rare solid epithelial tumors. Unexpectedly, related assays are also revealing a high number of tandem or chimeric transcripts in normal tissues including, in one provocative case, a template for a known fusion oncogene. These observations may force us to reassess long-held views on the definition of a gene. They also raise the possibility that some rearrangements might represent constitutive forms of a physiological chimeric transcript. Defining the chimeric transcriptome in both health (transcription-induced chimerism and intergenic splicing) and disease (mutation-associated fusion oncogenes) will play an increasingly important role in the diagnosis, prognosis, and therapy of patients with cancer.
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