Marigdalia K Ramirez-Fort1, Jianying Zeng2, Amir Feily3, Luis A Ramirez-Pacheco4, Joseph M Jenrette5, David L Mayhew6, Talal Syed7, S Lewis Cooper5, Craig Linden8, Witney S Graybill9, Lars E French10, Christopher S Lange11. 1. Radiation Oncology, Medical University of South Carolina, Charleston, SC, United States; Urological Oncology, Weill Cornell Medical College, New York, NY, United States. 2. Pathology, State University of New York Downstate Medical Center, Brooklyn, NY, United States. 3. Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran. 4. Jersey State Pain Management, Union City, NJ, United States. 5. Radiation Oncology, Medical University of South Carolina, Charleston, SC, United States. 6. Radiation Oncology, Tufts Medical Center, Boston, MA, United States; Medicine, Dana Farber Cancer Institute, Boston, MA, United States. 7. Radiation Oncology, State University of New York Downstate Medical Center, Brooklyn, NY, United States. 8. Radiology, State University of New York Downstate Medical Center, Brooklyn, NY, United States. 9. Gynecology Oncology, Medical University of South Carolina, Charleston, SC, United States. 10. Dermatology, Zurich University Hospital, Zurich, Switzerland. 11. Radiation Oncology, State University of New York Downstate Medical Center, Brooklyn, NY, United States. Electronic address: Christopher.Lange@downstate.edu.
Abstract
PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. MATERIALS AND METHODS: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. CONCLUSIONS: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy.
PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. MATERIALS AND METHODS: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. CONCLUSIONS: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy.
Authors: Marigdalia K Ramirez-Fort; Paula Suarez; Margely Carrion; Daniel Weiner; Claire Postl; Ricardo Arribas; Mehdi Sayyah; Digna V Forta; M Junaid Niaz; Amir Feily; Christopher S Lange; Zhahedia Zhaythseff Fort; Migdalia Fort Journal: Rep Pract Oncol Radiother Date: 2020-04-30
Authors: Ravi Mahalingam; Anne Gershon; Michael Gershon; Jeffrey I Cohen; Ann Arvin; Leigh Zerboni; Hua Zhu; Wayne Gray; Ilhem Messaoudi; Vicki Traina-Dorge Journal: Viruses Date: 2019-05-31 Impact factor: 5.048
Authors: Larissa Henze; Christoph Buhl; Michael Sandherr; Oliver A Cornely; Werner J Heinz; Yascha Khodamoradi; Til Ramon Kiderlen; Philipp Koehler; Alrun Seidler; Rosanne Sprute; Martin Schmidt-Hieber; Marie von Lilienfeld-Toal Journal: Ann Hematol Date: 2022-01-07 Impact factor: 3.673
Authors: Volodymyr V Oberemok; Kateryna V Laikova; Kseniya A Yurchenko; Irina I Fomochkina; Anatolii V Kubyshkin Journal: Inflamm Res Date: 2020-10-30 Impact factor: 4.575