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Dou L, Yan Y, Lu E, Li F, Tian D, Deng L, Zhang X, Zhang R, Li Y, Zhang Y, Sun Y. Composition analysis and mechanism of Guizhi Fuling capsule in anti-cisplatin-resistant ovarian cancer. Transl Oncol 2025; 52:102244. [PMID: 39662450 PMCID: PMC11683237 DOI: 10.1016/j.tranon.2024.102244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 11/18/2024] [Accepted: 12/07/2024] [Indexed: 12/13/2024] Open
Abstract
OBJECTIVE Cisplatin is the main chemotherapy drug for advanced ovarian cancer, but drug resistance often occurs. The aim of this study is to explore the molecular mechanism by which Guizhi Fuling capsule inhibits cisplatin resistance in ovarian cancer. METHODS First, differences in cisplatin resistance, PA2G4 gene expression, migration, and invasion in A2780 cells and A2780/DDP cells were analyzed by qRT-PCR, scratch assay, transwell, immunofluorescence, and western blotting. Then, LC-MS/MS analysis of GFC chemical composition. qRT-PCR, scratch tests, transwell, pseudopodium formation, immunofluorescence, and western blotting were used to explore the mechanism by which GFC inhibited A2780/DDP cell migration and invasion. Finally, the anti-tumor efficacy of GFC was verified by in vivo experiments. RESULTS A2780/DDP cells had a greater ability to migrate and invade compared to their parents. Cell viability experiments showed that the migration and invasion ability of A278/DDP cells were significantly inhibited with the increase of GFC concentration. qRT-PCR results showed that compared with the blank control group, cisplatin group and GFC group, the transcription level of PA2G4 gene in the combination treatment group was significantly reduced. We also found that GFC combined with cisplatin inhibited the PI3K/AKT/GSK-3β signaling pathway by targeting PA2G4 gene expression, inhibited the epithelial-mesenchymal transition signaling pathway, decreased cell adhesion and inhibited the formation of cell pseudopodias. CONCLUSION GFC combined with cisplatin can target PA2G4 gene to regulate PI3K/AKT/GSK-3β Signaling pathway, inhibiting the invasion and migration of cisplatin resistant A2780/DDP cells in ovarian cancer.
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Affiliation(s)
- Lei Dou
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Yan Yan
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Enting Lu
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Fangmei Li
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Dongli Tian
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Lei Deng
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Xue Zhang
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Rongjin Zhang
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Yin Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Yi Zhang
- Department of Gynecology, the First Hospital of China Medical University, Shenyang 110001, China.
| | - Ye Sun
- Department of Pathogenic Biology, College of Basic Medical Sciences, Shenyang Medical College, Shenyang 110034, China.
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Arnold CR, Mangesius J, Portnaia I, Ganswindt U, Wolff HA. Innovative therapeutic strategies to overcome radioresistance in breast cancer. Front Oncol 2024; 14:1379986. [PMID: 38873260 PMCID: PMC11169591 DOI: 10.3389/fonc.2024.1379986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/10/2024] [Indexed: 06/15/2024] Open
Abstract
Despite a comparatively favorable prognosis relative to other malignancies, breast cancer continues to significantly impact women's health globally, partly due to its high incidence rate. A critical factor in treatment failure is radiation resistance - the capacity of tumor cells to withstand high doses of ionizing radiation. Advancements in understanding the cellular and molecular mechanisms underlying radioresistance, coupled with enhanced characterization of radioresistant cell clones, are paving the way for the development of novel treatment modalities that hold potential for future clinical application. In the context of combating radioresistance in breast cancer, potential targets of interest include long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and their associated signaling pathways, along with other signal transduction routes amenable to pharmacological intervention. Furthermore, technical, and methodological innovations, such as the integration of hyperthermia or nanoparticles with radiotherapy, have the potential to enhance treatment responses in patients with radioresistant breast cancer. This review endeavors to provide a comprehensive survey of the current scientific landscape, focusing on novel therapeutic advancements specifically addressing radioresistant breast cancer.
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Affiliation(s)
| | - Julian Mangesius
- Department of Radiation-Oncology, Medical University of Innsbruck, Innsbruck, Austria
| | - Iana Portnaia
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Ute Ganswindt
- Department of Radiation-Oncology, Medical University of Innsbruck, Innsbruck, Austria
| | - Hendrik Andreas Wolff
- Department of Radiology, Nuclear Medicine, and Radiotherapy, Radiology Munich, Munich, Germany
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Shimomura O, Endo M, Makishima H, Yamada T, Hashimoto S, Numajiri H, Miyazaki Y, Doi M, Furuya K, Takahashi K, Moriwaki T, Hasegawa N, Yamamoto Y, Niisato Y, Kobayashi M, Mizumoto M, Nakai K, Saito T, Hoshiai S, Saida T, Mathis BJ, Mori K, Nakajima T, Tsuchiya K, Sakurai H, Oda T. Triple modal treatment comprising with proton beam radiation, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer: a phase I/II study protocol (TT-LAP trial). BMC Cancer 2023; 23:624. [PMID: 37403011 PMCID: PMC10320973 DOI: 10.1186/s12885-023-11110-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 06/26/2023] [Indexed: 07/06/2023] Open
Abstract
BACKGROUND Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .
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Affiliation(s)
- Osamu Shimomura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | - Masato Endo
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | | | - Takeshi Yamada
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | - Shinji Hashimoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | - Haruko Numajiri
- Department of Radiation oncology, University of Tsukuba, Ibaraki, Japan
| | - Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | - Manami Doi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | - Kinji Furuya
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | - Kazuhiro Takahashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan
| | | | - Naoyuki Hasegawa
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | | | - Yusuke Niisato
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | - Mariko Kobayashi
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | - Masashi Mizumoto
- Department of Radiation oncology, University of Tsukuba, Ibaraki, Japan
| | - Kei Nakai
- Department of Radiation oncology, University of Tsukuba, Ibaraki, Japan
| | - Takashi Saito
- Department of Radiation oncology, University of Tsukuba, Ibaraki, Japan
| | - Sodai Hoshiai
- Department of Radiology, University of Tsukuba, Ibaraki, Japan
| | - Tsukasa Saida
- Department of Radiology, University of Tsukuba, Ibaraki, Japan
| | - Bryan J Mathis
- International Medical Center, University of Tsukuba Hospital, Ibaraki, Japan
| | - Kensaku Mori
- Department of Radiology, University of Tsukuba, Ibaraki, Japan
| | | | - Kiichiro Tsuchiya
- Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan
| | - Hideyuki Sakurai
- Department of Radiation oncology, University of Tsukuba, Ibaraki, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
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Fiorentini G, Sarti D, Mambrini A, Hammarberg Ferri I, Bonucci M, Sciacca PG, Ballerini M, Bonanno S, Milandri C, Nani R, Guadagni S, Dentico P, Fiorentini C. Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer: A multicenter retrospective observational comparative study. World J Clin Oncol 2023; 14:215-226. [PMID: 37398545 PMCID: PMC10311475 DOI: 10.5306/wjco.v14.i6.215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/18/2023] [Accepted: 06/06/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electro-hyperthermia (mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer. AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer. METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer (stage III and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128 (59%) of them were treated with CHT (no-mEHT) and 89 (41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT. RESULTS Median patients' age was 67 years (range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group (20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses (45% vs 24%, P = 0.0018) and a lower number of progressions (4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions. CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage III-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.
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Affiliation(s)
- Giammaria Fiorentini
- Integrative Oncology, Integrative Oncology Outpatient Clinic, Bologna 40121, Italy
| | - Donatella Sarti
- Department of Oncology, Santa Maria della Misericordia Hospital, Urbino 60129, Italy
| | - Andrea Mambrini
- Department of Oncology, Azienda Sanitaria Locale Toscana Nord Ovest, Massa Carrara Hospital, Massa 54100, Italy
| | | | - Massimo Bonucci
- Integrative Oncology, Association Research Center for Integrative Oncology Treatments, Roma 00166, Italy
| | | | - Marco Ballerini
- Hyperthermia Unit, Bellessere Medical Center, Terni 05100, Italy
| | | | - Carlo Milandri
- Medical Oncology, San Donato Hospital, Arezzo 52100, Italy
| | - Roberto Nani
- Interventional Radiology Unit, Humanitas Gavazzeni, Bergamo 24121, Italy
| | - Stefano Guadagni
- Applied Clinical Sciences and Biotechnology, Section of General Surgery, University of L'Aquila, L'Aquila 67100, Italy
| | - Patrizia Dentico
- Hyperthermia Service, Medical Oncology Unit, San Giuseppe Hospital, Empoli 50053, Italy
| | - Caterina Fiorentini
- Prevention and Sports Medicine, University Hospital Klinikum rechts der Isar, Technical University of Munich, Munich 80331, Germany
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Lambin T, Lafon C, Drainville RA, Pioche M, Prat F. Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma. World J Gastroenterol 2022; 28:1288-1303. [PMID: 35645539 PMCID: PMC9099187 DOI: 10.3748/wjg.v28.i13.1288] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/10/2022] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment (TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients' quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy - most commonly using a local high single dose - are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.
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Affiliation(s)
- Thomas Lambin
- LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, Lyon 69003, France
- Department of Gastroenterology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69008, France
| | - Cyril Lafon
- LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, Lyon 69003, France
| | | | - Mathieu Pioche
- Department of Gastroenterology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69008, France
| | - Frédéric Prat
- Service d’Endoscopie Digestive, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy 92110, France
- INSERM U1016, Institut Cochin, Université de Paris, Paris 75014, France
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Present Practice of Radiative Deep Hyperthermia in Combination with Radiotherapy in Switzerland. Cancers (Basel) 2022; 14:cancers14051175. [PMID: 35267486 PMCID: PMC8909523 DOI: 10.3390/cancers14051175] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/15/2022] [Accepted: 02/18/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Moderate hyperthermia is a potent and evidence-based radiosensitizer. Several indications are reimbursed for the combination of deep hyperthermia with radiotherapy (dHT+RT). We evaluated the current practice of dHT+RT in Switzerland. METHODS All indications presented to the national hyperthermia tumor board for dHT between January 2017 and June 2021 were evaluated and treatment schedules were analyzed using descriptive statistics. RESULTS Of 183 patients presented at the hyperthermia tumor board, 71.6% were accepted and 54.1% (99/183) finally received dHT. The most commonly reimbursed dHT indications were "local recurrence and compression" (20%), rectal (14.7%) and bladder (13.7%) cancer, respectively. For 25.3% of patients, an individual request for insurance cover was necessary. 47.4% of patients were treated with curative intent; 36.8% were in-house patients and 63.2% were referred from other hospitals. CONCLUSIONS Approximately two thirds of patients were referred for dHT+RT from external hospitals, indicating a general demand for dHT in Switzerland. The patterns of care were diverse with respect to treatment indication. To the best of our knowledge, this study shows for the first time the pattern of care in a national cohort treated with dHT+RT. This insight will serve as the basis for a national strategy to evaluate and expand the evidence for dHT.
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Versteijne E, de Hingh IHJT, Homs MYV, Intven MPW, Klaase JM, van Santvoort HC, de Vos-Geelen J, Wilmink JW, van Tienhoven G. Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer: Chemotherapy or Chemoradiotherapy? Front Oncol 2022; 11:744161. [PMID: 35237500 PMCID: PMC8882845 DOI: 10.3389/fonc.2021.744161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 12/30/2021] [Indexed: 12/12/2022] Open
Abstract
Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC.
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Affiliation(s)
- Eva Versteijne
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Ignace H. J. T. de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven and GROW—School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
| | - Marjolein Y. V. Homs
- Department Medical Oncology, Erasmus Medical Center (MC) Cancer Institute, Rotterdam, Netherlands
| | - Martijn P. W. Intven
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Joost M. Klaase
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen, Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, Regionaal Academisch Kankercentrum Utrecht (RAKU), St Antonius Hospital, Nieuwegein, Netherlands
| | - Judith de Vos-Geelen
- Department of Internal Medicine, Division of Medical Oncology, GROW—School for Oncology and Developmental Biology, Maastricht University Medical Center (UMC+), Maastricht, Netherlands
| | - Johanna W. Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Geertjan van Tienhoven
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands
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Petenyi FG, Garay T, Muhl D, Izso B, Karaszi A, Borbenyi E, Herold M, Herold Z, Szasz AM, Dank M. Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients-A Single-Center Case-Control Study. Diseases 2021; 9:81. [PMID: 34842668 PMCID: PMC8628793 DOI: 10.3390/diseases9040081] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/03/2021] [Accepted: 10/30/2021] [Indexed: 02/05/2023] Open
Abstract
UNLABELLED Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients' oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients' overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort.
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Affiliation(s)
- Flora Greta Petenyi
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
| | - Tamas Garay
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Dorottya Muhl
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Blanka Izso
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
| | - Adam Karaszi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Erika Borbenyi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Magdolna Herold
- Department of Internal Medicine and Hematology, Semmelweis University, 1088 Budapest, Hungary;
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
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Herold Z, Szasz AM, Dank M. Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system. World J Gastrointest Oncol 2021; 13:1109-1120. [PMID: 34616516 PMCID: PMC8465447 DOI: 10.4251/wjgo.v13.i9.1109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/29/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatopancreatobiliary tumors are challenging to treat, and the advanced or metastatic forms have a very low 5-year survival rate. Several drug combinations have been tested, and new therapeutic approaches have been introduced in the last decades, including radiofrequency and heat based methods. Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant, tumoricidal, and chemoradiotherapy sensitizer effects. Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques. Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies. Hyperthermia in biliary cancers is a less investigated area. High local and overall responses to treatment, increased progression-free and overall survival, and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types. With the evolution of chemotherapeutic agents and the introduction of newer techniques, the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects. However, despite the many positive effects of hyperthermia, its use is still only known at the experimental level, and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.
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Affiliation(s)
- Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - A Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
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Ren G, Ju H, Wu Y, Song H, Ma X, Ge M, Qiu W, Chen Y, He Y, Zhuang Q, Meng J, Guo W. A multicenter randomized phase II trial of hyperthermia combined with TPF induction chemotherapy compared with TPF induction chemotherapy in locally advanced resectable oral squamous cell carcinoma. Int J Hyperthermia 2021; 38:939-947. [PMID: 34134574 DOI: 10.1080/02656736.2021.1937714] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Hyperthermia has been reported to cause cancer stage regression, thus providing surgical opportunities in patients with unresectable tumors and improving the quality of life of patients by preserving certain organs. METHODS A prospective open-label phase II trial was conducted to evaluate the efficacy of hyperthermia combined with induction chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients received hyperthermia combined with two cycles of 5-fluorouracil, cisplatin, and docetaxel (TPF) induction chemotherapy regimens or TPF induction chemotherapy alone, followed by radical surgery with postoperative radiotherapy. The primary endpoint was the clinical response rate of the induction chemotherapy. The secondary endpoints were overall survival (OS), disease-free survival (DFS), and toxicity. RESULTS A total of 120 patients were enrolled, and 115 patients were included in the clinical response analysis. The clinical response rate was significantly higher in the experimental arm than in the control arm (65.45% vs. 40.00%, p = 0.0088). There were no unexpected toxicities, and hyperthermia and induction chemotherapy did not increase the perioperative morbidity rate. Moreover, there was a significant improvement in DFS, but no significant difference in OS between the two arms. In the subgroup analysis, increased OS and DFS rates were associated with patients with favorable clinical response after induction chemotherapy in the total population, experimental arm, and control arm. CONCLUSIONS Our study demonstrates that hyperthermia combined with induction chemotherapy is associated with a high response rate and provides a new treatment option for patients with resectable stage III or IVA OSCC.
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Affiliation(s)
- Guoxin Ren
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Houyu Ju
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Yunteng Wu
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Hao Song
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Xuhui Ma
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Minghua Ge
- Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Weiliu Qiu
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Yazhu Chen
- Biomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai Med-X Engineering Center for Medical Equipment and Technology, Shanghai Jiao Tong University, Shanghai, China
| | - Yue He
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
| | - Qianwei Zhuang
- Department of Oromaxillofacial Head and Neck Surgery, College of Medicine, Affiliated Xuzhou Hospital, Southeast University, Xuzhou, China
| | - Jian Meng
- Department of Oromaxillofacial Head and Neck Surgery, College of Medicine, Affiliated Xuzhou Hospital, Southeast University, Xuzhou, China
| | - Wei Guo
- Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China
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11
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Han S, Cao C, Yuan Y, Chen J, Yin L, Xu H, Liu J, Wang W, Li Y, Wang L, Zhou S, Li F, Wang W, Ji J, Long H, Yin S, Li J, Han J, Liu R, Li M, Zhang X. Transcatheter Arterial Infusion Combined With Radioactive Particles in the Treatment of Advanced Body/Tail Pancreatic Cancer: A Retrospective Cohort Study. Pancreas 2021; 50:822-826. [PMID: 34347726 DOI: 10.1097/mpa.0000000000001851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail pancreatic cancer by assessing the short-term and overall survival rates. METHODS We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable, and no other confirmed malignant tumors, patients were assigned into 3 groups according to their treatment: routine intravenous chemotherapy, TAI, and TAI combined with radioactive particles. RESULTS The median survival time was 6 months in the control group, 10 months in the TAI group, and 13 months in the TAI combined group. The Kaplan-Meier estimates of the overall survival among the 3 groups, indicating that there is significant difference among 3 groups (P < 0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P < 0.002). CONCLUSIONS In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.
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Affiliation(s)
- Shilong Han
- From the Department of Interventional and Vascular Surgery
| | - Chuanwu Cao
- From the Department of Interventional and Vascular Surgery
| | - Yifeng Yuan
- From the Department of Interventional and Vascular Surgery
| | | | - Linan Yin
- Department of Interventional, Harbin Medical University Cancer Hospital, Harbin
| | - Huirong Xu
- Department of Interventional Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
| | - Jingzhou Liu
- Department of Interventional Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
| | - Wujie Wang
- Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan
| | - Yuliang Li
- Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan
| | - Lizhou Wang
- Department of Medical Imaging, Affiliated Hospital of Guizhou Medical University, Guizhou
| | - Shi Zhou
- Department of Medical Imaging, Affiliated Hospital of Guizhou Medical University, Guizhou
| | - Fenqiang Li
- Department of Interventional Radiology, First Hospital of Lanzhou University, Lanzhou
| | - Wenhui Wang
- Department of Interventional Radiology, First Hospital of Lanzhou University, Lanzhou
| | - Jiansong Ji
- Department of Interventional Radiology, Lishui Hospital of Zhejiang University, Lishui Central Hospital, Lishui, China
| | - Haideng Long
- Department of Interventional and Vascular Surgery, Hefei Hospital Affiliated to Anhui Medical University, Hefei
| | - Shiwu Yin
- Department of Interventional and Vascular Surgery, Hefei Hospital Affiliated to Anhui Medical University, Hefei
| | - Jue Li
- Heart, Lung and Blood Vessel Center, School of Medicine, Tongji University, Shanghai, China
| | - Jianjun Han
- Department of Interventional Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences
| | - Ruibao Liu
- Department of Interventional, Harbin Medical University Cancer Hospital, Harbin
| | | | - Xiaoping Zhang
- Institute of Interventional and Vascular surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai
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12
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Kok HP, Cressman ENK, Ceelen W, Brace CL, Ivkov R, Grüll H, Ter Haar G, Wust P, Crezee J. Heating technology for malignant tumors: a review. Int J Hyperthermia 2021; 37:711-741. [PMID: 32579419 DOI: 10.1080/02656736.2020.1779357] [Citation(s) in RCA: 184] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.
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Affiliation(s)
- H Petra Kok
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Erik N K Cressman
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, Ghent, Belgium
| | - Christopher L Brace
- Department of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Robert Ivkov
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.,Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
| | - Holger Grüll
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany
| | - Gail Ter Haar
- Department of Physics, The Institute of Cancer Research, London, UK
| | - Peter Wust
- Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Johannes Crezee
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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13
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Shimomura O, Oda T, Hashimoto S, Doi M, Hiroshima Y, Numajiri H, Takahashi K, Furuya K, Miyazaki Y, Owada Y, Ogawa K, Ohara Y, Hisakura K, Akashi Y, Enomoto T, Sakurai H. Survival impact on triple-modal strategy comprising hyperthermia, external radiation, and chemotherapy for unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma. Surg Oncol 2021; 37:101542. [PMID: 33740629 DOI: 10.1016/j.suronc.2021.101542] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/24/2021] [Accepted: 03/02/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Present treatment strategy for unresectable locally advanced (UR-LA) pancreatic ductal adenocarcinoma (PDAC) patients is controversial. Hence, a triple-modal therapy, which is a multidisciplinary strategy, was designed for patients with UR-LA PDAC by adding hyperthermia to conventional chemoradiotherapy at our institution. In this study we aimed to evaluate the effectiveness of this strategy. METHODS Data of 21 UR-LA PDAC patients who underwent the triple-modal treatment were retrospectively analyzed for evaluating the safety and oncological effect of the treatment. The treatment schedule included, five concurrent infusions of gemcitabine (800 mg/m2) followed by hyperthermia (1 h) and X-ray (2 Gy) or proton beam radiation (2.7 Gy) on days 1, 8, 15, 29, and 36. Additional radiotherapies applied a total dose of 50 Gy/25 fr for X-ray radiation or 67.5 Gy/25 fr for proton beam radiation. RESULTS Median overall survival (OS) was 23.6 months. Conversion surgery was performed in 5 patients (23.8%), and a R0 margin could be achieved in 4 of them; however, their median OS (16.3 months) tended to be shorter than that of the patients who did not undergo resection (23.6 months, p = 0.562). Further, the median OS of patients who underwent proton beam radiation (28.0 months) was significantly longer than that of patients who underwent X-ray radiation (13.9 months, p = 0.045). Most adverse events were manageable, except for one grade 3 gastric ulcer. The median tumor size and marker reduction rates were -17% and -91%, respectively. The tumor responses were partial response, stable disease, and progressive disease in 3, 15, and 3 patients, respectively. CONCLUSION Triple-modal strategy, especially when combined with proton beam radiation, is feasible and results in favorable survival outcomes in patients with UR-LA PDAC.
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Affiliation(s)
- Osamu Shimomura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
| | - Shinji Hashimoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Manami Doi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yuichi Hiroshima
- Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Haruko Numajiri
- Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Kazuhiro Takahashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Kinji Furuya
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Koichi Ogawa
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yusuke Ohara
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Katsuji Hisakura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Tsuyoshi Enomoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
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14
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Prokhorova A, Ley S, Helbig M. Quantitative Interpretation of UWB Radar Images for Non-Invasive Tissue Temperature Estimation during Hyperthermia. Diagnostics (Basel) 2021; 11:diagnostics11050818. [PMID: 33946581 PMCID: PMC8147219 DOI: 10.3390/diagnostics11050818] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/16/2021] [Accepted: 04/28/2021] [Indexed: 12/26/2022] Open
Abstract
The knowledge of temperature distribution inside the tissue to be treated is essential for patient safety, workflow and clinical outcomes of thermal therapies. Microwave imaging represents a promising approach for non-invasive tissue temperature monitoring during hyperthermia treatment. In the present paper, a methodology for quantitative non-invasive tissue temperature estimation based on ultra-wideband (UWB) radar imaging in the microwave frequency range is described. The capabilities of the proposed method are demonstrated by experiments with liquid phantoms and three-dimensional (3D) Delay-and-Sum beamforming algorithms. The results of our investigation show that the methodology can be applied for detection and estimation of the temperature induced dielectric properties change.
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15
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van der Horst A, Kok HP, Crezee J. Effect of gastrointestinal gas on the temperature distribution in pancreatic cancer hyperthermia treatment planning. Int J Hyperthermia 2021; 38:229-240. [PMID: 33602033 DOI: 10.1080/02656736.2021.1882709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
PURPOSE In pancreatic cancer treatment, hyperthermia can be added to increase efficacy of chemo- and/or radiotherapy. Gas in stomach, intestines and colon is often in close proximity to the target volume. We investigated the impact of variations in gastrointestinal gas (GG) on temperature distributions during simulated hyperthermia treatment (HT). METHODS We used sets of one CT and eight cone-beam CT (CBCT) scans obtained prior to/during fractionated image-guided radiotherapy in four pancreatic cancer patients. In Plan2Heat, we simulated locoregional heating by an ALBA-4D phased array radiofrequency system and calculated temperature distributions for (i) the segmented CT (sCT), (ii) sCT with GG replaced by muscle (sCT0), (iii) sCT0 with eight different GG distributions as visible on CBCT inserted (sCTCBCT). We calculated cumulative temperature-volume histograms for the clinical target volume (CTV) for all ten temperature distributions for each patient and investigated the relationship between GG volume and change in ΔT50 (temperature increase at 50% of CTV volume). We determined location and volume of normal tissue receiving a high thermal dose. RESULTS GG volume on CBCT varied greatly (9-991 cm3). ΔT50 increased for increasing GG volume; maximum ΔT50 difference per patient was 0.4-0.6 °C. The risk for GG-associated treatment-limiting hot spots appeared low. Normal tissue high-temperature regions mostly occurred anteriorly; their volume and maximum temperature showed moderate positive correlations with GG volume, while fat-muscle interfaces were associated with higher risks for hot spots. CONCLUSIONS Considerable changes in volume and position of gastrointestinal gas can occur and are associated with clinically relevant tumor temperature differences.
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Affiliation(s)
- Astrid van der Horst
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - H Petra Kok
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Johannes Crezee
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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16
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Rogers SJ, Datta NR, Puric E, Timm O, Marder D, Khan S, Mamot C, Knuchel J, Siebenhüner A, Pestalozzi B, Guckenberger M, Bodis S, Riesterer O. The addition of deep hyperthermia to gemcitabine-based chemoradiation may achieve enhanced survival in unresectable locally advanced adenocarcinoma of the pancreas. Clin Transl Radiat Oncol 2021; 27:109-113. [PMID: 33598571 PMCID: PMC7868682 DOI: 10.1016/j.ctro.2021.01.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023] Open
Abstract
Intensification of chemoradiation with hyperthermia was feasible in nine patients with LAPC. Only one grade three toxicity was reported and two tumours became resectable. The 24 months median OS and 100% 1 year OS are superior to historical series. Introduction Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. Methods Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. Results One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. Conclusions Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.
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Affiliation(s)
- S J Rogers
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - N R Datta
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - E Puric
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - O Timm
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - D Marder
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - S Khan
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - C Mamot
- Department of Medical Oncology and Haematology, Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland
| | - J Knuchel
- Department of Gastroenterology, Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland
| | - A Siebenhüner
- Department of Medical Oncology and Haematology, University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland
| | - B Pestalozzi
- Department of Medical Oncology and Haematology, University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland
| | - M Guckenberger
- Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Switzerland
| | - S Bodis
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - O Riesterer
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, 5001 Aarau, Switzerland.,Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Switzerland
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17
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Datta NR, Kok HP, Crezee H, Gaipl US, Bodis S. Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses. Front Oncol 2020; 10:819. [PMID: 32596144 PMCID: PMC7303270 DOI: 10.3389/fonc.2020.00819] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 04/27/2020] [Indexed: 12/14/2022] Open
Abstract
Moderate hyperthermia at temperatures between 40 and 44°C is a multifaceted therapeutic modality. It is a potent radiosensitizer, interacts favorably with a host of chemotherapeutic agents, and, in combination with radiotherapy, enforces immunomodulation akin to “in situ tumor vaccination.” By sensitizing hypoxic tumor cells and inhibiting repair of radiotherapy-induced DNA damage, the properties of hyperthermia delivered together with photons might provide a tumor-selective therapeutic advantage analogous to high linear energy transfer (LET) neutrons, but with less normal tissue toxicity. Furthermore, the high LET attributes of hyperthermia thermoradiobiologically are likely to enhance low LET protons; thus, proton thermoradiotherapy would mimic 12C ion therapy. Hyperthermia with radiotherapy and/or chemotherapy substantially improves therapeutic outcomes without enhancing normal tissue morbidities, yielding level I evidence reported in several randomized clinical trials, systematic reviews, and meta-analyses for various tumor sites. Technological advancements in hyperthermia delivery, advancements in hyperthermia treatment planning, online invasive and non-invasive MR-guided thermometry, and adherence to quality assurance guidelines have ensured safe and effective delivery of hyperthermia to the target region. Novel biological modeling permits integration of hyperthermia and radiotherapy treatment plans. Further, hyperthermia along with immune checkpoint inhibitors and DNA damage repair inhibitors could further augment the therapeutic efficacy resulting in synthetic lethality. Additionally, hyperthermia induced by magnetic nanoparticles coupled to selective payloads, namely, tumor-specific radiotheranostics (for both tumor imaging and radionuclide therapy), chemotherapeutic drugs, immunotherapeutic agents, and gene silencing, could provide a comprehensive tumor-specific theranostic modality akin to “magic (nano)bullets.” To get a realistic overview of the strength (S), weakness (W), opportunities (O), and threats (T) of hyperthermia, a SWOT analysis has been undertaken. Additionally, a TOWS analysis categorizes future strategies to facilitate further integration of hyperthermia with the current treatment modalities. These could gainfully accomplish a safe, versatile, and cost-effective enhancement of the existing therapeutic armamentarium to improve outcomes in clinical oncology.
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Affiliation(s)
- Niloy R Datta
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland
| | - H Petra Kok
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Hans Crezee
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Udo S Gaipl
- Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Stephan Bodis
- Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland
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18
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Fiorentini G, Sarti D, Gadaleta CD, Ballerini M, Fiorentini C, Garfagno T, Ranieri G, Guadagni S. A Narrative Review of Regional Hyperthermia: Updates From 2010 to 2019. Integr Cancer Ther 2020; 19:1534735420932648. [PMID: 33054425 PMCID: PMC7570290 DOI: 10.1177/1534735420932648] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/30/2020] [Accepted: 05/14/2020] [Indexed: 12/13/2022] Open
Abstract
The role of hyperthermia (HT) in cancer therapy and palliative care has been discussed for years in the literature. There are plenty of articles that show good feasibility of HT and its efficacy in terms of tumor response and survival improvements. Nevertheless, HT has never gained enough interest among oncologists to become a standard therapy in clinical practice. The main advantage of HT is the enhancement of chemotherapy (CHT), radiotherapy (RT), chemoradiotherapy (CRT), and immunotherapy benefits. This effect has been confirmed in several types of tumors: esophageal, gastrointestinal, pancreas, breast, cervix, head and neck, and bladder cancers, and soft tissue sarcoma. HT effects include oxygenation and perfusion changes, DNA repair inhibition and immune system activation as a consequence of new antigen exposure. The literature shows a wide variety of randomized, nonrandomized, and observational studies and both prospective and retrospective data to confirm the advantage of HT association to CHT and RT. There are still many ongoing trials on this subject. This article summarizes the available literature on HT in order to update the current knowledge on HT use in association with RT and/or CHT from 2010 up to 2019.
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Affiliation(s)
- Giammaria Fiorentini
- Azienda Ospedaliera “Ospedali Riuniti Marche Nord,” Pesaro, Italy
- Private Clinic Ravenna33, Ravenna, Italy
| | - Donatella Sarti
- Azienda Ospedaliera “Ospedali Riuniti Marche Nord,” Pesaro, Italy
| | - Cosmo Damiano Gadaleta
- Department of Interventional and Integrated Medical Oncology, National Cancer Research Centre, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
| | | | | | | | - Girolamo Ranieri
- Department of Interventional and Integrated Medical Oncology, National Cancer Research Centre, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
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Radiotherapy for Melanoma: More than DNA Damage. Dermatol Res Pract 2019; 2019:9435389. [PMID: 31073304 PMCID: PMC6470446 DOI: 10.1155/2019/9435389] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/26/2018] [Accepted: 03/04/2019] [Indexed: 12/20/2022] Open
Abstract
Despite its reputation as a radioresistant tumour, there is evidence to support a role for radiotherapy in patients with melanoma and we summarise current clinical practice. Melanoma is a highly immunogenic tumour and in this era of immunotherapy, there is renewed interest in the potential of irradiation, not only as an adjuvant and palliative treatment, but also as an immune stimulant. It has long been known that radiation causes not only DNA strand breaks, apoptosis, and necrosis, but also immunogenic modulation and cell death through the induction of dendritic cells, cell adhesion molecules, death receptors, and tumour-associated antigens, effectively transforming the tumour into an individualised vaccine. This immune response can be enhanced by the application of clinical hyperthermia as evidenced by randomised trial data in patients with melanoma. The large fraction sizes used in cranial radiosurgery and stereotactic body radiotherapy are more immunogenic than conventional fractionation, which provides additional radiobiological justification for these techniques in this disease entity. Given the immune priming effect of radiotherapy, there is a strong but complex biological rationale and an increasing body of evidence for synergy in combination with immune checkpoint inhibitors, which are now first-line therapy in patients with recurrent or metastatic melanoma. There is great potential to increase local control and abscopal effects by combining radiotherapy with both immunotherapy and hyperthermia, and a combination of all three modalities is suggested as the next important trial in this refractory disease.
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Fiorentini G, Sarti D, Casadei V, Milandri C, Dentico P, Mambrini A, Nani R, Fiorentini C, Guadagni S. Modulated Electro-Hyperthermia as Palliative Treatment for Pancreatic Cancer: A Retrospective Observational Study on 106 Patients. Integr Cancer Ther 2019; 18:1534735419878505. [PMID: 31561722 PMCID: PMC6767725 DOI: 10.1177/1534735419878505] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/09/2019] [Accepted: 08/29/2019] [Indexed: 12/17/2022] Open
Abstract
Background: Pancreatic adenocarcinoma has a poor prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT) has been increasingly used for pancreatic cancer palliative care and therapy. Objective: To monitor the efficacy and safety of mEHT for the treatment of advanced pancreatic cancer. Methods: We collected data retrospectively on 106 patients affected by stage III-IV pancreatic adenocarcinoma. They were divided into 2 groups: patients who did not receive mEHT (no-mEHT) and patients who were treated with mEHT. We performed mEHT applying a power of 60 to 150 W for 40 to 90 minutes. The mEHT treatment was associated with chemotherapy and/or radiotherapy for 33 (84.6%) patients, whereas 6 (15.4%) patients received mEHT alone. The patients of the no-mEHT group received chemotherapy and/or radiotherapy in 55.2% of cases. Results: Median age of the sample was 65.3 years (range = 31-80 years). After 3 months of therapy, the mEHT group had partial response in 22/34 patients (64.7%), stable disease in 10/34 patients (29.4%), and progressive disease in 2/34 patients (8.3%). The no-mEHT group had partial response in 3/36 patients (8.3%), stable disease in 10/36 patients (27.8%), and progressive disease in 23/36 patients (34.3%). The median overall survival of the mEHT group was 18.0 months (range = 1.5-68.0 months) and 10.9 months (range = 0.4-55.4 months) for the non-mEHT group. Conclusions: mEHT may improve tumor response and survival of pancreatic cancer patients.
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Affiliation(s)
| | - Donatella Sarti
- Azienda Ospedaliera “Ospedali Riuniti
Marche Nord,” Pesaro, Italy
| | - Virginia Casadei
- Azienda Ospedaliera “Ospedali Riuniti
Marche Nord,” Pesaro, Italy
| | | | | | | | - Roberto Nani
- University of Milano Bicocca, ASST Papa
Giovanni XXIII, Bergamo, Italy
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Immunotherapy, Radiotherapy, and Hyperthermia: A Combined Therapeutic Approach in Pancreatic Cancer Treatment. Cancers (Basel) 2018; 10:cancers10120469. [PMID: 30486519 PMCID: PMC6316720 DOI: 10.3390/cancers10120469] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42–43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients.
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