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1
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Özdemir İ, Zaman F, Doğan Baş D, Sari U, Öztürk Ş, Tuncer MC. Inhibitory effect of Curcumin on a cervical cancer cell line via the RAS/RAF signaling pathway. Histol Histopathol 2025; 40:327-334. [PMID: 39092501 DOI: 10.14670/hh-18-797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
OBJECTIVE Cervical cancer has a very important place in female infertility and ranks fourth among cancers affecting women. Curcumin (CUR) is closely associated with the expression and activity of various regulatory proteins. It is also known that curcumin has preventive and therapeutic effects on various types of cancer. In this study, the anticancer activities of curcumin were demonstrated in the human cervical cancer cell line (HeLa). METHODS qRT-PCR and western blot analyses were used to evaluate mRNA and protein expression of curcumin in HeLa and immortalized human skin keratinocyte cell lines (HaCaT) (proliferation and apoptosis regulatory markers of the RAS/RAF signaling pathway). MTT analysis was performed, showing HeLa and HaCaT cell proliferation depending on the dose and duration of curcumin and doxorubicin. A wound scratch healing assay was applied to examine cell migration and invasion of HeLa after curcumin application. To determine the role of curcumin and doxorubicin in the apoptosis of HeLa cells, the mRNA levels of caspase-3 were examined by qRT-PCR. The results were analyzed with a one-way ANOVA SPSS 20.0 program. RESULTS CUR (IC50: 242.8 μM) and DOX (IC50: 92.1 μM) were determined to have the ability to inhibit the proliferation of HeLa cells and induce apoptosis over a 72-hour period and dose-dependently. Moreover, the results revealed that the mRNA and protein expression levels of RAF and RAS in HeLa cells were downregulated by CUR and DOX. CONCLUSIONS The findings show that an alternative treatment method for cervical cancer can be developed with the application of CUR and DOX. Alternative methods for cervical cancer treatment may be developed using different methods in future studies.
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Affiliation(s)
- İlhan Özdemir
- Department of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum, Turkey
| | - Fuat Zaman
- Department of Obstetrics and Gynecology, Diyarlife Hospital, Diyarbakır, Turkey
| | | | - Umut Sari
- Department of Gynecology and Obstetrics, Umut Sarı Clinic, Istanbul, Turkey
| | - Şamil Öztürk
- Vocational School of Health Care Services, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
| | - Mehmet Cudi Tuncer
- Dicle University, Faculty of Medicine, Department of Anatomy, Diyarbakır, Turkey.
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Rai B, Dey T, Ballari N, Singh M, Miryala R, Srinivasa GY, Kataria V, Naseem R, Thakur S, Arun Singh O, Ghoshal S. Three-Dimensional Conformal Radiotherapy Versus Image-Guided Intensity Modulated External Beam Radiotherapy in Locally Advanced Cervical Cancer: A Phase III Randomized Control Study. Clin Oncol (R Coll Radiol) 2024; 36:728-737. [PMID: 39209678 DOI: 10.1016/j.clon.2024.08.004] [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: 01/04/2024] [Revised: 08/04/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
AIMS The standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities. MATERIALS AND METHODS This was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II-IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging. RESULTS Two hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms. CONCLUSION Based on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control.
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Affiliation(s)
- B Rai
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
| | - T Dey
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
| | - N Ballari
- Dept of Radiation Oncology, Homi Bhabha Cancer Hospital and Research Centre, Mullanpur, India.
| | - M Singh
- University Hospitals Birmingham, NHS Foundation Trust, India.
| | - R Miryala
- Dept of Radiation Oncology, Homi Bhabha Cancer Hospital and Research Centre, Vishakhapatnam, India.
| | - G Y Srinivasa
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
| | - V Kataria
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
| | - R Naseem
- Torbay and South Devon, NHS Foundation Trust, India.
| | - S Thakur
- Dept of Radiotherapy, Chitwan Medical College, Bharatpur, Nepal.
| | - O Arun Singh
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
| | - S Ghoshal
- Dept of Radiotherapy and Oncology, PGIMER, Chandigarh, India.
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Perrucci E, Macchia G, Cerrotta A, Andrulli AD, Autorino R, Barcellini A, Campitelli M, Corrao G, Costantini S, De Sanctis V, Di Muzio J, Epifani V, Ferrazza P, Fodor A, Garibaldi E, Laliscia C, Lazzari R, Magri E, Mariucci C, Pace MP, Pappalardi B, Pastorino A, Piccolo F, Scoglio C, Surgo A, Titone F, Tortoreto F, De Felice F, Aristei C. Prevention and management of radiotherapy-related toxicities in gynecological malignancies. Position paper on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology). LA RADIOLOGIA MEDICA 2024; 129:1329-1351. [PMID: 39198369 PMCID: PMC11379782 DOI: 10.1007/s11547-024-01844-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 07/01/2024] [Indexed: 09/01/2024]
Abstract
Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.
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Affiliation(s)
| | - Gabriella Macchia
- Radiation Oncology Unit, Responsible Research Hospital, Campobasso, Italy
| | - Annamaria Cerrotta
- Radiotherapy Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Rosa Autorino
- UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Amelia Barcellini
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
| | - Maura Campitelli
- UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giulia Corrao
- Department of Radiotherapy, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Sara Costantini
- Radiation Oncology Centre, Santa Maria Hospital, Terni, Italy
| | - Vitaliana De Sanctis
- Radiotherapy Oncology, Department of Medicine, Surgery and Translational Medicine, St. Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Jacopo Di Muzio
- Dipartimento Di Oncologia P.O. S. Anna - SS Radioterapia, A.O.U "Città Della Salute E Della Scienza", Turin, Italy
| | - Valeria Epifani
- Radiation Oncology Section, University of Perugia, Perugia, Italy.
| | | | - Andrei Fodor
- Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elisabetta Garibaldi
- Department of Radiotherapy, Ospedale Regionale Parini-AUSL Valle d'Aosta, Aosta, Italy
| | - Concetta Laliscia
- Department of Translational Medicine, Radiation Oncology Division, University of Pisa, Pisa, Italy
| | - Roberta Lazzari
- Department of Radiotherapy, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Elena Magri
- Department of Radiotherapy, Santa Chiara Hospital, Trento, Italy
| | - Cristina Mariucci
- Radiotherapy Department, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Maria Paola Pace
- UOC Radioterapia Oncologica, Ospedale Generale Provinciale di Macerata, AST Macerata, Italy
| | - Brigida Pappalardi
- Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Federica Piccolo
- Radiotherapy Unit, Ospedale di Circolo Fondazione Macchi, Varese, Italy
| | - Claudio Scoglio
- Radiotherapy Unit, Ospedale Maggiore di Trieste, Trieste, Italy
| | - Alessia Surgo
- Department of Radiation Oncology, General Regional Hospital "F. Miulli", Acquaviva delle Fonti, Bari, Italy
| | - Francesca Titone
- Radiation Oncology Unit, Department of Oncology, "Santa Maria della Misericordia" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | | | - Francesca De Felice
- Department of Radiotherapy, Policlinico Umberto I, Department of Radiological, Oncological and Pathological Sciences, "Sapienza" University of Rome, Rome, Italy
| | - Cynthia Aristei
- Radiation Oncology Section, University of Perugia and Perugia General Hospital, Perugia, Italy
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Uke A, Dahake SB, Luharia A, Luharia M, Mishra GV, Mahakalkar C. Investigating and Analyzing Prognostic Factors and Their Impact on Recurrent Cervical Cancers. Cureus 2024; 16:e65361. [PMID: 39184727 PMCID: PMC11344604 DOI: 10.7759/cureus.65361] [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: 05/21/2024] [Accepted: 07/25/2024] [Indexed: 08/27/2024] Open
Abstract
The incidence of cervical cancer in India is significantly high, and the average recurrence age is much less. The standard line of treatment consists of concurrent chemoradiotherapy. If a recurrence occurs, the treatment options or set of interventions are limited and suboptimal. Through this review, we have analyzed and classified the possible prognostic factors for cervical cancer into three broad categories, viz., (a) disease-related factors, (b) patient-related factors, and (c) treatment-related factors. Disease-related factors include tumor histology, tumor size, stage, parametrial involvement (PMI), Prognostic Nutritional Index (PNI), lymphovascular space invasion (LVSI), and nodal status. Patient-related factors include overall treatment time (OTT), nutritional status, hemoglobin level, comorbidities, and age. Treatment-related factors include addition of chemotherapy, techniques of external beam radiotherapy (EBRT), techniques of brachytherapy, and quality assurance for radiation therapy delivery. Out of these, extremely significant prognostic factors were tumor size and stage, nodal status, PMI, nutritional status, and addition of chemotherapy. Impactful factors include younger age, histology, LVSI, associated comorbidities, hemoglobin level, OTT, and patient-specific quality assurance. The factor that is not related or significant is the technique used for EBRT and brachytherapy delivery.
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Affiliation(s)
- Ashish Uke
- Radiation Oncology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Shweta B Dahake
- Medical Physics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Anurag Luharia
- Medical Physics and Radiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Monika Luharia
- Ayurveda, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Gaurav V Mishra
- Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Chanrashekhar Mahakalkar
- General Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Yang T, Zhao T, Ji Z, Lei R, Qu A, Jiang W, Deng X, Jiang P. The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience. Radiat Oncol 2024; 19:77. [PMID: 38909242 PMCID: PMC11193253 DOI: 10.1186/s13014-024-02476-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/17/2024] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.
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Affiliation(s)
- Tianyu Yang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Tiandi Zhao
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Zhe Ji
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Runhong Lei
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Ang Qu
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Weijuan Jiang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Xiuwen Deng
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Ping Jiang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China.
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Vourtsas P, Sarris K, Giakoumakis N, Kolitsi G, Kyprianou K, Mastronikoli S, Tsiambas E, Peschos D, Kardamakis D, Androutsopoulos G, Spyropoulou D. Comparative Analysis of External and Internal Radiotherapy- Dependent Plans in Patients with Gynecological Cancer. CANCER DIAGNOSIS & PROGNOSIS 2024; 4:352-358. [PMID: 38707738 PMCID: PMC11062162 DOI: 10.21873/cdp.10331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/08/2024] [Indexed: 05/07/2024]
Abstract
Background/Aim Radiotherapy plays a key role in the treatment of gynecological cancer. Modern radiotherapy techniques with external beams (e-RT) are applied in a broad spectrum of gynecological cancer cases. However, high radiation doses, affecting normal tissue adjacent to cancer, represent the main disadvantage of e-RT regimens. For this reason, brachytherapy (BT), an internal beam-based technique (i-RT), is suggested following e-RT. Our purpose was to compare e-RT plans using volumetric-modulated arc therapy (VMAT) with those using 3D conformal techniques (3D-CRT) and compare BT plans guided by 3D or 2D imaging based on the potential corresponding toxicity levels. Materials and Methods In this preliminary, non-randomized comparative retrospective study, 15 females suffering gynecological cancer were enrolled. Modern e-RT and i-RT (BT) techniques were applied. Results Concerning e-RT, D95/D99/rectum 2cc/bladder 2cc and small intestine 2cc were measured and compared; in i-RT, rectum 2cc/bladder 2cc were measured and compared. The median dose to the planning target volume in VMAT was 97.4 Gy compared with 92.9 Gy in 3D-CRT. Τhe rectum received almost 5 Gy less in VMAT compared to 3D-CRT (median of 43.5 Gy vs. 48.6 Gy; p=0.001). In the bladder, dose differences were minimal, while the small intestine received 47.6 Gy in VMAT (p=0.001). Regarding 3D-BT, the rectum received 63.1 Gy compared with 49.9 Gy (p=0.009) in 2D-BT. Concerning the bladder, mean 2D-BT and 3D-BT doses were 71.9 and 65 Gy, respectively, differing non-significantly. Conclusion VMAT was found to be superior to 3D-CRT, especially in dose distribution, volume coverage and protection of critical organs. Similarly, 3D-BT should be preferred over 2D-BT due to critical advantages.
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Affiliation(s)
- Panagiotis Vourtsas
- Department of Radiation Oncology, Medical School, University of Patras, Patras, Greece
| | | | | | | | | | | | - Evangelos Tsiambas
- Department of Cytopathology, 417 Army Equity Fund Hospital, Athens, Greece
| | - Dimitrios Peschos
- Department of Physiology, Medical School, University of Ioannina, Ioannina, Greece
| | - Dimitrios Kardamakis
- Department of Radiation Oncology, Medical School, University of Patras, Patras, Greece
| | | | - Despina Spyropoulou
- Department of Radiation Oncology, Medical School, University of Patras, Patras, Greece
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Kim MS, Yang SJ, Jung SY, Lee TY, Park JK, Park YG, Woo SY, Kim SE, Lee RA. Combination of phytochemicals, including ginsenoside and curcumin, shows a synergistic effect on the recovery of radiation-induced toxicity. PLoS One 2024; 19:e0293974. [PMID: 38241326 PMCID: PMC10798472 DOI: 10.1371/journal.pone.0293974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 10/20/2023] [Indexed: 01/21/2024] Open
Abstract
Radiotherapy is commonly used to treat solid cancers located in the pelvis. A considerable number of patients experience proctitis of varying severity, even for a considerable period after radiotherapy. These side effects are often long-lasting or progressively worsen despite multiple therapeutic efforts and are a primary cause of an unexpectedly low quality of life, even after successful cancer treatment. Therefore, this study evaluated the individual and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate compounds in treating radiation-induced proctitis. While the candidate compounds did not affect the proliferation and migration of cancer cells, they promoted the recovery of cell activity, including motility. They exhibited anti-inflammatory effects on human dermal fibroblasts or human umbilical vein endothelial cells within in vitro disease models. When each compound was tested, curcumin and ginsenoside were the most effective in cell recovery and promoted the migration of human dermal fibroblasts and cell restoration of human umbilical vein endothelial cells. The combination of ginsenoside and curcumin resulted in cell migration recovery of approximately 54%. In addition, there was a significant improvement in the length of the endothelial tube, with an increase of approximately 25%, suggesting that the ginsenoside-curcumin-containing combination was the most effective against radiation-induced damage. Furthermore, studies evaluating the effects of combined treatments on activated macrophages indicated that the compounds effectively reduced the secretion of inflammatory cytokines, including chemokines, and alleviated radiation-induced inflammation. In conclusion, our study provides valuable insights into using curcumin and ginsenoside as potential compounds for the effective treatment of radiation-induced injuries and highlights the promising therapeutic benefits of combining these two compounds.
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Affiliation(s)
- Min-Sung Kim
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - Su-Jeong Yang
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - Seo-Yeong Jung
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - Tae-Yong Lee
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - Jin-Kyung Park
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - Yun-Gyeong Park
- Central Research Center, CORESTEMCHEMON Inc., Seoul, South Korea
| | - So-Youn Woo
- Department of Microbiology, Ewha Womans University, College of Medicine, Seoul, South Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University, College of Medicine, Seoul, South Korea
| | - Ryung-Ah Lee
- Department of Surgery, Ewha Womans University, College of Medicine, Seoul, South Korea
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8
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Laan JJ, van Lonkhuijzen LRCW, Stokking JA, Barten DLJ, Hinnen KA, Pieters BR, Stalpers LJA, Westerveld H. The Effect of Contemporary Brachytherapy Practices on Prognosis in Women with Locally Advanced Cervical Cancer. Curr Oncol 2023; 30:4275-4288. [PMID: 37185439 PMCID: PMC10137238 DOI: 10.3390/curroncol30040326] [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: 02/16/2023] [Revised: 04/06/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
(1) Background: Over the past two decades use of new imaging modalities and the adaptation of applicators have allowed for advances in volumetric (3D) imaging-based brachytherapy practices for patients with locally advanced cervical cancer. The aim of this study was to compare the oncological outcome and toxicity for three consecutively introduced brachytherapy practices in a large single-center cohort; (2) Methods: Patients treated for cervical cancer with primary radiotherapy and curative intent were consecutively included in this retrospective, single-center cohort study from 2006 to 2019. This cohort was divided into three groups (CT, MRI, and MRI+needles) based on the timing of the introduction of a novel brachytherapy practice; 3D brachytherapy planning using CT- and MRI-guided adaptive brachytherapy and the use of parametrial interstitial needles, respectively. Actuarial estimates were compared between groups. Multivariable Cox regression analyses were performed to correct for other risk factors. Crude rates of severe (≥grade 3) late toxicity were reported; (3) Results: A total of 397 patients were included in this cohort. At a median follow-up of 40 months (interquartile range (IQR) 22-62), actuarial 3-year local control, pelvic control, disease-free survival, and overall survival for the entire cohort were 91% (95% (Confidence Interval (CI)) 88-94), 88% (95% CI 84-91), 69% (95% CI 64-74), and 75% (95% CI 70-79), respectively). Local control, disease-free survival, and overall survival were significantly improved in the MRI+needles group compared to the CT group (p = 0.040, p = 0.004, and p < 0.001, respectively). Independent risk factors for overall survival were treatment in either the CT or MRI group (vs. MRI+needles), older age at diagnosis, adeno (squamous) carcinoma, FIGO stage III/IV, and lymph node metastases. The crude rate of severe late toxicity was 27% in the CT, 26% in the MRI, and 20% in the MRI+needles group; (4) Conclusions: Prognosis in women with locally advanced cervical cancer treated with state-of-the-art MRI-guided adaptive brachytherapy combined with parametrial interstitial needles compares favorably to patients treated with more traditional CT only based brachytherapy.
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Affiliation(s)
- Janna J Laan
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands
| | - Luc R C W van Lonkhuijzen
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands
- Center for Gynaecologic Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Jaap A Stokking
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Danique L J Barten
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Karel A Hinnen
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Bradley R Pieters
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands
| | - Lukas J A Stalpers
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands
| | - Henrike Westerveld
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Radiotherapy, Erasmus Medical Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
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Winters TA, Cassatt DR, Harrison-Peters JR, Hollingsworth BA, Rios CI, Satyamitra MM, Taliaferro LP, DiCarlo AL. Considerations of Medical Preparedness to Assess and Treat Various Populations During a Radiation Public Health Emergency. Radiat Res 2023; 199:301-318. [PMID: 36656560 PMCID: PMC10120400 DOI: 10.1667/rade-22-00148.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 12/21/2022] [Indexed: 01/20/2023]
Abstract
During a radiological or nuclear public health emergency, given the heterogeneity of civilian populations, it is incumbent on medical response planners to understand and prepare for a potentially high degree of interindividual variability in the biological effects of radiation exposure. A part of advanced planning should include a comprehensive approach, in which the range of possible human responses in relation to the type of radiation expected from an incident has been thoughtfully considered. Although there are several reports addressing the radiation response for special populations (as compared to the standard 18-45-year-old male), the current review surveys published literature to assess the level of consideration given to differences in acute radiation responses in certain sub-groups. The authors attempt to bring clarity to the complex nature of human biology in the context of radiation to facilitate a path forward for radiation medical countermeasure (MCM) development that may be appropriate and effective in special populations. Consequently, the focus is on the medical (as opposed to logistical) aspects of preparedness and response. Populations identified for consideration include obstetric, pediatric, geriatric, males, females, individuals of different race/ethnicity, and people with comorbidities. Relevant animal models, biomarkers of radiation injury, and MCMs are highlighted, in addition to underscoring gaps in knowledge and the need for consistent and early inclusion of these populations in research. The inclusion of special populations in preclinical and clinical studies is essential to address shortcomings and is an important consideration for radiation public health emergency response planning. Pursuing this goal will benefit the population at large by considering those at greatest risk of health consequences after a radiological or nuclear mass casualty incident.
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Affiliation(s)
- Thomas A. Winters
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - David R. Cassatt
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - Jenna R. Harrison-Peters
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - Brynn A. Hollingsworth
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
- Current address: Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Carmen I. Rios
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - Merriline M. Satyamitra
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - Lanyn P. Taliaferro
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
| | - Andrea L. DiCarlo
- Radiation and Nuclear Countermeasures Program (RNCP), Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, Maryland
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10
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Ma CY, Zhao J, Gan GH, He XL, Xu XT, Qin SB, Wang LL, Li L, Zhou JY. Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy. World J Gastroenterol 2023; 29:1344-1358. [PMID: 36925455 PMCID: PMC10011961 DOI: 10.3748/wjg.v29.i8.1344] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 01/13/2023] [Accepted: 02/15/2023] [Indexed: 02/28/2023] Open
Abstract
BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors. Radiation enteritis (RE) leads to radiotherapy intolerance or termination of radiotherapy, which negatively impacts the therapeutic effect and seriously affects the quality of life of patients. If the incidence of RE in patients can be predicted in advance, and targeted clinical preventive treatment can be carried out, the side effects of radiotherapy in cervical cancer patients can be significantly reduced. Furthermore, accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.
AIM To analyze the relationships between severe acute RE (SARE) of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.
METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy (VMAT) from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University. Clinical and dose-volume histogram factors of patients were collected. Logistic regression analysis was used to evaluate the predictive value of each factor for SARE. A nomogram to predict SARE was developed (SARE scoring system ≥ 3 points) based on the multiple regression coefficients; validity was verified by an internal verification method.
RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy. The main adverse reactions were diarrhea, abdominal pain, colitis, anal swelling, and blood in the stool. There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups (P > 0.05). There were significant differences in the small intestine V20, V30, V40, and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery (P < 0.05). Univariate and multivariate analyses revealed anal bulge rating (OR: 14.779, 95%CI: 1.281-170.547, P = 0.031) and disease activity index (DAI) score (OR: 53.928, 95%CI: 3.822-760.948, P = 0.003) as independent predictors of SARE.
CONCLUSION Anal bulge rating (> 0.500 grade) and DAI score (> 2.165 points) can predict SARE. The nomogram shows potential value in clinical practice.
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Affiliation(s)
- Chen-Ying Ma
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Jing Zhao
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Guang-Hui Gan
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Xiao-Lan He
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Xiao-Ting Xu
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Song-Bing Qin
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Li-Li Wang
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Li Li
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
| | - Ju-Ying Zhou
- Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu Province, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, Jiangsu Province, China
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11
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Caron J, Gonzalez G, Pandey PK, Wang S, Prather K, Ahmad S, Xiang L, Chen Y. Single pulse protoacoustic range verification using a clinical synchrocyclotron. Phys Med Biol 2023; 68:10.1088/1361-6560/acb2ae. [PMID: 36634371 PMCID: PMC10567060 DOI: 10.1088/1361-6560/acb2ae] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 01/12/2023] [Indexed: 01/14/2023]
Abstract
Objective.Proton therapy as the next generation radiation-based cancer therapy offers dominant advantages over conventional radiation therapy due to the utilization of the Bragg peak; however, range uncertainty in beam delivery substantially mitigates the advantages of proton therapy. This work reports using protoacoustic measurements to determine the location of proton Bragg peak deposition within a water phantom in real time during beam delivery.Approach.In protoacoustics, proton beams have a definitive range, depositing a majority of the dose at the Bragg peak; this dose is then converted to heat. The resulting thermoelastic expansion generates a 3D acoustic wave, which can be detected by acoustic detectors to localize the Bragg peak.Main results.Protoacoustic measurements were performed with a synchrocyclotron proton machine over the exhaustive energy range from 45.5 to 227.15 MeV in clinic. It was found that the amplitude of the acoustic waves is proportional to proton dose deposition, and therefore encodes dosimetric information. With the guidance of protoacoustics, each individual proton beam (7 pC/pulse) can be directly visualized with sub-millimeter (<0.7 mm) resolution using single beam pulse for the first time.Significance.The ability to localize the Bragg peak in real-time and obtain acoustic signals proportional to dose within tumors could enable precision proton therapy and hope to progress towardsin vivomeasurements.
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Affiliation(s)
- Joseph Caron
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America
| | - Gilberto Gonzalez
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America
| | - Prabodh Kumar Pandey
- Department of Radiological Sciences, University of California at Irvine, Irvine, CA 92697, United States of America
| | - Siqi Wang
- The Department of Biomedical Engineering, University of California, Irvine, CA 92617, United States of America
| | - Kiana Prather
- University of Oklahoma College of Medicine, Oklahoma City, OK, 73104, United States of America
| | - Salahuddin Ahmad
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America
| | - Liangzhong Xiang
- Department of Radiological Sciences, University of California at Irvine, Irvine, CA 92697, United States of America
- The Department of Biomedical Engineering, University of California, Irvine, CA 92617, United States of America
- Beckman Laser Institute & Medical Clinic, University of California, Irvine, Irvine, CA 92612, United States of America
| | - Yong Chen
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America
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12
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Pettinato S, Girolami M, Rossi MC, Salvatori S. Accurate Signal Conditioning for Pulsed-Current Synchronous Measurements. SENSORS (BASEL, SWITZERLAND) 2022; 22:5360. [PMID: 35891039 PMCID: PMC9321935 DOI: 10.3390/s22145360] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/15/2022] [Accepted: 07/16/2022] [Indexed: 06/15/2023]
Abstract
This paper describes a compact electronic system employing a synchronous demodulation measurement method for the acquisition of pulsed-current signals. The fabricated prototype shows superior performance in terms of signal-to-noise ratio in comparison to conventional instrumentation performing free-running measurements, especially when extremely narrow pulses are concerned. It shows a reading error around 0.1% independently of the signal duty cycle (D) in the investigated D = 10−4−10−3 range. Conversely, high-precision electrometers display reading errors as high as 30% for a D = 10−4, which reduces to less than 1% only for D > 3 × 10−3. Field tests demonstrate that the developed front-end/readout electronics is particularly effective when coupled to dosimeters irradiated with the X-rays sourced by a medical linear accelerator. Therefore, it may surely be exploited for the real-time monitoring of the dosimeter output current, as required in modern radiotherapy techniques employing ultra-narrow pulses of high-energy photons or nuclear particles.
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Affiliation(s)
- Sara Pettinato
- Faculty of Engineering, Università degli Studi Niccolò Cusano, Via don Carlo Gnocchi 3, 00166 Rome, Italy;
- Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche (ISM-CNR), Strada Provinciale 35D 9, Montelibretti, 00010 Rome, Italy
| | - Marco Girolami
- Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche (ISM-CNR), Strada Provinciale 35D 9, Montelibretti, 00010 Rome, Italy
| | - Maria Cristina Rossi
- Department of Industrial, Electronic and Mechanical Engineering, Roma Tre University, Via Vito Volterra 62, 00146 Rome, Italy;
| | - Stefano Salvatori
- Faculty of Engineering, Università degli Studi Niccolò Cusano, Via don Carlo Gnocchi 3, 00166 Rome, Italy;
- Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche (ISM-CNR), Strada Provinciale 35D 9, Montelibretti, 00010 Rome, Italy
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Kang Z, Fu L, Liu J, Shi L, Li Y. A practical method to improve the performance of knowledge-based VMAT planning for endometrial and cervical cancer. Acta Oncol 2022; 61:1012-1018. [PMID: 35793274 DOI: 10.1080/0284186x.2022.2093615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
PURPOSE The aim of this work was to demonstrate a practical and effective method to improve the performance of RapidPlan (RP) model. METHODS 203 consecutive clinical VMAT plans (P0) for cervical and endometrial cancer were used to train an RP model (M0). The plans were then reoptimized by M0 to generate 203 new plans (P1). Compared with P0, 150 plans with a lower mean dose (MD) of bladder, rectum and PBM were selected from P1 to configure a new RP model (M1). A final RP model (M2) was trained using plans in M1 and the remaining 53 plans from P1 (excluding OARs with worse MD) and the corresponding plans from P0 (only including OARs with better MD). The models were validated on the mentioned 53 plans (closed-loop set) and 46 patient cohorts outside the training library (open-loop set). p < 0.05 was considered statistically significant. RESULTS For closed-loop validation, the difference of D2%, D98% and CI95% between groups was of no statistical significance, the homogeneity index (HI) was lower in the groups of RP models (p < 0.05). The MD of all OARs decreased monotonically in the sequence of the clinical group, group M0, M1 and M2, except the MD of bowel in M1 and MD of LFH in M2. Similarly, for open-loop validation, there was no significant difference in D2%, D98% and HI between groups, but CI95% was larger in the clinical group (p < 0.05). The MD of all OARs decreased monotonically in the sequence of the clinical group, group M0, M1 and M2, with the exception of bowel in M1. CONCLUSION The practical method of incorporating plan data of better-sparing OARs from both the clinical VMAT plans and the re-optimized plans could further improve the performance of the RP model.
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Affiliation(s)
- Zheng Kang
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.,Xiamen Key Laboratory of Radiation Oncology, Xiamen, China
| | - Lirong Fu
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jun Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Liwan Shi
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.,Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Yimin Li
- Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.,Xiamen Key Laboratory of Radiation Oncology, Xiamen, China.,Teaching Hospital of Fujian Medical University, Xiamen, China
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Using a Weekly Patient-Reported Outcome Questionnaire to Track Acute Toxicity in Patients Undergoing Pelvic Radiotherapy for Gynecologic Cancers. Curr Oncol 2022; 29:3306-3317. [PMID: 35621660 PMCID: PMC9140006 DOI: 10.3390/curroncol29050270] [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] [Received: 03/23/2022] [Revised: 04/28/2022] [Accepted: 05/03/2022] [Indexed: 11/17/2022] Open
Abstract
There are limited patient-reported outcome (PRO) data tracking changes in toxicity in patients actively undergoing radiotherapy. Between 2015−2019, acute toxicity was prospectively measured in 698 patients undergoing a 5-week course of pelvic radiotherapy for gynecologic cancers using a weekly PRO questionnaire. Our questionnaire was able detect a pattern of onset and resolution of acute gastrointestinal (GI) and genitourinary (GU) toxicity in 27 out of 32 questions. Logistic regression analysis showed that increasing GI and GU toxicity at week 2 could predict for severe toxicity at week 5. However, due to a low number of severe events, univariate results could not be productively added to a multivariate model. We observed a >70% response rate for all sections of the questionnaire, except for questions on sexual and vaginal health, which had a 13% average response rate. By demonstrating that PRO data can be used to track acute toxicity during radiotherapy, there is a need to further examine how this tool may be implemented in the clinic to provide complex, adaptive care, such as early side effect management, and modifying radiation delivery in real-time.
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Ahangari S, Littrup Andersen F, Liv Hansen N, Jakobi Nøttrup T, Berthelsen AK, Folsted Kallehauge J, Richter Vogelius I, Kjaer A, Espe Hansen A, Fischer BM. Multi-parametric PET/MRI for enhanced tumor characterization of patients with cervical cancer. Eur J Hybrid Imaging 2022; 6:7. [PMID: 35378619 PMCID: PMC8980118 DOI: 10.1186/s41824-022-00129-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 02/07/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Aim
The concept of personalized medicine has brought increased awareness to the importance of inter- and intra-tumor heterogeneity for cancer treatment. The aim of this study was to explore simultaneous multi-parametric PET/MRI prior to chemoradiotherapy for cervical cancer for characterization of tumors and tumor heterogeneity.
Methods
Ten patients with histologically proven primary cervical cancer were examined with multi-parametric 68Ga-NODAGA-E[c(RGDyK)]2-PET/MRI for radiation treatment planning after diagnostic 18F-FDG-PET/CT. Standardized uptake values (SUV) of RGD and FDG, diffusion weighted MRI and the derived apparent diffusion coefficient (ADC), and pharmacokinetic maps obtained from dynamic contrast-enhanced MRI with the Tofts model (iAUC60, Ktrans, ve, and kep) were included in the analysis. The spatial relation between functional imaging parameters in tumors was examined by a correlation analysis and joint histograms at the voxel level. The ability of multi-parametric imaging to identify tumor tissue classes was explored using an unsupervised 3D Gaussian mixture model-based cluster analysis.
Results
Functional MRI and PET of cervical cancers appeared heterogeneous both between patients and spatially within the tumors, and the relations between parameters varied strongly within the patient cohort. The strongest spatial correlation was observed between FDG uptake and ADC (median r = − 0.7). There was moderate voxel-wise correlation between RGD and FDG uptake, and weak correlations between all other modalities. Distinct relations between the ADC and RGD uptake as well as the ADC and FDG uptake were apparent in joint histograms. A cluster analysis using the combination of ADC, FDG and RGD uptake suggested tissue classes which could potentially relate to tumor sub-volumes.
Conclusion
A multi-parametric PET/MRI examination of patients with cervical cancer integrated with treatment planning and including estimation of angiogenesis and glucose metabolism as well as MRI diffusion and perfusion parameters is feasible. A combined analysis of functional imaging parameters indicates a potential of multi-parametric PET/MRI to contribute to a better characterization of tumor heterogeneity than the modalities alone. However, the study is based on small patient numbers and further studies are needed prior to the future design of individually adapted treatment approaches based on multi-parametric functional imaging.
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