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Nigro MC, Marchetti A, Fumagalli ER, De Luca I, Bertuzzi AF, Grimaudo MS, Grignani G, D’Ambrosio L, Merlini A, Badalamenti G, Incorvaia L, Dimino A, Gasperoni S, Vincenzi B, Fanti S, Di Federico A, Campana D, Pantaleo MA, Nannini M. 18F-Fluorodeoxyglucose Uptake in PDGFRA-Mutant Gastrointestinal Stromal Tumors. JAMA Netw Open 2025; 8:e2456058. [PMID: 39853981 PMCID: PMC11762236 DOI: 10.1001/jamanetworkopen.2024.56058] [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] [Received: 07/25/2024] [Accepted: 11/15/2024] [Indexed: 01/26/2025] Open
Abstract
Importance The D842V platelet-derived growth factor receptor α (PDGFRA) mutation identifies a molecular subgroup of gastrointestinal stromal tumors (GISTs), primarily resistant to standard tyrosine kinase inhibitors and with an overall more indolent behavior. Although functional imaging with 18F-fluorodeoxyglucose-labeled positron emission tomography ([18F]FDG-PET) plays a proven role in GISTs, especially in early assessment of tumor response, less is known about [18F]FDG uptake according to the GIST molecular subtypes. Objective To evaluate the degree of [18F]FDG uptake in PDGFRA-mutant GISTs and better define the role of functional imaging in this rare and peculiar subset of GISTs. Design, Setting, and Participants This multi-institutional retrospective cohort study involving 7 GIST reference centers in Italy included patients with PDGFRA-mutant GIST who underwent [18F]FDG-PET from January 1, 2000, to December 31, 2023. Data on the maximum standardized uptake value (SUVmax) of primary tumor or metastatic disease were collected. Exposure PDGFRA-mutant GIST and [18F]FDG-PET. Main Outcome and Measure The primary outcome was the degree of [18F]FDG uptake of PDGFRA-mutant GISTs, with a focus on the D842V-mutant subgroup. Secondary objectives were to assess the association between the degree of [18F]FDG uptake and main clinicopathologic features. Results A total of 71 patients with PDGFRA-mutant GISTs were included in the analysis: 37 (52.1%) in the D842V subgroup (group A) and 34 (47.9%) in the non-D842V subgroup (group B). Additionally, 70 patients with KIT exon 11-mutant GIST served as a control group (group C). For all 141 participants, the median age at diagnosis was 59 (range, 26-89) years, and 81 patients (57.4%) were male. Overall, the median SUVmax was 4.4 (IQR, 0-10.1), while the median SUVmax for group A was 0 (IQR, 0-3.2); for group B, 3.6 (IQR, 0-5.1); and for group C, 10.1 (IQR, 5.1-13.9). The median SUVmax of PDGFRA-mutant GISTs was significantly lower than the median value of KIT exon 11-mutant GISTs (0 [IQR, 0-4.3] vs 10.1 [IQR, 5.1-14.0]; P < .001). Median [18F]FDG uptake was significantly lower in the D842V subgroup compared with the non-D842V subgroup (0 [IQR, 0-3.2] vs 3.6 [IQR, 0-5.1]; P = .02). Moreover, the triad of gastric primary tumor, tumor size greater than 10 cm, and SUVmax of 5.75 or less was associated with identification of PDGFRA-mutant GISTs. Conclusions and Relevance In this cohort study of patients with PDGFRA-mutant GISTs, the D842V-mutant GISTs were associated with an overall lower [18F]FDG uptake compared with other GIST subgroups. Therefore, the role of functional imaging with [18F]FDG-PET in this subset of GISTs may be limited and should be further explored for its potential prognostic and predictive value.
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Affiliation(s)
- Maria Concetta Nigro
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Andrea Marchetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Elena Rosa Fumagalli
- Medical Oncology Unit 2, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori, Milano, Italy
| | - Ida De Luca
- Medical Oncology Unit 2, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori, Milano, Italy
| | - Alexia Francesca Bertuzzi
- Department of Medical Oncology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Maria Susanna Grimaudo
- Department of Medical Oncology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Giovanni Grignani
- Department of Medical Oncology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, Italy
- Candiolo Cancer Institute, Fondazione del Piemonte–IRCCS, Candiolo (Turin), Turin, Italy
| | - Lorenzo D’Ambrosio
- Department of Medical Oncology, University of Turin, Turin, Italy
- Azienda Ospedaliera Universitaria San Luigi Gonzaga University Hospital, Orbassano, Italy
| | - Alessandra Merlini
- Candiolo Cancer Institute, Fondazione del Piemonte–IRCCS, Candiolo (Turin), Turin, Italy
- Department of Medical Oncology, University of Turin, Turin, Italy
| | - Giuseppe Badalamenti
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Lorena Incorvaia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Alessandra Dimino
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Silvia Gasperoni
- Department of Oncology, Clinical Oncology Unit, University Hospital Careggi, Firenze, Italy
| | - Bruno Vincenzi
- Department of Medical Oncology, Campus Biomedico University of Rome, Rome, Italy
| | - Stefano Fanti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Nuclear Medicine, IRCCS, Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
| | | | - Davide Campana
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Margherita Nannini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Department of Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
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Hirota S, Tateishi U, Nakamoto Y, Yamamoto H, Sakurai S, Kikuchi H, Kanda T, Kurokawa Y, Cho H, Nishida T, Sawaki A, Ozaka M, Komatsu Y, Naito Y, Honma Y, Takahashi F, Hashimoto H, Udo M, Araki M, Nishidate S. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology. Int J Clin Oncol 2024; 29:647-680. [PMID: 38609732 PMCID: PMC11130037 DOI: 10.1007/s10147-024-02488-1] [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: 12/27/2023] [Accepted: 02/12/2024] [Indexed: 04/14/2024]
Abstract
The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.
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Affiliation(s)
- Seiichi Hirota
- Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
| | - Ukihide Tateishi
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hidetaka Yamamoto
- Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shinji Sakurai
- Department of Diagnostic Pathology, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Japan
| | - Hirotoshi Kikuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Toshirou Nishida
- Department of Surgery, Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | - Akira Sawaki
- Department of Medical Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshito Komatsu
- Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan
| | - Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshitaka Honma
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Fumiaki Takahashi
- Department of Information Science, Iwate Medical University, Morioka, Japan
| | | | - Midori Udo
- Nursing Department, Osaka Police Hospital, Osaka, Japan
| | - Minako Araki
- Association of Chubu GIST Patients and Their Families, Nagoya, Japan
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Kus T, Cicin I. A perspective: the integration of ctDNA into Response Evaluation Criteria in Solid Tumours 1.1 for phase II immunotherapy clinical trials. Immunotherapy 2024; 16:319-329. [PMID: 38197142 DOI: 10.2217/imt-2023-0184] [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: 08/08/2023] [Accepted: 12/14/2023] [Indexed: 01/11/2024] Open
Abstract
A consensus guideline, iRECIST, was developed by the Response Evaluation Criteria in Solid Tumours (RECIST) working group for the use of the modified RECIST version 1.1 in cancer immunotherapy trials. iRECIST was designed to separate pseudoprogression from real progression. However, this is not the only ambiguous situation. In clinical immunotherapy trials, stable disease may reflect three tumor responses, including real stable disease, progressive disease and responsive disease. The prediction of a "true complete/partial response" is also important. Much data has accumulated showing that ctDNA can guide decisions at this point; thus, integrating ctDNA into the RECIST 1.1 criteria may help to distinguish a true tumor response type earlier in patients treated with immunotherapy; however, prospectively designed validation studies are needed.
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Affiliation(s)
- Tulay Kus
- School of Medicine, Department of Medical Oncology, Gaziantep University, Gaziantep, 27310, Turkey
| | - Irfan Cicin
- Department of Medical Oncology, Istinye University Topkapı Health Sciences Campus, Istanbul, 34295, Turkey
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Mugiya T, Mothibe M, Khathi A, Ngubane P, Sibiya N. Glycaemic abnormalities induced by small molecule tryosine kinase inhibitors: a review. Front Pharmacol 2024; 15:1355171. [PMID: 38362147 PMCID: PMC10867135 DOI: 10.3389/fphar.2024.1355171] [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: 12/13/2023] [Accepted: 01/12/2024] [Indexed: 02/17/2024] Open
Abstract
In light of the expected increase in the prevalence of diabetes mellitus due to an aging population, sedentary lifestyles, an increase in obesity, and unhealthy diets, there is a need to identify potential pharmacological agents that can heighten the risk of developing diabetes. Similarly, it is equally important to also identify those agents that show blood glucose-lowering properties. Amongst these agents are tyrosine kinase inhibitors used to treat certain types of cancers. Over the last two decades, there has been an increase in the use of targeted chemotherapy for cancers such as renal cell carcinoma, chronic leukaemia, and gastrointestinal stromal tumours. Small molecule tyrosine kinase inhibitors have been at the forefront of targeted chemotherapy. Studies have shown that small molecule tyrosine kinase inhibitors can alter glycaemic control and glucose metabolism, with some demonstrating hypoglycaemic activities whilst others showing hyperglycaemic properties. The mechanism by which small molecule tyrosine kinase inhibitors cause glycaemic dysregulation is not well understood, therefore, the clinical significance of these chemotherapeutic agents on glucose handling is also poorly documented. In this review, the effort is directed at mapping mechanistic insights into the effect of various small molecule tyrosine kinase inhibitors on glycaemic dysregulation envisaged to provide a deeper understanding of these chemotherapeutic agents on glucose metabolism. Small molecule tyrosine kinase inhibitors may elicit these observed glycaemic effects through preservation of β-cell function, improving insulin sensitivity and insulin secretion. These compounds bind to a spectrum of receptors and proteins implicated in glucose regulation for example, non-receptor tyrosine kinase SRC and ABL. Then receptor tyrosine kinase EGFR, PDGFR, and FGFR.
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Affiliation(s)
- Takudzwa Mugiya
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
| | - Mamosheledi Mothibe
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
| | - Andile Khathi
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Phikelelani Ngubane
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Ntethelelo Sibiya
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa
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Tassinari E, Conci N, Battisti G, Porta F, Di Scioscio V, Pirini MG, de Biase D, Nigro MC, Iezza M, Castagnetti F, Lovato L, Fanti S, Pantaleo MA, Nannini M. Metabolic pseudoprogression in a patient with metastatic KIT exon 11 GIST after 1 month of first-line imatinib: a case report. Front Oncol 2023; 13:1310452. [PMID: 38188286 PMCID: PMC10769864 DOI: 10.3389/fonc.2023.1310452] [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: 10/09/2023] [Accepted: 11/27/2023] [Indexed: 01/09/2024] Open
Abstract
BACKGROUND Positron emission tomography (PET) with 18-fluorodeoxyglucose (18FDG) has proven to be highly sensitive in the early assessment of tumor response in gastrointestinal stromal tumors (GIST), especially in cases where there is doubt or when the early prediction of the response could be clinically useful for patient management. As widely known, kinase mutations have an undoubtful predictive value for sensitivity to imatinib, and the inclusion of KIT and PDGFRa mutational analysis in the diagnostic workup of all GIST is now considered standard practice. CASE PRESENTATION Herein, we described in detail a case of an exon 11 KIT mutated-metastatic GIST patient, who presented an unexpected metabolic progression at the early 18FDG-PET evaluation after 1 month of first-line imatinib, unconfirmed at the liver biopsy performed near after, which has conversely shown a complete pathological response. CONCLUSIONS This report aims to highlight the existence of this metabolic pseudoprogression in GIST at the beginning of imatinib therapy in order to avoid early treatment discontinuation. Therefore, an early metabolic progression during a molecular targeted therapy always deserves to be evaluated in the context of the disease molecular profiling, and in case of a discordant finding between functional imaging and molecular background, a short-term longitudinal control should be suggested.
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Affiliation(s)
- Elisa Tassinari
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Nicole Conci
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giacomo Battisti
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna-Policlinico di Sant’Orsola, Bologna, Italy
| | - Francesco Porta
- Department of Pediatric and Adult Cardio-Thoracovascular, Oncoematologic and Emergencies Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Valerio Di Scioscio
- Department of Pediatric and Adult Cardio-Thoracovascular, Oncoematologic and Emergencies Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Giulia Pirini
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna-Policlinico di Sant’Orsola, Bologna, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology (FaBit), University of Bologna, Bologna, Italy
| | - Maria Concetta Nigro
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Miriam Iezza
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Hematology “Lorenzo E Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Fausto Castagnetti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Hematology “Lorenzo E Ariosto Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Luigi Lovato
- Department of Pediatric and Adult Cardio-Thoracovascular, Oncoematologic and Emergencies Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Stefano Fanti
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna-Policlinico di Sant’Orsola, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Margherita Nannini
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Tzikos G, Menni AE, Krokou D, Vouchara A, Doutsini S, Karlafti E, Karakatsanis A, Ioannidis A, Panidis S, Papavramidis T, Michalopoulos A, Paramythiotis D. Gastrointestinal Stromal Tumors: Our Ten-Year Experience of a Single-Center Tertiary Hospital. J Pers Med 2023; 13:1254. [PMID: 37623504 PMCID: PMC10455766 DOI: 10.3390/jpm13081254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 07/31/2023] [Accepted: 08/11/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. They have variable clinical presentation, prognosis, and molecular characteristics. Here, we present the results of our retrospective study including patients operated on for GIST during the last decade. METHODS All the patients who underwent GIST resection during the decade 2008-2018 were included in the study. The diagnosis was based on the pathology report. All the data were collected and analyzed statistically using the Statistical Package for Social Science v25.0. Finally, after having applied the proper search terms, a comprehensive review of articles published in the Medline database was held. RESULTS Thirty-two patients (sixteen women) were included in the study with a mean age of 69.6 years old (SD = 13.9). Twenty-one patients had a GIST in the stomach, eight in the small intestine, and three had an extra GIST. Of the 29 patients contacted, 21 were alive with a mean survival time of 74.3 months (SD = 49.6 months, min: 3.0 months, max: 161.0 months), whereas eight patients passed away. Finally, 13 patients were treated with tyrosine kinase inhibitors (TKIs) of whom only one died, while 9 patients passed away from those treated with surgery alone (p = 0.031). CONCLUSIONS Our results were in concordance with the existing data in the literature. GISTs require patient-based therapeutical management depending on the histology of the tumors. Gastric tumors present a better prognosis than those localized in the intestine, while the use of TKIs has led to an improvement in patient survival rate.
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Affiliation(s)
- Georgios Tzikos
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Alexandra-Eleftheria Menni
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Despoina Krokou
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Angeliki Vouchara
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Soultana Doutsini
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Eleni Karlafti
- Emergency Department, AHEPA University General Hospital of Thessaloniki, 54636 Thessaloniki, Greece;
| | - Anestis Karakatsanis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Aristeidis Ioannidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Stavros Panidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Theodosios Papavramidis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Antonios Michalopoulos
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
| | - Daniel Paramythiotis
- 1st Propedeutic Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.-E.M.); (D.K.); (A.V.); (S.D.); (A.K.); (A.I.); (S.P.); (T.P.); (A.M.); (D.P.)
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Sugiyama Y, Komo T, Tazaki T, Kohyama M, Takahashi S, Sasaki M. Gastric volvulus associated with shrinkage of a gastrointestinal stromal tumor by neoadjuvant imatinib: a case report. J Med Case Rep 2023; 17:15. [PMID: 36642746 PMCID: PMC9841698 DOI: 10.1186/s13256-022-03735-7] [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: 08/19/2022] [Accepted: 12/23/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND During neoadjuvant chemotherapy for giant gastrointestinal stromal tumors, changes in gastrointestinal stromal tumor size are rarely associated with events such as perforation and bleeding that require emergency surgery. Moreover, it is very rare for gastrointestinal stromal tumors to shrink and become mobile, resulting in gastric volvulus. Herein, we report a case of gastrointestinal stromal tumor shrinkage during neoadjuvant imatinib treatment, resulting in gastric volvulus that required surgery. To the best of our knowledge, this is the first reported occurrence of gastric volvulus during neoadjuvant imatinib treatment for a giant gastrointestinal stromal tumor. CASE PRESENTATION A 58-year-old Japanese woman who was diagnosed with a giant gastric gastrointestinal stromal tumor and administered neoadjuvant imatinib presented to our hospital with complaints of abdominal pain and retching. Enhanced computed tomography revealed that the gastrointestinal stromal tumor had shrunk and shifted in position, and the stomach had organoaxially twisted. Accordingly, the patient was diagnosed with gastric volvulus caused by a gastric gastrointestinal stromal tumor. Conservative treatment did not improve the volvulus; hence, laparotomy was performed. The tumor developed from the lesser curvature of the stomach and caused rotation of the gastric body. The local gastric wall was resected. Histopathological examination confirmed the diagnosis of gastrointestinal stromal tumor. The patient received adjuvant imatinib for 3 years and has been alive for 5 years without recurrence. CONCLUSIONS Gastric volvulus can be caused by the laxity of the ligaments that hold the stomach and gastric ptosis or esophageal hernia and diaphragmatic hernia; therefore, gastric gastrointestinal stromal tumors rarely cause gastric volvulus. However, a risk of torsion exists if the gastrointestinal stromal tumor develops extramural to lesser curvature and attains a certain size.
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Affiliation(s)
- Yoichi Sugiyama
- grid.414159.c0000 0004 0378 1009Department of Surgery, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, 738-8503 Japan
| | - Toshiaki Komo
- grid.414159.c0000 0004 0378 1009Department of Surgery, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, 738-8503 Japan
| | - Tatsuya Tazaki
- grid.414159.c0000 0004 0378 1009Department of Surgery, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, 738-8503 Japan
| | - Mohei Kohyama
- grid.414159.c0000 0004 0378 1009Department of Surgery, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, 738-8503 Japan
| | - Shinya Takahashi
- grid.257022.00000 0000 8711 3200Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551 Japan
| | - Masaru Sasaki
- grid.414159.c0000 0004 0378 1009Department of Surgery, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, 738-8503 Japan
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Suto H, Inui Y, Okamura A. Is CT or FDG-PET more useful for evaluation of the treatment response in metastatic HER2-positive breast cancer? a case report and literature review. Front Oncol 2023; 13:1158797. [PMID: 37152012 PMCID: PMC10157226 DOI: 10.3389/fonc.2023.1158797] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 04/05/2023] [Indexed: 05/09/2023] Open
Abstract
Response evaluation criteria in solid tumors version 1.1 (RECIST ver1.1) has been widely adopted to evaluate treatment efficacy in solid tumors, including breast cancer (BC), in clinical trials and clinical practice. RECIST is based mainly on computed tomography (CT) images, and the role of fluorodeoxyglucose-positron emission tomography (FDG-PET) is limited. However, because the rate of tumor shrinkage on CT does not necessarily reflect the potential remaining tumor cells, there may be a discrepancy between the treatment response and prognosis in some cases. Here we report a case of metastatic human epidermal growth factor receptor 2 (HER2)-positive BC where FDG-PET was preferable to CT for evaluation of the treatment response. A 40-year-old woman became aware of a lump in her right breast in September 201X. She was pregnant and underwent further examinations, including a biopsy, in November. The diagnosis was HER2-positive BC (cT2N2bM1, stage IV). Trastuzumab plus pertuzumab plus docetaxel (TPD) therapy was initiated in December 201X. CT performed in February 201X+1 showed cystic changes in the metastatic lesions in the liver, and the treatment response was stable disease (SD) according to RECIST. However, FDG-PET in March 201X+1 did not detect abnormal uptake of FDG in the hepatic lesions. The disease remained stable thereafter. Thus, tumor shrinkage may not be apparent in situations where the response to treatment results in rapid changes in blood flow within the tumor, which is associated with cystic changes. When patients with hypervascular liver metastases receive treatment with highly effective regimens, the target lesion may show cystic changes rather than shrinkage, as observed in the present case. Therefore, FDG-PET is sometimes superior to CT in judging a tumor response.
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Affiliation(s)
- Hirotaka Suto
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
- *Correspondence: Hirotaka Suto,
| | - Yumiko Inui
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Atsuo Okamura
- Department of Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
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9
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Weeda YA, Kalisvaart GM, van Velden FHP, Gelderblom H, van der Molen AJ, Bovee JVMG, van der Hage JA, Grootjans W, de Geus-Oei LF. Early Prediction and Monitoring of Treatment Response in Gastrointestinal Stromal Tumors by Means of Imaging: A Systematic Review. Diagnostics (Basel) 2022; 12:2722. [PMID: 36359564 PMCID: PMC9689665 DOI: 10.3390/diagnostics12112722] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 05/11/2025] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms. Tyrosine kinase inhibitor (TKI) therapy is currently part of routine clinical practice for unresectable and metastatic disease. It is important to assess the efficacy of TKI treatment at an early stage to optimize therapy strategies and eliminate futile ineffective treatment, side effects and unnecessary costs. This systematic review provides an overview of the imaging features obtained from contrast-enhanced (CE)-CT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT to predict and monitor TKI treatment response in GIST patients. PubMed, Web of Science, the Cochrane Library and Embase were systematically screened. Articles were considered eligible if quantitative outcome measures (area under the curve (AUC), correlations, sensitivity, specificity, accuracy) were used to evaluate the efficacy of imaging features for predicting and monitoring treatment response to various TKI treatments. The methodological quality of all articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies, v2 (QUADAS-2) tool and modified versions of the Radiomics Quality Score (RQS). A total of 90 articles were included, of which 66 articles used baseline [18F]FDG-PET and CE-CT imaging features for response prediction. Generally, the presence of heterogeneous enhancement on baseline CE-CT imaging was considered predictive for high-risk GISTs, related to underlying neovascularization and necrosis of the tumor. The remaining articles discussed therapy monitoring. Clinically established imaging features, including changes in tumor size and density, were considered unfavorable monitoring criteria, leading to under- and overestimation of response. Furthermore, changes in glucose metabolism, as reflected by [18F]FDG-PET imaging features, preceded changes in tumor size and were more strongly correlated with tumor response. Although CE-CT and [18F]FDG-PET can aid in the prediction and monitoring in GIST patients, further research on cost-effectiveness is recommended.
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Affiliation(s)
- Ylva. A. Weeda
- Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Gijsbert M. Kalisvaart
- Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | | | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Aart. J. van der Molen
- Department of Radiology, Section of Abdominal Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Judith V. M. G. Bovee
- Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Jos A. van der Hage
- Department of Surgical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Willem Grootjans
- Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Biomedical Photonic Imaging Group, University of Twente, 7522 NB Enschede, The Netherlands
- Department of Radiation Science & Technology, Technical University of Delft, 2629 JB Delft, The Netherlands
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10
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Sharma A, Ravindra SG, Singh TP, Kumar R. Role of Positron Emission Tomography/Computed Tomography in Gastrointestinal Malignancies: A Brief Review and Pictorial Essay. Indian J Nucl Med 2022; 37:249-258. [PMID: 36686294 PMCID: PMC9855232 DOI: 10.4103/ijnm.ijnm_208_21] [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: 12/24/2021] [Revised: 03/02/2022] [Accepted: 03/16/2022] [Indexed: 11/07/2022] Open
Abstract
Positron emission tomography/computed tomography (PET/CT) is increasingly becoming a mainstay in diagnosis and management of many malignant disorders. However, its role in the assessment of gastro-intestinal lesions is still evolving. The aim of this review was to demonstrate the areas, where PET/CT is impactful and where it has limitations. This will allow for us to reduce unnecessary investigations and develop methods to overcome the limitations.
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Affiliation(s)
- Anshul Sharma
- Department of Nuclear Medicine, HBCH and RC (TMC), Mullanpur, Punjab, India
| | - Shubha G Ravindra
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Tejesh Pratap Singh
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
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11
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Zarrabi KK, Galloway TJ, Flieder DB, Kumar SS, Judd J, Bauman JR. Assessing plasma circulating tumor human papillomavirus (HPV) DNA in determining treatment response in HPV-associated oropharyngeal cancer. Head Neck 2022; 44:E25-E30. [PMID: 35546490 DOI: 10.1002/hed.27081] [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] [Received: 11/23/2021] [Revised: 03/24/2022] [Accepted: 04/27/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma is a subset of head and neck cancer with a unique mechanism of carcinogenesis. Local disease is treated definitively with a multimodal approach. Navigating recurrences can be challenging, as they are sometimes indiscernible from de novo primary malignancies. Identification of dynamic biomarkers that are specific to HPV-mediated disease may assist in disease monitoring. We present a 78-year-old man who developed a squamous cell carcinoma in the lung 7 years after completing definitive chemoradiation for his p16+ head and neck squamous cell carcinoma. METHODS A novel assay for plasma circulating tumor HPV DNA was employed and provided a tool for longitudinal disease monitoring during therapy. CONCLUSION We bring attention to a novel assay and highlight its potential for use in the treatment paradigm of HPV-mediated oropharyngeal carcinoma.
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Affiliation(s)
- Kevin K Zarrabi
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Thomas J Galloway
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Douglas B Flieder
- Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Sameera S Kumar
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Julia Judd
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Jessica R Bauman
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
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12
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18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs. Cancers (Basel) 2022; 14:cancers14061507. [PMID: 35326662 PMCID: PMC8945925 DOI: 10.3390/cancers14061507] [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: 01/04/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary Epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with advanced-stage lung adenocarcinoma with EGFR mutations. However, 17–31% of these patients do not respond to therapy, making early evaluation of treatment response crucial. This prospective study investigates the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for timely prediction of response and survival of these patients. We evaluated 30 patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations, receiving first-line EGFR-TKI therapy. 18F-FDG PET/CT was performed before and two weeks after initiation of treatment. Positron Emission Tomography Response Criteria in Solid Tumors served as an independent predictor of non-progressive disease; baseline and change of metabolic tumor volume represented independent predictors of progression-free survival and overall survival, respectively. Therefore, 18F-FDG PET/CT is an early predictor of outcomes and individual prognosis of patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKI therapy. Abstract This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.
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13
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Ishida T, Takahashi T, Nishida T, Ohnishi H, Tsuboyama T, Sato S, Nakahara Y, Miyazaki Y, Takeno A, Kurokawa Y, Saito T, Yamashita K, Tanaka K, Yamamoto K, Makino T, Yamasaki M, Motoori M, Kimura Y, Nakajima K, Eguchi H, Doki Y. New response evaluation criteria using early morphological change in imatinib treatment for patients with gastrointestinal stromal tumor. Gastric Cancer 2022; 25:218-225. [PMID: 34417657 DOI: 10.1007/s10120-021-01234-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 08/11/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The introduction of molecularly targeted drugs, including imatinib, has greatly improved the prognosis of gastrointestinal stromal tumor (GIST), and based on the different response image, the methods of response evaluation have been established for GISTs. Furthrmore, the best response evaluation using them has been reported to be associated with progression-free survival (PFS) in imatinib treatment. However, since it is more important to predict the clinical outcomes of imatinib treatment in "early treatment phase", new predicting factor in earlier stage is desired to work out the whole strategy of each patient. Early morphological change (EMC) was previously reported as a predictive marker for molecularly targeted drugs in metastatic colorectal cancer. The purpose of the present study was to verify the efficacy of EMC in predicting the outcome in patients with GIST receiving imatinib at early evaluation. METHODS We retrospectively reviewed 66 patients. EMC in computed tomography (CT) image was evaluated, and the patients were categorized into two groups: active MR (morphological response) (+) group and active MR (-) group. We investigated the association between the presence of active MR and clinical outcomes. RESULTS Forty-five patients had active MR ( +). The median progression-free survival (PFS) in patients with/without active MR was 49/23 months (P = 0.0039). CONCLUSION The evaluation criteria based on EMC could be a sensitive method to predict the clinical outcome of imatinib treatment for patients with unresectable GIST.
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Affiliation(s)
- Tomo Ishida
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Toshirou Nishida
- Department of Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78, Fukushima, Fukushima-ku, Osaka, Japan
| | - Hiromitsu Ohnishi
- Department of Radiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takahiro Tsuboyama
- Department of Radiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shinsuke Sato
- Department of Gastroenterological Surgery, Shizuoka General Hospital, 4-27-1, Kita Ando Aoi-ku, Shizuoka, Japan
| | - Yujiro Nakahara
- Department of Gastroenterological Surgery, Osaka Police Hospital, 10-31Kitayama-choTennouji-ku, Osaka, Japan
| | - Yasuhiro Miyazaki
- Department of Surgery, Osaka General Medical Center, 3-1-56, Bandai-Higashi, Sumiyoshi-ku, Osaka, Japan
| | - Atsushi Takeno
- Departmrent of Surgery, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takuro Saito
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuyoshi Yamamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, 3-1-56, Bandai-Higashi, Sumiyoshi-ku, Osaka, Japan
| | - Yutaka Kimura
- Department of Surgery, Kinki University Faculty of Medicine, 377-2, Ohno-Higashi, Sayama, Osaka, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
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14
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Casali PG, Blay JY, Abecassis N, Bajpai J, Bauer S, Biagini R, Bielack S, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brodowicz T, Buonadonna A, De Álava E, Dei Tos AP, Del Muro XG, Dufresne A, Eriksson M, Fedenko A, Ferraresi V, Ferrari A, Frezza AM, Gasperoni S, Gelderblom H, Gouin F, Grignani G, Haas R, Hassan AB, Hindi N, Hohenberger P, Joensuu H, Jones RL, Jungels C, Jutte P, Kasper B, Kawai A, Kopeckova K, Krákorová DA, Le Cesne A, Le Grange F, Legius E, Leithner A, Lopez-Pousa A, Martin-Broto J, Merimsky O, Messiou C, Miah AB, Mir O, Montemurro M, Morosi C, Palmerini E, Pantaleo MA, Piana R, Piperno-Neumann S, Reichardt P, Rutkowski P, Safwat AA, Sangalli C, Sbaraglia M, Scheipl S, Schöffski P, Sleijfer S, Strauss D, Strauss SJ, Hall KS, Trama A, Unk M, van de Sande MAJ, van der Graaf WTA, van Houdt WJ, Frebourg T, Gronchi A, Stacchiotti S. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2022; 33:20-33. [PMID: 34560242 DOI: 10.1016/j.annonc.2021.09.005] [Citation(s) in RCA: 313] [Impact Index Per Article: 104.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 09/01/2021] [Accepted: 09/04/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- P G Casali
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-oncology University of Milan, Milan, Italy
| | - J Y Blay
- Centre Leon Berard and UCBL1, Lyon, France
| | - N Abecassis
- Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal
| | - J Bajpai
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - S Bauer
- Department of Medical Oncology, Interdisciplinary Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany
| | - R Biagini
- Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy
| | - S Bielack
- Klinikum Stuttgart-Olgahospital, Stuttgart, Germany
| | - S Bonvalot
- Department of Surgery, Institut Curie, Paris, France
| | | | - J V M G Bovee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - K Boye
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - T Brodowicz
- Vienna General Hospital (AKH), Medizinische Universität Wien, Vienna, Austria
| | - A Buonadonna
- Centro di Riferimento Oncologico di Aviano, Aviano, Italy
| | - E De Álava
- Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain
| | - A P Dei Tos
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - X G Del Muro
- Integrated Unit ICO Hospitalet, HUB, Barcelona, Spain
| | - A Dufresne
- Département d'Oncologie Médicale, Centre Leon Berard, Lyon, France
| | - M Eriksson
- Skane University Hospital-Lund, Lund, Sweden
| | - A Fedenko
- P. A. Herzen Cancer Research Institute, Moscow, Russian Federation
| | - V Ferraresi
- Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - A Ferrari
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - A M Frezza
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - S Gasperoni
- Department of Oncology and Robotic Surgery, Azienda Ospedaliera Universitaria Careggi, Florence, Italy
| | - H Gelderblom
- Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands
| | - F Gouin
- Centre Leon-Berard Lyon, Lyon, France
| | - G Grignani
- Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy
| | - R Haas
- Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands
| | - A B Hassan
- Oxford University Hospitals NHS Foundation Trust and University of Oxford, Oxford, UK
| | - N Hindi
- Department of Medical Oncology, Fundación Jimenez Diaz, University Hospital, Advanced Therapies in Sarcoma Lab, Madrid, Spain
| | - P Hohenberger
- Mannheim University Medical Center, Mannheim, Germany
| | - H Joensuu
- Helsinki University Hospital (HUH) and University of Helsinki, Helsinki, Finland
| | - R L Jones
- Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - C Jungels
- Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - P Jutte
- University Medical Center Groningen, Groningen, The Netherlands
| | - B Kasper
- Mannheim University Medical Center, Mannheim, Germany
| | - A Kawai
- Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - K Kopeckova
- University Hospital Motol, Prague, Czech Republic
| | - D A Krákorová
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - A Le Cesne
- Department of Cancer Medicine, Gustave Roussy, Villejuif, France
| | - F Le Grange
- Department of Oncology, University College London Hospitals NHS Foundation Trust (UCLH), London, UK
| | - E Legius
- Department for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - A Leithner
- Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
| | - A Lopez-Pousa
- Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain
| | - J Martin-Broto
- Department of Medical Oncology, Fundación Jimenez Diaz, University Hospital, Advanced Therapies in Sarcoma Lab, Madrid, Spain
| | - O Merimsky
- Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel
| | - C Messiou
- Department of Radiology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - A B Miah
- Department of Oncology, Royal Marsden Hospital and Institute of Cancer Research, London, UK
| | - O Mir
- Department of Ambulatory Cancer Care, Gustave Roussy, Villejuif, France
| | - M Montemurro
- Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - C Morosi
- Department of Radiology, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - E Palmerini
- Department of Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - M A Pantaleo
- Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria, di Bologna, Bologna, Italy
| | - R Piana
- Azienda Ospedaliero, Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | | | - P Reichardt
- Helios Klinikum Berlin Buch, Berlin, Germany
| | - P Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - A A Safwat
- Aarhus University Hospital, Aarhus, Denmark
| | - C Sangalli
- Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - M Sbaraglia
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - S Scheipl
- Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria
| | - P Schöffski
- Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium
| | - S Sleijfer
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - D Strauss
- Department of Surgery, Royal Marsden Hospital, London, UK
| | - S J Strauss
- Department of Oncology, University College London Hospitals NHS Foundation Trust (UCLH), London, UK
| | - K Sundby Hall
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - A Trama
- Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - M Unk
- Institute of Oncology of Ljubljana, Ljubljana, Slovenia
| | - M A J van de Sande
- Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - W T A van der Graaf
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - W J van Houdt
- Department of Surgical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - T Frebourg
- Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France
| | - A Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
| | - S Stacchiotti
- Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
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15
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Van den Abbeele AD, Sakellis CG, George S. PET imaging of Gastrointestinal Stromal Tumors (GIST). Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00110-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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16
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Farag S, IJzerman NS, Houdijk MPM, Reyners AKL, Arens AI, Grünhagen DJ, Desar IME, Gelderblom H, Steeghs N, de Geus-Oei LF. Early response evaluation using 18F-FDG-PET/CT does not influence management of patients with metastatic gastrointestinal stromal tumors (GIST) treated with palliative intent. Nuklearmedizin 2021; 60:411-416. [PMID: 34479374 DOI: 10.1055/a-1542-6211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
AIM The aim of this study was to investigate the impact of 18F-FDG-PET/CT on treatment decision making in metastatic gastrointestinal stromal tumor (GIST) patients. METHODS This study retrospectively evaluated 18F-FDG-PET/CT scans to monitor response of metastatic GIST patients treated with palliative intent. Data from the Dutch GIST Registry was used. Early scans (<10 weeks after start of treatment) and late scans (>10 weeks after start of treatment) were scored on the impact in change of treatment. RESULTS Sixty-one PET/CT scans were performed for treatment evaluation in 39 patients with metastatic GIST of which 36 were early scans and 25 were late scans. Early PET/CT scans led to a change in management in 5.6% of patients and late PET/CT scans led to a change in management in 56% of patients. Change in management was more often seen after scans with lack of metabolic response (48% vs. 11% in scans with metabolic response, p=0.002). Neither metabolic response nor change in treatment were more often seen in patients with KIT mutations compared to patients with non-KIT mutations (metabolic response 65% KIT vs. 46% non-KIT, p=0.33, and change in management 28% KIT vs. 21% non-KIT, p=0.74). CONCLUSION 18F-FDG-PET/CT is not recommended for early response evaluation in an unselected patient population with metastatic GIST, since it does not influence treatment decisions. 18F-FDG-PET/CT, however, can be useful for late response assessment, especially in case of indeterminate CT results.
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Affiliation(s)
- Sheima Farag
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
| | - Nikki S IJzerman
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands
| | | | - An K L Reyners
- Department of Medical Oncology, University Medical Centre Groningen, Groningen, Netherlands
| | - Anne Ij Arens
- Department of Radiology, Nuclear Medicine and Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
| | - Dirk J Grünhagen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Ingrid M E Desar
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
| | - Neeltje Steeghs
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
- Department of Biomedical Photonic Imaging Group, University of Twente, Enschede, Netherlands
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Liao CY, Jen JH, Chen YW, Li CY, Wang LW, Liu RS, Huang WS, Lu CF. Comparison of Conventional and Radiomic Features between 18F-FBPA PET/CT and PET/MR. Biomolecules 2021; 11:1659. [PMID: 34827657 PMCID: PMC8615400 DOI: 10.3390/biom11111659] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 12/12/2022] Open
Abstract
Boron-10-containing positron emission tomography (PET) radio-tracer, 18F-FBPA, has been used to evaluate the feasibility and treatment outcomes of Boron neutron capture therapy (BNCT). The clinical use of PET/MR is increasing and reveals its benefit in certain applications. However, the PET/CT is still the most widely used modality for daily PET practice due to its high quantitative accuracy and relatively low cost. Considering the different attenuation correction maps between PET/CT and PET/MR, comparison of derived image features from these two modalities is critical to identify quantitative imaging biomarkers for diagnosis and prognosis. This study aimed to investigate the comparability of image features extracted from 18F-FBPA PET/CT and PET/MR. A total of 15 patients with malignant brain tumor who underwent 18F-FBPA examinations using both PET/CT and PET/MR on the same day were retrospectively analyzed. Overall, four conventional imaging characteristics and 449 radiomic features were calculated from PET/CT and PET/MR, respectively. A linear regression model and intraclass correlation coefficient (ICC) were estimated to evaluate the comparability of derived features between two modalities. Features were classified into strong, moderate, and weak comparability based on coefficient of determination (r2) and ICC. All of the conventional features, 81.2% of histogram, 37.5% of geometry, 51.5% of texture, and 25% of wavelet-based features, showed strong comparability between PET/CT and PET/MR. With regard to the wavelet filtering, radiomic features without filtering (61.2%) or with low-pass filtering (59.2%) along three axes produced strong comparability between the two modalities. However, only 8.2% of the features with high-pass filtering showed strong comparability. The linear regression models were provided for the features with strong and moderate consensus to interchange the quantitative features between the PET/CT and the PET/MR. All of the conventional and 71% of the radiomic (mostly histogram and texture) features were sufficiently stable and could be interchanged between 18F-FBPA PET with different hybrid modalities using the proposed equations. Our findings suggested that the image features high interchangeability may facilitate future studies in comparing PET/CT and PET/MR.
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Affiliation(s)
- Chien-Yi Liao
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; (C.-Y.L.); (J.-H.J.)
| | - Jun-Hsuang Jen
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; (C.-Y.L.); (J.-H.J.)
| | - Yi-Wei Chen
- Department of Radiation Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (Y.-W.C.); (L.-W.W.)
| | - Chien-Ying Li
- Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Ling-Wei Wang
- Department of Radiation Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (Y.-W.C.); (L.-W.W.)
| | - Ren-Shyan Liu
- Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei 11220, Taiwan;
| | - Wen-Sheng Huang
- Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Chia-Feng Lu
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; (C.-Y.L.); (J.-H.J.)
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18
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Ko CC, Yeh LR, Kuo YT, Chen JH. Imaging biomarkers for evaluating tumor response: RECIST and beyond. Biomark Res 2021; 9:52. [PMID: 34215324 PMCID: PMC8252278 DOI: 10.1186/s40364-021-00306-8] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size evaluated by RECIST is often correlated with survival length and has been considered as a surrogate endpoint of therapeutic efficacy. However, the detection of morphologic change alone may not be sufficient for assessing response to new anti-cancer medication in all solid tumors. During the past fifteen years, several molecular-targeted therapies and immunotherapies have emerged in cancer treatment which work by disrupting signaling pathways and inhibited cell growth. Tumor necrosis or lack of tumor progression is associated with a good therapeutic response even in the absence of tumor shrinkage. Therefore, the use of unmodified RECIST criteria to estimate morphological changes of tumor alone may not be sufficient to estimate tumor response for these new anti-cancer drugs. Several studies have reported the low reliability of RECIST in evaluating treatment response in different tumors such as hepatocellular carcinoma, lung cancer, prostate cancer, brain glioma, bone metastasis, and lymphoma. There is an increased need for new medical imaging biomarkers, considering the changes in tumor viability, metabolic activity, and attenuation, which are related to early tumor response. Promising imaging techniques, beyond RECIST, include dynamic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), diffusion-weight imaging (DWI), magnetic resonance spectroscopy (MRS), and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). This review outlines the current RECIST with their limitations and the new emerging concepts of imaging biomarkers in oncology.
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Affiliation(s)
- Ching-Chung Ko
- Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan.,Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Lee-Ren Yeh
- Department of Radiology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Yu-Ting Kuo
- Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan.,Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jeon-Hor Chen
- Department of Radiology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan. .,Tu & Yuan Center for Functional Onco-Imaging, Department of Radiological Sciences, University of California, 164 Irvine Hall, Irvine, CA, 92697 - 5020, USA.
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Duclos V, Iep A, Gomez L, Goldfarb L, Besson FL. PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology. Int J Mol Sci 2021; 22:4159. [PMID: 33923839 PMCID: PMC8073681 DOI: 10.3390/ijms22084159] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 04/14/2021] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level.
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Affiliation(s)
- Valentin Duclos
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Alex Iep
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Léa Gomez
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Lucas Goldfarb
- Service Hospitalier Frédéric Joliot-CEA, 91401 Orsay, France;
| | - Florent L. Besson
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
- Université Paris Saclay, CEA, CNRS, Inserm, BioMaps, 91401 Orsay, France
- School of Medicine, Université Paris Saclay, 94720 Le Kremlin-Bicêtre, France
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20
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Yokoyama K, Tsuchiya J, Nakamoto Y, Tateishi U. Additional Value of [ 18F]FDG PET or PET/CT for Response Assessment of Patients with Gastrointestinal Stromal Tumor Undergoing Molecular Targeted Therapy: A Meta-Analysis. Diagnostics (Basel) 2021; 11:diagnostics11030475. [PMID: 33800310 PMCID: PMC8000740 DOI: 10.3390/diagnostics11030475] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/04/2021] [Accepted: 03/05/2021] [Indexed: 12/12/2022] Open
Abstract
To assess the additional value of 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography (PET) or PET/CT over conventional morphological imaging techniques in the treatment response assessment of gastrointestinal stromal tumor (GIST) to molecular targeted therapy (MTT), we performed a meta-analysis of all the available studies to compare the predictive value of [18F]FDG PET or PET/CT and conventional imaging techniques for assessing the response to MTT in GIST. We determined the sensitivities and specificities across studies, we calculated the positive and negative likelihood ratios (LR) and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. Pooled analysis included 4 studies comprising 88 patients. The performance characteristics in [18F]FDG PET or PET/CT and CT were as follows: sensitivity, 89% (95% confidence interval (CI) 78, 95), 52% (39, 64); specificity, 65% (44, 83), 92% (75, 99); diagnostic odds ratios (DOR), 5.8 (2.0, 16.8 4.9 (1.5, 16.1); positive LR, 1.9 (1.1, 3.4), 3.0 (1.1, 8.1); and negative LR, 0.23 (0.03, 1.6), 0.66 (0.42, 1.0), respectively. In SROC curves, the area under the curve (AUC) was 0.81 (SE, 0.11) and 0.71 (SE, 0.13) and the Q* index was 0.74 and 0.66, respectively. [18F]FDG PET/CT had higher sensitivity, while DOR and SROC curves showed better diagnostic performance in [18F]FDG PET and PET/CT studies as compared to CT.
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Affiliation(s)
- Kota Yokoyama
- Department of Diagnostic Radiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (J.T.); (U.T.)
- Correspondence: ; Tel.: +81-3-5803-5311; Fax: +81-3-5803-0147
| | - Junichi Tsuchiya
- Department of Diagnostic Radiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (J.T.); (U.T.)
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University, Kyoto 606-8507, Japan;
| | - Ukihide Tateishi
- Department of Diagnostic Radiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (J.T.); (U.T.)
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21
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Mankoff DA. PET Imaging in Cancer Clinical Trials. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00082-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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22
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Albano D, Bosio G, Tomasini D, Bonù M, Giubbini R, Bertagna F. Metabolic behavior and prognostic role of pretreatment 18F-FDG PET/CT in gist. Asia Pac J Clin Oncol 2020; 16:e207-e215. [PMID: 32762133 DOI: 10.1111/ajco.13366] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 04/20/2020] [Indexed: 02/06/2023]
Abstract
AIM The metabolic behavior and the prognostic value of 18 F-FDG-PET/CT in gastrointestinal stromal tumor (GIST) is not well investigated. The aim of this study was to analyze the metabolic behavior of GIST and the prognostic role of pretreatment PET/CT features. METHODS In this retrospective study, we included 35 patients with a diagnosis of GIST who underwent a pretreatment 18 F-FDG-PET/CT scan. We analyzed PET images visually and semiquantitatively by measuring several metabolic parameters as the maximum standardized uptake value corrected for body weight (SUVbw), for lean body mass (SUVlbm), for body surface area (SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The Kaplan-Meier method was used to measure the progression free survival (PFS) and overall survival curves. RESULTS Twenty-nine (82%) patients showed a positive 18 F-FDG-PET/CT, whereas the remaining 6 had no hypermetabolic lesions. 18 F-FDG-avidity was significantly related with mitotic index, tumor stage and tumor risk group. Instead, semiquantitative PET/CT parameters correlated only with tumor risk group. Disease progression occurred in 16 patients whereas death in seven. 18 F-FDG-avidity, MTV and TLG were the only variables significantly associated with PFS. CONCLUSION An 82% rate of PET avidity in GIST was found and it was correlated with stage, tumor risk group and mitotic index. Only baseline 18 F-FDG-avidity, MTV and TLG were independently correlated with PFS.
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Affiliation(s)
- Domenico Albano
- Nuclear Medicine Department, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
| | - Giovanni Bosio
- Nuclear Medicine Department, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
| | - Davide Tomasini
- Department of Radiation Oncology, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
| | - Marco Bonù
- Department of Radiation Oncology, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
| | - Raffaele Giubbini
- Nuclear Medicine Department, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
| | - Francesco Bertagna
- Nuclear Medicine Department, University of Brescia and Spedali Civili of Brescia, Brescia, Italy
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Donegani MI, Ferrarazzo G, Marra S, Miceli A, Raffa S, Bauckneht M, Morbelli S. Positron Emission Tomography-Based Response to Target and Immunotherapies in Oncology. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:373. [PMID: 32722205 PMCID: PMC7466359 DOI: 10.3390/medicina56080373] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/11/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022]
Abstract
2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a promising tool to support the evaluation of response to either target therapies or immunotherapy with immune checkpoint inhibitors both in clinical trials and, in selected patients, at the single patient's level. The present review aims to discuss available evidence related to the use of [18F]FDG PET (Positron Emission Tomography) to evaluate the response to target therapies and immune checkpoint inhibitors. Criteria proposed for the standardization of the definition of the PET-based response and complementary value with respect to morphological imaging are commented on. The use of PET-based assessment of the response through metabolic pathways other than glucose metabolism is also relevant in the framework of personalized cancer treatment. A brief discussion of the preliminary evidence for the use of non-FDG PET tracers in the evaluation of the response to new therapies is also provided.
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Affiliation(s)
- Maria Isabella Donegani
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Giulia Ferrarazzo
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Stefano Marra
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Alberto Miceli
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Stefano Raffa
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Matteo Bauckneht
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Silvia Morbelli
- Nuclear Medicine Unit, Department of Health SciencesUniversity of Genoa, 16132 Genoa, Italy; (M.I.D.); (G.F.); (S.M.); (A.M.); (S.R.); (M.B.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
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Arshad J, Ahmed J, Subhawong T, Trent JC. Progress in determining response to treatment in gastrointestinal stromal tumor. Expert Rev Anticancer Ther 2020; 20:279-288. [PMID: 32191549 DOI: 10.1080/14737140.2020.1745068] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Introduction: Gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal tumor of the gastrointestinal system. Multiple advances in the management of GIST from the discovery of KIT/PDGRA and other genetic alterations have led to the development of multiple tyrosine kinase inhibitors. Response assessment in GIST is determined with iRECIST (Response Evaluation Criteria in Solid Tumors), PERCIST (PET response criteria in solid tumors), or Choi criteria. Molecular genotyping of the tissue samples is the recent standard for diagnosis, treatment, and response to treatment.Areas covered: In this study, we provide a brief overview of the history of the GIST, molecular sequencing, available treatment options and clinical trials, radiologic response assessment, and the role of ctDNA in response evaluation.Expert opinion: Future GIST management is related to the development of sensitive assays to detect genetic alterations for initial diagnosis, treatment selection, monitoring the response to treatment, resistant mutations, and predicting survival.
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Affiliation(s)
- Junaid Arshad
- Miller School of Medicine/Sylvester Comprehensive Cancer Centre, University of Miami, Miami, FL, USA
| | - Jibran Ahmed
- Department of Hematology and Medical Oncology, Westchester Medical Center, Valhalla, NY, USA
| | - Ty Subhawong
- Miller School of Medicine/Sylvester Comprehensive Cancer Centre, University of Miami, Miami, FL, USA
| | - Jonathan C Trent
- Miller School of Medicine/Sylvester Comprehensive Cancer Centre, University of Miami, Miami, FL, USA
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25
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Albano D, Mattia B, Giubbini R, Bertagna F. Role of 18F-FDG PET/CT in restaging and follow-up of patients with GIST. Abdom Radiol (NY) 2020; 45:644-651. [PMID: 31646354 DOI: 10.1007/s00261-019-02274-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE Gastrointestinal stromal tumor (GIST) is a rare tumor with high risk of recurrence and poor prognosis in case of advanced GIST. The aim of this study was to evaluate the possible role of 18F-FDG PET/CT in restaging GIST. METHODS Fifty-four patients (30 male) with histological proven GIST underwent 100 18F-FDG PET/CT for restaging in suspected recurrence or during follow-up. Histopathology results and/or clinical/imaging follow-up for at least 12 months were considered as reference standard. Moreover, the diagnostic accuracy and clinical impact of 18F-FDG PET/CT were calculated. RESULTS Twenty-seven (27%) 18F-FDG PET/CT were positive, while the remaining 73 (73%) were negative. Sensitivity, specificity, PPV, NPV, and accuracy of PET/CT were 89% (95% CI 72-98%), 97% (95% CI 90-100%), 93% (95% CI 76-98%), 96% (95% CI 89-98%), and 95% (95% CI 89-98%). 18F-FDG PET/CT had a positive clinical impact in 18/100 studies changing the management, in 8 cases switching from local therapy to systemic therapy due to the detection of disseminate disease at PET/CT, in three cases recognizing relapse not detected by conventional imaging, and in 7 cases demonstrating to be true negative and avoiding unnecessary therapies. CONCLUSIONS 18F-FDG PET/CT seems to be an accurate method for detection and localization of local and distant recurrence in GIST with good sensitivity and specificity and significant impact on clinical decision-making.
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Affiliation(s)
- Domenico Albano
- Nuclear Medicine, Spedali Civili Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy.
| | - Bonacina Mattia
- Nuclear Medicine, Spedali Civili Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Raffaele Giubbini
- Nuclear Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Italy
| | - Francesco Bertagna
- Nuclear Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Italy
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Aykan NF, Özatlı T. Objective response rate assessment in oncology: Current situation and future expectations. World J Clin Oncol 2020; 11:53-73. [PMID: 32133275 PMCID: PMC7046919 DOI: 10.5306/wjco.v11.i2.53] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 11/05/2019] [Accepted: 11/28/2019] [Indexed: 02/06/2023] Open
Abstract
The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials. World Health Organization and Response Evaluation Criteria in Solid Tumors (RECIST) are anatomic response criteria developed mainly for cytotoxic chemotherapy. These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography (CT) or magnetic resonance imaging. Anatomic response criteria may not be optimal for biologic agents, some disease sites, and some regional therapies. Consequently, modifications of RECIST, Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors. Despite its limitations, RECIST v1.1 is validated in prospective studies, is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents. Finally, some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors. Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging. Some graphical methods may be useful to show longitudinal change in the tumor burden over time. Tumor tissue is a tridimensional heterogenous mass, and tumor shrinkage is not always symmetrical; thus, metabolic response assessments using positron emission tomography (PET) or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments. The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage, possibly preventing delays in drug approval. Computer-assisted automated volumetric assessments, quantitative multimodality imaging in radiology, new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
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Affiliation(s)
- Nuri Faruk Aykan
- Department of Medical Oncology, Istinye University Medical School, Bahcesehir Liv Hospital, Istanbul 34510, Turkey
| | - Tahsin Özatlı
- Department of Medical Oncology, Istinye University Medical School, Bahcesehir Liv Hospital, Istanbul 34510, Turkey
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Rare Tumors GI Group, Farhat F, Farsi AA, Mohieldin A, Bahrani BA, Sbaity E, Jaffar H, Kattan J, Rasul K, Saad K, Assi T, Morsi WE, Abood RA. Comprehensive review into the challenges of gastrointestinal tumors in the Gulf and Levant countries. World J Clin Cases 2020; 8:487-503. [PMID: 32110658 PMCID: PMC7031830 DOI: 10.12998/wjcc.v8.i3.487] [Citation(s) in RCA: 4] [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: 09/24/2019] [Revised: 12/13/2019] [Accepted: 01/01/2020] [Indexed: 02/05/2023] Open
Abstract
Although gastrointestinal stromal tumors (GISTs) are rare, with an incidence of 1/100000 per year, they are the most common sarcomas in the peritoneal cavity. Despite considerable progress in the diagnosis and treatment of GIST, about half of all patients are estimated to experience recurrence. With only two drugs, sunitinib and regorafenib, approved by the Food and Drug Administration, selecting treatment options after imatinib failure and coordinating multidisciplinary care remain challenging. In addition, physicians across the Middle East face some additional and unique challenges such as lack of published local data from clinical trials, national disease registries and regional scientific research, limited access to treatment, lack of standardization of care, and limited access to mutational analysis. Although global guidelines set a framework for the management of GIST, there are no standard local guidelines to guide clinical practice in a resource-limited environment. Therefore, a group of 11 experienced medical oncologists from across the Gulf and Levant region, part of the Rare Tumors Gastrointestinal Group, met over a period of one year to conduct a narrative review of the management of GIST and to describe regional challenges and gaps in patient management as an essential step to proposing local clinical practice recommendations.
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Affiliation(s)
| | - Fadi Farhat
- Hammoud Hospital UMC, Saida PO Box 652, Lebanon
| | | | - Ahmed Mohieldin
- Medical Oncology Department, Kuwait Cancer Control Center, Kuwait PO Box 42262, Kuwait
| | - Bassim Al Bahrani
- Medical Oncology Department, Royal Hospital, Muscat PO Box 1331, Oman
| | - Eman Sbaity
- Division of General Surgery, American University of Beirut, Beirut 1107 2180, Lebanon
| | - Hassan Jaffar
- Oncology Department, Tawam Hospital, Al Ain PO Box 15258, United Arab Emirates
| | - Joseph Kattan
- Hemato-oncology Department, Hotel Dieu de France, Beirut, Lebanon
| | - Kakil Rasul
- Hemato-oncology Department, National Center for Cancer Care and Research, Doha, Qatar
| | - Khairallah Saad
- Pathology Department, Institute National de Pathologic, Beirut, Lebanon
| | - Tarek Assi
- Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Waleed El Morsi
- Pfizer Oncology-Emerging Markets, Dubai Media City, Dubai, United Arab Emirates
| | - Rafid A Abood
- Oncology Department, Basra College of Medicine, Basra, Iraq
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PET in Gastrointestinal, Pancreatic, and Liver Cancers. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis. Mol Imaging Biol 2019; 22:515-525. [DOI: 10.1007/s11307-019-01365-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Vaidya T, Agrawal A, Mahajan S, Thakur MH, Mahajan A. The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part I). Mol Diagn Ther 2019; 23:1-26. [PMID: 30411216 DOI: 10.1007/s40291-018-0366-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The present era of precision medicine sees 'cancer' as a consequence of molecular derangements occurring at the commencement of the disease process, with morphologic changes happening much later in the process of tumorigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), play an integral role in the detection of disease at a macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumorigenesis, and thus has the potential to play a key role in heralding the transition from the concept of 'one size fits all' to 'precision medicine'. Integration of MFI with other fields of tumour biology such as genomics has spawned a novel concept called 'radiogenomics', which could serve as an indispensable tool in translational cancer research. With recent advances in medical image processing, such as texture analysis, deep learning, and artificial intelligence (AI), the future seems promising; however, their clinical utility remains unproven at present. Despite the emergence of novel imaging biomarkers, a majority of these require validation before clinical translation is possible. In this two-part review, we discuss the systematic collaboration across structural, anatomical, and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.
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Affiliation(s)
- Tanvi Vaidya
- Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Tata Memorial Centre, Room no. 125, Dr E Borges Road, Parel, Mumbai, Maharashtra, 400012, India
| | - Archi Agrawal
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, 400012, India
| | - Shivani Mahajan
- Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Tata Memorial Centre, Room no. 125, Dr E Borges Road, Parel, Mumbai, Maharashtra, 400012, India
| | - Meenakshi H Thakur
- Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Tata Memorial Centre, Room no. 125, Dr E Borges Road, Parel, Mumbai, Maharashtra, 400012, India
| | - Abhishek Mahajan
- Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Tata Memorial Centre, Room no. 125, Dr E Borges Road, Parel, Mumbai, Maharashtra, 400012, India.
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Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy. Cancers (Basel) 2019; 11:cancers11020131. [PMID: 30678055 PMCID: PMC6407112 DOI: 10.3390/cancers11020131] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 01/11/2019] [Accepted: 01/13/2019] [Indexed: 12/11/2022] Open
Abstract
Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.
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Rojas JD, Dayton PA. In Vivo Molecular Imaging Using Low-Boiling-Point Phase-Change Contrast Agents: A Proof of Concept Study. ULTRASOUND IN MEDICINE & BIOLOGY 2019; 45:177-191. [PMID: 30318123 DOI: 10.1016/j.ultrasmedbio.2018.08.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 06/26/2018] [Accepted: 08/10/2018] [Indexed: 06/08/2023]
Abstract
Sub-micron phase-change contrast agents (PCCAs) have been proposed as a tool for ultrasound molecular imaging based on their potential to extravasate and target extravascular markers and also because of the potential to image these contrast agents with a high contrast-to-tissue ratio. We compare in vivo ultrasound molecular imaging with targeted low-boiling-point PCCAs and targeted microbubble contrast agents. Both agents were targeted to the intravascular (endothelial) integrin αvß3via a cyclic RGD peptide (cyclo-Arg-Gly-Asp-D-Tyr-Cys) mechanism and imaged in vivo in a rodent fibrosarcoma model, which exhibits angiogenic microvasculature. Signal intensity was measured using two different techniques, conventional contrast-specific imaging (amplitude/phase modulation) and a droplet vaporization imaging sequence, which detects the unique signature of vaporizing PCCAs. Data indicate that PCCA-specific imaging is more sensitive to small numbers of bound agents than conventional contrast imaging. However, data also revealed that contrast from targeted microbubbles was greater than that provided by PCCAs. Both control and targeted PCCAs were observed to be retained in tissue post-vaporization, which was expected for targeted agents but not expected for control agents. The exact mechanism underlying this observation remains unknown.
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Affiliation(s)
- Juan D Rojas
- Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, North Carolina, USA
| | - Paul A Dayton
- Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, North Carolina, USA.
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Xie X, Chen H, Yang H, Lin H, Zhou S, Shen R, Lu C, Ling L, Lin W, Liao Z. Predictive value of positron emission tomography for the prognosis of molecularly targeted therapy in solid tumors. Onco Targets Ther 2018; 11:8885-8899. [PMID: 30573975 PMCID: PMC6290871 DOI: 10.2147/ott.s178076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective This study aimed at comprehensively exploring the value applying positron emission tomography (PET) to predict the effect of molecularly targeted therapy in solid tumors. Materials and methods A systematic search was performed for potentially relevant studies from the time of inception to February 2017. The primary endpoints were progression-free survival (PFS), overall survival (OS), and time to progression (TTP). The results were analyzed by Review Manager version 5.3 (RevMan 5.3) statistical software. Subgroup analyses were implemented based on the type of molecularly targeted agents (monoclonal antibodies arm and small molecular targeted agents arm), mechanism (erlotinib/gefitinib arm and bevacizumab arm), radioactive tracers, type of tumor, and reevaluated PET timing. Results Twenty-six studies incorporating 865 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a decrease in maximal standard uptake value (SUVmax), which was associated with a significantly prolonged PFS (HR =0.41, 95% CI [0.29, 0.59]; P<0.00001), OS (HR =0.52, 95% CI [0.40, 0.67]; P<0.00001), and TTP (HR =0.30, 95% CI [0.14, 0.66]; P=0.003). Similar results were obtained in the subgroup analyses of PFS in erlotinib/gefitinib arm and small molecular targeted agents arm; and OS in lung cancer arm, erlotinib/gefitinib arm, bevacizumab arm, small molecular targeted agents arm, monoclonal antibodies arm, 18F-fluorodeoxythymidine (18F-FLT) arm, 18F-fluorodeoxyglucose (18F-FDG) arm, and early PET timing arm. Conclusion Our study demonstrated that PET was a favorable approach to predict the prognosis of molecularly targeted therapy for solid tumors. PET assessment within 2 weeks could be useful to predict clinical outcome.
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Affiliation(s)
- Xianhe Xie
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Huijuan Chen
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Haitao Yang
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Heng Lin
- Department of Oncology, Fuzhou Pulmonary Hospital, Fuzhou, Fujian, People's Republic of China
| | - Sijing Zhou
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Ruifen Shen
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Cuiping Lu
- Department of Medical Oncology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian, People's Republic of China
| | - Liting Ling
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Wanzun Lin
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
| | - Ziyuan Liao
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China,
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Zukić D, Byrd DW, Kinahan PE, Enquobahrie A. Calibration Software for Quantitative PET/CT Imaging Using Pocket Phantoms. Tomography 2018; 4:148-158. [PMID: 30320214 PMCID: PMC6173789 DOI: 10.18383/j.tom.2018.00020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Multicenter clinical trials that use positron emission tomography (PET) imaging frequently rely on stable bias in imaging biomarkers to assess drug effectiveness. Many well-documented factors cause variability in PET intensity values. Two of the largest scanner-dependent errors are scanner calibration and reconstructed image resolution variations. For clinical trials, an increase in measurement error significantly increases the number of patient scans needed. We aim to provide a robust quality assurance system using portable PET/computed tomography “pocket” phantoms and automated image analysis algorithms with the goal of reducing PET measurement variability. A set of the “pocket” phantoms was scanned with patients, affixed to the underside of a patient bed. Our software analyzed the obtained images and estimated the image parameters. The analysis consisted of 2 steps, automated phantom detection and estimation of PET image resolution and global bias. Performance of the algorithm was tested under variations in image bias, resolution, noise, and errors in the expected sphere size. A web-based application was implemented to deploy the image analysis pipeline in a cloud-based infrastructure to support multicenter data acquisition, under Software-as-a-Service (SaaS) model. The automated detection algorithm localized the phantom reliably. Simulation results showed stable behavior when image properties and input parameters were varied. The PET “pocket” phantom has the potential to reduce and/or check for standardized uptake value measurement errors.
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Affiliation(s)
| | - Darrin W Byrd
- Department of Radiology, University of Washington, Seattle, WA
| | - Paul E Kinahan
- Department of Radiology, University of Washington, Seattle, WA
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Rojas JD, Papadopoulou V, Czernuszewicz TJ, Rajamahendiran RM, Chytil A, Chiang YC, Chong DC, Bautch VL, Rathmell WK, Aylward S, Gessner RC, Dayton PA. Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma. IEEE Trans Biomed Eng 2018; 66:873-880. [PMID: 30059292 DOI: 10.1109/tbme.2018.2860932] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies. OBJECTIVE Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size. METHODS Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy. RESULTS Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology ([Formula: see text]). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity. CONCLUSION/SIGNIFICANCE Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.
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Czernuszewicz TJ, Papadopoulou V, Rojas JD, Rajamahendiran RM, Perdomo J, Butler J, Harlacher M, O’Connell G, Zukić D, Aylward SR, Dayton PA, Gessner RC. A new preclinical ultrasound platform for widefield 3D imaging of rodents. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2018; 89:075107. [PMID: 30068108 PMCID: PMC6045495 DOI: 10.1063/1.5026430] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.
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Affiliation(s)
| | - Virginie Papadopoulou
- Joint Department of Biomedical Engineering, The University of North Carolina and North Carolina State University, Chapel Hill, North Carolina 27599, USA
| | - Juan D. Rojas
- Joint Department of Biomedical Engineering, The University of North Carolina and North Carolina State University, Chapel Hill, North Carolina 27599, USA
| | | | - Jonathan Perdomo
- SonoVol, Inc., Research Triangle Park, North Carolina 27709, USA
| | - James Butler
- SonoVol, Inc., Research Triangle Park, North Carolina 27709, USA
| | - Max Harlacher
- SonoVol, Inc., Research Triangle Park, North Carolina 27709, USA
| | - Graeme O’Connell
- SonoVol, Inc., Research Triangle Park, North Carolina 27709, USA
| | - Dženan Zukić
- Kitware, Inc., Carrboro, North Carolina 27510, USA
| | | | - Paul A. Dayton
- Joint Department of Biomedical Engineering, The University of North Carolina and North Carolina State University, Chapel Hill, North Carolina 27599, USA
| | - Ryan C. Gessner
- SonoVol, Inc., Research Triangle Park, North Carolina 27709, USA
- Author to whom correspondence should be addressed: . Current address: First Flight Venture Center, 2 Davis Dr., Research Triangle Park, NC 27709-3169. Telephone: 844-766-6865 x707
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Mankoff DA, Katz SI. PET imaging for assessing tumor response to therapy. J Surg Oncol 2018; 118:362-373. [PMID: 29938396 DOI: 10.1002/jso.25114] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/28/2018] [Indexed: 12/19/2022]
Abstract
Positron emission tomography (PET) is a radioisotope imaging technique capable of quantifying the regional distribution of molecular imaging probes targeted to biochemical pathways and processes allowing direct measurement of biochemical changes induced by cancer therapy, including the activity of targeted growth pathways and cellular populations. In this manuscript, we review the underlying principles of PET imaging, choices for PET radiopharmaceuticals, methods for tumor analysis and PET applications for cancer therapy response assessment including potential future directions.
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Affiliation(s)
- David A Mankoff
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sharyn I Katz
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Ellis S, Reader AJ. Penalized maximum likelihood simultaneous longitudinal PET image reconstruction with difference-image priors. Med Phys 2018; 45:3001-3018. [PMID: 29697144 DOI: 10.1002/mp.12937] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 02/27/2018] [Accepted: 04/12/2018] [Indexed: 11/07/2022] Open
Abstract
PURPOSE Many clinical contexts require the acquisition of multiple positron emission tomography (PET) scans of a single subject, for example, to observe and quantitate changes in functional behaviour in tumors after treatment in oncology. Typically, the datasets from each of these scans are reconstructed individually, without exploiting the similarities between them. We have recently shown that sharing information between longitudinal PET datasets by penalizing voxel-wise differences during image reconstruction can improve reconstructed images by reducing background noise and increasing the contrast-to-noise ratio of high-activity lesions. Here, we present two additional novel longitudinal difference-image priors and evaluate their performance using two-dimesional (2D) simulation studies and a three-dimensional (3D) real dataset case study. METHODS We have previously proposed a simultaneous difference-image-based penalized maximum likelihood (PML) longitudinal image reconstruction method that encourages sparse difference images (DS-PML), and in this work we propose two further novel prior terms. The priors are designed to encourage longitudinal images with corresponding differences which have (a) low entropy (DE-PML), and (b) high sparsity in their spatial gradients (DTV-PML). These two new priors and the originally proposed longitudinal prior were applied to 2D-simulated treatment response [18 F]fluorodeoxyglucose (FDG) brain tumor datasets and compared to standard maximum likelihood expectation-maximization (MLEM) reconstructions. These 2D simulation studies explored the effects of penalty strengths, tumor behaviour, and interscan coupling on reconstructed images. Finally, a real two-scan longitudinal data series acquired from a head and neck cancer patient was reconstructed with the proposed methods and the results compared to standard reconstruction methods. RESULTS Using any of the three priors with an appropriate penalty strength produced images with noise levels equivalent to those seen when using standard reconstructions with increased counts levels. In tumor regions, each method produces subtly different results in terms of preservation of tumor quantitation and reconstruction root mean-squared error (RMSE). In particular, in the two-scan simulations, the DE-PML method produced tumor means in close agreement with MLEM reconstructions, while the DTV-PML method produced the lowest errors due to noise reduction within the tumor. Across a range of tumor responses and different numbers of scans, similar results were observed, with DTV-PML producing the lowest errors of the three priors and DE-PML producing the lowest bias. Similar improvements were observed in the reconstructions of the real longitudinal datasets, although imperfect alignment of the two PET images resulted in additional changes in the difference image that affected the performance of the proposed methods. CONCLUSION Reconstruction of longitudinal datasets by penalizing difference images between pairs of scans from a data series allows for noise reduction in all reconstructed images. An appropriate choice of penalty term and penalty strength allows for this noise reduction to be achieved while maintaining reconstruction performance in regions of change, either in terms of quantitation of mean intensity via DE-PML, or in terms of tumor RMSE via DTV-PML. Overall, improving the image quality of longitudinal datasets via simultaneous reconstruction has the potential to improve upon currently used methods, allow dose reduction, or reduce scan time while maintaining image quality at current levels.
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Affiliation(s)
- Sam Ellis
- School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, UK
| | - Andrew J Reader
- School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, UK
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Maleddu A, Pantaleo MA, Castellucci P, Astorino M, Nanni C, Nannini M, Busato F, Di Battista M, Farsad M, Lodi F, Boschi S, Fanti S, Biasco G. 11C-Acetate PET for Early Prediction of Sunitinib Response in Metastatic Renal Cell Carcinoma. TUMORI JOURNAL 2018; 95:382-4. [DOI: 10.1177/030089160909500320] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Sunitinib is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties used for treatment of renal cell carcinoma and gastrointestinal stromal tumors at a dose of 50 mg/day consecutively for 4 weeks followed by 2 weeks off per cycle. At present, no data are available on the early prediction of sunitinib response in renal cell carcinoma. We report a clinical case of a patient with metastatic renal cell carcinoma diagnosed with 11C-acetate PET and conventional CT and treated with sunitinib. Partial and complete remission documented by CT was preceded by early functional tumor inhibition shown by 11C-acetate-PET after only 14 days of therapy. This case report highlights some interesting points related to the potential role of a novel non-FDG PET tracer, 11C-acetate, in the early prediction of the response to targeted therapies in metastatic renal cell carcinoma.
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Affiliation(s)
- Alessandra Maleddu
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
| | - Maria A Pantaleo
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
| | | | - Maria Astorino
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
| | - Cristina Nanni
- Nuclear Medicine Service, University of Bologna, Bologna, Italy
| | - Margherita Nannini
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
| | - Fiorenza Busato
- Malpighi Radiology Unit, Department of Digestive Diseases and Internal Medicine, University of Bologna, Bologna, Italy
| | - Monica Di Battista
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
| | - Mohsen Farsad
- Nuclear Medicine Service, University of Bologna, Bologna, Italy
| | - Filippo Lodi
- PET Radiopharmacy Nuclear Medicine Service, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Stefano Boschi
- PET Radiopharmacy Nuclear Medicine Service, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Stefano Fanti
- Nuclear Medicine Service, University of Bologna, Bologna, Italy
| | - Guido Biasco
- Institute of Hematology and Medical Oncology “L.&A. Seragnoli”, University of Bologna, Bologna, Italy
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Schliep S, Agaimy A, Cavallaro A, Kiesewetter F, Schuler G, Heinzerling L. Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports. J Immunother Cancer 2018; 6:2. [PMID: 29332608 PMCID: PMC5767974 DOI: 10.1186/s40425-017-0309-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 12/10/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor. CASE PRESENTATION Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations. In both patients histologic assessment revealed a complete response with necrotic and scarred lesions free of tumor. One of the patients had started immunotherapy 20 months before with an initial partial response. CONCLUSIONS This phenomenon of a concealed complete response can lead to overtreatment or unnecessary change in treatment. Thus, it is essential to raise awareness for it. Correct identification of responders to immune checkpoint inhibitor therapy is crucial to spare patients immune-mediated side effects and unnecessary as well as expensive treatment. Regression of metastases without decline in size, in these cases manifesting as complete responses, are probably more common than expected and identified to date. Until such responses can be readily identified by new imaging techniques, we recommend liberal biopsies for histologic assessment of progressive metastases in patients during and/or after immune checkpoint inhibitor therapy.
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Affiliation(s)
- Stefan Schliep
- Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Germany
| | - Alexander Cavallaro
- Institute of Radiology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany
| | - Franklin Kiesewetter
- Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany
| | - Gerold Schuler
- Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany
| | - Lucie Heinzerling
- Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
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Montemurro M, Cioffi A, Dômont J, Rutkowski P, Roth AD, von Moos R, Inauen R, Toulmonde M, Burkhard RO, Knuesli C, Bauer S, Cassier P, Schwarb H, Le Cesne A, Koeberle D, Bärtschi D, Dietrich D, Biaggi C, Prior J, Leyvraz S. Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumor: A multicenter, 2-stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07). Cancer 2018; 124:1449-1454. [DOI: 10.1002/cncr.31234] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Revised: 12/06/2017] [Accepted: 12/15/2017] [Indexed: 11/09/2022]
Affiliation(s)
| | - Angela Cioffi
- Medical Oncology-Sarcoma; Gustave Roussy Institute; Villejuif France
| | - Julien Dômont
- Medical Oncology-Sarcoma; Gustave Roussy Institute; Villejuif France
| | - Piotr Rutkowski
- Soft Tissue/Bone Sarcoma and Melanoma; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology; Warsaw Poland
| | - Arnaud D. Roth
- Division of Oncology; Geneva University Hospital; Geneva Switzerland
| | - Roger von Moos
- Medical Oncology and Hematology; Cantonal Hospital Graubunden; Chur Switzerland
| | - Roman Inauen
- Department of Oncology; Cantonal Hospital St. Gallen; St. Gallen Switzerland
| | | | - Roger O. Burkhard
- Oncology Center; Hirslanden Hospital and Health Care; Zurich Switzerland
| | - Claudio Knuesli
- Medical Oncology; Hospital St. Claraspital; Basel Switzerland
| | - Sebastian Bauer
- Department of Medical Oncology, Sarcoma Center, West German Cancer Center; University of Duisburg-Essen; Essen Germany
| | | | - Heike Schwarb
- Oncology/Internal Medicine; Cantonal Hospital Baden; Baden Switzerland
| | - Axel Le Cesne
- Medical Oncology-Sarcoma; Gustave Roussy Institute; Villejuif France
| | - Dieter Koeberle
- Department of Oncology/Hematology; Cantonal Hospital St. Gallen; St. Gallen Switzerland
| | - Daniela Bärtschi
- Coordinating Center; Swiss Group for Clinical Cancer Research; Bern Switzerland
| | - Daniel Dietrich
- Coordinating Center; Swiss Group for Clinical Cancer Research; Bern Switzerland
| | - Christine Biaggi
- Coordinating Center; Swiss Group for Clinical Cancer Research; Bern Switzerland
| | - John Prior
- Nuclear Medicine and Molecular Imaging; University Hospital of Lausanne; Lausanne Switzerland
| | - Serge Leyvraz
- Medical Oncology; University Hospital of Lausanne; Lausanne Switzerland
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Vitiello GA, Medina BD, Zeng S, Bowler TG, Zhang JQ, Loo JK, Param NJ, Liu M, Moral AJ, Zhao JN, Rossi F, Antonescu CR, Balachandran VP, Cross JR, DeMatteo RP. Mitochondrial Inhibition Augments the Efficacy of Imatinib by Resetting the Metabolic Phenotype of Gastrointestinal Stromal Tumor. Clin Cancer Res 2017; 24:972-984. [PMID: 29246941 DOI: 10.1158/1078-0432.ccr-17-2697] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 11/10/2017] [Accepted: 12/05/2017] [Indexed: 12/14/2022]
Abstract
Purpose: Imatinib dramatically reduces gastrointestinal stromal tumor (GIST) 18F-FDG uptake, providing an early indicator of treatment response. Despite decreased glucose internalization, many GIST cells persist, suggesting that alternative metabolic pathways are used for survival. The role of mitochondria in imatinib-treated GIST is largely unknown.Experimental Design: We quantified the metabolic activity of several human GIST cell lines. We treated human GIST xenografts and genetically engineered KitV558del/+ mice with the mitochondrial oxidative phosphorylation inhibitor VLX600 in combination with imatinib and analyzed tumor volume, weight, histology, molecular signaling, and cell cycle activity. In vitro assays on human GIST cell lines were also performed.Results: Imatinib therapy decreased glucose uptake and downstream glycolytic activity in GIST-T1 and HG129 cells by approximately half and upregulated mitochondrial enzymes and improved mitochondrial respiratory capacity. Mitochondrial inhibition with VLX600 had a direct antitumor effect in vitro while appearing to promote glycolysis through increased AKT signaling and glucose transporter expression. When combined with imatinib, VLX600 prevented imatinib-induced cell cycle escape and reduced p27 expression, leading to increased apoptosis when compared to imatinib alone. In KitV558del/+ mice, VLX600 alone did not induce tumor cell death, but had a profound antitumor effect when combined with imatinib.Conclusions: Our findings show that imatinib alters the metabolic phenotype of GIST, and this may contribute to imatinib resistance. Our work offers preclinical proof of concept of metabolic targeting as an effective strategy for the treatment of GIST. Clin Cancer Res; 24(4); 972-84. ©2017 AACR.
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Affiliation(s)
- Gerardo A Vitiello
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Benjamin D Medina
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Shan Zeng
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Timothy G Bowler
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jennifer Q Zhang
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jennifer K Loo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nesteene J Param
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Mengyuan Liu
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Alec J Moral
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Julia N Zhao
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ferdinand Rossi
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Cristina R Antonescu
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Justin R Cross
- The Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
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Genomic Characterization of Lung Cancer and Its Impact on the Use and Timing of PET in Therapeutic Response Assessment. PET Clin 2017; 13:33-42. [PMID: 29157384 DOI: 10.1016/j.cpet.2017.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Significant advances in understanding the genomic landscape of non-small cell lung cancer (NSCLC) together with the coupling discovery of key oncogenic drivers and the development of effective targeted and immunotherapeutic agents have revolutionized the management of this malignancy. Although these therapies have resulted in improved outcomes for a subgroup of patients, their benefit may not necessarily be reflected by conventional response assessment criteria, because these therapeutic agents differ in their mechanism of action and response time compared with cytotoxic chemotherapy. Here the authors review available therapies in NSCLC and the utility of PET in therapeutic response assessment.
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Farag S, Geus-Oei LFD, van der Graaf WT, van Coevorden F, Grunhagen D, Reyners AK, Boonstra PA, Desar I, Gelderblom H, Steeghs N. Early Evaluation of Response Using 18F-FDG PET Influences Management in Gastrointestinal Stromal Tumor Patients Treated with Neoadjuvant Imatinib. J Nucl Med 2017; 59:194-196. [DOI: 10.2967/jnumed.117.196642] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 08/10/2017] [Indexed: 12/16/2022] Open
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Delyon J, Chevret S, Jouary T, Dalac S, Dalle S, Guillot B, Arnault JP, Avril MF, Bedane C, Bens G, Pham-Ledard A, Mansard S, Grange F, Machet L, Meyer N, Legoupil D, Saiag P, Idir Z, Renault V, Deleuze JF, Hindie E, Battistella M, Dumaz N, Mourah S, Lebbe C. STAT3 Mediates Nilotinib Response in KIT-Altered Melanoma: A Phase II Multicenter Trial of the French Skin Cancer Network. J Invest Dermatol 2017; 138:58-67. [PMID: 28843487 DOI: 10.1016/j.jid.2017.07.839] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 06/18/2017] [Accepted: 07/14/2017] [Indexed: 01/30/2023]
Abstract
Mutated oncogenic KIT is a therapeutic target in melanoma. We conducted a multicenter phase II trial on the KIT inhibitor nilotinib in patients with unresectable melanoma harboring KIT alteration. The primary endpoint was the response rate (complete response or partial response following Response Evaluation Criteria in Solid Tumors criteria) at 6 months. Pharmacodynamic studies using KIT sequencing, qPCR array, and immunostaining of downstream KIT effectors were performed during treatment. Twenty-five patients were included and received 400 mg oral nilotinib twice daily. At 6 months, nilotinib induced tumor response in four patients. The best overall response rate was 20% and the disease control rate was 56%, limited to patients harboring exon 11 or 13 mutations. Four patients exhibited durable response, including three persisting (3.6 and 2.8 years for two patients with stage IIIC and 2.5 years for one with IVM1b melanoma). A reduction in signal transducer and activator of transcription (STAT) 3 phosphorylation and its effectors (BCL-2, MCL-1) in tumors during follow-up was significantly associated with clinical response. In the KIT-mutated melanoma cell line M230, nilotinib reduced STAT3 signaling and STAT inhibitors were as efficient as KIT inhibitors in reducing cell proliferation. Our study evidences a significant association between STAT3 inhibition and response to nilotinib, and provides a rationale for future research assessing STAT inhibitors in KIT-mutated melanoma.
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Affiliation(s)
- Julie Delyon
- Service de Dermatologie, and CIC (Centre d'Investigations Cliniques), AP-HP, Hôpital Saint-Louis, Paris, France; INSERM, UMR-976, AP-HP, Hôpital Saint-Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
| | - Sylvie Chevret
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Biostatistique et Information Médicale, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Thomas Jouary
- Unité Onco-dermatologie, Hôpital François Mitterrand, Pau, France
| | - Sophie Dalac
- Service de Dermatologie, CHU Dijon Bourgogne, Dijon, France
| | - Stephane Dalle
- Cancer Research Center of Lyon, INSERM U1052, CNRS UMR5286, Claude Bernard Lyon 1 University, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France
| | | | | | - Marie-Françoise Avril
- Service de Dermatologie, AP-HP, Hôpital Cochin, Paris, France; Université Paris Descartes, Paris, France
| | - Christophe Bedane
- Unité d'oncologie thoracique et cutanée, Hopital Dupuytren, Limoges, France
| | - Guido Bens
- Service de Dermatologie, Centre hospitalier régional d'Orléans, Orléans, France
| | | | - Sandrine Mansard
- Dermatology Department, CHU de Clermont Ferrand, Clermont Ferrand, France
| | - Florent Grange
- Dermatology Department, Reims University Hospital, Reims, France
| | - Laurent Machet
- Department of Dermatology, Centre Hospitalier Regional et Universitaire (CHRU) de Tours, Tours, France; Inserm U930, University Francois Rabelais de Tours, Tours, France
| | - Nicolas Meyer
- Dermatologie, Institut Universitaire du Cancer et CHU de Toulouse, Toulouse, France; Inserm UMR 1037, CRCT, Toulouse, France
| | | | - Philippe Saiag
- Université de Versailles St-Quentin, EA 4340, Boulogne-Billancourt, France; Service de Dermatologie Générale et Oncologique, AP-HP, Hôpital Ambroise Paré, Boulogne-Billancourt, France
| | - Zakia Idir
- AP-HP, Département de la Recherche Clinique et du Développement, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Victor Renault
- Laboratory for Bioinformatics, CEPH-Fondation Jean Dausset, Paris, France
| | - Jean-François Deleuze
- Centre National de Génotypage, CEA, Evry, France; CEPH-Fondation Jean Dausset, Paris, France
| | - Elif Hindie
- Service de Médecine Nucléaire, CHU de Bordeaux, LabEx TRAIL, Université de Bordeaux, Bordeaux, France
| | - Maxime Battistella
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM, UMR_S1165, Paris, France; Pathology department, Hopital Saint-Louis, AP-HP, Paris, France
| | - Nicolas Dumaz
- INSERM, UMR-976, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Samia Mourah
- INSERM, UMR-976, AP-HP, Hôpital Saint-Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire de Pharmacologie Biologique, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Celeste Lebbe
- Service de Dermatologie, and CIC (Centre d'Investigations Cliniques), AP-HP, Hôpital Saint-Louis, Paris, France; INSERM, UMR-976, AP-HP, Hôpital Saint-Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Suzuki K, Muto Y, Ichida K, Fukui T, Takayama Y, Kakizawa N, Kato T, Hasegawa F, Watanabe F, Kaneda Y, Kikukawa R, Saito M, Tsujinaka S, Futsuhara K, Takata O, Noda H, Miyakura Y, Kiyozaki H, Konishi F, Rikiyama T. Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis. Oncol Lett 2017; 14:1491-1499. [PMID: 28789370 PMCID: PMC5529781 DOI: 10.3892/ol.2017.6338] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 02/13/2017] [Indexed: 12/12/2022] Open
Abstract
Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.
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Affiliation(s)
- Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yuta Muto
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Kosuke Ichida
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Taro Fukui
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yuji Takayama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Nao Kakizawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Takaharu Kato
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Fumi Hasegawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yuji Kaneda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Rina Kikukawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Masaaki Saito
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Shingo Tsujinaka
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Kazushige Futsuhara
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Osamu Takata
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yasuyuki Miyakura
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Hirokazu Kiyozaki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Fumio Konishi
- Department of Surgery, Nerima-Hikarigaoka Hospital, Tokyo 179-0072, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
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Ravoori MK, Singh SP, Lee J, Bankson JA, Kundra V. In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse Model. Radiology 2017; 285:830-838. [PMID: 28707963 DOI: 10.1148/radiol.2017161772] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 106 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and 18F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with 18F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized 13C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when 18F-FDG PET/CT does not indicate a response. © RSNA, 2017 Online supplemental material is available for this article.
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Affiliation(s)
- Murali K Ravoori
- From the Departments of Cancer Systems Imaging (M.K.R., S.P.S., V.K.), Imaging Physics (J.L., J.A.B.), and Diagnostic Radiology (V.K.), University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Sheela P Singh
- From the Departments of Cancer Systems Imaging (M.K.R., S.P.S., V.K.), Imaging Physics (J.L., J.A.B.), and Diagnostic Radiology (V.K.), University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Jaehyuk Lee
- From the Departments of Cancer Systems Imaging (M.K.R., S.P.S., V.K.), Imaging Physics (J.L., J.A.B.), and Diagnostic Radiology (V.K.), University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - James A Bankson
- From the Departments of Cancer Systems Imaging (M.K.R., S.P.S., V.K.), Imaging Physics (J.L., J.A.B.), and Diagnostic Radiology (V.K.), University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Vikas Kundra
- From the Departments of Cancer Systems Imaging (M.K.R., S.P.S., V.K.), Imaging Physics (J.L., J.A.B.), and Diagnostic Radiology (V.K.), University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
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Jeong S, Eskandari R, Park SM, Alvarez J, Tee SS, Weissleder R, Kharas MG, Lee H, Keshari KR. Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer. SCIENCE ADVANCES 2017; 3:e1700341. [PMID: 28630930 PMCID: PMC5473678 DOI: 10.1126/sciadv.1700341] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 04/26/2017] [Indexed: 06/10/2023]
Abstract
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 107, which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 103-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism.
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Affiliation(s)
- Sangmoo Jeong
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Roozbeh Eskandari
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Sun Mi Park
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Julio Alvarez
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Sui Seng Tee
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Ralph Weissleder
- Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
- Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA
| | - Michael G. Kharas
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Weill Cornell Medical College, New York, NY 10065, USA
| | - Hakho Lee
- Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Radiology, Harvard Medical School, Boston, MA 02114, USA
| | - Kayvan R. Keshari
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Weill Cornell Medical College, New York, NY 10065, USA
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Choi H. Role of Imaging in Response Assessment and Individualised Treatment for Sarcomas. Clin Oncol (R Coll Radiol) 2017; 29:481-488. [PMID: 28506521 DOI: 10.1016/j.clon.2017.04.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 03/21/2017] [Accepted: 04/05/2017] [Indexed: 02/07/2023]
Abstract
The first systematic response evaluation criteria were established by WHO, based on the tumor size changes shortly after the computed tomography (CT) technique became available to the daily practice. RECIST, a simplified version of WHO criteria, and its newer version, RECIST1.1 are the currently available international response evaluation criteria in solid tumors and remains based on tumor size changes. While the introduction of molecularly targeted drugs has significantly improved the survival in patient with sarcomas, the evaluation of tumor response has become more complicated. Increasing number of studies have reported the lack of shrinkage in responding tumors and raised concerns of significant underestimation of responses using RECIST. The first such observation was made on gastrointestinal stromal tumor (GIST) treated with imatinib. In GISTs responding to imatinib, the degree of contrast enhancement on CT typically decreases significantly compared with the baseline, and, regardless of whether tumors shrink, heterogeneous hyperattenuating tumors become homogeneous hypoattenuating tumors with a smaller enhancing solid component. In current oncology practice, CT is a widely accepted method of evaluating tumor response. CT images are relatively simple to acquire and can be reasonably reproduced with no significant technical obstacles. FDG-PET is highly sensitive and specific in identifying responding sarcomas. It has mostly been used as a problem solver and for those with marginally resectable GIST. More recently, the utility of whole body MRI is undergoing exploration. This article discusses the traditional size-based response evaluation criteria, and introduces new evidence based response evaluation based on changes in morphology in addition to changes in tumor size on CT images, and whole body imaging is introduced at the end.
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Affiliation(s)
- H Choi
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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