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Fiore M, Petrianni GM, Trecca P, D’Ercole G, Coppola A, La Vaccara V, Taralli S, Cimini P, Greco C, Ippolito E, Calcagni ML, Beomonte Zobel B, Caputo D, Coppola R, Ramella S, D’Angelillo RM. The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies. Int J Surg 2024; 110:6081-6091. [PMID: 37737898 PMCID: PMC11486963 DOI: 10.1097/js9.0000000000000755] [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: 07/28/2023] [Accepted: 09/04/2023] [Indexed: 09/23/2023]
Abstract
AIM The aim was to investigate the use of comprehensive pretreatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18F-FDG-positron emission tomography (PET)/computed tomography (CT) scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in CRT combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control, and metastasis-free survival. RESULTS Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared tonon-resected patients (median PFS, 22.5 months vs. 9.5 months, P <0.001; median OS, 38.2 months vs. 13 months, P <0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to the upfront CRT group (median PFS, 19 months vs. 9.9 months, P <0.001; median OS, 19.3 months vs. 14.6 months, P <0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI: 0.12-1.02, P =0.05), and this data was confirmed at multivariate analysis (95% CI: 0.09-0.98, P =0.04). Hematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS The use of comprehensive pretreatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.
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Affiliation(s)
- Michele Fiore
- Department of Medicine and Surgery, Research Unit of Radiation Oncology
- Operative Research Unit of Radiation Oncology
| | | | | | - Gabriele D’Ercole
- Department of Medicine and Surgery, Research Unit of Radiation Oncology
| | - Alessandro Coppola
- Dipartimento di Chirurgia, Sapienza Università di Roma, Viale Regina Elena 326
| | | | - Silvia Taralli
- Dipartimento di Diagnostica per Immagini, Nuclear Medicine Unit, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS
| | - Paola Cimini
- Operative Research Unit of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, Roma
| | - Carlo Greco
- Department of Medicine and Surgery, Research Unit of Radiation Oncology
- Operative Research Unit of Radiation Oncology
| | - Edy Ippolito
- Department of Medicine and Surgery, Research Unit of Radiation Oncology
- Operative Research Unit of Radiation Oncology
| | - Maria Lucia Calcagni
- Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore
- Dipartimento di Diagnostica per Immagini, Nuclear Medicine Unit, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS
| | - Bruno Beomonte Zobel
- Department of Medicine and Surgery, Research Unit of Radiology
- Operative Research Unit of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, Roma
| | - Damiano Caputo
- Department of Surgery and Research Unit of General Surgery, Università Campus Bio-Medico di Roma
- Operative Research Unit of General Surgery Unit
| | - Roberto Coppola
- Department of Surgery and Research Unit of General Surgery, Università Campus Bio-Medico di Roma
- Operative Research Unit of General Surgery Unit
| | - Sara Ramella
- Department of Medicine and Surgery, Research Unit of Radiation Oncology
- Operative Research Unit of Radiation Oncology
| | - Rolando Maria D’Angelillo
- Radiation Oncology, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy
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Martins A, Ferreira BC, Gaspar MM, Vieira S, Lopes J, Viana AS, Paulo A, Mendes F, Campello MPC, Martins R, Reis CP. Enhanced Cytotoxicity against a Pancreatic Cancer Cell Line Combining Radiation and Gold Nanoparticles. Pharmaceutics 2024; 16:900. [PMID: 39065597 PMCID: PMC11280324 DOI: 10.3390/pharmaceutics16070900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/28/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumor cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83 ± 20 nm and 49 ± 12 nm, respectively. For RT alone, a reduction in cell viability of up to 33 ± 12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 μM showed a reduction in cell viability of 20 ± 4% and 35 ± 4%, respectively, while for BBN-AuNPs, at 50 and 200 μM, a reduction in cell viability of 25 ± 3% and 37 ± 3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26 ± 3% and 22 ± 2% between RT + HAOA-AuNPs at 400 μM and RT + BBN-AuNPs at 50 μM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.
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Affiliation(s)
- Alexandra Martins
- Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
| | - Brigida C Ferreira
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
| | - Maria Manuela Gaspar
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
- iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
| | - Sandra Vieira
- Champalimaud Foundation, Radiotherapy, 1400-038 Lisboa, Portugal
| | - Joana Lopes
- iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
| | - Ana S Viana
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
| | - António Paulo
- C2TN-Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
- DECN-Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
| | - Filipa Mendes
- C2TN-Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
- DECN-Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
| | - Maria Paula Cabral Campello
- C2TN-Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
- DECN-Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal
| | - Rui Martins
- Centro de Estatística e Aplicações da Universidade de Lisboa, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
| | - Catarina Pinto Reis
- Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
- iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
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Roy Chaudhuri T, Lin Q, Stachowiak EK, Rosario SR, Spernyak JA, Ma WW, Stachowiak MK, Greene MK, Quinn GP, McDade SS, Clynes M, Scott CJ, Straubinger RM. Dual-Hit Strategy for Therapeutic Targeting of Pancreatic Cancer in Patient-Derived Xenograft Tumors. Clin Cancer Res 2024; 30:1367-1381. [PMID: 38270582 PMCID: PMC11019863 DOI: 10.1158/1078-0432.ccr-23-0131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/21/2023] [Accepted: 01/23/2024] [Indexed: 01/26/2024]
Abstract
PURPOSE Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) "primes" PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial-mesenchymal transition (EMT). We aimed to identify the signal derangements responsible for EMT induction and reverse them and devise approaches to stratify SHHi-responsive tumors noninvasively based on clinically-quantifiable parameters. EXPERIMENTAL DESIGN Animals underwent diffusion-weighted magnetic resonance (DW-MR) imaging for measurement of intratumor diffusivity. In parallel, tissue-level deposition of nanoparticle probes was quantified as a marker of vascular permeability/perfusion. Transcriptomic and bioinformatic analysis was employed to investigate SHHi-induced gene reprogramming and identify key "nodes" responsible for EMT induction. RESULTS Multiple patient tumor isolates responded to short-term SHH inhibitor exposure with increased vascular patency and permeability, with proportionate increases in tumor diffusivity. Nonresponding PDXs did not. SHHi-treated tumors showed elevated FGF drive and distinctly higher nuclear localization of fibroblast growth factor receptor (FGFR1) in EMT-polarized tumor cells. Pan-FGFR inhibitor NVP-BGJ398 (Infigratinib) reversed the SHHi-induced EMT marker expression and nuclear FGFR1 accumulation without compromising the enhanced permeability effect. CONCLUSIONS This dual-hit strategy of SMO and FGFR inhibition provides a clinically-translatable approach to compromise the profound impermeability of PDAC tumors. Furthermore, clinical deployment of DW-MR imaging could fulfill the essential clinical-translational requirement for patient stratification.
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Affiliation(s)
- Tista Roy Chaudhuri
- Department of Pharmaceutical Sciences, University at
Buffalo, State University of New York, Buffalo, NY 14214
| | - Qingxiang Lin
- Department of Cell Stress Biology, Roswell Park
Comprehensive Cancer Center, Buffalo, NY 14263
| | - Ewa K. Stachowiak
- Department of Pathology and Anatomical Sciences, University
at Buffalo, State University of New York, Buffalo, NY 14214
| | - Spencer R. Rosario
- Department of Bioinformatics and Biostatistics, Roswell
Park Comprehensive Cancer Center, Buffalo, NY 14263
| | - Joseph A. Spernyak
- Department of Cell Stress Biology, Roswell Park
Comprehensive Cancer Center, Buffalo, NY 14263
| | - Wen Wee Ma
- Department of Hematology and Oncology, Taussig Cancer
Institute, Cleveland Clinic, Cleveland, OH, 44106
| | - Michal K. Stachowiak
- Department of Pathology and Anatomical Sciences, University
at Buffalo, State University of New York, Buffalo, NY 14214
| | - Michelle K. Greene
- The Patrick G Johnston Centre for Cancer Research, School
of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast,
Belfast BT9 7AE, UK
| | - Gerard P. Quinn
- The Patrick G Johnston Centre for Cancer Research, School
of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast,
Belfast BT9 7AE, UK
| | - Simon S. McDade
- The Patrick G Johnston Centre for Cancer Research, School
of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast,
Belfast BT9 7AE, UK
| | - Martin Clynes
- The National Institute for Cellular Biotechnology, Dublin
City University, Glasnevin 9, Dublin, Ireland
| | - Christopher J. Scott
- The Patrick G Johnston Centre for Cancer Research, School
of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast,
Belfast BT9 7AE, UK
| | - Robert M. Straubinger
- Department of Pharmaceutical Sciences, University at
Buffalo, State University of New York, Buffalo, NY 14214
- Department of Cell Stress Biology, Roswell Park
Comprehensive Cancer Center, Buffalo, NY 14263
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Jethwa KR, Kim E, Berlin J, Anker CJ, Tchelebi L, Abood G, Hallemeier CL, Jabbour S, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Williams V, Russo S. Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma: Systematic Review and Guidelines. Am J Clin Oncol 2024; 47:185-199. [PMID: 38131628 DOI: 10.1097/coc.0000000000001076] [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: 12/23/2023]
Abstract
For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and "Preferred Reporting Items for Systematic Reviews and Meta-analyses" 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.
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Affiliation(s)
- Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Jordan Berlin
- Department of Medicine, Division of Hematology-Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Christopher J Anker
- Department of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | | | | | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington DC
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, NY
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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Caputo D, Quagliarini E, Coppola A, La Vaccara V, Marmiroli B, Sartori B, Caracciolo G, Pozzi D. Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection. Int J Surg 2023; 109:2934-2940. [PMID: 37352522 PMCID: PMC10583897 DOI: 10.1097/js9.0000000000000558] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 06/02/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to the lack of effective early-stage detection strategies. Even though the link between inflammation and PDAC has been demonstrated and inflammatory biomarkers proved their efficacy in predicting several tumours, to date they have a role only in assessing PDAC prognosis. Recently, the studies of interactions between nanosystems and easily collectable biological fluids, alone or coupled with standard laboratory tests, have proven useful in facilitating PDAC diagnosis. Notably, tests based on magnetic levitation (MagLev) of biocoronated nanosystems have demonstrated high diagnostic accuracy in compliance with the criteria stated by WHO. Herein, the author developed a synergistic analysis that combines a user-friendly MagLev-based approach and common inflammatory biomarkers for discriminating PDAC subjects from healthy ones. MATERIALS AND METHODS Plasma samples from 24 PDAC subjects and 22 non-oncological patients have been collected and let to interact with graphene oxide nanosheets.Biomolecular corona formed around graphene oxide nanosheets have been immersed in a Maglev platform to study the levitation profiles.Inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), and platelet to lymphocyte ratio have been calculated and combined with results obtained by the MagLev platform. RESULTS MagLev profiles resulted significantly different between non-oncological patients and PDAC and allowed to identify a MagLev fingerprint for PDAC. Four inflammatory markers were significantly higher in PDAC subjects: neutrophils ( P =0.04), NLR ( P =4.7 ×10 -6 ), dNLR ( P =2.7 ×10 -5 ), and platelet to lymphocyte ratio ( P =0.002). Lymphocytes were appreciably lower in PDACs ( P =2.6 ×10 -6 ).Combining the MagLev fingerprint with dNLR and NLR returned global discrimination accuracy for PDAC of 95.7% and 91.3%, respectively. CONCLUSIONS The multiplexed approach discriminated PDAC patients from healthy volunteers in up to 95% of cases. If further confirmed in larger-cohort studies, this approach may be used for PDAC detection.
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Affiliation(s)
- Damiano Caputo
- Research Unit of Generale Surgery, Department of Medicine and Surgery, University Campus Bio-Medico di Roma
- Operative Research Unit of General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo
| | | | - Alessandro Coppola
- Department of Surgery, Sapienza University of Rome, Viale Regina Elena, Rome, Italy
| | - Vincenzo La Vaccara
- Operative Research Unit of General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo
| | - Benedetta Marmiroli
- Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse, Graz, Austria
| | - Barbara Sartori
- Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse, Graz, Austria
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Elkhamisy SA, Valentini C, Lattermann A, Radhakrishna G, Künzel LA, Löck S, Troost EGC. Normo- or Hypo-Fractionated Photon or Proton Radiotherapy in the Management of Locally Advanced Unresectable Pancreatic Cancer: A Systematic Review. Cancers (Basel) 2023; 15:3771. [PMID: 37568587 PMCID: PMC10416887 DOI: 10.3390/cancers15153771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/13/2023] Open
Abstract
LAPC is associated with a poor prognosis and requires a multimodal treatment approach. However, the role of radiation therapy in LAPC treatment remains controversial. This systematic review aimed to explore the role of proton and photon therapy, with varying radiation techniques and fractionation, in treatment outcomes and their respective toxicity profiles. METHODS Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed. RESULTS A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3-22.9 months and 8.5-20 months, respectively. For the PBT group, the range of median OS was 18.4-22.3 months. CONCLUSION CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety.
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Affiliation(s)
- Sally A. Elkhamisy
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Chiara Valentini
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Annika Lattermann
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | | | - Luise A. Künzel
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association/Helmholtz-Zentrum Dresden—Rossendorf (HZDR), 01307 Dresden, Germany
| | - Steffen Löck
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association/Helmholtz-Zentrum Dresden—Rossendorf (HZDR), 01307 Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Esther G. C. Troost
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany; (S.A.E.); (A.L.)
- The Christie Hospital NHS Foundation Trust, Manchester M20 4BX, UK;
- National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association/Helmholtz-Zentrum Dresden—Rossendorf (HZDR), 01307 Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, 01328 Dresden, Germany
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Fiore M, Coppola A, Petrianni GM, Trecca P, D’Ercole G, Cimini P, Ippolito E, Caputo D, Beomonte Zobel B, Coppola R, Ramella S. Advances in pre-treatment evaluation of pancreatic ductal adenocarcinoma: a narrative review. J Gastrointest Oncol 2023; 14:1114-1130. [PMID: 37201095 PMCID: PMC10186502 DOI: 10.21037/jgo-22-1034] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/08/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer. METHODS We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed. KEY CONTENT AND FINDINGS Each imaging modality (endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, positron emission tomography/computed tomography, staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed. CONCLUSIONS A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease.
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Affiliation(s)
- Michele Fiore
- Research Unit of Radiation Oncology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | | | - Gian Marco Petrianni
- Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Pasquale Trecca
- Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Gabriele D’Ercole
- Research Unit of Radiation Oncology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Paola Cimini
- Operative Research Unit of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Edy Ippolito
- Research Unit of Radiation Oncology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Damiano Caputo
- Department of Surgery and Research Unit of General Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of General Surgery Unit Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Bruno Beomonte Zobel
- Operative Research Unit of Radiology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Roberto Coppola
- Department of Surgery and Research Unit of General Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of General Surgery Unit Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Sara Ramella
- Research Unit of Radiation Oncology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
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8
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Caputo D. Hot topics in pancreatic cancer management. World J Gastrointest Surg 2023; 15:121-126. [PMID: 36896312 PMCID: PMC9988649 DOI: 10.4240/wjgs.v15.i2.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 10/27/2022] [Accepted: 01/17/2023] [Indexed: 02/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a sneaky and lethal disease burdened by poor prognosis. PDAC is often detected too late to be successfully cured, and it has been estimated that it will be a leading cause of cancer-related deaths in the near future. During the last decade, multimodal treatments involving surgery, chemotherapy and radiotherapy have contributed to improving the prognosis of this disease; however, long-term results are still not satisfactory. Postoperative morbidity and mortality rates remain high, and systemic treatments are burdened by toxicity in both neoadjuvant and adjuvant settings. Advancements in technologies, targeted therapies, immunotherapy and PDAC microenvironment modulation strategies may represent useful potential weapons in the future. Nevertheless, in the fight against this dreadful disease, there is an urgent need for new, cheap and user-friendly tools for early detection. In this field, promising results have been found in nanotechnologies and “omics” analyses that search for new biomarkers to be used in primary and secondary prevention. However, there are many issues that need to be solved before considering these tools in daily clinical practice. This editorial reported the state of the art of pancreatic cancer management.
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Affiliation(s)
- Damiano Caputo
- Department of General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome 00128, Italy
- General Surgery Research Unit, University Campus Bio-Medico di Roma, Rome 00128, Italy
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9
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Wang C, Chen H, Deng X, Xu W, Shen B. Real-world implications of nonbiological factors with staging, clinical management, and prognostic prediction in pancreatic ductal adenocarcinoma. Cancer Med 2023; 12:651-662. [PMID: 35661437 PMCID: PMC9844656 DOI: 10.1002/cam4.4910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 04/06/2022] [Accepted: 05/25/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system focuses on traditional biological factors (BFs). The present study incorporates nonbiological factors (NBFs) into the AJCC-TNM staging system in terms of the advanced clinical management and prognostic-prediction accuracy of pancreatic ductal adenocarcinoma (PDAC). METHODS Eight thousand three hundred and thirty eligible patients with PDAC were obtained from Surveillance, Epidemiology, and End Results database between January 1, 2011, and December 31, 2015. Multivariate Cox proportional hazards regression analysis and Kaplan-Meier curves were used to testify the feasibility of cancer-specific survival (CSS) prediction based on TNM-NBF stages. RESULTS The large population-based study demonstrated that NBFs (insurance status, marital status, county-level median household income, and unemployment) were significant prognostic indicators (p < 0.005), and multivariate Cox regression analysis demonstrated that the NBF1 stage carried a 29.4% increased risk of cancer-specific mortality than NBF0 stage (p < 0.001). The concordance index of TNM-NBF stage was 0.755 (95% confidence interval: 0.740-0.769). CONCLUSIONS The novel NBF stage was independently associated with CSS of PDAC. In addition, combining TNM with the NBF stage could provide better clinical management and prognostic-prediction accuracy.
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Affiliation(s)
- Chao Wang
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Haoda Chen
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Xiaxing Deng
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Wei Xu
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
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10
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Caputo D, Girgis M. Editorial: Improving surgical outcomes after pancreatic resection. Front Oncol 2022; 12:1024928. [PMID: 36505812 PMCID: PMC9732718 DOI: 10.3389/fonc.2022.1024928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 09/28/2022] [Indexed: 11/27/2022] Open
Affiliation(s)
- Damiano Caputo
- Department of Surgery and Research Unit of General Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Operative Research Unit of General Surgery Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Mark Girgis
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
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11
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Tomasello G, Ghidini M, Ghidini A, Trevisan F, Celotti A, Russo A, Gambini D, Indini A, Rijavec E, Bareggi C, Galassi B, Petrelli F. Total neoadjuvant therapy for initially inoperable pancreatic cancer: A systematic review of phase 2-3 studies. Radiother Oncol 2021; 164:13-19. [PMID: 34509562 DOI: 10.1016/j.radonc.2021.09.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Patients with initially inoperable non-metastatic pancreatic cancer (PC) have a poor prognosis, often similar to those with metastatic disease. Neoadjuvant chemotherapy (CT) plus concomitant or sequential radiotherapy (RT) may cause tumor shrinkage and allow for radical surgery. We pooled data of studies in which patients with locally advanced (unresectable) or borderline resectable PC were treated with a course of induction (or consolidation) CT followed or preceded by neoadjuvant CTRT regimen. MATERIALS AND METHODS We searched articles, including phase 2 or 3 studies, published in English from 2010 up to December 2020 in PubMed, SCOPUS, the Cochrane Library, and EMBASE. The primary outcomes were the pooled radical and R0 resection rates, median PFS and OS of included patients (those included in the intent to treat analysis). RESULTS A total of 28 studies were finally considered eligible for inclusion in quantitative analysis for a total of 2446 patients with locally advanced/borderline resectable PC. Overall the pooled rate of resection was 29.7% (95%CI 26.7-32.8%). In patients who completed the CT + CTRT program, the overall resection rate was 31.8% (95% 28.4-35.4%). After exclusion of studies that included resectable PCs, the overall resection rate was 19.9% (95%CI 17.3-22.7%). In studies were all patients had unresectable PC (n = 20 studies), the resection rate was 12.1% (95%CI 10-14.5%). In two studies that enrolled all borderline resectable PCs the resection rate was 59.2% (95%CI 48.9-68.8%). The pooled R0 resection rate was 68.7% (95%CI 64.7-72.3%). The median pooled OS was 15.7 months (95%CI 14-17.2 months) and the median pooled PFS was 10.7 (95%CI 9.3-12.1 months). CONCLUSIONS Surgery is a treatment option in about one third of patients with initially inoperable PC, following total neoadjuvant therapy. In unresectable cases the resection rate was 12%. Median OS and PFS rates were comparable with historical data of advanced PCs. Optimal integration and sequence of chemo- and radiotherapy in unresectable PC must still be defined.
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Affiliation(s)
- Gianluca Tomasello
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Ghidini
- Medical Oncology Unit, Casa di Cura Igea, Milan, Italy; GISCAD (Gruppo Italiano Studio Carcinomi Apparato Digerente)
| | | | - Andrea Celotti
- General Surgery 2, ASST Bergamo Ovest, Ospedale di Treviglio, Italy
| | - Alessandro Russo
- General Surgery 2, ASST Bergamo Ovest, Ospedale di Treviglio, Italy
| | - Donatella Gambini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alice Indini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Erika Rijavec
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudia Bareggi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Barbara Galassi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Fausto Petrelli
- Oncology Unit, ASST Bergamo Ovest, Ospedale di Treviglio, Italy; GISCAD (Gruppo Italiano Studio Carcinomi Apparato Digerente)
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12
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O'Kane GM, Ladak F, Gallinger S. Avancées dans la prise en charge de l’adénocarcinome canalaire pancréatique. CMAJ 2021; 193:E1362-E1370. [PMID: 34462299 PMCID: PMC8432315 DOI: 10.1503/cmaj.201450-f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Affiliation(s)
- Grainne M O'Kane
- Centre d'oncologie Princess Margaret (O'Kane, Gallinger), Réseau universitaire de santé de Toronto, Toronto, Ont.; Université de l'Alberta (Ladak), Edmonton, Alb. Grainne.O'
| | - Farah Ladak
- Centre d'oncologie Princess Margaret (O'Kane, Gallinger), Réseau universitaire de santé de Toronto, Toronto, Ont.; Université de l'Alberta (Ladak), Edmonton, Alb
| | - Steven Gallinger
- Centre d'oncologie Princess Margaret (O'Kane, Gallinger), Réseau universitaire de santé de Toronto, Toronto, Ont.; Université de l'Alberta (Ladak), Edmonton, Alb
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13
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Affiliation(s)
- Grainne M O'Kane
- Princess Margaret Cancer Centre (O'Kane, Gallinger), University Health Network, Toronto, Toronto, Ont.; University of Alberta (Ladak), Edmonton, Alta. Grainne.O'
| | - Farah Ladak
- Princess Margaret Cancer Centre (O'Kane, Gallinger), University Health Network, Toronto, Toronto, Ont.; University of Alberta (Ladak), Edmonton, Alta
| | - Steven Gallinger
- Princess Margaret Cancer Centre (O'Kane, Gallinger), University Health Network, Toronto, Toronto, Ont.; University of Alberta (Ladak), Edmonton, Alta
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14
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Coppola A, La Vaccara V, Fiore M, Farolfi T, Ramella S, Angeletti S, Coppola R, Caputo D. CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis. Front Oncol 2021; 11:690580. [PMID: 34123859 PMCID: PMC8190389 DOI: 10.3389/fonc.2021.690580] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC. METHODS Preoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction. RESULTS Increased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p <0.001). This ability, confirmed in all the series by ROC curve analysis (Ca 19.9 ≥32 U/ml), was lost in the presence of hypoalbuminemia. Furthermore, Ca 19.9 at the cut off >418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059). CONCLUSIONS In R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.
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Affiliation(s)
| | | | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Tommaso Farolfi
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
| | - Sara Ramella
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, Campus Bio-Medico University, Rome, Italy
| | - Roberto Coppola
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
| | - Damiano Caputo
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
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15
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Fiore M, Taralli S, Trecca P, Scolozzi V, Marinelli L, Triumbari EKA, Caputo D, Angeletti S, Ciccozzi M, Coppola A, Greco C, Ippolito E, Calcagni ML, Coppola R, Ramella S. A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer. Cancers (Basel) 2020; 12:2016. [PMID: 32717967 PMCID: PMC7464714 DOI: 10.3390/cancers12082016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66-19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64-57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9-10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.
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Affiliation(s)
- Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Silvia Taralli
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
| | - Pasquale Trecca
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Valentina Scolozzi
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
| | - Luca Marinelli
- Radiation Oncology, S. Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy;
| | - Elizabeth K. A. Triumbari
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
- Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Damiano Caputo
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Massimo Ciccozzi
- Unit of Medical Statistic and Molecular Epidemiology, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Alessandro Coppola
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Carlo Greco
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Edy Ippolito
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Maria Lucia Calcagni
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
- Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Roberto Coppola
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Sara Ramella
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
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16
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Oba A, Ho F, Bao QR, Al-Musawi MH, Schulick RD, Del Chiaro M. Neoadjuvant Treatment in Pancreatic Cancer. Front Oncol 2020; 10:245. [PMID: 32185128 PMCID: PMC7058791 DOI: 10.3389/fonc.2020.00245] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 02/13/2020] [Indexed: 12/13/2022] Open
Abstract
Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.
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Affiliation(s)
- Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States.,Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Felix Ho
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States
| | - Quoc Riccardo Bao
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States.,Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy
| | - Mohammed H Al-Musawi
- Clinical Trials Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, CO, United States
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17
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Lee JE, Lee HS, Chung MJ, Park JY, Park SW, Song SY, Bang S. Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer. Gut Liver 2020; 14:135-143. [PMID: 30974927 PMCID: PMC6974334 DOI: 10.5009/gnl18419] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 02/03/2019] [Accepted: 02/07/2019] [Indexed: 12/17/2022] Open
Abstract
Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19- 9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabinebased FL.
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Affiliation(s)
- Jeung Eun Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Hee Seung Lee
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Moon Jae Chung
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Jeong Youp Park
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Seung Woo Park
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Si Young Song
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Seungmin Bang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
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18
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Fiorentino A, Laudicella R, Ciurlia E, Annunziata S, Lancellotta V, Mapelli P, Tuscano C, Caobelli F, Evangelista L, Marino L, Quartuccio N, Fiore M, Borghetti P, Chiaravalloti A, Ricci M, Desideri I, Alongi P. Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 2. Crit Rev Oncol Hematol 2019; 139:117-124. [PMID: 30940428 DOI: 10.1016/j.critrevonc.2019.03.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/14/2019] [Accepted: 03/14/2019] [Indexed: 02/07/2023] Open
Abstract
AIM Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer. METHODS A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume. RESULTS FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer. CONCLUSION Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.
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Affiliation(s)
- Alba Fiorentino
- Radiotherapy Oncology Department, General Regional Hospital "F. Miulli", Acquaviva delle Fonti-Bari, Italy.
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morphofunctional Imaging, University of Messina, Italy
| | - Elisa Ciurlia
- Radiotherapy Oncology Department, Vito Fazzi Hospital, Lecce, Italy
| | - Salvatore Annunziata
- Fondazione Policlinico A. Gemelli IRCCS-Università Cattolica Sacro Cuore, Roma, Italy
| | - Valentina Lancellotta
- Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Roma, Italy
| | - Paola Mapelli
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carmelo Tuscano
- Radiotherapy Oncology Department, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Federico Caobelli
- Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Laura Evangelista
- Nuclear Medicine Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Lorenza Marino
- Radiotherapy Oncology Department, REM, Viagrande, Catania, Italy
| | | | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Paolo Borghetti
- Radiation Oncology Department University and Spedali Civili, Brescia, Italy
| | - Agostino Chiaravalloti
- IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy
| | - Maria Ricci
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Isacco Desideri
- Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Section of Radiation Oncology, University of Florence, Italy
| | - Pierpaolo Alongi
- Department of Radiological Sciences, Nuclear Medicine Service, Fondazione Istituto G. Giglio, Cefalu, Italy
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Seufferlein T, Hammel P, Delpero JR, Macarulla T, Pfeiffer P, Prager GW, Reni M, Falconi M, Philip PA, Van Cutsem E. Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence. Cancer Treat Rev 2019; 77:1-10. [PMID: 31163334 DOI: 10.1016/j.ctrv.2019.05.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 05/26/2019] [Indexed: 02/08/2023]
Abstract
Surgical resection of pancreatic cancer offers a chance of cure, but currently only 15-20% of patients are diagnosed with resectable disease, while 30-40% are diagnosed with non-metastatic, unresectable locally advanced pancreatic cancer (LAPC). Treatment for LAPC usually involves systemic chemotherapy, with the aim of controlling disease progression, reducing symptoms and maintaining quality of life. In a small proportion of patients with LAPC, primary chemotherapy may successfully convert unresectable tumours to resectable tumours. In this setting, primary chemotherapy is termed 'induction therapy' rather than 'neoadjuvant'. There is currently a lack of data from randomized studies to thoroughly evaluate the benefits of induction chemotherapy in LAPC, but Phase II and retrospective data have shown improved survival and high R0 resection rates. New chemotherapy regimens such as nab-paclitaxel + gemcitabine and FOLFIRINOX have demonstrated improvement in overall survival for metastatic disease and shown promise as neoadjuvant treatment in patients with resectable and borderline resectable disease. Prospective trials are underway to evaluate these regimens further as induction therapy in LAPC and preliminary data indicate a beneficial effect of FOLFIRINOX in this setting. Further research into optimal induction schedules is needed, as well as guidance on the patients who are most suitable for induction therapy. In this expert opinion article, a panel of surgeons, medical oncologists and gastrointestinal oncologists review the available evidence on management strategies for LAPC and provide their recommendations for patient care, with a particular focus on the use of induction chemotherapy.
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Affiliation(s)
| | - Pascal Hammel
- Hôpital Beaujon (AP-HP), Clichy, and Université Paris VII-Denis Diderot, France.
| | | | | | | | - Gerald W Prager
- Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University Vienna, Austria.
| | - Michele Reni
- Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
| | - Massimo Falconi
- Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy.
| | - Philip A Philip
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
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Bradley A, Van Der Meer R. Neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic cancer: A Markov decision analysis. PLoS One 2019; 14:e0212805. [PMID: 30817807 PMCID: PMC6394923 DOI: 10.1371/journal.pone.0212805] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/09/2019] [Indexed: 12/16/2022] Open
Abstract
Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and two-way deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway. Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient’s likelihood of receiving multimodal treatment in either pathway.
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Affiliation(s)
- Alison Bradley
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Cancer Unit, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
- * E-mail:
| | - Robert Van Der Meer
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
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21
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How to treat borderline resectable pancreatic cancer: current challenges and future directions. Jpn J Clin Oncol 2018; 48:205-213. [DOI: 10.1093/jjco/hyx191] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 12/18/2017] [Indexed: 01/08/2023] Open
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Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients. PLoS One 2017; 12:e0186341. [PMID: 29023527 PMCID: PMC5638513 DOI: 10.1371/journal.pone.0186341] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 10/01/2017] [Indexed: 01/10/2023] Open
Abstract
PURPOSE The role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy. METHODS We retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60-66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23). RESULTS 10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ≥ 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ΔCA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049). CONCLUSION Dose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.
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