64c125a4a093f195920006801421382a  324039.pdf
f9568642b973375adc98d9dbdf04c068c93135d7  324039.pdf
0209610cb4d8a95eb585702829815df35aa485c4a869e690a736788f7f378c20  324039.pdf

Title:           Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study
Subject:         DOI: 10.1093/oncolo/oyae300
The Oncologist, Volume. 30, Issue. 8, 16 November 2024
Abstract 
Introduction:  The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience.
Methods:  We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties.
Results:  The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables.
Conclusions:  The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.
Author:          Pilar García-Alfonso
Creator:         Adobe InDesign 15.1 (Windows)
Producer:        Adobe PDF Library 15.0; modified using iTextSharp.LGPLv2.Core 3.7.4.0
CreationDate:    Thu Aug 28 14:51:41 2025 CEST
ModDate:         Wed Jan 14 09:34:21 2026 CET
Custom Metadata: no
Metadata Stream: yes
Tagged:          yes
UserProperties:  no
Suspects:        no
Form:            none
JavaScript:      no
Pages:           10
Encrypted:       no
Page size:       595.276 x 782.362 pts
Page rot:        0
File size:       1918298 bytes
Optimized:       no
PDF version:     1.4


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
FCXJKT+UniversLTStd-CnObl            Type 1C           WinAnsi          yes yes yes     86  0
FKVJKT+UniversLTStd-Cn               Type 1C           WinAnsi          yes yes yes     87  0
OLDBGB+UniversLTStd-BoldCn           Type 1C           WinAnsi          yes yes yes     88  0
CWCCUZ+UniversLTStd-Bold             Type 1C           Custom           yes yes yes     89  0
YLAZQH+MyriadPro-Bold                Type 1C           WinAnsi          yes yes yes     90  0
ORVRGB+MyriadPro-Regular             Type 1C           WinAnsi          yes yes yes     91  0
HJJBMP+UniversLTStd-Light            Type 1C           Custom           yes yes yes     92  0
YRSPQH+SabonLTStd-Roman              Type 1C           Custom           yes yes yes     93  0
HKXUVV+ArialMT                       TrueType          WinAnsi          yes yes no       1  0
AAKMSD+UniversLTStd-Obl              Type 1C           WinAnsi          yes yes yes    130  0
JYYOOL+UniversLTStd                  Type 1C           WinAnsi          yes yes yes    131  0
HDXCMP+SabonLTStd-Italic             Type 1C           WinAnsi          yes yes yes    155  0
EZDAWV+SabonLTStd-Bold               Type 1C           WinAnsi          yes yes yes    156  0
ZFMREF+SabonLTStd-BoldItalic         Type 1C           WinAnsi          yes yes yes    157  0
ORCDGB+UniversLTStd-LightObl         Type 1C           WinAnsi          yes yes yes    203  0
ZSPMEF+GandhariUnicode-Roman         Type 1C           Custom           yes yes yes    326  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2026-01-15 04:12:09 CET
 RepresentationInformation: 324039.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2026-01-14 09:46:09 CET
  Size: 1918298
  Format: PDF
  Version: 1.4
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  Profile: Tagged PDF
  PDFMetadata: 
   Objects: 1914
   FreeObjects: 1
   IncrementalUpdates: 0
   DocumentCatalog: 
    ViewerPreferences: 
     HideToolbar: false
     HideMenubar: false
     HideWindowUI: false
     FitWindow: false
     CenterWindow: false
     DisplayDocTitle: true
     NonFullScreenPageMode: UseNone
     Direction: L2R
     ViewArea: CropBox
     ViewClip: CropBox
     PrintArea: CropBox
     PageClip: CropBox
    PageLayout: OneColumn
    PageMode: UseOutlines
    Language: en-US
    Outlines: 
     Item: 
      Title: Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study
      Children: 
       Item: 
        Title: Introduction
       Item: 
        Title: Method
       Item: 
        Title: Results
        Children: 
         Item: 
          Title: Patient care during the pandemic
         Item: 
          Title: Organizational changes and status of centers
         Item: 
          Title: Survival-based outcomes and frailties
       Item: 
        Title: Discussion
       Item: 
        Title: Acknowledgments
       Item: 
        Title: References
   Info: 
    Title: Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study
    Author: Pilar García-Alfonso
    Subject: DOI: 10.1093/oncolo/oyae300
The Oncologist, Volume. 30, Issue. 8, 16 November 2024
Abstract 
Introduction:  The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience.
Methods:  We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties.
Results:  The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables.
Conclusions:  The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.
    Creator: Adobe InDesign 15.1 (Windows)
    Producer: Adobe PDF Library 15.0; modified using iTextSharp.LGPLv2.Core 3.7.4.0
    CreationDate: Thu Aug 28 15:21:41 CEST 2025
    ModDate: Wed Jan 14 09:34:21 CET 2026
    Trapped: False
   ID: 0xbd5cee61f878c9dce962478b10f5eb16, 0x11981e6ab21e4f4c7cbcabe2838e6336
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 120
      ImageHeight: 43
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 12
      ImageHeight: 9
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 88
      ImageHeight: 55
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 45
      ImageHeight: 36
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 118
      ImageHeight: 54
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 38
      ImageHeight: 94
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 27
      ImageHeight: 42
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 18
      ImageHeight: 11
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 54
      ImageHeight: 172
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 44
      ImageHeight: 87
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 63
      ImageHeight: 99
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 44
      ImageHeight: 57
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 4
      ImageHeight: 4
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 160
      ImageHeight: 91
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 55
      ImageHeight: 92
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 6
      ImageHeight: 8
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 17
      ImageHeight: 6
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 30
      ImageHeight: 13
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 46
      ImageHeight: 52
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 11
      ImageHeight: 11
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 1
      ImageHeight: 300
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1
      ImageHeight: 300
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 15
      ImageHeight: 26
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 7
      ImageHeight: 3
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 33
      ImageHeight: 29
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 2
      ImageHeight: 3
      ColorSpace: CMYK
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 30
      ImageHeight: 34
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 10
      ImageHeight: 36
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 78
      ImageHeight: 68
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 38
      ImageHeight: 61
      ColorSpace: palette color
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
     Intent: RelativeColorimetric
     Decode: 0, 255
     Name: X
   Fonts: 
    Type1: 
     Font: 
      BaseFont: AAKMSD+UniversLTStd-Obl
      FontSubset: true
      FirstChar: 32
      LastChar: 116
      FontDescriptor: 
       FontName: AAKMSD+UniversLTStd-Obl
       Flags: Nonsymbolic, Italic
       FontBBox: -174, -272, 1145, 947
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: JYYOOL+UniversLTStd
      FontSubset: true
      FirstChar: 32
      LastChar: 122
      FontDescriptor: 
       FontName: JYYOOL+UniversLTStd
       Flags: Nonsymbolic
       FontBBox: -168, -250, 992, 947
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: ZSPMEF+GandhariUnicode-Roman
      FontSubset: true
      FirstChar: 31
      LastChar: 31
      FontDescriptor: 
       FontName: ZSPMEF+GandhariUnicode-Roman
       Flags: Serif, Nonsymbolic
       FontBBox: -752, -250, 1779, 944
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ORCDGB+UniversLTStd-LightObl
      FontSubset: true
      FirstChar: 78
      LastChar: 116
      FontDescriptor: 
       FontName: ORCDGB+UniversLTStd-LightObl
       Flags: Nonsymbolic, Italic
       FontBBox: -151, -274, 1144, 957
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: FCXJKT+UniversLTStd-CnObl
      FontSubset: true
      FirstChar: 32
      LastChar: 116
      FontDescriptor: 
       FontName: FCXJKT+UniversLTStd-CnObl
       Flags: Nonsymbolic, Italic
       FontBBox: -172, -270, 1064, 989
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: FKVJKT+UniversLTStd-Cn
      FontSubset: true
      FirstChar: 32
      LastChar: 250
      FontDescriptor: 
       FontName: FKVJKT+UniversLTStd-Cn
       Flags: Nonsymbolic
       FontBBox: -166, -250, 1000, 989
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: OLDBGB+UniversLTStd-BoldCn
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: OLDBGB+UniversLTStd-BoldCn
       Flags: Nonsymbolic
       FontBBox: -83, -250, 1000, 969
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: CWCCUZ+UniversLTStd-Bold
      FontSubset: true
      FirstChar: 31
      LastChar: 243
      FontDescriptor: 
       FontName: CWCCUZ+UniversLTStd-Bold
       Flags: Nonsymbolic
       FontBBox: -167, -250, 995, 938
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: YLAZQH+MyriadPro-Bold
      FontSubset: true
      FirstChar: 42
      LastChar: 42
      FontDescriptor: 
       FontName: YLAZQH+MyriadPro-Bold
       Flags: Nonsymbolic
       FontBBox: -163, -250, 1256, 989
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: ORVRGB+MyriadPro-Regular
      FontSubset: true
      FirstChar: 42
      LastChar: 42
      FontDescriptor: 
       FontName: ORVRGB+MyriadPro-Regular
       Flags: Nonsymbolic
       FontBBox: -157, -250, 1126, 952
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: HDXCMP+SabonLTStd-Italic
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: HDXCMP+SabonLTStd-Italic
       Flags: Serif, Nonsymbolic, Italic
       FontBBox: -146, -228, 1059, 927
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: HJJBMP+UniversLTStd-Light
      FontSubset: true
      FirstChar: 31
      LastChar: 243
      FontDescriptor: 
       FontName: HJJBMP+UniversLTStd-Light
       Flags: Nonsymbolic
       FontBBox: -151, -250, 1000, 957
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: EZDAWV+SabonLTStd-Bold
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: EZDAWV+SabonLTStd-Bold
       Flags: Serif, Nonsymbolic
       FontBBox: -163, -228, 1000, 968
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
     Font: 
      BaseFont: YRSPQH+SabonLTStd-Roman
      FontSubset: true
      FirstChar: 29
      LastChar: 248
      FontDescriptor: 
       FontName: YRSPQH+SabonLTStd-Roman
       Flags: Serif, Nonsymbolic
       FontBBox: -165, -228, 1000, 944
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ZFMREF+SabonLTStd-BoldItalic
      FontSubset: true
      FirstChar: 78
      LastChar: 78
      FontDescriptor: 
       FontName: ZFMREF+SabonLTStd-BoldItalic
       Flags: Serif, Nonsymbolic, Italic
       FontBBox: -147, -238, 1080, 955
       FontFile3: true
      Encoding: WinAnsiEncoding
      ToUnicode: true
    TrueType: 
     Font: 
      BaseFont: HKXUVV+ArialMT
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: HKXUVV+ArialMT
       Flags: Nonsymbolic
       FontBBox: -664, -324, 2000, 1039
       FontFile2: true
      Encoding: WinAnsiEncoding
   XMP: <x:xmpmeta xmlns:x="adobe:ns:meta/" x:xmptk="Adobe XMP Core 6.0-c002 79.164460, 2020/05/12-16:04:17        ">
   <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xmp="http://ns.adobe.com/xap/1.0/" xmlns:xmpMM="http://ns.adobe.com/xap/1.0/mm/" xmlns:stEvt="http://ns.adobe.com/xap/1.0/sType/ResourceEvent#" xmlns:stRef="http://ns.adobe.com/xap/1.0/sType/ResourceRef#" xmlns:xmpRights="http://ns.adobe.com/xap/1.0/rights/" xmlns:pdf="http://ns.adobe.com/pdf/1.3/">
         <dc:format>application/pdf</dc:format>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">DOI: 10.1093/oncolo/oyae300
The Oncologist, Volume. 30, Issue. 8, 16 November 2024
Abstract 
Introduction:  The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience.
Methods:  We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties.
Results:  The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables.
Conclusions:  The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">© The Author(s) 2024. Published by Oxford University Press.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Pilar García-Alfonso</rdf:li>
               <rdf:li> Paula Jimenez-Fonseca</rdf:li>
               <rdf:li> Javier Soto-Alsar</rdf:li>
               <rdf:li> Iosune Baraibar</rdf:li>
               <rdf:li> Cristina Santos</rdf:li>
               <rdf:li> Adelaida La Casta</rdf:li>
               <rdf:li> Ismael Ghanem</rdf:li>
               <rdf:li> Gema Pulido Cortijo</rdf:li>
               <rdf:li> Axel Mariño Méndez</rdf:li>
               <rdf:li> Roberto Pazo-Cid</rdf:li>
               <rdf:li> Ruth Vera</rdf:li>
               <rdf:li> Marcos Melián</rdf:li>
               <rdf:li> Julia Alcaide</rdf:li>
               <rdf:li> Begoña Graña</rdf:li>
               <rdf:li> David Páez</rdf:li>
               <rdf:li> Inmaculada Gallego</rdf:li>
               <rdf:li> Miriam Lobo</rdf:li>
               <rdf:li> Miguel Borregón</rdf:li>
               <rdf:li> Ana Fernández Montes</rdf:li>
               <rdf:li> Eva Martínez de Castro</rdf:li>
               <rdf:li> Alberto Carmona-Bayonas</rdf:li>
               <rdf:li> Enrique Aranda</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>gastrointestinal cancer </rdf:li>
               <rdf:li>coronavirus disease 2019 </rdf:li>
               <rdf:li>Spain </rdf:li>
               <rdf:li>PANDORA-TTD20 </rdf:li>
               <rdf:li>RETUD registry </rdf:li>
               <rdf:li>spatial frailties.</rdf:li>
            </rdf:Bag>
         </dc:subject>
         <xmp:CreateDate>2025-08-28T18:21:41+05:30</xmp:CreateDate>
         <xmp:MetadataDate>2026-01-14T08:34:21+00:00</xmp:MetadataDate>
         <xmp:ModifyDate>2026-01-14T08:34:21+00:00</xmp:ModifyDate>
         <xmp:CreatorTool>Adobe InDesign 15.1 (Windows)</xmp:CreatorTool>
         <xmpMM:InstanceID>uuid:26e7c7ed-db35-4301-a413-6d25d59018bd</xmpMM:InstanceID>
         <xmpMM:OriginalDocumentID>xmp.did:62536b05-d23c-e441-8b83-3cf623a2daf6</xmpMM:OriginalDocumentID>
         <xmpMM:DocumentID>xmp.id:96c19d24-84b3-744c-bccf-a8e8ba2654ab</xmpMM:DocumentID>
         <xmpMM:RenditionClass>proof:pdf</xmpMM:RenditionClass>
         <xmpMM:History>
            <rdf:Seq>
               <rdf:li rdf:parseType="Resource">
                  <stEvt:action>converted</stEvt:action>
                  <stEvt:parameters>from application/x-indesign to application/pdf</stEvt:parameters>
                  <stEvt:softwareAgent>Adobe InDesign 15.1 (Windows)</stEvt:softwareAgent>
                  <stEvt:changed>/</stEvt:changed>
                  <stEvt:when>2025-08-28T18:21:41+05:30</stEvt:when>
               </rdf:li>
            </rdf:Seq>
         </xmpMM:History>
         <xmpMM:DerivedFrom rdf:parseType="Resource">
            <stRef:instanceID>xmp.iid:105a8537-44c0-3748-953d-a2820e34fa8c</stRef:instanceID>
            <stRef:documentID>xmp.did:7970bc4a-0a68-574e-a1e1-58fa615fd822</stRef:documentID>
            <stRef:originalDocumentID>xmp.did:62536b05-d23c-e441-8b83-3cf623a2daf6</stRef:originalDocumentID>
            <stRef:renditionClass>default</stRef:renditionClass>
         </xmpMM:DerivedFrom>
         <xmpRights:Marked>True</xmpRights:Marked>
         <pdf:Producer>Adobe PDF Library 15.0; modified using iTextSharp.LGPLv2.Core 3.7.4.0</pdf:Producer>
         <pdf:Trapped>False</pdf:Trapped>
      </rdf:Description>
   </rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Sequence: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 151, 599, 155, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 157, 599, 159, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 161, 599, 165, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 292, 599, 296, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 298, 599, 301, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 397, 599, 400, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 488, 599, 491, 586
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 127, 584, 131, 571
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 229, 584, 233, 571
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 320, 584, 324, 571
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 435, 584, 439, 571
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 155, 569, 159, 556
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 255, 569, 258, 556
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 314, 569, 321, 556
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 403, 569, 410, 556
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 481, 569, 489, 556
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 122, 554, 129, 541
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 191, 554, 198, 541
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 308, 554, 315, 541
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 387, 554, 394, 541
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 487, 554, 494, 541
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 168, 539, 175, 526
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 175, 541, 189, 527
      Annotation: 
       Subtype: Link
       Rect: 313, 539, 320, 526
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 462, 539, 469, 526
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 469, 541, 483, 527
      Annotation: 
       Subtype: Link
       Rect: 127, 524, 131, 511
       ActionDest: 33
      Annotation: 
       Subtype: Link
       Rect: 453, 180, 539, 170
      Annotation: 
       Subtype: Link
       Rect: 388, 57, 531, 48
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 220, 432, 223, 422
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 225, 432, 228, 422
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 229, 410, 232, 400
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 234, 410, 237, 400
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 113, 399, 116, 389
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 117, 399, 120, 389
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 194, 388, 197, 378
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 199, 388, 202, 378
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 174, 366, 180, 356
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 136, 355, 139, 345
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 76, 333, 82, 323
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 255, 322, 261, 312
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 263, 322, 269, 312
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 198, 289, 204, 279
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 206, 289, 212, 279
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 141, 278, 147, 268
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 141, 267, 147, 257
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 68, 245, 74, 235
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 178, 234, 184, 224
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 185, 234, 191, 224
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 193, 234, 199, 224
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 196, 179, 202, 169
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 208, 157, 214, 147
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 201, 146, 207, 136
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 230, 124, 236, 114
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 238, 124, 244, 114
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 192, 91, 198, 81
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 346, 201, 352, 191
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 502, 113, 505, 103
       ActionDest: 40
      Annotation: 
       Subtype: Link
       Rect: 366, 69, 372, 59
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 373, 69, 379, 59
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 529, 58, 535, 48
       ActionDest: 41
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 261, 708, 267, 697
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 118, 664, 124, 653
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 125, 664, 131, 653
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 133, 664, 139, 653
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 231, 609, 291, 598
      Annotation: 
       Subtype: Link
       Rect: 48, 598, 67, 587
      Annotation: 
       Subtype: Link
       Rect: 144, 598, 245, 587
      Annotation: 
       Subtype: Link
       Rect: 106, 510, 136, 499
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 48, 499, 146, 488
      Annotation: 
       Subtype: Link
       Rect: 201, 488, 291, 477
      Annotation: 
       Subtype: Link
       Rect: 48, 477, 57, 466
      Annotation: 
       Subtype: Link
       Rect: 88, 477, 93, 466
      Annotation: 
       Subtype: Link
       Rect: 362, 697, 392, 686
       ActionDest: 36
      Annotation: 
       Subtype: Link
       Rect: 333, 565, 363, 554
       ActionDest: 36
      Annotation: 
       Subtype: Link
       Rect: 309, 477, 405, 466
      Annotation: 
       Subtype: Link
       Rect: 309, 389, 405, 378
      Annotation: 
       Subtype: Link
       Rect: 309, 334, 405, 323
      Annotation: 
       Subtype: Link
       Rect: 354, 202, 455, 191
      Annotation: 
       Subtype: Link
       Rect: 349, 169, 445, 158
      Annotation: 
       Subtype: Link
       Rect: 312, 136, 348, 125
       ActionDest: 37
      Annotation: 
       Subtype: Link
       Rect: 390, 81, 428, 70
       ActionDest: 37
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 324, 488, 357, 477
       ActionDest: 37
      Annotation: 
       Subtype: Link
       Rect: 399, 367, 435, 356
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 458, 367, 547, 356
      Annotation: 
       Subtype: Link
       Rect: 303, 356, 313, 345
      Annotation: 
       Subtype: Link
       Rect: 446, 301, 482, 290
       ActionDest: 39
      Annotation: 
       Subtype: Link
       Rect: 414, 268, 517, 257
      Annotation: 
       Subtype: Link
       Rect: 390, 246, 490, 235
      Annotation: 
       Subtype: Link
       Rect: 356, 180, 458, 169
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 143, 150, 149, 139
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 396, 84, 402, 73
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 403, 84, 409, 73
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 442, 51, 448, 40
       ActionDest: 41
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 61, 318, 67, 307
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 102, 285, 108, 274
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 272, 208, 278, 197
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 279, 208, 285, 197
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 251, 186, 257, 175
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 259, 186, 265, 175
       ActionDest: 41
      Annotation: 
       Subtype: Link
       Rect: 206, 164, 212, 153
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 214, 164, 220, 153
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 194, 153, 200, 142
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 279, 98, 285, 87
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 493, 230, 499, 219
       ActionDest: 42
      Annotation: 
       Subtype: Link
       Rect: 500, 230, 506, 219
       ActionDest: 42
    Page: 
     Sequence: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 90, 119, 124, 108
       ActionDest: 38
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 487, 301, 547, 290
      Annotation: 
       Subtype: Link
       Rect: 303, 290, 333, 279
      Annotation: 
       Subtype: Link
       Rect: 317, 195, 492, 186
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 386, 165, 542, 156
      Annotation: 
       Subtype: Link
       Rect: 317, 155, 420, 146
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 509, 135, 547, 126
      Annotation: 
       Subtype: Link
       Rect: 317, 125, 419, 116
      Annotation: 
       Subtype: Link
       Rect: 317, 115, 410, 106
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 317, 95, 547, 86
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 317, 85, 324, 76
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 386, 65, 537, 56
      Annotation: 
       Subtype: Link
       Rect: 317, 55, 501, 46
       ActionDest: 34
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 254, 709, 291, 700
      Annotation: 
       Subtype: Link
       Rect: 62, 699, 232, 690
      Annotation: 
       Subtype: Link
       Rect: 62, 689, 99, 680
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 193, 669, 291, 660
      Annotation: 
       Subtype: Link
       Rect: 62, 659, 105, 650
      Annotation: 
       Subtype: Link
       Rect: 62, 649, 252, 640
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 619, 289, 610
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 579, 235, 570
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 549, 200, 540
      Annotation: 
       Subtype: Link
       Rect: 62, 539, 205, 530
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 509, 289, 500
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 469, 204, 460
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 419, 251, 410
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 379, 257, 370
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 254, 349, 291, 340
      Annotation: 
       Subtype: Link
       Rect: 62, 339, 148, 330
      Annotation: 
       Subtype: Link
       Rect: 62, 329, 274, 320
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 132, 289, 275, 280
      Annotation: 
       Subtype: Link
       Rect: 62, 279, 179, 270
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 209, 259, 291, 250
      Annotation: 
       Subtype: Link
       Rect: 62, 249, 96, 240
      Annotation: 
       Subtype: Link
       Rect: 62, 239, 260, 230
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 204, 219, 291, 210
      Annotation: 
       Subtype: Link
       Rect: 62, 209, 137, 200
      Annotation: 
       Subtype: Link
       Rect: 62, 199, 205, 190
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 209, 179, 291, 170
      Annotation: 
       Subtype: Link
       Rect: 62, 169, 123, 160
      Annotation: 
       Subtype: Link
       Rect: 62, 159, 177, 150
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 204, 139, 291, 130
      Annotation: 
       Subtype: Link
       Rect: 62, 129, 137, 120
      Annotation: 
       Subtype: Link
       Rect: 62, 119, 236, 110
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 62, 99, 222, 90
      Annotation: 
       Subtype: Link
       Rect: 62, 89, 246, 80
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 209, 59, 291, 50
      Annotation: 
       Subtype: Link
       Rect: 62, 49, 135, 40
      Annotation: 
       Subtype: Link
       Rect: 323, 729, 485, 720
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 379, 699, 534, 690
      Annotation: 
       Subtype: Link
       Rect: 323, 689, 552, 680
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 323, 679, 340, 670
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 406, 649, 549, 640
      Annotation: 
       Subtype: Link
       Rect: 323, 639, 492, 630
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 345, 599, 461, 590
      Annotation: 
       Subtype: Link
       Rect: 323, 589, 473, 580
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 345, 559, 504, 550
      Annotation: 
       Subtype: Link
       Rect: 323, 549, 552, 540
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 323, 539, 347, 530
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 384, 519, 551, 510
      Annotation: 
       Subtype: Link
       Rect: 323, 509, 388, 500
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 422, 499, 552, 490
      Annotation: 
       Subtype: Link
       Rect: 323, 489, 367, 480
      Annotation: 
       Subtype: Link
       Rect: 323, 479, 456, 470
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 414, 459, 552, 450
      Annotation: 
       Subtype: Link
       Rect: 323, 449, 352, 440
      Annotation: 
       Subtype: Link
       Rect: 323, 439, 366, 430
       ActionDest: 34
      Annotation: 
       Subtype: Link
       Rect: 383, 429, 510, 420
      Annotation: 
       Subtype: Link
       Rect: 323, 419, 422, 410
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 430, 399, 552, 390
      Annotation: 
       Subtype: Link
       Rect: 323, 389, 440, 380
      Annotation: 
       Subtype: Link
       Rect: 323, 379, 463, 370
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 466, 349, 552, 340
      Annotation: 
       Subtype: Link
       Rect: 323, 339, 459, 330
      Annotation: 
       Subtype: Link
       Rect: 323, 329, 370, 320
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 323, 309, 426, 300
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 392, 289, 505, 280
      Annotation: 
       Subtype: Link
       Rect: 323, 279, 422, 270
       ActionDest: 35
      Annotation: 
       Subtype: Link
       Rect: 466, 269, 552, 260
      Annotation: 
       Subtype: Link
       Rect: 323, 259, 383, 250
      Annotation: 
       Subtype: Link
       Rect: 323, 249, 409, 240
       ActionDest: 37
      Annotation: 
       Subtype: Link
       Rect: 466, 229, 552, 220
      Annotation: 
       Subtype: Link
       Rect: 323, 219, 386, 210
      Annotation: 
       Subtype: Link
       Rect: 323, 209, 493, 200
       ActionDest: 37
      Annotation: 
       Subtype: Link
       Rect: 323, 169, 517, 160
       ActionDest: 37
      Annotation: 
       Subtype: Link
       Rect: 470, 139, 552, 130
      Annotation: 
       Subtype: Link
       Rect: 323, 129, 398, 120
      Annotation: 
       Subtype: Link
       Rect: 323, 119, 459, 110
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 376, 89, 527, 80
      Annotation: 
       Subtype: Link
       Rect: 323, 79, 511, 70
       ActionDest: 38
    Page: 
     Sequence: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 56, 709, 249, 700
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 248, 689, 285, 680
      Annotation: 
       Subtype: Link
       Rect: 56, 679, 187, 670
      Annotation: 
       Subtype: Link
       Rect: 56, 669, 256, 660
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 203, 639, 285, 630
      Annotation: 
       Subtype: Link
       Rect: 56, 629, 125, 620
      Annotation: 
       Subtype: Link
       Rect: 56, 619, 283, 610
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 56, 589, 186, 580
      Annotation: 
       Subtype: Link
       Rect: 56, 579, 185, 570
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 460, 729, 547, 720
      Annotation: 
       Subtype: Link
       Rect: 317, 719, 384, 710
      Annotation: 
       Subtype: Link
       Rect: 317, 709, 551, 700
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 317, 699, 406, 690
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 509, 679, 547, 670
      Annotation: 
       Subtype: Link
       Rect: 317, 669, 433, 660
      Annotation: 
       Subtype: Link
       Rect: 317, 659, 363, 650
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 464, 649, 547, 640
      Annotation: 
       Subtype: Link
       Rect: 317, 639, 406, 630
      Annotation: 
       Subtype: Link
       Rect: 317, 629, 545, 620
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 339, 599, 495, 590
      Annotation: 
       Subtype: Link
       Rect: 317, 589, 545, 580
       ActionDest: 38
      Annotation: 
       Subtype: Link
       Rect: 380, 559, 546, 550
  Checksum: fa845558
   Type: CRC32
  Checksum: 64c125a4a093f195920006801421382a
   Type: MD5
  Checksum: f9568642b973375adc98d9dbdf04c068c93135d7
   Type: SHA-1
  Checksum: 0209610cb4d8a95eb585702829815df35aa485c4a869e690a736788f7f378c20
   Type: SHA-256