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Advanced Ovarian Cancer. A multimodal diagnostic approach to predict outcome

Asp, Mihaela LU orcid (2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Primary debulking surgery (PDS) followed by platinum-based postoperative chemotherapy is
the standard of care for advanced ovarian cancer (AOC). Absence of macroscopic residual
disease after debulking surgery is the strongest prognostic factor achieved by surgery. Correct
characterization of the tumor specimen and tumor spread in combination with patient’s
characteristics such as age, comorbidity, and personal wishes, can help to select more effective
therapeutic approaches for each patient before initial intervention.
The overall aim of this thesis were to evaluate diagnostic, from the preoperative to the
intraoperative stage, to investigate how an accurate diagnosis could predict surgical outcome
and... (More)
Primary debulking surgery (PDS) followed by platinum-based postoperative chemotherapy is
the standard of care for advanced ovarian cancer (AOC). Absence of macroscopic residual
disease after debulking surgery is the strongest prognostic factor achieved by surgery. Correct
characterization of the tumor specimen and tumor spread in combination with patient’s
characteristics such as age, comorbidity, and personal wishes, can help to select more effective
therapeutic approaches for each patient before initial intervention.
The overall aim of this thesis were to evaluate diagnostic, from the preoperative to the
intraoperative stage, to investigate how an accurate diagnosis could predict surgical outcome
and survival in patients with advanced ovarian cancer.
Study I: A retrospective population-based review was conducted of 328 biopsies, in order to
assess the adequacy, accuracy and safety of tru-cut biopsy in gynecological malignancies from
the perspective of a daily clinical practice. The tru-cut biopsy was shown to be a reliable and
safe diagnostic method, with adequacy of 86.3%, accuracy of 97.5% and a complication rate of
1.3%. The adequacy of tru-cut biopsy depends on the site of the tissue sample, indications for
the biopsy and the experience of the operator.
Study II: A single-center, retrospective population-based study was conducted on 358 patients,
to evaluate the reliability of intraoperative FS diagnosis for planning the treatment of patients
with suspected ovarian cancer (OC), from a multidisciplinary perspective. Prevalence,
sensitivity, specificity, positive predictive value and negative predictive value for invasive
malignancies on FS were 54.0%, 88.1%, 98.8%, 98.9% and 87.6% respectively. Malignancy
was observed to be underestimated, but overestimation in malignancy grading was rare.
Borderline-related tumors were more likely to be incorrectly graded by FS, as were rare tumor
types. Despite diagnostic difficulties, in some of the cases, the oral communication during
deliverance of frozen section diagnosis resulted in adequate treatment decisions, which
minimalized the risk for reoperation or delay of chemotherapy treatment.
Studies III and IV: A single-center, retrospective population-based study was conducted on 118
patients with AOC, to determine whether the PCI and the quantity of ascites visualized by
computed tomography (CT) could assess the extent of the tumor (S-PCI) and residual disease
(RD) for AOC patients treated with PDS. Furthermore, in study IV, we examine the impact of
the tumor extent on survival. CT-PCI correlated well with S-PCI and the risk of RD, with a cutoff
of 21 for CT-PCI (0.715, p = 0.000). The risk of RD was 3.5 times higher when the quantity
of ascites on CT (CTascites) was estimated to be above 1000ml. Regardless of the completeness
of cytoreductive surgery or the complication rate, the extent of the tumor at the beginning of
surgery seemed to affect OS in patients with AOC. PCI above 18.5 doubled the risk of dying
of the disease. CT-PCI seemed to play a prognostic role for PFS, but its prognostic role for OS
is still to be investigated.
Conclusions: The existing methods of preoperative material retrieval and histopathological
diagnosis of ovarian cancer are reliable, when performed by highly trained specialists. The
preoperative CT is accessible and can be used by an experienced radiologist as a single
technique to select patients as candidates for PDS. The complete removal of the tumor is a very
important prognostic factor for prognosis in AOC, but patient’s status and tumor biology are
also important factors in the decisionmaking on a treatment plan. This thesis maintain the idea
that centralization of cancer care to tertiary centres results in highly specialized pathology,
radiology, oncology and surgical departments, and that the multidisciplinary diagnostic and
therapeutic efforts improve health care, and possibly the outcome, for patients with AOC. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Assoc.prof.MD Stålberg, Karin, Department of Obstetrics and Gynaecology, Gynaecologic Cancer Surgery, Uppsala University Hospital/Uppsala University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Advanced ovarian cancer, multidisciplinary, tru-cut biopsy, frozen section, peritoneal cancer index, CT, primary debulking surgery, cytoreductive surgery, survival
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2022: 155
pages
101 pages
publisher
Lund University, Faculty of Medicine
defense location
Föreläsningssalen, Avdelningen för obstetrik och gynekologi, Skånes Universitetssjukhus i Lund. Join by Zoom: https://lu-se.zoom.us/j/68383072041?pwd=N2FrenZGOXZyTElUbUN4S3NNTVk5Zz09 Meeting ID: 683 8307 2041 Password: 892948
defense date
2022-12-02 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-317-2
language
English
LU publication?
yes
id
c92bb807-95d0-44a6-8260-f5241e6b4f24
date added to LUP
2022-11-03 16:00:37
date last changed
2022-11-15 10:23:59
@phdthesis{c92bb807-95d0-44a6-8260-f5241e6b4f24,
  abstract     = {{Primary debulking surgery (PDS) followed by platinum-based postoperative chemotherapy is<br/>the standard of care for advanced ovarian cancer (AOC). Absence of macroscopic residual<br/>disease after debulking surgery is the strongest prognostic factor achieved by surgery. Correct<br/>characterization of the tumor specimen and tumor spread in combination with patient’s<br/>characteristics such as age, comorbidity, and personal wishes, can help to select more effective<br/>therapeutic approaches for each patient before initial intervention.<br/>The overall aim of this thesis were to evaluate diagnostic, from the preoperative to the<br/>intraoperative stage, to investigate how an accurate diagnosis could predict surgical outcome<br/>and survival in patients with advanced ovarian cancer.<br/>Study I: A retrospective population-based review was conducted of 328 biopsies, in order to<br/>assess the adequacy, accuracy and safety of tru-cut biopsy in gynecological malignancies from<br/>the perspective of a daily clinical practice. The tru-cut biopsy was shown to be a reliable and<br/>safe diagnostic method, with adequacy of 86.3%, accuracy of 97.5% and a complication rate of<br/>1.3%. The adequacy of tru-cut biopsy depends on the site of the tissue sample, indications for<br/>the biopsy and the experience of the operator.<br/>Study II: A single-center, retrospective population-based study was conducted on 358 patients,<br/>to evaluate the reliability of intraoperative FS diagnosis for planning the treatment of patients<br/>with suspected ovarian cancer (OC), from a multidisciplinary perspective. Prevalence,<br/>sensitivity, specificity, positive predictive value and negative predictive value for invasive<br/>malignancies on FS were 54.0%, 88.1%, 98.8%, 98.9% and 87.6% respectively. Malignancy<br/>was observed to be underestimated, but overestimation in malignancy grading was rare.<br/>Borderline-related tumors were more likely to be incorrectly graded by FS, as were rare tumor<br/>types. Despite diagnostic difficulties, in some of the cases, the oral communication during<br/>deliverance of frozen section diagnosis resulted in adequate treatment decisions, which<br/>minimalized the risk for reoperation or delay of chemotherapy treatment.<br/>Studies III and IV: A single-center, retrospective population-based study was conducted on 118<br/>patients with AOC, to determine whether the PCI and the quantity of ascites visualized by<br/>computed tomography (CT) could assess the extent of the tumor (S-PCI) and residual disease<br/>(RD) for AOC patients treated with PDS. Furthermore, in study IV, we examine the impact of<br/>the tumor extent on survival. CT-PCI correlated well with S-PCI and the risk of RD, with a cutoff<br/>of 21 for CT-PCI (0.715, p = 0.000). The risk of RD was 3.5 times higher when the quantity<br/>of ascites on CT (CTascites) was estimated to be above 1000ml. Regardless of the completeness<br/>of cytoreductive surgery or the complication rate, the extent of the tumor at the beginning of<br/>surgery seemed to affect OS in patients with AOC. PCI above 18.5 doubled the risk of dying<br/>of the disease. CT-PCI seemed to play a prognostic role for PFS, but its prognostic role for OS<br/>is still to be investigated.<br/>Conclusions: The existing methods of preoperative material retrieval and histopathological<br/>diagnosis of ovarian cancer are reliable, when performed by highly trained specialists. The<br/>preoperative CT is accessible and can be used by an experienced radiologist as a single<br/>technique to select patients as candidates for PDS. The complete removal of the tumor is a very<br/>important prognostic factor for prognosis in AOC, but patient’s status and tumor biology are<br/>also important factors in the decisionmaking on a treatment plan. This thesis maintain the idea<br/>that centralization of cancer care to tertiary centres results in highly specialized pathology,<br/>radiology, oncology and surgical departments, and that the multidisciplinary diagnostic and<br/>therapeutic efforts improve health care, and possibly the outcome, for patients with AOC.}},
  author       = {{Asp, Mihaela}},
  isbn         = {{978-91-8021-317-2}},
  issn         = {{1652-8220}},
  keywords     = {{Advanced ovarian cancer, multidisciplinary, tru-cut biopsy, frozen section, peritoneal cancer index, CT, primary debulking surgery, cytoreductive surgery, survival}},
  language     = {{eng}},
  number       = {{2022: 155}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Advanced Ovarian Cancer. A multimodal diagnostic approach to predict outcome}},
  url          = {{https://lup.lub.lu.se/search/files/127566180/Advanced_Ovarian_Cancer..pdf}},
  year         = {{2022}},
}