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Hanoi medical universitydOAN TIEN LUU STUDY THE VALUE OF MR IMAGING IN OVARIAN CANCER DIAGNOSIS Specilised : Radiology Code : 62720166 Summarise of thesis of Philosophy doctor Han

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Hanoi medical university

dOAN TIEN LUU

STUDY THE VALUE OF MR IMAGING

IN OVARIAN CANCER DIAGNOSIS

Specilised : Radiology Code : 62720166

Summarise of thesis of Philosophy doctor

Hanoi - 2019 Thesis made in hannoi medical university

THESIS SUPERVISORS:

1 Ass Prof BUI VAN LENH

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Reviewer 1: Ass Prof Thai Khac Chau

Reviewer 2: Ass Prof Nguyen Dinh Tuan

Reviewer 3: Ass Prof Lam Khanh

Thesis will be protected in congress university level of Hanoi Medical University

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to the thesis

1 Đoàn Tiến Lưu, Bùi Văn Lệnh, Vũ Bá Quyết (2019),

“Nghiên cứu áp dụng thang điểm cộng hưởng từ trong chẩn

đoán khả năng ác tính của u buồng trứng”, Tạp chí Y học thực hành, số tháng 1 năm 2019 (1089), trang 86 - 90.

2 Đoàn Tiến Lưu, Bùi Văn Lệnh, Vũ Bá Quyết (2019),

“Nghiên cứu giá trị của xung cộng hưởng từ động học sau tiêm thuốc đối quang từ trong chẩn đoán phân biệt u buồng

trứng ác tính với u buồng trứng lành tính”, Tạp chí Y học thực hành, số tháng 3 năm 2019 (1098), trang 23 – 27.

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Ovarian cancer is the third most common cancer, after cervicalcancer and endometrial cancer, but is the leading cause of death amongfemale genital cancers The disease has a poor prognosis because themajority of cases are detected late Most cases have pelvic invasion andperitoneal metastases when detected To change the prognosis, earlydetection and proper treatment should be made

Recently, with the development of new magnetic resonance pulsechains (CHT), it has faster shooting time, better resolution of images,analysis of many characteristics of tumor tissue, differentiating cancertissue from benign tissue At the same time, it is easier to surveyed theentire abdominal cavity to detect peritoneal metastases, lymph nodemetastasis Magnetic resonance (MR) imaging is increasingly showingadvantages in definitive diagnosis and diagnosis of ovarian cancer stage There have been studies of the value of MR imaging in the diagnosis

of ovarian cancer in developed countries However, in Vietnam, there are

no studies, especially studies on MR machines with advanced softwarefor diagnosing ovarian cancer So we conducted a research on the topic

"Study the value of MR imaging in diagnosing ovarian cancers" with thefollowing three research objectives:

1 Describe the MR imaging characteristics of ovarian cancer

2 Evaluate the value of MR imaging in the differential diagnosis ofovarian cancer with benign ovarian tumors

3 Evaluate the value of MR imaging in the diagnosis of ovariancancer stage

* Urgency of the project: Finding out a medical imaging modality

which has hight value in diagnosis of ovarian cancers and staging ovariancancers MR imaging with 1,5T machines, many new sequences, hashight potential in accurately differentiating between ovarian cancers andbenign ovarian tumors, in staging ovarian cancers

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* New contributions of the thesis: This thesis is the first

Vietnamese research of values of MR imaging in diagnosis of ovariancancers The study outcomes showed efficacy of MR imaging indiffentiating between ovarian cancers and benign ovarian tumors, and instaging ovarian cancer Ovarian cancer’s tissues are always restricteddiffusion (hight intensity on DW-b1000) Cutt-off of ADC value ≤1,26x10-3 mm2/s has moderate value in diffentiating between ovariancancers and benign ovarian tumors Ovarian tumor’s tissue withenhanced curve type II or type III is the most important characteristics indiagnosis of ovarian cancers Diffusion imaging (DW-b1000) has hightsensitive in discovering peritoneal metastases

THESIS OUTLINE

This thesis covers 131 pages, including: preamle (2 pages), chapter1: The Overview (37 pages), chapter 2: Material and method (19 pages),chapter 3: Study outcomes (28 pages), chapter 4: Discussion (42 pages),Conclusions (2 pages), Recommendation (1 page) The thesis consists of

35 tables, 3 charts, 3 diagram, 29 figures There are 105 references, ofwhich 5 in Vietnamese and 100 in English

CHAPTER 1: OVERVIEW

1.1 GENERAL ON OVARIAN CANCERS

1.1.1 Epidemiology of ovarian cancers

Ovarian cancer represents the sixth most commonly diagnosedcancer among women in the world, and causes more deaths per year thanany other cancer of the female reproductive system it accounts for about4% of all cancers in women It is the third common after cervical cancerand endometrial cancer

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An estimated 1 in 70 women in the United States will developovarian cancer in their lifetime On a worldwide basis, an estimated204,000 new cases are diagnosed and 125,000 women die of ovariancancer annually In 2007, approximately 22,430 new cases of ovariancancer will be diagnosed and 15,280 ovarian cancer-related deaths areexpected in the United States Mortality is high because women typicallypresent with late-stage disease when the overall 5-year relative survivalrate is 45% Thus, the public health burden is significant.

Ovarian cancer affects women in the age 20 - 80 years and oldermore frequently than younger women More than 80% of all ovariancancers occur in women in the age more than 40 years old

1.1.2 Hispathology of ovarian cancers

- Over 90% of ovarian neoplasms arise from the epithelial surface ofthe ovary, the rest from germ cells or stromal cells The epithelialneoplasms are classified as serous (30–70%), endometrioid (10–20%),mucinous (5–20%), clear cell (3–10%), and undifferentiated (1%)

- 5% - 10% of ovarian cancers are of germ cell origin, includeddysgerminoma, endodermal sinus tumor, embryonal carcinoma,choriocarcinoma, malignant teratoma

- Sex cord-stromal are rare, <5% of ovarian cancers, includedmalignant granulosa cell tumor, Sertoli-Leydig cell tumor, fibrosarcoma

1.1.3 Ovarian cancer staging

Stage I: Tumor confined to ovaries

- IA Tumor limited to 1 ovary, capsule intact, no tumor on surface,negative washings

- IB Tumor involves both ovaries otherwise like IA

- IC Tumor limited to 1 or both ovaries IC1 Surgical spill IC2Capsule rupture before surgery or tumor on ovarian surface IC3Malignant cells in the ascites or peritoneal washings

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Stage II: Tumor involves 1 or both ovaries with pelvic extension

(below the pelvic brim) or primary peritoneal cancer

- IIA Extension and/or implant on uterus and/or Fallopian tubes

- IIB Extension to other pelvic intraperitoneal tissues

Stage III: Tumor involves 1 or both ovaries with cytologically or

histologically confirmed spread to the peritoneum outside the pelvis and/

or metastasis to the retroperitoneal lymph nodes

- IIIA ( Positive retroperitoneal lymph nodes and /or microscopicmetastasis beyond the pelvis) IIIA1 Positive retroperitoneal lymph nodesonly IIIA1(i) Metastasis ≤ 10 mm IIIA1(ii) Metastasis > 10 mm IIIA2Microscopic, extrapelvic (above the brim) peritoneal involvement ±positive retroperitoneal lymph nodes

- IIIB Macroscopic, extrapelvic, peritoneal metastasis ≤ 2 cm ±positive retroperitoneal lymph nodes Includes extension to capsule ofliver/spleen

- IIIC Macroscopic, extrapelvic, peritoneal metastasis > 2 cm ±positive retroperitoneal lymph nodes Includes extension to capsule ofliver/spleen

Stage IV: Distant metastasis excluding peritoneal metastasis

- IVA Pleural effusion with positive cytology

- IVB Hepatic and/or splenic parenchymal metastasis, metastasis toextraabdominal organs (including inguinal lymph nodes and lymph nodesoutside of the abdominal cavity)

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- Localizer sequence in the three spatial planes;

- Axial T2-weighted single-shot fast spin-echo (SSFSE) sequence,section thickness 6 mm, interslice gap 0.6 mm, used as secondlocaliser to identify the longitudinal axis of the uterus in the case

of laterally deviated uterus

- Sagittal T2-weighted fast spin-echo (FSE) sequence parallel tothe longitudinal axis of the uterus (identified on the previousSSFSE sequence), section thickness 4 mm, interslice gap 1 mm

- Oblique coronal T2-weighted FSE sequence parallel to thelongitudinal axis of the uterus, section thickness 4 mm, interslicegap 1 mm

- Oblique axial T2-weighted FSE sequence perpendicular to thelongitudinal axis of the uterus, section thickness 4 mm, interslicegap 1 mm

- Axial oblique fat suppressed T2-weighted FSE sequence, sectionthickness 4 mm; interslice gap 1 mm

- Axial T1-weighted gradient-echo (GRE) sequence in-out shift imaging), section thickness 6 mm; interslice gap 0,6 mm

(chemical Axial DWI SE EPI (TR/TE 3000/74,1; flip angle 90°; sectionthickness 5 mm; interslice gap 1 mm

- Axial oblique T1-weighted 3D gradient-echo liver acquisitionwith volume acquisition (LAVA) sequence with fat suppression,section thickness 3.4 mm; overlap locations −1.7 mm

After i.v administration of 0.1 mmol/kg paramagnetic contrastagent (Dotarem) at a flow rate of 2 ml/s, followed by 20 ml of salinesolution at the same flow rate, the following sequences are acquired:

- Dynamic axial T1-weighted 3D gradient-echo LAVA with fatsuppression, section thickness 3.4 mm, overlap locations

−1.7 mm, 10 sequences acquired in 6 minutes after contrastadministration

CHAPTER 2:

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OBJECTS AND METHOD 2.1 Materials

Objects included 184 patients with ovarian tumors (93 patients withovarian cancers and 91 patients with benign ovarian tumors)

All the patients got pelvis and abdominal MR imaging to diagnoseovarian cancers at Radiology department of Hanoi University Hospital,operated at Oncology department of Hanoi University Hospital andNational hospital of obstetrics and gynecology, from November 2013 toAugust 2017

2.2 Study methods

Prospective, descriptive cross-sectional study

2.2.1 Study equipments

- MR system 1.5T Signa X (GE Healthcare)

- Paramagnetic contrast agent (Dotarem) 0,5mmol/1ml

2.2.2 Study design

- Select eligible patients

- Various MR criterias were evaluated on the basis of severalpreviously published terms:

+ A purely cystic lesion was defined by the absence of solid tissueand the absence of internal enhancement after injection and corresponded

to a unilocular cyst or hydrosalpinx, both of which have low T1-weightedand high T2-weighted MR signal intensities

+ A purely endometriotic mass was defined as a lesion that displayedhigh T1- weighted signal intensity that was greater than or equal to that

of subcutaneous fat, shading on T2-weighted MR images, and no solidtissue

+ A purely fatty mass was defined as a lesion that displayed high weighted signal intensity that decreased after fat saturation and thatdisplayed no solid tissue

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T1-+ Readers also recorded enhancement of the cyst wall, bi- ormultilocularity, and the presence of thickened regular septa or grouped septa + The presence of a solid tissue and its morphology (solid portion,vegetation, thickened irregular septa) were also evaluated Then, T2-weighted signal intensity within the solid tissue (low or intermediatecompared with that of the outer myometrium) and b = 1000 sec/mm2–weighted signal intensity within the solid tissue (high b = 1000 sec/mm2–weighted signal intensity compared with that of serous fluid [urine in thebladder or cerebrospinal fluid]) were analyzed As previouslydemonstrated, we described lesions that displayed both low T2 and b =

1000 sec/mm2–weighted signal intensity within the solid tissue

+ Finally, readers analyzed the perfusion-weighted images at astandard workstation by using the breast or prostate perfusion tool andselecting two regions of interest—one in the external myometrium and one

in the most enhancing part of any solid tissue We classified theenhancement of the solid tissue by using a previously published time–signal intensity curve classification A gradual increase in the signalintensity of the solid tissue, without a well-defined “shoulder,” was defined

as curve type 1 A moderate initial increase in the signal intensity of solidtissue relative to that of myometrium, followed by a plateau, was defined

as curve type 2 An initial increase in the signal intensity of solid tissuethat was steeper than that of myometrium was defined as curve type 3 + The presence of free fluid in peritoneal cavity

+ Peritoneal implants was also noted: Nodular thickening of theperitoneum that is restricted diffusion (hight intensisty on DW-b1000) andenhances after gadolinium chelate injection

+ Pelvis invasion: Normally, there is a hight intensity interface onT2W between ovarian tumors and rectum, uterus, blader and pelvis wall.When we can not see this interface or the interface is irregular or retracted,

it is said that there is pelvis invasion

+ Metastases lymph nodes: Oval or round in shape, transversediameter over 8mm, hyperintensity on DW-b1000, enhances after

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gadolinium chelate injection, beside to pelvis vessels and aorta, vena cavaand superior mesenteric vessels.

+ Diagnosis of malignant ovarian tumors based on MR criterias,comparing MR imaging diagnosis with surgery diagnosis to asses thevalues of MR imaging in diagnosis malignant ovarian tumors

+ Staging ovarian cancers based on MR imaging diagnosis ofperitoneal implants, metastases lymph nodes, pelvis invasion

+ Calculating the malignancy ratio of tumors according to MRcharacteristics, following malignancy ratio to rank ovarian tumors inThomassin's ADNEX MR scoring system, the ADNEX MR scoringsystem has 5 scores (score 1: no tumors; score 2: benign tumors; score 3:tumors with low malignancy ratio; score 4: tumors with high malignancyratio; score 5: almost certainly malignant)

- Based on MR imaging’s diagnosis of invasion of malignant ovariantumors, diagnosis of peritoneal metastases, visceral metastases, lymph

node metastases, to diagnose of pre-operative disease stage Compare the

results of MR imaging’s diagnosis of ovarian cancer stage with stagingovarian cancer after surgery and hispathologic results Calculate theaccuracy of MR imaging in diagnosing ovarian cancer stage

CHAPTER 3:

RESEARCH OUTCOMES

3.1 General characteristics of the research object

184 cases of ovarian tumors in the study, there were 93 malignantcases (50.5%), 91 cases of benign tumors (49.5%) Malignant epithelialneoplasms account for the majority (84.6%), germ cell malignancy 8.3%,and genital cord cell cancers 7.1%

Patients with ovarian cancer had an average age of 49.5 ± 14.8 years,72.1% at age 40 - 69 years

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Clinical signs of malignant ovarian tumors were nonspecific, each ofwhich showed signs of <50% of cases, but gynecological examinationpalpable the masses in 88.7% of cases.

Level of serum CA15 has the sensitivity of 94.9% with stage III, IVovarian cancers, 78.9% with stage II ovarian cancers, 57.1% with stage Iovarian cancers

3.2 MR imaging’s characteristics of ovarian cancer

Malignant ovarian tumors have an average size of 93.9 ± 37.8mm.93.6% cases of ovarian cancers had complex structure (tissue andcystic structure), 3.2% completed tissue structure, 3.2% purely cysticstructure

Malignant ovarian tumors had serous fluid (increased signal onT2W, decreased signal on T1W) in 84.4% of cases; mosaic fluid,increased signal on T1W and T2W compartments and decreased signal

on T1W, increased signal on T2W compartments (mucus, protein-richfluid) in 10% of cases; chronic bleeding fluid, increased signal on T1W,T1W fat-saturation, decreased T2W signal in 5,6% of cases

100% of malignant tumors’ tissues increased signal on DW-b1000,94.4% of soft tissues had time–signal intensity curve type 2 or type 3,5.6% of soft tissues had time–signal intensity curve type 1

3.3 The value of MR in differential diagnosis of malignant ovarian tumors with benign ovarian tumors

3.3.1 Analysis of MR characteristics to diagnose of malignant ovarian tumors

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Table 3.1: Multivariate analysis of MR characteristics for diagnosing

malignant ovarian tumors

Malignant

characteristics Malignant Benign

Univariate analysis Multivariate analysis

(0,181 – 9,913)

(10,047 – 334,845)

When analyzing univariate, the MR characteristics of ovariantumors, size of tumor ≥ 80mm, multilocularity, wall thickness ≥ 3mm,vegetations, tissues increase signal on DW-b1000, tissue’s ADC value ≤

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