# Radiation Oncology/Ovary/Overview

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Ovarian Cancer Overview

## Epidemiology

* Median age 60's, peak incidence 80's
* 22K cases per year in US; 4th most common cancer in women
* 14K deaths per year in US; 5th most common cause of cancer death in women

## Risk factors

* Genetics
** One first-degree relative: 4-5% lifetime risk
** Two first-degree relatives: 25-50% lifetime risk
** BRCA1/BRCA2
** HNPCC
* Hormone exposure: nulliparity, early menarche, late menopause, hormone replacement
* Ovarian trauma, including multiple cycles of ovulation
* Environmental: endometriosis, obesity, smoking, diet

## Screening

* Prostate, Lung, Colorectal, and Ovarian Screening Trial (1993-2001)
** Randomized. 34,261 women in the screening arm. General population, age 55-74. Transvaginal ultrasound and CA-125. Screening compliance 83% to 78%
** 2009 PMID 19305319 -- "Results from four rounds of ovarian cancer screening in a randomized trial." (Partridge E, Obstet Gynecol. 2009 Apr;113(4):775-82.)
*** Outcome: Data from first 4 annual screens. Positive screen ~5% (about 2/3 TVU and 1/3 CA-125). Ratio of surgery to cancer detection 20:1. Overall yield ~5/10,000 screened. Majority (72%) late stage.
*** Conclusion: Ratio of surgeries to screen-detected cancers high, and most were late stage

## Presentation

* Generally present with ill-defined symptoms and diagnosis may be delayed
** Abdominal pain, nausea, anorexia, early satiety or constipation.
** Irregular vaginal bleeding
** Dyspareunia
** Urinary symptoms
* Palpable adnexal mass
** Pre-menopausal: 5% risk of malignancy
** Post-menopausal: 30-60% risk of malignancy
* Paraneoplastic presentation (rare):
** Leser-Trelat Sign – Sudden multiple seborrheic keratoses
** Trousseau’s Syn – Migratory thrombophlebitis
* Hormonal effects – Germ Cell Tumors
** Precocious puberty, amenorrhea, virilization
* Meigs' syndrome - Ascites, an ovarian tumor, and right-sided pleural effusion
* 80% have spread beyond the ovary at presentation.

## Anatomy

* Located in lateral pelvis, beneath external illiac artery and in front of internal illiac artery
* Attached to the uterus by ovarian ligament and the body wall by suspensory ligament; within the broad ligament
* There are 3 major tissue types in the ovary, which give rise to different types of tumors:
** Surface: covered by ovarian epithelium
** Stroma:
*** Soft tissue consisting of spindle-shaped cells (regarded by some anatomists as unspited muscle cells and others as connective-tissue cells)
*** On the surface of the ovary, this tissue is much condensed, and forms a layer (tunica albuginea) composed of short connective-tissue fibers, with fusiform cells between them
** Follicle:
*** Single oocyte
*** Granulosa cells surround the oocyte and respond to FSH and LH
*** Theca is the surrounding protective layer

## Work Up

* Transvaginal ultrasonography (TVU) is more sensitive compared to CT
** Classic TVU finding is a “complex” cyst, defined as containing both solid and cystic components
** "Simple" cyst, defined as having thin walls, fluid-filled, without a mass component, septations, or internal echogenicity is frequently benign but workup must be individualized
* Percutaneous biopsy should be avoided due to risk of cyst rupture and seeding into peritoneal cavity
* Surgery
** Exploratory laparotomy performed to 1) confirm pathology, 2) stage patient, and 3) perform maximum cyto-reduction (residual disease <1cm)
** Should be performed by a GYN Oncologist
** Ascites or peritoneal washings
** Inspection of serosal surfaces with biopsy of any suspicious lesions
** Inspect stomach, small bowel, large bowel, peritoneum, mesentery, and solid organs
** TAH/BSO
** Infracolic omentectomy
** Pelvic and paraortic LN sampling
** Peritoneal biopsies
** Pelvic cul-de-sac biopsy
** Bladder
** Bil Sidewalls
** Bil Paracolic gutters
** Diaphragm

### Ovarian-Adnexal Reporting & Data System (O-RADS™)

* O-RADS™ is an acronym for an Ovarian-Adnexal Imaging-Reporting-Data System which will function as a quality assurance tool and clinical support system for the standardized description of ovarian/adnexal pathology and its management.
* A uniform vocabulary using the most predictive internationally agreed upon lexicon descriptors for describing the imaging characteristics of ovarian/adnexal masses has been applied to a data-based risk stratification classification for consistent interpretations leading to appropriate management in clinical practice.
* The system’s goal is to optimize ovarian cancer outcomes while minimizing unnecessary surgery in patients at low risk of malignancy.
* Rochelle F Andreotti et al. O-RADS US Risk Stratification and Management System: A Consensus Guideline from the ACR Ovarian-Adnexal Reporting and Data System Committee. Radiology. 2020 Jan;294(1):168-185. (PMID: 31687921)
* Elizabeth A Sadowski et al. O-RADS MRI Risk Stratification System: Guide for Assessing Adnexal Lesions from the ACR O-RADS Committee. Radiology. 2022 Apr;303(1):35-47. (PMID: 35040672)

## Pathology

* Epithelial tumors - most common, 65%
** Serous tumors: 25% of ovarian tumors, 40% of epithelial tumors
*** Benign (60%): Serous cystadenoma, cystadenofibroma
*** Borderline (15%): Serous borderline tumors, microinvasive serous carcinoma
*** Malignant (25%): Serous cystadenocarcinoma, serous carcinoma, serous micropapillary carcinoma, serous psammomacarcinoma
** Mucinous tumors: 15% of ovarian tumors, 25% of epithelial tumors
*** Benign (80%): Mucinous cystadenoma, mucinous adenofibroma
*** Borderline (10%): Mucinous borderline tumors, microinvasive mucinous carcinoma
*** Malignant (10%): Mucinous cystadenocarcinoma, mucinous carcinoma
** Endometrioid tumors: 20% of ovarian tumors, 35% of epithelial tumors
*** Benign: Endometrioid cystadenoma, endometrioid adenofibroma
*** Borderline: Endometrioid borderline tumors
*** Malignant (Majority): Endometrioid carcinoma
** Brenner tumors (benign, borderline, or malignant) - composed of urothelial-like cells
** Other: Clear cell adenocarcinoma, urothelial carcinoma (transitional cell), mixed epithelial-papillary cystadenoma of borderline malignancy of mullerian type
* Sex cord - stromal tumors - 8%
** Stromal cells: fibroblasts, theca cells, Leydig cells
** Primitive sex cords: granulosa cells, Sertoli cells
** Are hormonally active. Affect all age groups. 70% are Stage I at diagnosis (unlike epithelial tumors which are usually Stage III-IV).
* Germ cell tumors - 15%
** Benign: mature teratoma
** Malignant: 90% of malignant tumors are epithelial: dysgerminoma, immature teratoma, yolk sac tumor (endodermal sinus tumor), embryonal carcinoma
* Note: Borderline tumors (tumors of Low Malignant Potential; LMP) have absence of stromal invasion

## Epithelial Ovarian Cancer

* Please see the epithelial ovarian cancer page

## Sex cord-stromal tumors

* Granulosa cell tumors
** About 5% of malignant ovarian tumors. The most common malignant sex cord-stromal tumor
** More common in post-menopausal women
** Present with vaginal bleeding (due to hormone)
** May be associated with endometrial hyperplasia, endometrial polyps, or endometrial carcinoma
** Most patients have an excellent prognosis, 90% 10-year survival
** May have late recurrence, 10-20 years after treatment
* Fibroma, Fibrothecoma, and Thecoma
** 4% of ovarian tumors
** These 3 tumors form a spectrum of benign tumors
** Occur in pre- and post-menopausal women
** Fibroma is most common sex cord tumor
** Thecomas are active (as compared to fibromas) and can have estrogenic activity
* Sertoli-Leydig cell tumor
** Very rare (<0.5% of ovarian tumors)
** Young women
** Symptoms are related to virilizing hormones
** Most behave in a benign fashion but can act malignant
** Recur relatively soon after treatment
* Treatment approach includes surgery, and adjuvant platinum-based chemotherapy for high risk Stage I and Stage II-IV

## Germ cell tumors

* 30% of ovarian tumors, but only 1-3% of malignant ovarian tumors
* More common in younger women and also more likely to be malignant (up to 1/3)
* Symptoms
** Due to rapid growth of tumor, resulting in stretching of the ovarian capsule; leads to early diagnosis
** Abdominal pain, distension, pelvic fullness, and urinary symptoms
* Histology:
** Dysgerminoma (counterpart to seminoma)
** Nondysgerminoma
* Serum levels
** Endodermal sinus tumor (yolk sac tumor): AFP elevated
** Embryonal carcinoma: AFP and bHCG elevated
** Choriocarcinoma: bHCG elevated
** Pure immature teratoma: normal AFP and bHCG; though AFP may be elevated in 30%
** Mature cystic teratoma (dermoid cyst): normal AFP and bHCG
* Most common malignant germ cell tumor is dysgerminoma which occur most commonly in adolescence
* Stage I 60-70%
* Surgery: Principles of management similar to epithelial ovarian CA, except fertility can be preserved with ipsilateral salpingo-oopherectomy
* Adjuvant chemotherapy:
** Adjuvant BEP for 3-4 cycles
** Stage I disgerminoma can be observed (DeVita, 8th ed.) if fertility preservation is important, with 15-20% recurrence rate. Salvage with chemotherapy is high
* Role for RT limited, due to excellent chemo responsiveness and impact on fertility