Radiation Oncology/Ovary/Overview

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 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. (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. (35040672) Pathology thumb|right thumb|right 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