gynecologic malignancies: ovarian cancer · 2019. 10. 25. · cancer syndromes syndrome gynecologic...
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KRISTEN STARBUCK, MD
ROSWELL PARK CANCER INSTITUTE
DEPARTMENT OF SURGERY
DIVISION OF GYNECOLOGIC ONCOLOGY
APRIL 19TH, 2018
GYNECOLOGIC MALIGNANCIES: Ovarian Cancer
Objectives
Basic Cancer Statistics
Discuss subtypes, surgical treatment, medical
treatment, preventative, and novel treatment of:
Ovarian cancer
(Tomorrow):
Endometrial cancer
Cervical Cancer
Vulvar/Vaginal Cancer
US Mortality (2016) Age-adjusted mortality rates
Heart disease: 611,105
Cancer: 584,881
Chronic lower respiratory diseases: 149,205
Accidents (unintentional injuries): 130,557
Stroke (cerebrovascular diseases): 128,978
Alzheimer's disease: 84,767
Diabetes: 75,578
Influenza and Pneumonia: 56,979
Nephritis, nephrotic syndrome, and nephrosis: 47,112
Intentional self-harm (suicide): 41,149
Source CDC 2018.
US Mortality (2016)
Heart disease: 635,260 23.1%
Cancer: 598,038 21.8%
Accidents (unintentional injuries): 161,374 5.9%
Chronic lower respiratory diseases: 154,596
Stroke (cerebrovascular diseases): 142,142
Alzheimer's disease: 116,103
Diabetes: 80,058
Influenza and Pneumonia: 51,537
Nephritis, nephrotic syndrome, and nephrosis: 50,046
Intentional self-harm (suicide): 44,965
Source CDC 2018.
US Cancer Incidence and Mortality (2015)
Projected new cancer cases and deaths,
2018
Cancer statistics, 2018, Volume: 68, Issue: 1, Pages: 7-30, First published: 04 January 2018, DOI: (10.3322/caac.21442)
Trends in age-adjusted cancer incidence, 1975-2014
Ovarian Cancer
Incidence/Prevalence
Cancer.gov / SEER.gov
Stage at diagnosis and survival
Risk Factors for Ovarian Cancer
Increased Risk Decreased Risk
Age Oral Contraceptive Pills
Family History of Ovarian Cancer
Pregnancy
Infertility Tubal Ligation
Low Parity Breastfeeding
Oral Contraceptive Pills
*
Hereditary Breast and Ovarian
Cancer Syndromes
Hereditary Breast and Ovarian
Cancer Syndromes
Syndrome Gynecologic
Cancer Gene Mutation
Breast/Ovarian
Cancer
Ovary BRCA 1(30-40%risk OC)
BRCA 2 (15-25% risk OC)
HNPCC
(Lynch
Syndrome)
Uterine,
Ovary
MSH2, MLH1, MSH6
(40-60% risk uterine, 6-
20% risk OC) *
Family
History of
Ovarian Cancer
Lifetime Risk
None 1.4%
1 First
Degree relative
5%
2 First
Degree relatives
7%
Hereditary Breast and Ovarian
Cancer Syndromes
Ovarian Cancer Preventative
Measures for BRCA 1 & 2 Patients
Birth Control Pills
Reduce risk by 45-60%
Tubal Ligation (BTL)
Reduces risk by ~60%
BTL & Birth Control Pills
Reduce risk by 72%
Bilateral Salpingo-oophorectomy
Reduces risk by 80%
Reduces risk of breast cancer by 50%
Ovarian Cancers
Histologic Distribution
Germ Cell Cancers
Derived from germ cell of
ovary
2-3% are malignant
Most common germ cell tumor
Mature Cystic Teratoma
(Dermoid Cyst)
Most common malignant germ
cell cancer
Dysgerminoma
Sex Cord-Stromal Cancers
Granulosa Stromal Cell
Tumors
Precocious puberty
Abnormal bleeding
Thecoma
Benign, hormone-producing
Fibroma
Benign, connective
tissue
Sertoli-Leydig Tumors
Masculinization
Hirsutism
Histologic subtypes of epithelial ovarian carcinoma and associated mutations/molecular
aberrations. *, CHK2, BARD1, BRIP1, PALB2, RAD50, RAD51C, ATM, ATR, EMSY, Fanconi
anemia genes.
Susana Banerjee, and Stanley B. Kaye Clin Cancer Res
2013;19:961-968
©2013 by American Association for Cancer Research
Symptoms of Ovarian Cancer
Bloating
Vague abdominal discomfort
Abdominal pain
Urinary frequency/
urgency
Pelvic pressure or
pain
Dyspepsia
HIGH SUSPICION
Diagnosis of Ovarian Cancer
Routine pelvic exams in asymptomatic women detect only
1 in 10,000 ovarian cancers
Tumor Markers
Histology Tumor Marker
Epithelial Ovarian Cancer CA 125
Dysgerminoma LDH
Endodermal Sinus Tumor AFP
Choriocarcinoma hCG
Granulosa Cell Tumor Inhibin B
Embryonal Cell Tumor hCG
Ultrasound Findings
Current Standard of Care for Advanced Ovarian Cancer
Surgical staging by gynecologic
oncologist with maximum tumor
debulking
1 cm of residual tumor
6 cycles of platinum based chemotherapy with a taxane
Treatment-Staging Surgery
Peritoneal washings: diaphragm, right and left abdomen, and pelvis
Inspection and palpation of all peritoneal surfaces
Biopsy or smear from right hemidiaphragm
Biopsy all suspicious lesions
Infracolic omentectomy
Biopsy or resection of any adhesions
Random biopsy of peritoneum of bladder reflection, cul-de-sac, both paracolic gutters, and pelvic side walls
Pelvic and para-aortic lymph node dissection
TAH, BSO
“Surgical bulk resection is of little
value unless all gross tumor is excised”
Neoadjuvant Chemotherapy
Chemotherapy given before surgery
Allows patients who have unresectable disease at initial surgery to have a higher chance of being maximally cytoreduced
Useful for patients who are medically compromised
Ongoing research into molecular changes pre- and post-chemotherapy
Fertility Sparing Surgery
Stage 1 disease
Nulliparous women
Unilateral salpingo-oophorectomy, hysteroscopy and curettage, cytology, peritoneal biopsy, lymph node dissection, omentectomy
Hysterectomy and contralateral salpingo-oophorectomy when child bearing is complete
Common Sites of Spread
Stages
1- one or both ovaries
II-other pelvic organs
III-outside the pelvis/peritoneal mets
IV-distant mets excluding peritoneal mets
Treatment-Chemotherapy
Intraperitoneal Chemotherapy
Higher doses of chemotherapy
Longer half life
Works best on minimal disease
Platinum-sensitivity and response to
subsequent treatment
Goals for Improving Patient Survival
Enrollment in clinical trials
Aggressive surgical management by well trained specialists
Maximal tumor cytoreduction
Adjuvant chemotherapy with platinum and taxane based regimens
Current Standard of Care for Early Stage Ovarian Cancer
Walsh, SGO 2016
Ovarian Cancer: Future Research Directions
Effective screening- currently no effective screening
Early detection- biomarker development
Prevention
Overcoming chemo-resistance Targeted therapies
Parp inhibition Folate receptor alpha-targeting Ab Mucin-targeting Ab
Immunotherapy*
Checkpoint inhibition Cancer testis antigens Immunoprofiling TIL therapy/ACT Genetically modified TCR and CAR-T cell therapies
NY-ESO-1 Predicts an aggressive
phenotype of ovarian cancer
Szender et al., 2017
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