Ovarian Cancer Treatment – The Latest and Greatest

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Mills-Peninsula Health Services Cancer Symposium - John K. Chan, M.D., Division of Gynecologic Oncology, UCSF University School of Medicine

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  • Add – fertility preservation Add – stress and cancer anil sood Add – cost of bev Add – cost of robot
  • Better reponsder Worth testing further
  • Although there are other types of ov ca, such as germ and stromal, we will be discussing the most common and lethal type of ov ca - epithelial carcinomas
  • OF THE ESTIMATED 12,800 WOMEN IN THE UNITED STATES IN WHOM OF DIAGNOSIS OF CERVICAL CANCER WAS EXPECTED IN 2000, NEARLY 5000 WILL ULTIMATELY DIE OF THE DISEASE BECAUSE OF THE INADEQUACIES OF CURRENT TREATMENT. TODAY IN THE UNITED STATES, CERVICAL CANCER DISPROPORTIONATELY AFFECTS WOMEN OF LOW SOCIOECONOMIC STATUS PARTLY BECAUSE SUCH WOMEN HAVE INSUFFICIENT ACCESS TO THE KNOWLEDGE OF SCREENING PROGRAMS FOR CERVICAL CANCER .
  • The primary goals of surgery include…
  • Avastin is a recombinant humanized monoclonal antibody of the IgG 1 isotype. 1 Avastin has been shown to bind all isoforms of VEGF (VEGF-A). 2 At least 4 different VEGF isoforms, with different molecular weights (206, 189, 165, and 121 kD) and heparin-binding properties, are created by alternative splicing of the VEGF-A gene. 3 The estimated half-life of Avastin is about 20 days (with a range of 11 to 50 days). 1 1. Avastin™ (Avastin) PI. February 2004. 2. Presta et al. Cancer Res . 1997;57:4593. 3. Ferrara et al. Nat Med. 2003;9:669. KEY MESSAGE Avastin is a recombinant humanized monoclonal antibody that specifically binds to the VEGF ligand.
  • 2008
  • This slide is showing the concept of the dose-dense chemohterapy according to the Norton-Simon mode. The Norton-Simon model with conventional chemotherapy suggestes: When the tumor volume is large, the regression of tumor cell is slow, when the tumor bolume has been small, the good response will be achieved, but the amplidude of the tumor growth speed is gonna be large, so the it is difficult to achieve total tumor cell kill. The concept of dose-dense therapy simply consistes of shortening the interval of chemotherapy. The Norton Simon model is suggesting shortening interval of chemotherapy may produce more tumor cell kill than conventional chemotherapy.
  • I am showing the schema of JGOG 3016 in this slide. The JGOG Statistical and Data Center randomly assigned patients to either conventional TC group or dose-dense TC treatment groups, with stratification according to residual disease, FIGO stage, and histology. In c-TC group, Paclitaxel 180mg/m2 combined with Carboplatin AUC6.0 were administered day1, while in dd-TC group, Paclitaxel administration was split into 3 days; 80mg/m2 on days 1,8,15 and Carboplatin AUC6.0 on day 1. In each arms, treatment was repeated every 21 days for 6 cycles and when patient shows clinical response the treatment should be extended to 9 cycles.
  • The overall survival is shown in this slide. Yellow line indicates dose-desne TC. 3-year survival was 65.1% in conventional TC and 72.1% in dose-dense TC. There was significantly statistical difference between two arms. The P value was 0.0325.  
  • 2008
  • Many authorities believe that we basically have one chance at cure. Once they recur, they will ultimately die from chemo and it does not matter what we give them. So choose a drug that has low toxicity.
  • ON Kaplan-Meier ANALYSIS THE 5 year Disease SPECific SURIVIVAL OF WOMEN with presumed stage I ovarian cancer was only 87% for those who did not undergo a lymphadenectomy compared to 93% for those who did.
  • Key Point HPV depends on the differentiation of the epithelium to regulate its replication and complete its life cycle. High-grade lesions are characterized by abnormal proliferation up to the lower two thirds of the epithelium in CIN 2 and up to the full epithelium in CIN 3 lesions. Background HPV DNA replicates as the basal cells differentiate and progress to the surface of the epithelium. 1 Expression of viral proteins E6 and E7 by the infected host cell is thought to delay cell-cycle arrest and differentiation, which are normally observed as uninfected epithelial cells move up from the basement membrane and mature. The delay of cell-cycle arrest allows further HPV replication in suprabasal epithelial cells. 2 CIN lesions are graded based on the extent of abnormal proliferation of the basal layer of the cervical epithelium. In moderate dysplasia (CIN 2), proliferation occurs up to the upper two thirds; and in severe dysplasia (CIN 3)/CIS, the entire epithelium is abnormal. 3 Infection with high-risk HPV types sometimes results in integration of the viral DNA into the host genome. If integration interrupts the viral E2 gene, E6 and E7 are consequently overexpressed, causing HPV-infected cells to acquire extended life spans, retain the capacity to proliferate, and develop and perpetuate mutations in the germline DNA. These cells mark dysplasia of the cervical epithelium. 2 References 1. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev . 2003;16:1–17. 2. Frazer IH. Nature Rev Immunol . 2004;4:46 – 54. 3. Bonnez W. Papillomavirus. In: Richman DD, Whitley RJ, Hayden FJ, eds. Clinical Virology . 2nd ed. Washington, DC: American Society for Microbiology Press; 2002:569 – 612. 1/Goodman/ p. 1559/ Figure 2 1/Burd/p. 5/col 1/¶3. 2/Frazer/ p.47/ col 2/¶2 2/Doorbar/ p. S9/ Figure 1 3/Bonnez/p 574/col 2/ ¶1;p.576/Figure 12. 2/Frazer/ p.47/ col 1/ ¶2; col 2/¶1 3/Bonnez/p.576/Figure 12.
  • More specifically, the da Vinci Surgical System was designed to address the deficiencies of minimally invasive surgical technology. The da Vinci System incorporates a high-resolution stereo vision system designed to provide surgeons with unparalleled image quality, improved contrast and full depth of field, compared to a standard 2D laparoscopic image. The da Vinci EndoWrist instruments are the only fully articulating laparoscopic instruments available. They offer 7 degrees of freedom and 180 degrees of articulation, which provides natural movement much like the human wrist. The EndoWrist instruments are reusable, providing between 8 – 20 lives depending on the type of instrument. A complete line of both 8 mm and 5 mm EndoWrist instruments is available, with over 40 tip configurations optimized for specific applications. The da Vinci System’s intuitive movement offers surgeons the benefits of fingertip control, motion scaling and tremor reduction -- features designed to provide unparalleled precision, dexterity and control.
  • Script: “ The da Vinci System is a robotic and computer-assisted surgical platform that was designed to transcend the limitations of both open and laparoscopic surgery. Core technology common to all da Vinci models allows physicians to perform major surgery through just a few small incisions. Let me review the basic components of a da Vinci System just briefly … The system is comprised of three key components that each play an integral role in delivering these benefits to patients… A high definition (HD) 3D vision system … A patient cart with four robotic arms, which translates the surgeon’s hand and wrist movements at the console to the instrument tips and endoscope throughout the surgery … And an ergonomically designed surgeon console, where the surgeon sits to perform the procedure. In this picture, you see an optional second console, which I’ll discuss shortly. … Together, these three components provide physicians capabilities that take surgery beyond the limits of the human hand.”
  • Persistent viral infection with carcinogenic HPV types causes virtually all cancer of the cervix and most cases of anal cancer. The carcinogenic types of HPV 16 and HPV 18, which are targeted by the current HPV vaccines, cause approximately 70 percent of all cervical cancers worldwide and 72 percent of anal cancers. HPV 6 and HPV 11 cause approximately 90 percent of genital warts. (See  'Epidemiology' above.) The quadrivalent vaccine (Gardasil) includes HPV types 6, 11, 16, and 18, whereas the bivalent vaccine (Cervarix) includes HPV types 16 and 18. (See  'Available vaccines'  above.) HPV immunization is most effective among individuals who have not yet been infected with HPV (eg, before sexual debut). (See  'Timing of immunization'  above.) Multicenter, double-blind, placebo-controlled trials have demonstrated efficacy of both quadrivalent and bivalent HPV vaccines against incident and persistent cervical HPV infection due to vaccine types and the development of cervical intraepithelial neoplasia. Quadrivalent HPV vaccine also has demonstrated high efficacy against vaccine type-associated vaginal and vulvar intraepithelial neoplasia in addition to genital warts associated with HPV 6 and HPV 11. The efficacy of either HPV vaccine for the prevention of anal intraepithelial neoplasia has not been studied in females. (See  'Efficacy and immunogenicity in females'  above.) We recommend HPV immunization of females, as advised by multiple expert panels ( Grade 1A ). Routine immunization should be offered to girls 11 to 12 years of age, but can be administered as early as nine years. Catch-up vaccination should be offered for females aged 13 to 26 years who have   not been previously vaccinated. (See  'Recommendations for HPV immunization in females'  above.) Quadrivalent HPV vaccine is effective in preventing genital warts in young males and anal intraepithelial neoplasia among men who have sex with men (MSM). There are no data on the efficacy of bivalent vaccine to prevent anal intraepithelial neoplasia in males. (See  'Efficacy and immunogenicity in males'  above.) We recommend the use of quadrivalent HPV vaccine in males, as advised by expert panels ( Grade 1B ). Routine immunization should be offered to boys aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 who have not been previously vaccinated. For MSM, catch-up vaccination should be offered up to age 26. (See 'Efficacy and immunogenicity in males'  above.) Although neither HPV vaccine contains live virus, use in pregnancy is not recommended because of limited data on safety. (See  'Pregnant females'  above.) Serologic testing or HPV DNA testing is not required prior to immunization. (See  'Prevaccination assessment'  above.) We suggest immunization of immunocompromised or immunosuppressed individuals with the HPV vaccine following the same guidelines as for immunocompetent patients ( Grade 2C ). Catch-up vaccination among these patients is recommended up to age 26 years. Cytologic screening continues to play an important role in detection and treatment of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ and prevention of cervical cancer in these high-risk patients. (See  'Immunization in special patient populations'  above and  "Screening for cervical cancer: Rationale and recommendations"  and  "Anal intraepithelial neoplasia: Diagnosis, screening, prevention, and treatment" .) The quadrivalent vaccine (Gardasil) is administered in three doses at time zero, and at two and six months of follow-up. The bivalent vaccine (Cervarix) is administered in three doses at time zero, and at one and six months of follow-up. (See  'Vaccine dose and administration'  above.) In prelicensure clinical trials and postlicensure monitoring, vaccines have been demonstrated to be generally safe. (See  'Vaccine safety' above.) Cervical cancer screening is recommended for any woman 21 years of age or older. Clinicians should be aware that HPV immunization is not effective in clearing cytologically evident disease or HPV infection that is already present. (See  'Importance of cancer screening'  above and "Screening for cervical cancer: Rationale and recommendations" .) Use of UpToDate is subject to the  Subscription and License Agreement . REFER
  • Ovarian Cancer Treatment – The Latest and Greatest

    1. 1. Gynecologic CancersOvarian Cancer Treatment – The Latest and Greatest John K. Chan, M.D. Division of Gynecologic OncologyUCSF University School of Medicine John K. Chan
    2. 2. Gynecologic CancersNo relevant financial disclosures John K. Chan
    3. 3. Gynecologic Cancers Overview• Ovarian cancer – Awareness – symptoms? – Screening – blood test or ultrasound? – Treatment / prevention – surgery and chemotherapy – Personalized novel therapy – are we there yet?• Endometrial cancer – Robotic surgery – Man vs. machine? John K. Chan
    4. 4. Gynecologic Cancers Ovarian Cancer John K. Chan
    5. 5. Gynecologic CancersOvarian Cancer – clinical presentation John K. Chan
    6. 6. Gynecologic Cancers Ovarian - benigncystadenoma teratoma fibroma John K. Chan
    7. 7. Gynecologic CancersOvarian mucinous cystadenoma John K. Chan
    8. 8. Gynecologic CancersOvarian carcinoma John K. Chan
    9. 9. Gynecologic Cancers Symptoms of “silent killer”72% of women had Early stage (high risk) patients recurring symptoms - median of 2: Over 70% had one or more• Back pain (45%) symptoms present 1-3• Fatigue (34%) months before diagnosis:• Bloating (27%) • Abdomino-pelvic pain (38%)• Constipation (24%) • Fullness / girth (27%)• Urinary symptoms (16%) • Abnormal bleeding (16%)Goff et al, JAMA 2004 Chan et al, SGO 2009 John K. Chan
    10. 10. Gynecologic Cancers Screening on ovarian cancer mortality: Prostate, Lung, Colorectal and Ovarian (PLCO) Trial Total 388 cancers Annual screening 212 screened (5.7 / 10,000 78,216 CA-125 - 6 years person years)postmenop 176 unscreened (4.7 / 10,000 TV ultrasound - 4 years ausal (n=39,105) person years) womenaged 55 to No reduction in ovarian 74 years(1993-2001) cancer mortality. Usual care (n=39,111) False-positive screening test result associated with complications Buys JAMA 2011 John K. Chan
    11. 11. Gynecologic Cancers Ovarian cancer• 1 out of 70 U.S. women• 25,000 cases annually• 14,000 deaths annually• 4th in cancer related deaths among women• Mean age at diagnosis 59 years John K. Chan
    12. 12. Gynecologic CancersFemale Reproductive Tract New Cases Deaths Breast 192,200 40,200 Colorectal 68,100 29,000 Lung/Bronchus 78,800 67,300 Endometrium 38,300 6,600 Ovary 23,400 13,900 Cervix 13,900 4,400 Vulva 3,600 800 American Cancer Society John K. Chan
    13. 13. Gynecologic Cancers Reproductive factors• Increased risk - • Decreases risk -• Nulliparity • Oral contraceptives• Infertility protective - 50% decrease with 5 or more years of use. • Multiparity • Lactation John K. Chan
    14. 14. Gynecologic Cancers Primary Therapy – ovarian cancer• Goals of Surgery – Diagnosis – Staging (early stage disease) – Cytoreduction (advanced disease)• Adjuvant Chemotherapy – Except stage IA or IB and grade I or II or clear cell histology John K. Chan
    15. 15. Gynecologic Cancers Surgery with maximum cytoreduction effortPlatinum + Taxane Chemotherapy (Carboplatin + Paclitaxel) John K. Chan
    16. 16. Gynecologic Cancers 40• Significant survival advantage for 38 Median Survival (Months) women optimally cytoreduced 36 34• Procedures may include: 32 – En bloc resection of uterus, 30 ovaries and pelvic tumor 28 – Omentectomy 26 – Selective lymphadenectomy 24 – Bowel resection 22 – Removal of diaphragmatic 20 and peritoneal implants 0 10 20 30 40 50 60 70 80 90 100 – Splenectomy, appendectomy % Cytoreduction Bristow, J., Clin. Oncol. 20: 1248, 2002 John K. Chan
    17. 17. Gynecologic CancersUS News and World Report Tewari, Chan SGO 2013 Liou, Chan J. Surg Onc 2005 John K. Chan
    18. 18. Intraperitoneal vs. IV therapy Long- term Survival • Median OS • Median PFS 62.0 vs 51.0 mo, p=0.04825.0 vs 20.0 mo, p=0.02 Tewari, Chan SGO 2013
    19. 19. Gross vs Microscopic Disease • IP therapy – Advantages in both microscopic and macroscopic residual disease – 65% vs 58% microscopic – 44% vs 35% gross residual Gross residual 1.82-fold increase in risk for death
    20. 20. Gynecologic Cancers Bevacizumab (rhuMAB VEGF)• Recombinant humanized monoclonal IgG1 antibody1• Recognizes all isoforms of VEGF-A2• Estimated half-life is approximately 20 days (range, 11-50 days)1• Randomized trials establish efficacy in colon, breast, lung, and renal cancer1. Avastin [package insert]. South San Francisco, CA: Genentech, Inc.; 2007; 2. Presta, et al. CancerRes. 1997;57:4593. John K. Chan
    21. 21. Gynecologic Cancers Mechanism of action of anti-angiogenic agents Early effects Continued effects Regression 1,2 Normalisation 2 Inhibition 1Reduces tumor massEnhances activity of Efficacy of continued therapyconcomitant therapiesPrevents growth ofmicrometastases 1. Baluk et al. Curr Opin Genet Dev 2005 2. Willett et al. Nat Med 2004 John K. Chan
    22. 22. Gynecologic Cancers GOG-0218 study schema Arm Carboplatin AUC 6 Paclitaxel 175 mg/m2 I Previously untreated (CP + PLA epithelial ovarian, primary Placebo → PLA) peritoneal, or fallopian tube cancer 1:1:1 Carboplatin AUC 6 II • Stage III optimal (macroscopic) • Stage III Paclitaxel 175 mg/m2 (CP + BEV suboptimal Bevacizumab → PLA) • Stage IV 15 mg/kg Placebo n=1800 (planned) Carboplatin AUC 6 Stratification variables: Paclitaxel 175 mg/m2 III • GOG performance status (CP + BEV → BEV) • Stage/debulking status Bevacizumab 15 mg/kg Cytotoxic (6 Maintenance 15 monthsBurger et al. J Clin Oncol 2010;28(18S): Abstr LBA1 cycles) (16 cycles) John K. Chan
    23. 23. 23 Gynecologic Cancers 1.0 GOG-0218: Investigator- Arm I Arm II Arm IIIProportion surviving progression free CP CP + BEV CP + BEV → BEV 0.9 Assessed PFS (n=625) (n=625) (n=623) 423 418 360 Patients with event, n (%) 0.8 (67.7) (66.9) (57.8) Median PFS, months 10.3 11.2 14.1 0.7 Stratified analysis HR 0.908 0.717 (95% CI) (0.759–1.040) (0.759– (0.625–0.824) (0.625– 0.6 One-sided p-value (log rank) 0.080* <0.0001* 0.5 0.4 0.3 0.2 CP (Arm I) + BEV (Arm II) 0.1 + BEV → BEV maintenance (Arm III) 0 0 12 24 36 Months since randomization *p-value boundary = 0.0116 John K. Chan
    24. 24. 24 Gynecologic Cancers Arm III Arm I Arm II CP + BEV → GOG-0218: Overall Survival CP (n=625) CP + BEV (n=625) BEV (n=623) Analysis Patients with events, n (%) 156 (25.0) 150 (24.0) 138 (22.2) 1.0 At time of final PFS analysis (January 2010) OS, months Median 39.3 38.7 39.7 Stratified analysis 1.036 0.915 0.9 HR (95% CI) (0.827–1.297) (0.827– (0.727–1.152) (0.727– One-sided p-value 0.361 0.252 0.8Proportion surviving 0.7 0.6 0.5 0.4 0.3 0.2 CP (Arm I) + BEV (Arm II) 0.1 + BEV → BEV maintenance (Arm III) 00 12 24 36 48 Months since randomization John K. Chan
    25. 25. Gynecologic CancersConventional chemotherapy 1012 1010 108 106 104 102 0 2 4 6 8 10 12 14 16 18 20Dose-dense chemotherapy 1012 1010 108 106 104 102 10 2 4 6 8 10 12 14 16 18 20 Larry Norton, The Oncologist 2001;6(suppl 3):30 John K. Chan
    26. 26. Gynecologic Cancers Ovarian Epithelial, Primary Peritoneal, or Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube cancer Fallopian Tube cancer FIGO Stage II-IV FIGO Stage II-IV Randomization Stratification; Residual disease: <1cm, > 1cm FIGO Stage : II vs. III vs. IV Histology : clear cell/mucinous vs.serous/othersConventional TC (c-TC)Conventional TC (c-TC) Dose-dense weekly TC (dd-TC) Dose-dense weekly TC (dd-TC)  Paclitaxel 180mg/m22,day 1  Paclitaxel 180mg/m , day 1   Paclitaxel 80mg/m22,days 1,8,15   Paclitaxel 80mg/m , days 1,8,15  Carboplatin AUC 6.0, day 1  Carboplatin AUC 6.0, day 1   Carboplatin AUC 6.0, day 1   Carboplatin AUC 6.0, day 1  every 21 days for 6-9 cycles  every 21 days for 6-9 cycles   every 21 days for 6-9 cycles   every 21 days for 6-9 cycles N. Katsumata, John K. Chan Lancet 2009
    27. 27. Gynecologic CancersOverall survival Proportion surviving progression-free 1.0 0.8 Proportion surviving 0.6 0.4 0.2 0.0 0 6 12 18 24 30 36 42 48 54 60 Months from randomization Treatment n Event 3-yr survival P value HR 95%CI c-TC 319 124 65.1% dd-TC 312 96 72.1% 0.0325 0.749 0.574-0.976 John K. Chan
    28. 28. Gynecologic Cancers Conclusions• Dose-dense paclitaxel with 3 weekly carboplatin should be a new standard chemotherapy for ovarian cancer• Limitations – Pharmacogenetic and tumor difference – asians vs. non-asians toxicity and efficacy less convenient more toxic global implications John K. Chan
    29. 29. Gynecologic Cancers GOG 262 IV carboplatin AUC 6 q3w 3-weekly IV paclitaxel 175 mg/m2 Bevacizumab 15 mg/kg q3w Suboptimal stage III/IV epithelial ovarian, PP or FT cancer IV carboplatin AUC 6 q3w Weekly IV paclitaxel 80 mg/m2Open: SEPT 2010 Bevacizumab 15 mg/kg q3wTarget Accrual: 625 pts Optional* bevacizumab on cycle 2 x 6 then maintenance bevacizumab 15 mg/kg IV day 1 every 21 days until progression or adverse effects preclude further treatment.Chan J PI John K. Chan
    30. 30. Gynecologic Cancers Recurrent Ovarian Cancer -What is the Optimal Agent, Optimal Dose, & Schedule John K. Chan
    31. 31. Gynecologic Cancers Ovarian Carcinoma: Natural History Progression DeathDiagnosis Evaluation Secondary ? SLL SurgerySymptomsSymptoms Chemotherapy #1 Consolidation Consolidation Chemo #2 Chemo #2 Chemo #3+ Chemo #3+ Supportive Surgical Evaluation Care Curative intent Palliative intent John K. Chan
    32. 32. Gynecologic Cancers Small Molecules Toxin MAbs TKIs conjugates AntisenseMolecular therapy Ligand – block receptor Ligand Ligand Ligand – inhibit tyrosine kinase – conjugate ligand – anti-sense ligand KK K KTKI KK KK Signal Signal Cell Protein transduction transduction death synthesis John K. Chan
    33. 33. Gynecologic Cancers Predicting Sensitivity: An Integrated Approach mRNAArray CGH Expression Mutations Sensitivity Predictor John K. Chan
    34. 34. Gynecologic Cancers• 13,321 women with ovarian cancer in California.• Only a third of patients received the best possible care by NCCN• More experienced surgeons (>10 ovarian cancer and hospitals that treated >20 year) associated with better outcomes John K. Chan
    35. 35. Gynecologic Cancers The Role of the physicians in Early Detection• Consider referral or consultation - Gynecologic Oncologist – Postmenopausal and one of the following: • elevated CA125, ascites, nodular or fixed mass, metastasis, or family history of breast or ovarian cancer – Premenopausal and one of the following: • elevated CA125 (>200), ascites, metastasis, or family history of breast or ovarian cancer ACOG Committee Opinion #280, December 2002 John K. Chan
    36. 36. Gynecologic CancersKaplan-Meier 5 yr disease-specific survival - gynecologic oncologist careNorthern CaliforniaCalifornia CancerRegistry 1994 and 1996 1,491 women Gyn Onc (n=509) stage IC-IV ovarian cancer No Gyn Onc (n=982) Gynecologic oncologist 39% (p<0.001) No gynecologic oncologist 30% Chan et al Obgyn 2007 John K. Chan
    37. 37. Gynecologic Cancers Kaplan-Meier five-year disease-specific survival based on gynecologic oncologist care Gyn Onc (n=100) No Gyn Onc (n=211) Gyn Onc (n=398) No Gyn Onc (n=692)Early-stage: Late-stage:Gynecologic oncologist 66% Gynecologic oncologist 31%No gynecologic oncologist 61% No gynecologic oncologist 23%(p=0.157) (p<0.001) Chan et al Obgyn 2007 John K. Chan
    38. 38. Gynecologic CancersChronic stress promotes tumor growth and angiogenesisMouse model of ovarian cancerTumors in stressedAnimals showed markedlyincreased vascularization andtumor growth via cAMP–PKAsignaling pathway Thaker, Sood Nat Med 2006 John K. Chan
    39. 39. Gynecologic CancersCervical Cancer John K. Chan
    40. 40. Gynecologic CancersThe Global Burden of Cancer to Women Worldwide Parkin DM et al CA Cancer J Clin 2005;55;74-108 John K. Chan
    41. 41. Screening Guidelines - Review Screening interval Initiate Age 21-29 Age >30 DiscontACS / 21 Cytology every Co-testing HPV and cytology 65ASCCP / three years every five years (preferred)ASCP (2012) Cytology every three years (acceptable)US 21 Cytology every Cytology every three years 65Preventive three years Alternative: co-testing HPV andServices cytology every five years¥Task Force(2012)ACOG 21 Cytology every Co-testing HPV and cytology 65(2012) three years every five years (preferred) Cytology every three years John K. Chan, M.D.
    42. 42. Gynecologic Cancers Biology of HPV Infection: High-Grade Lesions1–3 Normal HPV Infection Cervical Cancer Cervix (CIN* 2) (CIN* 3) (Invasive) Infectious Viral Perinuclear Clearing Particles (Koilocytosis) Episome Basal cell layer*CIN = cervical intraepithelial neoplasia; ICC = invasive cervical cancer1. Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564. Adapted with permission from the Massachusetts Medical Society.2. Doorbar J. J Clin Virol. 2005;32(suppl):S7–S15. 3. Bonnez W. In: Richman DD, Whitley RJ, Hayden FJ, eds. Washington, DC:American Society for Microbiology Press; 2002:557–596. John K. Chan
    43. 43. Gynecologic Cancers John K. Chan
    44. 44. Gynecologic Cancers HPV L1 VLP Vaccine SynthesisL1 gene Empty viralon HPV capsids DNA Elicits immune response in Yeast cell DNA host Transcription L1 gene inserted Capsid proteins into genome of mRNA yeast cell tRNA Translation rRNA Yeast Cell (or Baculovirus Expression System) John K. Chan
    45. 45. Gynecologic Cancers Chan, Berek JCO 2007 John K. Chan
    46. 46. Gynecologic Cancers Prophylactic HPV Vaccines• Quadra-valent (Merck) • Bi-valent (GSK) – Recombinant L1 proteins using yeast – Recombinant L1 proteins using baculovirus – 100% effective in preventing persistent – 100% effective in preventing persistent HPV infection HPV infection – Phase III Study completed – Phase III study ongoing • HPV L1 Types 6, 11, 16 & 18 vs. • HPV L1 Types 16 & 18 vs. Hepatitis A adjuvant • Endpoint CIN 2+ • Endpoint CIN2+ Villa LL et al Harper DM et al Lancet Oncol. 2005 May;6(5):271-8. Lancet. 2004 Nov 13-19;364(9447):1757-65. John K. Chan
    47. 47. Gynecologic CancersAdvisory Committee on Immunization Practices —(Pediatric, gynecologic, and family practice) females aged 11 to 12 (as young as age 9) Catch-up vaccination 13 to 26 years (Bivalent or quadrivalent) males aged 11 or 12 years (as young as 9) Catch-up 13 to 21 years (Quadrivalent) John K. Chan
    48. 48. Gynecologic Cancers Conclusions• The incidence of cervical cancer is decreasing• Vaccines will eliminate this disease in a generation• Multimodality therapy in almost every scenario of invasive disease• Clinical and translational trials ongoing investigating new agents John K. Chan
    49. 49. Gynecologic Cancers Uterine Cancer John K. Chan
    50. 50. Gynecologic Cancers Robotic Surgical System • Unparalleled Precision Dexterity and Control – High resolution 3D visualization – Fully articulating EndoWrist® instruments – Intuitive movement, motion scaling, tremor reduction John K. Chan
    51. 51. Gynecologic CancersRobotic surgery – public perception John K. Chan
    52. 52. Gynecologic CancersRobotic surgery vs. laparoscopicsurgerySafe and feasible. ?better thanlaparoscopyAdvantages - Decreases physiciantremor, fatigueDisadvantages - Increase OR time,cost, bulky, no tactile feedbackTransition from open to laparoscopicsurgery, Market pressuresEvidence based practice vs. state ofart (novel technologies) Venkat, Chan et al, Gyn Onc 2011 John K. Chan
    53. 53. Gynecologic Cancers Review• Ovarian cancer – Surgery – optimal surgery – high volume surgeons – Adjuvant chemotherapy – intraperitoneal & weekly therapy• Cervix cancer – Prevention – New screening & HPV vaccine• Endometrial cancer – Robotic Laparoscopy John K. Chan
    54. 54. Gynecologic Cancers johnkchanmd@gmail.com (415) 306-4668 John K. Chan

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