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Mayella Mercado - Montemar, M.D. Dr. Ahmed Abanamy Hospital Department of Obstetrics & Gynaecology Powerpoint Templates Page 1 Objective: • To present the management of debilitated patient diagnosed to have ovarian cancer • To discuss the role of ancillary procedures and tumour markers in the diagnosis and management of ovarian cancer • To discuss the preventive measures of ovarian cancer Powerpoint Templates Page 2 General Data: • • • • • • E.G. 53 years old Married Muslim Riyadh, K.S.A. May 23, 2013 Powerpoint Templates Page 3 Chief complaint: Abdominal enlargement x 6 months Powerpoint Templates Page 4 HPI: 6 months PTA Abdominal discomfort & distension (-) early satiety, DOB, abdominal fullness, dyspepsia, bowel habit changes Powerpoint Templates (+) Consult Ranitidine Mefenamic acid for whole abdominal CT scan Page 5 Abdominal enlargement 3 months PTA Loss of appetite Weight loss of 20% Abdominal fullness Powerpoint Templates Page 6 4 weeks PTA (+) persistence of signs & symptoms (+) DOB (+) Body malaise Powerpoint Templates (+) Consult Whole abdominal UTZ (+) Referred to MOH Page 7 Whole abdominal UTZ • Ascites, seen in the perihepatic, perispleenic, paracolic and pelvic region • Large pelvo-abdominal cystic mass: a large multiloculated mass in the midpelvic abdomen seen above the urinary bladder which measured 8.6 x 9.0 x 8.7 cm • Cholelithiasis with gallbladder wall thickening • None visualized right kidney maybe due to overlying bowel gas Powerpoint Templates Page 8 1 week PTA Persistence of s/sx Powerpoint Templates (+) consult Whole abdominal CT scan Page 9 Whole abdominal CT scan • Absent uterus (s/p subtotal hysterectomy) • Pelvo-abdominal mass t/c ovarian new growth: huge multiloculated mass noted in the midline extending to the left hemi abdomen approximately measuring 18.39 x 11.31 x 16.08 cm. Some locules contain anechoic fluid while some contain very fine scattered echoes. Locule walls with solid components and slightly thickened at 3-4 mm • The peritoneum is outlined by anechoic fluid • Normal ovarian structures Powerpoint Templates Page 10 5 days PTA severe weakness noted by relatives Powerpoint Templates - Government hospital - Hydrated - CBC - CA 125 - Advised admission Page 11 CBC • • • • • • Hgb- 10.7 g/dL Hct- 0.33 WBC- 9.72 Segmenters- 82.1 Lymphocytes- 13.1 Platelets- 471 Powerpoint Templates Page 12 CA 125 143 U/mL (< 35 u/ml) Powerpoint Templates Page 13 Few hours PTA (+) Consult Private GYN OPD Admission Powerpoint Templates Page 14 Menstrual history: • • • • Menarche: 11 years old Interval: 28-30 days Duration: 3-4 days Amount: moderately soaked, 2-3 pads/day • (+) dysmenorrhoea Powerpoint Templates Page 15 OB history: G4P3 (3103) G1 1972 LSCS I due to CPD LTBG BW: 2.7 kg CGH (-) FMC G2 1975 LSCS II LTBG BW: 2.7 kg OM (-) FMC G3 1977 VBAC stillbirth ? BW JRRMMC (?) FMC G4 1978 LSCS III LTBG JRRMMC PPH due to BW: 3.1 kg intractable uterine atony Subtotal hysterectomy Powerpoint Templates Page 16 Gyne History: • (-) history of contraceptive use • (-) history of STD • (-) history of dyspareunia and post-coital bleeding • Last pap smear was 1977 (normal), no further check-up since then Powerpoint Templates Page 17 PMH: • (+) HPN with poor medical compliance – HBP: 150/100 mmHg – UBP: 120/80 mmHg Powerpoint Templates Page 18 Family History: • • • • (+) HPN, paternal side (-) DM (-) Asthma (-) Malignancy Powerpoint Templates Page 19 Personal, Sexual and Social History: • • • • • • • Coitarche: 15 years old Monogamous Housewife Unemployed High fat and meat diet Non- smoker Non-alcoholic beverage drinker Powerpoint Templates Page 20 Review of Systems: • Unremarkable Powerpoint Templates Page 21 P.E. • General Survey: conscious, coherent, weak and dry looking, ambulatory, not in cardio-respiratory distress • BP: 120/70 mmHg HR: 110 bpm RR: 21 cpm Temp: 36.5 C BMI: 21.6 kg Powerpoint Templates Page 22 P.E. HEENT: Pale palpebral conjunctivae, anicteric sclera, no naso-aural discharge, no tonsillopharyngeal congestion Powerpoint Templates Page 23 • Neck: Supple, no neck vein engorgement, no palpable cervical LN • Chest/Lungs: Symmetrical chest expansion, no retractions, decrease breath sounds, bibasal • CVS: Adynamic precordium, normal rate, regular rhythm, no murmur Powerpoint Templates Page 24 • Abdomen: globular with abdominal girth of 100.5 cm, (+) fluid wave, (+) shifting dullness, (+) fixed, palpable, solid mass at the hypogastric area, non tender, approximately measuring 8.0 x 8.0 cm Powerpoint Templates Page 25 • Speculum examination: cervix smooth with minimal mucoid discharge, non foul smelling, no bleeding • Internal Examination: cervix firm, closed Powerpoint Templates Page 26 Initial Impression: Gravida 4 Para 4 (3-1-0-3) Pelvo-abdominal mass probably Ovarian in origin, t/c malignancy, Anemia 2⁰, HPN Stage II, s/p Subtotal Hysterectomy (1978) Powerpoint Templates Page 27 Course in the Ward Powerpoint Templates Page 28 Date Problem Diagnosis On Pelvo- Ovarian admission abdominal New Management - For Exploratory Laparotomy, PFC, BSO, Frozen section, if malignant, IO, BLND, Complete Surgical mass Growth probably probably Referral to IM for CP clearance : ovarian malignant - Low salt low fat diet - PNSS 1L x 8 hours - For CBC, Na, K, TPAG, CEA, 12 L Staging once CP cleared ECG, CXR, CT Scan of whole abdomen - Monitor VS Q 1 hour - Measure abdominal girth daily - Maintain on high back rest Powerpoint Templates Page 29 Date Problem Diagnosis CBC- Hgb: 8.5 g/dL Na- 128 (135-147 meq/L) admission K- 5.6 (3.5-5.0 meq/L) Albumin- 3.15 (3.5-5.5 g/dL) Globulin- 4.29 (2.3-3.5 g/dL) A/G ratio- 0.7 (0.8-2.0) CEA- 4.41 (< 2.5 ng/mL) CXR- (+) layering of fluid, left hemithorax 12 L ECG – NSR, Intraventricular wall possible anteroseptal wall infarct Whole abdominal CT Scan- not done On t/c Ovarian Management - IV once a day Cancer, followed by Pleural effusion left, probably Furosemide 20 mg IV - malignant, Ascites 2⁰, Anemia 2⁰, Hypertension Albumin 25% 50 cc Blood transfusion of 1 unit PRBC - Repeat CBC with platelet count 6 hours post BT was normal Stage II Powerpoint Templates Page 30 Date Problem Diagnosis Management On (+) difficulty of Pleural effusion left, - O2 at 2-3 LPM admission breathing probably malignant - IVF x 16 hours BP: 120-140/80-110 Ascites 2⁰ - Amlodipine 5 mg mmHg Anemia 2⁰- corrected CR: 90-102 bpm Hypertension Stage Cardiopulmonary RR: 20-26 cpm II clearance: tablet OD - Temp: afebrile High risk for contemplated procedure C/L: (+) poor inspiratory effort (↓) breath sounds, bibasal Powerpoint Templates Page 31 Date Hospital day 1 Problem (+) weak looking HEENT: pale palpebral conjunctivae, there were no palpable masses noted on the supra and infraclavicular area, thyroid and breast Powerpoint Templates Page 32 Abdomen: globular, dull in percussion, (+) fluid wave with palpable irregular nodular pelvo- abdominal mass enlarged to 6 months size since with a floater, solid which is palpable at the left hypochondriac area Powerpoint Templates Page 33 IE: Cervix is 2.5 cm, firm, closed, nontender and posteriorly directed, anterior fornix is distended probably due to ascitic fluid RVE: There is a multinodular firm to stony mass distending the posterior fornix with very limited mobility Powerpoint Templates Page 34 Date Diagnosis Management Hospital Ovarian New Growth Gyne – Onco Notes: day 1 highly suspicious of - malignancy with pelvic Add Ensure 150 cc, 4 scoops + 120 cc water every 4 hours and peritoneal spread - Moriamin forte 1 tablet OD (upon review of - For Paracentesis, Neoadjuvant imaging test) chemotherapy, 3 courses, 21 days apart with Ascites Massive 2⁰, Paclitaxel and Carboplatin followed by Anemia 2⁰ Interval debulking Surgery 2 weeks after the 3rd cycle. Then post-operative chemotherapy, 3 cycles to complete 6 cycles Powerpoint Templates Page 35 Date Problem Diagnosis Hospital (+) difficulty of Pleural day 1 breathing effusion left, Management - Repeat CXR showed BP: 120-130/90-100 probably progression of the mmHg malignant left sided pleural CR: 90-102 bpm Hypertension effusion and RR: 20-23 cpm Stage II diminished lung Temp: afebrile volume bilaterally C/L: crackles mid to base, right lung field Powerpoint Templates Page 36 Date Problem Diagnosis Hospital (+) shortness of breath day 2 (+) speaks in short t/c Malignant Pleural sentences Effusion BP: 120/70 mmHg CR: 82 bpm Management Referral to Pulmonology - Strict aspiration precaution - Limit fluid intake to 4 L/day - O2 at 2-3 LPM - CXR (AP sitting view) showed persistence of the RR: 25 cpm left sided pleural effusion O2 Sat: 99% with suggestive marginal C/L: slight respiratory progression, both lungs distress, decrease breath remain hypoaerated sound, left mid to base, - Furosemide 20 mg IV with BP precautions crackles, right base Powerpoint Templates Page 37 Date Problem Diagnosis Hospital (+) shortness t/c Malignant day 2 of breath Pleural Management - Ultrasound of the chest: bilateral pleural effusion with septations with approximate (+) tachypnea Effusion volume of 65 cc on the right and BP: 110130/80-90 691 cc on the left - ABG: mmHg Mixed Respiratory Alkalosis & CR: 80-90 Metabolic Acidosis with Mild bpm Hypoxemia - RR: 21-26 NaHCO3 600 mg/tablet, 1 tablet TID cpm Temp: afebrile Powerpoint Templates Page 38 Date Problem Diagnosis Hospital (+) uncontrolled BP HPN day 2 BP: 130-140/100 mmHg CR: 80-90 cpm Stage II Management - Revised Anti-hypertensive medications: - Losartan 50 mg tablet OD RR: 24 cpm - Amlodipine 5 mg tablet OD Temp: afebrile - Metoprolol 50 mg tablet BID - Maintain systolic BP at < 130 mmHg and diastolic BP at < 100 mmHg Powerpoint Templates Page 39 Date Problem Diagnosis Management Hospital (+) coffee ground vomitus, Upper GI bleed Referral to day 2 300 cc probably 2⁰ to (+) on and off epigastric pain for 1 year, burning in stress ulcer, character Acute Peptic (+) feeling of bloatedness Disease (+) constipation Gastroenterology - For NGT insertion but patient refused - Pantoloc 40 mg OD - Motilium 10 mg/ BP: 120/90 mmHg tablet, 1 tablet CR: 96 bpm TID before meals RR: 23 cpm - Temp: afebrile Maintain on high back rest Powerpoint Templates Page 40 Paracentesis: -Post paracentesis – drained 3.35 L serosangenous ascitic fluid, abdominal girth of 96 cm (from 103 cm) -Ascitic fluid analysis was suspicious for adenocarcinoma Powerpoint Templates Page 41 Date Hospital day 3 Diagnosis Problem (+)Weak looking Management Ovarian New Growth - CBC, platelet count, highly suspicious of urinalysis, SGPT, malignancy with SGOT, BUN, Crea, BP: 100/60 mmHg pelvic and peritoneal Total Bilirubin, CR: 100 bpm spread (upon review B1,B2 were all of imaging test) normal (+) dyspnea (+) DOB (+) cyanosis RR: 25-30 cpm Temp: afebrile (+) Pale palpebral conjunctivae Anemia 2⁰ (+) pale nail beds - Ascites Massive 2⁰ CBC – anemia with Hgb of - 1st cycle chemotherapy was rendered 8.5 g/dL from 108 hence blood transfusion of 4 units PRBC - Repeat Hgb & Hct post Powerpoint Templates blood transfusion, improved Page 42 Date Problem Diagnosis Management Hospital (+) occasional difficulty of day 4 breathing Onco, Cardio, Pulmo, Conscious, coherent, and Gastro stand point - Discharge from Gyne- BP: 110-120/80-90 mmHg CR: 100 bpm RR: 25-30 cpm Temp: afebrile C/L: (↓) breath sound, left lung field and right mid to base lung field Abdomen: globular, soft, (+) fluid wave, (+) palpable mass at the hypogastric area Powerpoint Templates Page 43 Final diagnosis: Gravida 4 Para 4 (3-1-0-3) Ovarian New Growth highly suspicious of malignancy w/ pelvic and peritoneal spread, t/c Malignant Pleural effusion, Massive Ascites 2⁰, Anemia 2 ⁰corrected, Electrolyte derangementresolved, Upper GI Bleed probably 2⁰ to Stress ulcer, Acute Peptic Diseaseresolved, Hypertension Stage IIresolved, Chemotherapy (Carboplatin/Paclitaxel) x 1st cycle, Blood transfusion, s/p Subtotal Hysterectomy (1978) Powerpoint Templates Page 44 Clinical Discussion Powerpoint Templates Page 45 E.G. 53 yo G4P3 (3103) Salient Feature: ONG Highly suspicious of malignancy Others Malignant Pleural effusion Electrolyte derangement Ascites 2⁰ HPN St II Anemia 2⁰ Upper GI bleed APD Powerpoint Templates Page 46 Increases the risk for developing ovarian cancer 1. A strong family history of either breast or ovarian CA Level II-2, Grade B 2. Long term use of unopposed estrogen or estrogenprogestin Level II-2, Grade B 3. Endometriosis Level II-3, Grade B 4. PID Level II-3, Grade C 5. PCOS Level II-3, Grade C 6. Adult obesity and obesity in early adulthood Level II-3, Grade C 7. Cigarette smoking increases the risk of development for mucinous EOC Level II-2, Grade B 8. High meat and fat intake Level II-2, Grade B 2nd Edition of Clinical Practice Guidelines for the Obstetrician Gynecologists Powerpoint Templates Page 47 (November 2010) Lesser or no risk for developing ovarian cancer 1. Ages at menarche and menopause Level II-3, Grade C 2. Use of fertility drugs Level II-2, Grade B 3. Alcohol intake Level II-2, Grade B 4. Perineal talc use Level II-2, Grade B 2nd Edition of Clinical Practice Guidelines for the Obstetrician Gynecologists Powerpoint Templates Page 48 (November 2010) E.G. 53 yo G4P3 (3103) Clinical Manifestation Symptoms Early stage • asymptomatic Late stage • Bowel obstruction due to intra-abdominal masses • DOB due to pleural effusion Toralba et. al., Ovarian Cancer: Diagnosis, Staging and Management, 2010 Annual Powerpoint Templates Page 49 Postgraduate Course E.G. 53 yo G4P3 (3103) Clinical Manifestation Signs Pelvic mass • Most important sign of ovarian cancer • Irregular, solid features & nodularity Abdominal distension • Ascites Abdominal masses • Omental caking Pleural effusion Nodal metastasis • Difficulty of breathing • Inguinal and supraclavicular nodes Toralba et. al., Ovarian Cancer: Diagnosis, Staging and Management, 2010 Annual Powerpoint Templates Page 50 Postgraduate Course What ancillary procedure will we request ? • • • • • Transvaginal ultrasound Whole abdominal ultrasound Doppler studies Whole abdominal CT scan MRI De los Reyes, et. al. Pelvo-abdominal Mass: Diagnosis and Management, JRRMMC Powerpoint Templates Page 51 2010 Annual Postgraduate Course , July 2010 Ultrasound in Ovarian Neoplasm • Useful in discriminating benign from malignant adnexal masses • Detects earliest possible architectural changes in the ovary • Assessment include both ovarian volume and morphology Powerpoint Templates Page 52 Role of UTZ in Ovarian Neoplasm – Morphological parameters used: • • • • • • • Complex cysts Septations Loculations Papillary projections Irregular cyst walls Echogenicity Ascites Powerpoint Templates Page 53 E.G. 53 yo G4P3 (3103) Whole abdominal UTZ • Ascites, seen in the perihepatic, perispleenic, paracolic and pelvic region • Large pelvo-abdominal cystic mass: a large multiloculated mass in the midpelvic abdomen seen above the urinary bladder which measures 8.6 x 9.0 x 8.7 cm Powerpoint Templates Page 54 Color flow Doppler • Uses altered blood flow patterns to differentiate malignant from physiologic and benign lesions • Neovascularization: an obligate early event in tumor growth and neoplasia • Malignancy = RI <0.4 or 0.6 Powerpoint Templates Page 55 CT scan in Ovarian Cancer Suspect • Helpful in identifying the extent of clinical disease » Togashi K. Eur, 2008 • 70-90% accurate in pre-operative staging of ovarian cancer » Brislow et.al Cancer • Preferably w/ contrast » Togashi K. Eur, 2008 Powerpoint Templates Page 56 CT scan in Ovarian Cancer Suspect • Currently: – Detect recurrent or persistent ovarian cancer – Monitor tumor response to subsequent therapy Powerpoint Templates Page 57 E.G. 53 yo G4P3 (3103) Whole abdominal CT scan • Pelvo-abdominal mass t/c ovarian new growth: huge multiloculated mass noted in the midline extending to the left hemiabdomen approximately measuring 18.39 x 11.31 x 16.08 cm. Some locules contain anechoic fluid while some contain very fine scattered echoes. Locule walls with solid components but slightly thickened at 3-4 cm • The peritoneum outlined by anechoic fluid Powerpoint Templates Page 58 MRI in Ovarian Cancer • Distinguish benign from malignant ovarian masses • Overall accuracy rate = 93% Powerpoint Templates Page 59 What tumor markers will we request ? • • • • • • CA 125 HE 4 CEA AFP hCG CA 19-9 Powerpoint Templates Page 60 E.G. 53 yo G4P3 (3103) CA 125 CEA •143 U/mL •(<35 U/mL) •4.41 ng/mL •(2.5 ng/mL) Powerpoint Templates Page 61 CA 125 • Is expressed in approximately 80% of ovarian epithelial cancers but less frequently by mucinous types • Postmenopausal patients w/ an adnexal mass and high serum CA 125 level (>95 U/mL) there is a 96% positive predictive value for malignancy Templates Di Saia PJ, Creasman WT, Clin Powerpoint Gynecol Onco, 7th ed, 2007 Page 62 CEA • Negative in all normal ovarian tissue • Most frequently positive in mucinous cancer (70-80 %) • In serous tumor, CEA is much less frequent positive (20 %) • Endometriod Ca, Brenner tumor are also frequently CEA positive • Clear cell carcinoma is less frequently CEA positive Powerpoint Templates 5th Edition of Clinical Practice Guidelines , SGOP (August 2008) Page 63 Other ancillary procedure? • CXR • Colonoscopy • Routine hematologic and chemical assessments Powerpoint Templates Page 64 What is the role of paracentesis? • to relieve abdominal pressure from ascites • to diagnose spontaneous bacterial peritonitis and other infections (e.g. abdominal TB) • to diagnose metastatic cancer • to diagnose blood in peritoneal space in trauma McVay PA, Toy PT (1991). "Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities". Transfusion 31 (2): 164–71. doi:10.1046/j.1537-2995.1991.31291142949.x. PMID 1996485. Powerpoint Templates Page 65 Ginès P, Cárdenas A, Arroyo V, Rodés J (2004). "Management of cirrhosis and ascites". N. Engl. J. Med. 350 (16): 1646–54. doi:10.1056/NEJMra035021. PMID 15084697. E.G. 53 yo G4P3 (3103) Ascitic fluid analysis Chemical Analysis Albumin 5.317 mg/dL RBC Count 204/cu.mm Fresh RBC 61% Cell Count Crenated RBC 39% WBC Count 56/cu.mm Diff count: Segmenters 15% Lymphocytes 73% Monocytes 12% Powerpoint Templates Cytology – Ascitic fluid smears show many lymphocytes, macrophages and mesothelial cells with few cultures of atypical cells suspicious for adenocarcinoma Page 66 Surgery-Specific Risk High risk: cardiac risk often > 5% Aortic repair (aneurysmal, dissection) Noncarotid major vascular (infrainguinal and intraabdominal) Peripheral vascular surgery Anticipated prolonged surgical procedures with large fluid shifts and/or blood loss Major emergency procedures, particularly in the elderly Intermediate risk: cardiac risk generally < 5% Major intraabdominal (nonvascular) Intrathoracic (nonendoscopic) Major orthopedic Carotid endarterectomy Major head and neck Radical prostatectomy Low risk: cardiac risk generally < 1% Opthalmologic (excluding prolonged retinal) Minor head and neck Minor prostate (such as cystoscopy or TURP) Biopsies and superficial procedures ACC/AHA Guideline Update for Perioperative Cardiovascular Evaluation for Noncardiac Surgery—Executive Templates Page 67 Summary A Report of the American CollegePowerpoint of Cardiology/American Heart Association Task Force on Practice Guidelines, 2002; 105: 1257-1267 Clinical criteria for high-risk surgical patients used by Shoemaker and colleagues and adapted by Boyd and colleagues Previous severe cardiorespiratory illness- MI, COPD, Stroke Late stage vascular disease involving aorta Age > 70 years with limited physiological reserve in one or more vital organs Extensive surgery for carcinoma Acute abdominal catastrophe with haemodynamic instability (e.g. peritonitis, perforated viscus, pancreatitis) Acute massive blood loss > 8 units Septicaemia Positive blood culture or septic focus Respiratory failure: PaO2 < 8.0 kPa on FIO2 > 0.4 or mechanical ventilation > 48 hours Acute renal failure: urea > 20 mmol/l or creatinine > 260 mmol/l O Boyd et.al. The General Intensive Care Unit, The Royal Sussex County Hospital, Crit Care. 2005; 9(4): 390– Powerpoint Templates Page 68 396., Brighton, UK Tote S P , Grounds R M Br. J. Anaesth. 2006;97:4-11 • Primary cytoreductive surgery – When performing surgery in women with ovarian cancer, whether before chemotherapy or after neoadjuvant chemotherapy, the objective should be complete resection of all macroscopic disease [Based on limited, contradictory evidence from two Cochrane systematic reviews and two small randomised controlled trials] Page C. Redman et. Al. Recognition and initialPowerpoint management Templates of ovarian cancer: summary of NICE guidance BMJ 2011; 342:d2073 doi: 10.1136/bmj.d2073 (Published 21 April 2011) 69 • The aim of surgery in earlier years was optimal debulking with residual disease up to 1 cm after surgery – Meta-analysis involving 3 prospective RCT w/ > 3,000 patients showed that there is still significant benefit for residuals up to 1 cm compared w/ larger remaining tumor masses, but the largest benefit could be reached by complete resection Toralba et. al., Ovarian Cancer: Diagnosis, Staging and Management, 2010 Annual Powerpoint Templates Page 70 Postgraduate Course Amount of Residual Median Survival 95% Confidence interval No visible residual tumor 99.1 months 83.5 Residual tumor 110mm 36.2 months 34.6-39.4 Larger than 10 mm 29.6 months 27.4-32.2 Toralba et. al., Ovarian Cancer: Diagnosis, Staging and Management, 2010 Annual Powerpoint Templates Page 71 Postgraduate Course • Neoadjuvant chemoptherapy – Indications: • All Stage IV except patients with minimal pleural effusion or supraclavicular node involvement • Gross upper abdominal tumour on imaging • Clinically non-resectable pelvic disease • Significant and non-resectable retroperitoneal lymphadenopathy Page 72 Evidence Based Guidelines for the Powerpoint ManagementTemplates of Epithelial Ovarian Cancer – A WHO Initiative – Protocol • 3 cycles of platinum-based combination chemotherapy (CAP or Platinum-Taxane) • Interval cytoreductive surgery w/in 3-4 weeks of completing the 3rd treatment cycle • The aim is to remove all macroscopic tumor • 3 further post-operative treatment cycles Powerpoint Templates Page 73 WHO Evidence Based Guidelines for the Management of Epithelial Ovarian Cancer – European Organization Research & Treatment for Cancer (EORTC) trial: • 3 cycles of neoadjuvant chemotherapy followed by surgery and further 3 postoperative cycles in Stage IIC-IV ovarian cancer were 719 patients were randomized • Rate of optimal debulking was low at initial surgery (48%) and was increased to (83%) after interval debulking • Lower rate of peri-operative complications in the interval debulking arm and better overall performance Powerpoint Templates Toralba et. al., Ovarian Cancer: Diagnosis, Staging and Management, 2010 Annual Page 74 Postgraduate Course • First-line chemotherapy consist of platinum (cisplatin or carboplatin) in combination w/ paclitaxel • The combination are generally well tolerated even at full doses of both drugs. Shorter infusion of paclitaxel (< 3 hours) is better tolerated hematologically but w/ increased risk of arthralgiamyalgia & neuropathy Bookman MA. Trials with Impact on Clinical Management First Line. Int J Gynecol Cancer 2009; 19: Powerpoint Templates Page 75 S55-S65 • Phase III trial by GOG-158 – Carboplatin/paclitaxel treatment offered efficacy comparable w/ that of cisplatin/paclitaxel but did not exhibit the cumulative nephrotoxicity associated with cisplatin therapy Dunton et. al. Management of Treatment related Toxicity in Advanced Ovarian Cancer, The Powerpoint Templates Page 76 Oncologist, 2002 • International Collaborative Ovarian Neoplasm Group studies – Use of Carboplatin as a single agent was an acceptable alternative first-line therapy for patients w/ advanced ovarian cancer Dunton et. al. Management of Treatment related Toxicity in Advanced Ovarian Cancer, The Powerpoint Templates Page 77 Oncologist, 2002 • Myelosuppression is the main toxicity associated with carboplatin, there is also a significant risk of neurotoxicity and hypersensitivity reactions • Cleveland Clinic Cancer Center – reported that hypersensitivity to carboplatin developed in 12% of carboplatin-treated patients Markman M, Kennedy A, Webster K et al. Clinical features of hypersensitivity reactions Powerpoint Templates Page 78 to carboplatin. J Clin Oncol 1999;17:1141, The Oncologist 2002 • Paclitaxel exhibits high antitumor activity when used in combination w/ carboplatin • The use maybe limited by cumulative peripheral neuropathy • The acute dose-limiting toxicity is granulocytopenia • Others: alopecia, nausea, vomiting, diarrhea, mucositis, and hypersensitivity Muggia FM, Braly PS, Brady MF et al. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study.79 J Powerpoint Templates Page Clin Oncol 2000;18:106–115. • Prophylactic treatment with steroids and antihistamines and a slow infusion rate may minimize this risk, although fatal anaphylaxis has still been reported despite these precautions • As a consequence, patients should be closely monitored during all courses of cisplatin or carboplatin/ paclitaxel therapy Zweizig S, Roman LD, Muderspach LI. Death from anaphylaxis to cisplatin: a case report. Gynecol Oncol 1994;53:121–122. Onoyama Y, Umezu T, Kuriaki Y et al. Hypersensitivity reactions to cisplatin following multiple uncomplicated Powerpoint Templates Page courses: a report on two cases. J Obstet Gynaecol Res 1997;23:347–352. 80 • The odds of achieving a complete response following first line treatment are only about 5%. • The duration of this complete response is usually less than 6 months. • The possibility of cure is unknown, but is probably only a percentage point at most. • The odds of cure if the second line treatment does not work are too low to calculate. William M. Rich, M.D., Clinical Professor of Obstetrics and Gynecology, University of California, San Francisco, Director of Gynecologic Oncology, University Medical Center Powerpoint Templates Page 81 Fresno, California • Laparoscopic assesment is ideal/optional approach to all suspicious adnexal mass identified as: – has complex morphology on imaging – Associated w/ normal or mildly elevated CA 125 Powerpoint Templates Page 82 WHO Evidence Based Guidelines for the Management of Epithelial Ovarian Cancer • Progress in laparoscopy for ovarian cancer has been considerably slow – Rare chance of early diagnosis for ovarian cancer – Concern for overall oncological safety including the risk of tumor seeding – Higher rate of capsular rupture Ghezzi F, Cromi A, Siesto G, et al. Laparoscopy Staging of Early Ovarian Cancer Our Experience Powerpoint Templates Page 83 and Review of the Literature. Int Gynecol Cancer 2009; 19:S7-S13 Follow-up • Every 3 months for 4 visits, every 4 months for 3 visits, every 6 months for 6 visits, then annually • Determination of appropriate tumor markers every visit • TVS +/- Doppler studies every 4-6 months De los Reyes, et. al. Pelvo-abdominal Mass: Diagnosis and Management, JRRMMC Powerpoint Templates Page 84 2010 Annual Postgraduate Course , July 2010 Follow-up • CXR if indicated by signs and symptoms • Annual MRI or CT scan for the first 3 years post-treatment is recommended or when indicated De los Reyes, et. al. Pelvo-abdominal Mass: Diagnosis and Management, JRRMMC Powerpoint Templates Page 85 2010 Annual Postgraduate Course , July 2010 Summary Powerpoint Templates Page 86 1⁰ Preventive measures: 1. BSO is the preventive measure of choice for women w/ known germline mutation in BRCA 1 or BRCA 2 2. OCP confers long-term protection against ovarian CA 3. Analgesics such as aspirin, NSAIDS, acetaminophen are potential chemopreventive agents for ovarian CA 4. Increasing parity reduces the risk of EOC 5. Lactation confers protection against ovarian cancer risk most significant with duration of 18 months or more Powerpoint Templates CPG for the OB-GYN, SGOP, Nov. 2010 Page 87 1⁰ Preventive measures: 6. Tubal ligation confers a reduction in the risk for ovarian cancer 7. Carotenoids significantly protect against ovarian CA, either as food or as supplements 8. The consumption of tea may reduce the risk of EOC 9. Recreational physical activity confers at best a week to modest protection against EOC Powerpoint Templates CPG for the OB-GYN, SGOP, Nov. 2010 Page 88 2⁰ Preventive measures: 1. For the general population, there is no evidence yet to support routine screening for ovarian cancer using pelvic exam, CA-125, TVS 2. Although there is the lack of evidence for routine screening among BRCA mutation carriers who have not undergone risk-reducing BSO, carriers are advised semi-annual screening using pelvic exam, CA-125, TVS Powerpoint Templates CPG for the OB-GYN, SGOP, Nov. 2010 Page 89 Conclusion • The outcome for women with ovarian cancer is generally poor • Most women have had symptoms for months before presentation, and as these are frequently non-specific, delays often occur between presentation and referral to a specialist. • Greater awareness of the disease and appropriate initial investigations are needed to enable earlier referral Powerpoint Templates Page 90 and optimum treatment. Powerpoint Free Powerpoint Templates Templates Page 91