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Role of the Naturopathic P hysician in Gynecological O ncology-Making a difference

Role of the Naturopathic P hysician in Gynecological O ncology-Making a difference. Naini Kohli, ND, FABNO Consultant, Naturopathic Oncology. Cancer Treatment Centers of America Eastern Regional Medical Center, Philadelphia, PA. Learning Objectives. Overview

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Role of the Naturopathic P hysician in Gynecological O ncology-Making a difference

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  1. Role of the Naturopathic Physician in Gynecological Oncology-Making a difference Naini Kohli, ND, FABNO Consultant, Naturopathic Oncology Cancer Treatment Centers of America Eastern Regional Medical Center, Philadelphia, PA Naini Kohli NYANP

  2. Learning Objectives • Overview • Naturopathic adjunctive management for specific gynecological cancers • Evidence-based life style and naturopathic strategies for prevention • Clinical pearls for supportive care and managing aftermath of treatment. Naini Kohli NYANP

  3. Gynecological Malignancies Naini Kohli NYANP

  4. 2015 projections for Gynecological Cancers Series 1 new cases Series 2 anticipated deaths Naini Kohli NYANP

  5. Endometrial Cancer • Most common cancer of the female reproductive organs. • Primarily a disease of postmenopausal women, 25% of cases occur in premenopausal patients, with 5% of cases in patients younger than 40 years • More common in white women, but more black women die from it. • There are over 600,000 women who are survivors of this cancer. Naini Kohli NYANP

  6. Predisposing factors • Exposure to high circulating levels of estrogens with low levels of progestogens. • 25% decline in mortality in last 30 years due to decreased use of unopposed estrogens. • Infertility, obesity, dysfunctional bleeding due to anovulation and patients with granulosa theca cell ovarian tumors are at high risk. • Diabetes mellitus, cigarette smoking, and less physical activity are related risk factors. • Tamoxifen use has been reported to increases endometrial cancer by 10%. • HNPCC increases risk by 20% Naini Kohli NYANP

  7. Signs and Symptoms Postmenopausal women • 90% of patients complain of abnormal vaginal discharge, and 80% of these women experience abnormal bleeding. • 15% of postmenopausal women presenting with abnormal bleeding will be found to have endometrial carcinoma. • Signs and symptoms of more advanced disease include pelvic pressure and other symptoms indicative of uterine enlargement or extra uterine tumor spread. • Premenopausal women • The diagnosis of endometrial cancer may be difficult to make in premenopausal patients. The physician must maintain a high index of suspicion in this group of patients and perform endometrial sampling in any women who complain of prolonged, heavy menstrual periods or inter menstrual spotting Naini Kohli NYANP

  8. Diagnosis • Trans vaginal Ultra sound (TVS) endometrial thickness • Endometrial biopsy • Pre-op work-up CT/MRI • Staging – surgical / histological / nodes Naini Kohli NYANP

  9. Treatment options-ASCO Guidelines Naini Kohli NYANP

  10. Chemotherapy Options Combination • Carboplatin +Paclitaxel • Doxorubicin+Cyclophosphamide • Doxorubicin+Cisplatin • Doxorubicin+Paclitaxel • Doxorubicin+Paclitaxel+Cisplatin+ Filgrastin • Cyclophosphamide + Cisplatin +Doxorubicin • Paclitaxel+Ifosfamide • Gemcitabine+ Cisplatin Single agent • Doxorubicin • Megestrol • Paclitaxel • Topotecan Naini Kohli NYANP

  11. Ovarian cancer-Epidemiology • Fifth leading cause of cancer deaths among womenand has the highest mortality rate among all female reproductive cancers. • Primarily a disease of post menopausal women, mostly 50-75 years with a peak at 61.5 per 100,000 women aged 75-79 years. • Whites > Hispanic > Native American > Black > Asians and Pacific Islanders • Highest rate in industrialized nations and lowest in under developed nationsexcept Japan- incidence is 3 per 100,000 Naini Kohli NYANP

  12. Inherited mutations in BRCA1 and BRCA2 increase the risk for ovarian and breast cancers. Though are more common among women of Ashkenazi Jewish ancestry, they are not restricted to this population and can occur in women of any ethnicity. • Women with a BRCA1 mutation have about a 40% lifetime risk for ovarian cancer. whereas with a BRCA2 mutation the risk is about 10 – 20% (Lifetime ovarian cancer risk for women in the general public is about 1.4%.) • HNPCC. Women who have genetic mutations associated with hereditary non-polyposis colorectal cancer (HNPCC) have about a 12% lifetime risk of developing ovarian cancer Naini Kohli NYANP

  13. Ovarian Screening Methods for Average-Risk Women Transvaginal ultrasound: poor sensitivity in early-stage disease, cannot reliably distinguish benign from malignant changes. CA-125: poor sensitivity in early stage disease Pelvic exam Naini Kohli NYANP clinicaloptions.com/oncology

  14. Primary treatment • Optimal cytoreduction or debulking • Residual tumor deposits should be less than 1 cm in size. • Patients with optimally debulked disease have better chances of achieving complete clinical response to chemotherapy Naini Kohli NYANP

  15. Standard of Care- 2006 • Maximum attempt at surgical cytoreduction • Chemotherapy following surgery • Regimen of choice Paclitaxel 175 mg/m2/3h , Carboplatin AUC 6-7.5 Repeat every 3 weeks x 6 cycles Intravenous (IV) with Intraperitoneal (IP) has been shown to give better results in Stage 3 and 4 patients Naini Kohli NYANP

  16. Response Rate after Relapse Naini Kohli NYANP

  17. Additional chemotherapy agents following failure of Cisplatin or Carboplatin with Paclitaxel or Docetaxel • Doxorubicin (Doxil) • Gemcitabine(Gemzar) • Topotecan • Etoposide • Pemetrexel • Bevacizumab(Avastin) Naini Kohli NYANP

  18. Cervical cancer • Cervical cancer was once one of the most common causes of cancer death for American women • Now gone down by more than 50% due to increased use of the Pap test and later on the introduction of the HPV vaccine. • Currently, an estimated 249,496 women are living with cervical cancer in the United States. Naini Kohli NYANP

  19. Pre disposing factors • Disease of midlife, most cases are found in women younger than 50. It rarely develops before age of 20. • Hispanic women are most likely to get cervical cancer, followed by African-Americans, Asians and Pacific Islanders, and whites. • American Indians and Alaskan natives have the lowest risk of cervical cancer in this country. Naini Kohli NYANP

  20. Updated Cervical Cancer Screening Guidelines • Cervical cancer screening every 2 years - age 21-30 years. • 30 and older with three consecutive normal Pap tests can be screened every three years. • Women with risk factors like HIV positivity; immunosuppression; DES exposure in utero; or history of treatment for cervical intraepithelial neoplasia (CIN) 2, CIN 3, or cervical cancer may need to be screened more frequently. • Women who have had a total hysterectomy for benign conditions can stop being screened for cervical cancer unless they have a history of high-grade CIN. Naini Kohli NYANP

  21. ACOG notes that women may be able to stop cervical cancer screening at age 65 or 70 if they’ve had three or more normal Pap results in a row and no abnormal Pap in the previous ten years. • Women at high-risk of cervical cancer may need to continue screening beyond this age. • Women who have been vaccinated against human papillomavirus (HPV) should follow the same screening guidelines as unvaccinated women. Naini Kohli NYANP

  22. Natural history of cervical carcinogenesis • Premalignant changes form a continuum from low to high grade SIL or cervical, vaginal or vulvar intraepithelial neoplasia 1,2 or 3. • These lesions can persist, progress or regress. • Family history, HPV, cigarette smoking and nutrient deficiencies may be contributory • Inflammation, nutrition and other viruses are likely to be involved in affecting the outcome. • 90% of cancers are squamous and 10% adenocarcinomas Naini Kohli NYANP

  23. Risk factors CIN Multiple sexual partners HPV, HIV Smoking Signs and symptoms • Post coital bleed, Intermenstrual bleed • Discharge , Post menstrual bleeding . • Ulcer /mass .visible / palpable • Late stage – organ symptomss/ mass Naini Kohli NYANP

  24. Diagnosis • Biopsy • Staging – Clinical / Histological • Pre-op work-up • EUA / Cystoscopy / CT / IVP Naini Kohli NYANP

  25. Management • Ia1Microinvasion-Cone biopsy which could be diagnostic or therapeutic • I – IIa Surgery / Radiotherapy • Advanced , Radiotherapy, chemotherapy • Prognosis overall 65% 5 year Naini Kohli NYANP

  26. Chemotherapy Combination Single • Cisplatin and XRT • Cisplatin and Topotecan • Bleomycin, Ifosamide,mesna and cisplatin/carboplatin(BIP/BIC) • Cisplatin and 5 FU/ vinorelebine/Irinotecan?gemcitabine • Carboplatin, Taxotere( Docetaxel) • Paclitaxel • Docetaxel • Irinotecan • Topotecan • Pemetrexel Naini Kohli NYANP

  27. Vulvar cancer • Accounts for 4% of cancers of the female reproductive organ malignancies and 0.6% of all cancers in women. • Average American woman has 1 in 333 chance of developing vulvar cancer at some point in life. • Predominantly a disease of postmenopausal women. • Ninety percent of cancers are squamous in origin, while melanomas, adenocarcinomas, basal cell carcinomas, verrucous carcinomas, sarcomas, and other rare malignancies also occur. Naini Kohli NYANP

  28. Commonly site is the labia majora but the labia minorabut may occur in clitoris, and perineum. • Vulvar intraepithelial neoplasia (VIN) III is a precursor lesion in some patients, and should be effectively treated by superficial excision, with or without laser therapy, when diagnosed (Jones & Rowan, 1994; Herod et al, 1996). • Treatment of invasive vulvar cancer needs an individualized multidisciplinary approach,. Naini Kohli NYANP

  29. Investigations to assist diagnosis include: • Pap smear of the cervix to rule out Carcinoma insitu • Colposcopy of the cervix and vagina because of the common association with other squamous intraepithelial lesions • CT-scan of the pelvis and groins is often helpful to detect any enlarged lymph nodes in the groins or pelvis, particularly in the presence of palpable groin nodes • Routine full blood count, biochemical profile and chest x-ray (CXR) pre-operatively Naini Kohli NYANP

  30. Treatment • Wide local excision • Radical vulvectomy • Bilat groin lymphadenectomy+/- radiotherapy • Prognosis I >90% 5yr, III/IV 40% 5 yrs Naini Kohli NYANP

  31. Vaginal Cancer • Only about 1 of every 1,100 women will develop vaginal cancer in her lifetime • Age > 60 years • No specific risk factors • 95% squamous • Signs and Symptoms Pruritus , bleeding , discharge Ulcer , Mass, Inguinal lymphadenopathy Naini Kohli NYANP

  32. Diagnosis • Biopsy • Staging – surgical / histological • Pre-op work-up Naini Kohli NYANP

  33. Preventing gynecological malignancies Naini Kohli NYANP

  34. Primary prevention became possible with identification of human papilloma virus and creation of virus like particles in the laboratory • 20 different types have been isolated and implicated in vaginal, vulvar and oral cancers. • Majority of cervical cancers are caused by types 16 and 18. • Prophylactic vaccination has transformed the prospects for reducing the incidence of this disease on a global scale, achieving more than 98% protection in randomized clinical trials against precursor lesions such as CIN grade 2/3 and adenocarcinoma in situ Naini Kohli NYANP

  35. Gardasil is a quadrivalent vaccine approved by the FDA in 2006 for prophylactic vaccination in girls and women aged 9 to 26 years,ableto trigger an antibody response against the HPV types represented in the vaccine. • Cervarix is a bivalent vaccine also approved by the FDA to prevent cervical dysplasia and cervical cancer caused by HPV types 16 and 18 • CDC recommends 3 doses for all females aged 11-26 years at 0, 2 and 6 months • A novel vaccine that covers five additional subtypes of HPV (31, 33, 45, 52, and 58) in addition to the 6, 11, 16, and 18, has completed phase III testing. Naini Kohli NYANP

  36. Manipulating Estrogen metabolic pathways • Increasing the ratio of 2 Hydroxyestrone and 16 alpha-hydroxyestrone. • Indoles ( DIM, I3C, Sulphoraphane) • Flavonoids Bazzan et al. Journal of Translational Medicine 2013, 11:252 Page 3 of 4 http://www.translational-medicine.com/content/11/1/252 Naini Kohli NYANP

  37. Retinoids • Vitamin A (natural),synthetic derivative –fenretinoid( 4 OH fenretinamid or 4FHR) • Control cell growth and differentiation at the level of gene expression through interaction with nuclear receptors • Inhibit proliferation, progression, induce terminal differentiation and stimulate intracellular communication • 13 cis retinoic acid has been shown to reverse or suppress oral leukoplakia and second primaries of the upper aero digestive tract. • Topical tretinoin 0.372% has been shown to reverse low grade uterine cervical moderate dysplasia in a randomized clinical trial. Naini Kohli NYANP

  38. Side effects • Beware of potential dose related toxicity • Tend to accumulate in the liver and cause hepatic damage • Eye damage • Most relevant to prevention of gynecological cancers is that they are teratogens Naini Kohli NYANP

  39. Anti-oxidants • Carcinogen blocking agents act by preventing conversion of a procarcinogen into an active carcinogen- eg. inhibition of nitrosocarcingen formation by ascorbic acid, alpha tocopherol and the phenols. • Agents enhancing phase 2 carcinogen detoxifying enzymes including glutathione S transferase Naini Kohli NYANP

  40. Naini Kohli NYANP

  41. Prevention of Ovarian Cancer • Chemoprevention • Oral contraceptive pills • Limit clomiphene citrate • Surgical prevention • Oophorectomy: 80% risk reduction in high-risk women[1] • Bilateral tubal ligation: 72% risk reduction when used with oral contraception[2] 1. Finch A, et al. JAMA. 2006;296:185-192.2. Narod SA, et al. Lancet. 2001;357:1467-1470. Naini Kohli NYANP clinicaloptions.com/oncology

  42. Ovarian Cancer and Green Tea • No experimental human study assessing the effects of green tea in EOC progression is available • Post-diagnosis green tea intake with EOC progression 1observational cohort study. • Post-diagnostic tea intake and 3-year survival was assessed in 244 women with EOC. • Compared to non-drinkers, women who drank more than one cup of tea daily after EOC diagnosis had a lower risk of mortality (HR: 0.43, 95% CI: [0.20; 0.92]) when standard risk factors for EOC progression were taken into account. Naini Kohli NYANP

  43. 10 year Meta-analysis of the correlation between drinking green tea and the risk of female ovarian tumors . • 6 case control studies and cohort studies with 9113 participants, 3842 cases, and 5271 control cases were included. • Drinking green tea was found to decrease the risk of ovarian cancer (odds ratio = 0.81; 95% confidence interval = 0.73-0.89; P < .0001). Naini Kohli NYANP

  44. Green tea and prevention Naini Kohli NYANP

  45. Mainly focuses on supporting healing and repair Radiation sensitization Side effect management Immune support Side effect management Immune support Improving effectiveness Dealing with sequel of treatments QOL issues Secondary prevention Naini Kohli NYANP

  46. Evidence based naturopathic strategies- areas of focus Naini Kohli NYANP

  47. General surgical support • Good multi-vitamin and mineral formula • Arnica • Modified Citrus Pectin • Probiotics • Adaptogenicherbs after surgery to help with recovery Naini Kohli NYANP

  48. Side effects of chemotherapy Nausea • Ginger encourages movement through the bowels while decreasing intestinal spasm • Digest Dis Sci 2005 Oct 1;50(10) • Treatment of nausea with use of ginger root produced similar results as compared to a popular anti-nausea medication • J Ethnopharmacol.1998 Aug;62(1):49-55. • Reduced nausea in women receiving Cisplatin for gynecologic cancers.Ryu SY, et. Al. Major clinical research advances in gynecologic cancer 2009. J GynecolOncol. 2009 Dec;20(4):203-9. • Peppermint essential oil (Lua PL, Zakaria NS. J Altern Complement Med. 2012.) Naini Kohli NYANP

  49. IVC • Reduction in treatment related toxicity with paclitaxel/carboplatin + IVC (13 patients) vs. standard treatment alone (12 patients). • Patients were followed for 5 years. • Overall survival tended toward improvement .(median time to progression was 8.75 months longer in the Cp+Pax+IVC arm than in the Cp+Pax arm. These results did not achieve statistical significance because the study was not statistically powered to detect efficacy. Naini Kohli NYANP

  50. Cisplatin Vinca alkaloids Dorsal root ganglion Chemotherapy induced Peripheral neuropathy- sites of action. Taxanes- Stocking & glove distribution & perioral numbness suggests DRG neuropathy Cisplatin- accumulates in DRG Carboplatin Oxaliplatin - – impairs voltage-gated sodium channels Vinca alkaloids- – mitotic inhibitor, impairs axonal transport & impairs regeneration – mixed motor, sensory & autonomic Naini Kohli NYANP

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