Chemotherapy and Radiotherapy

1. Chemotherapy and Radiotherapy Dr. SuraFindakly MBChB, DGO, CABOG

2. Learning objectives: 1.Describe the clinical uses and evaluation parameters of chemotherapy. 2.Name the types of chemotherapeutic agents. 3.Identify side effects chemotherapy and its uses in different gynecological malignancies. 4.Recognize types of radiotherapy. 5.List side effects of radiotherapy and reproduce its uses in different gynecological malignancies.

3. principle of chemotherapy attain maximal therapeutic cytotoxic effects upon cancer cells without extreme toxicity to normal tissues.

4. Clinical uses of chemotherapy 1-Primary Therapy. first-line treatment. 2-Adjuvant Therapy. undergone primary surgical staging and cytoreduction but are known to be at high risk for the presence of micrometastases, and recurrence, or have persistent disease at the end of primary surgery. 3-Neoadjuvant Therapy. before cytoreductive surgery. 4-Salvage Therapy. recurrent disease after first-line chemotherapy.

5. Evaluation parameters defined by (WHO) 1-Complete Response. Disappearance of all evidence of disease for at least 1 month. 2-Partial Response. The reduction of each measurable lesion by at least 50% for at least 1 month 3-Stable Disease. Maintenance for each lesion of criteria less than those required for either a partial response or increasing disease. 4-progressive Disease. Increase of a lesion by at least 25% or the appearance of a new lesion within 1 month.

6. Chemotherapeutic Agents *Alkylating agents are cell cycle nonspecific. prevents DNA duplication. egCyclophosphamide *Antimetabolitesare similar in chemical structure to metabolites required by both normal and tumorous cells for cell division to occur.eg methotrexate. *Vinca alkaloids They bind to tubules, interfere with spindle formation. arrest of metaphase and inhibits mitosis.eg Vincrestine, vinblastine *Antitumor antibiotics have many different modes of action, including increasing cell membrane permeability, inhibiting DNA and RNA synthesis, and blocking DNA replication.

7. Common Side Effects of Chemotherapy 1-Local and dermal: alopecia (reversible) and photosensitivity, phlebitis, tissue necrosis. 2-Myelosuppression.(Neutropenia , Anemia, Thrombocytopenia) 3-Infections. the severity and duration of the neutropenia and integrity of mucous membranes and skin. Fever in a neutropenic patient is sufficient evidence of occult infection 4-Cardiac Side Effects Daunorubicin and doxorubicin irreversible cardiomyopathies: CHF, pleural effusions, heart dilation, and venous congestion. Paclitaxel (Taxol) may cause asymptomatic and transient and atypical chest pain during infusion. resolve with slowing of infusion. 5-PulmonarySide Effects Bleomycin sulfate may cause significant pulmonary fibrosis, lung examination , Pulmonary function tests baseline pulmonary capacity before the first dose, repeated as needed

8. Common Side Effects of Chemotherapy 6-Hepatic. Transient elevations in LFT 7.Gastrointestinal Stomatitis and mucositis …antimetabolites, methotrexate and paclitaxel. Nausea and vomiting. Diarrhea… nephrotoxicity or electrolyte disturbances. 8-Acute allergic reactionsetoposide.Bleomycin can cause anaphylaxis, skin reactions, fever, chills, and pulmonary fibrosis. 9.Genitourinary Hemorrhagic cystitiscyclophosphamide Nephrotoxicitycisplatin. Irreversible renal damage 10.Neurotoxicity. vinca alkaloids peripheral, central, and visceral neuropathies. Tinnitus or high-frequency hearing loss .. cisplatin

9. Chemotherapy in Gynecologic Cancers 1-Ovarian Cancerafter initial surgery. platinum (cisplatin , carboplatin) and paclitaxel in epithelial ovarian cancer. malignant germ cells: bleomycin, etoposide, and cisplatin (BEP) 2-Endometrial Canceradvanced or recurrent metastatic doxorubicin, platinum, and paclitaxel. 3-Cervical Cancerchemoradiation cisplatin or a combination of cisplatin and 5-FU

10. R adiotherapy kills cells by the use of ionizing radiation: • X -rays • g amma-rays • β -particles. can lead to breakage of DNA directly or indirectly via production of free radicals with curative and palliative intent

11. Delivery of radiotherapy Radiation may be given by external beam therapy and/or brachytherapy. 1. External beam therapy: • radiation is distant from the patient 2. Brachytherapy: • placement of radioactive source directly within or around the tumour site (e.g. intravaginal/ intrauterine brachytherapy for cervical cancer) • advantage —higher radiation dose to the tumour, lower exposure to normal tissue. • Side effects may be reduced by giving radiotherapy in divided doses so that normal tissues can recover. 3. Interstitial implants are another form of brachytherapy. Various sources of radiation may be configured as radioactive wires or seeds and placed directly within tissues. Hollow guide needles are to a target tumor volume. After the position of the guide needles is confirmed radiologically, they can be threaded with the radioactive sources and the hollow guides removed.

12. Toxicity of radiotherapy . The severity of normal tissue reaction to radiation depends on: total dose, dose fraction, treatment volume, and radiation energy. 1-Skin Toxicity. erythema, desquamation, and pruritus 2-Hematologic Toxicity. The volume of marrow irradiated and the total radiation dose determine the severity of myelosuppression 3-Gastrointestinal Toxicity Acute Complications. Nausea, vomiting, and diarrhea commonly occur 2 to 6 hours after abdominal or pelvic irradiation. Long-term Complications. Chronic diarrhea, obstruction (bowel adhesions), and fistula formation <1% of cases 4-Genitourinary Toxicity Cystitis: pain, urgency, hematuria, and urinary frequency. Vesicovaginal fistulas and ureteral strictures Vulvovaginitis:erythema, inflammation, mucosal atrophy, inelasticity, and vaginal ulcer. Adhesions and stenosis of the vagina ….Rx vaginal dilation

13. 1-Cervical Cancer Radiation therapy with curative intent uses both external-beam and intracavitary radiation. Palliative radiation for advanced cervical cancer may use either modality for control of bleeding, management of disease in the pelvis, and relief of pain. The goal of external irradiation in cervical cancer is to sterilize metastatic disease to pelvic lymph nodes and the parametria and/or to decrease the size of the cervix to allow optimal placement of intracavitary radioactive sources. Definitive radiation therapy is an acceptable alternative to radical surgery for women with early stage disease (stages IA, IB1, and nonbulky IIA). concurrent cisplatin-based chemotherapy The treatment volume for women undergoing adjuvant external radiation therapy usually involves the whole pelvis, with larger fields for patients with higher stage disease. Patients with known or suspected metastatic disease to periaortic lymph nodes may be considered for extended field irradiation

14. 2- Endometrial Cancer • after surgical staging : estimated risk recurrence • adnexal or pelvic metastases,involvement of lymphovascular space, grade 2 disease with invasion > 50% into the myometrium, or grade 3 disease with any amount of myometrial invasion: high risk of recurrenceadjuvant radiation therapy. • For high-risk disease confined to the uterus, whole-pelvic therapy or vaginal brachytherapymay be used. • For high-risk disease outside of the uterus but confined to the pelvis, whole-pelvis radiation with or without vaginal brachytherapyshould be employed. • Women with more extensive disease undergo extended-field radiation or whole-abdomen radiation. • Primary radiation therapy may be employed in women who are considered to be at high surgical risk, such as the elderly and those with significant comorbidities.

15. Ovarian &Vaginal Cancer 3-Ovarian Cancer: Radiotherapy controversial 4-Vaginal Cancer Radiotherapy : primary treatment for vaginal cancer. squamous cell carcinoma: whole-pelvic radiation therapy followed by intracavitary or interstitial brachytherapy. lesions involving the lower third of the vagina should have the inguinal and femoral lymph nodes included in the external-beam treatment field. Extended field radiation to include periaorticlymph nodes may be needed if imaging studies reveal bulky pelvic or periaorticdisease.

16. 5-Vulvar Cancer • squamous cell in origin. • the mainstay of treatment of stages I and II vulvar cancer is surgical, radical vulvectomy plus inguinal and pelvic lymphadenectomy. • Adjuvant radiation therapy benefits patients with close or positive surgical margins, as well as patients with positive inguinal lymph nodes. • In patients with vulvarsquamous cancer (stage III or IV) chemoradiationmay reduce the need for more radical surgery; primary pelvic exenteration.

17. SUMMARY: Knowing chemotherapy and radiotherapy types, side effects and its uses in different gynecological malignancies is important to prevent and treat complications of their use.

18. THANK YOU