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Radiotherapy practices in GYN malignancies

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A brief overview of radiotherapy practices and practical guidelines in the management of Gynecological malignancies

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Radiotherapy practices in GYN malignancies

  1. 1. Radiotherapy Practices in Gynecological malignancies DR AJEET KUMAR GANDHI MD (AIIMS), DNB (GOLD MEDALIST) UICCF (MSKCC,USA) ASSISTANT PROFESSOR, RADIATION ONCOLOGY DR RMLIMS, LUCKNOW
  2. 2. Optimum radiotherapy utilization rates: Gynecological cancer Delaney G. Cancer 2004;101:671–92 Tumor Site Optimal utilization rate Carcinoma uterine cervix 55-60% Carcinoma endometrium 35-46% Carcinoma Vagina 90-100% Carcinoma Vulva 60%
  3. 3. Carcinoma Cervix
  4. 4. FIGO STAGING (2009)
  5. 5. Staging work up  Clinical examination including detailed Pelvic examination [under sedation/Anesthesia]  HMG/LFT/KFT  Chest X-Ray  Biopsy from the cervical growth  CECT Abdomen/Pelvis or CEMRI Abdomen/Pelvis  Cystoscopy and Sigmoidoscopy: Only in case of clinical or radiological suspicion of involvement  Bone Scan/CECT Chest [Optional]  Whole body PET-CT [Optional]
  6. 6. Management options: Early Cervical Cancers [Stage I-IIA]  Radical Surgery*  Radical RT  Radical CTRT  NACT  Radical Surgery*  BRT  Radical Surgery*  Concomitant Chemoradiation Adjuvant Hysterectomy * Adjuvant RT+/- CT
  7. 7. Management options: Early Cervical Cancers [Stage IA 1-2]  Surgery mainstay of treatment  Carcinoma in situ: [Multifocal CIS, CIS involving cervix and vagina, Recurrent CIS]  Equivalent LDR doses of 45-50 Gray at point A  Invasive [Medically In-operable patients/ Refusal to surgery]  Equivalent LDR doses of 60-75 Gray at Point A  HDR Brachytherapy alone :5- 7 Gray per # in 5-8#
  8. 8. Study Design Result Remarks Landoni F. Lancet 1997 IB-IIA (Surgery vs. RT) PORT added for high risk patients RCT 5 year DFS (83%),OS (74%) and recurrence rates (25- 26%) identical in both arms Increased morbidity in surgery arm [28% vs. 14%] Piver MS. Am J Clin Oncol 1988 IB (Surgery vs. RT) Non-RCT 5 Year DFS for Surgery vs. RT [92.3% vs. 91.1%] 5 Year OS rates equivalent Perez CA. IJROBP 1987 IB-IIA (RT vs. RT + Surgery) Stage IB: 5 Year DFS 80% vs. 82% Stage IIA: 5 year DFS 56% vs. 79% No difference in grade 2-3 complications NO study till date compares Surgery to CTRT (considered the standard of care now)!!! Management options: Early Cervical Cancers [Stage IB-IIA]
  9. 9. Management options: Early Cervical Cancers [Stage IB-IIA]  Usually a combined decision [Institutional policy, Waiting lists]  Surgery:  Young age  Not suitable for Chemotherapy  Anticipation for the need of PORT  Adenocarcinoma histology  Others: Pregnancy, associated uterine pathologies (pyometra, fibroid, pyosalpinx)  Chemoradiation:  Medically inoperable patients  Imaging s/o pelvic lymphadenopathy  Postmenopausal patients  Parametrium borderline positivity on clinical/imaging
  10. 10. Study Design Result Remarks Rotman M. IJROBP 2006 Sedlis A. Gynecol Oncol 1999 IB (Surgery f/b RT versus Observation) in intermediate risk patients (2 or more of DSI,LVSI, >4 cm) RCT Recurrence rates: 17% vs. 30.7% No difference in OS Song S. Gynecol Oncol 2012 Retrospective analysis of RT vs. CTRT in intermediate risk patients (n=110) 5 year RFS: 85% vs. 93.8% Significant decrease in pelvic recurrence (p=0.012); distant mets (p=0.027) Acute grade ¾ GI & Chronic toxicity not different Okazawa M. Int J Gynecol Cancer 2013 316 patients (stage IB1-IIB) 124: RT 192: CCRT High risk group: RT vs. CCRT 5 year PFS: 44.3% vs. 72%; 5 year OS: 59.1 vs. 78.2% (P=0.005) Intermediate risk: 5 year PFS: 77.5% vs. 90.2% (P=0.049); No difference in OS Management options: Early Cervical Cancers [Adjuvant treatment]
  11. 11. Adjuvant treatment: Early Cervical Cancer  Adjuvant RT:  Any 2 of the risk factors (Intermediate group): Deep stromal invasion, LVSI, Large tumor size >4 cm  Adjuvant CTRT:  Pelvic lymph node +ve, parametrial +ve, margin +ve  Radiation dose:  EBRT: 50.4 Gray/28#/5.5 weeks  Brachytherapy: Intra Vaginal Brachytherapy 8 Gray/ 2#
  12. 12. Carcinoma cervix following Inadvertent simple hysterectomy  Inadvertent versus Intentional  30% of patients with SH presents with gross residual disease*  Invasive tumor, gross residual tumor:  EBRT (50.4 Gray) preferably with Chemotherapy  f/b brachytherapy : Interstitial or Intravaginal *Sharma DN et al. Asian Pac J Cancer Prev 2011;12:1537–1541 **Saibish kumar et al. Int J Radiat Oncol Biol Phys 2005;63:828–833
  13. 13. Management options: Advanced Cervical Cancers [Stage IIB-IVA]  Concomitant Chemoradiation +BRT  Radical RT(EBRT + BRT)  NACT Concomitant Chemoradiation +BRT  Concomitant Chemoradiation +BRT  Adjuvant CT
  14. 14. Concurrent CRT Results of Meta-analyses  Vale et al ; JCO : 2008  18 trials, 4818 pts  CRT vs RT –  19% reduction in risk of death  absolute surv. benefit -6% at 5 yrs  absolute DFS benefit of 8% at 5 yrs  5yr loco-regional DFS – 9% benefit  5 yr survival benefit –  stage Ib –IIa – 10%  stage IIb – 7%  stage III-IVa – 3%  CRT (platinum vs non-platinum) – no difference  Cycle length or dose intensity of cisplatin – no difference
  15. 15. Definitive Extended field irradiation Author N Study Design Clinical Outcome Acute Toxicity (Grade 3-4) Varia MA et al* [GOG Study] 95 Pelvic + Para-Aortic Irradiation with concurrent Cisplatin + 5 FU The 3-year OS and PFI rate were 39% and 34%, Gastrointestinal: 18.6% & Hematological :15.1% William Small Jr et al #[RTOG 0116 Study] 26 Pelvic + Para-Aortic Irradiation with concurrent Cisplatin weekly Estimated disease- free and overall survival at 18 months are 46% and 60%. The acute Grade 3/4 toxicity rate, excluding Grade 3 leukopenia was 81%. Late Grade 3/4 toxicity was 40%. *Int. J. Radiation Oncology Biol. Phys., Vol. 42, No. 5, pp. 1015–1023, 1998 #Int. J. Radiation Oncology Biol. Phys., Vol. 68, No. 4, pp. 1081–1087, 2007
  16. 16. Dose and fractionation: EBRT  EBRT:  50.40 Gy/28#/5.5 weeks [No MLS]  Concurrent chemotherapy* (Cisplatin 40 mg/m2) *Avoid in selected cases (non functioning kidney, poor PS)
  17. 17. Dose and fractionation: Brachytherapy  Brachytherapy:  ICRT: 7 Gy/3#/3 weeks  ISBT: 8-10 Gray/2#/2 weeks  Indications of ISBT: • Distorted anatomy/non-negotiable OS • Distal vaginal involvement • Bulky parametrial disease • Cervical stump carcinoma and vault recurrence
  18. 18. Definitive extended field CTRT  45 Gray/25#/5 weeks with concurrent cisplatin*  Boost (10 Gray) to pelvic or para- aortic lymph nodes as required  Brachytherapy: ICRT: 7 Gy/3#/3 weeks ISBT: 8-10 Gray/2#/2 weeks *Selected patients
  19. 19. Recurrent carcinoma cervix  Loco-regional failure after previous surgery (no radiotherapy):  EBRT (45-50 Gray) with concurrent chemotherapy->BRT  After definitive radiotherapy:  Surgery (central recurrences) +/- IORT  Re-irradiation: EBRT 36-45 Gray-> BRT (ISBT 15-20 Gray in 3-5#)  Chemotherapy f/b Reirradiation  Isolated Para-aortic recurrences:  EBRT 45-50 Gray with/without concurrent chemotherapy
  20. 20. Haemostatic & Palliative RT in carcinoma cervix  EBRT  20-30 Gray in 5-10 fractions  Brachytherapy  Haemostatic ICRT/ Ovoid: 8-10 Gray
  21. 21. Treatment Overview Early Stage Carcinoma Cervix Stage I A1-2 Stage I B-IIA Surgery Brachytherapy+/- EBRT Surgery (Adjuvant RT/CTRT) CTRT (50.4 Gray/28#/5.5 weeks-> BRT)
  22. 22. Treatment Overview Late stage Ca Cervix Stage IIB-IIIB Stage IV Radiotherapy ± Chemo *Stage IVA Stage IVB EBRT + Brachytherapy (ICRT/ISBT) [50.4 Gray/28#/5.5 weeks with concurrent cisplatin 40 mg/m2] *Selected cases Palliative RT Palliative CT
  23. 23. Carcinoma Endometrium
  24. 24. FIGO STAGING 2009
  25. 25. WORK-UP  Hemogram, LFT, KFT  Chest X-ray  Endometrial biopsy or aspiration curettage  Imaging: TVS/ CT scan/ MRI of abdomen & pelvis  Optional  Cystoscopy , procto-sigmoidoscopy  Whole body PET CT
  26. 26. EARLY ENDOMETRIAL CANCER-RISK STRATIFICATION  FIGO 2009 Stage I EC  Risk factors for cancer recurrence in Stage I  >1/2 myometrial invasion  Grade 3  Risk grouping  High (both risk factors)  Intermediate (any one risk factor)  Low (grade1/2 with <50% myoinvasion) Other risk factors: Age >60 years LVSI
  27. 27. Adjuvant RT: Stage I Endometrial Carcinoma
  28. 28. Current Protocol: Operated G I G II G III IA Observation Observation Observation or IVBT* IB IVBT EBRT+ IVBT EBRT+ IVBT II EBRT + IVBT III EBRT + IVBT + Chemotherapy *Adverse risk Factors [Myoinvasion, Age >60 years, LVSI] ** Stage IV: Palliative RT/ Chemotherapy
  29. 29. Dose Practices: Post -op EBRT doses  45 Gray in 25# over 5 weeks (stage I)  50.4 Gray in 28# over 5.5 weeks (stage II-III)  45-50.4 Gray (Medically in-operable case) Brachytherapy alone  7 Gy X 3 sessions, each 1 week apart. Brachytherapy in Combination with EBRT  6 Gy X 2 sessions 1 week apart Chemotherapy (Stage III)  Sandwich/Sequential 6 cycles of chemotherapy (Paclitaxel/Carboplatin)
  30. 30. Uterine Sarcomas
  31. 31. FIGO 2009 Staging for LMS and ESS FIGO staging for uterine sarcoma. Int J Gynaecol Obstet 2009;104:179
  32. 32. FIGO 2009 Staging Adenosarcoma FIGO staging for uterine sarcoma. Int J Gynaecol Obstet 2009;104:179 Carcinosarcoma is staged according to the FIGO staging for endometrial adenocarcinoma
  33. 33.  Adjuvant radiotherapy  Carcinosarcoma ( staged and treated as endometrial adenocarcinoma)  Leiomyosarcoma: Stage II-IVA  ESS: Stage II-IVA  Undifferentiated endometrial sarcoma: stage I-IVA Reed N.S et al, European J of Cancer 44(2008) 808-818 Sampath S et al, Int J Rad Oncol Bio. Phys,76;3:728 Role of pelvic radiotherapy
  34. 34.  Not well defined  Our practice: IVBT (same as endometrial cancers) Brachytherapy in uterine sarcoma
  35. 35. Follow up policy: Cervix & Endometrium  First visit : 1 months after completion of brachytherapy [Clinical examination]  Second visit: 3 months [Clinical examination + pap smear]  Third visit: 6 months [Clinical + CECT abdomen/pelvis]  6 monthly till 2 years  Yearly follow up thereafter
  36. 36. Carcinoma Vulva
  37. 37. STAGING :FIGO 2009
  38. 38. WORK UP AND EVALUATION  Pelvic Examination preferably under GA.  Biopsy from primary vulval lesion and also from the nodes if clinically or radiologically visible.  Hemogram/LFTs/KFTs/HIV serology  Chest X-Ray  CECT Abdomen and Pelvis/MRI Pelvis  Cystoscopy and proctosigmoidoscopy (Optional)  PET/CT(Optional).
  39. 39. SURGERY o Radical wide local excision with 1 cm* margin all around with or with I/L or C/L groin dissection: Current standard of practice o Radical vulvectomy:  Multifocal Invasive cancers  Invasive cancers with extensive VIN  Extensive vulvular dystrophy *Heaps J M et al, Obste Gyanacol 38:1990
  40. 40. RADIATION THERAPY  Currently used in variety of settings:  Radical Brachytherapy (Stage IA/B)  Postoperative RT/CTRT(?)  Preoperative RT/CTRT  Definitive CTRT  Salvage RT/CTRT  Palliative RT
  41. 41. Post-operative Radiotherapy  Close (<8-10 mm),positive margins*  Depth of invasion >5 mm  LVSI  More than equal to 2 regional nodes  Extracapsular perinodal spread
  42. 42. Pre-operative RT/CTRT  An anticipated clinical margin of <1 cm*  Tumor abutting Pubic arch, anal sphincter or >1.5 cm of distal urethra  Tumor involving clitoris/vaginal intraoitus(Sexual preservation)  Extensive (matted, fixed, ulcerated) or unresectable groin metastasis.** **Gustavo M et al, a GOG study ,IJROBP 48:2000 *GOG protocol 101 study
  43. 43. DOSE AND FRACTIONATION: EBRT Post-operative RT: 50.4 Gray Pre-operative RT: 45-50.4 Gray Definitive RT: 45-50.4 Gray (boost 10-15 Gray)
  44. 44. Brachytherapy Brachytherapy: Alone: 45-50 Gray/15-18# Boost:18-21 Gray/6-7# Recurrent: Individualized
  45. 45. Carcinoma Vagina
  46. 46. FIGO STAGING 2002/2009 • Stage I Confined to Vaginal Wall • Stage II Invades paravaginal tissues but not pelvic wall. • Stage IIA Subvaginal infiltration (not PM) • Stage IIB PM infiltration not upto LPW • Stage III Extended to pelvic sidewall • Stage IVA Bowel or Bladder • Stage IVB Distant mets
  47. 47. WORK UP AND EVALUATION History and clinical examination Colposcopy Biopsy/Cervical cytology CECT Abdomen/Pelvis Chest X-ray Cystoscopy/Urethroscopy (ant) Sigmoidoscopy (post)
  48. 48.  RT is the preferred Rx for most patients.  Ca-in-situ: local surgical excision/RT  Early stage: surgery or RT (mostly RT)  Locally advanced: definitive RT  Distant mets: Pall RT +/- chemo
  49. 49. Surgery: Indication  Stage I disease in the upper posterior vagina/distal vagina  Stage IVa disease, particularly in the presence of a rectovaginal or vesicovaginal fistula  Central recurrence after radiotherapy
  50. 50.  Intracavitary RT or Interstitial BT alone  EBRT + ICRT  EBRT + Interstitial BT RADIOTHERAPY
  51. 51. Radiotherapy practices: Stage 0-1  Vaginal intra-epithelial neoplasia:  Brachytherapy alone (30 Gray in 5#; 60 Gray LDR equivalent)  Stage I:  Brachytherapy alone (60-70 Gray equivalent)  EBRT (45-50.4 Gray) f/b Brachytherapy* (7-10 Gray in 2-3#) *For more infiltrative and poorly differentiated lesions
  52. 52. Radiotherapy practices: Stage II-IVA  Stage II:  EBRT (45-50.4 Gray) f/b Brachytherapy (7-10 Gray in 2-3#)  Stage III-IVA (selected cases)  EBRT (45-50.4 Gray) with concurrent chemotherapy**  Interstitial Brachytherapy (7-10 Gray in 2-3#) * No randomized data (Extrapolation) oLesions <0.5 cm: Intravaginal brachytherapy oLesions >0.5 cm thick or lateral extension: Interstitial brachytherapy
  53. 53. Brachytherapy in carcinoma Vagina
  54. 54. Carcinoma Ovary
  55. 55. Whole abdominal radiotherapy: IMRT
  56. 56. Current role of radiotherapy  Salvage radiotherapy: isolated pelvic recurrences  Palliative radiotherapy  Intra-operative RT for recurrent cancers  Consolidative radiotherapy after adjuvant chemotherapy  Risk stratifications of abdomino-pelvic failures [J Gynecol Oncol 2013; 24:146-53]  WAR 30 Gray/20# (IMRT) well tolerated  Ongoing OVAR-IMRT-02 [Rochet N. BMC Cancer 2011; 11:41]
  57. 57. Conclusion  Radiotherapy plays an important and vital role in the management of gynecological malignancies  Carcinoma cervix: Radical, Adjuvant [RT for all stages!!]  Carcinoma endometrium: Adjuvant, Radical  Carcinoma Vulva: Pre-operative, Adjuvant, Radical  Carcinoma Vagina: Radical, Adjuvant  Palliation and haemostatic for all gynecological malignancies Multidisciplinary decision making and individualization of treatment for each case is the key to success!!
  58. 58. Thanks for your kind attention!!
  • nzaalypir

    Sep. 15, 2021
  • SanandanPatel

    Jul. 2, 2021
  • ShubhiJain70

    Apr. 13, 2021

A brief overview of radiotherapy practices and practical guidelines in the management of Gynecological malignancies

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