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Dr Ankita Patel
MD(Radiation Oncology)
Apex Hospital
Varanasi
HIGH PRECISION RADIOTHERAPY
AND SYSTEMIC THERAPIES IN
GYNAEC...
AIM..
WHEN TO CONSIDER????
HOW???
ROADMAP
• Comparison of classification systems of endometrial cancer.
• Risk stratification
• Guide to adjuvant treatment ...
CA ENDOMETRIUM
EPIDEMIOLOGY
• Uterine cancer is the most common gynecological cancer in high-income
countries and the second most common ...
Etiological factors:
• unopposed / excessive estrogen exposure
Predisposing factors:
• Nulliparity, early menarche/late me...
LYNCH SYNDROME
Comparison of classification systems of
endometrial cancer
Murali, Lancet Oncol 2014
• LIMITATIONS
1) Based on clinical and epidemiological characteristics of
women with endometrial ca in Soviet Union 30 yea...
HISTO-MOLECULAR SUBTYPES OF
ENDOMETRIAL CANCER
Murali, Lancet Oncol 2014
MOLECULAR CLASSIFICATION
Integrated Genomic Characterization of Endometrial Carcinoma
The Cancer Genome Atlas Research Network
COMPREHENSIVE GENOMIC AND
TRANSCRIPTOMIC ANALYSIS OF ENDOMETRIAL
CANCER- FOUR GENOMIC CLASSES
Murali R, Lancet Oncol, 2014...
ENDOMETRIAL CANCER
SURGERY IS (STILL) THE CORNERSTONE OF
TREATMENT
• Hysterectomy + BSO is the cornerstone in the therapy ...
ESMO/ESGO/ESTRO CONSENSUS CONFERENCE ON
ENDOMETRIAL CANCER
WHAT ARE THE INDICATIONS FOR LYMPHADENECTOMY?
1. Lymphadenectom...
ENDOMETRIAL CANCER: FIGO STAGING SURGICAL &
PATHOLOGICAL
New FIGO staging (2009)
Pathological assessment includes: Myometr...
• The majority of patients with
endometrial cancer have a low
risk of recurrence and are
managed by surgery alone .
• Risk...
What is early stage high risk Endometrial cancer
• Most recurrences in patients with early stage disease occurred in
whom ...
• Using the National Cancer Database (NCDB), Li et al tried to refine
the definition of high intermediate risk by analyzin...
LOW RISK
IA
GRADE 1,2
LVSI-VE
NO ADJ TREATMENT
INTERMEDIATE RISK
IB
GRADE 1,2
LVSI-VE
ADJ BRACHYTHERAPY
NO ADJ TREATMENT I...
HIGH INTERMEDIATE RISK
STAGE IA, GRADE 3
STAGE I, GRADE 1-2,LVSI UNEQUIVOCALLY POSITIVE
SURGICAL STAGING DONE, NODE –VE
AD...
HIGH RISK
STAGE I B , GRADE 3
REGARDLESS OF LVSI STATUS
SURGICAL STAGING DONE, NODE –VE
• ADJ EBRT WITH LIMITED FIELDS
• A...
HIGH RISK
STAGE II
SIMPLE HYSTERECTOMY, SURGICAL STAGING
DONE, NODE –VE
• GRADE 1,2,LVSI-: VAGINAL BRACHY
• GRADE3 /LVSI+:...
HIGH RISK
STAGE III AND NO RESIDUAL DISEASE
EBRT
CHEMOTHERAPY
EBRT AND CHEMOTHERAPY IN
COMBINATION
HIGH RISK
NON ENDOMETRIOID
SEROUS AND CLEAR CELL AFTER
COMPREHENSIVE STAGING
• CONSIDER CHEMOTHERAPY;CLINICAL
TRIALS ARE E...
HIGH PRECISION RADIOTHERAPY
STEPS of EBRT by LA
• Immobilization by thermoplastic cast
• RTP Scan(Radiotherapy Planning Scan)
• Treatment planning and...
Immobilization by thermoplastic cast
RTP (Radiotherapy Treatment Planning)SCAN by
laser – CT System and lead pellets and fiducials
TPS (Teletherapy Planning system)
(Xio , Monte Carlo Based Planning System as approved by US FDA and AERB)
DOSES
• Gupta N, Prakash C, Chakrabarty K, Giri
U, Patel A, Choudhary S.Potential
Advantages of Bone Marrow Sparing
IMRT in Canc...
EXECUTION
Verification by CBCT( cone beam CT)
SORBO
PLANNING
Indications for Adjuvant Systemic Therapy in
Endometrial Carcinoma
Cytotoxic chemotherapy not standard, but in study
• Can...
ESMO/ESGO/ESTRO Consensus Conference on
Endometrial Cancer
Hormonale therapy in recurrent/metastatic disease
• Hormone the...
Hormonal Therapies in Palliative Setting
Progestins
• As treatment for advanced and recurrent disease
1984: compiled data ...
Cytotoxic Chemotherapy in EC
Chemonaive patients
GENOMIC ALTERATIONS IN GENOMIC SUBTYPES OF ENDOMETRIAL
CANCER POTENTIALLY PREDICTIVE OF RESPONSE TO TARGETED
THERAPY
Integrated molecular endometrial cancer classification. A proposed model of the integration of molecular subtype and
clini...
CERVICAL CANCER
2018 FIGO STAGING SYSTEM FOR UTERINE
CERVICAL CANCER
TREATMENT ALGORITHM FOR CERVICAL
CANCER
POSTOPERATIVE RT AND CTRT
• Positive nodes
• Positive Parametria
• Positive margins
If all negative, look for the Sedlis c...
3D CONFORMAL RT
IMRT
IMRT sagittal (A) and axial paraaortic nodes at the level of the kidneys (B) of an extended pelvic
and paraaortic ext...
INTERFRACTION ORGAN MOTION
TUMOR SHRINKAGE
ADAPTIVE RADIOTHERAPY
MRI T2 weighted images of the same patient 4 weeks and 35Gy apart
Huh, SJ et al Radi...
IMRT VS 3D
• Several retrospective studies with encouraging results
(tumor control and toxicity)
• Typically lower GI toxi...
IMRT VS 3D
Isohashi F et al Rad Oncology 2015
Chronic GI toxicity (>Grade 2) V40: volume of small bowel >40Gy
Isohashi F e...
• Gupta N, Prakash C, Chakrabarty K, Giri
U, Patel A, Choudhary S.Potential
Advantages of Bone Marrow Sparing
IMRT in Canc...
BRACHYTHERAPY
Insertion of An Afterloading Device Inside The Uterus-cervix-vagina
BRACHYTHERAPY UNIT
Location of point A and point B using the method recommended in International
Commission on Radiation Units and Measuremen...
Illustration of the central dose escalation achieved when combining
intracavitary brachytherapy with external-beam radioth...
• Magnetic resonance imaging (A and B) versus computed tomography (C and D) axial and sagittal views of
an intracavitary t...
• Magnetic resonance
imaging–based interstitial
brachytherapy showing the
central tandem with
adjacent interstitial needle...
BRACHYTHERAPY IS ESSENTIAL
GENERAL FACTS ABOUT CHEMOTHERAPY
• Chemotherapy is typically single agent cisplatin
• Delivered weekly during external RT
...
• Grade 3-4 acute toxicities increase with CTRT
• 2-10 fold increase in leucopenia p<0.001
• 3-10 fold increase in thrombo...
RECURRENT AND METASTATIC CERVICAL
CANCER
• Systemic Treatment : How to improve beyond
Platinum Doublets?
1. Anti-Angiogene...
RATIONALE FOR TARGETING VEGF IN
TREATMENT OF CERVICAL CANCER
• Angiogenesis is critical in tumor growth and survival and h...
IMMUNOTHERAPY: THE NEXT FRONTIER
ANTI-PROGRAMMED DEATH (PD)-1 THERAPY FOR CERVICAL CANCER
RATIONALE
• Human papillomavirus...
SIDE EFFECTS
Reference :https://www.cancerresearchuk.org/about-cancer/cervical-cancer/treatment/radiotherapy/side-effects
...
USE OF VAGINAL DILATOR
Vaginal Dilator stretches the Vagina and helps to stop it from Narrowing
Reference :https://www.can...
KEGELSEXERCISESTRENGTHEN
THEPELVICFLOORMUSCLES
http://www.lymphedemablog.com/2012/07/03/complete-decongestive-therapy-in-the-treatment-of-
lymphedema/
COMBINEDDECONGESTI...
https://onlinelibrary.wiley.com/doi/abs/10.1002/jbio.201700004
Faradic Stimulation
Faradic Stimulation to
Improve the Musc...
PRIMARYTHERAPYANDSURVIVALBYDISEASEEXTENT
THANKYOU! STAY SAFE,STAY HEALTHY,STAY POSITIVE!
IMMUNOTHERAPY: THE NEXT FRONTIER
Anti-programmed death (PD)-1 therapy for cervical cancer
Rationale
• Human papillomavirus...
TAKE HOME MESSAGES
• Chemoradiation for advanced carcinoma of the cervix is a well
established standard of care
• Single a...
• Role of chemotherapy is evolving over time:
• Radiosensitizer
• Neoadjuvant
• Exclusive
• Metastatic Disease
• Bevacizum...
REHABILITATION
OVARIAN CANCER- DISEASE OF MANY SUBTYPES
CHANGING TIMES FOR THE GYNAECOLOGICAL CANCERS
THE TREATMENT OF GYNAECOLOGICAL CANCERS IS UNDERGOING RAPID
CHANGES….
Surgery- diagnosis, staging and
treatment
• aim complete cytoreduction
• maximal surgical effort : bilateral salpino-
ooph...
ADVANCED STAGE
How to select patients for primary debulking surgery
or neoadjuvant chemotherapy?
Summary of recommendation...
OVARIAN CANCER- FIRST LINE SYSTEMIC THERAPY
NEOADJUVANT (NACT)
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
Ca endometrium for gynaecologists
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CA ENDOMETRIUM AND CA CERVIX FOR VARANASI OBSTETRICS AND GYNAECOLOGY SOCIETY

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Ca endometrium for gynaecologists

  1. 1. Dr Ankita Patel MD(Radiation Oncology) Apex Hospital Varanasi HIGH PRECISION RADIOTHERAPY AND SYSTEMIC THERAPIES IN GYNAECOLOGICAL MALIGNANCIES
  2. 2. AIM.. WHEN TO CONSIDER???? HOW???
  3. 3. ROADMAP • Comparison of classification systems of endometrial cancer. • Risk stratification • Guide to adjuvant treatment (highly conformal radiotherapy (brachy/ebrt), chemotherapy) • Ca Cervix-treatment Algorithm • 3DCRT versus IMRT • Indications of POST OP RT/CTRT in Ca Cervix
  4. 4. CA ENDOMETRIUM
  5. 5. EPIDEMIOLOGY • Uterine cancer is the most common gynecological cancer in high-income countries and the second most common gynecological cancer worldwide when both high- and low-income countries are considered (cervical cancer is more common in worldwide statistics) . • Over 90 percent of uterine cancers are endometrial, originating in the epithelium; most of the remainder are mesenchymal, originating in the myometrial muscle or, less commonly, the endometrial stroma
  6. 6. Etiological factors: • unopposed / excessive estrogen exposure Predisposing factors: • Nulliparity, early menarche/late menopause • obesity, diabetes, hypertension • treatment with tamoxifen Genetic susceptibility: Lynch type II syndrome
  7. 7. LYNCH SYNDROME
  8. 8. Comparison of classification systems of endometrial cancer Murali, Lancet Oncol 2014
  9. 9. • LIMITATIONS 1) Based on clinical and epidemiological characteristics of women with endometrial ca in Soviet Union 30 years back. Characteristics of current patients is different. 2) Does not account for Ca endometrium occuring in Lynch Syndrome who are genrally thin and not associated with hyperplasia. 3) 10-19% EC are of high grade and clinical/histo/molecular features intermediate between type I and Type II. 4) Not all serous ca behave prototypical type II. Murali, Lancet Oncol 2014
  10. 10. HISTO-MOLECULAR SUBTYPES OF ENDOMETRIAL CANCER Murali, Lancet Oncol 2014
  11. 11. MOLECULAR CLASSIFICATION
  12. 12. Integrated Genomic Characterization of Endometrial Carcinoma The Cancer Genome Atlas Research Network
  13. 13. COMPREHENSIVE GENOMIC AND TRANSCRIPTOMIC ANALYSIS OF ENDOMETRIAL CANCER- FOUR GENOMIC CLASSES Murali R, Lancet Oncol, 2014 POLE: Polymerase E ultramutation MSI: Microsatellite instability
  14. 14. ENDOMETRIAL CANCER SURGERY IS (STILL) THE CORNERSTONE OF TREATMENT • Hysterectomy + BSO is the cornerstone in the therapy of endometrial carcinoma* • The uterus should be removed whenever feasible • Hysterectomy enhances twofold the chances of cure • Uterus pathology provides the best information on the risk factors of this tumor: histologic grade and myometrial invasion *Mangioni C, 1988
  15. 15. ESMO/ESGO/ESTRO CONSENSUS CONFERENCE ON ENDOMETRIAL CANCER WHAT ARE THE INDICATIONS FOR LYMPHADENECTOMY? 1. Lymphadenectomy (LND) is a staging procedure. 2. LND not recommended for low-risk patients. (2 negative trials) 3. For patients with intermediate risk (G2 and pT1b or G3 and pT1a) data are scarce and conflicting. LND can be considered for staging purposes. 4. For high-risk patients (>=pT1b and G3), LND is recommended, even though two RCT which included also these patients did not show survival benefit. 5. Retrospective analyses, however, suggested that LND might lead to survival benef Colombo et al. Ann Oncol 2016; 27: 16-41
  16. 16. ENDOMETRIAL CANCER: FIGO STAGING SURGICAL & PATHOLOGICAL New FIGO staging (2009) Pathological assessment includes: Myometrial invasion, cervical involvement, tumor size and location, extension to fallopian tubes and ovaries, grade and histological subtypes, lymphovascular space invasion (LVSI), nodal status. 75% STAGE 1
  17. 17. • The majority of patients with endometrial cancer have a low risk of recurrence and are managed by surgery alone . • Risk groups have been devised based on clinicopathological prognostic factors to identify patients at risk of recurrence who may benefit from adjuvant therapy.
  18. 18. What is early stage high risk Endometrial cancer • Most recurrences in patients with early stage disease occurred in whom tumors exhibited multiple high-risk features. • Investigators from the GOG (Gynecologic Oncology Group) and PORTEC (Post Operative Radiation Therapy in Endometrial Carcinoma) defined “high intermediate risk” subgroups—about 1/3 of their intermediate risk patients—that had relatively high rates of recurrence • These patients appeared to benefit from post-operative radiation. 22 Creutzberg CL et al. PORTEC Study Group. post operative RT in endometrial carcinoma. Lancet 2000;355:1404–11. Keys HM et al. Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744–51.
  19. 19. • Using the National Cancer Database (NCDB), Li et al tried to refine the definition of high intermediate risk by analyzing outcomes of 30,986 patients who met either the PORTEC or GOG high intermediate risk criteria. • found no significant benefit from adjuvant radiation therapy for 5920 relatively favorable cancers that were deemed high intermediate risk solely by PORTEC • Molecular markers promise to yield powerful, independent information about the biology of endometrial cancers, their potential to spread, and their response to various treatments. 23 Li. Int J Gynecolo Oncol 2019.
  20. 20. LOW RISK IA GRADE 1,2 LVSI-VE NO ADJ TREATMENT INTERMEDIATE RISK IB GRADE 1,2 LVSI-VE ADJ BRACHYTHERAPY NO ADJ TREATMENT IF AGE<60 YEARS
  21. 21. HIGH INTERMEDIATE RISK STAGE IA, GRADE 3 STAGE I, GRADE 1-2,LVSI UNEQUIVOCALLY POSITIVE SURGICAL STAGING DONE, NODE –VE ADJ BRACHY NO ADJ TREATMENT IS AN OPTION NO SURGICAL STAGING DONE ADJ EBRT FOR LVSI UNEQUIVOCALLY POSITIVE ADJ BRACHYTHERAPY ALONE FOR GRADE 3,LVSI –VE SYSTEMIC THERAPY IS OF UNCERTAIN BENEFIT
  22. 22. HIGH RISK STAGE I B , GRADE 3 REGARDLESS OF LVSI STATUS SURGICAL STAGING DONE, NODE –VE • ADJ EBRT WITH LIMITED FIELDS • ADJ BRACHY MAY BE CONSIDERED AS ALTERNATIVE • ADJ CHEMO IS UNDER INVESTIGATION • NO SURGICAL STAGING DONE • ADJ EBRT IS GENERALLY RECOMMENDED FOR PELVIC CONTROL AND RFS • SEQUENTIAL CHEMOTHERAPY MAY BE CONSIDERED TO IMPROVE PFS AND CSS • THERE IS MORE EVIDENCE TO SUPPORT CHEMOTHERAPY IN COMBINATION RATHER THAN EITHER TREATMENT MODALITY ALONE.
  23. 23. HIGH RISK STAGE II SIMPLE HYSTERECTOMY, SURGICAL STAGING DONE, NODE –VE • GRADE 1,2,LVSI-: VAGINAL BRACHY • GRADE3 /LVSI+: LIMITED FIELD EBRT+BRACHY BOOST+ -CHEMO(UNDER INVESTIGATION) • SIMPLE HYSTERECTOMY, NO SURGICAL STAGING DONE • EBRT+BRACHY BOOST • GRADE 3/LVSI+ : SEQUENTIAL CHEMOTHERAPY
  24. 24. HIGH RISK STAGE III AND NO RESIDUAL DISEASE EBRT CHEMOTHERAPY EBRT AND CHEMOTHERAPY IN COMBINATION
  25. 25. HIGH RISK NON ENDOMETRIOID SEROUS AND CLEAR CELL AFTER COMPREHENSIVE STAGING • CONSIDER CHEMOTHERAPY;CLINICAL TRIALS ARE ENCOURAGED • STAGE IA, LVSI-VE: VAGINAL BRACHYTHERAPY ONLY WITHOUT CHEMOTHERAPY • STAGE>IB: EBRT MAY BE CONSIDERED IN ADDITION TO CHEMOTHERAPY,ESPECIALLY FOR NODE POSITIVE DISEASE. • CARCINOSARCOMA AND UNDIFFERENTIATED TUMORS • CHEMOTHERAPY • CONSIDER EBRT (CLINICAL TRIALS)
  26. 26. HIGH PRECISION RADIOTHERAPY
  27. 27. STEPS of EBRT by LA • Immobilization by thermoplastic cast • RTP Scan(Radiotherapy Planning Scan) • Treatment planning and Optimisation. • Plan Evaluation. • Treatment Delivery. • Daily Verification.
  28. 28. Immobilization by thermoplastic cast
  29. 29. RTP (Radiotherapy Treatment Planning)SCAN by laser – CT System and lead pellets and fiducials
  30. 30. TPS (Teletherapy Planning system) (Xio , Monte Carlo Based Planning System as approved by US FDA and AERB)
  31. 31. DOSES
  32. 32. • Gupta N, Prakash C, Chakrabarty K, Giri U, Patel A, Choudhary S.Potential Advantages of Bone Marrow Sparing IMRT in Cancer Cervix: A Dosimetric Evaluation [Internet].2019 April [Cited November2, 2020];13(4):XC01-XC05. OUR DOSIMETRIC STUDY
  33. 33. EXECUTION
  34. 34. Verification by CBCT( cone beam CT)
  35. 35. SORBO
  36. 36. PLANNING
  37. 37. Indications for Adjuvant Systemic Therapy in Endometrial Carcinoma Cytotoxic chemotherapy not standard, but in study • Can be considered for HR patients and /or with nodal metastases • Evaluated in combination with RT (PORTEC 3 study in HR patients*: EBRT vs EBRT + CDDP→4xTC): Overall no improvement in FFS or OS, but in stage III it did: FFS↑ (11% at 5 years) • Hormonal therapy not standard. Several negative trials *PORTEC 3: eligible are FIGO stage I, grade 3 ± LVSI; stage II or III; serous / clear cell tumors
  38. 38. ESMO/ESGO/ESTRO Consensus Conference on Endometrial Cancer Hormonale therapy in recurrent/metastatic disease • Hormone therapy (HT) indicated (100% consensus) • HT likely more effective in G1 or 2 endometrioid ca or with ER+ or PgR+ status (100% consensus) • Biopsy of recurrent disease could be considered, as there might be differences in receptor status in primary and metastatic tumor (100% consensus) • HT is the preferred frontline systemic therapy for patients with HR positive tumors, grade 1 or 2 and without rapidly progressive disease. Progestins are generally recommended (100% consensus) Colombo et al. Ann Oncol 2016; 27: 16-41
  39. 39. Hormonal Therapies in Palliative Setting Progestins • As treatment for advanced and recurrent disease 1984: compiled data 34% RR, 13% NC duration of response 16-28 months (Kaupilla) Later studies found only 15.8% and 11.2% RR • Type of progestin and route of administration do not seem to be of major importance • GOG trial: 200 mg vs 1000 mg/d oral MPA ->no difference (Thigpen, 1991)
  40. 40. Cytotoxic Chemotherapy in EC Chemonaive patients
  41. 41. GENOMIC ALTERATIONS IN GENOMIC SUBTYPES OF ENDOMETRIAL CANCER POTENTIALLY PREDICTIVE OF RESPONSE TO TARGETED THERAPY
  42. 42. Integrated molecular endometrial cancer classification. A proposed model of the integration of molecular subtype and clinicopathological features. The relative weight of each molecular or pathological parameter and the optimal treatment algorithms within each molecular subtype need to be further refined through clinical trials. However, this integrated model yields opportunities in research and clinical care to interrogate within consistently classified, molecularly similar EC subsets. TAKE HOME MESSAGE
  43. 43. CERVICAL CANCER
  44. 44. 2018 FIGO STAGING SYSTEM FOR UTERINE CERVICAL CANCER
  45. 45. TREATMENT ALGORITHM FOR CERVICAL CANCER
  46. 46. POSTOPERATIVE RT AND CTRT • Positive nodes • Positive Parametria • Positive margins If all negative, look for the Sedlis criteria (GOG 92)
  47. 47. 3D CONFORMAL RT
  48. 48. IMRT IMRT sagittal (A) and axial paraaortic nodes at the level of the kidneys (B) of an extended pelvic and paraaortic external-beam field in a patient with stage IIIB cervical cancer and common iliac lymph node metastases. Care is be taken to fully treat the tumor accounting for potential motion due to tumor shrinkage, resulting in a field that closely resembles a four-field treatment in the pelvis, but spares small bowel, kidneys, and spinal cord in the paraaortic region.
  49. 49. INTERFRACTION ORGAN MOTION
  50. 50. TUMOR SHRINKAGE ADAPTIVE RADIOTHERAPY MRI T2 weighted images of the same patient 4 weeks and 35Gy apart Huh, SJ et al Radiother. Oncol. 2004
  51. 51. IMRT VS 3D • Several retrospective studies with encouraging results (tumor control and toxicity) • Typically lower GI toxicity with IMRT • RTOG 0418 phase II study; Reported on favorable hematological toxicity if constraints were respected (V40 <37%) Klopp AH et al. Int J Rad Oncol B P 2013 Isohashi F et al Rad Oncology 2015
  52. 52. IMRT VS 3D Isohashi F et al Rad Oncology 2015 Chronic GI toxicity (>Grade 2) V40: volume of small bowel >40Gy Isohashi F et al Rad Oncology 2015
  53. 53. • Gupta N, Prakash C, Chakrabarty K, Giri U, Patel A, Choudhary S.Potential Advantages of Bone Marrow Sparing IMRT in Cancer Cervix: A Dosimetric Evaluation [Internet].2019 April [Cited November2, 2020];13(4):XC01-XC05. OUR DOSIMETRIC STUDY
  54. 54. BRACHYTHERAPY Insertion of An Afterloading Device Inside The Uterus-cervix-vagina
  55. 55. BRACHYTHERAPY UNIT
  56. 56. Location of point A and point B using the method recommended in International Commission on Radiation Units and Measurements (ICRU) 38 (updated in ICRU 89, 2016).
  57. 57. Illustration of the central dose escalation achieved when combining intracavitary brachytherapy with external-beam radiotherapy.
  58. 58. • Magnetic resonance imaging (A and B) versus computed tomography (C and D) axial and sagittal views of an intracavitary tandem and ring insertion for high-dose-rate afterloading brachytherapy. • Computerized brachytherapy or magnetic resonance imaging dosimetry allows visualization of dose in the traditional planes of calculation (coronal, sagittal, and transverse), but also permits three-dimensional representation of dose distribution that may be exploited to conform better to unusual tumor geometries.
  59. 59. • Magnetic resonance imaging–based interstitial brachytherapy showing the central tandem with adjacent interstitial needles placed through the vaginal ring, permitting brachytherapy dose to the residual parametrial disease.
  60. 60. BRACHYTHERAPY IS ESSENTIAL
  61. 61. GENERAL FACTS ABOUT CHEMOTHERAPY • Chemotherapy is typically single agent cisplatin • Delivered weekly during external RT • NO CT during brachytherapy • Drugs other than Cisplatin failed to show superiority • Adjuvant CT is gaining momentum particularly for high risk patients
  62. 62. • Grade 3-4 acute toxicities increase with CTRT • 2-10 fold increase in leucopenia p<0.001 • 3-10 fold increase in thrombocytopenia p=0.005 • 2 fold increase in GI toxicity p<0.001 • Kirwan JM, et al. Radiother Oncol. 2003 • CTRT metaanalysis, J Clin Onc 2008 • Late complications were not sufficiently studied with CTRT; but the data is not in favour of a major increase of these late effects
  63. 63. RECURRENT AND METASTATIC CERVICAL CANCER • Systemic Treatment : How to improve beyond Platinum Doublets? 1. Anti-Angiogenesis Therapy: The role of Anti-VEGF(Bevacizumab): GOG#240 2. Immunotherapy: Next Frontier Checkpoint inhibitors: Anti-PD1/PD-L1
  64. 64. RATIONALE FOR TARGETING VEGF IN TREATMENT OF CERVICAL CANCER • Angiogenesis is critical in tumor growth and survival and has been generally considered a very attractive target for cancer therapy. • Overexpression of VEGF has been associated with tumor progression and poor prognosis in several tumors, including cervical cancer. Ferrara N. .Endocr Rev 2004. • More specifically, intratumoral protein levels of VEGF have been shown to be increased in cervical cancer compared to normal cervical tissue, and higher VEGF levels correlate with higher stage increased risk of lymph nodes metastasis , poor disease-free and overall survival. Cheng WF. Obstet Gynecol 2000. Loncaster JA, Br J Cancer 2000.
  65. 65. IMMUNOTHERAPY: THE NEXT FRONTIER ANTI-PROGRAMMED DEATH (PD)-1 THERAPY FOR CERVICAL CANCER RATIONALE • Human papillomavirus (HPV) infection is the cause of more than 90% of cervical cancers. • PD-L1 has been shown to be a solid biomarker of HPV infection of the cervix . PD-L1 is significantly up-regulated in cervical cancer and detectable by IHC in tumor cells: • Squamous Cervical cancer between 54%- 80% according to different series • Adenocarcinoma: 14% • PD-L1 expression reduces the immune response since it is able to bind to PD1 on T lymphocytes, thereby inhibiting their function. Liu C, et al. Mol Med Rep 2017;15:1063–1070; Mezache L, et al. Mod Pathol 2015;28:1594–1602; Heeren AM et al. Mod Pathol. 2016;29:753– 763.
  66. 66. SIDE EFFECTS Reference :https://www.cancerresearchuk.org/about-cancer/cervical-cancer/treatment/radiotherapy/side-effects https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1046/j.0004-8666.2003.00040.x • Sore and Red Skin in the Treatment area • Fibrosis of muscles • Narrower and Less Stretchy Vagina • Vaginal Oedema and Lower Limb Lymphoedema (In can happen after the Surgery if the Inguinal Lymph nodes are involved and dissected )(In 18% patients lymphoedema can occur. Among them 53% of these were diagnosed within 3 months of treatment, a further 18% within 6 months, 13% within 12 months and the remaining 16% up to 5 years following treatment.) • Vulvodynia • Urinary incontinence
  67. 67. USE OF VAGINAL DILATOR Vaginal Dilator stretches the Vagina and helps to stop it from Narrowing Reference :https://www.cancerresearchuk.org/about-cancer/cervical-cancer/treatment/radiotherapy/side-effects
  68. 68. KEGELSEXERCISESTRENGTHEN THEPELVICFLOORMUSCLES
  69. 69. http://www.lymphedemablog.com/2012/07/03/complete-decongestive-therapy-in-the-treatment-of- lymphedema/ COMBINEDDECONGESTIVE THERAPYTOREDUCELYMPHOEDEMA • C Intermittent Pneumatic Compression Multi Layered Lymphoedema Bandaging Lower Limb Lymphoedema
  70. 70. https://onlinelibrary.wiley.com/doi/abs/10.1002/jbio.201700004 Faradic Stimulation Faradic Stimulation to Improve the Muscle power of Pelvic Floor Muscles to improve Urinary Incontinence
  71. 71. PRIMARYTHERAPYANDSURVIVALBYDISEASEEXTENT
  72. 72. THANKYOU! STAY SAFE,STAY HEALTHY,STAY POSITIVE!
  73. 73. IMMUNOTHERAPY: THE NEXT FRONTIER Anti-programmed death (PD)-1 therapy for cervical cancer Rationale • Human papillomavirus (HPV) infection is the cause of more than 90% of cervical cancers • PD-L1 has been shown to be a solid biomarker of HPV infection of the cervix • PD-L1 is significantly up-regulated in cervical cancer and detectable by immunohistochemistry in tumor cells: • Squamous Cervical cancer between 54%- 80% according to different series • •Adenocarcinoma: 14% • PD-L1 expression reduces the immune response since it is able to bind to PD1 on T lymphocytes, thereby inhibiting their function. • These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer Liu C, et al. Mol Med Rep 2017;15:1063–1070; Mezache L, et al. Mod Pathol 2015;28:1594–1602; Heeren AM et al. Mod Pathol. 2016;29:753–763.
  74. 74. TAKE HOME MESSAGES • Chemoradiation for advanced carcinoma of the cervix is a well established standard of care • Single agent Cisplatin remains the best concurrent chemotherapy at present • The role of adjuvant chemotherapy is not fully established. A phase III trial is in progress • Brachytherapy is essential for an optimal local disease control and survival • Hysterectomy is not better than BCT AND is not needed after CTRT+ brachytherapy; BUT may be helpful when brachy is not available
  75. 75. • Role of chemotherapy is evolving over time: • Radiosensitizer • Neoadjuvant • Exclusive • Metastatic Disease • Bevacizumab is the only treatment able to increase OS during thelast 20 years in the metastatic setting • Immunotherapy promising
  76. 76. REHABILITATION
  77. 77. OVARIAN CANCER- DISEASE OF MANY SUBTYPES
  78. 78. CHANGING TIMES FOR THE GYNAECOLOGICAL CANCERS THE TREATMENT OF GYNAECOLOGICAL CANCERS IS UNDERGOING RAPID CHANGES….
  79. 79. Surgery- diagnosis, staging and treatment • aim complete cytoreduction • maximal surgical effort : bilateral salpino- oopherectomy, hysterectomy, peritoneal washings, omentectomy, intestinal resection, peritoneal stripping, diaphragmatic resection, removal of bulky para-aortic lymph nodes and splenectomy • Fertility sparing surgery - could be considered in early- stage disease, but always after informing the patient about the potential risks
  80. 80. ADVANCED STAGE How to select patients for primary debulking surgery or neoadjuvant chemotherapy? Summary of recommendations LoE GoR Consensus The selection of patients for primary debulking surgery or neo-adjuvant treatment must be performedin a specialist ovarian cancer centre (according to the ESGO Quality recommendations 2017) in a multidisciplinary setting IV A Yes: 100% (40 voters) Complete tumour resection at upfront debulking is the most important prognostic factor for patients with advanced ovarian cancer and is the main goal of surgery IV A Yes: 100% (40 voters) When complete surgery with no macroscopic visible disease appears feasible (both spread of disease and general condition of the patient), primary upfront debulking should be offered IV B Yes: 100% (40 voters Diagnostic work-up with computed tomography, positron emission tomography- computed tomography, or diffusion-weighted whole body magnetic resonance imaging, and expert ultrasound or diagnostic aparoscopy should be used to assess the extent of disease III C Yes: 100% (40 voters
  81. 81. OVARIAN CANCER- FIRST LINE SYSTEMIC THERAPY NEOADJUVANT (NACT)

CA ENDOMETRIUM AND CA CERVIX FOR VARANASI OBSTETRICS AND GYNAECOLOGY SOCIETY

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