Ca Vagina

Slide 1 : RT TECHNIQUE VAGINA CANCER S. Narudom 21/07/53

Slide 2 : Anatomy The vagina is a muscular dilatable tubular structure averaging 7.5 cm in length that extends from the cervix to the vulva. The vaginal wall is composed of three layers: the mucosa, muscularis, and adventitia. The inner mucosal layer is formed by a thick, nonkeratinizing, stratified squamous epithelium.

Slide 3 : The upper anterior vagina drains along cervical channels to the interiliac and parametrial nodes. The posterior vagina drains into the inferior gluteal, presacral, and anorectal nodes. The distal vagina lymphatics follow drainage patterns of the vulva into the inguinal and femoral nodes and to the pelvic nodes.

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Slide 5 : Epidemiology and Etiological Risk Factors Only 1% to 2% of all female genital neoplasias. Most of vaginal neoplasms, 80% to 90%, are metastatic from other primary gynecologic (cervix or vulva) and nongynecologic sites.

Slide 6 : Vaginal Intraepithelial Neoplasia and Squamous Cell Carcinoma Risk factors for SCC include; Prior history of HPV infection. Cervical intraepithelial neoplasia (CIN). Immunosuppression. Possibly previous pelvic irradiation.

Slide 7 : Clear-Cell Adenocarcinoma An increased incidence of clear-cell adenocarcinoma (CCA) of the vagina in young women related to in utero exposure to diethylstilbestrol (DES) during the first 16 weeks of pregnancy.

Slide 8 : Pathology Nonepithelial Tumors Epithelial Neoplasms

Slide 9 : Epithelial Neoplasms VAIN is a precursor of SCC and is graded from I to III VAIN I; typically involves the lower third to one-half of the epithelium. VAIN II; one-half to two-thirds of the thickness of the epithelium. VAIN III; more than three fourths of the thickness.

Slide 10 : SCC represents 80% to 90% of primary malignant vaginal neoplasms. Difficult histologically to distinguish a primary vaginal SCC from recurrent cervical or vulvar disease.

Slide 11 : Recommendations of FIGO, a tumor of the vagina that involves the cervix or vulva should be classified as a primary cervical or vulvar cancer. Additionally, for a neoplasm to be considered vaginal primary, there must not have been a cervical cancer for 5 years prior to the diagnosis .

Slide 12 : Vaginal Adenosis and Clear-Cell Adenocarcinoma Adenosis is the most common histological abnormality in women exposed to DES in utero. DES-associated CCA has a predilection for the upper third of the vagina and the ectocervix. Three basic histologic patterns—tubulocystic (most common), solid, papillary, or mixed cell.

Slide 13 : Melanocytic Tumors Malignant melanoma is the second most common cancer of the vagina, accounting for 2.8% to 5% of all vaginal neoplasms .

Slide 14 : Nonepithelial Tumors Sarcomas represent 3% of primary vaginal cancers. Malignant Lymphoma and Leukemia. Neuroendocrine small-cell carcinoma in the vagina(very aggressive tumors).

Slide 15 : Clinical Presentation VAIN most often is asymptomatic. Invasive disease; irregular vaginal bleeding, often postcoital, is the most common presenting symptom.

Slide 16 : Staging

Slide 17 : Squamous Cell Carcinoma: Treatment Options and Outcome by Federation of Gynecology and Obstetrics Stages. Treatment

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Slide 19 : Invasive Squamous Cell Carcinoma

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Slide 24 : Surgery Surgery is mainly limited to disease for stage I patients involving the upper posterior vagina. In patients with an intact uterus, upper vaginectomy to achieve at least 1-cm margins, and pelvic lymphadenectomy may be performed. In patients with a prior hysterectomy, radical upper vaginectomy and pelvic lymphadenectomy may be an option.

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Slide 28 : Role of Chemotherapy and Radiation Recently published data on locally advanced cervical cancer have demonstrated an advantage in locoregional control, overall survival, and disease-free survival for patients receiving cisplatin-based chemotherapy concurrently with RT. Based on these data, consideration should be given to a similar approach in patients with advanced vaginal cancer.

Slide 29 : Radiotherapy Techniques External Beam Radiotherapy The treatment is generally delivered using opposed anterior and posterior fields (AP/PA). High-energy photons (>10 MV) are usually preferred.

Slide 30 : Treatment portals cover at least the true pelvis with a 1.5- to 2-cm margin beyond the pelvic rim. Superiorly, the field extends to either L4–L5 or L5–S1 to cover the pelvic lymph nodes up to the common iliacs, and extends distally to the introitus to include the entire vagina. Lateral fields (if used) should extend anteriorly to the pubic symphysis, and at least to the junction of S2–S3 posteriorly.

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Slide 34 : In patients with tumors involving the middle and lower vagina with clinically negative groins, the bilateral inguino-femoral lymph node regions should be treated electively to 45–50 Gy. Planning CT is recommended to adequately determine the depth of the inguino-femoral nodes. In patients with clinically palpable inguinal nodes, additional doses of 15–20 Gy.

Slide 35 : Inguinal radiation

Slide 36 : Inguinal RT Photon through-and-through Wide AP + Wide PA Simple technique Homogeneous

Slide 37 : Inguinal RT Electron tag Narrow AP + Narrow PA Skin match of electron & AP Very low femor dose Very high matchline dose

Slide 38 : Inguinal RT Electron thunderbird (RTOG 9811) Wide AP + Narrow PA Skin match of electron & exit of PA Low femor dose High matchline dose

Slide 39 : Inguinal RT Photon thunderbird (Segmental boost) Wide AP + Narrow PA Deep match vs Skin match Same isocenter Need CT simulation

Slide 40 : Inguinal RT Photon thunderbird (Modified segmental boost) Wide AP + Narrow PA Tilt gantry to match beam Same isocenter Need CT simulation

Slide 41 : Inguinal RT IMRT Sophisticated technique Low dose to OARs

Slide 42 : Comparison of RT technique Fracture ~ 11% at 5-yr Fibrosis Time consuming, Inhomogeneous 3D 2D IMRT

Slide 43 : Low-Dose-Rate Intracavitary Brachytherapy Low-doserate ICB (LDR-ICB) is performed using vaginal cylinders such as Burnett, Bloedorn, Delclos or MIRALVA loaded with cesium-137radioactive sources.

Slide 44 : Delclos afterloading vaginal cylinders have a central hollow metallic cylinder in which the sources are placed, and plastic rings of varying diameter (2.5–4 cm), 2.5 cm in length, are inserted over the cylinder. Some cylinders have a lead shielding to protect selected portions of the vagina, the bladder and/or the rectum.

Slide 45 : The largest possible diameter should be used to improve the ratio of mucosa to tumor dose and eliminate vaginal rogations. In general, the vulva is sutured-closed with proline or silk for the duration of the implant in order to secure the position of the applicators.

Slide 46 : In patients with upper vagina lesions with less than 0.5 cm depth of invasion. Vaginal colpostats alone (after hysterectomy) or in combination with intrauterine tandem, loaded with 137Cs sources similar to that used in treatment of cervical cancer, can be used to treat the proximal vagina. Dose of 65–70 Gy, estimated to 0.5 cm depth, including the contribution of EBRT if given.

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Slide 49 : MIRALVA vaginal applicator, which incorporates two ovoid sources and a central tandem that can be used to treat the entire vagina (alone, or in combination with the uterine cervix). The applicator has vaginal apex caps and additional cylinder sleeves to allow for increased dimensions.

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Slide 51 : High-Dose-Rate Intracavitary Brachytherapy High-dose-rate ICB (HDR-ICB) is typically performed with a 10 Ci single iridium-192 (192Ir) source. The applicators are similar to those described for LDR, consisting of vaginal cylinders of 2.5–4 cm in diameter.

Slide 52 : Include; The radiobiological equivalency of HDR to LDR. Fractionation schedule. Total dose. Specification of dose prescription. How to combine HDR with EBRT and/or LDR brachytherapy. Many aspects remain unknown or not wellunderstood in the use of HDR-ICB.

Slide 53 : Generally,300 cGy to 800 cGy (median 700 cGy) and the number of insertions ranges from 1 to 6 (median 3). 20–28 Gy in three to four fractions, calculated at 0.5 cm from the surface of the applicator.

Slide 54 : Interstitial Brachytherapy Permanent (198Gold or 125Iodine) Temporary implant (192Ir)

Slide 55 : The advantages of temporary implants are readily controlled distribution of the radioactive sources and easier modification of the dose distribution. The advantages of a permanent seed implant include relative safety/simplicity, easy applicability, cost-effectiveness.

Slide 56 : Temporary implants are more common used in the curative treatment of larger gynecological malignancies. Permanent implants are usually performed for smaller volume disease. Interstitial procedure can performing by; freehand implants or template systems (To assist in pre-planning and to guide and secure the position of the needles).

Slide 57 : Commercially available templates include; Syed-Neblett device (SNIT). The modified Syed-Neblett. The MUPIT (Martinez Universal Perineal Interstitial Template).

Slide 58 : The Syed-Neblett device consists of two identical superimposed Lucite plates, each about 1 cm thick, held together by six screws. Both plates are drilled in an identical pattern of predetermined needle positions that can be afterloaded with iridium-192

Slide 59 : The modified Syed-Neblett applicator consists; Perineal template. Vaginal obturator. 17-gauge hollow guides of various lengths.

Slide 60 : This makes possible to combine an interstitial and intracavitary application simultaneously. The vaginal obturator has 7 grooves on its surface for the placement of guide needles and is centrally drilled so it can allow the placement of a tandem. The vaginal obturator is 2 cm in diameter, and 12 cm or 15 cm in length.

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Slide 66 : MUPIT consists; Two acrylic cylinders. An acrylic template with predrilled holes that serve as guides for trocars. A cover plate. Some of the guide holes on the template are angled outward to permit a wide lateral coverage without danger of striking the ischium.

Slide 67 : The cylinders have an axial hole large enough to pass a central tandem or suction tube for drainage of secretions. The cylinders are placed in the vagina and rectum and then fastened to the template. So that a fixed geometric relationship among the tumor volume, normal structures and source placement.

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Slide 69 : The major advantage of these systems is Greater control of the placement of the sources relative to tumor volume and critical structures due to the fixed geometry provided by the template and cylinders.

Slide 70 : To improve the accuracy of target localization and needle placement, can performed with; Under transrectal ultrasound (TRUS). CT or MRI-planned implants with endorectal coil. Laparotomy and laparoscopic guidance.

Slide 71 : Dose Using conventional LDR-ICB techniques, the entire vaginal mucosa should receive between 60 Gy and 70 Gy. MacLeod et al. (1997) used HDR-ICB to treat 14 patients with VAIN 3 with a dose of 34–45 Gy in 4.5-Gy to 8.5-Gy fractions, with a local control of 78.5%. FIGO Stage 0: VAIN – CIS

Slide 72 : At the present time, no definite conclusions can be drawn from the limited data published in the literature regarding the use of HDR-ICB. Ogino et al. (1998) reported 6 patients treated with HDR to a mean dose of 23.3 Gy (range 15–30 Gy), none of whom developed recurrent disease.

Slide 73 : ICB prescribing 65–70 Gy at 0.5 cm depth beyond the vaginal surface. FIGO stage-I There are no well-established criteria regarding the use of EBRT. There is general consensus that EBRT (20–50 Gy) is advisable for larger, more infiltrating or poorly differentiated tumors that may have a higher risk of lymph node metastasis.

Slide 74 : FIGO stage-II Generally, 40–50 Gy is delivered to the whole pelvis, followed by an additional boost of 30–35 Gy given with brachytherapy. Parametrial infiltration, a “boost” with EBRT and/or an interstitial implant to deliver a minimum tumor dose of 70–75 Gy and 55–60 Gy to the pelvic side wall.

Slide 75 : FIGO stages III–IV 45–50 Gy EBRT to the pelvis and in some cases, additional parametrial dose with midline shielding to deliver up to 60 Gy to the pelvic side walls. ITB brachytherapy boost is performed to deliver a minimum tumor dose of 75–80 Gy. If brachytherapy is not feasible, a shrinking-field technique can be used to deliver a tumor dose around 65–70 Gy.

Slide 76 : Dose Limitation Upper vaginal mucosa tolerance is 120 Gy. Mid-vaginal mucosal tolerance is 80–90 Gy. Lower vaginal mucosa tolerance is 60–70 Gy. Vaginal doses >50–60 Gy increase risk of significant vaginal fibrosis and stenosis. Limit bladder <=65 Gy and rectum <=60 Gy.

Slide 77 : Ovarian failure occurs with 5–10 Gy. Sterilization occurs with 2–3 Gy.

Slide 78 : Simulation The open or “frog leg” position is useful when treating the inguinal area to minimize skin reactions from skin folds. A small radio-opaque marker seed inserted in the distal portion of the tumor may help when designing the treatment fields.

Slide 79 : Several maneuvers could be used to minimize marginal misses including: – Instilling a fixed volume of saline in the bladder for simulation and daily treatment using a Foley catheter. – Creating a vaginal/tumor internal target volume (ITV) by fusing the vaginal contour when the bladder is empty and full.

Slide 80 : Treatment of Adenocarcinoma of Vagina Diethylstilbestrol ( DES) clear cell adenocarcinoma (CCA) Non-diethylstilbestrol associated adenocarcinoma of the vagina (NDAV)

Slide 81 : The 5-year survival for NDAV is 34% versus 84% for CCA. NDAV is more likely than CCA to present with, or later develop, lung metastases or metastases to supraclavicular nodes. There is insufficient evidence to make recommendation regarding the optimal management of CCA or NDAV.

Slide 82 : Non-diethylstilbestrol-Associated Adenocarcinoma of the Vagina One retrospective series of 26 patients with NDAV Treated with EBRT followed by brachytherapy or EBRT alone reported a 5-year overall survival of 34%, with a pelvic disease control of 31%. The authors also recommended pelvic EBRT even for superficial stage I adenocarcinomas.

Slide 83 : Clear Cell Adenocarcinoma Surgery may preserve ovarian function, but it is morbid because it includes radical hysterectomy, vaginectomy, pelvic lymphadenectomy, and paraaortic lymph node sampling. If elected, definitive radiation techniques are the same as those described for stages II, III, IV

Slide 84 : Melanoma of Vagina High incidence of distant metastasis remains a major factor in limiting curability. The overall 5-year relative survival rate is 14%. Wide local excision with 1 to 2 cm margins should be the surgical treatment of choice for most primary vaginal melanomas.

Slide 85 : The role of adjuvant RT is unclear, but it appears to improve local control and even survival in some series. The role of systemic chemotherapy or immunotherapy has been very disappointing in the limited published data.

Slide 86 : Some authors recommend fractions > 400 cGy for vaginal melanoma to improve local control based on limited experience. In a retrospective study of 14 patients with vaginal Melanoma concluded that radiotherapy may be of value as an alternative to surgery or as an adjunct modality in patients with lesions < 3 cm in diameter.

Slide 87 : Sarcomas of the Vagina Sarcomas represent 3% of vaginal primaries. Histopathological grade appears to be the most important predictor of outcome. Radical surgical resection, such as posterior pelvic exenteration, offers the best chance for cure for vaginal leiomyosarcomas.

Slide 88 : The role of adjuvant chemotherapy and RT in vaginal sarcomas has not been clearly defined. Adjuvant RT seems indicated in patients with high-grade tumors and locally recurrent low-grade sarcomas. Doxorubicin remains the standard therapy for leiomyosarcoma.

Slide 89 : Embryonal rhabdomyosarcoma of the vagina After complete resection, irradiation of the entire pelvis is not required, thus avoiding its adverse effects. A series of reports from the IRSG, survival rates in excess of 85% have been achieved utilizing vincristine, actinomycin-D, and cyclophosphamide (VAC) chemotherapy and wide excision with or without adjuvant RT. Most common pediatric vaginal tumor.

Slide 90 : Several non-IRSG series have shown that combination chemotherapy with or without RT leads to sufficient tumor shrinkage, and that less radical resections can become feasible, allowing preservation of anatomy and function.

Slide 91 : Lymphomas of the Vagina More recent reports suggest that combination radiation and chemotherapy can achieve excellent results, and, therefore, radical surgery should be avoided.

Slide 92 : Yolk Sac (Endodermal Sinus) Tumors of the Vagina The role of radiation in this disease is limited because of the younger age at presentation and preservation of ovarian function is desired. RT would potentially increase the risk for secondary malignancies

Slide 93 : Recurrence

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Slide 96 : Recurrence

Slide 97 : COMPLICATIONS Cystitis (~50%). Proctitis (~40%). Vaginal stenosis and fibrosis (~50%). Vaginal dryness and atrophy. Pubic hair loss. Vaginal necrosis (<5–15%).

Slide 98 : Radiation-induced menopause may occur. Rectovaginal or vesicovaginalfistula (<5%). Small bowel obstruction. Lymphedema (increased risk in post-op setting). Urethral stricture (rare).

Slide 99 : Thank You For You Attention.