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2.3 Female - Gynaecological Cancers Cheat Sheet (DRAFT) by

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Types of Gynaec­olo­gical Cancers

Cervical Cancer
Uterine Cancer
Ovarian Cancer
Endome­trial Cancer
Cancer of the Vulva

Anatomy of the Uterus

The uter­us, located in the pelvis between the rectum and the bladder, is divided into the body (corpus) and the cerv­ix, separated by the isthmus.
The uterus is attached to the pelvis primarily by the broad (later­al) and round (anter­o-l­ate­ral) ligaments.
The utero sacral ligaments at the lower uterine segment and the cardinal ligaments at the upper lateral margin of the cervix contribute to supporting the uterus.
The main artery supplying the uterus is the uterine artery, a branch of the hypo-g­astric artery.
The uterus has a rich lymphatic network; the lower and mid-third of which drain laterally along the para-m­etrium into the para-c­ervical lymph nodes and from here to the external iliac nodes (obturator nodes are the innermost component) and hypo-g­astric nodes.
The pelvic lymphatics drain into the common iliac and peri-a­ortic lymph nodes. However, the lymphatics from the upper corpus and fundus pass laterally across the broad ligaments continuous with those of the ovary directly into the peri-a­ortic and upper abdominal lymph nodes.
Finally, there are lymphatic channels that drain along the round ligaments to the femoral nodes. The anatomic distri­bution of the lymphatics represents the basis for radiation therapy delive­ry.

Termin­ology

Epid­emi­ology is literally translated from Greek, means "the study of people­". Used to mean the study of diseases in popula­tions. Epidem­iology has three main aims:
1. To describe disease patterns in human popula­tions.
2. To identify the causes of diseases (also known as aetiol­ogy).
3. To provide data essential for the manage­ment, evaluation and planning of services for the preven­tion, control and treatment of disease.
Aeti­olo­gy: the causes of disease and factors underlying their spread.
Staging System: Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body.
Mana­gement options: Treatment choices.

Cancer of the Vulva

Vulval cancer is relatively rare
Trea­tment management approa­ches: a combin­ation of surgery, chemot­herapy, external beam radiation therapy (EBRT) and brachy­the­rapy, which may be delivered with low dose rate (LDR) or high dose rate (HDR) brachy­the­rapy.

Endome­trial Cancer

Intr­a-c­avitary vaginal brachy­therapy (IVB) is an integral component in the adjuvant management of selected patients with early stage endome­trial cancer (EC).
Potential advantages of IVB when compared with EBRT include lower costs, lower morbidity and patient conven­ience; the main disadv­antage is that it does not address the pelvis and, therefore, should be limited to patients in whom the pelvic failure rate is estimated to be small and the vagina represents the organ at risk for recurr­ence.
There are no standa­rdised treatment recomm­end­ations

Cervical Cancer

If there is less than 3 mm of invasion below the basement membrane, the risk of pelvic nodal spread is less than 1%.
treatment options include a simple hyster­ectomy or, if preser­vation of fertility is desired, cervical conisation and careful follow-up.
Cervical conisa­tion: A procedure which excises a cone of tissue (mucous membrane) off the cervix for purpose of diagno­stics and therap­eutics (removes precan­cerous cells).
If the focus of invasion extends 3 mm or more or if there is lymph vascular space involv­ement, the risk of nodal spread increases to 2–8% and most oncolo­gists recommend a (modified) radical hyster­ectomy with pelvic lympha­den­ectomy or definitive radiot­herapy.
The advantage to a surgical approach is the possible preser­vation of ovarian function, the fact that the entire uterus is removed for analysis and the lack of long-term radiation side effects.
The advantages to definitive radiot­her­apy includes the lack of a need for prolonged general anesth­esia, especially if high-d­ose­-rate (HDR) brachy­therapy is to be used.
For more advanced disease the management is generally definitive radiot­herapy with both external beam and brachy­the­rapy.
Low-do­se-rate (LDR) brachy­therapy has the longest experience record but as HDR brachy­therapy has become widely available this approach is also favour­able. There are advantages and disadv­antages to each. Concurrent chemot­herapy is also widely used in this group.

Carcinoma of the Vagina

The incidence rate is low.
Radi­ation therapy does provide excellent tumour control in early and superf­icial lesions, with satisf­actory functional results.
This makes it imperative that radiation therapy techniques yielding optimal tumour control and functional results are utilised.
Otimal therapy for each stage is not well-d­efined in the litera­ture.
Intra-­cav­itary and inters­titial irradi­ation is used in small superf­icial stage-I disease. A combin­ation of external beam radiation therapy, intra-­cav­itary brachy­therapy (ICB) and/or inters­titial brachy­therapy (ITB) with or without chemot­herapy is used in more extensive stage-I and stages II–IV disease.

Cervical Cancer Simulation and Planning

Design of the radiation treatment program depends on the extent and volume of the tumour.
Most patients receive a combin­ation of external beam treatments and brachy­the­rapy, although very early lesions may be treated with brachy­therapy alone.
Advanced tumours require more external beam therapy. This is in part because the periphery of large tumours are inadeq­uately treated with brachy­therapy due to the rapid decrease in dose incurring at a distance from the implant.
To treat advanced tumours, the majority of the external beam therapy is given prior to initiating brac­hyt­her­apy to shrink the tumour. This leads to a techni­cally superior brachy­therapy applic­ation and may result in radi­obi­olo­gical advant­ages.
Cancer of the uterine cervix spreads in a very predic­table manner, first spreading laterally to the para cervical nodes, then to the internal common iliac and finally to the para-a­ortic nodes.
The large range of organ motion in the pelvis creates challenges for Radiation Therapists and Oncolo­gist, however the benefits of smaller PTV (planning target volumes) are extremely important as the PTV volume is directly related to the treatment toxici­tie­s/side effects.
External Beam:
The patient may be positioned supi­ne, prone or prone on belly-­boa­rd.
It could be argued that the patient will be more stable in the supine positi­on, therefore the treatment delivery will be more accurate.
When the treatment fields are as large as they are for gynaec­olo­gical malign­ancies, side effects induced become paramount. Therefore some centres will treat all of these patients prone on bellyboard to reduce small bowel toxici­ty.
Small bowel cont­rast will be admini­stered prior to the patient getting on the simulator couch to help visualised the volume of the organ within the treatment fields. If large amounts of small bowel are included, the radiation oncologist may alter the field size or add shielding to minimise toxicity.
If large amounts of small bowel are included, the radiation oncologist may alter the field size or add shielding to minimise toxici­ty.
Vaginal markers are necessary, patients may have had gold seeds implanted or the radiation oncologist will insert a contra­st-­coated tampon into the vagina. The vagina is not easily visualised on CT, so the tampon assists the radiation oncologist in orient­ating to the patient’s individual anatomy when defining the radiation fields.
The CT scan acquired and transf­erred to the treatment planning computer.
The radiation oncolo­gists will mark the target volumes on the CT, or MRI.
For patients with cervical cancer the target volume is the cervix, uterus, uteros­acral ligaments and nodes deemed at risk or known to harbour metastatic disease. The uterus is easily seen by means of CT scan or MRI. More difficult to visualise are ligaments which need to be included, especially in more advanced disease states. The bladder and rectum are outlined, as is the small bowel and kidneys.

Female pelvis imaging outlined

Cervical Cancer Dose/f­rac­tio­nation

Daily doses of 1.8 – 2.0 Gy are generally delivered. Depending on the treatment intent and combin­ation of external beam radiation and brachy­the­rapy, total dose will range from 45 – 55Gy.
Many studies or clinical trials utilise 50.4 Gy in 28 fracti­ons. Treatment will be delivered once daily, 5 fractions per week, over 5.5 weeks.
External beam treatment may be delivered in a phased approach, whereby the treatment fields are reduced down for the later fractions to reduce toxicity.
Eval­uation of the plan. Plan criteria:
-the isocentre is in the correct position
-the dose distri­bution is homoge­neous meeting ICRU dose recomm­end­ations, and
-dose to critical struct­ures: small bowel, rectum, femoral head, and bladder using dose volume histog­rams.
Organ at risk tolerance dose guidel­ines:
Small bowel < 30% to receive ≥ 40 Gy
Rectum < 60% to receive ≥ 30 Gy
Bladder < 35% to receive ≥ 45 Gy
Femoral head ≤ 15% to receive ≥ 30 Gy

Treatment

Whole pelvis radiot­herapy (RT) for gynaec­olo­gical cancer has remained largely unchanged for decades, and the associated gast­roi­nte­stinal, genito­uri­nary, and haemat­olo­gical toxici­ties resulting from these large fields have been accepted as unavoi­dable. The addition of conc­urrent chemo-­rad­iot­her­apy improves the overall survival rates for cervical cancer, at the cost of incr­eased acute toxicity. Late Grade 3 or 4 toxicity is estimated to affect ≤20% of patien­ts.
IMRT is the external beam treatment technique of choice for gynaec­olo­gical cancers.
Dose fracti­onation sche­dules could include:
-50.4 Gy/1.8 fractions to pelvic lymph nodes + 20 Gy to cervix
-50.4 Gy/1.8 fractions + 6 Gy brachy­therapy + cisplatin
-Pre-operative Conformal RT: 46.4 Gy∗ (42.8–­46.4)
-Post-operative: 50.4 Gy∗ (50.4–64)

VERIFI­CATION and LOCALI­SATION

Internal organ motion (IOM) is an important factor in gynaec­olo­gical patients. Movement of the cervix and uterus have signif­icant impacts on margins.
The uterus has been found to move with respect to bladder filling and the largest effect is in the Sup/Inf direction. The median movement if the corpus uterus has been found to be 7mm in several studies with a range of 3-15mm recorded, the the cervix 4mm, with a range of 1-6mm.
Daily online verifi­cation may be required for treating tumours with very small margins or those likely to have large internal movements.

Anatomical structures in the pelvic region

Compli­cations

Cancer of the Cervix and Endome­trium side effects depend on multiple factors.
Trea­tment related factors include the size of the treatment volume, treatment fields delivered, critical struct­ures, fraction size, total dose, whether the patient is having external beam and/ or brachy­therapy and/ or concurrent cytotoxic chemot­herapy, and the brachy­therapy technique used.
Pati­ent­-re­lated factors include: the stage and extent of the disease, weight, age, smoking history and number of previous abdominal surgical procedures
Side effects:
Acute sequelae including: diarrhea, bowel irritation (gas and/or cramping), cystitis, skin erythema, fatigue, and lowered peripheral blood counts, ovarian failure occurs in nearly all patients.
Gast­ro-­int­estinal (GI) side effects may also present early into the course of treatment.
Mild bladder irrita­tion, the patient should be informed to increase their fluid intake
If extended fields are used to treat patients then this may cause nausea and sometimes gastric irrita­tion.
If the patient is on conc­urrent chemot­her­apy for the disease all of the above reactions are likely to be of incr­eased severi­ty.
Brac­hyt­herapy risks include: uterus rupture, fever, and the usual risks of anaest­hesia.
The long term compli­cat­ions include: rectal bleeding, stricture, ulcera­tion, fistula, small bowel obstru­ction occurs very rarely, a constant low risk of urinary tract compli­cat­ions.
Radi­ati­on-­induced injury to the small and/or large bowel is not simply dependent on radiation dose, fractions, amount of exposure and fields selected alone. There appears to be a complex intera­ction of patient, genetic and treatment factors that contribute to incidence, severity and chronicity of symptoms
Late injury due to small vessel injury with endoth­elial damage, inflam­mation fibrosis, ischaemia and necrosis typically becomes sympto­matic after a latent period between the end of acute effects and the develo­pment of late effects, but there may be a continuous progre­ssion from oedema, mucosal and submucosal inflam­mation and persistent ulceration to fibrosis
Clinically severe late radiation damage can present as stri­ctures and stenoses with obstru­ction, fistulas and bowel perfor­ation
There is a risk of vaginal shorte­ning partic­ularly in older and post menopausal women. This can be very distre­ssing and be a sensitive issue for patients and their partners to deal with.
Advice should be given to the patient on sexual activity during and after the course of treatment.
Some indivi­duals or couples may require sexual coun­sel­ling for issues related to the diagnosis and so should be referred to the approp­riate member of the mult­i-d­isc­ipl­inary team.

Follow up

The radiation oncologist will follow up the patient around six weeks post completion of the radiation therapy.
After six weeks any radiat­ion­-in­duced side effects should have subsided, and there should be some indication of tumour response.
After six weeks any radiat­ion­-in­duced side effects should have subsided, and there should be some indication of tumour response.
  

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