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HDR Therapy for Uterus Cancer

High Dose Rate (HDR) Machines produce radiation that can be inserted through a a catheter (tube.) This allows a device that can be inserted in the uterus or vagina and then attached to this machine. The treatment can be completed in minutes (because of the high does rate) rather than traditional radium or cesium insertions (that took 48 to 72 hours.) (Picture on left, tube inside the uterus, on the right the more common situation of cylinder in vagina used to prevent a vaginal cuff recurrence after hysterectomy.)

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Side effects are uncommon (go  here.) CT images of the HDR in the pelvis will demonstrate the amount of radiation that reaches other organs (e.g., the bladder or rectum) see here and hereInsertion of an HDR vaginal tube will probably be more effective than external beam irradiation at preventing vaginal cuff recurrences (relapse after surgery: 18%, external beam: 7%, HDR: 0% in GOG) and HDR has less complications than external beam radiation (4% versus 38%.) In theory for women with high risk features (high grade, deep invasion, vascular invasion) postOp pelvic irradiation should be better than vaginal cuff HDR, but in many studies HDR alone may prove quite effective (particularly if the surgeon has already removed the nodes and found them to be negative...  see study and read the review from the Mayo Clinic. The dose guidelines for endometrial cancer are noted here.

There is considerable variation as to the dose used, commonly 700cGy X 3 or 500cGy X 5 usually measured at a depth of 5mm, some recent data (from IJROBP 1998;42:1033) are noted below:
patients total dose(Gy) fraction size(Gy) dose point vaginal recur.
256 35 7 5mm 1.2%
404 27-36 4.5-9 1cm 0.7%
946 21 7 5mm 0-2.4%
63 32.4 16.2 surface 0%
143 34 8.5 surface 1.4%
A common dose protocol (Leibel Text of Rad 1998:245) is EBT (45Gy with midline block for last 540cGy) + HDR (500cGy X 3 at 5mm) or for HDR alone 700cGy X 3

Selected Bibliography
Gynecol Oncol 1998 Oct;71(1):72-6

Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy.

Weiss. 122 patients with moderate-risk (78) and high-risk (44) endometrial carcinoma underwent adjuvant vaginal irradiation. All patients received three fractions of 7 Gy specified on the surface of the vaginal cylinder.Relapses occurred in 12 (9. 8%) patients on average after 25.6 months. Seven (5.7%) patients had a sole pelvic recurrence; in 2 (1.6%) of those the relapse was located in the vagina only. Three (2.5%) patients had a pelvic relapse combined with distant metastases. Distant metastases alone were diagnosed in 2 (1.6%) patients. A tumor recurrence was diagnosed in 3 of 78 (3.8%) patients with moderate-risk disease and in 9 of 44 (20.5%) patients with high-risk disease. The estimated 5-year relapse-free survival was 94% for patients with moderate-risk and 74% for patients with high-risk tumors

Int J Radiat Oncol Biol Phys 1998 Dec 1;42(5):1033-9

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer.

MacLeod . A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. RESULTS: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded

Obstet Gynecol 1996 Jun;87(6):1041-4

Surgical staging and high dose rate brachytherapy for endometrial cancer: limiting external radiotherapy to node-positive tumors.

Fanning. High dose rate brachytherapy was delivered postoperatively in three fractions for a total of 2100 cGy. Surgical staging and high dose rate brachytherapy without external radiotherapy for stage I-IIIA endometrial cancer were associated with minimal morbidity and produced excellent survival.

Int J Radiat Oncol Biol Phys 1998 Aug 1;42(1):101-4

Is there a role for a brachytherapy vaginal cuff boost in the adjuvant management of patients with uterine-confined endometrial cancer?

Greven.

There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer.

Am J Clin Oncol 1997 Jun;20(3):254-8

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis.

Hong.  69 women diagnosed with FIGO stages I and II carcinoma of the endometrium underwent postoperative adjuvant irradiation (RT) under protocol with high dose rate (HDR) afterloading vaginal apex brachytherapy. The 5-year disease-free survival was 92% and the overall survival rate was 79%. It appears that HDR vaginal brachytherapy is prevention of vaginal recurrence in endometrial carcinoma and should be considered an effective treatment option.

Int J Radiat Oncol Biol Phys 1985 Mar;11(3):473-8

Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique.

Mandell

 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and all Stage II patients in combination with surgery and intravaginal radiation. Vault radiation was delivered with a remote afterloading technique to a point .5 cm from the surface of the applicator; a total dose of 21 Gy was delivered in three fractions spaced two weeks apart over four elapsed weeks. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%.

Int J Radiat Oncol Biol Phys 1994 Nov 15;30(4):831-7

Postoperative high dose-rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: a long-term follow-up.

Nori. The actuarial progression-free survival rate was 96.6%. Post-treatment grade 1-2 actuarial complication rate was 9.5%, including cystitis (4.5%), vaginal stenosis (2.5%), proctitis (1.5%), vaginal necrosis (0.5%), and partial bowel obstruction (0.5%). Neither grade 3-4 complications nor additional late complications were observed in any of our patients. Relapse rate was only 3.7%.

Int J Radiat Oncol Biol Phys 1995 Jul 30;32(5):1439-43

Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a phase II clinical protocol.

Noyes High dose rate brachytherapy was delivered using an Iridium-192 HDR remote afterloader.  A dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63 patients.  no patient has developed a vaginal cuff recurrence.

Int J Radiat Oncol Biol Phys 1990 Jul;19(1):49-54

Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma.

Randall. After surgery and external radiation therapy, 103 patients (65.6%) received a vaginal cuff boost of 3000-5000 cGy surface dose (Group I) and 54 (34.4%) did not (Group II). One hundred and two Group I and 52 Group II patients were evaluable for analysis. Median follow-up was 78.0 months for Group I and 60.0 months for Group II. Despite a preponderance of poor prognostic factors in Group II, no significant difference in local failure was seen.  Based on this retrospective study, intracavitary vaginal cuff boost after surgery and postoperative external beam radiation therapy does not appear to improve local control in early endometrial adenocarcinoma.

Gynecol Oncol 1997 Aug;66(2):300-7

Isolated vaginal recurrences in endometrial carcinoma: treatment results using high-dose-rate intracavitary brachytherapy and external beam radiotherapy.

Pai . To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications.