Radiation Oncology/Endometrium/Definitive RT

Definitive Radiation Therapy (Inoperable Patients)

Brachytherapy applicator types:

• Standard tandem & ovoid
• Rotte applicator (HDR) - Y-shaped device for maximizing uterine coverage
• Simon-Heyman capsules - Intrauterine sources

Brachytherapy alone

• PMID 3698503, 1986 (1965–70) — "Results of intracavitary radium treatment for adenocarcinoma of the body of the uterus." Jones DA et al. Clin Radiol. 1986 Mar;37(2):169-71.
  • Non randomized. 160 pts. LDR intracavitary radium alone. Either two insertions (75 Gy over 10 days) or one insertion (50 Gy over 4 days).
  • Primary tumor control 77% (two insertions) vs 67% (one insertion). 5-yr and 10-yr OS 73%/62% vs 58%/34%.

• MDACC, 1993 (1960–86) - PMID 8244810 — "Treatment of endometrial carcinoma with radiation therapy alone." Kupelian PA et al. Int J Radiat Oncol Biol Phys. 1993 Nov 15;27(4):817-24.
  • Retrospective. 152 pts. 116 with brachytherapy alone, the rest with tele + brachy.
  • 5-yr disease-specific survival was 87% for Stage I, 88% Stage II, 49% for Stage III-IV. Worse outcome for papillary serous, 43% for Stage I-II.
  • Patients were twice as likely to die from intercurrent illness than from uterine cancer at 10 years.

• Vienna, 1997 (1981–92) - PMID 9069308 — "Primary treatment of endometrial carcinoma with high-dose-rate brachytherapy: results of 12 years of experience with 280 patients." Knocke TH et al. Int J Radiat Oncol Biol Phys. 1997 Jan 15;37(2):359-65.
  • 280 pts. 8.5 Gy x 4-5 fractions (intrauterine) weekly and 7 Gy x 1-2 (vaginal cylinder).
  • Mean f/u 55 mo. 5-yr OS 52%, DSS 76%, LC 75%.

External Beam RT + brachytherapy

• Washington U., 1987 - PMID 3558039 — "Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone." Grigsby PW et al. Int J Radiat Oncol Biol Phys. 1987 Apr;13(4):483-8.
  • 69 pts. Stage I. BT alone in 11, BT + low dose EBRT in 9, and "definitive" BT + high dose EBRT in 49.

• France, 1988 (1975–84) - PMID 3182345 — "Radiation therapy alone for medically inoperable patients with adenocarcinoma of the endometrium." Taghian A et al. Int J Radiat Oncol Biol Phys. 1988 Nov;15(5):1135-40.
  • 104 pts

• PMID 8226152, 1993 — "Primary radiation therapy for endometrial carcinoma: a case controlled study." Rose PG et al. Int J Radiat Oncol Biol Phys. 1993 Oct 20;27(3):585-90.
  • Retrospective. 64 pts. Stage I+II. 10 had brachytherapy alone, the rest had tele + brachy.
  • No difference in survival between these pts treated with primary radiotherapy and surgically-treated case controls.

• France, 1993 (1967–86) - PMID 8491680 — "Exclusive radiation therapy in endometrial carcinoma." Rouanet P et al. Int J Radiat Oncol Biol Phys. 1993 May 20;26(2):223-8.
  • Retrospective. 250 pts. All pts treated with 45 Gy EBRT followed by BT.
  • 5-yr OS 58%, DFS 55%.

• Washington U, 1996 (1965–90) - PMID 12118561 — "Medically inoperable stage I endometrial carcinoma: a few dilemmas in radiotherapeutic management." Chao CK et al. Int J Radiat Oncol Biol Phys. 1996 Jan 1;34(1):27-31.
  • 101 pts, clinical Stage I. EBRT only in 3 pts, brachy only in 26, EBRT + BT in 10, and whole pelvis with midline shield + BT in 62. Brachytherapy consisted of tandem + colpostats + Simon-Heyman capsules.
  • Median f/u 6.3 yrs. 5-yr pelvic control 88-100%.
  • Conclusion: radiation therapy should be continued regardless of a negative D&C specimen at the time of the 2nd intracavitary implant.

• Yale, 1996 (1975–92) - PMID 8626131 — "Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium." Fishman DA et al. Gynecol Oncol. 1996 May;61(2):189-96.
  • 54 pts.
  • Inoperable patients who did not die from intercurrent disease had a median 5-year survival which approaches that of operable patients

• McGill University, 2005 (1984–2003) - PMID 16099598 — "Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma." Niazi TM et al. Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1108-13.
  • 38 pts. 76% clinical Stage I. Treatment: HDR brachy alone in 79%, EBRT+BT in 21%. Brachytherapy technique: tandem alone, biconcave butterfly tandem, or tandem + colpostats (in Stage II pts). Median dose 24 Gy, in 3 fractions 1 week apart. Dose prescribed at 2 cm from central axis or at uterine surface (if using MRI). EBRT: median dose 42 Gy. Brachytherapy dose same if EBRT given.
  • Median f/u 57 mo. 22 deaths (32% died of disease, 68% from other causes). 29% experienced failure.

Non-standard fractionation:

• U.Pittsburgh, 2006 - PMID 16644466 — "Twice-daily high-dose-rate brachytherapy for medically inoperable uterine cancer." Gerszten K et al. Brachytherapy. 2006 Apr-Jun;5(2):118-21.
  • 22 pts. Twice-daily HDR in 5 fractions over 3 days. Pts received EBRT + HDR or HDR alone (favorable pts). Rotte applicator. Post-implant imaging with prescription dose covering "uterine points" based on CT imaging (not 3D planning). 4 Gy x 5 (if EBRT given) or 7 Gy x 5 (HDR alone).
  • No significant acute complications. 2 of 22 with Grade 1 proctitis.

Summary of doses used:

• EBRT + brachytherapy:
  • EBRT + 4700 mgh
  • EBRT 45 Gy + 30 Gy LDR at 1.5–2 cm
  • ABS recommendations (PMID 11020575) - 45 Gy EBRT + HDR 8.5 Gy x 2, 6.3 Gy x 3, or 5.2 Gy x 4 (all at 2 cm)
• Brachytherapy alone:
  • LDR 65 Gy (2 insertions of 32.5 Gy - at 1.5 cm lateral to the tandem)
  • LDR 60 Gy (2 x 30 Gy - at 2.0 cm)
  • LDR 72 Gy (2 x 36 Gy - at Point A)
  • LDR 80 Gy
  • LDR 3600 mgh x 2 (Kupelian, IJROBP 1993)
  • LDR 4000 mgh x 2 (Bond, Clin Oncol 1997)
  • HDR 10 Gy x 5 at 2 cm (Herbolsheimer, Endocuriether Hypertherm Oncol 1992)
  • HDR 8.5 Gy x 4 at 2 cm (Knocke, IJROBP 1997)
  • HDR (6 Gy x 5) x 2 (Bond, ibid.)
  • ABS recommendations (see above) - HDR 8.5 Gy x 4, 7.3 Gy x 5, 6.4 Gy x 6, or 5.7 Gy x 7 (all at 2 cm)

Treatment complications:

• Washington U, 1995 (1965–91) - PMID 7995766 — "Brachytherapy-related complications for medically inoperable stage I endometrial carcinoma." Chao CK et al. Int J Radiat Oncol Biol Phys. 1995 Jan 1;31(1):37-42.
  • 96 pts. Tandems + ovoids + Simon-Heyman capsules in all pts.
  • Morbidity rate: 4% (4 pts - 2-MI, 1-CHF, 1-PE), Mortality rate: 2% (2 pts - 1-MI, 1-PE).
  • Acceptable morbidity and mortality for high risk pts.