Radiation Oncology/Endometrium/Clear Cell

Endometrium Clear Cell Carcinoma

Pathology

• Endometrioid (75-80%)
• Clear cell (5-10%)
  • Clear due to presence of glycogen
  • Tubulocystic, papillary, or solid patterns
  • Psammoma bodies not as common
  • Have to be present in at least 25-50% (depending on pathologist) of sample to qualify as clear cell
  • Aggressive, with myometrial invasion in ~80%
• Papillary serous (1-5%)
  • Complex papillary architecture, similar to papillary serous CA of ovary
  • Presence of psammoma bodies
  • Marked nuclear atypia
  • Believed to transform from endometrial surface epithelium
• Mixed pattern
  • Serous and endometrioid histology present next to each other in the specimen
  • If >50% serous component, classified as papillary serous
  • If 10-50% serous component, classified as mixed serous
• Rare tumor types (<2%)
  • Mucinous, squamous cell, transitional cell, small cell

Whole Abdomen RT

• GOG 94 (1986-1994)
  • 2006 PMID 16213007 -- "Adjuvant whole abdominal irradiation in clinical stages I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the Gynecologic Oncology Group." (Sutton G, Gynecol Oncol. 2006 Feb;100(2):349-54.)
  • Phase II. 21 patients treated with TAH/BSO, PPALND, WART 30/20 and pelvic boost to 50 Gy
  • Outcome: >50% failures within RT field
    • UPSC: 5-year OS 38%, PFS 38%
    • Clear cell: 5-year OS 54%, PFS 54%
  • Toxicity: 17% Grade 3-4 GI toxicity (SBO, proctitis, N/V)
  • Conclusion: WART alone not adequate, chemotherapy needs to be a component of treatment. Clear cell better outcome than UPSC

• Stanford; 2000 (1979-1998) PMID 11020574 -- "Treatment of high-risk uterine cancer with whole abdominopelvic radiation therapy." (Smith RS, Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):767-78.)
  • Retrospective. 48 patients with Stage III-IV endometrial ACA (n=22) or Stage I-IV UPSC or CC (n=26), treated with postop WART. Median dose 30 Gy abdomen (in 1.2-1.5 Gy/fx) and 50 Gy pelvis (in 1.2-1.8 Gy/fx). PALN boost to 44 Gy in 9 patients. Vaginal brachy in 24 patients. Mean F/U 3.1 years
  • Outcome: 3-year OS all patients 77%, ACA 89% vs. UPSC/CC 68%; UPSC/CC Stage I-II OS 87% vs. Stage III-IV 61%; DFS 87% vs. 31%
  • Toxicity: major complications (SBO) 7%, no deaths, 23% required break >1 week
  • Conclusion: WART is safe, effective. Recommend with vaginal cuff brachy for Stage I-II. Recommend with concurrent or sequential chemo in Stage III-IV UPSC/CC until results of GOG 94 and GOG 122 become available (see Advanced Stage chapter).

Retrospective results

• U. Chicago; 2003 (1980-2000) PMID 12654437 PDF -- "Outcome and patterns of failure in pathologic stages I-IV clear-cell carcinoma of the endometrium: implications for adjuvant radiation therapy." (Murphy KT, Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1272-6.)
  • 38 pts with clear cell histology who were treated with TAH/BSO. 22 received post-op RT.
  • 5-yr DFS 38.5%. Median time to failure 18 mos. There was no correlation of outcome with stage, myometrial invasion, cervical invasion, peritoneal fluid, or extrauterine involvement. Of 16 relapses (42%), 8 failed in the pelvis; no pelvic failures for those treated with RT. 6 pts (16%) para-aortic node recurrence; 5% - abdomen; 24% - distant.
  • Conclusion: Recommend RT to the pelvis, even in early stage cases.

Phosphorus-32 (P³²)

• HOG 97-01 PMID 15721431 -- "Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study." (Fakiris AJ, Gynecol Oncol. 2005 Mar;96(3):818-23.)
  • Phase II. 21 patients s/p TAH-BSO, residual peritoneal disease <3mm, negative PPALN. Intraperitoneal P-32 15 mCi within 8 weeks. Vaginal BT. Median F/U
  • Outcome: 2-year OS 89%, DFS 80%; recurrences 5/21, but only 2/21 intraperitoneal
  • Toxicity: No Grade 2-4
  • Conclusion: Adjuvant intraperitoneal P-32 and vaginal BT feasible, well tolerated