Radiation Oncology/Endometrium/UPSC

From Wikibooks, open books for an open world
Jump to: navigation, search


Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

Endometrial Carcinoma: Main Page | Staging | Overview | Early Stage | Locally Advanced Stage | UPSC | Clear Cell | Brachytherapy | Recurrence | Randomized | GOG Trials

Leiomyosarcoma: Main Page


Uterine Papillary Serous Carcinoma

Overview[edit]

  • Please also see Endometrium Overview page
  • First identified at Stanford in 1982, where it comprised ~10% of Stage I endometrial CA but resulted in 50% of relapses. Many relapses were characterized by upper abdominal failure
  • Due to similar behavior as ovarian carcinoma, adjuvant abdominal radiation was proposed
  • GOG started a trial in 1986 (GOG 94) to evaluate treatment of advanced endometrial cancer with whole abdominal RT (WART), pelvic RT, and para-aortic boost as necessary. Eligible patients included Stage I-II UPSC and CC. Over 50% of failures for UPSC/CC patients were within the radiation field. WART alone is not sufficient
  • Evidence suggests better outcome for clear cell than for UPSC

Pathology[edit]

  • 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

Pathology[edit]

  • Stanford; 1982 PMID 7102898 -- "Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma." (Hendrickson M, Am J Surg Pathol. 1982 Mar;6(2):93-108.)
    • Retrospective. 256 Stage I uterine adenoCA reviewed, 26 UPSC identified. High cytologic anaplasia and papillary growth pattern. Frequent LVI+, frequent Stage IC (40% vs. 12%)
    • Outcome: relapse rate ~50% vs. 5%; Stage IC relapse 63% vs. 30%. Tendency to relapse over peritoneal surfaces
    • Conclusion: Clinically aggressive, similar to ovarian CA


Stage I[edit]

  • Mayo; 2007 (1982-2005) PMID 17688926 -- "Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma." (Thomas MB, Gynecol Oncol. 2007 Aug 2; [Epub ahead of print])
    • Retrospective. 42 patients (IA 15, IB 21, IC 6). 81% LND, 69% omentectomy, 45% peritoneal biopsies. Median F/U 3.2 years
    • Outcome: 5-year OS 85%, PFS 78%. By stage OS IA 100%, IB 89%, IC 60%.
    • Recurences: LN recurrence in LND 0/34 vs. no LND 1/8 (NS); none in IA regardless of post-op therapy; 0/20 IB and IC who had vaginal BT vs. 2/7 with no vaginal BT (SS). Hematogenous/peritoneal recurrence in 0/6 patients with chemo vs. 3/13 patients with no chemo.
    • Conclusion: Observation reasonable for IA if LND done; for IB and IC consider chemotherapy and vaginal brachytherapy
  • Yale; 1998 PMID 9422561 -- "Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy." (Turner BC, Int J Radiat Oncol Biol Phys. 1998 Jan 1;40(1):77-84.)
    • Retrospective. 38 patients treated with TAH/BSO, +/-LND, with combinations of chemo and RT. 20 patients vaginal LDR with WART or WPRT (6/20 had complete surgical staging, 2/20 concurrent chemo). 18 patients vaginal HDR (15/18 had complete surgical staging, 5/18 concurrent chemo).
    • Outcome: 5-year OS complete surgical staging and HDR /chemo 100% vs. incomplete staging HDR/chemo 61% vs. complete staging LDR/WART 100% vs. incomplete staging LDR/WART 65%. OS by stage IA 100%, Stage IB 71%, Stage IC 40%
    • Toxicity: WART and/or LDR had Grade 3-4 toxicity in 15%, complications from vaginal HDR minimal
    • Conclusion: If complete surgical staging, can be effectively and safely treated with vaginal HDR and chemotherapy

"Sandwich" chemotherapy and radiation[edit]

  • Albert Einstein; 2012 PMID 22035806 -- "Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma." (Einstein MH, Gynecol Oncol. 2012 Jan;124(1):21-5. Epub 2011 Oct 27.)
    • Phase II. 81 patients (89% completed chemo->RT and are reported here), surgically staged UPSC, no visible residual. Stage I/II 82%, Stage III/IV 18%. Adjuvant paclitaxel 175 mg/m2 and carboplatin AUC 6 Q3 weeks x 3 cycles, followed by RT (pelvis 45/25, PA if 2+ pelvic nodes or documented PA disease, HDR vaginal brachytherapy 5 Gy x 3 at 0.5 cm), followed by chemotherapy x 3 cycles. Protocol completion 83%
    • Outcome: Stage I/II OS 6.3 years, Stage III/IV OS 3.0 years. 3-year OS 84% and 50%. PFS 5.4 years and 2.1 years
    • Toxicity: G3/4 non-hematologic toxicity 2.5%
    • Conclusion: RT-chemotherapy "sandwich" is well and highly efficacious in completely resected UPSC

Patterns of Failure[edit]

  • Westmead Hospital, Sydney, Australia; 2009 (1995-2006) PMID 19694700 -- "Uterine papillary serous carcinoma: patterns of failure and survival." (Wang W, Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):419-25.)
    • Retrospective. ? patients, TAH/BSO/surgical staging, majority with platinum-based chemotherapy and radiotherapy
    • Outcome: 2-year OS 65%, 5-year OS 43%. Macroscopic residual disease only predictor of survival (if R2, median OS 11 months). Site of recurrence vagina (n=5; for VBT 1/16 recurrences, for EBRT 4/7 recurrences), pelvic LN (n=24), para-aortic LN (n=6), inguinal LN (n=2), abdomen (n=11), and distant mets (n=7)
    • Conclusion: Recommend optimal cytoreduction; vaginal brachytherapy should be considered as a component of adjuvant raditherapy. Abdominal failure most common

Whole Abdomen RT[edit]

  • 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).


Phosphorus-32 (P32)[edit]

  • 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

Reviews[edit]

  • 2009: SGO PMID 19592079 PDF -- "Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review." (Boruta DM, Gynecol Oncol. 2009 Oct;115(1):142-53.)