Portec 1

Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial

Pubmed

Hypothesis:
Addition of external beam radiation after surgery in early stage endometrial cancer improves survival

Site:
Endometrium

Experimental arm:
Surgery followed by 46 Gy in 2 Gy daily fractions, 3 or 4 field technique (Fields: superior border at L5/S1)

Standard Arm:
Surgery alone

Eligibility Criteria

  • TAH/BSO without routine LND with these criteria
    Invasion Grade
    >50% (deep) 1
    any 2
    <50% superficial 3
  • WHO score of 0-2
  • Histologies allowed:
    • Endometrioid (also including adenocarcinoma with squamous features)
    • Adenocarcinoma not otherwise specified
    • Adenosquamous carcinoma
    • Papillary serous carcinoma
    • Clear-cell carcinoma

Primary Outcome:
Locoregional recurrence and overall survival

Results:

Outcome EBRT Observation p-value
Locoregional Recurrences 4% 14% SS
Overall Survival** 81% 84% NS
Major Toxicity 25% 6% SS
  • 73% recurrences in the vagina. Rate of distal mets same ~7% each arm
  • Prognostic Factors: Age >60, G3, IC predictive for LR; If 2 of 3 criteria, LR 23% vs. 4% (SS)

Conclusions:
Postoperative radiation improves locoregional control, but no survival benefit


See Radiation Oncology WikiBook for more details ↩︎

GOG 99

GOG 99

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

Pubmed

Hypothesis:
Addition of external beam radiation to postoperative therapy in intermediate risk endometrial cancer improves recurrence free survival

Site: Endometrium

Study population:
Inclusion: Derived from GOG 33

  • Intermediate Group: Any myometrial invasion with any grade and negative lymph node involvement i.e ([FIGO] stage IB, IC, IIA (occult), and IIB [occult]) – 5-year recurrence rate of 20 – 25%
  • Lymph node – Sampling/debulking if suspicious; Full lymphadenectomy if no enlarged or suspicious nodes
  • Revised during the course of study to enroll only “high intermediate risk” group : Expected 25% recurrence risk:
GOG 99 High Intermediate risk Group. Also used in GOG 249
    -  Age
    -  G2-3 tumor
    -  LVI
    -  Outer 1/3 myometrial invasion

1) >70 yrs old with only 1 other risk factor
2) >50 yrs old with 2 risk factors
3) any age with 3 risk factors

Excluded: High risk pathologies i.e. Clear cell and Papillary Serous, laparoscopic surgery excluded.

Experimental arm:
190 patients: External beam radiation 50.4 Gy given in 28 fractions. No Vag brachytherapy

Standard Arm:
202 patients: No additional therapy after surgery

Outcomes: Experimental arm vs. Standard arm (OR and p-values)

  • Primary Outcome (Recurrence Free @ 24 months) – 3% vs. 12% (OR – 0.42, p=0.007)
  • Secondary Outcome (Overall Survival @ 48 months) – 92% vs. 86% (OR – 0.86, p = 0.557)
  • Local Recurrences – 1.6% vs. 8.9% (p = ss)
  • Significantly Different Toxicity (Grade 2 or greater):
    • Hematologic: 7.4% vs 2.5% (p = ss)
    • GI : 34% vs. 2.5% (p = ss)

Conclusions:

  • Radiation reduced local recurrences but did not improve overall survival
  • Many deaths in the study were not endometrial cancer specific, therefore study underpowered to detect difference in overall survival even if it existed.
  • HIR group (132 total patients) : Defined above
    • Reduction in Hazard of isolated recurrence (RH: 0.37)
    • Reduction in Distant metastatic recurrence related to RT (RH: 0.46)
  • 2/3rd of recurrences and 2/3rd of cancer deaths in this group.
  • HIR – 19% improvement in cumulative recurrence at 24 months compared to no adjuvant therapy group vs LIR group 4% improvement compared to no adjuvant therapy group.

This study was the basis of GOG 249 selection criteria.


PORTEC 3

Pubmed

Study Summary by: Dr. Kevin McCool

Title: Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomized, phase 3 trial

Hypothesis: To investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.

Standard Arm: EBRT (48.6 Gy in 1.8 Gy fractions)

Experimental Arm: EBRT (48.6 Gy) Chemotherapy (Cisplatin 50 mg/m2 in weeks 1 and 4 during RT followed by 4 cycles of Carboplatin AUC5 and Paclitaxel 175 mg/m2)

Design: Open-label, randomized, multi-center (UK, Australia, Italy, Canada, France)Inclusion Criteria:
– Endometrioid:

  • Stage IA Grade 3 with with LVSI

  • Stage IB Grade 3

  • Any Stage II or  III.

  • Serous or Clear Cell: Stage IA (with invasion), IB, II, III

Exclusion Criteria (outside of usual): Carcinosarcoma, prior malignancy within 10 years, prior radiotherapy, hormonal therapy, chemotherapy, bulky cervical involvement with radical hysterectomy, residual macroscopic disease

Primary Endpoint: Co-primary endpoints were failure-free survival (FFS) and overall survival (OS)

Outcomes: ChemoRT vs. RT alone (HR and p-value)

  • OS: 81.8% vs.76.6% [HR 0.76 (p=0.109)]
  • FFS: 75.5% vs. 68.6%[HR 0.71 (p=0.022) favoring chemotherapy RT]
  • Subgroup analysis: Stage III patients
    • 5 year FFS = 69.3% vs 58.0% (HR=0.66, p=0.031)
    • 5 year OS = 78.7% vs. 69.8% (HR=0.71, p=0.13)

Serious Adverse Events: ChemoRT vs. RT alone (p-value)

  • Any hematologic: 45% vs. 5% (p<0.0001)
  • GI: 14% vs. 5% (p<0.0001)
  • Neuropathy: 7% vs. 0% (p<0.0001)
  • At 12 months no significant difference in any grade 3 toxicity

Conclusions:

  • Improvement in FFS with the addition of chemotherapy. OS unchanged
  • Significant improvement in FFS
  • Most benefit in patients with stage III
  • Age is a significant predictor on risk adjustment. Patients above 70 benefit from chemoradiation (however toxicity discussion is warranted)

GOG 161

Phase III Trial of Ifosfamide With or Without Paclitaxel in Advanced Uterine Carcinosarcoma: A Gynecologic Oncology Group Study

Pubmed

Hypothesis:Addition of paclitaxel to ifosfamide improve OS/ PFS in carcinosarcoma (GOG 108 there was no advantage to the combination of ifosfamide and cisplatin vs. ifosfamide alone related to median survival. GOG 130-B revealed a substantial response rate of carcinosarcoma to single-agent paclitaxel.)

Site: Uterus

Experimental arm: Ifosfamide 1.6 g/m2 IV daily for 3 days (1.2 g/m2 for irradiated patients) plus Paclitaxel 135 mg/m2 by 3 hour infusion day 1

Standard Arm: Ifosfamide 2 g/m2 IV for 3 days

Mesna iv or oral 1

Primary Outcome: Overall survival (OS)

Results:

Outcome Ifos Ifos Taxol p-value
OS (months)2 8.4 13.5 SS
PFS (months) 3.6 5.8 SS
ORR3 29% 45% SS
Toxicity
G1-4 neuropathy 8% 30% SS
Alopecia 40% 58% SS
Thrombocytopenia 11% 46% SS
G3-G4 Neutropenia 53% 44% NS

CNS related toxicity was similar in two arms

Conclusions:

  • Combination chemotherapy with Ifosfamide Taxol improves OS.
  • Treatment effect not different based on prior radiation or previous site of disease
  • No Quality of life assessments in this study

  1. Read GOG 261 design and mesna dosing schedules ↩︎
  2. Hazard Ratio: 0.69 (95% CI, 0.49 to 0.97; P = .03) ↩︎
  3. Overall Response Rate ↩︎