Endometrial and Ovarian Cancer - American Society for Radiation [PDF]

Post Operative Radiation Therapy in. Endometrial Carcinoma. • Selected Clinical Stage I. Grade 1 > ½ MI. Grade 2 a

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Endometrial and Ovarian Cancer William Small Jr., MD Professor and Chairman Loyola University, Chicago

Learning Objectives: •Discuss the role of radiation therapy in early stage and advanced stage endometrial cancer. •Review controversies in Radiation Techniques. Explain the role of surgery and surgical staging in the management of endometrial cancer. •Review the role of chemotherapy in the management of early and advanced stage endometrial cancer. •Review the role of Radiation in Ovarian Cancer.

Who will win the Super Bowl this Year ?

1. The Chicago Bears. 2. The NFL team from Chicago. 3. I don’t care as long as the Packers are not in the Super Bowl.

Endometrial Cancer Estimated New Cancer Cases and Deaths by Sex, 2014 Women Incidence

Deaths

All

810,320

275,710

Breast

232,670

40,000

Lung

108,210

72,330

Colon/Rectum

65,002

24,040

Uterine

52,630

8,590

American Cancer Society, Surveillance Research, 2012

“The reports of my death have been greatly exaggerated.” -Mark Twain

“There are three kinds of lies: Lies, Damned Lies, and Statistics.” -Benjamin Disraeli -Mark Twain

FIGO 1988

Surgical staging System Early stage disease • Stage I IA Limited to the endometrium IB < half of the endometrium IC > half of the endometrium • Stage II Corpus and cervix IIA Endocervical glands only IIB Endocervical stromal invasion

FIGO 1988

Surgical staging System Late stage disease • Stage III IIIA Tumor Involves the serosa and/or adenexa (direct extension or metastasis) and/or cancer cells in ascites or peritoneal washings IIIB Vaginal Involvement III C Metastasis to Pelvic or Para-aortic Lymph Nodes • Stage IV IVA Tumor Involves the bladder or bowel mucosa IVB Distant Metastasis

FIGO 2009

Surgical staging System Early stage disease • Stage I IA No or < half of the endometrium IB = or > half of the endometrium • Stage II Corpus and cervix Endocervical stromal invasion

Int J Obs Gyn, May 2009,

FIGO 2009

Surgical staging System Late stage disease • Stage III IIIA Tumor Involves the serosa and/or adenexa (direct extension or metastasis) IIIB Vaginal and/or parametrial Involvement III C1 Metastasis to Pelvic Lymph Nodes IIIC2 Metastasis to Para-aortic +/- pelvic Lymph Nodes • Stage IV IVA Tumor Involves the bladder or bowel mucosa IVB Distant Metastasis and/or inguinal metastasis

Post Operative Radiotherapy Early Stage Disease Very contentious Disease All Patients Receive Adjuvant RT Even Low Grade Minimally Invasive Tumors

No Patients Receive adjuvant RT Even High Grade Deeply Invasive Tumors

Center A

Center B

Postoperative RT Rationale • Early stage patient with adverse pathologic features are at risk for extra uterine disease and recurrence • Most commonly cited pathologic factors -Myometrial Invasion (MI) -Tumor Grade -Cervical involvement - Age - LVSI • Importance demonstrated in GOG33

GOG 33 • Surgical Pathologic study of 621 stage I pts Positive Pelvic LNs

Positive PA LNs

Grade 1

3%

2%

2

9%

5%

3

18%

None

1%

1%

Superficial

5%

3%

Middle

6%

1%

Deep

25%

P half

15.1

MI

Unfortunately Grade and Myometrial invasion not combined in the analysis Price et al. Am J Obstet Gynecol 1965; 91:1060

What evidence supports the use of Adjuvant Radiation Therapy is Stage I & II Endometrial Carcinoma ?

Retrospective studies also suggest benefit of Adjuvant RT in patients with adverse pathologic factors Pelvic Recurrence with RT

Pelvic Recurrence without RT

Carey 1995 High Risk pts Deep MI, G3, +Cx, Adenos.

3.9%

14.3%

Pitson 2002 Stage II (55% IIA)

5.6%

22.2%

Carey et al, Gynecol Oncol 1995; 57:138 Piston et al, Int J Radiation Oncol Bio Phys 2002; 53:862

Retrospective studies also suggest benefit of Adjuvant RT in patients with adverse pathologic factors • In a retrospective review of 927 patients Stage I&II pts Vaginal Recurrence with RT – either Vault or Total Vagina

Vaginal Recurrence without RT

Stage I Low Risk G 1 – 2, 1/3 MI

1.3%

11.7%

Stage II

5.2 %

12.8%

Elliot at al., Int J Gyne cancer 1994; 4 : 84

Post operative RT Stage I & II Disease • Five prospective randomized trials have been conducted to evaluate post operative radiotherapy in early stage disease – – – – –

Norwegian Trial PORTEC 1 GOG 99 ASTEC/EN 5 PORTEC 2

Norwegian Trial • Clinical Stage I • 540 Patients • TAH + BSO without LN Sampling • No assessment of peritoneal cytology

Vaginal Brachytherapy LDR 60 Gy @vaginal surface Arm 1

Arm 2

Pelvic RT 40 Gy Midline block after 20 Gy

No further therapy

Aalders et al, Obstet Gynecol 1980; 56(4);419

Norwegian Trial • Pelvic RT reduces vaginal / pelvic failures in patients with high risk features (deep MI & G3 Tumors)

Vaginal/Pelvic recurrence

Grade 1 – < ½ MI 2 Tumors > ½ MI

No RT 4% 9.8%

With RT 2.3% 9.4%

Grade 3 Tumors

5.6% 19.6%

2.1% 4.5 %

< ½ MI > ½ MI

Aalders et al, Obstet Gynecol 1980; 56(4);419

Norwegian Trial • No Overall survival benefit with Radiotherapy 5 Years Survival Rate Pelvic RT 89% No Pelvic RT 91% Only in Patients with deeply invasive Grade 3 Tumors Death from Cancer Pelvic RT 18.2% No Pelvic RT 27.5% Aalders et al, Obstet Gynecol 1980; 56(4);419

LVSI 





LVSI was evaluated in the last 151 patients on trial. Vessel invasion seen in 19.9 % of the patients. Local recurrence 21 % in the no Pelvic RT group versus none in the Pelvic RT group.

Aadlers Trial: Conclusions • Grade 3> 50 % invasion – pelvic RT. • All patients with LVSI receive pelvic RT • All other patients with invasion receive VBT.

PORTEC Trial Post Operative Radiation Therapy in Endometrial Carcinoma • Selected Clinical Stage I Grade 1 > ½ MI Grade 2 any MI Grade 3 < ½ MI • 715 Patients • TAH + BSO without LN Sampling • All histologies

• Regimen 1 Pelvic radiotheraoy 46 Gy / 23 Fractions No Vaginal Brachytherapy

• Regimen 2 No further Treatment

• • • •

HIR Definition – Recent Publication

Age > 60 Grade 3 Invasion >50% HIR defined as: 2 of those 3 factors present (except for grade 3 with deep invasion = high risk, eligible for PORTEC3)

Fig. 3

Source: International Journal of Radiation Oncology * Biology * Physics (DOI:10.1016/j.ijrobp.2011.04.013 ) Copyright © Elsevier Inc. Terms and Conditions

PORTEC – 10-year outcome with PA review Locoregional recurrence (actuarial rates) All pts

5-yr

10-yr

p

RT No RT

3% 13%

5% 14%

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