Radiation Therapy With or Without Chemotherapy in Patients With Stage I or Stage II Cervical Cancer Who Previously Underwent Surgery

• RFS [ Time Frame: From protocol registration to date of first documented recurrence, death or date of last contact, assessed up to 11 years ] [ Designated as safety issue: No ]
  Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha=0.05) will be used to compare RFS between treatment arms.
  
  

• OS [ Time Frame: From entry into the study to death; or for living patients, the date of last contact regardless of whether or not this contact is on a subsequent protocol, assessed up to 11 years ] [ Designated as safety issue: No ]
  Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha=0.05) will be used to compare OS between treatment arms.
  
  
• Local control [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  Assessed with Exact Logistic Regression adjusted known prognostic factors.
  
  
• Site(s) of recurrence [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  The site(s) of first disease recurrence will be classified as: pelvic-only, extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment group. The test of the hypothesis that the probability of local failure is independent of randomized treatment will be assessed with exact logistic regression adjusted know prognostic factors.
  
  
• Incidence of adverse events graded according to the active version of CTCAE [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  In addition to displaying frequency of adverse events for each grade category, significance of observed differences between treatment arms within each category will be analyzed using Fishers' exact test.
  
  
• Patient risk-benefit [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  
• Treatment compliance [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  Assessed by the number of cycles and amount of chemoradiotherapy administered, treatment span, incidence and duration of treatment delays, reason for delays, and reason why off study therapy.
  
  
• Quality of life, assessed using the FACT-Cx TOI, FACT-GOG/neurotoxicity 4 subscale, and the Brief Pain Inventory (BPI) [ Time Frame: Up to 9 months following the first day of treatment ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To determine if post-operative adjuvant chemo-radiation therapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in stage I-IIA cervical cancer patients with intermediate-risk factors after treatment with radical hysterectomy.

SECONDARY OBJECTIVES:

I. To determine whether post-operative adjuvant CRT can improve overall survival (OS) when compared to RT alone in stage I-IIA cervical cancer patients with intermediate risk factors after treatment with radical hysterectomy.

II. To assess differences (across treatment arms) in incidence and severity of therapy-attributed adverse events utilizing the active version of Common Terminology Criteria for Adverse Events (CTCAE).

III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine whether post-operative adjuvant CRT improves the health-related quality-of-life (QOL) (compared to RT alone) as measured by Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Trial Outcome Index (TOI) and produce favorable toxicity profiles (with particular focus on treatment related genitourinary, gastrointestinal, neurological, pain and sexual adverse events).

TERTIARY OBJECTIVES:

I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical-pathologic characteristics in patients randomized to post-operative adjuvant CRT compared to RT alone.

II. To bank deoxyribonucleic acid (DNA) from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients randomized to post-operative adjuvant CRT compared to RT alone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.

ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.