Palliative Radiation for Advanced Cervical Cancer

This is a prospective randomised open label Phase III study. This study is is proposed to compare a rapid fractionation schedule of 1 week compared to a protracted schedule of 6-8 weeks for palliation for locally advanced cervical cancer. The primary objective of the study is pain relief in the experimental arm as compared to the control arm from treatment until 12 weeks from start of radiotherapy. Patients with locally advanced cervical cancer (Stage III B-IV A) deemed unsuitable for full course radical pelvic radiotherapy or chemoradiation, patients whose anticipated survival is less than 12 months will be included in the study. Patients with distant metastasis and those with retroviral disease will be excluded from the study. The patients will be randomised in one of the two groups:

Arm A : Control Arm - Long Course Palliative Radiation: Week 1: All the patients will receive external sitting of radiation treatment, first fraction of 10 Gy. Week 4: All the patients will receive external sitting of radiation treatment, second fraction of 10 Gy. Week 7: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#.The patients which will be found unsuitable for brachytherapy will receive another sitting of external radiation, third fraction of 10 Gy. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/ no • Vaginal discharge- yes/no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity.

Arm B: Experimental arm- Short Course Palliative radiation. Week 1: Patients will be treated with short course radiotherapy (25Gy/5#). The dose fractionation of 25 Gy in 5# over a week will be used. Week 4: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#. The patients who will be found unsuitable for brachytherapy will be kept under observation. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/no • Vaginal discharge- yes/ no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity. Follow up: Patients follow up will be utilizing standard of care imaging and lab investigations used for the patients. Patients will be evaluated every 3 months for the study duration.There is no potential direct benefit to the study participants. However the aim is to use the available information to evolve treatment in future. The variables to be estimated are pain relief, disease related symptoms relief, CTCAE Toxicity, Quality of Life,overall survival and compliance to therapy.

• Pain Relief (Numerical pain rating scale will be used) [Time frame: 6 months, 9 months, 12 months]
• Presence or absence of vaginal bleeding and/or discharge and relief in vaginal bleeding (as reported by the patient) [Time frame: 1 week,4 week,7week,12 weeks]
• Change in use of analgesics (WHO ladder) [Time frame: 12 weeks, 3 month, 9 month, 12 month]
• Compliance to therapy [Time frame: 7 week,12 week, 3 month, 9 month, 12 month]
• Quality of Life using EORTC QLQC30 questionnaires [Time frame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.]
• Quality of Life using EORTC QLQC-15 Pall questionnaires [Time frame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.]
• Quality of Life using Cx-24 questionnaires [Time frame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.]
• Acute gastrointestinal and genitourinary toxicities [Time frame: Within 90 days of Radiotherapy]
• Late gastrointestinal and genitourinary toxicities [Time frame: After 90 days of Radiotherapy]
• Overall survival, defined as time from randomization until death due to any cause. [Time frame: 1 year]
• Patterns of terminal event (Due to local relapse or Distant Metastasis) [Time frame: By telephonic interview of the relatives at 3, 6, 9 or 12 months, as applicable]