Radiation Oncology/Cervix/Randomized

In the process of being cross-linked ...

HPV screening vs Pap smear

• Finland (2003-2005) -- HPV DNA screen vs conventional cytology
  • 2010 PMID 20423964 Full Text -- "Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme" (Anttila A, BMJ 2010;340:c1804)
  • Randomized. 58,076 women, age 30-60, routine population-based screening program. Arm 1) HPV DNA test vs Arm 2) conventional cytological screening. Primary outcome cervical cancer, CIN-III and carcinoma in situ (both reported as CIN-III+)
    • Outcome: CIN-III+ HPV 76 cases (6 cervical CA) vs cytology 53 cases (8 cervical CA)
    • Conclusion: Primary HPV screening more sensitive than conventional cytology in detecting CIN-III+ lesions; number of cervical cancer small

PET Staging

• Chang Gung University, Taiwan (2002-2006) -- pretreatment PET vs no PET
  • Randomized. 129 patients, Stage I-IVA cervical cancer, positive pelvic but negative PALN by MRI. Arm 1) pretreatment PET vs Arm 2) no PET. Treated with chemo-RT, standard pelvic fields. If PET+, extended to include PALN
  • 2010 PMID 19464824 -- "A prospective randomized trial to study the impact of pretreatment FDG-PET for cervical cancer patients with MRI-detected positive pelvic but negative para-aortic lymphadenopathy." (Tsai CS, Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):477-84. Epub 2009 May 21.)
    • Outcome: PET identified 11% extra-pelvic mets; of these 57% remained disease free after modified fields. 4-year DFS PET+ 75% vs. PET- 77% (NS); 4-year OS 79% vs 85% (NS)
    • Conclusion: Pretreatment PET can improve detection of pelvic mets, but may not translate into survival benefit

RT Technique

Brachytherapy

• Osaka (Japan)(1983-1989) -- HDR fractional dose 7.5 Gy/fx vs. 6.0 Gy/fx
  • Randomized. 165 patients with cervix adenoCA, Stage IA-IV. Treated with 2 separated dose schedules depending on stage. Arm 1) EBRT + BT using 7.5 Gy/fx (either 37.5/5 or 30/4 or 22.5/3) vs. Arm 2) EBRT + BT using 6.0 Gy/fx (either 36/6 or 30/5 or 18/3).
  • 5-years; 1994 PMID 7974179 -- "A prospective randomized study concerning the point A dose in high-dose rate intracavitary therapy for carcinoma of the uterine cervix. The final results." (Chatani M, Strahlenther Onkol. 1994 Nov;170(11):636-42.)
    • Outcome: 5-year CSS: Stage I 100% vs. 100%, Stage II 82% vs. 85%, Stage III 62% vs. 52%, Stage IV 22% vs. 31% (all NS). No difference in LRF or DM
    • Toxicity: No difference
    • Conclusion: No difference between the two treatment schedules; small number of fractions at 7.5 Gy/fx may be advantageous due to short duration

Circadian Variation

• Lucknow, India -- morning RT vs evening RT
  • Randomized. 229 patients, cervical CA. Arm 1) morning (8-10 AM) vs Arm 2) evening (6-8 PM) RT. Primary outcome mucositis
  • 2010 PMID 20162717 -- "Circadian variation in radiation-induced intestinal mucositis in patients with cervical carcinoma." (Shukla P, Cancer. 2010 Feb 16. [Epub ahead of print])
    • Outcome: Overall diarrhea AM 87% vs PM 68% (SS), Grade 3-4 diarrhea 14% vs 5% (SS)
    • Conclusion: Significant difference between morning and evening arms suggest influence of circadian rhythms

Hypoxia

Anemia

• GOG 191 (2001-2003) -- Chemo-RT +/- EPO
  • Randomized. Closed prematurely due to concerns about thromboembolic events. 109 patients accrued (<25% planned). Cervical cancer, Stage IIB-IVA, Hgb <14.0 Arm 1) Chemo-RT vs. Arm 2) Chemo-RT + recombinant Epo 40,000 units QW
  • 3-years; 2008 PMID 18037478 -- "Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer." (Thomas G, Gynecol Oncol. 2008 Feb;108(2):317-25. Epub 2007 Nov 26.) Median F/U 3 years
    • Outcome: 3-year PFS control 65% vs. EPO 58%; OS 75% vs. 61% (insufficient numbers)
    • Rate of thromboembolism: control 8% vs. EPO 19% (NS), no deaths
    • Conclusion: Thromboembolism common; impact of Hgb >12.0 remains undetermined

Hyperbaric Oxygen

• RTOG 70-01 (1972-1975) -- RT in air vs. RT in HBO
  • Randomized. Stopped early due to slow accrual. 58 patients with Stage IIB-IVA cervix. Arm 1) RT 50/25 in air vs. Arm 2) RT 40/10 in HBO. Brachytherapy in both arms. Only 19/29 HBO patients received most of their EBRT in the chamber
  • 1981 PMID 7028700 -- "Hyperbaric oxygen therapy for carcinoma of the cervix--stages IIB, IIIA, IIIB and IVA: results of a randomized study by the Radiation Therapy Oncology Group." (Brady LW, Int J Radiat Oncol Biol Phys. 1981 Aug;7(8):991-8.)
    • Outcome: Local failure air 24% vs. HBO 26% (NS); DFS air 52% vs. HBO 73% (NS)
    • Complications: both arms 24% (NS)
    • Conclusion: Study too small; no difference; HBO technically difficult to administer
  • Comment: Test of hypofractionation + HBO vs. standard fractionation; study too small