Radiation Oncology/Anal canal/RT Technique

Anal Cancer RT Technique

RT dose escalation

 * RTOG 92-08 (1992-6) -- split course 59.6 Gy
 * Preliminary results: 1996 PMID 9166533 -- "Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08." (John M, Cancer J Sci Am. 1996 Jul-Aug;2(4):205-11.)
 * Phase II, dose-escalation, split course RT. 47 patients, cancer >= 2cm. RT 59.6 Gy split course with 2-week break. Initial pts treated 1992-3. Comparison with RTOG 87-04
 * After unexpectedly high rates of colostomy (23%), treatment break was eliminated. 20 additional patients were treated (1995-6). 9 completed protocol, 9 required treatment break anyway. Median RT dose 41 Gy ( Abstract ASTRO 1997). Colostomy rate 11%
 * Conclusion: No improvement in local control in split-course RT. Suggest continuous RT, but may have to accept higher acute toxicity
 * 10-years: 2008 PMID 18472363 -- "Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08." (Konski A, Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):114-8.)
 * DFS: 5-yr 53%, 8-yr 34% (break); vs 80%/63% (no break). Colostomy-free survival: 58%/34% vs 75%/63%.
 * Pts treated with mandatory break had worse OS, DFS, and CFS compared with 87-04, whereas pts treated with no mandatory break were similar to historical controls. However, the trial was small and not powered to compare efficacy endpoints.

Segmental boost technique
Uses wide AP field, narrow PA field, and angled photon inguinal fields (matched to the divergence of the PA field). Single isocenter technique.
 * Yale, 2004
 * 2004 PMID 15275740 -- "Improved treatment of pelvis and inguinal nodes using modified segmental boost technique: dosimetric evaluation." (Moran MS, Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1523-30.)
 * 2010 PMID 19596174 -- "Clinical utility of the modified segmental boost technique for treatment of the pelvis and inguinal nodes." (Moran MS, Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):1026-36.)

Inguinal node photon boost

 * Indianapolis, 2001 PMID 11295207 &mdash; "A technique for inguinal node boost using photon fields defined by asymmetric collimator jaws." Dittmer PH et al. Radiother Oncol. 2001 Apr;59(1):61-4.
 * Treats the pelvis using PA field, pelvis + inguinals using AP field, plus a further boost to the inguinals using AP photons with asymmetric collimator jaws (using the same isocenter).

"Diamond" technique

 * McGill
 * 2007 PMID 17276620 &mdash; "Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy." (Vuong T, Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1394-400.)
 * 2003 PMID 12788191 &mdash; "Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a phase II study." (Vuong T, Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):823-31.)

IMRT

 * RTOG 0529
 * Multi-institutional Phase II. 52 evaluable patients, T3-T4N0 (54% stage II, 25% Stage IIIA, 25% Stage IIIB). Dose stage dependent. Dose-painted IMRT vs conventional RT, with concurrent 5FU/Mitomycin on day #1 and day #29
 * 2013 PMID 23154075 -- "RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal" (Kachnic LA, Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):27-33. doi: 10.1016/j.ijrobp.2012.09.023.)
 * Toxicity: Grade 2+ RTOG 0529 77% vs RTOG 9811 77% (NS), primary end point not met. Reduction in acute G2 hematologic 73% vs 85% (SS), G3 GI 21% vs 36% (SS), and G3 dermatologic 23% vs 49% (SS).
 * Quality: Plan revision rate 81%
 * Conclusion: Primary endpoint not met, but IMRT associated with significant improvement in some toxicity. However, high plan revision rate
 * 2022 PMID 34400269 -- "Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer" (Kachnic LA, Int J Radiat Oncol Biol Phys. 2022 Jan 1;112(1):146-157. doi: 10.1016/j.ijrobp.2021.08.008. Epub 2021 Aug 14.). Median F/U 7.9 years
 * Outcome: 5-year locoregional failure 16%, colostomy failure 10%, DM 16%, OS 76%, DFS, 70%, colostomy-free survival 74%. Persistent disease 10%, locoregional failure 15% patients.
 * Toxicity: Grade 2 55%; Grade 3 16%; Grade 4 0%; Grade 5 4% (sinus brady, myelodysplasia). Sexual dysfunction 21%
 * Conclusion: Dose painted IMRT with 5FU/MMC comparable long term efficacy as conventional radiation, with enhanced normal tissue protection


 * Multicenter; 2007 (2000-2006) PMID 17925552 -- "Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience." (Salama JK, J Clin Oncol. 2007 Oct 10;25(29):4581-6.
 * Prospective. 53 patients (62% T-2, 67% N0, 15% HIV+) treated with concurrent chemo (5-FU/mitomycin, or FU alone) and RT. Primary sites and involved LN median 51.5 Gy, pelvis and inguinal LN median 45 Gy. Median F/U 14 months
 * Toxicity: Grade 3 GI 15%, dermatologic 38%; Grade 4 leukopenia 30%, neutropenia 34%. Treatment break in 41%, median 4 days
 * Conclusion: Effective, and compares favorably with historical standards


 * France (Montpellier), 2007 PMID 18005443 &mdash; "Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans." (Menkarios C, Radiat Oncol. 2007 Nov 15;2:41.)
 * Treatment planning study. Compared: 1) AP/PA + 3D-CRT boost, 2) Pelvic IMRT + 3D-CRT boost, 3) Pelvic IMRT + IMRT boost, 4) IMRT with simultaneous integrated boost.
 * Conclusion: Compared to conventional plan, all IMRT plans reduced the dose to bowel, bladder, genitalia, and bone marrow.


 * U Chicago, 2005 PMID 16168830 "Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome." Milano MT et al. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):354-61.
 * IMRT remarkably well tolerated, with minimal toxicity.

Contouring

 * RTOG Atlas
 * RTOG Anorectal Contouring Guidelines
 * 2009 PMID 19117696 -- "Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas." (Myerson RJ, Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):824-30. Epub 2008 Dec 29.)