# Radiation Oncology/Anal canal/RT Technique

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
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 — "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 — "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 — "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 — "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.)