Radiation Oncology/Rectum/RT Salvage

Reviews:
 * 1998: PMID 9457833 - "In search of a dose-response relationship with radiotherapy in the management of recurrent rectal carcinoma in the pelvis: a systematic review." Wong R et al. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):437-46.
 * Optimal dose fractionation remains undefined.

Recurrence (no prior RT)

 * Peter MacCallum, 1997 (1981-90) PMID 9276368 -- "Radiotherapy treatment for isolated loco-regional recurrence of rectosigmoid cancer following definitive surgery: Peter MacCallum Cancer Institute experience, 1981-1990." (Guiney MJ,Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1019-25.)
 * Retrospective, 135 pts. Pts without prior RT treated to 1) 50-60 Gy / 2 Gy fractions ("radical" group), 2) 45 Gy / 3 Gy fractions w/ 1 week break ("high-dose palliative"), or 3) <45 Gy ("low-dose palliative").
 * Symptom relief rate of 85%, 81%, and 56%. Median survival 17.9, 14.8, and 9 months.
 * Conclusion: Similar response rate for 50-60 Gy radical group and 45 Gy hypofractionated group.

Reirradiation

 * MDACC, 2010 (2001-2005) PMID 19695792 -- "Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation." (Das P, Int J Radiat Oncol Biol Phys. 2010 May 1;77(1):60-5.)
 * 50 pts. Treated 150 cGy BID to 39 Gy (if interval >= 1 yr since prior RT; n=47) or 30 Gy (if <1 yr; n=3). 96% received concurrent chemo. 36% underwent surgical resection following RT.
 * 3-yr freedom from local progression 33% (47% for pts having surgery vs 21% for those without). 3-yr OS 39% (66%-surgery;27%-without).
 * Toxicity: 3-yr rate of gr3-4 late toxicity 35%.
 * Conclusion: hyperfractionated accelerated reirradiation was well tolerated with low rates of acute toxicity and moderate rates of late toxicity.


 * Italy (STORM) (1997-2001) -- Phase II
 * 59 pts. Multicenter study (STORM = Study Group for Therapies of Rectal Malignancies). RT to GTV + 4 cm radial margin to 30 Gy (1.2 Gy BID) plus boost (2 cm margin) to 10.8 Gy (1.2 BID), total dose 40.8 Gy in 34 fx. Concomitant 5-FU (225 mg/m2/d). Surgery performed 6-8 wks after chemo/RT. Adjuvant chemo with raltitrexed (antimetabolite) given after surgery.
 * 2006 PMID 16414206 -- "Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study." (Valentini V, Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1129-39.)
 * Median 27 months interval between prior RT and re-RT. 86% completed treated without interruption. Overall response rate to chemo/RT 44.1%. 66% of pts completed surgery; R0 resection in 35%, R0-R1 in 35%. 5 pts (8.5%) had pCR. Sphincter-sparing operation in 7 of 24 (29%) with R0-R1 resection. 15 pts had macroscopic residual (R2 resection). Pain relief in 20/24 pt (83%). Despite 87% of pts having tumor in contact with the pelvic sidewall, 35% achieved R0 resections.
 * Tox: No gr4-5 acute tox. Late toxicity was infrequent. 6/39 (15%) operated pts had post-op complications.
 * Median f/u 36 mo. 5-yr LC 38%, DMFS 42%, DFS 29%. In R0 pts: 69%, 69%, 50%.  MS 42 mo. 5-yr OS 39% (65% in R0-R1 pts, 22% in pts treated w/o surgery or with R2 resection). 3-yr LC 17% in pts without R0 resection
 * Conclusion: hyperfractionated chemoradiation was associated with a low rate of acute toxicity and acceptable late complication rate.


 * University of Kentucky, 2002 (1987-2000) -
 * 2002 (1987-2000) PMID 12209702 -- "Long-term results of reirradiation for patients with recurrent rectal carcinoma." Mohiuddin M et al. Cancer. 2002 Sep 1;95(5):1144-50.
 * 103 pts who developed locoregional recurrence after surgery with pre-op or post-op RT. Previously treated to median dose of 50.4 Gy. Time to recurrence 2 to 86 months (Median: 19m). Reirradiation with concurrent 5-FU continuous infusion. Treated with opposed laterals or posterior field and 2 laterals. Treated presacral area and GTV (with 2-4 cm margin) to either 30 Gy (1.2 Gy BID) or 30.6 Gy (1.8 Gy QD) followed by a boost of 6-20 Gy to GTV (2 cm margin). Median reirradiation dose 34.8 Gy.
 * 41 pts were surgically explored after treatment, and 34 underwent resection (6 pts with sphincter sparing). Median f/u 24 months. 5-yr OS 19%. Higher survival for those undergoing resection. Acute and late toxicity was tolerable. Bleeding palliated in 100% of pts.
 * 1997 (1987-1992) PMID 9336144 -- "Curative surgical resection following reirradiation for recurrent rectal cancer." (Mohiuddin M, Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):643-9.)
 * 39 pts.


 * Thomas Jefferson University (1987-93) - Phase I/II
 * 1993 (1987-91) PMID 8262842 -- "Reirradiation for rectal cancer and surgical resection after ultra high doses." (Mohiuddin M, Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1159-63.)
 * 32 pts, treated with curative intent after surgical resection.
 * 1997 (1987-93) PMID 9240647 -- "Palliative reirradiation for recurrent rectal cancer." (Lingareddy V, Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):785-90.)
 * 52 pts, palliative reirradiation without surgery.