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Erschienen in: Strahlentherapie und Onkologie 7/2020

12.03.2020 | Original Article

Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer+

verfasst von: Franco Campostrini, MD, Andrea Remo, MD, Laura Astati, BS, Manuel Zorzi, MD, Giulia Capodaglio, ScD, Alberto Buffoli, MD, Gaia Moretti, M Ph, Barbara Della Monica, M Ph, Caterina Zanella, MD, Giuseppe Verlato, PhD

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 7/2020

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Abstract

Purpose

The impact of acute histopathological changes (HC) of the rectum on development of late clinical proctitis (LCP) after external radiotherapy (RT) for prostate cancer is poorly explored and was the primary end point of this prospective study.

Methods

In 70 patients, 15 HC of early rectal biopsies after RT were identified, whereby RT was conventional 2D RT in 41 cases and conformational 3D RT in 29. Associations of HC in anterior and posterior rectal walls (ARW, PRW) with LCP, acute endoscopic (AEP) and acute clinical proctitis (ACP) were statistically evaluated considering as explicative variables the patient general characteristics and the HC.

Results

The mean patients’ follow-up was 123.5 months (24–209). The median prostatic dose was 72 Gy (2 Gy/fraction). For the 41 and 29 patients the ARW and PRW doses were 64 and 49 Gy vs. 63 and 50 Gy, respectively. The incidence of LCP ≥ grade 2 at 10 years was 12.9%. The univariate (p = 0.02) and Kaplan–Meyer methods (p = 0.007) showed that the gland (or crypts) loss in the ARW was significantly associated with LCP. AEP and ACP occurred in 14.3 and 55.7% of cases. At multivariate level AEP significantly correlated with hemorrhoids (p = 0.014) and neutrophilia in ARW (p = 0.042).

Conclusions

Early after RT, substantial gland loss in ARW is predictive of LCP. To reduce this complication with conventional fractionation, we suggest keeping the mean dose to ARW ≤48–52 Gy.
Literatur
1.
Zurück zum Zitat Hoffman KE, Voong KR, Pugh TJ, Skinner H, Levy LB, Takiar V et al (2014) Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial. Int J Radiat Oncol Biol Phys 88:1074–1084CrossRef Hoffman KE, Voong KR, Pugh TJ, Skinner H, Levy LB, Takiar V et al (2014) Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial. Int J Radiat Oncol Biol Phys 88:1074–1084CrossRef
2.
Zurück zum Zitat Aluwini S, Pos F, Schimmel E, Krol S, van der Toorn PP, de Jager H et al (2016) Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): late toxicity results from a randomised, non-inferiority, phase 3 trial. Lancet Oncol 17:464–467CrossRef Aluwini S, Pos F, Schimmel E, Krol S, van der Toorn PP, de Jager H et al (2016) Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): late toxicity results from a randomised, non-inferiority, phase 3 trial. Lancet Oncol 17:464–467CrossRef
3.
Zurück zum Zitat Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D et al (2016) Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5‑year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 17:1047–1060CrossRef Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D et al (2016) Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5‑year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 17:1047–1060CrossRef
4.
Zurück zum Zitat Arcangeli G, Saracino B, Arcangeli S, Gomellini S, Petrongari MG, Sanguineti G et al (2017) Moderate hypofractionation in high-risk, organ-confined prostate cancer: final results of a phase III randomized trial. J Clin Oncol 35:1891–1897CrossRef Arcangeli G, Saracino B, Arcangeli S, Gomellini S, Petrongari MG, Sanguineti G et al (2017) Moderate hypofractionation in high-risk, organ-confined prostate cancer: final results of a phase III randomized trial. J Clin Oncol 35:1891–1897CrossRef
5.
Zurück zum Zitat Onjukka E, Fiorino C, Cicchetti A, Palorini F, Improta I, Gagliardi G et al (2019) Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT. Acta Oncol 12:1–8 Onjukka E, Fiorino C, Cicchetti A, Palorini F, Improta I, Gagliardi G et al (2019) Patterns in ano-rectal dose maps and the risk of late toxicity after prostate IMRT. Acta Oncol 12:1–8
6.
Zurück zum Zitat Hoffman KE, Voong KR, Levy LB, Allen PK, Choi S, Schlembach PJ et al (2018) Randomized trial of hypofractionated, dose-escalated, intensity-modulated radiation therapy (IMRT) versus conventionally fractionated IMRT for localized prostate cancer. J Clin Oncol 36:2943–2949CrossRef Hoffman KE, Voong KR, Levy LB, Allen PK, Choi S, Schlembach PJ et al (2018) Randomized trial of hypofractionated, dose-escalated, intensity-modulated radiation therapy (IMRT) versus conventionally fractionated IMRT for localized prostate cancer. J Clin Oncol 36:2943–2949CrossRef
7.
Zurück zum Zitat Catton CN, Lukka H, Gu CS, Martin JM, Supiot S, Chung PWM et al (2017) Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer. J Clin Oncol 35:1884–1890CrossRef Catton CN, Lukka H, Gu CS, Martin JM, Supiot S, Chung PWM et al (2017) Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer. J Clin Oncol 35:1884–1890CrossRef
8.
Zurück zum Zitat Bolzicco G, Favretto MS, Satariano N, Scremin E, Tambone C, Tasca A (2013) A single-center study of 100 consecutive patients with localized prostate cancer treated with stereotactic body radiotherapy. BMC Urol 13:49CrossRef Bolzicco G, Favretto MS, Satariano N, Scremin E, Tambone C, Tasca A (2013) A single-center study of 100 consecutive patients with localized prostate cancer treated with stereotactic body radiotherapy. BMC Urol 13:49CrossRef
9.
Zurück zum Zitat Musunuru HB, Quon H, Davidson M, Cheung P, Zhang L, D’Alimonte L et al (2016) Dose-escalation of five-fraction SABR in prostate cancer: toxicity comparison of two prospective trials. Radiother Oncol 118:112–117CrossRef Musunuru HB, Quon H, Davidson M, Cheung P, Zhang L, D’Alimonte L et al (2016) Dose-escalation of five-fraction SABR in prostate cancer: toxicity comparison of two prospective trials. Radiother Oncol 118:112–117CrossRef
10.
Zurück zum Zitat Paleny R, Bremer M, Walacides D, Mainwaring S, Weber K, Henkenberens C (2019) Comparison of relative and absolute rectal dose-volume parameters and clinical correlation with acute and late radiation proctitis in prostate cancer patients. Strahlenther Onkol 195:103–112CrossRef Paleny R, Bremer M, Walacides D, Mainwaring S, Weber K, Henkenberens C (2019) Comparison of relative and absolute rectal dose-volume parameters and clinical correlation with acute and late radiation proctitis in prostate cancer patients. Strahlenther Onkol 195:103–112CrossRef
11.
Zurück zum Zitat Michalsky JF, Gay H, Jackson A, Tucker SL, Deasy JO (2010) Radiation dose-volume effects in radiation-induced rectal injury. Int J Radiat Oncol Biol Phys 76(3 Suppl):S123–S129CrossRef Michalsky JF, Gay H, Jackson A, Tucker SL, Deasy JO (2010) Radiation dose-volume effects in radiation-induced rectal injury. Int J Radiat Oncol Biol Phys 76(3 Suppl):S123–S129CrossRef
12.
Zurück zum Zitat Grodsky MB, Sidani SM (2015) Radiation proctopathy. Clin Colon Rectal Surg 28:103–111CrossRef Grodsky MB, Sidani SM (2015) Radiation proctopathy. Clin Colon Rectal Surg 28:103–111CrossRef
13.
Zurück zum Zitat Campostrini F, Musola R, Marchiaro G, Lonardi F, Verlato G (2013) Role of early proctoscopy in predicting late symptomatic proctitis after external radiation therapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 85:1031–1037CrossRef Campostrini F, Musola R, Marchiaro G, Lonardi F, Verlato G (2013) Role of early proctoscopy in predicting late symptomatic proctitis after external radiation therapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 85:1031–1037CrossRef
14.
Zurück zum Zitat Reddy EK, Giri S, Mansfield CM (1984) External radiation therapy of localized prostatic cancer. J Natl Med Assoc 76:61–66PubMedPubMedCentral Reddy EK, Giri S, Mansfield CM (1984) External radiation therapy of localized prostatic cancer. J Natl Med Assoc 76:61–66PubMedPubMedCentral
15.
Zurück zum Zitat Dewit L, van der Schueren E (1984) Radiation treatment planning for the localized prostatic carcinoma: methods and rationale. Strahlentherapie 8:474–484 Dewit L, van der Schueren E (1984) Radiation treatment planning for the localized prostatic carcinoma: methods and rationale. Strahlentherapie 8:474–484
16.
Zurück zum Zitat Campostrini F, Garusi G, Donati E (1995) A practical technique for conformal simulation in radiation therapy of pelvic tumors. Int J Radiat Oncol Biol Phys 15:355–365CrossRef Campostrini F, Garusi G, Donati E (1995) A practical technique for conformal simulation in radiation therapy of pelvic tumors. Int J Radiat Oncol Biol Phys 15:355–365CrossRef
17.
Zurück zum Zitat Pollack A, Zagars GK, Starkschall G, Childress CH, Kopplin S, Boyer AL et al (1996) Conventional vs. conformal radiotherapy for prostate cancer: preliminary results of dosimetry and acute toxicity. Int J Radiat Oncol Biol Phys 34:555–564CrossRef Pollack A, Zagars GK, Starkschall G, Childress CH, Kopplin S, Boyer AL et al (1996) Conventional vs. conformal radiotherapy for prostate cancer: preliminary results of dosimetry and acute toxicity. Int J Radiat Oncol Biol Phys 34:555–564CrossRef
18.
Zurück zum Zitat Wachter S, Gerstner N, Goldner G, Pötzi R, Wambersie A, Pötter R (2000) Endoscopic scoring of late rectal mucosa damage after conformal radiotherapy for prostate carcinoma. Radiother Oncol 54:11–19CrossRef Wachter S, Gerstner N, Goldner G, Pötzi R, Wambersie A, Pötter R (2000) Endoscopic scoring of late rectal mucosa damage after conformal radiotherapy for prostate carcinoma. Radiother Oncol 54:11–19CrossRef
19.
Zurück zum Zitat Hanauer SB, Robinson M, Pruitt R, Lazenby AJ, Persson T, Nilsson LG et al (1998) Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group. Gastroenterology 115:525–532CrossRef Hanauer SB, Robinson M, Pruitt R, Lazenby AJ, Persson T, Nilsson LG et al (1998) Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group. Gastroenterology 115:525–532CrossRef
20.
Zurück zum Zitat Hovdenak N, Fajardo LF, Hauer Jensen M (2000) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 48:1111–1117CrossRef Hovdenak N, Fajardo LF, Hauer Jensen M (2000) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 48:1111–1117CrossRef
21.
Zurück zum Zitat Leupin N, Curschmann J, Kranzbühler H, Maurer CA, Laissue JA, Mazzucchelli L (2002) Acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer. Am J Surg Pathol 26:498–504CrossRef Leupin N, Curschmann J, Kranzbühler H, Maurer CA, Laissue JA, Mazzucchelli L (2002) Acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer. Am J Surg Pathol 26:498–504CrossRef
22.
Zurück zum Zitat Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRef Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRef
23.
Zurück zum Zitat Crespi M, Delvaux M, Schaprio M, Venables C, Zwiebel F (1996) Working Party Report by the Committee for Minimal Standards of Terminology and Documentation in Digestive Endoscopy of the European Society of Gastrointestinal Endoscopy. Minimal standard terminology for a computerized endoscopic database. Ad hoc Task Force of the Committee. Am J Gastroenterol 91:191–216PubMed Crespi M, Delvaux M, Schaprio M, Venables C, Zwiebel F (1996) Working Party Report by the Committee for Minimal Standards of Terminology and Documentation in Digestive Endoscopy of the European Society of Gastrointestinal Endoscopy. Minimal standard terminology for a computerized endoscopic database. Ad hoc Task Force of the Committee. Am J Gastroenterol 91:191–216PubMed
24.
Zurück zum Zitat Wolff D, Stieler F, Welzel G, Lorenz F, Abo-Madyan Y, Mai S et al (2009) Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer. Radiother Oncol 93:226–233CrossRef Wolff D, Stieler F, Welzel G, Lorenz F, Abo-Madyan Y, Mai S et al (2009) Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer. Radiother Oncol 93:226–233CrossRef
25.
Zurück zum Zitat Gelfand MD, Tepper M, Katz LA, Binder HJ, Yesner R, Floch MH (1968) Acute irradiation proctitis in man. Development of eosinophilic crypt abscesses. Gastroenterology 1:401–411CrossRef Gelfand MD, Tepper M, Katz LA, Binder HJ, Yesner R, Floch MH (1968) Acute irradiation proctitis in man. Development of eosinophilic crypt abscesses. Gastroenterology 1:401–411CrossRef
26.
Zurück zum Zitat Tepper M, Vidone RA, Hayes MA, Lindenmuth WW, Kligerman MM (1968) Preoperative irradiation in rectal cancer: initial comparison of clinical tolerance, surgical and pathologic findings. AJR Am J Roentgenol 102:587–595CrossRef Tepper M, Vidone RA, Hayes MA, Lindenmuth WW, Kligerman MM (1968) Preoperative irradiation in rectal cancer: initial comparison of clinical tolerance, surgical and pathologic findings. AJR Am J Roentgenol 102:587–595CrossRef
27.
Zurück zum Zitat Weisbrot IM, Liber AF, Gordon BS (1975) The effects of therapeutic radiation on colonic mucosa. Cancer 36:931–940CrossRef Weisbrot IM, Liber AF, Gordon BS (1975) The effects of therapeutic radiation on colonic mucosa. Cancer 36:931–940CrossRef
28.
Zurück zum Zitat Haboubi NY, Schofield PF, Rowland PL (1988) The light and electron microscopic features of early and late phase radiation-induced proctitis. Am J Gastroenterol 83:1140–1144PubMed Haboubi NY, Schofield PF, Rowland PL (1988) The light and electron microscopic features of early and late phase radiation-induced proctitis. Am J Gastroenterol 83:1140–1144PubMed
29.
Zurück zum Zitat Sedgwick DM, Howard GCW, Ferguson A (1994) Pathogenesis of acute radiation injury to the rectum. A prospective study in patients. Int J Colorect Dis 9:23–30CrossRef Sedgwick DM, Howard GCW, Ferguson A (1994) Pathogenesis of acute radiation injury to the rectum. A prospective study in patients. Int J Colorect Dis 9:23–30CrossRef
31.
Zurück zum Zitat Richter KK, Wang J, Fagerhol MK, Hauer-Jensen M (2001) Radiation-induced granulocyte transmigration predicts development of delayed structural changes in rat intestine. Radiother Oncol 59:81–85CrossRef Richter KK, Wang J, Fagerhol MK, Hauer-Jensen M (2001) Radiation-induced granulocyte transmigration predicts development of delayed structural changes in rat intestine. Radiother Oncol 59:81–85CrossRef
32.
Zurück zum Zitat Gulliford SL, Foo K, Morgan RC, Aird EG, Bidmead AM, Critchley H et al (2010) Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397. Int J Radiat Oncol Biol Phys 76:747–754CrossRef Gulliford SL, Foo K, Morgan RC, Aird EG, Bidmead AM, Critchley H et al (2010) Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397. Int J Radiat Oncol Biol Phys 76:747–754CrossRef
33.
Zurück zum Zitat Smit WG, Helle PA, van Putten WL, Wijnmaalen AJ, Seldenrath JJ, van der Werf-Messing BH (1990) Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int J Radiat Oncol Biol Phys 18:23–29CrossRef Smit WG, Helle PA, van Putten WL, Wijnmaalen AJ, Seldenrath JJ, van der Werf-Messing BH (1990) Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int J Radiat Oncol Biol Phys 18:23–29CrossRef
34.
Zurück zum Zitat Zilli T, Jorcano S, Escudé L, Linero D, Rouzaud M, Dubouloz A et al (2011) Twice-weekly hypofractionated intensity-modulated radiotherapy for localized prostate cancer with low-risk nodal involvement. Toxicity and outcome from a dose escalation pilot study. Int J Radiat Oncol Biol Phys 81:382–389CrossRef Zilli T, Jorcano S, Escudé L, Linero D, Rouzaud M, Dubouloz A et al (2011) Twice-weekly hypofractionated intensity-modulated radiotherapy for localized prostate cancer with low-risk nodal involvement. Toxicity and outcome from a dose escalation pilot study. Int J Radiat Oncol Biol Phys 81:382–389CrossRef
35.
Zurück zum Zitat Ren W, Sun C, Lu N, Xu Y, Han F, Liu YP et al (2016) Dosimetric comparison of intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy in patients with prostate cancer: a meta-analysis. J Appl Clin Med Phys 17:254–262CrossRef Ren W, Sun C, Lu N, Xu Y, Han F, Liu YP et al (2016) Dosimetric comparison of intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy in patients with prostate cancer: a meta-analysis. J Appl Clin Med Phys 17:254–262CrossRef
36.
Zurück zum Zitat Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M et al (2019) Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5‑year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 394:385–395CrossRef Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M et al (2019) Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5‑year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 394:385–395CrossRef
37.
Zurück zum Zitat Kittel JA, Reddy CA, Smith KL, Stephans KL, Tendulkar RD, Ulchaker J et al (2015) Long-term efficacy and toxicity of low-dose-rate 125I prostate Brachytherapy as Monotherapy in low-, intermediate-, and high-risk prostate cancer. Int J Radiat Oncol Biol Phys 92:884–893CrossRef Kittel JA, Reddy CA, Smith KL, Stephans KL, Tendulkar RD, Ulchaker J et al (2015) Long-term efficacy and toxicity of low-dose-rate 125I prostate Brachytherapy as Monotherapy in low-, intermediate-, and high-risk prostate cancer. Int J Radiat Oncol Biol Phys 92:884–893CrossRef
38.
Zurück zum Zitat Mendez LC, Morton GC (2018) High dose-rate brachytherapy in the treatment of prostate cancer. Transl Androl Urol 2018(7):357–370CrossRef Mendez LC, Morton GC (2018) High dose-rate brachytherapy in the treatment of prostate cancer. Transl Androl Urol 2018(7):357–370CrossRef
39.
Zurück zum Zitat Rodda S, Tyldesley S, Morris WJ, Keyes M, Halperin R, Pai H et al (2017) ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys 8:286–295CrossRef Rodda S, Tyldesley S, Morris WJ, Keyes M, Halperin R, Pai H et al (2017) ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys 8:286–295CrossRef
Metadaten
Titel
Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer+
verfasst von
Franco Campostrini, MD
Andrea Remo, MD
Laura Astati, BS
Manuel Zorzi, MD
Giulia Capodaglio, ScD
Alberto Buffoli, MD
Gaia Moretti, M Ph
Barbara Della Monica, M Ph
Caterina Zanella, MD
Giuseppe Verlato, PhD
Publikationsdatum
12.03.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 7/2020
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-020-01590-3

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