Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial

被引：8

作者：

Huddart, R. ^{[1
,21
]}

Hafeez, S. ^{[1
]}

Omar, A. ^{[2
,3
]}

Alonzi, R. ^{[4
]}

Birtle, A. ^{[5
]}

Cheung, K. C. ^{[2
,3
]}

Choudhury, A. ^{[6
]}

Foroudi, F. ^{[7
]}

Gribble, H. ^{[3
]}

Henry, A. ^{[8
,9
]}

Hilman, S. ^{[7
,10
]}

Hindson, B. ^{[11
]}

Lewis, R. ^{[3
]}

Muthukumar, D. ^{[12
]}

Mclaren, D. B. ^{[13
]}

Mcnair, H. ^{[1
,2
]}

Nikapota, A. ^{[14
]}

Olorunfemi, A. ^{[3
]}

Parikh, O. ^{[15
]}

Philipps, L. ^{[3
]}

Rimmer, Y. ^{[16
]}

Syndikus, I. ^{[17
]}

Tolentino, A. ^{[3
]}

Varughese, M. ^{[18
]}

Vassallo-Bonner, C. ^{[19
]}

Webster, A. ^{[20
]}

Griffin, C. ^{[3
]}

Hall, E. ^{[3
]}

机构：

[1] Inst Canc Res, Div Radiotherapy & Imaging, London, England

[2] Royal Marsden NHS Fdn Trust, Radiotherapy Dept, London, England

[3] Inst Canc Res, Clin Trials & Stat Unit, London, England

[4] East & North Hertfordshire NHS Trust, Mt Vernon Canc Ctr, Clin Oncol, Stevenage, Middx, England

[5] Lancashire Teaching Hosp NHS Trust, Canc Oncol, Preston, Lancs, England

[6] Christie NHS Fdn Trust, Translat Radiobiol, Manchester, England

[7] Austin Hlth, Radiat Oncol, Heidelberg, Australia

[8] Univ Leeds, Leeds, England

[9] Leeds Teaching Hosp NHS Trust, Leeds, England

[10] Univ Hosp Bristol & Weston NHS Fdn Trust, Clin Oncol, Bristol, England

[11] Te Whatu Ora, Canterbury Reg Canc & Haematol Serv, Christchurch, New Zealand

[12] East Suffolk & North Essex NHS Fdn Trust, Oncol, Colchester, England

[13] NHS Lothian, Edinburgh Canc Ctr, Dept Clin Oncol, Edinburgh, Scotland

[14] Brighton & Sussex Univ Hosp NHS Trust, Clin Pharmacol, Brighton, England

[15] Lancashire Teaching Hosp NHS Trust, Burnley, England

[16] Cambridge Univ Hosp NHS Fdn Trust, Dept Oncol, Cambridge, England

[17] Clatterbridge Canc Ctr, Dept Radiotherapy, Liverpool, England

[18] Royal Devon & Exeter NHS Fdn Trust, Dept Oncol, Exeter, England

[19] Inst Canc Res, Patient Representat, London, England

[20] Univ Coll Hosp, Natl Radiotherapy Trials Qual Assurance Grp RTTQA, London, England

[21] Inst Canc Res, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England

来源：

CLINICAL ONCOLOGY | 2023年 / 35卷 / 09期

关键词：

Acute toxicity; bladder; chemotherapy; radiotherapy; RADIOTHERAPY; CHEMOTHERAPY; BC2001; QUESTIONNAIRE; GEMCITABINE; THERAPY;

D O I：

10.1016/j.clon.2023.05.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aims: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination.Materials and methods: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests.Results: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20-or 32-fraction cohorts.Conclusion: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.(C) 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

引用

页码：586 / 597

页数：12

共 16 条

[1] Development of the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [J].

Basch, Ethan ;

Reeve, Bryce B. ;

Mitchell, Sandra A. ;

Clauser, Steven B. ;

Minasian, Lori M. ;

Dueck, Amylou C. ;

Mendoza, Tito R. ;

Hay, Jennifer ;

Atkinson, Thomas M. ;

Abernethy, Amy P. ;

Bruner, Deborah W. ;

Cleeland, Charles S. ;

Sloan, Jeff A. ;

Chilukuri, Ram ;

Baumgartner, Paul ;

Denicoff, Andrea ;

St Germain, Diane ;

O'Mara, Ann M. ;

Chen, Alice ;

Kelaghan, Joseph ;

Bennett, Antonia V. ;

Sit, Laura ;

Rogak, Lauren ;

Barz, Allison ;

Paul, Diane B. ;

Schrag, Deborah .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2014, 106 (09)

[2] Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials [J].

Caffo, Orazio ;

Thompson, Catherine ;

De Santis, Maria ;

Kragelj, Borut ;

Hamstra, Daniel A. ;

Azria, David ;

Fellin, Gianni ;

Pappagallo, Giovanni L. ;

Galligioni, Enzo ;

Choudhury, Ananya .

RADIOTHERAPY AND ONCOLOGY, 2016, 121 (02) :193-198

[3]

Choudhury A, 2021, LANCET ONCOL, V22, P246, DOI 10.1016/S1470-2045(20)30607-0

[4] Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer [J].

Choudhury, Ananya ;

Swindell, Ric ;

Logue, John P. ;

Elliott, P. Anthony ;

Livsey, Jacqueline E. ;

Wise, Marcus ;

Symonds, Paul ;

Wylie, James P. ;

Ramani, Vijay ;

Sangar, Vijay ;

Lyons, Jeanette ;

Bottomley, Ian ;

McCaul, Damian ;

Clarke, Noel W. ;

Kiltie, Anne E. ;

Cowan, Richard A. .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (06) :733-738

[5] Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712A Randomized Phase II Trial [J].

Coen, John J. ;

Zhang, Peixin ;

Saylor, Philip J. ;

Lee, Cheryl T. ;

Wu, Chin-Lee ;

Parker, William ;

Lautenschlaeger, Timothy ;

Zietman, Anthony L. ;

Efstathiou, Jason A. ;

Jani, Ashesh B. ;

Kucuk, Omer ;

Souhami, Luis ;

Rodgers, Joseph P. ;

Sandler, Howard M. ;

Shipley, William U. .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (01) :44-+

[6] Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation [J].

Coppin, CML ;

Gospodarowicz, MK ;

James, K ;

Tannock, IF ;

Zee, B ;

Carson, J ;

Pater, J ;

Sullivan, LD .

JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (11) :2901-2907

[7] Protocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance [J].

Hafeez, Shaista ;

Webster, Amanda ;

Hansen, Vibeke N. ;

McNair, Helen A. ;

Warren-Oseni, Karole ;

Patel, Emma ;

Choudhury, Ananya ;

Creswell, Joanne ;

Foroudi, Farshad ;

Henry, Ann ;

Kron, Tomas ;

McLaren, Duncan B. ;

Mitra, Anita, V ;

Mostafid, Hugh ;

Saunders, Daniel ;

Miles, Elizabeth ;

Griffin, Clare ;

Lewis, Rebecca ;

Hall, Emma ;

Huddart, Robert .

BMJ OPEN, 2020, 10 (12)

[8] Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) [J].

Herdman, M. ;

Gudex, C. ;

Lloyd, A. ;

Janssen, M. F. ;

Kind, P. ;

Parkin, D. ;

Bonsel, G. ;

Badia, X. .

QUALITY OF LIFE RESEARCH, 2011, 20 (10) :1727-1736

[9] Radiotherapy With Concurrent Carbogen and Nicotinamide in Bladder Carcinoma [J].

Hoskin, Peter J. ;

Rojas, Ana M. ;

Bentzen, Soren M. ;

Saunders, Michele I. .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (33) :4912-4918

[10] Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial [J].

Huddart, Robert A. ;

Hall, Emma ;

Lewis, Rebecca ;

Porta, Nuria ;

Crundwell, Malcolm ;

Jenkins, Peter J. ;

Rawlings, Christine ;

Tremlett, Jean ;

Campani, Leila ;

Hendron, Carey ;

Hussain, Syed A. ;

James, Nicholas D. .

EUROPEAN UROLOGY, 2020, 77 (02) :260-268

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