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1
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Hafeez S, Warren-Oseni K, Jones K, Mohammed K, El-Ghzal A, Dearnaley D, Harris V, Khan A, Kumar P, Lalondrelle S, McDonald F, Tan M, Thomas K, Thompson A, McNair HA, Hansen VN, Huddart RA. Bladder Tumor-Focused Adaptive Radiation Therapy: Clinical Outcomes of a Phase I Dose Escalation Study. Int J Radiat Oncol Biol Phys 2025; 121:165-175. [PMID: 39069239 DOI: 10.1016/j.ijrobp.2024.07.2317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 06/22/2024] [Accepted: 07/04/2024] [Indexed: 07/30/2024]
Abstract
PURPOSE We determine the maximum tolerated tumor-focused dose (MTD) for the radical treatment of muscle invasive bladder cancer enabled by image guided adaptive radiation therapy and long-term clinical outcomes. METHODS AND MATERIALS Fifty-nine patients with T2 to T4aN0M0 unifocal urothelial muscle invasive bladder cancer suitable for daily radical radiation therapy were recruited prospectively to an ethics-approved protocol (NCT01124682). The uninvolved bladder (PTVbladder) was planned to 52 Gy in 32 fractions. The bladder tumor (PTVtumor) was planned to an assigned dose level of 68, 70, 72, or 74 Gy. If organ at risk dose constraints were violated, then PTVtumor was planned to 64 Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using Common Terminology Criteria for Adverse Events v3.0; late toxicity was evaluated using Radiation Therapy Oncology Group criteria. The MTD was predefined as the highest dose level with an estimated probability of ≤ 15% ≥ G3 late toxicity and an observed rate of <50% acute G3 and <10% acute G4 toxicity. RESULTS Twenty-six patients were assigned to 68 Gy, of whom 6 were planned to 64 Gy; 29 patients were assigned to 70 Gy of whom 1 was planned to 68 Gy, 2 patients were assigned and planned to 72 Gy; no patients were assigned to 74 Gy. Three patients did not complete the treatment as planned, of whom only 1 patient stopped treatment because dose-limiting toxicity occurred. The MTD was 70 Gy. Acute genito-urinary and gastro-intestinal G3 acute toxicity was seen in 19% and 7% of patients, respectively. No acute G4 genito-urinary or gastro-intestinal toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% of patients, respectively. The 5-year overall survival was 58% (95% CI, 44%-71%). The bladder preservation rate was 89% (95% CI, 88%-96%) with 6 patients not retaining native bladder function. CONCLUSIONS Bladder tumor-focused dose escalation to 70 Gy using image guided adaptive radiation therapy is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomized control trial (RAIDER NCT02447549).
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Affiliation(s)
- Shaista Hafeez
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom.
| | - Karole Warren-Oseni
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Kelly Jones
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Kabir Mohammed
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Amir El-Ghzal
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - David Dearnaley
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Victoria Harris
- Guy's & St. Thomas' NHS Foundation Trust, London, United Kingdom
| | - Atia Khan
- North Middlesex University Hospital, London, United Kingdom
| | - Pardeep Kumar
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Susan Lalondrelle
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Fiona McDonald
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Melissa Tan
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Karen Thomas
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Alan Thompson
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Helen A McNair
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Vibeke N Hansen
- Laboratory of Radiation Physics, Odense University Hospital, Denmark
| | - Robert A Huddart
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
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2
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Ditonno F, Veccia A, Montanaro F, Pettenuzzo G, Franco A, Manfredi C, Triggiani L, De Nunzio C, De Sio M, Cerruto M, Crivellaro S, Kutikov A, Autorino R, Antonelli A. Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies. BJU Int 2024; 134:684-695. [PMID: 38622957 DOI: 10.1111/bju.16366] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
OBJECTIVE To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. MATERIALS AND METHODS In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. RESULTS No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. CONCLUSION Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.
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Affiliation(s)
- Francesco Ditonno
- Department of Urology, Rush University Medical Center, Chicago, IL, USA
- Department of Urology, University of Verona, Verona, Italy
| | | | | | | | - Antonio Franco
- Department of Urology, Rush University Medical Center, Chicago, IL, USA
- Department of Urology, Sant'Andrea Hospital, La Sapienza University, Rome, Italy
| | - Celeste Manfredi
- Department of Urology, Rush University Medical Center, Chicago, IL, USA
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, "Luigi Vanvitelli" University, Naples, Italy
| | - Luca Triggiani
- Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy
| | - Cosimo De Nunzio
- Department of Urology, Sant'Andrea Hospital, La Sapienza University, Rome, Italy
| | - Marco De Sio
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, "Luigi Vanvitelli" University, Naples, Italy
| | | | - Simone Crivellaro
- Department of Urology, University of Illinois at Chicago, Chicago, IL, USA
| | - Alexander Kutikov
- Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Riccardo Autorino
- Department of Urology, Rush University Medical Center, Chicago, IL, USA
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3
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Kraszkiewicz M, Napieralska A, Wydmański J, Suwiński R, Majewski W. Evaluation of Efficacy and Tolerance of Radical Radiotherapy and Radiochemotherapy in Treatment of Locally Advanced, Unresectable Rectal Cancer. Technol Cancer Res Treat 2022; 21:15330338221086085. [PMID: 35296187 PMCID: PMC9123928 DOI: 10.1177/15330338221086085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: A retrospective evaluation of tolerance and efficacy of
two schemes of neoadjuvant treatment in patients (pts) with unresectable rectal
cancer: radiochemotherapy (CRT) and radiotherapy (RT), including conventional
and accelerated hyperfractionation. Material and Method: A total of
145 consecutive pts with unresectable, locally advanced rectal cancer. The
schemes used are RT in 73 (50%) or CRT in 72 (50%). In CRT, 54 Gy in 1.8 Gy
fractions was given with chemotherapy, In the RT group, conventional
fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). HART
was introduced at first as an alternative to CFRT, after radiobiological studies
suggesting a therapeutic gain of hyperfractionation in other cancers, and second
to administer relatively high dose needed in unresectable cancer, which is not
feasible in hypofractionation because of critical organs sensitivity to high
fraction doses (fd). HART was an alternative option in pts with medical
contraindications to chemotherapy and to shorten overall treatment time with
greater radiobiological effectiveness than CFRT. Results: Objective
response (OR) in the RT and CRT group was 60% versus 75%. Resection rate (RR) in
RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability
were significant factors for OR. Performance status (PS), tumor mobility, and
neoadjuvant treatment method were significant for RR.
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Affiliation(s)
- M Kraszkiewicz
- Maria Sklodowska-CUrie National Research Institute of Oncology Gliwice Branch, Radiotherapy Department, Gliwice, Poland
| | - A Napieralska
- Maria Sklodowska-CUrie National Research Institute of Oncology Gliwice Branch, Radiotherapy Department, Gliwice, Poland
| | - J Wydmański
- Maria Sklodowska-CUrie National Research Institute of Oncology Gliwice Branch, Radiotherapy Department, Gliwice, Poland
| | - R Suwiński
- Maria Sklodowska-CUrie National Research Institute of Oncology Gliwice Branch, II Radiotherapy and Chemotherapy Teaching Hospital, Gliwice, Poland
| | - W Majewski
- Maria Sklodowska-CUrie National Research Institute of Oncology Gliwice Branch, Radiotherapy Department, Gliwice, Poland
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Sargos P, Supiot S, Créhange G, Fromont-Hankard G, Barret E, Beauval JB, Brureau L, Dariane C, Fiard G, Gauthé M, Mathieu R, Roubaud G, Ruffion A, Renard-Penna R, Neuzillet Y, Rouprêt M, Ploussard G. Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d'Urologie. Cancers (Basel) 2021; 13:6070. [PMID: 34885179 PMCID: PMC8656987 DOI: 10.3390/cancers13236070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 11/26/2021] [Accepted: 11/28/2021] [Indexed: 11/23/2022] Open
Abstract
Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.
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Affiliation(s)
- Paul Sargos
- Department of Radiotherapy, Institut Bergonié, 33000 Bordeaux, France;
| | - Stéphane Supiot
- Department of Radiotherapy, Insitut de Cancérologie de l’Ouest, 44800 St-Herblain, France;
| | - Gilles Créhange
- Department of Radiotherapy, Institut Curie, 75005 Paris, France;
| | | | - Eric Barret
- Department of Urology, Institut Mutualiste Montsouris, 75014 Paris, France;
| | | | - Laurent Brureau
- Department of Urology, CHU de Pointe-à-Pitre, University of Antilles, University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)—UMR_S 1085, 97110 Pointe-à-Pitre, France;
| | - Charles Dariane
- Department of Urology, Hôpital Européen Georges-Pompidou, APHP, Paris—Paris University—U1151 Inserm-INEM, Necker, 75015 Paris, France;
| | - Gaëlle Fiard
- Department of Urology, Grenoble Alpes University Hospital, Université Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France;
| | - Mathieu Gauthé
- Unité de Recherche Clinique en Économie de la Santé, CRESS METHODS INSERM UMR 1153, 75000 Paris, France;
| | - Romain Mathieu
- Department of Urology, CHU Rennes, 35033 Rennes, France;
| | - Guilhem Roubaud
- Department of Medical Oncology, Institut Bergonié, 33000 Bordeaux, France;
| | - Alain Ruffion
- Service d’Urologie Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69002 Lyon, France;
- Equipe 2, Centre d’Innovation en Cancérologie de Lyon (EA 3738 CICLY), Faculté de Médecine Lyon Sud, Université Lyon 1, 69002 Lyon, France
| | - Raphaële Renard-Penna
- Department of Radiology, Sorbonne University, AP-HP, Pitie-Salpetriere Hospital, 75013 Paris, France;
| | - Yann Neuzillet
- Department of Urology, Hôpital Foch, 92151 Suresnes, France;
| | - Morgan Rouprêt
- Department of Urology, Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Pitie-Salpetriere Hospital, 75013 Paris, France;
| | - Guillaume Ploussard
- Department of Urology, La Croix du Sud Hôpital, 31130 Quint Fonsegrives, France;
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5
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The Journey of Radiotherapy Dose Escalation in High Risk Prostate Cancer; Conventional Dose Escalation to Stereotactic Body Radiotherapy (SBRT) Boost Treatments. Clin Genitourin Cancer 2021; 20:e25-e38. [PMID: 34740548 DOI: 10.1016/j.clgc.2021.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 07/08/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023]
Abstract
High risk prostate cancer (HR-PrCa) is a subset of localized PrCa with significant potential for morbidity and mortality associated with disease recurrence and metastasis. Radiotherapy combined with Androgen Deprivation Therapy has been the standard of care for many years in HR-PrCa. In recent years, dose escalation, hypo-fractionation and high precision delivery with immobilization and image-guidance have substantially changed the face of modern PrCa radiotherapy, improving treatment convenience and outcomes. Ultra-hypo-fractionated radiotherapy delivered with high precision in the form of stereotactic body radiation therapy (SBRT) combines delivery of high biologically equivalent dose radiotherapy with the convenience of a shorter treatment schedule, as well as the promise of similar efficacy and reduced toxicity compared to conventional radiotherapy. However, rigorous investigation of SBRT in HR-PrCa remains limited. Here, we review the changes in HR-PrCa radiotherapy through dose escalation, hypo- and ultra-hypo-fractionated radiotherapy boost treatments, and the radiobiological basis of these treatments. We focus on completed and on-going trials in this disease utilizing SBRT as a sole radiation modality or as boost therapy following pelvic radiation.
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6
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Khalifa J, Supiot S, Pignot G, Hennequin C, Blanchard P, Pasquier D, Magné N, de Crevoisier R, Graff-Cailleaud P, Riou O, Cabaillé M, Azria D, Latorzeff I, Créhange G, Chapet O, Rouprêt M, Belhomme S, Mejean A, Culine S, Sargos P. Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder. Radiother Oncol 2021; 161:95-114. [PMID: 34118357 DOI: 10.1016/j.radonc.2021.06.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 05/05/2021] [Accepted: 06/03/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations. METHODS AND MATERIALS In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy. RESULTS A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence. CONCLUSION The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.
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Affiliation(s)
- Jonathan Khalifa
- Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, France
| | - Stéphane Supiot
- Department of Radiotherapy, Institut de Cancérologie de l'Ouest, Nantes Saint-Herblain, France
| | - Géraldine Pignot
- Department of Urology, Institut Paoli Calmettes, Marseille, France
| | | | - Pierre Blanchard
- Department of Radiotherapy, Institut Gustave Roussy, Villejuif, France
| | - David Pasquier
- Department of Radiotherapy, Centre Oscar Lambret, Lille, France
| | - Nicolas Magné
- Department of Radiotherapy, Institut de Cancérologie Lucien Neuwirth, Saint Priest en Jarez, France
| | | | - Pierre Graff-Cailleaud
- Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, France
| | - Olivier Riou
- Department of Radiotherapy, Institut du Cancer de Montpellier, France
| | | | - David Azria
- Department of Radiotherapy, Institut du Cancer de Montpellier, France
| | - Igor Latorzeff
- Department of Radiotherapy, Clinique Pasteur, Toulouse, France
| | | | - Olivier Chapet
- Department of Radiotherapy, Hospices Civils de Lyon, France
| | - Morgan Rouprêt
- Department of Urology, Hôpital Pitié-Salpétrière, APHP Sorbonne Université, Paris, France
| | - Sarah Belhomme
- Department of Medical Physics, Institut Bergonié, Bordeaux, France
| | - Arnaud Mejean
- Department of Urology, Hôpital Européen Georges-Pompidou, Paris, France
| | - Stéphane Culine
- Department of Medical Oncology, Hôpital Saint-Louis, Paris, France
| | - Paul Sargos
- Department of Radiotherapy, Institut Bergonié, Bordeaux, France.
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7
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Hafeez S, Lewis R, Hall E, Huddart R. Advancing Radiotherapy for Bladder Cancer: Randomised Phase II Trial of Adaptive Image-guided Standard or Dose-escalated Tumour Boost Radiotherapy (RAIDER). Clin Oncol (R Coll Radiol) 2021; 33:e251-e256. [PMID: 33766502 DOI: 10.1016/j.clon.2021.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/18/2021] [Accepted: 02/19/2021] [Indexed: 11/21/2022]
Affiliation(s)
- S Hafeez
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, UK.
| | - R Lewis
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UKS
| | - E Hall
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UKS
| | - R Huddart
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, UK
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8
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Fonteyne V, Sargos P. What is the Optimal Dose, Fractionation and Volume for Bladder Radiotherapy? Clin Oncol (R Coll Radiol) 2021; 33:e245-e250. [PMID: 33832838 DOI: 10.1016/j.clon.2021.03.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/04/2021] [Accepted: 03/17/2021] [Indexed: 11/29/2022]
Abstract
External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with different treatment volumes have been described with similar tumour control and, so far, clear recommendations on the optimal radiotherapy regimen and treatment volume are lacking. The current review summarises EBRT literature on dose prescription, fractionation as well as treatment volume in order to guide clinicians in their daily practice when treating patients with muscle-invasive bladder cancer. Taking into account literature on repopulation, continuous-course radiotherapy can be used safely in daily practice where a split-course should only be reserved for those patients who are fit enough to undergo a radical cystectomy in case of a poor early response. A recent meta-analysis has proven that hypofractionated radiotherapy is superior to conventional radiotherapy with regards to invasive locoregional control with similar toxicity profiles. In the absence of node-positive disease, the target volume can be restricted to the bladder. In order to compensate for organ motion, very large margins need to be applied in the absence of image-guided radiotherapy (IGRT). Therefore, the use of IGRT or an adaptive approach is recommended. Based on the available literature, one can conclude that moderate hypofractionated radiotherapy to a dose of 55 Gy in 20 fractions to the bladder only, delivered with IGRT, can be considered standard of care for patients with node-negative invasive bladder cancer.
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Affiliation(s)
- V Fonteyne
- Department of Radiotherapy-Oncology, Ghent University Hospital, Ghent, Belgium.
| | - P Sargos
- Department of Radiotherapy, Institut Bergonié, Bordeaux, France
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9
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Muscle-invasive Bladder Cancer in the Elderly Patient With a Focus on Hypofractionated Radiotherapy. Clin Oncol (R Coll Radiol) 2021; 33:369-375. [PMID: 33612421 DOI: 10.1016/j.clon.2021.02.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/25/2021] [Accepted: 02/03/2021] [Indexed: 02/07/2023]
Abstract
Muscle-invasive bladder cancer is most frequently diagnosed in older patients and the presence of multimorbidity and frailty is common. This means that many patients are unsuitable for definitive treatment with radical cystectomy/(chemo)radiotherapy and are at risk of poor survival outcomes and considerable disease-related morbidity. Screening tools for functional status may be useful to determine the most appropriate treatment for an older person and to identify patients most likely to benefit from comprehensive geriatric assessment and its targeted prehabilitation interventions. For patients unsuitable for definitive treatment, ultrahypofractionated radiotherapy schedules may provide good local control with acceptable toxicity. Short fractionated palliative radiotherapy schedules can provide effective symptom control for patients unsuitable for longer courses of treatment.
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10
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Choudhury A, Porta N, Hall E, Song YP, Owen R, MacKay R, West CML, Lewis R, Hussain SA, James ND, Huddart R, Hoskin P. Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol 2021; 22:246-255. [PMID: 33539743 PMCID: PMC7851111 DOI: 10.1016/s1470-2045(20)30607-0] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/28/2020] [Accepted: 09/29/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Two radiotherapy fractionation schedules are used to treat locally advanced bladder cancer: 64 Gy in 32 fractions over 6·5 weeks and a hypofractionated schedule of 55 Gy in 20 fractions over 4 weeks. Long-term outcomes of these schedules in several cohort studies and case series suggest that response, survival, and toxicity are similar, but no direct comparison has been published. The present study aimed to assess the non-inferiority of 55 Gy in 20 fractions to 64 Gy in 32 fractions in terms of invasive locoregional control and late toxicity in patients with locally advanced bladder cancer. METHODS We did a meta-analysis of individual patient data from patients (age ≥18 years) with locally advanced bladder cancer (T1G3 [high-grade non-muscle invasive] or T2-T4, N0M0) enrolled in two multicentre, randomised, controlled, phase 3 trials done in the UK: BC2001 (NCT00024349; assessing addition of chemotherapy to radiotherapy) and BCON (NCT00033436; assessing hypoxia-modifying therapy combined with radiotherapy). In each trial, the fractionation schedule was chosen according to local standard practice. Co-primary endpoints were invasive locoregional control (non-inferiority margin hazard ratio [HR]=1·25); and late bladder or rectum toxicity, assessed with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic tool (non-inferiority margin for absolute risk difference [RD]=10%). If non-inferiority was met for invasive locoregional control, superiority could be considered if the 95% CI for the treatment effect excluded the null effect (HR=1). One-stage individual patient data meta-analysis models for the time-to-event and binary outcomes were used, accounting for trial differences, within-centre correlation, randomised treatment received, baseline variable imbalances, and potential confounding from relevant prognostic factors. FINDINGS 782 patients with known fractionation schedules (456 from the BC2001 trial and 326 from the BCON trial; 376 (48%) received 64 Gy in 32 fractions and 406 (52%) received 55 Gy in 20 fractions) were included in our meta-analysis. Median follow-up was 120 months (IQR 99-159). Patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0·71 [95% CI 0·52-0·96]). Both schedules had similar toxicity profiles (adjusted RD -3·37% [95% CI -11·85 to 5·10]). INTERPRETATION A hypofractionated schedule of 55 Gy in 20 fractions is non-inferior to 64 Gy in 32 fractions with regard to both invasive locoregional control and toxicity, and is superior with regard to invasive locoregional control. 55 Gy in 20 fractions should be adopted as a standard of care for bladder preservation in patients with locally advanced bladder cancer. FUNDING Cancer Research UK.
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Affiliation(s)
- Ananya Choudhury
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
| | - Nuria Porta
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Emma Hall
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Yee Pei Song
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Ruth Owen
- Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
| | - Ranald MacKay
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Rebecca Lewis
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Syed A Hussain
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Nicholas D James
- Radiotherapy and Imaging Division, The Institute of Cancer Research, London, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Robert Huddart
- Radiotherapy and Imaging Division, The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK
| | - Peter Hoskin
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Mount Vernon Cancer Centre, Northwood, UK
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11
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Cabaillé M, Khalifa J, Tessier AM, Belhomme S, Créhange G, Sargos P. [A review of adaptive radiotherapy for bladder cancer]. Cancer Radiother 2021; 25:271-278. [PMID: 33402293 DOI: 10.1016/j.canrad.2020.08.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 07/30/2020] [Accepted: 08/03/2020] [Indexed: 11/26/2022]
Abstract
PURPOSE Radiation therapy (RT) for muscle invasive bladder cancer (MIBC) is challenging, with observed variations in bladder shape and size resulting in inappropriate coverage of the target volumes (CTV). Large margins were historically applied around the CTV, increasing the dose delivered to organs at risk (OAR). With repositioning imaging and visualization of soft tissues during image guided RT, an opportunity to consider these movements and deformations appeared possible with an adaptive RT approach (ART). MATERIALS AND METHODS A bibliographic search on the PubMed database has been done in January 2019. Studies focusing on patients with MIBC, treating on ART, with the objectives of feasibility, clinical and/or dosimetric evaluation and comparison with a standard irradiation technique were eligible. The purpose of this review was to define the different ART techniques used in clinical practice, to discuss their advantages compared to conventional RT in terms of target volume's coverage and OAR dose and to describe their feasibility in clinical practice. RESULTS A total of 30 studies were selected. The strategies known as "composite offline", "plan of the day" not individualized or individualized, and "re-optimization" have been identified. All the studies have shown a significant benefit of ART in target coverage and dose of OAR, especially the rectum and small bowel. All ART plans produced are not used during RT sessions. Inter-observer variability for the selection of these plans can be observed. The practical implementation within a department required staff education and training, and increases the duration of treatment preparation. The "A-POLO" approach seems to be the most suitable for practice. CONCLUSION ART is the technique of choice for bladder cancer RT. The "plan of the day" approach, individualized according to the A-POLO methodology, seems to be the most effective. The emergence of daily re-optimization, especially using MRI-Linac, is promising. The correlation between dosimetric benefits and clinical efficacy and safety results should be demonstrated into future trials.
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Affiliation(s)
- M Cabaillé
- Département de radiothérapie, Institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France
| | - J Khalifa
- Département de radiothérapie, Institut universitaire du Cancer de Toulouse-Oncopole, 1, avenue Irène-Joliot-Curie, 31100 Toulouse, France
| | - A M Tessier
- Département de radiothérapie, Institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France
| | - S Belhomme
- Département de physique médicale, Institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France
| | - G Créhange
- Département de radiothérapie, Institut Curie, 25, rue d'Ulm, 75005 Paris, France
| | - P Sargos
- Département de radiothérapie, Institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France.
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12
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Hafeez S, Webster A, Hansen VN, McNair HA, Warren-Oseni K, Patel E, Choudhury A, Creswell J, Foroudi F, Henry A, Kron T, McLaren DB, Mitra AV, Mostafid H, Saunders D, Miles E, Griffin C, Lewis R, Hall E, Huddart R. 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. BMJ Open 2020; 10:e041005. [PMID: 33384390 PMCID: PMC7780718 DOI: 10.1136/bmjopen-2020-041005] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 11/03/2020] [Accepted: 11/12/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity. METHODS AND ANALYSIS Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes. ETHICS AND DISSEMINATION This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER NCT02447549; Pre-results.
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Affiliation(s)
- Shaista Hafeez
- Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
- Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK
| | - Amanda Webster
- National Radiotherapy Trials Quality Assurance Group (RTTQA), Mount Vernon Hospital, Northwood, UK
| | - Vibeke N Hansen
- Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark
| | - Helen A McNair
- Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
- Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK
| | - Karole Warren-Oseni
- Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK
| | - Emma Patel
- National Radiotherapy Trials Quality Assurance Group (RTTQA), Mount Vernon Hospital, Northwood, UK
| | - Ananya Choudhury
- Division of Cancer Studies, The University of Manchester, Manchester, UK
- Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, UK
| | - Joanne Creswell
- Department of Urology, James Cook University Hospital, Middlesbrough, UK
| | - Farshad Foroudi
- Department of Radiation Oncology, Austin Health, Heidelberg, Victoria, Australia
| | - Ann Henry
- Leeds Institute of Medical Research, University of Leeds, Leeds, West Yorkshire, UK
- Department of Clinical Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Tomas Kron
- Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Duncan B McLaren
- Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK
| | - Anita V Mitra
- Cancer Services, University College London Hospitals NHS Foundation Trust, London, UK
| | - Hugh Mostafid
- The Stokes Centre for Urology, Royal Surrey Hospital NHS Foundation Trust, Guildford, Surrey, UK
| | - Daniel Saunders
- Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Elizabeth Miles
- National Radiotherapy Trials Quality Assurance Group (RTTQA), Mount Vernon Hospital, Northwood, UK
| | - Clare Griffin
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Rebecca Lewis
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Emma Hall
- Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
| | - Robert Huddart
- Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
- Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK
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13
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Tholomier C, Marcq G, Shinde-Jadhav S, Ayoub M, Huang JM, Kool R, Skowronski R, Brimo F, Mansure JJ, Kassouf W. Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer. Bladder Cancer 2020. [DOI: 10.3233/blc-200315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.
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Affiliation(s)
- Côme Tholomier
- Department of Surgery>, Division of Urology, McGill University, McGill University Health Centre, Montréal, QC, Canada
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Gautier Marcq
- Department of Surgery>, Division of Urology, McGill University, McGill University Health Centre, Montréal, QC, Canada
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Surashri Shinde-Jadhav
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Mina Ayoub
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Jia Min Huang
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Ronald Kool
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Rodrigo Skowronski
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Fadi Brimo
- Department of Pathology, McGill University, McGill University Health Center, Montréal, QC, Canada
| | - Jose Joao Mansure
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Wassim Kassouf
- Department of Surgery>, Division of Urology, McGill University, McGill University Health Centre, Montréal, QC, Canada
- Urologic oncology Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
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14
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Hamad J, McCloskey H, Milowsky MI, Royce T, Smith A. Bladder preservation in muscle-invasive bladder cancer: a comprehensive review. Int Braz J Urol 2020; 46:169-184. [PMID: 31961624 PMCID: PMC7025842 DOI: 10.1590/s1677-5538.ibju.2020.99.01] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 01/02/2020] [Indexed: 01/17/2023] Open
Abstract
Background Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or may wish to avoid the morbidity of cystectomy due to quality of life concerns. Bladder preservation therapies have emerged as alternatives treatment options that can provide comparable oncologic outcomes while maintaining patients’ quality of life. Objective To review bladder preservation therapies, patient selection criteria, and functional and oncologic outcomes for BPT in muscle-invasive bladder cancer. Materials and Methods We conducted a comprehensive literature review of bladder preservation therapies in Pubmed and Embase. Discussion The ideal patient for BPT has low-volume T2 disease, absence of CIS, absence of hydronephrosis, and a maximal TURBT with regular surveillance. Technological advancements involving cancer staging, TURBT technique, and chemotherapy and radiation therapy regimens have improved BPT outcomes, with oncologic outcomes now comparable to those of radical cystectomy. Advancements in BPT also includes a heightened focus on improving quality of life for patients undergoing bladder preservation. Preservation strategies with most evidence for use include trimodality therapy and partial cystectomy with pelvic lymph node dissection. Conclusions This review highlights the breadth of strategies that aim to preserve a patient’s bladder while still optimizing local tumor control and overall survival. Future areas for innovation include the use of predictive biomarkers and implementation of immunotherapy, moving the field towards patient-tailored care.
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Affiliation(s)
- Judy Hamad
- University of North Carolina at Chapel Hill School of Medicine; Chapel Hill, NC, USA
| | - Hannah McCloskey
- 2 Department of Urology, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
| | - Matthew I Milowsky
- Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
| | - Trevor Royce
- Department of Radiation Oncology, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
| | - Angela Smith
- Department of Urology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
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15
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Accelerated Hypofractionated Radiation Therapy for Elderly Frail Bladder Cancer Patients Unfit for Surgery or Chemotherapy. Am J Clin Oncol 2019; 42:179-183. [DOI: 10.1097/coc.0000000000000491] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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16
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Di Franco R, Borzillo V, Ravo V, Ametrano G, Falivene S, Cammarota F, Rossetti S, Romano FJ, D'Aniello C, Cavaliere C, Iovane G, Piscitelli R, Berretta M, Muto P, Facchini G. Rectal/urinary toxicity after hypofractionated vs conventional radiotherapy in low/intermediate risk localized prostate cancer: systematic review and meta analysis. Oncotarget 2017; 8:17383-17395. [PMID: 28129649 PMCID: PMC5370048 DOI: 10.18632/oncotarget.14798] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 12/07/2016] [Indexed: 12/18/2022] Open
Abstract
Purpose The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. Methods PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. Results The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. Conclusions Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.
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Affiliation(s)
- Rossella Di Franco
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Valentina Borzillo
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Vincenzo Ravo
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Gianluca Ametrano
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Sara Falivene
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Fabrizio Cammarota
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Sabrina Rossetti
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy
| | - Francesco Jacopo Romano
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy
| | - Carmine D'Aniello
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Division of Medical Oncology, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO", Napoli
| | - Carla Cavaliere
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy
| | - Gelsomina Iovane
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale' - IRCCS , Naples , Italy
| | - Raffaele Piscitelli
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy
| | - Massimiliano Berretta
- Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy
| | - Paolo Muto
- Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Napoli, Italy
| | - Gaetano Facchini
- Progetto ONCONET2.0 - Linea progettuale 14 per l'implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo - Regione Campania, Italy.,Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale' - IRCCS , Naples , Italy
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17
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Korpics M, Block AM, Altoos B, Martin B, Carey K, Welsh J, Harkenrider MM, Solanki AA. Maximizing survival in patients with muscle-invasive bladder cancer undergoing curative bladder-preserving radiotherapy: the impact of radiotherapy dose escalation. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s13566-017-0319-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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18
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Hafeez S, McDonald F, Lalondrelle S, McNair H, Warren-Oseni K, Jones K, Harris V, Taylor H, Khoo V, Thomas K, Hansen V, Dearnaley D, Horwich A, Huddart R. Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment. Int J Radiat Oncol Biol Phys 2017; 98:115-122. [PMID: 28586948 PMCID: PMC5392498 DOI: 10.1016/j.ijrobp.2017.01.239] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 01/23/2017] [Accepted: 01/31/2017] [Indexed: 11/25/2022]
Abstract
PURPOSE AND OBJECTIVES We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. METHODS AND MATERIALS Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A "plan of the day" radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 months using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. RESULTS Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). CONCLUSION Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.
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MESH Headings
- Aged
- Aged, 80 and over
- Carcinoma, Squamous Cell/mortality
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/radiotherapy
- Carcinoma, Transitional Cell/mortality
- Carcinoma, Transitional Cell/pathology
- Carcinoma, Transitional Cell/radiotherapy
- Cystectomy
- Disease Progression
- Female
- Gastrointestinal Diseases/etiology
- Humans
- Kaplan-Meier Estimate
- Male
- Prospective Studies
- Radiation Dose Hypofractionation
- Radiation Injuries/pathology
- Radiotherapy Planning, Computer-Assisted
- Radiotherapy, Image-Guided/adverse effects
- Radiotherapy, Image-Guided/methods
- Time Factors
- Treatment Outcome
- Urinary Bladder/radiation effects
- Urinary Bladder Neoplasms/mortality
- Urinary Bladder Neoplasms/pathology
- Urinary Bladder Neoplasms/radiotherapy
- Urination Disorders/etiology
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Affiliation(s)
- Shaista Hafeez
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey.
| | | | | | - Helen McNair
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - Karole Warren-Oseni
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - Kelly Jones
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | | | | | | | - Karen Thomas
- The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - Vibeke Hansen
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - David Dearnaley
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - Alan Horwich
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
| | - Robert Huddart
- The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, Sutton, Surrey
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19
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Abstract
Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes.
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Hafeez S, Warren-Oseni K, McNair HA, Hansen VN, Jones K, Tan M, Khan A, Harris V, McDonald F, Lalondrelle S, Mohammed K, Thomas K, Thompson A, Kumar P, Dearnaley D, Horwich A, Huddart R. Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer. Int J Radiat Oncol Biol Phys 2016; 94:1022-30. [PMID: 27026308 DOI: 10.1016/j.ijrobp.2015.12.379] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 12/20/2015] [Accepted: 12/29/2015] [Indexed: 11/17/2022]
Abstract
PURPOSE Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. METHODS AND MATERIALS A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A "plan of the day" approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage. RESULTS A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D98 (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. CONCLUSIONS Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.
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Affiliation(s)
- Shaista Hafeez
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.
| | - Karole Warren-Oseni
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Helen A McNair
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Vibeke N Hansen
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Kelly Jones
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Melissa Tan
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Attia Khan
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Victoria Harris
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Fiona McDonald
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Susan Lalondrelle
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Kabir Mohammed
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Karen Thomas
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Alan Thompson
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Pardeep Kumar
- The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - David Dearnaley
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Alan Horwich
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
| | - Robert Huddart
- The Institute of Cancer Research, London, United Kingdom; The Royal Marsden National Health Service Foundation Trust, London, United Kingdom
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Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study. Int J Radiat Oncol Biol Phys 2016; 94:60-66. [DOI: 10.1016/j.ijrobp.2015.09.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/04/2015] [Accepted: 09/09/2015] [Indexed: 11/17/2022]
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Muscle-invasive bladder cancer treated with TURB followed by concomitant boost with small reduction of radiotherapy field with or without of chemotherapy. Rep Pract Oncol Radiother 2015; 21:31-6. [PMID: 26900355 DOI: 10.1016/j.rpor.2015.09.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 06/15/2015] [Accepted: 09/02/2015] [Indexed: 11/21/2022] Open
Abstract
AIM To evaluate the clinical outcome and toxicity of the treatment of muscle-invasive bladder cancer (MIBC) that combined transurethral resection of bladder tumor (TURB) with "concomitant boost" radiotherapy delivered over a shortened overall treatment time of 5 weeks, with or without concurrent chemotherapy. BACKGROUND Local control of MIBC by bladder-sparing approach is unsatisfactory. In order to improve the effectiveness of radiotherapy, we have designed a protocol that combines TURB with a non-conventionally fractionated radiotherapy "concomitant boost". MATERIALS AND METHODS Between 2004 and 2010, 73 patients with MIBC cT2-4aN0M0, were treated with "concomitant boost" radiotherapy. The whole bladder with a 2-3 cm margin was irradiated with fractions of 1.8 Gy to a dose of 45 Gy, with a "concomitant boost" to the bladder with 1-1.5 cm margin, during the last two weeks of treatment, as a second fraction of 1.5 Gy, to a total dose of 60 Gy. Radiochemotherapy using mostly cisplatin was delivered in 42/73(58%) patients, 31/73(42%) patients received radiotherapy alone. RESULTS Acute genitourinary toxicity of G3 was scored in 3/73(4%) patients. Late gastrointestinal toxicity higher than G2 and genitourinary higher than G3 were not reported. Complete remission was achieved in 48/73(66%), partial remission in 17/73(23%), and stabilization disease in 8/73(11%) patients. Three- and five-year overall, disease specific and invasive locoregional disease-free survival rates were 65% and 52%, 70% and 59%, 52% and 43%, respectively. CONCLUSIONS An organ-sparing approach using TURB followed by radio(chemo)therapy with "concomitant boost" in patients with MIBC allows to obtain long-term survival with acceptable toxicity.
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Whalley D, Caine H, McCloud P, Guo L, Kneebone A, Eade T. Promising results with image guided intensity modulated radiotherapy for muscle invasive bladder cancer. Radiat Oncol 2015; 10:205. [PMID: 26407726 PMCID: PMC4583158 DOI: 10.1186/s13014-015-0499-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Accepted: 09/03/2015] [Indexed: 01/06/2023] Open
Abstract
AIM To describe the feasibility of image guided intensity modulated radiotherapy (IG-IMRT) using daily soft tissue matching in the treatment of bladder cancer. METHODS Twenty-eight patients with muscle-invasive carcinoma of the bladder were recruited to a protocol of definitive radiation using IMRT with accelerated hypofractionation with simultaneous integrated boost (SIB). Isotropic margins of .5 and 1 cm were used to generate the high risk and intermediate risk planning target volumes respectively. Cone beam CT (CBCT) was acquired daily and a soft tissue match was performed. Cystoscopy was scheduled 6 weeks post treatment. RESULTS The median age was 83 years (range 58-92). Twenty patients had stage II or III disease, and eight were stage IV. Gross disease received 66 Gy in 30 fractions in 11 patients (ten with concurrent chemotherapy) or 55 Gy in 20 fractions for those of poorer performance status or with palliative intent. All patients completed radiation treatment as planned. Three patients ceased chemotherapy early due to toxicity. Six patients (21 %) had acute Grade ≥ 2 genitourinary (GU) toxicity and six (21 %) had acute Grade ≥ 2 gastrointestinal (GI) toxicity. Five patients (18 %) developed Grade ≥2 late GU toxicity and no ≥2 late GI toxicity was observed. Nineteen patients underwent cystoscopy following radiation, with complete response (CR) in 16 cases (86 %), including all patients treated with chemoradiotherapy. Eight patients relapsed, four of which were local relapses. Of the patients with local recurrence, one underwent salvage cystectomy. For patients treated with definitive intent, freedom from locoregional recurrence (FFLR) and overall survival (OS) was 90 %/100 % for chemoradiotherapy versus 86 %/69 % for radiotherapy alone. CONCLUSION IG- IMRT using daily soft tissue matching is a feasible in the treatment of bladder cancer, enabling the delivery of accelerated synchronous integrated boost with good early local control outcomes and low toxicity.
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Affiliation(s)
- D Whalley
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia.
| | - H Caine
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia.
| | - P McCloud
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia. .,McCloud Consulting Group, 7-9 Merriwa Street, Gordon, NSW, 2072, Australia.
| | - L Guo
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia.
| | - A Kneebone
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia. .,McCloud Consulting Group, 7-9 Merriwa Street, Gordon, NSW, 2072, Australia.
| | - T Eade
- Northern Sydney Cancer Centre, Radiation Oncology, Royal North Shore Hospital, Reserve Road, St Leonards, Sydney, NSW, 2065, Australia. .,Northern Clinical School, University of Sydney, Camperdown, NSW, 2050, Australia.
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McDonald F, Waters R, Gulliford S, Hall E, James N, Huddart RA. Defining bowel dose volume constraints for bladder radiotherapy treatment planning. Clin Oncol (R Coll Radiol) 2015; 27:22-9. [PMID: 25445550 DOI: 10.1016/j.clon.2014.09.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 09/01/2014] [Accepted: 09/23/2014] [Indexed: 10/24/2022]
Abstract
AIMS Increases to radiotherapy dose are constrained by normal tissue effects. The relationship between bowel dose volume data and late bowel toxicity in patients with muscle-invasive bladder cancer treated with radical radiotherapy was assessed. MATERIALS AND METHODS The bowel was contoured retrospectively on radiotherapy plans of 47 patients recruited to the BC2001 trial (CRUK/01/004). The relationship between bowel volume at various dose levels and prospectively collected late bowel toxicity was explored. RESULTS Fifteen per cent and 6% of patients experienced grade 1 and grade 2 or more late bowel toxicity, respectively. The mean bowel volume was significantly less at doses ≥50 Gy in those treated with reduced high dose volume radiotherapy compared with standard radiotherapy. The probability of late bowel toxicity increased as bowel volume increased (P ≤ 0.05 for dose levels 30-50 Gy). No grade 2 or more late bowel toxicity was observed in patients with bowel volumes under the thresholds given in the model that predict for 25% probability of late bowel toxicity. CONCLUSIONS There is a dose volume effect for late bowel toxicity in radical bladder radiotherapy. We have modelled the probability of late bowel toxicity from absolute bowel volumes to guide clinicians in assessing radical bladder radiotherapy plans. Thresholds predicting for a 25% probability of late bowel toxicity are proposed as dose volume constraints.
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Affiliation(s)
- F McDonald
- Academic Radiotherapy Unit, Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - R Waters
- Clinical Trials and Statistics Unit, Institute of Cancer Research, London, UK
| | - S Gulliford
- Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK
| | - E Hall
- Clinical Trials and Statistics Unit, Institute of Cancer Research, London, UK
| | - N James
- Clinical Trials Unit Gibbet Hill Campus, University of Warwick, Coventry, UK
| | - R A Huddart
- Academic Radiotherapy Unit, Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
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Tree AC, Khoo VS, van As NJ, Partridge M. Is biochemical relapse-free survival after profoundly hypofractionated radiotherapy consistent with current radiobiological models? Clin Oncol (R Coll Radiol) 2014; 26:216-29. [PMID: 24529742 DOI: 10.1016/j.clon.2014.01.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/19/2013] [Accepted: 01/02/2014] [Indexed: 11/25/2022]
Abstract
AIMS The α/β ratio for prostate cancer is thought to be low and less than for the rectum, which is usually the dose-limiting organ. Hypofractionated radiotherapy should therefore improve the therapeutic ratio, increasing cure rates with less toxicity. A number of models for predicting biochemical relapse-free survival have been developed from large series of patients treated with conventional and moderately hypofractionated radiotherapy. The purpose of this study was to test these models when significant numbers of patients treated with profoundly hypofractionated radiotherapy were included. MATERIALS AND METHODS A systematic review of the literature with regard to hypofractionated radiotherapy for prostate cancer was conducted, focussing on data recently presented on prostate stereotactic body radiotherapy. For the work described here, we have taken published biochemical control rates for a range of moderately and profoundly fractionated schedules and plotted these together with a range of radiobiological models, which are described. RESULTS The data reviewed show consistency between the various radiobiological model predictions and the currently observed data. CONCLUSION Current radiobiological models provide accurate predictions of biochemical relapse-free survival, even when profoundly hypofractionated patients are included in the analysis.
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Affiliation(s)
- A C Tree
- Royal Marsden NHS Foundation Trust, London, UK.
| | - V S Khoo
- Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK
| | - N J van As
- Royal Marsden NHS Foundation Trust, London, UK
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The role of radiotherapy in bladder cancer. Urologia 2014; 80:202-6. [PMID: 24526596 DOI: 10.5301/ru.2013.11554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2013] [Indexed: 11/20/2022]
Abstract
In this article we report on the current role of radiotherapy in the management of non-muscle invasive as well as in muscle invasive bladder cancer.
Radiotherapy seems to have no role in non-muscle invasive bladder cancer.
In muscle invasive bladder tumors, the role of radiotherapy is under investigation in view of new radiotherapy techniques and novel cytotoxic and biological agents.
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Assessment of the radiation-equivalent of chemotherapy contributions in 1-phase radio-chemotherapy treatment of muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys 2014; 88:927-32. [PMID: 24462386 DOI: 10.1016/j.ijrobp.2013.11.242] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Revised: 11/18/2013] [Accepted: 11/25/2013] [Indexed: 12/25/2022]
Abstract
PURPOSE To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. RESULTS The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.
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28
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Nishioka K, Shimizu S, Shinohara N, Ito YM, Abe T, Maruyama S, Kinoshita R, Harada K, Nishikawa N, Miyamoto N, Onimaru R, Shirato H. Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer. Jpn J Clin Oncol 2013; 44:28-35. [PMID: 24302759 PMCID: PMC3880146 DOI: 10.1093/jjco/hyt182] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. METHODS Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. RESULTS Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. CONCLUSIONS Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.
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Affiliation(s)
- Kentaro Nishioka
- *Department of Radiation Medicine, Hokkaido University Graduate School of Medicine/School of Medicine, Sapporo, Japan.
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Plataniotis GA, Dale RG. Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control. World J Radiol 2013; 5:267-274. [PMID: 24003352 PMCID: PMC3758494 DOI: 10.4329/wjr.v5.i8.267] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 06/26/2013] [Accepted: 08/06/2013] [Indexed: 02/06/2023] Open
Abstract
The purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.9% vs 64.4% (Wilcoxon rank-sum test, P = 0.001). Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT, in addition to concurrent RCT. The RCT studies included the one-phase type (where a full dose of RCT was given and then assessment of response and cystectomy for non-responders followed) and the two-phase types (where an assessment of response was undertaken after an initial RCT course, followed 6 wk later by a consolidation RCT for those patients with a CR). CR rates between the two subgroups of RCT studies were 79.6% (one phase) vs 71.6% (two-phase) (P = 0.015). The average achievable tumour control rates, with an acceptable rate of side effects have been around 70%, which may represent a plateau. Further increase in CR response rates demands for new chemotherapeutic agents, targeted therapies, or modified fractionation in various combinations. Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain.
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Smith ZL, Christodouleas JP, Keefe SM, Malkowicz SB, Guzzo TJ. Bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC): a review of the literature and a practical approach to therapy. BJU Int 2013; 112:13-25. [DOI: 10.1111/j.1464-410x.2012.11762.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Zachary L. Smith
- Division of Urology; Hospital of the University of Pennsylvania; Philadelphia; PA; USA
| | - John P. Christodouleas
- Department of Radiation Oncology; Hospital of the University of Pennsylvania; Philadelphia; PA; USA
| | - Stephen M. Keefe
- Department of Medicine; Division of Hematology/Oncology; Hospital of the University of Pennsylvania; Philadelphia; PA; USA
| | - S. Bruce Malkowicz
- Division of Urology; Hospital of the University of Pennsylvania; Philadelphia; PA; USA
| | - Thomas J. Guzzo
- Division of Urology; Hospital of the University of Pennsylvania; Philadelphia; PA; USA
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High precision bladder cancer irradiation by integrating a library planning procedure of 6 prospectively generated SIB IMRT plans with image guidance using lipiodol markers. Radiother Oncol 2012; 105:174-9. [DOI: 10.1016/j.radonc.2012.08.011] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Revised: 08/02/2012] [Accepted: 08/14/2012] [Indexed: 11/21/2022]
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Panteliadou M, Giatromanolaki A, Touloupidis S, Destouni E, Tsoutsou PG, Pantelis P, Abatzoglou I, Sismanidou K, Koukourakis MI. Treatment of invasive bladder cancer with conformal hypofractionated accelerated radiotherapy and amifostine (HypoARC). Urol Oncol 2012; 30:813-20. [DOI: 10.1016/j.urolonc.2010.09.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2010] [Revised: 09/05/2010] [Accepted: 09/07/2010] [Indexed: 10/18/2022]
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Hindson BR, Turner SL, Millar JL, Foroudi F, Gogna NK, Skala M, Kneebone A, Christie DRH, Lehman M, Wiltshire KL, Tai KH. Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2011 consensus guidelines for curative radiotherapy for urothelial carcinoma of the bladder. J Med Imaging Radiat Oncol 2012; 56:18-30. [PMID: 22339742 DOI: 10.1111/j.1754-9485.2011.02336.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Curative radiotherapy, with or without concurrent chemotherapy, is recognized as a standard treatment option for muscle-invasive bladder cancer. It is commonly used for two distinct groups of patients: either for those medically unfit for surgery, or as part of a 'bladder preserving' management plan incorporating the possibility of salvage cystectomy. However, in both situations, the approach to radiotherapy varies widely around the world. The Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recognised a need to develop consistent, evidence-based guidelines for patient selection and radiotherapy technique in the delivery of curative radiotherapy. Following a workshop convened in May 2009, a working party collated opinions and conducted a wide literature appraisal linking each recommendation with the best available evidence. This process was subject to ongoing re-presentation to the Faculty of Radiation Oncology Genito-Urinary Group members prior to final endorsement. These Guidelines include patient selection, radiation target delineation, dose and fractionation schedules, normal tissue constraints and investigational techniques. Particular emphasis is given to the rationale for the target volumes described. These Guidelines provide a consensus-based framework for the delivery of curative radiotherapy for muscle-invasive bladder cancer. Widespread input from radiation oncologists treating bladder cancer ensures that these techniques are feasible in practice. We recommend these Guidelines be adopted widely in order to encourage a uniformly high standard of radiotherapy in this setting, and to allow for better comparison of outcomes.
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Affiliation(s)
- Benjamin R Hindson
- William Buckland Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia.
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Thariat J, Aluwini S, Pan Q, Caullery M, Marcy PY, Housset M, Lagrange JL. Image-guided radiation therapy for muscle-invasive bladder cancer. Nat Rev Urol 2011; 9:23-9. [DOI: 10.1038/nrurol.2011.173] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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35
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Harris VA, McDonald FMA, Huddart R. Latest advances in cone-beam CT for bladder radiotherapy. ACTA ACUST UNITED AC 2011. [DOI: 10.2217/iim.11.20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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36
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‘Plan of the day’ adaptive radiotherapy for bladder cancer using helical tomotherapy. Radiother Oncol 2011; 99:55-60. [DOI: 10.1016/j.radonc.2011.01.027] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2010] [Revised: 01/31/2011] [Accepted: 01/31/2011] [Indexed: 11/21/2022]
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38
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Majewski W, Tarnawski R. Acute and Late Toxicity in Radical Radiotherapy for Bladder Cancer. Clin Oncol (R Coll Radiol) 2009; 21:598-609. [DOI: 10.1016/j.clon.2009.04.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2007] [Revised: 02/26/2009] [Accepted: 04/28/2009] [Indexed: 11/16/2022]
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Poortmans PM, Richaud P, Collette L, Ho Goey S, Pierart M, Van Der Hulst M, Bolla M. Results of the phase II EORTC 22971 trial evaluating combined accelerated external radiation and chemotherapy with 5FU and cisplatin in patients with muscle invasive transitional cell carcinoma of the bladder. Acta Oncol 2009; 47:937-40. [PMID: 18568488 DOI: 10.1080/02841860801888799] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION We prospectively evaluated concomitant radiotherapy and chemotherapy for advanced bladder cancer in a phase II EORTC trial to test whether it could be further studied as a potential treatment of bladder cancer. PATIENTS AND METHODS Patients up to 75 years of age with invasive transitional-cell carcinoma of the bladder up to 5 cm, stage pT2 to pT3b, N0M0, without residual macroscopical tumour after transurethral excision were eligible. Radiotherapy consisted of 2 fractions of 1.2 Gy daily up to 60 Gy delivered in a period of 5 weeks. During the first and the last week, cisplatin 20 mg/m(2)/day and 5 FU 375 mg/m(2)/day were given concomitantly. RESULTS The study was interrupted early due to poor recruitment. Nine patients of the originally 43 planned were treated. Mean age was 63 years. Five patients had tumour stage pT2, 1 stage pT3a and 3 stage pT3b. All patients completed radiotherapy and chemotherapy as scheduled. Only one grade 3 and no grade 4 toxicity was seen. All patients were evaluated 3 months after treatment: eight patients had no detectable tumour and one had para-aortic lymph nodes. During further follow-up, a second patient got lymph node metastases and two patients developed distant metastases (lung in the patient with enlarged lymph nodes at the first evaluation and abdominal in one other). Those three patients died at respectively 19, 14, and 18 months after registration. Late toxicity was limited and often temporary. After 26 to 57 months of follow-up, no local recurrences were seen. Six patients remained alive without disease. DISCUSSION Despite the small cohort, this combination of concomitant chemotherapy and accelerated hyperfractionated radiotherapy for invasive bladder cancer seemed to be well tolerated and to result in satisfactory local control with limited early and late toxicity. It could therefore be considered for study in further clinical trials.
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Zapatero A, Martin de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol 2009; 28:368-74. [PMID: 19362865 DOI: 10.1016/j.urolonc.2009.01.031] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2008] [Revised: 01/21/2009] [Accepted: 01/22/2009] [Indexed: 10/20/2022]
Abstract
PURPOSE To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS). MATERIALS AND METHODS Between 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity. RESULTS The mean follow-up for the whole series was 54 months (range 9-156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade >/=2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532). CONCLUSION These data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders.
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Affiliation(s)
- Almudena Zapatero
- Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid, Spain.
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Thariat J, Caullery M, Ginot A, Hannoun-Lévi JM, Barrière J, Buthaud X, Marcié S, Bondiau PY, Housset M, Lagrange JL, Amiel J, Gérard JP. Techniques et innovations en radiothérapie pour le traitement conservateur des cancers infiltrants localisés de vessie. Prog Urol 2009; 19:85-93. [DOI: 10.1016/j.purol.2008.11.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2008] [Revised: 10/29/2008] [Accepted: 11/03/2008] [Indexed: 10/21/2022]
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Conservative treatment in patients with muscle-invasive bladder cancer by transurethral resection, neoadjuvant chemotherapy with gemcitabine and cisplatin, and accelerated radiotherapy with concomitant boost plus concurrent cisplatin – assessment of response and toxicity. Rep Pract Oncol Radiother 2008. [DOI: 10.1016/s1507-1367(10)60016-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Koukourakis MI, Tsolos C, Touloupidis S. Radical hypofractionated accelerated radiotherapy with cytoprotection for invasive bladder cancer. Urology 2007; 69:245-50. [PMID: 17320657 DOI: 10.1016/j.urology.2006.09.064] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2006] [Revised: 08/17/2006] [Accepted: 09/29/2006] [Indexed: 10/23/2022]
Abstract
OBJECTIVES To report a series of patients with bladder cancer treated with hypofractionated accelerated radiotherapy with amifostine cytoprotection, with or without concurrent liposomal doxorubicin. Radiochemotherapy has been shown to be an effective alternative to cystectomy. METHODS A total of 38 patients with invasive bladder cancer were treated with 15 consecutive fractions of 3.4 Gy (2.7 Gy to the pelvis and a 0.7-Gy concomitant boost to the bladder; total biologic dose 66 to 72 Gy in 19 days). An individualized amifostine dose of up to 1000 mg was given subcutaneously before each radiotherapy fraction. Nineteen patients received concomitant liposomal doxorubicin (25 mg/m2 every 2 weeks for six cycles). RESULTS Of the 38 patients, 33 tolerated a daily amifostine dose of 750 to 1000 mg well. For these patients, the acute radiation toxicity in the bladder and rectum was minimal. Liposomal doxorubicin did not increase radiation sequela and had no systemic side effects. At a median follow-up of 22 months, severe late sequelae were infrequent (5.5% dysuria grade 2, 7.8% frequency grade 1, and 2.8% incontinence grade 2). Cystoscopy confirmed significant bladder shrinkage in 8% of patients. Intermittent rectal urgency was noted in only 5.5% of patients. A complete response was obtained in 32 (84.2%) of 38 patients. Despite the 10% greater complete response rate noted in patients receiving chemotherapy, the difference did not reach statistical significance. The 2-year local relapse-free survival rate was 80%. CONCLUSIONS Hypofractionated accelerated radiotherapy with amifostine cytoprotection with or without concomitant liposomal doxorubicin provided high control rates of bladder cancer with low toxicity, and also had the advantage of reducing by 4 weeks the overall treatment time compared with standard radiotherapy.
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Affiliation(s)
- Michael I Koukourakis
- Department of Radiotherapy and Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
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Pos FJ, Hart G, Schneider C, Sminia P. Radical radiotherapy for invasive bladder cancer: What dose and fractionation schedule to choose? Int J Radiat Oncol Biol Phys 2006; 64:1168-73. [PMID: 16376486 DOI: 10.1016/j.ijrobp.2005.09.023] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2005] [Revised: 09/12/2005] [Accepted: 09/13/2005] [Indexed: 11/28/2022]
Abstract
PURPOSE To establish the alpha/beta ratio of bladder cancer from different radiotherapy schedules reported in the literature and provide guidelines for the design of new treatment schemes. METHODS AND MATERIALS Ten external beam radiotherapy (EBRT) and five brachytherapy schedules were selected. The biologically effective dose (BED) of each schedule was calculated. Logistic modeling was used to describe the relationship between 3-year local control (LC3y) and BED. RESULTS The estimated alpha/beta ratio was 13 Gy (95% confidence interval [CI], 2.5-69 Gy) for EBRT and 24 Gy (95% CI, 1.3-460 Gy) for EBRT and brachytherapy combined. There is evidence for an overall dose-response relationship. After an increase in total dose of 10 Gy, the odds of LC3y increase by a factor of 1.44 (95% CI, 1.23-1.70) for EBRT and 1.47 (95% CI, 1.25-1.72) for the data sets of EBRT and brachytherapy combined. CONCLUSION With the clinical data currently available, a reliable estimation of the alpha/beta ratio for bladder cancer is not feasible. It seems reasonable to use a conventional alpha/beta ratio of 10-15 Gy. Dose escalation could significantly increase local control. There is no evidence to support short overall treatment times or large fraction sizes in radiotherapy for bladder cancer.
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Affiliation(s)
- Floris J Pos
- Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Abstract
The most effective non-surgical treatment for bladder cancer remains radiotherapy. The dramatic technical developments in radiotherapy have enabled greater accuracy and reliability based on three-dimensional imaging for both planning and verification. Particle therapy, in particular using protons, provides further opportunities for optimising radiation delivery and dose escalation. Novel fractionation schedules with both hyperfractionation and hypofractionation may have added benefits. Chemoradiation has been shown in one randomised-controlled trial to improve the results of radiotherapy alone, and requires further investigation. Hypoxia modification using carbogen and nicotinamide has also shown promising results in a phase II trial, and is now in phase III evaluation. Novel drug agents for bladder cancer are few, but the anti-EGFR agents and anti-angiogenic agents may have promise; the development of anti-apoptotic agents and antisense gene therapy may also become a component of the future multimodality management of this tumour.
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Affiliation(s)
- R Alonzi
- Mount Vernon Hospital, Northwood, Middlesex, UK
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