Longitudinal Evaluation of Intestinal, Haematological and Urinary Toxicity From Pelvic Irradiation for Prostate Cancer

Prostate Cancer Clinical Trial

— IHU-WPRT-TOX  

Official title:

Longitudinal Evaluation of Intestinal, Haematological and Urinary Toxicity From Pelvic Irradiation for Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02803086
• Other study ID #: IRCCS San Raffaele
• Status: Active, not recruiting
• Start date: February 2014
• Est. completion date: December 2026

Study information

• Verified date: January 2023
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The prophylactic irradiation of pelvic lymph-nodes by means of Whole-Pelvis Radiotherapy (WPRT) in the treatment of prostate cancer (PCa) is aimed at the timely eradication of microscopic lymph-nodal metastases. Nevertheless, even though delivered by means of modern Intensity-Modulated Radiotherapy (IMRT) techniques, WPRT may result in intestinal, hematologic and urinary toxicity (IT, HT, UT, respectively) severely affecting patients' daily health-related quality-of-life (HRQoL) within the so-called and inadequately investigated Pelvic Radiation Disease.

The aim of this study is to develop sophisticated predictive models of IMRT-WPRT induced patient-reported HT, IT and UT in PCa. The possible correlation between several clinical factors and radiation doses received by various pelvic structures (i.e. pelvic bones subvolumes, intestinal loops, sigmoid, rectum and bladder) and risk and severity of patient-reported IT, UT and HT will be analyzed and robust multi-variable models will be developed and internally validated. A secondary end-point will be the identification of specific symptoms affecting patients' HRQoL during irradiation and in the long term, overall and in different therapeutic settings (radical, adjuvant and salvage). Lastly, possible correlation between HT and UT/IT will be investigated.

Description:

Experimental Design:

Hypothesis. Dose-volume histograms (DVHs) of bowel, sigmoid colon and rectum are expected to be predictive of IT prospectively self-assessed by patients by means of IBDQ (Inflammatory Bowel Disease Questionnaire). Similarly, DVHs of pelvic bony subvolumes (lumbar-sacral, iliac and the lower pelvis) should predict HT, while DVHs and dose-surface histograms (DSHs) of the bladder are expected to be predictive of UT self-assessed by patients by means of IPSS (International Prostate Symptoms Score) and ICIQ-SF (International Consultation on Incontinence Questionnaire- short form) questionnaires. Moreover, some specific urinary and intestinal-rectal symptoms are expected to lead to impairment in emotional, social and systemic domains, as assessed by the IBDQ questionnaire, more than others, with several possible "clusters" of symptoms prevailing in different treatment settings. Finally, the intestinal, urinary and hematologic toxicity profile of WPRT IMRT could emerge to be extremely different in patients treated with radical (RAD), adjuvant (ADV) or salvage (SALV) intent.

Task1. The principal aim of the project is to develop sophisticated quantitative predictive models of IT, UT and HT (without the confounding bias of chemotherapy) from WPRT IMRT in both radical and postoperative treatment of localized PCa. The possible correlation between the radiation doses received by different pelvic structures and different toxicities will be analyzed.

Task2. To try to individuate the intestinal/rectal and urinary symptoms most negatively affecting the Emotional, Social and Systemic patient domains, with the ultimate objective of "focusing" the quantitative predictive models including both clinical and physico-dosimetric parameters only upon these main symptoms. This approach could theoretically permit the creation of a "shortened and radiotherapy adapted" version of the IBDQ questionnaire.

Task3. A thorough assessment of the different self-assessed toxicity profiles to be expected in patients treated with RAD, ADV or SALV intent will be carried out, with the ultimate aim of accumulating a set of extremely detailed information to be provided to patients in order to offer them appropriate counselling after the initial diagnosis of PCa with regard to the choice between radiotherapy vs surgery. In those selecting the latter and in the presence of risk factors at prostatectomy suggesting a possible role for postoperative radiotherapy, the ultimate objective would be that of assisting patients in the always extremely problematic choice between immediate adjuvant and timely, postponed, salvage irradiation in the case of biochemical recurrence.

Task4. Secondary end-points: to search for a possible correlation between HT and IT/UT.

Throughout the treatment period, patients will be seen every 2 weeks for toxicity monitoring. Subsequently, a follow-up visit will be performed at 3 months from the end of treatment, and every six months thereafter, up to 5 years.

Intestinal and urinary toxicities, including urinary incontinence, will be self-assessed by patients by means of the Italian validated version of the IBDQ, IPSS and ICIQ-SF questionnaires: at baseline (no more than 30 days before RT start), at radiotherapy mid-point and end, at 3, 6,12, 18, 24, 30, 36, 42, 48, 54 and 60 months from radiotherapy conclusion.

A blood sample for white blood cells (WBC), with absolute neutrophil and lymphocyte counts (ANC and ALC, respectively), red blood cells (RBC) and platelets (PLT) counts will be collected at the same time intervals. In addition to the self-reported assessment of rectal/bowel and urinary symptoms during and after radiotherapy, an evaluation of acute and late IT and UT will be performed by the medical staff for possible future comparison between its subjective and objective measurement. IT, HT and UT will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. completion date: December 2026
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with with an ECOG PS 0-1

• Patients with histologically proven adenocarcinoma of the prostate

• WPRT can be delivered with both static and rotational IMRT techniques such as volumetric modulated arc therapy (VMAT) or Tomotherapy

• Both conventionally (1.8-2 Gy/fraction) and moderately hypo-fractionated (= 2.7 Gy/fraction) regimens with simultaneous integrated boost (SIB) approach are allowed; in any case the daily dose delivered to the pelvic nodes should be in the range of 1.8-2.0 Gy/fr

Exclusion Criteria:

• Patients older than 80 years at the time of enrollment

• Missing written informed consent

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele	Milan

Sponsors (15)

Lead Sponsor

Collaborator

IRCCS San Raffaele

Arcispedale Santa Maria Nuova-IRCCS, Associazione Italiana per la Ricerca sul Cancro, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria, Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy, Azienda Sanitaria dell'Alto Adige, Azienda Sanitaria Locale di Biella, Azienda Sanitaria Locale To4, Azienda U.S.L. della Valle d'Aosta, Candiolo Cancer Institute - IRCCS, Centro AKTIS Diagnostica e Terapia, Cliniche Humanitas Gavazzeni, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, IRCCS Centro di Riferimento Oncologico della Basilicata, Regina Elena Cancer Institute

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Bresolin A, Faiella A, Garibaldi E, Munoz F, Cante D, Vavassori V, Waskiewicz JM, Girelli G, Avuzzi B, Villa E, Magli A, Noris Chiorda B, Gatti M, Ferella L, Maggio A, Landoni V, Aimonetto S, Sini C, Rancati T, Sanguineti G, Valdagni R, Di Muzio N, Fiorino C, Cozzarini C. Acute patient-reported intestinal toxicity in whole pelvis IMRT for prostate cancer: Bowel dose-volume effect quantification in a multicentric cohort study. Radiother Oncol. 2021 May;158:74-82. doi: 10.1016/j.radonc.2021.02.026. Epub 2021 Feb 25. — View Citation

Cozzarini C, Fiorino C, Da Pozzo LF, Alongi F, Berardi G, Bolognesi A, Briganti A, Broggi S, Deli A, Guazzoni G, Perna L, Pasetti M, Salvadori G, Montorsi F, Rigatti P, Di Muzio N. Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):191-9. doi: 10.1016/j.ijrobp.2010.09.027. Epub 2010 Nov 23. — View Citation

Cozzarini C, Fiorino C, Deantoni C, Briganti A, Fodor A, La Macchia M, Noris Chiorda B, Rancoita PM, Suardi N, Zerbetto F, Calandrino R, Montorsi F, Di Muzio N. Higher-than-expected severe (Grade 3-4) late urinary toxicity after postprostatectomy hypofractionated radiotherapy: a single-institution analysis of 1176 patients. Eur Urol. 2014 Dec;66(6):1024-30. doi: 10.1016/j.eururo.2014.06.012. Epub 2014 Jun 27. — View Citation

Cozzarini C, Noris Chiorda B, Sini C, Fiorino C, Briganti A, Montorsi F, Di Muzio N. Hematologic Toxicity in Patients Treated With Postprostatectomy Whole-Pelvis Irradiation With Different Intensity Modulated Radiation Therapy Techniques Is Not Negligible and Is Prolonged: Preliminary Results of a Longitudinal, Observational Study. Int J Radiat Oncol Biol Phys. 2016 Jun 1;95(2):690-5. doi: 10.1016/j.ijrobp.2016.01.022. Epub 2016 Jan 28. — View Citation

Munoz F, Sanguineti G, Bresolin A, Cante D, Vavassori V, Waskiewicz JM, Girelli G, Avuzzi B, Garibaldi E, Faiella A, Villa E, Magli A, Noris Chiorda B, Gatti M, Rancati T, Valdagni R, Di Muzio NG, Fiorino C, Cozzarini C. Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy. Cancers (Basel). 2021 Jun 29;13(13):3243. doi: 10.3390/cancers13133243. — View Citation

Sini C, Fiorino C, Perna L, Noris Chiorda B, Deantoni CL, Bianchi M, Sacco V, Briganti A, Montorsi F, Calandrino R, Di Muzio N, Cozzarini C. Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation. Radiother Oncol. 2016 Jan;118(1):79-84. doi: 10.1016/j.radonc.2015.11.020. Epub 2015 Dec 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic toxicity	if any, acute (	5 years
Primary	Intestinal toxicity	a worsening of 2 points or more with respect to baseline of the 10 IBDQ items investigating the Bowel Domain (items # 1, 5, 9, 13, 17, 20, 22, 24, 26 and 29, frequency of bowel movements, liquid defecation, abdominal cramps, abdominal pain, gas passage, abdominal bloating, rectal bleeding, urge to go to bathroom even if empty intestine, accidental soiling and nausea/feeling sick, respectively) and of the three cumulative items evaluating the impact of Bowel Symptoms on the Emotional, Social and Systemic Domains.	5 years