Predictors of Normal Tissue Response From the Microenvironment in Radiotherapy for Prostate and Head-and-neck Cancer

NCT03294122 | Unknown

• 1 other identifier: INT 11/17
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The main idea behind MICRO-LEARNER is to provide new insights about the response of healthy tissues to radiation by using information from the micro-environment obtained by biological measurements and imaging. This new knowledge will be included in current available predictive models of radio-induced toxicity, thus allowing to add unique biological characteristics of patients to dosimetry and treatment/clinical related variables. MICRO-LEARNER focuses on prostate cancer (PCa) and head-and-neck cancer (HNCa). For both cancers, radiotherapy is effectively used as curative treatment, in single modality or within a multidisciplinary approach including surgery (PCa) and/or chemotherapy (HNCa). Prediction and reduction of radio-induced side effects are becoming a priority: for PCa, high survival rates should be accompanied by a very low rate of moderate/severe toxicities; for HNCa, there is the need to tailor radiation dose according to disease recurrence risk profile. The shared aim of both cancers is to balance the improvement in outcome with a well-tolerated toxicity profile. Recent research indicates that the intestinal/salivary bacteria are strongly suspected of being very important in mediating the response to inflammation and lesions. Although their balance deeply changes during radiotherapy, studies done so far in the field of the microbiota-host relationship in radiotherapy have not addressed their role in insurgence of radiation toxicity. In this study, the investigators will assess how microbial populations evolve and how this influences the host and radiation induced toxicity in a significant number of patients. Moreover, the individual response at the tissue microstructure level, through analysis of images with advanced bioengineering techniques, will be determined. Results from this research, besides suggesting new ways to predict patients at risk of relevant side-effects, may also suggest possible treatments to change the baseline microbiota of patients at high risk or to modify it during therapy, in order to mitigate toxicity. Understanding the microbiota-radiotherapy interaction may thus lead to novel, effective and inexpensive ways of assessing and managing complications of cancer treatment.

Conditions

Prostate Cancer; Head and Neck Cancer

Keywords

Radiotherapy; Adverse effects; Prostate cancer; Head and neck cancer; Patient risk stratification; Mathematical models; Microbiome; Inflammatory cytokines; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Acute toxicity

  If any, acute (\<within 90 days from radiotherapy completion) Grade 1, Grade 2, Grade 3-4 disorder, according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system, and its association with clinical variables, absorbed dose, microbioma characteristics and radiomic features.

  <90 days after radiotherapy

Secondary Outcomes (1)

• Late toxicity

  3 months - 3 years after radiotherapy

Study Arms (4)

PCa patients - Discovery cohort

External beam radiotherapy for prostate cancer

Radiation: External beam radiotherapy for prostate cancer

HNCa patients - Discovery cohort

External beam radiotherapy for head and neck cancer

Radiation: External beam radiotherapy for head and neck cancer

PCa patients - Validation cohort

External beam radiotherapy for prostate cancer

Radiation: External beam radiotherapy for prostate cancer

HNCa patients - Validation cohort

External beam radiotherapy for head and neck cancer

Radiation: External beam radiotherapy for head and neck cancer

Interventions

External beam radiotherapy for prostate cancer RADIATION

Patients will receive radiotherapy for prostate cancer and possible adjuvant hormone therapies as foreseen by international guidelines. No modification of standard regimens is considered. PCa patients are treated with 78 Gy, 2Gy/fraction, in exclusive setting and with 70 Gy, 2Gr/fraction in the post-prostatectomy setting. Lymph node irradiation is performed (50 Gy, 2Gy/fraction) when indicated by risk class.

PCa patients - Discovery cohort; PCa patients - Validation cohort

External beam radiotherapy for head and neck cancer RADIATION

Patients will receive radiotherapy for head and neck cancer and possible concomitant chemotherapies as foreseen by international guidelines. No modification of standard regimens is considered. In curative setting, HNCa patients are treated at a total dose of 70 Gy, 59.4 Gy and 56.1 Gy in 33 fractions to high risk Planning Target Volume (PTV), intermediate risk and low risk PTV, respectively. In high risk post-operative setting they are treated with 66 Gy (according to histopathological features), 60 Gy and 56.1 Gy to high, intermediate and low risk PTV, respectively; while, in intermediate risk post-operative case, intermediate and low risk PTV are irradiated with 60 Gy and 54 Gy, respectively. Chemotherapy will be platinum based (weekly or 3-weekly cisplatin).

HNCa patients - Discovery cohort; HNCa patients - Validation cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing external beam radiotherapy for prostate or head and neck cancer at the Radiation Oncology 1 and Radiation Oncology 2 units of the Istituto Nazionale dei Tumori.

You may qualify if:

• Patients with histologically confirmed diagnosis of PCa candidate to exclusive or post-surgical radiotherapy, in both case it can be associated to hormone therapy
• Prognostic risk included in the very low, low, intermediate or high risk classes following the NCCN Clinical Practice Guidelines in Oncology and patients with oligometastatic disease treated with curative doses to the prostate (≥70 Gy at 2 Gy per fraction)
• Written informed consent to the study

You may not qualify if:

• Previous pelvic radiotherapy
• Autoimmune disease (scleroderma,Chron's disease and ulcerative colitis), chronic kidney disease requiring dyalis
• Patients with malignant neoplasm in treatment with local or systemic therapies, except for patients with PCa and skin cancers
• Refusal to accept the study participation modalities
• ECOG PS ≤ 3
• Histologically confirmed diagnosis of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx, paranasal sinuses and nasal cavity, salivary glands)
• Non-metastatic stage III-IV cancer of the pharinx, larynx according to AJCC VII edition. Patients with stage III-IV cancer of salivary glands o paranasal sinuses. Patients with stage I-II cancer of pharinx and larynx only if neck lymph nodes or oral mucosa are included in the irradiated volume
• Indication to exclusive or post-surgical radiotherapy (associated or not to systemic therapy according to internal guidelines)
• Written informed consent to the study
• Previous head and neck radiotherapy
• Connective tissue disease (lupus erythematosus or scleroderma) or other concomitant head and neck cancers, except for in situ skin cancers not requiring radiotherapy or systemic therapies.
• Refusal to accept the study participation modalities

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (7)

• Valdagni R, Kattan MW, Rancati T, Yu C, Vavassori V, Fellin G, Cagna E, Gabriele P, Mauro FA, Baccolini M, Bianchi C, Menegotti L, Monti AF, Stasi M, Giganti MO, Fiorino C. Is it time to tailor the prediction of radio-induced toxicity in prostate cancer patients? Building the first set of nomograms for late rectal syndrome. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1957-66. doi: 10.1016/j.ijrobp.2011.03.028. Epub 2011 Jun 2.

  PMID: 21640511 BACKGROUND

• Palorini F, Rancati T, Cozzarini C, Improta I, Carillo V, Avuzzi B, Casanova Borca V, Botti A, Degli Esposti C, Franco P, Garibaldi E, Girelli G, Iotti C, Maggio A, Palombarini M, Pierelli A, Pignoli E, Vavassori V, Valdagni R, Fiorino C. Multi-variable models of large International Prostate Symptom Score worsening at the end of therapy in prostate cancer radiotherapy. Radiother Oncol. 2016 Jan;118(1):92-8. doi: 10.1016/j.radonc.2015.11.036. Epub 2016 Jan 6.

  PMID: 26777123 BACKGROUND

• Bossi P, Bergamini C, Miceli R, Cova A, Orlandi E, Resteghini C, Locati L, Alfieri S, Imbimbo M, Granata R, Mariani L, Iacovelli NA, Huber V, Cavallo A, Licitra L, Rivoltini L. Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016 Dec 1;96(5):959-966. doi: 10.1016/j.ijrobp.2016.08.047. Epub 2016 Sep 6.

  PMID: 27745982 BACKGROUND

• Orlandi E, Giandini T, Iannacone E, De Ponti E, Carrara M, Mongioj V, Stucchi C, Tana S, Bossi P, Licitra L, Fallai C, Pignoli E. Radiotherapy for unresectable sinonasal cancers: dosimetric comparison of intensity modulated radiation therapy with coplanar and non-coplanar volumetric modulated arc therapy. Radiother Oncol. 2014 Nov;113(2):260-6. doi: 10.1016/j.radonc.2014.11.024. Epub 2014 Nov 29.

  PMID: 25467003 BACKGROUND

• De Cecco L, Nicolau M, Giannoccaro M, Daidone MG, Bossi P, Locati L, Licitra L, Canevari S. Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data. Oncotarget. 2015 Apr 20;6(11):9627-42. doi: 10.18632/oncotarget.3301.

  PMID: 25821127 BACKGROUND

• Doldi V, Callari M, Giannoni E, D'Aiuto F, Maffezzini M, Valdagni R, Chiarugi P, Gandellini P, Zaffaroni N. Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation. Oncotarget. 2015 Oct 13;6(31):31441-60. doi: 10.18632/oncotarget.5056.

  PMID: 26375444 BACKGROUND

• Ferreira MR, Muls A, Dearnaley DP, Andreyev HJ. Microbiota and radiation-induced bowel toxicity: lessons from inflammatory bowel disease for the radiation oncologist. Lancet Oncol. 2014 Mar;15(3):e139-47. doi: 10.1016/S1470-2045(13)70504-7.

  PMID: 24599929 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples of all patients, stool samples of prostate cancer patients, salivary samples of head and neck cancer patients

MeSH Terms

Conditions

Prostatic Neoplasms; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Riccardo Valdagni, MD, PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

• Ester Orlandi, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

• Nice Bedini, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

• Loris De Cecco, PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

• Nadia Zaffaroni, PhD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

• Tiziana Rancati, MS

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

Central Study Contacts

Riccardo Valdagni, MD, PhD

CONTACT

+0039 02-23903034; riccardo.valdagni@istitutotumori.mi.it

Tiziana Rancati, MS

CONTACT

+0039 02-23903786; tiziana.rancati@istitutotumori.mi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: September 26, 2017
• Study Start: February 2, 2017
• Primary Completion: July 31, 2019
• Study Completion: December 31, 2019
• Last Updated: October 3, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)