Hypofractionated Radiosurgery to Treat Residual/Recurrent Non Secreting Pituitary Adenoma (HYPOADENO) (HYPOADENO)

HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY/MULTISESSION RADIOSURGERY (HSFRT/MSRS) IN RESIDUAL/ RECURRENT NON SECRETING PITUITARY ADENOMAS AN EXPLORATORY STUDY

Single session stereotactic radiosurgery (SRS) is commonly used for patients with non-functioning adenomas. However the SRS can be limited by the proximity of the tumor with the surrounding critical structures (i.e., the optic chiasm).

The goal of the present prospective phase II trial is to investigate early and early delayed toxicity for cranial nerves and pituitary function after hypofractionated stereotactic radiotherapy/multisession radiosurgery (hSFRT/mSRS) in residual/ recurrent non secreting pituitary adenomas. Secondary end points are late toxicity and tumour growth local control.

All the enrolled patients will undergo radiosurgical treatment with a hypofractionation schedule Following radiotherapy, follow-up will be scheduled every 6 months during the first year post-radiosurgery and then annually, with the same tests.

The baseline examination and the follow-up assessment will include magnetic resonance imaging (MRI), full blood counts and blood chemistry tests, neuro-ophtalmology evaluation, physical and psychological examination that included a quality-of-life (EORTC Quol 30; BN 20) and a Hospital Anxiety and Depression Scale (HADS).

Study Overview

• Status: Completed
• Conditions: Pituitary Adenoma; Pituitary Neoplasms
• Intervention / Treatment: Radiation: hypofractionated radiosurgery

Detailed Description

Aims The main aim of our study is to analyze the effect of 5-session hypofractionated radiotherapy/multisession radiosurgery in treating NFAs in terms of toxicity and local control.

Study design This study is an exploratory study: patient's and treatment's data will be prospectively collected in a database and they will then be described and analyzed.

Criteria of analysis

All these points will be recorded and analyzed:

• Local control measured from the date of mSRS until progression or death, censored at the time of last clinical follow-up or imaging.
• Overall survival measured from the date of diagnosis until death, censored at the time of last clinical follow-up or imaging.
• Visual acuity improvement/worsening will be defined by reading increases/decreases equal of 1 or more lines; visual field will be considered improved or worsened for decreases or increase in the extension of the defect area. In order to compare pre- and post-treatment data, the results will be registered.
• Pituitary toxicity will be defined as a clinically relevant reduction compared to the baseline of ACTH, GH, TSH, testosterone in men, period disturbances in women, new onset of diabetes insipidus due to ADH deficiency. Hormonal changes will be defined relevant if a medical therapy change\introduction become mandatory.
• Other treatment-related toxicity based on CTCAE v4.0.
• Presence of adverse events based on CTCAE v4.0.
• Quality of life evaluated by "Quality of life EORTC - QLQ C30 and BN20" and "Hospital Anxiety and Depression Scale (HADS)". (25-28) (Appendix 1 and 2)

Study population Patients suffering from recurrent/residual non secreting pituitary adenoma. Twenty-five patients will be enrolled.

Study treatment Patients will receive hSFRT/mSRS in 5 consecutive days over 7 elapsed days, with extension over a weekend allowed.

Radiation treatment features Following sub-total surgery or in case of progressive disease patients will be enrolled and a CT and MRI simulation will be performed. A treatment for hypofractionated stereotactic radiotherapy/multifraction radiosurgery (hSHRT/mSRS) will be planned. The planning tumor volume (PTV) will be the residual/recurrent tumor + 0-2 mm as defined on the MRI images. To better define the tumor volume T1 with and without contrast enhancement, with and without fat saturation and T2 axial voloumetric sequences will be acquired and then fused. The prescription isodose line will cover at least 95% of the PTV; undercoverage to 90% will be allowed near organs at risk. Normal organ dose constraints will be 98% of the optic pathways receiving less than 27.5 Gy and brainstem maximum point dose of 30 Gy in 5 fractions, undercovering the PTV to meet these limits.

Patient Assessment and Outcome Reporting The baseline examination will include simulation CT and magnetic resonance imaging (MRI), thereafter full blood counts and blood chemistry tests, neuro-ophtalmology evaluation, physical and psychological examination that included a quality-of-life (EORTC Quol 30; BN 20) and a Hospital Anxiety and Depression Scale (HADS).

Following radiotherapy, follow-up will be scheduled every 6 months during the first year post-radiosurgery and then annually, with the same tests.

Tumor progression will be defined according to the modified WHO criteria as an increase in tumor size by 25 percent. Consensus between the two examining radiologists will be achieved if the target lesions selected differed between the two radiologists. In case of tumor progression, patients will be treated at the investigators' discretion.

Toxicity and adverse events will be graded according to the National Cancer Institute Common Toxicity Criteria, version 4.0, with a score of 1 indicating mild adverse effects, a score of 2 moderate adverse effects, a score of 3 severe adverse effects, and a score of 4 life-threatening adverse effects.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan
    • Milan, Milan, Italy, 20133
      • Fondazione IRCCS Istituto Neurologico C Besta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Residual or progressive non secreting pituitary adenoma;
• Exclusion of other treatment approach (second surgery, wait and scan; suppressive therapy) by a multidisciplinary team
• Age ≥ 18 years; KPS ≥ 70
• Written privacy consent;
• Ability to give informed consent;

Exclusion Criteria:

• Previous cranial irradiation;
• Diagnosis of secreting adenoma;
• pregnancy status;
• unable to undergo MRI or CT scans;
• unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiosurgery; Patients suffering from residual/recurrent non functioning pituitary adenoma wil undergo to hypofractionated radiosurgery	Radiation: hypofractionated radiosurgery; The total dose will be 25 Gy, delivered in 5 fractions, in 5 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early and late treatment related toxicity	- Treatment-related toxicity based on CTCAE v4.0.	From the treatment to 36th month post-treatment
Impact of the treatment on visual acuity	- Visual acuity (VA) improvement/worsening will be defined by reading increases/decreases equal of 1 or more lines (Vdetermined by the best performance on the Snellen Chart).	From the treatment time to the 36th month post-treatment
Impact of the treatment on the visual field	The visual field (VF) is a continuous quantitative variable described by the mean deviation (VFMD) value, which is a summary measure of vision average loss across the visual field. VFMD values at follow-up visits that are less negative than the baseline are considered an improvement, while more negative values are considered a worsening.	From the treatment time to the 36th month post-treatment
Impact of the treatment on the pituitary function	Pituitary toxicity will be defined as a clinically relevant reduction compared to the baseline of ACTH, GH, TSH, testosterone in men, period disturbances in women, new onset of diabetes insipidus due to ADH deficiency. Hormonal changes will be defined relevant if a medical therapy change\introduction become mandatory.	From the treatment time to the 36th month post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor control	Tumor progression will be defined according to the modified WHO criteria as an increase in tumor size by 25 percent	From the treatment time to the 36th month post-treatment
Impact of the treatment on the quality of life	Quality of life will be evaluated acoording to Quality of life (EORTC QLQ C30 - QLQ BN 20) variations	From the treatment time to the 36th month post-treatment.
Impact of the treatment on anxiety and depression	Anxiety and Depression experienced by the patients will be evaluated according to "Hospital Anxiety and Depression Scale (HADS)" variations.	From the treatment time to the 36th month post-treatment

Collaborators and Investigators

• Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): May 20, 2025
• Study Completion (Actual): May 20, 2025

Study Registration Dates

• First Submitted: January 31, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: radiosurgery; multisession radiosurgery; non functioning pitutary adenoma; hypofractionated radiosurgery
• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Pituitary Diseases; Pituitary Neoplasms
• Other Study ID Numbers: HYPO_ADENO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No