Radiation- Induced Alopecia in Patients Undergoing Radiation Therapy to the Brain

Patients with primary or metastatic cancers to the brain need to undergo partial or whole brain radiotherapy. Alopecia is an inadvertent side effect of Radiation therapy to the brain. Much of this alopecia occurs in patches and is often associated with permanent loss of hair. Irradiation-induced epilation is due to high susceptibility of anagen follicles to radiation. Loss of hair can be stressful and distressing for cancer patients.

Various studies have tried to address the issue of threshold dose for radiotherapy induced alopecia. The severity and type of skin response and consequent alopecia to radiation is decided by multitude of factors - total dose and dose fractionation, quality of radiation, area or volume of tissue irradiated, anatomic site and vascular response. Studies have shown that 3Gy produces complete, reversible anagen alopecia and permanent alopecia begins to occur at 5Gy.

At higher dose rates the susceptibility of hair melanocytes is much more than epidermal melanocytes. Freysz et al in a retrospective analysis of 18 patients deduced that a cumulative dose as high as 12Gy results in alopecia that is reversible.Temporary alopecia is seen in most patients receiving WBRT with conventional fractionation. Most of these studies are either small reports or were done before the advent of modern technology. The advent of precision radiotherapy techniques has made it possible to utilize techniques that reduce the dose to the scalp in an attempt to minimize the chances of radiation- induced alopecia.

In a first, a phase II dosimetric and clinical study by De Puysseleyr et al concluded that Volumetric Modulated Arc Therapy (VMAT)- WBRT delivers lower scalp doses as compared to conventional parallel opposed fields but the study was closed prematurely as it failed to show any clinical benefit in terms of preventing alopecia. They however, concluded that the threshold Treatment Planning System (TPS) dose for temporary alopecia is around 10Gy in 5 fractions.

In a study by Ting et al alopecia was observed in half of the patients undergoing Whole Brain Radiotherapy (WBRT) to a dose of 30Gy/10 fractions did not have significant alopecia. The remaining half had mild alopecia. In the study by Mahadevan A et al, hippocampus sparing WBRT also spares hair follicle bearing regions of the scalp while maintaining strict compliance to hippocampus avoidance zone. There is no consensus regarding the threshold TPS dose for alopecia as the study of dose received by hair follicles during intensity modulated radiotherapy for whole brain is limited by lack of knowledge of dose-effect relation of temporary alopecia.

Rivero M et al have reported zero incidence of alopecia in the departmental protocol that they have developed for patients undergoing WBRT using 20Gy/5#s using SIB (40Gy/5#s) by VMAT. The different dose weightage and dose volumes practiced in their department have yielded excellent cosmetic outcomes.

The objective alopecia scoring scales have their own issues of inter-observer variability. EORTC BN20 questionnaire though a validated tool, is largely subjective. Since the expectation of a patient being treated by VMAT despite adequate counseling may be disproportionate to the reality of treatment outcomes, there may be marked deviation of scores to extremes. Severity of Alopecia Tool (SALT Score) is more objective with again the limitation of inter-observer variability. In order to minimize subjectivity, we will use SALT scoring system to analyze the degree of alopecia. SALT Score of 0 indicates no alopecia whereas score of 100 indicates complete baldness.

The investigators have been been using scalp contouring and scalp sparing radiotherapy technique to decrease the dose to the scalp with the aim to reduce alopecia.

This study aims to prospectively study the extent of alopecia by modern treatment techniques and assess the factors affecting the same.

Aims and Objectives:

This study will be conducted on patients receiving Whole brain radiotherapy (WBRT)/ Partial Brain RT using volumetric modulated arc therapy (VMAT) or intensity modulated radiotherapy (IMRT) at Radiation Oncology Department of FMRI, Gurgaon, Haryana with the following end points

Materials and Methods The study will include 50 patients undergoing partial / whole brain radiation therapy who will be assessed prospectively for radiation- induced alopecia.

Contouring: For whole brain radiation only, the whole scalp will be contoured. For partial brain irradiation contouring of lateral lesions partial scalp will be done. Partial scalp contouring shall be done by drawing 2-3 cm beyond the PTV edge in all directions. Partial scalp shall be considered as an organ at risk (OAR).

Planning: The treatment planning and treatment delivery of patients shall be done as per existing routine in the department. All contouring will be done at Monaco / BrainLab Contouring stations and planning will be done on Monaco Treatment planning system Version 5.11.01 using full or partial arc Volumetric modulated arc therapy (VMAT) technique. Patients treated by other techniques such as IMRT and 3-D CRT will also be included in this study and analysed. During radiotherapy planning dose constraints will be given without affecting the PTV coverage.

Following measurements shall be done -

1. Objective, Clinical and photographic analysis- Photographic and Clinical review record of the scalp(excluding the face of the patient) will include four views- Right lateral, Left lateral, top view and rear view of the scalp. These shall be done at following intervals- a) Before starting RT b) RT Conclusion c) First follow-up at 1 month. Hair loss will be quantified using the SALT Score. (14)
2. Dosimetric measurements: This shall have two subcomponents
3. A measurement of surface dose uses optically stimulated luminescence (OSL) dosimeters that shall be placed over the scalp for first 5 fractions in case of conventional or fractionated Stereotactic Radiotherapy (SRT), for the entire duration of short course treatments and for first 5 fractions in case of palliative whole brain radiation given over 10 fractions. OSL will be placed on the scalp at the centre of arc span of the beams lateral and AP-PA views at the beam entry points. For reproducibility, OSL position will be marked on the Thermoplastic mask. Dose to OSL will be calculated after taking measurements during delivery of therapeutic dose.
4. Treatment Planning system (TPS) measurements: In the TPS, the average, maximum dose and dose per unit volume will be reported for the whole scalp and partial scalp. In addition the routing measurements of dosimetry related to planning target volume(PTV) and organs at risk (OAR) shall be done as per existing norms

Statistical Methods Mean dose to the point of the OSL will be calculated from the Treatment planning system (TPS), and further the statistical co-relation between the measured and calculated dose will be evaluated by student t test using a 95% confidence interval. Mean scalp dose will be evaluated from the TPS. Further mean TPS calculated dose, measured dose and clinical outcome (degree of alopecia using SALT score) will be co-related using paired sample t test.