Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation

Wang, Kyle; Tobillo, Rachel; Mavroidis, Panayiotis; Pappafotis, Ryan; Pearlstein, Kevin A.; Moon, Dominic H.; Mahbooba, Zahra; Deal, Allison M.; Holmes, Jordan A.; Sheets, Nathan; Kasibhatla, Mohit S.; Pacholke, Heather D.; Royce, Trevor J.; Weiner, Ashley A.; Shen, Colette J.; Zagar, Timothy M.; Marks, Lawrence B.; Chera, Bhishamjit S.

doi:10.1016/j.ijrobp.2019.07.015

Cited by 15 publications

(18 citation statements)

References 31 publications

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“…In the recent prospective study, 46% of patients experienced dry eye symptoms one month after radiotherapy. These symptoms can begin immediately after therapy and be sustained for up to six months [3]. Dry eye syndrome after radiotherapy results not only in acute discomfort, but also in chronic disease during the patient’s remaining years.…”

Section: Discussionmentioning

confidence: 99%

“…Ionizing radiation causes damage in normal tissues located in the field of radiation and induces both functional and morphological changes in glandular tissues, including the salivary gland, thryroid gland, and lacrimal gland (LG) [1,2,3]. Dry eye syndrome is relatively common as a symptom of dose-/volume-dependent acute and late toxicity after radiotherapy [3,4,5,6], the significance of which has been overlooked due to its apparent harmlessness. However, the patients experience complications in daily tasks, such as constant irritation and blurred vision [7], which may in turn lead to psychotic complications [8].…”

Section: Introductionmentioning

confidence: 99%

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Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Kim

Yoo

Jung

et al. 2019

IJMS

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Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation–induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Kim

Yoo

Jung

et al. 2019

IJMS

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“…The proportion of patients with an increase in dry eye symptoms was significantly higher at 1 month (≥1 point Subjective Evaluation of Symptom of Dryness increase) for lacrimal V20Gy at least 79% was 46% while less than 79% associated with 15% ( P = .02). 66 Importantly, this appears to be a previously over-looked toxicity to WBRT. However, care should be taken in attempting to spare the lacrimal glands as this toxicity measure is not validated and modifications in the field to spare lacrimal glands may compromise dose to the cribriform plate although this may be possible with HA-WBRT.…”

Section: Radiotherapymentioning

confidence: 99%

Multidisciplinary patient-centered management of brain metastases and future directions

Palmer

Trifiletti

Gondi

et al. 2020

Neuro-Oncology Advances

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The incidence of brain metastasis is increasing as improvements in systemic therapy lead to increased survival. This provides new and challenging clinical decisions for patients who are trying to balance the risk of recurrence or progression with treatment-related side effects, and it requires appropriate management strategies from multidisciplinary teams. Improvements in prognostic assessment and systemic therapy with increasing activity in the brain allow for individualized care to better guide the use of local therapies and/or systemic therapy. Here, we review the current landscape of brain-directed therapy for the treatment of brain metastasis in the context of recent improved systemic treatment options. We also discuss emerging treatment strategies including targeted therapies for patients with actionable mutations, immunotherapy, modern whole-brain radiation therapy, radiosurgery, surgery, and clinical trials.

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“…Whole brain radiation (WBRT) is a common treatment for patients with brain metastases [ 1 – 6 ]. Many patients who receive WBRT have a poor prognosis, and it is important to minimize both acute and late toxicities.…”

Section: Introductionmentioning

confidence: 99%

“…More-recently, in a prospective study, we reported that patients receiving standard WBRT (without prospective delineation of the parotid or lacrimal glands) resulted in clinically-significant acute xerostomia and dry eye in roughly 35% and 25% of cases, respectively with toxicity rates associated with glandular doses [ 1 , 10 ]. In those reports, a summary of the reported toxicities was provided together with a statistical analysis of their correlation against given dose volume metrics.…”

Section: Introductionmentioning

confidence: 99%

NTCP modeling and dose–volume correlations for acute xerostomia and dry eye after whole brain radiation

et al. 2021

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Background Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. Methods Patients received WBRT to 25–40 Gy in 10–20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0–100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman–Kutcher–Burman (LKB) and Relative Seriality (RS) NTCP models. Results Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy–V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69–0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy–V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. Conclusions Xerostomia was most associated with parotid V10Gy–V20Gy, and dry eye with lacrimal V10Gy–V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.

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Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation

Cited by 15 publications

References 31 publications

Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Multidisciplinary patient-centered management of brain metastases and future directions

NTCP modeling and dose–volume correlations for acute xerostomia and dry eye after whole brain radiation

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