HS-PCI in Locally Advanced Adenocarcinoma of the Lung

The primary aim of this study is evaluate the impact of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) on survival status in patients with nodal-positive (locally advanced) adenocarcinoma by comparing overall survival rates of patients undergoing HS-PCI to that of patients without this intervention. In addition, this study aims to investigate whether HS-PCI is detrimental on neurocognitive function and to evaluate its impact on the patient's quality of life.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

1. Cytologically or histologically confirmed adenocarcinoma of the lung
2. Clinical Stage III with lymph node stage N1-N3
3. Stable disease or any response after definitive or adjuvant radio(chemo)therapy (defined by local standards)
4. No more than 8 weeks after completion of prior radio(chemo)therapy
5. Any acute/subacute ≥ grade 3 toxicities from previous therapy must have resolved to ≤ grade 2 at the time of study entry
6. Age ≥ 18 years and \< 75 years
7. ECOG Performance Status ≤ 1
8. Signed study-specific informed consent prior to study entry.

Exclusion Criteria:

1. Stage III with T4 N0
2. Evidence of progressive disease at the time of study entry
3. Brain or leptomeningeal metastases (cMRI not older than 2 weeks)
4. Evidence of extracranial distant metastatic disease
5. Prior cranial irradiation
6. Patients enrolled in other clinical studies that apply or test lung cancer-directed investigational agents/procedures
7. Patients with synchronous or prior malignancy, other than non-melanomatous skin cancer unless disease free greater than 3 years
8. Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus; patients with childbearing potential must practice appropriate contraception.
9. Patients that are unable to undergo repetitive MRI scans
10. Medical conditions that contra-indicate intensive neurocognitive testing (e.g., history of mental retardation, aphasia of any kind, hearing impairment)

• BACKGROUNDGondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27. PMID 25349290
• BACKGROUNDGhia A, Tome WA, Thomas S, Cannon G, Khuntia D, Kuo JS, Mehta MP. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):971-7. doi: 10.1016/j.ijrobp.2007.02.016. Epub 2007 Apr 18. PMID 17446005
• BACKGROUNDHarth S, Abo-Madyan Y, Zheng L, Siebenlist K, Herskind C, Wenz F, Giordano FA. Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy. Radiother Oncol. 2013 Oct;109(1):152-8. doi: 10.1016/j.radonc.2013.09.009. Epub 2013 Oct 4. PMID 24100152
• BACKGROUNDGore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol. 2011 Jan 20;29(3):272-8. doi: 10.1200/JCO.2010.29.1609. Epub 2010 Dec 6. PMID 21135270
• BACKGROUNDGiordano FA, Welzel G, Abo-Madyan Y, Wenz F. Potential toxicities of prophylactic cranial irradiation. Transl Lung Cancer Res. 2012 Dec;1(4):254-62. doi: 10.3978/j.issn.2218-6751.2012.10.03. PMID 25806190