RTOG 0933 A Phase II Trial of Hippocampal

RTOG 0933 A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases

The Purpose � To determine any good or bad effects that avoiding the hippocampus has on memory

RTOG 0933 � Radiation Therapy Oncology Group (RTOG) ◦ NCI-funded clinical trial organization � Protocol Finalized December 5, 2011 � Accrued 113 patients � CLOSED November 7, 2012

The Hope � The hippocampus is important for memory � The hope is that avoiding it will decrease memory loss and reduce deterioration of thinking ability after whole brain therapy � Currently no proof that this will happen

Background

Why Whole Brain RT? � Rapid � Can palliation of symptoms delay NCF decline � Might also cause NCF decline ◦ 1 -4 months memory effects � Unclear: � Still confounding effects of mets standard technique for brain mets

The Hippocampus 2. 1. 3. 1. Hippocampus. Neurology Channel Website. http: //thebrainlabs. com/Images/hippocampus. gif. Accessed June 30, 2015. 2. Mayer KC. Hippocampus. Neuro 24 Website. http: //www. neuro 24. de/hip 0006. jpg. Accessed June 30, 2015 3. Hippocampus. Wikipedia Website. https: //upload. wikimedia. org/wikipedia/commons/5/5 b/Hippocampus_and_seahorse_cropped. JPG. Updated June 21, 2015. Accessed June 30, 2015.

Hippocampus Sensitivity � Neuronal progenitor cells could be damaged ◦ Radiation may cause apoptosis � Inflammation interferes with stem cell differentiation � Still not 100% clear in human model

Credentialing http: //winnipeghonda. ca/wp-content/uploads/2015/01/check. png

Facility Credentialing � General IMRT planning � Hippocampus contouring � Protocol-specific � Neurocognitive HA whole brain planning test administration

Trust But Verify � Plans will be sent to central review board � Plans returned with feedback in <3 days ◦ Check of hippocampus contours ◦ Check of plan parameters � Treatment may commence once satisfied

Patient Selection

Patient Selection � General characteristics � Histology � Brain condition � General health � Concurrent treatments � Tumor location

General Patient Characteristics � Age > 18 � Can tolerate MRI � Not pregnant ◦ No magnetic metal ◦ No claustrophobia ◦ Will not become pregnant � Speaks English ◦ Has signed a consent form

Histology � Brain lesion must be metastasis ◦ Must have proof of other malignancy within 5 years � Can not be: ◦ Hematopoietic malignancy ◦ Germ cell malignancy ◦ Small cell lung cancer

Brain Condition � No leptomeningeal mets � No hydrocephalus D E prior brain surgery � No biopsy within 1 week T C E � No prior brain radiation � No history of SRS R J E Schizencephaly. Image of the Week Website. http: //www. bimjonline. com/Imageoftheweek/Imagewk 29(19 -11 -2012). htm. Published 2012. Accessed June 30, 2015.

Patient Health � H&P performed within 30 days � Karnofsky � No Performance Score >= 70 heart issues within 6 months � No severe liver issues � No severe respiratory issues � No major bacterial infections

Concurrent Treatments � Disqualifiers: ◦ Concurrent chemo (or within 1 week after) ◦ Treatment involves surgery ◦ Treatment involves SRS

Tumor Location � Can not be within 5 mm of either hippocampus � (that’s about it)

Getting started

Patient Workup � Imaging: ◦ Recent MRI ◦ CT Simulation � Neurocognitive � Quality Function Test of Life Assessment

MRI Requirements � MRI within 30 days prior to registration � Sequences ◦ T 1 with gadolinium ◦ T 2 � 1. 5 ◦ ◦ SPGR MP-RAGE TFE FLAIR mm maximum slice thickness

CT Requirements � Non-contrast � Entire � 2. 5 head region mm maximum slice thickness

Neurocognitive Test � Immediate recall � Immediate recognition ◦ Repeat a list of words ◦ Identify words that were in the list � Delayed recall (after 20 mins) ◦ Recall prior words

Quality of Life Survey � Examines feelings of well-being ◦ Physical ◦ Social ◦ Emotional ◦ Functional

Making a Plan

Contouring � Standard optics ◦ Lenses, eyes, optic nerves, chiasm � Hippocampus � HA: Hippocampal Avoidance ◦ 5 mm expansion of Hippocampus � CTV: Brain to C 1 or C 2 � PTV: CTV minus HA

Fusion � MR(s) should be fused to planning CT ◦ Should use semi-automatic technique � Ideally MR was acquired in nearly same plane angle as CT

Dose & Fractionation � 30 Gy in 10 fx � Daily, � PTV 5 x per week D 90% > Rx (30 Gy) D 2% < 37. 5 Gy � PTV D 98% > 25 Gy

Planning: Tomotherapy � Specific machine parameters ◦ Field width, pitch, modulation factor � Selected ◦ PTV plan constraints: �Max < 30 Gy �V 30 Gy > 96% ◦ Hippocampus �Max < 6 gy �V 3 Gy < 20%

Planning: Linac � 2 Choices of 9 -Beam Arrangement ◦ Specific couch and gantry positions ◦ Non-coplanar � Selected ◦ PTV plan constraints: �Max < 34 Gy �Min > 32 Gy ◦ Hippocampus �Max < 11 Gy �V 9 Gy < 40%

Followup Telephone. DCHoos Website. http: //dchoos. org/wp-content/resources/telephone. jpg Uploaded December 12, 2011. Accessed June 30, 2015.

Followup After Treatment � Every 2 months for 6 months ◦ (every 3 months after that) ◦ Physical exam ◦ MRI of the brain ◦ 20 minute Cognitive Test �(Extra tests at 2, 4, and 12 months)

Benefits to Patients � If hypothesis is true, fewer memory and cognitive problems after whole brain RT ◦ Better quality of life ◦ Less dependence on caretakers � Who benefits? ◦ Brain is a common site of metastasis ◦ Whole brain RT is sometimes prophylactic

Benefits to Organizations � Better outcomes for patients ◦ Less follow-up care � Competitive advantage?

Thank you