Hippocampal Sparing Research Articles

179. Whole brain radiotherapy with hippocampal sparing and Simultaneous Integrated Boost for patients with one to four metastases with Helical Tomotherapy

PurposeHippocampal avoidance during irradiation is hypothesized to reduce the risk of memory function decline. This study is designed to evaluate the dosimetric and clinical results of Helical Tomotherapy (HT) whole brain radiotherapy with hippocampal avoidance (WBHA) and Simultaneous Integrated Boost (SIB). MethodsA total of 19 patients with 1 to 4 brain metastases (BM), diameter ⩽3 cm, absent or controlled extracranial disease were planned for WBHA with SIB using HT, from September 2014 to November 2017. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been registered with the planning CT image set. The hippocampal Planning Risk Volume was generated using a 5 mm uniform margin around the hippocampi. The BM were contoured on T1-weighted MRI registered with the planning computed tomography (CT), and the BM-PTV was the BM expanded 3 mm in all directions. The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume, expanded 3 mm in all directions, minus hippocampal PRV and BM-PTVs. HT plans were generated with the following parameters: field width set at 1.05 cm, pitch 0.287, modulation factor (MF) set in the range 2–3 leading to a final value of 2 on average (range 1.3–2.8). Prescription dose was 30 Gy for WB-PTV and 40 Gy for each BM-PTVs in 10 fractions. ResultsDosimetric result were reported in Table 1: all the parameter analysed were very promising and in accord to the RTOG 0933 trial [1]. The mean treatment time was 8.7 min (range 6.5–12.6 min). ConclusionsHT plans achieved three objectives: quite homogeneous whole brain dose distribution; conformal hippocampal avoidance; and high coverage to the BM. [Display omitted]

Influence of volumetric modulated arc therapy and FET-PET scanning on treatment outcomes for glioblastoma patients

BackgroundWe sought to assess the influence of the clinical introduction of new radiotherapy technologies on glioblastoma patients’ outcomes. MethodsNewly diagnosed glioblastoma patients treated with 60 Gy and temozolomide (2005–2014) were analyzed. The patients’ GTV and CTV were defined based on MR (n = 521) or FET-PET/MR (n = 190), and were treated using conformal radiotherapy (CRT, n = 159) or image-guided volumetric modulated arc therapy with hippocampal sparing (IG-VMAT, n = 362). Progression-free survival (PFS) was assessed using the McDonald criteria. Associations between clinical data, dosimetry data, treatment technology, for PFS and overall survival (OS) were explored. ResultsThe PFS (7 months) and OS (15 months) were unaffected by CRT, IG-VMAT and FET-PET technology. Mean brain dose was correlated with tumor volume, and was lower for IG-VMAT vs. CRT (p < 0.001). Larger mean brain dose was associated with inferior PFS (univariate/multivariate Cox models, p < 0.001) and OS (univariate, p < 0.001). Multivariate Cox models revealed association of larger mean brainstem dose (p < 0.001), BTV (p = 0.045), steroid use at baseline (p = 0.003), age (p = 0.019) and MGMT status (p = 0.022) with lower OS. ConclusionsIntroduction of hippocampal-sparing IG-VMAT technology appeared to be safe, and may have reduced toxicity and cognitive impairment. Larger mean brain dose was strongly associated with inferior PFS and OS.

Hippocampal Sparing Preserves Neurocognitive Functions in Patients of Pituitary Adenoma Treated with IG-IMRT Technique

Hippocampal Sparing Preserves Neurocognitive Functions in Patients of Pituitary Adenoma Treated with IG-IMRT Technique

A Need for Contouring Education in Latin America: Evaluating an E-contouring Experience with Novel Reporting of DICE Metrics

As the technology for radiation oncology advances, therapy is able to be delivered in a more conformal fashion with a goal of both greater targeting of the tumor as well as avoidance of healthy structures. However, greater conformality requires the ability to correctly identify and contour both tumor volumes and organs at risk. One method of delivering content, particularly for practitioners abroad, is through e-contouring sessions. E-contouring allows for interactive didactic sessions allowing participants to see contouring of structures in real time. This represents the first international education intervention in Latin America utilizing e-contouring reporting DICE coefficients. An e-contouring workshop was undertaken in Lima, Peru at the 2018 eCancer conference. Registered students had access to an online platform beginning two weeks before the workshop along with case vignettes. Seven cases were presented with indications for radiation: locally advanced lung, lung SBRT, post-operative cervix, anaplastic astrocytoma, hippocampal sparing whole-brain, and two cases of linear accelerator based stereotactic radiosurgery for brain metastases. Each case listed various structures to contour for designated slices. Concordance of student responses with educator contours was measured using DICE coefficients. Post-educational intervention, students were given two weeks to redo homework assignments with intent to compare DICE coefficients with paired t-test. Fifty-five people registered for the contouring workshop and 13 (24%) completed homework pre-workshop. For the four non-palliative cases, the total mean DICE coefficient was 0.58. Average DICE scores pre-workshop for the entire case, which included organs at risk, and tumor volumes, are shown in the table. Of the 13 students who completed homework pre-workshop, only one student attempted the post-intervention homework with no significant change in DICE score. We present the first e-contouring experience with DICE coefficients in Latin America. Approximately a quarter of the registered students completed homework. The remaining pre-intervention scores serve as a diagnostic and highlight the importance of a need for contouring education with a majority of scores below 0.70. Unfortunately, participation in pre-assessment homework was low and post-assessment homework was minimal which does not allow for meaningful assessment of retained knowledge. Future e-contouring courses in Latin America would benefit by completing post-assessments at the time of workshop.Abstract TU_3_2919; Table 1CaseDICE scoreLocally Advanced Lung Cancer0.52GTVp0.85GTVn0.48SBRT Lung0.63ITV0.49Post-op Cervix0.52CTV0.45Anaplastic Astrocytoma0.66CTV0.74 Open table in a new tab

Hippocampal Sparing Fractionated Whole Brain Irradiation Attenuates Microglia Activation and Preserves Immature Neurons Two Months after Treatment

Hippocampal Sparing Fractionated Whole Brain Irradiation Attenuates Microglia Activation and Preserves Immature Neurons Two Months after Treatment

MS18.02 Treatment of Elderly Patients with SCLC

MS18.02 Treatment of Elderly Patients with SCLC

MA22.11 Risk of Hippocampal Metastases in Small Cell Lung Cancer: Implications for Hippocampal Sparing Cranial Irradiation

MA22.11 Risk of Hippocampal Metastases in Small Cell Lung Cancer: Implications for Hippocampal Sparing Cranial Irradiation

Advantages of intensity modulated proton therapy during hippocampal avoidance whole brain radiation therapy.

Intensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT). Ten adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = [D5% - D95%]/[Dmean] × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing. IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half. This manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted.

P05.86 Hippocampal sparing in primary central nervous system lymphoma. Is it routinely possible?

P05.86 Hippocampal sparing in primary central nervous system lymphoma. Is it routinely possible?

Sex and age interact to determine clinicopathologic differences in Alzheimer\u2019s disease

Women reportedly make up two-thirds of Alzheimer’s disease (AD) dementia sufferers. Many estimates regarding AD, however, are based on clinical series lacking autopsy confirmation. The Florida Autopsied Multi-Ethnic (FLAME) cohort was queried for AD cases with a total of 1625 identified ranging in age from 53 to 102 years at death. Standard neuropathologic procedures were employed and clinical information was retrospectively collected. Clinicopathologic and genetic data (MAPT and APOE) were stratified by sex. Within the neuropathologically diagnosed AD cohort, the overall number of women and men did not differ. Men were younger at onset of cognitive symptoms, had a shorter disease duration, and more often had atypical (non-amnestic) clinical presentations. The frequency of autopsy-confirmed AD among women and men stratified by age at death revealed an inverse U-shaped curve in men and a U-shaped curve in women, with both curves having inflections at approximately 70 years of age. Regional counts of neurofibrillary tangles differed in women and men, especially when examined by age intervals. Women had overall greater severity of neurofibrillary tangle counts compared to men, especially in the hippocampus. Men were more often classified as hippocampal sparing AD, whereas limbic predominant AD was more common in women. Men and women did not differ in frequency of MAPT haplotype or APOE genotype. Atypical clinical presentations, younger age at onset and shorter disease duration were more frequent in men, suggesting that the lower reported frequency of AD in men may be due to more frequent atypical clinical presentations not recognized as AD. Our data suggest that neuropathologically diagnosed AD cases have the same frequency of women and men, but their clinical presentations and ages at onset tend to differ.

Mechanisms and Therapy for Cancer Metastasis to the Brain.

Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60–70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry. Molecular alterations not always reflect those of the primary tumor. More sophisticated methods of tumor analysis detecting circulating biomarkers in fluids (liquid biopsy), including circulating DNA, circulating tumor cells, and extracellular vesicles, containing tumor DNA and macromolecules (microRNA), have shown promise regarding tumor treatment response and progression. The choice of therapeutic approaches is guided by prognostic scores (Recursive Partitioning Analysis and diagnostic-specific Graded Prognostic Assessment-DS-GPA). The survival benefit of surgical resection seems limited to the subgroup of patients with controlled systemic disease and good performance status. Leptomeningeal disease (LMD) can be a complication, especially in posterior fossa metastases undergoing a “piecemeal” resection. Radiosurgery of the resection cavity may offer comparable survival and local control as postoperative whole-brain radiotherapy (WBRT). WBRT alone is now the treatment of choice only for patients with single or multiple BMs not amenable to surgery or radiosurgery, or with poor prognostic factors. To reduce the neurocognitive sequelae of WBRT intensity modulated radiotherapy with hippocampal sparing, and pharmacological approaches (memantine and donepezil) have been investigated. In the last decade, a multitude of molecular abnormalities have been discovered. Approximately 33% of patients with non-small cell lung cancer (NSCLC) tumors and epidermal growth factor receptor mutations develop BMs, which are targetable with different generations of tyrosine kinase inhibitors (TKIs: gefitinib, erlotinib, afatinib, icotinib, and osimertinib). Other “druggable” alterations seen in up to 5% of NSCLC patients are the rearrangements of the “anaplastic lymphoma kinase” gene TKI (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib). In human epidermal growth factor receptor 2-positive, breast cancer targeted therapies have been widely used (trastuzumab, trastuzumab-emtansine, lapatinib-capecitabine, and neratinib). Novel targeted and immunotherapeutic agents have also revolutionized the systemic management of melanoma (ipilimumab, nivolumab, pembrolizumab, and BRAF inhibitors dabrafenib and vemurafenib).

Treatment Design and Rationale for a Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for SCLC: PREMER Trial on Behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Radiation Oncology Group-Radiation Oncology Clinical Research Group

BackgroundProphylactic cranial irradiation (PCI) is part of the usual treatment in most patients with small-cell lung cancer (SCLC) and response after treatment of the primary tumor. Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy might play a role in radiation-induced neurocognitive decline. Patients and MethodsThis study is a multicenter phase III trial (NCT02397733) randomizing SCLC patients after informed consent, to receive standard PCI treatment or PCI with hippocampus avoidance (PCI-HA) by using intensity modulated radiation therapy or volumetric modulated arc therapy. The primary objective is assessment of hippocampus-dependent memory functioning and safety after PCI with or without hippocampus sparing by the Free and Cued Selective Reminding Test. Secondary objectives are assessment of other neurotoxicity/quality of life, radiological brain abnormalities on magnetic resonance images, and evaluation of the incidence and location of brain metastases after PCI-HA compared with standard PCI. The originally planned sample size (n = 150) has been calculated to detect a 50% difference in the 3-month delayed recall score between the 2 treatment arms, with a statistical power of 80% (β = 20%) and a significance level of 5% (α = 5%), with a maximum loss to follow-up of 10%. ConclusionThis study is an important step in introducing a new therapeutic approach to patients with SCLC candidates for PCI.

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

OC-0420: Evaluating the variability of hippocampal contouring and dosimetric effect in Hippocampal sparing WBRT

OC-0420: Evaluating the variability of hippocampal contouring and dosimetric effect in Hippocampal sparing WBRT

EP-1189: A systematic review on neurocognitive impairment in hippocampal sparing radiotherapy

EP-1189: A systematic review on neurocognitive impairment in hippocampal sparing radiotherapy

PO-0737: Is there a role for hippocampal sparing consolidation radiotherapy in primary CNS lymphoma (PCNSL)?

PO-0737: Is there a role for hippocampal sparing consolidation radiotherapy in primary CNS lymphoma (PCNSL)?

EP-1928: VMAT-SIB WBRT hippocampal sparing in patients with large single metastasis

EP-1928: VMAT-SIB WBRT hippocampal sparing in patients with large single metastasis

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PurposeThe aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. Patients and methodsRetrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/β ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. ResultsAmong constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. ConclusionVolumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

The Road Less Traveled: Should We Omit Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer?

New randomized data from Japan have raised questions regarding the use of prophylactic cranial irradiation for patients with extensive-stage small-cell lung cancer but without detectable brain metastases on magnetic resonance imaging. In the present focused review, we examine the general role of prophylactic cranial irradiation in the management of small-cell lung cancer and present relevant controversies from both sides of the discussion. Future directions for clinical investigation and research are also highlighted. Strategies for neurocognitive protection, including memantine use and hippocampal sparing using modulated radiotherapy techniques, are also presented.

Abstract P1-17-06: Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016

Abstract Background: Breast cancer (BC) is one of the most common malignancies affecting women. Brain metastatses (BM) are frequently seen in BC, and can have devastating consequences with significant associated morbidity and mortality. Whole brain radiotherapy (WBRT) is commonly used to treat BM, with variable use of stereotactic radiotherapy (SRT). This study reports on the outcomes of BC patients with BM who received central nervous system (CNS) radiotherapy over a 17-year period at the Royal Marsden Hospital (RMH). Methods: We included all BC patients who had WBRT with or without SRT for intra-parenchymal BM secondary to BC at RMH between 2000 and 2016 inclusive. Instances of meningeal involvement were excluded from analysis. Data collected included age, histological subtype, tumor grade, stage at original BC presentation, receptor status, date of BM diagnosis, number of metastases, size of largest BM, Eastern Cooperative Oncology Group (ECOG) score, presence of extra-cranial metastases (ECM), neurosurgery (NS) and stereotactic radiotherapy (SRT) details, and date of last follow up or death. Univariate and multivariate analyses were performed to analyze the effect of each variable on overall survival (OS) from date of BM. Results: A total of 426 patients were included with a median age of 54 years at BM diagnosis and a median time to BM from BC diagnosis of 43 months. At diagnosis, 94% had invasive ductal carcinoma (IDC) and 70% had Grade 3 disease. Stage IV disease at original BC presentation was seen in 18% of patients. Estrogen receptor (ER+) was positive in 57% (n = 236), progesterone receptor (PR+) in 44% (n = 147), and HER2 (HER2+) in 44% (n = 166). Twenty-two percent (n = 89) were triple negative (TN). Median number of BM was 4 (range 1 – 205) and 20% (n = 72) of patients had only 1 BM. Average size of the largest lesion was 26 mm (range 1 – 75). The ECOG score was 0 – 1 in 61% of patients. Ten percent of patients (n = 44) underwent SRT and 10% (n = 43) underwent NS. Three hundred and eighty patients had died at the time of analysis. Median OS from date of BM was 6.4 months. On univariate analysis, age &amp;lt; 60 years at BC diagnosis (8.1 vs. 4.0 months, p = 0.0007) and BM diagnosis (8.0 vs. 5.6 months, p = 0.03), ECOG status 0-1 (9.6 vs. 4.0 months, p = &amp;lt;0.0001), ER+ (8.0 vs. 6.0 months, p = 0.0007), PR+ (7.6 vs. 6.9 months, p = 0.04), HER2+ (10.5 vs. 5.6 months, p &amp;lt; 0 .0001), SRT (20.3 vs. 5.9 months, p &amp;lt; 0.0001) and NS (20.3 vs. 6.2 months, p &amp;lt; 0.0001) significantly predicted for improved OS. Triple negative status predicted for worse survival (5.6 months vs. 8.1 months, p &amp;lt; 0.0001). On multivariate analysis, ECOG status, ER+, HER2+, treatment with SRT and NS were independent predictors for OS. Conclusions: This study confirms substantial heterogeneity of prognosis in patients with BM from BC, with significantly improved survival in patients selected for SRT or surgery. Further studies are required to optimize the role of CNS radiotherapy techniques such as SRT and hippocampal sparing WBRT in patients with a favorable prognosis. Citation Format: Kothari G, De Ieso PB, Mohammed K, Ross GM. Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-06.