المؤلفون: Glitza Oliva, Isabella C., Ferguson, Sherise D., Bassett, Roland, Foster, Alexandra P., John, Ida, Hennegan, Tarin D., Rohlfs, Michelle, Richard, Jessie, Iqbal, Masood, Dett, Tina, Lacey, Carol, Jackson, Natalie, Rodgers, Theresa, Phillips, Suzanne, Duncan, Sheila, Haydu, Lauren, Lin, Ruitao, Amaria, Rodabe N., Wong, Michael K., Diab, Adi, Yee, Cassian, Patel, Sapna P., McQuade, Jennifer L., Fischer, Grant M., McCutcheon, Ian E., O’Brien, Barbara J., Tummala, Sudhakar, Debnam, Matthew, Guha-Thakurta, Nandita, Wargo, Jennifer A., Burton, Elizabeth M., Tawbi, Hussein A., Davies, Michael A.

المساهمون: U.S. Department of Health & Human Services | NIH | National Cancer Institute, Additional funding for this research: Philanthropic contributions to the Melanoma Moon Shots Program of MD Anderson., Additional funding for this research: Philanthropic contributions to the Melanoma Moon Shots Program of MD Anderson and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

المصدر: Nature Medicine ; volume 29, issue 4, page 898-905 ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الوصف: There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256 .

الإتاحة: https://doi.org/10.1038/s41591-022-02170-xTest
https://www.nature.com/articles/s41591-022-02170-x.pdfTest
https://www.nature.com/articles/s41591-022-02170-xTest

المؤلفون: Rodriguez, Andrew, Wang, Chenyang, Loghin, Monica, Guha-Thakurta, Nandita, O'Brien, Barbara

المصدر: Neuro-Oncology Advances ; volume 5, issue Supplement_3, page iii25-iii25 ; ISSN 2632-2498

مصطلحات موضوعية: Surgery, Oncology, Neurology (clinical)

الوصف: Leptomeningeal metastasis (LM) is an aggressive cancer complication with poor prognosis. Prompt diagnosis based on clinical findings, neuroaxis imaging, and cerebrospinal fluid (CSF) cytology- critical for appropriate, timely management. However, diagnosis is often challenging- as imaging lacks specificity and CSF cytology lacks sensitivity. Classic LM imaging findings include cerebellar folia, cranial nerve, and cauda equina enhancement. Of 103 patients with solid tumor brain metastasis referred to Neuro-Oncology at MD Anderson Cancer Center from 2016-2022 for evaluation of suspected LM on stereotactic radiosurgery (SRS) planning MRI, 15 had limited (≤5) nodular or linear focal enhancement in supratentorial sulci, without classic LM imaging. Upon initial workup, none had symptoms, neurologic deficits, or spine imaging consistent with LM; 10 underwent ≥1 lumbar puncture (median 1; range, 0-4) of which 2 (13%) had CSF cytology-confirmed disseminated LM. Majority were female (n=10); median age 60 years (range, 29-87). Most had lung (n=6) or breast (n=5) cancer. Five (33%) had history of craniotomy and resection of metastasis, with 1 resection cavity near supratentorial findings subsequently confirmed as LM. Both patients with confirmed LM received whole-brain radiation (WBRT)- instead of planned SRS- and intrathecal chemotherapy. One died 10.5m following diagnosis; the other continues therapy 11.6m later. In the remaining 13, the suspicious LM findings were determined to represent parenchymal/dural metastasis, treatment effect, or vascularity. Six were dispositioned to SRS, 3 to WBRT. One was ultimately diagnosed with LM (cytology-confirmed) 10m following WBRT. Nine subsequently received systemic therapy for intracranial and/or systemic disease. Median OS was 11 months (range, 4-37) from LM suspicion; 6 remain alive. In this small series, a minority of patients with supratentorial focal enhancing lesions without classic imaging findings were diagnosed with disseminated LM. Further study is needed to ...

الإتاحة: https://doi.org/10.1093/noajnl/vdad070.097Test
https://academic.oup.com/noa/article-pdf/5/Supplement_3/iii25/51037654/vdad070.097.pdfTest

المؤلفون: Altan, Mehmet, Wang, Yan, Song, Juhee, Welsh, James, Tang, Chad, Guha-Thakurta, Nandita, Blumenschein, George R, Carter, Brett W, Wefel, Jeffrey S, Ghia, Amol J, Yeboa, Debra N, McAleer, Mary Frances, Chung, Caroline, Woodhouse, Kristina D, McGovern, Susan L, Wang, Chenyang, Kim, Betty Y S, Weinberg, Jeffrey S, Briere, Tina M, Elamin, Yasir Y, Le, Xiuning, Cascone, Tina, Negrao, Marcelo V, Skoulidis, Ferdinandos, Ferrarotto, Renata, Heymach, John V, Li, Jing

المساهمون: Bristol-Myers Squibb, NIH/NCI

المصدر: Journal for ImmunoTherapy of Cancer ; volume 11, issue 7, page e006871 ; ISSN 2051-1426

الوصف: Background Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. Patients and methods This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). Results Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7–24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%. Conclusion Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.

الإتاحة: https://doi.org/10.1136/jitc-2023-006871Test

المؤلفون: Sahin, Onur, Kamel, Serageldin, Wahid, Kareem A, Dede, Cem, Taku, Nicolette, He, Renjie, Naser, Mohamed A, Sharafi, Setareh, Mäkitie, Antti, Kann, Benjamin H, Kaski, Kimmo, Sahlsten, Jaakko, Jaskari, Joel, Amit, Moran, Chronowski, Gregory M, Diaz, Eduardo M, Garden, Adam S, Goepfert, Ryan P, Guenette, Jeffrey P, Gunn, G Brandon, Hirvonen, Jussi, Hoebers, Frank, Hutcheson, Katherine A, Guha-Thakurta, Nandita, Johnson, Jason, Kaya, Diana, Khanpara, Shekhar D, Nyman, Kristofer, Lai, Stephen Y, Lango, Miriam, Learned, Kim O, Lee, Anna, Lewis, Carol M, Maniakas, Anastasios, Moreno, Amy C, Myers, Jeffery N, Phan, Jack, Pytynia, Kristen B, Rosenthal, David I, Sandulache, Vlad C, Schellingerhout, Dawid, Shah, Shalin J, Sikora, Andrew G, Mohamed, Abdallah S R, Chen, Melissa M, Fuller, Clifton D

المصدر: medRxiv

الوصف: Extranodal extension (pENE) is a critical prognostic factor in oropharyngeal cancer (OPC) that drives therapeutic disposition. Determination of pENE from radiological imaging has been associated with high inter-observer variability. However, the impact of clinician specialty on human observer performance of imaging-detected extranodal extension (iENE) remains poorly understood.

العلاقة: https://doi.org/10.1101/2023.02.25.23286432Test; https://pubmed.ncbi.nlm.nih.gov/36865096Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980252Test/

الإتاحة: https://doi.org/10.1101/2023.02.25.23286432Test
https://pubmed.ncbi.nlm.nih.gov/36865096Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980252Test/

المؤلفون: Al Feghali, Karine A, Randall, James W, Liu, Diane D, Wefel, James S, Brown, Paul D, Grosshans, David R, McAvoy, Sarah A, Farhat, Maguy A, Li, Jing, McGovern, Susan L, McAleer, Mary F, Ghia, Amol J, Paulino, Arnold C, Sulman, Erik P, Penas-Prado, Marta, Wang, Jihong, deGroot, John, Heimberger, Amy B, Armstrong, Terri S, Gilbert, Mark R, Mahajan, Anita, Guha-Thakurta, Nandita, Chung, Caroline

المصدر: Neuro-Oncology Advances ; ISSN 2632-2498

الوصف: Background This secondary image analysis of a randomized trial of proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment vs. Response Assessment in Neuro-Oncology (RANO). Methods Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. ‘Clinical progression’ was based on a clinical radiology report of progression and/or change in treatment for progression. Results Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (Range: 9.4-14.7) months; 10.8 months IMRT vs. 11.2 months PT (p=0.14). Median RANO PFS was 8.2 (Range: 6.9, 12): 8.9 months IMRT vs. 6.6 months PT (p=0.24). RANO PFS was significantly shorter than clinical PFS overall (p=0.001) and for both the IMRT (p=0.01) and PT (p=0.04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. Conclusion Based on this secondary analysis of a trial of PT vs. IMRT for GBM, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.

الإتاحة: https://doi.org/10.1093/noajnl/vdab073Test

المؤلفون: Ghia, Amol J, Guha-Thakurta, Nandita, Song, Juhee, Thall, Peter, Briere, Tina M, Settle, Stephen H, Sharp, Hadley J, Li, Jing, McAleer, MaryFrances, Chang, Eric L, Tatsui, Claudio E, Brown, Paul D, Rhines, Laurence D

المساهمون: National Cancer Institute, NIH

المصدر: North American Spine Society Journal (NASSJ) ; volume 6, page 100066 ; ISSN 2666-5484

مصطلحات موضوعية: Neurology (clinical), Orthopedics and Sports Medicine, Surgery

الإتاحة: https://doi.org/10.1016/j.xnsj.2021.100066Test
https://api.elsevier.com/content/article/PII:S2666548421000184?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666548421000184?httpAccept=text/plainTest

المؤلفون: Debnam, J. Matthew, Guha-Thakurta, Nandita

المصدر: Imaging Atlas of Ophthalmic Tumors and Diseases ; page 309-332 ; ISBN 9783031174780 9783031174797

الإتاحة: https://doi.org/10.1007/978-3-031-17479-7_9Test

المؤلفون: Debnam, James M., Said, Ryan B., Liu, Heng-Hsiao, Sun, Jia, Wang, Jihong, Wei, Wei, Suki, Dima, Mayer, Rory R., Chi, T. Linda, Ketonen, Leena, Guha-Thakurta, Nandita, Weinberg, Jeffrey S.

المصدر: Cancer Imaging ; volume 20, issue 1 ; ISSN 1470-7330

مصطلحات موضوعية: Radiology, Nuclear Medicine and imaging, Oncology, General Medicine, Radiological and Ultrasound Technology

الوصف: Background To test the hypothesis that intraventricular ADC values can be used to determine the presence of neoplastic leptomeningeal disease (LMD). Materials and methods ADC values were measured at multiple sites in the ventricular system in 32 patients with cytologically-proven LMD and 40 control subjects. Multiple linear regression analysis was used to determine the mean difference of ADCs between the LMD and control groups after adjusting for ventricle size and tumor type. Receiver operating characteristics (ROC) analysis was performed and optimal ADC value cut-off point for predicting the presence of LMD. ADC was compared to T1 enhancement and FLAIR signal hyperintensity for determining the presence of LMD. Results After adjusting for ventricular volume and tumor type, the mid body of lateral ventricles showed no significant difference in ventricular volume and a significant difference in ADC values between the control and LMD groups ( p > 0.05). In the mid-body of the right lateral ventricle the AUC was 0.69 (95% CI 0.57–0.81) with an optimal ADC cut off point of 3.22 × 10 − 9 m 2 /s (sensitivity, specificity; 0.72, 0.68). In the mid-body of left lateral ventricle the AUC was 0.7 (95% CI 0.58–0.82) with an optimal cut-off point of 3.23 × 10 − 9 m 2 /s (0.81, 0.62). Using an average value of HU measurements in the lateral ventricles the AUC was 0.73 (95% CI 0.61–0.84) with an optimal cut off point was 3.11 × 10 − 9 m 2 /s (0.78, 0.65). Compared to the T1 post-contrast series, ADC was predictive of the presence of LMD in the mid-body of the left lateral ventricle ( p = 0.036). Conclusion Complex interactions affect ADC measurements in patients with LMD. ADC values in the lateral ventricles may provide non-invasive clues to the presence of LMD.

الإتاحة: https://doi.org/10.1186/s40644-020-00305-2Test

المؤلفون: Augustyn, Alexander, Patel, Roshal, Ludmir, Ethan, Haydu, Lauren, Guha-Thakurta, Nandita, Bishop, Andrew, Chung, Caroline, Ghia, Amol, McAleer, Mary Frances, McGovern, Susan, Wang, Chenyang, Woodhouse, Kristina, Yeboa, Debra, Ferguson, Sherise, Kim, Betty, Glitza, Isabella, Li, Jing

المصدر: Neuro-Oncology ; volume 22, issue Supplement_2, page ii184-ii184 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الوصف: INTRODUCTION We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other. METHODS Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured. RESULTS Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified. CONCLUSIONS Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.

الإتاحة: https://doi.org/10.1093/neuonc/noaa215.766Test
http://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_2/ii184/34690247/noaa215.766.pdfTest

المؤلفون: Ng, Sweet Ping, Cardenas, Carlos E, Elhalawani, Hesham, Pollard, Courtney, Elgohari, Baher, Fang, Penny, Meheissen, Mohamed, Guha-Thakurta, Nandita, Bahig, Houda, Johnson, Jason M., Kamal, Mona, Garden, Adam S, Reddy, Jay P., Su, Shirley Y., Ferrarotto, Renata, Frank, Steven J., Brandon Gunn, G., Moreno, Amy C., Rosenthal, David I., Fuller, Clifton D., Phan, Jack

المصدر: Physics and Imaging in Radiation Oncology ; volume 14, page 1-5 ; ISSN 2405-6316

مصطلحات موضوعية: Radiology, Nuclear Medicine and imaging, Radiation

الإتاحة: https://doi.org/10.1016/j.phro.2020.04.001Test
https://api.elsevier.com/content/article/PII:S2405631620300105?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2405631620300105?httpAccept=text/plainTest