Blood eosinophil counts as predictive marker in advanced melanoma patients treated with anti-PD1 therapies.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 66-66
Author(s):  
Lydia Gaba ◽  
Iván Victoria ◽  
Francisco Aya ◽  
Gustavo Ruiz ◽  
Estela Pineda ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Predictive Marker ◽  
Blood Eosinophil ◽  
Free Survival ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Line Setting ◽  
Eosinophil Counts ◽  
Important Marker

66 Background: Anti-PD1 antibodies (Abs) Nivolumab (Nivo) and Pembrolizumab (Pembro) have both demonstrated to improve the overall survival (OS) in patients (pts) with advanced or metastatic melanoma (MM) in the first line setting. We previously reported that an increase in absolute eosinophil counts (AEC) of 100/mm3 over baseline at week 3 and an AEC > 400/mm3 at week 12 during anti-PD1 treatment (tmt) might identify pts with MM most likely to experience long-term disease control (1). AEC could serve as an important marker allowing the detection of those patients who may benefit from the therapy with anti-PD1 Abs. Methods: This retrospective observational study included pts with MM who received anti-PD1 tmt in a single institution. The objective was to identify whether an increase over the upper limit of normal AEC (>400/mm3) at any time during the tmt could predict better outcomes. Blood tests were performed before every tmt administration. Progression free survival (PFS) and OS were evaluated. Descriptive statistics were used to analyze patient baseline characteristics. PFS and OS were estimated by the Kaplan-Meier method. Results: From March 2013 to February 2016, 50 pts were treated with anti-PD1 Abs (39 pts with Pembro and 11 pts with Nivo). Median age was 58 years (33-84). 72% had received previous systemic tmt for MM, 64% had stage M1c disease, and 50% had elevated LDH levels. BRAF V600 mutations were observed in 34%. The median time to increase AEC > 400/mm2 was 42 (14-196) days. Pts who experienced an increase > 400/mm3 at 12 weeks demonstrated better outcomes in terms of PFS (21,9 [95% CI: 11,1-32,6] vs. 7,5 [95% CI: 4,3-10,7] months, p=0.017) and OS (38,0 [95% CI: 30,8-45,1] vs. 20,5 [95% CI: 15,7-25,3] months, p=0.025) compared with those who did not. Moreover, according to our previous results, pts with an increase of at least 100/mm3 in AEC over the baseline at 12 weeks also showed better OS (32,5 [95% CI: 26,3-38,8] vs. 16,3 [95% CI: 11,1-21,6] months, p=0.008). Conclusions: An increase in AEC of 100/mm3 over baseline and an absolute AEC > 400/mm3 at week 12 during anti-PD1 tmt might identify pts with MM most likely to experience clinical benefit with anti-PD1 Abs which could be relevant for pts management.

scholarly journals Hosszú távú progressziómentes túlélés relabált, refrakter myeloma multiplex tisztán orális ixazomib-lenalidomid-dexametazon kezelésével

2021 ◽  
Vol 162 (36) ◽  
pp. 1451-1458
Author(s):  
Apor Hardi ◽  
Gergely Varga ◽  
Zsolt Nagy ◽  
Szabolcs Kosztolányi ◽  
László Váróczy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Staging System ◽  
Term Therapy ◽  
Sustained Remission ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier

Összefoglaló. Bevezetés: A myeloma multiplex mindmáig alapvetően gyógyíthatatlan betegség, ezért nagy klinikai jelentőségük van az eredményes mentő kezeléseknek. A szájon át adható első proteaszómagátlóval, az ixazomibbal kiegészített lenalidomid-dexametazon terápia jól tolerálható, csak orális szerekből álló kombináció, mely hazánkban 2015 áprilisától kezdődően a „Named Patient Program” keretén belül vált elérhetővé relabált, refrakter myeloma multiplexes betegek kezelésére. Célkitűzés: Kutatásunk célja az ixazomib-lenalidomid-dexametazon kezelés mellett a hosszú távon progressziómentes túlélők célzott vizsgálata. Módszer: A program keretében összesen 7 centrumban 80 visszaeső beteg részesült e triplet kezelésben, adataikat retrospektíven elemeztük. Leíró statisztikai és Kaplan–Meier-analízist végeztünk. Eredmények: A betegek nagyobb hányada reagált: 63,75%-os válaszarány mellett 14 (17,5%) betegnél nem volt terápiás válasz/stabil betegség alakult ki, és 15-nél (18,75%) a betegség a kezelés mellett is progrediált. A progressziómentes túlélés a teljes betegcsoportban 10,6 hónapnak adódott, ugyanakkor 16 beteg (18,75%) két éven túl progressziómentesnek bizonyult, sőt közülük 11-nél a betegség még 3 év után sem progrediált. Tanulmányunkban a fenti, hosszú távú túlélő betegcsoport tulajdonságait tárjuk fel. Megbeszélés: A folyamatos terápia a myeloma multiplex kezelésében meghatározóvá vált. Ezért fontos ismernünk, hogy kik lehetnek azok a betegek, akik különösen sokat profitálnak egy bizonyos terápiából. A hosszú távon progressziómentes túlélők között az immunglobulin-nehézláncot érintő transzlokációk vagy triszómiák közül (trend szintjén) az utóbbiak kedvezőbb progressziómentes túléléssel bírtak, de progressziómentes platót mindkét betegcsoportban észleltünk. A betegség tumortömegét mérő nemzetközi stádiumbeosztás (ISS) nem jelezte előre a hosszú túlélést. Gyógyszerelhagyáshoz vezető mellékhatást a hosszú távú túlélő csoportban egyet sem regisztráltunk; az észlelt mellékhatások nagy része enyhe volt. Következtetések: Munkánk során az ixazomib-lenalidomid-dexametazon kombinációt effektívnek és biztonságosnak találtuk relabált, refrakter myeloma multiplex kezelésére, mely a betegek mintegy hatodánál több éven át eredményesen alkalmazható. Cikkünkkel a hazai beteganyagon szerzett tapasztalatainkat szeretnénk megosztani a COVID–19-világjárvány alatt különösen aktuálissá vált, tisztán orális terápiás lehetőségről. Orv Hetil. 2021; 162(36): 1451–1458. Summary. Introduction: Despite great advances in therapy, multiple myeloma is still a largely incurable disease, therefore the importance of salvage therapies is paramount. The first oral proteasome inhibitor ixazomib in combination with lenalidomide-dexamethasone is a tolerable, orally administered regime, which has become available for Hungarian relapsed, refractory multiple myeloma patients from April 2015 in the Named Patient Program. Objective: Our goal was to investigate the long-time progression-free surviving patient population treated with the ixazomib-lenalidomide-dexamethasone triplet. Method: We retrospectively studied a total of 80 patients from 7 centers who received the triplet combination. Survival analyses were performed. Results: Two-third of the patients responded: the overall response rate was 63.75%. 14 patients (17.5%) did not respond/had stable disease and 15 patients (18.75%) outright progressed upon therapy. Although progression-free survival was only 10.6 months for the entire patient cohort, the disease in a subgroup of 16 patients did not progress within two years. In fact, 11 of them were still in sustained remission after 3 years of therapy. Our goal was to analyze the characteristics of this subgroup. Discussion: The idea of long-term therapy of multiple myeloma is gaining widespread acceptance. Therefore it is important to know which patients may benefit the most from certain therapies. Among these 16 long-term responder patients, reciprocal translocation of the immunoglobulin heavy chain seemed to lack an adverse impact on progression-free survival; comparable to trisomies, both curves had a progression-free plateau. The International Staging System (ISS) score at the start of therapy did not predict long-term survivorship. Most of the side effects in this subgroup were mild, manageable, none led to therapy discontinuation. Conclusion: Ixazomib-lenalidomide-dexamethasone was confirmed to be an effective and safe combination for relapsed, refractory multiple myeloma, and one-sixth of the treated patients were able to receive it for several years, effectively. This fully oral therapeutic option is at its best during the present COVID–19 pandemic. Orv Hetil. 2021; 162(36): 1451–1458.

scholarly journals Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients

2018 ◽  
Vol 10 ◽  
pp. 175883401774974 ◽  
Author(s):  
Niki Karachaliou ◽  
Maria Gonzalez-Cao ◽  
Guillermo Crespo ◽  
Ana Drozdowskyj ◽  
Erika Aldeguer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Free Survival ◽  
Melanoma Patients ◽  
Ifn Γ ◽  
Nsclc Patients ◽  
Important Marker

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.

Stereotactic radiosurgery for recurrent vestibular schwannoma after previous resection

2017 ◽  
Vol 126 (5) ◽  
pp. 1506-1513 ◽  
Author(s):  
Marshall J. Huang ◽  
Hideyuki Kano ◽  
Seyed H. Mousavi ◽  
Ajay Niranjan ◽  
Edward A. Monaco ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Stereotactic Radiosurgery ◽  
Vestibular Schwannoma ◽  
Progression Free Survival ◽  
Median Length ◽  
Trigeminal Neuropathy ◽  
Free Survival ◽  
Kaplan Meier ◽  
Facial Function

OBJECTIVEThe goal of this retrospective cohort study was to assess long-term outcomes in patients with vestibular schwannoma (VS) who underwent stereotactic radiosurgery (SRS) after initial microsurgical resection.METHODSFrom the authors' database of 1770 patients with VS, the authors retrospectively analyzed data from 173 Gamma Knife SRS procedures for VS after 1 (128 procedures) or multiple (45 procedures) microsurgical resections. The median length of the interval between the last resection and SRS was 42 months (range 2–329 months). The median length of clinical follow-up was 74 months (range 6–285 months). Progression-free survival after SRS was determined with Kaplan-Meier analysis.RESULTSAt the time of SRS, the hearing of 161 patients (93%) was Gardner-Robertson Class V, and 81 patients (47%) had facial neuropathy (i.e., facial function with House-Brackmann [HB] grades of III–VI), 87 (50%) had trigeminal neuropathy, and 71 (41%) reported imbalance or disequilibrium disorders. The median tumor volume was 2.7 cm3 (range 0.2–21.6 cm3), and the median dose to the tumor margin was 13 Gy (range 11–20 Gy). Radiosurgery controlled growth of 163 (94%) tumors. Progression-free survival after SRS was 97% at 3 years, 95% at 5 years, and 90% at 10 years. Four patients with delayed tumor progression underwent repeat SRS at a median of 35 months (range 23–64 months) after the first SRS. Four patients (2.3%) with tumor progression underwent repeat resection at a median of 25 months (range 19–33 months). Among the patients with any facial dysfunction (indicated by HB grades of II–VI), 19% had improvement in this condition after SRS, and 5.5% with some facial function (indicated by HB grades of I–V) developed more facial weakness. Among patients with trigeminal neuropathy, 20% had improvement in this condition, and 5.8% developed or had worsened trigeminal neuropathy after SRS.CONCLUSIONSStereotactic radiosurgery offered a safe and effective long-term management strategy for VS patients whose tumors remained or recurred after initial microsurgery.

Expression of Complement Regulatory Protein CD55 on Tumor Cells Has an Adverse Effect on the Outcome of Follicular Lymphoma Patients Treated with Immunochemotherapy

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1297-1297
Author(s):  
Antti Sommarhem ◽  
Sirpa Leppä ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Seppo Meri
Keyword(s):  
Follicular Lymphoma ◽  
Regulatory Protein ◽  
Progression Free Survival ◽  
Mrna Levels ◽  
Free Survival ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Oligonucleotide Microarray Analysis

Abstract The addition of rituximab to chemotherapy has considerably improved the outcome of follicular lymphoma (FL) patients, but the lengths of remissions are still variable. Activation of the C system has been shown to be an important effector mechanism of rituximab. The aim of this study was to evaluate whether differences in the expression of CD20 and C regulatory molecules (C-REG) in lymphoma cells correlate to the clinical course of FL. We used oligonucleotide microarray analysis to study mRNA levels of CD20, CD46 (MCP), CD55 (DAF) and CD59 (protectin) in the FL tissue of 23 patients treated with R-CHOP. The median follow-up time was 55 months. The patients were divided into long-term (progression free survival (PFS) >35 mo) and short-term (PFS <21 mo) responders, and mRNA levels were compared between the groups. High CD55 expression was observed more often in FL patients who relapsed early resulting in a shorter progression free survival (p=0.027). Median PFS time for patients with a low CD55 level was significantly longer than for those with high CD55 expression (not reached vs. 20 mo, p=0.003). The results were validated prospectively by analyzing the protein levels of CD20 and C-REGs with flow cytometry. The results of a pilot study of 12 FL patients showed that relative expression of CD20 to CD55 in CD20 positive cell population was higher in patients in remission in comparison to ones who relapsed. According to Kaplan-Meier estimates, the patients with low CD20/CD55 and CD20/C-REGave (average C regulator expression) ratios relapsed more often than the other patients. The results suggest that the expression of C regulators, especially of CD55, affects the efficacy of immunochemotherapy, and that C regulatory molecules represent an effective escape mechanism of immunochemotherapy in FL.

Stereotactic Radiosurgery for Neurofibromatosis 2—Associated Vestibular Schwannomas

Neurosurgery ◽  
2013 ◽  
Vol 74 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Grant W. Mallory ◽  
Bruce E. Pollock ◽  
Robert L. Foote ◽  
Matthew L. Carlson ◽  
Colin L. Driscoll ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nerve Function ◽  
Facial Nerve Function ◽  
Free Survival ◽  
Kaplan Meier

Abstract BACKGROUND: Management of neurofibromatosis type 2 (NF2)—associated vestibular schwannomas (VSs) remains controversial. Stereotactic radiosurgery (SRS) with conventional dosing is less effective for NF2-related VS compared with sporadic lesions. OBJECTIVE: To evaluate optimal SRS dose parameters for NF2-related VS and to report long-term outcomes. METHODS: A prospective database was reviewed and outcome measures, including radiographic progression, American Academy of Otolaryngology—Head and Neck Surgery hearing class, and facial nerve function, were analyzed. Progression-free survival was estimated with Kaplan-Meier methods. Associations between tumor progression and radiosurgical treatment parameters, tumor volume, and patient age were explored with the use of Cox proportional hazards regression. RESULTS: Between 1990 and 2010, 26 patients with 32 NF2-related VSs underwent SRS. Median marginal dose and tumor volume were 14 Gy and 2.7 cm3, respectively. Twenty-seven tumors (84%) showed no growth (median follow-up, 7.6 years). Kaplan-Meier estimates for 5- and 10-year progression-free survival were 85% and 80%, respectively. Cox proportional hazards demonstrated a significant inverse association between higher marginal doses and tumor progression (hazard ratio, 0.49; 95% confidence interval, 0.17-0.92; P = .02). Audiometric data were available in 30 ears, with 12 having class A/B hearing before SRS. Only 3 maintained serviceable hearing at the last follow-up. Four underwent cochlear implantation. Initially, 3 achieved open-set speech recognition, although only 1 experienced long-term benefit. Facial nerve function remained stable in 50% of cases. CONCLUSION: Higher marginal doses than commonly prescribed for sporadic VS were associated with improved tumor control in patients with NF2. Hearing outcomes were poor even when contemporary reduced marginal doses were used. However, SRS allows an anatomically preserved cochlear nerve and may permit hearing rehabilitation with cochlear implantation. Further consideration should be given to optimum dosing to achieve long-term control while maximizing functional outcomes.

scholarly journals Treatment of Syringomyelia Related to Nontraumatic Arachnoid Pathologies of the Spinal Canal

Neurosurgery ◽  
2012 ◽  
Vol 72 (3) ◽  
pp. 376-389 ◽  
Author(s):  
Jörg Klekamp
Keyword(s):  
Progression Free Survival ◽  
Magnetic Resonance Images ◽  
Long Term Results ◽  
Csf Flow ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Kaplan Meier ◽  
History Of

Abstract BACKGROUND: Disturbances of cerebrospinal fluid (CSF) flow are the commonest cause of syringomyelia. Spinal arachnopathies may lead to CSF flow obstructions but are difficult to diagnose. Consequently, associated syringomyelias are often categorized as idiopathic. OBJECTIVE: To present and analyze the diagnosis of and long-term outcomes in an observational study of patients with nontraumatic arachnopathies from 1991 to 2011. METHODS: A total of 288 patients (mean age, 47 ± 15 years; follow-up, 54 ± 46 months) were evaluated. Decompression with arachnolysis, untethering, and duraplasty for restoration of CSF flow was recommended to patients with neurological progression. Neurological examinations, magnetic resonance images, and follow-up data were evaluated. Individual symptoms were analyzed during the first postoperative year, and long-term outcomes were analyzed with Kaplan-Meier statistics to determine rates of progression-free survival. RESULTS: In total,189 patients either refused an operation or were managed conservatively for lack of progression. Among 79 unoperated patients with follow-up information available for up to 8 years, 2 patients deteriorated. Ninety-nine patients with progressive symptoms underwent 116 operations: 108 decompressions and 8 other surgeries. Three months postoperatively, 53% considered their status improved and 37% were unchanged. In the long term, surgery on arachnopathies limited to 2 spinal segments was followed by progression-free survival for 78% over 10 years, in contrast to 31% with extensive arachnopathies. CONCLUSION: Surgery on nontraumatic arachnopathies related to syringomyelia should be reserved for patients with progressive symptoms. Arachnolysis, untethering, and duraplasty provide good long-term results for focal arachnopathies. For extensive pathologies with a history of subarachnoid hemorrhage or meningitis, treatment remains a major challenge.

scholarly journals Immune-Related Adverse Events in PD-1 Treated Melanoma and Impact Upon Anti-Tumor Efficacy: A Real World Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Melissa L. Bastacky ◽  
Hong Wang ◽  
Dylan Fortman ◽  
Zahra Rahman ◽  
Gerard P. Mascara ◽  
...  
Keyword(s):  
Adverse Events ◽  
Statistical Significance ◽  
Single Agent ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Integrated Network ◽  
Free Survival ◽  
Melanoma Patients ◽  
Grade 3

BackgroundAnti-PD-1 immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of melanoma by producing durable long-term responses in a subset of patients. ICI-treated patients develop unique toxicities - immune related adverse events (irAEs) – that arise from unrestrained immune activation. The link between irAE development and clinical outcome in melanoma and other cancers is inconsistent; and little data exists on the occurrence of multiple irAEs. We sought to characterize development of single and multiple irAEs, and association of irAE(s) development with clinical variables and impact upon outcomes in advanced melanoma patients treated with anti-PD-1 ICIs.MethodsWe conducted a retrospective study of 190 patients with metastatic melanoma treated with single-agent anti-PD-1 ICI therapy between June 2014 and August 2020 at a large integrated network cancer center identified through retrospective review of pharmacy records. irAEs were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Results190 patients were evaluated of whom 114 patients (60.0%) experienced ≥1 irAE, including 30 (15.8%) with grade 3/4 irAEs. The occurrence of any irAE was strongly associated with the development of investigator-assessed response to anti-PD-1 therapy (p &lt; 0.0001); whether evaluated by current (p=0.0082) or best (p=0.0001) response. In patients with ≥2 irAEs, distinct patterns were observed. Median progression-free survival (PFS) and overall survival (OS) were greater in those with any irAE compared to those without (PFS, 28 months vs. 5 months, p &lt; 0.0001; OS, not reached vs. 9 months, p &lt; 0.0001). Development of ≥2 irAEs had a trend towards improved PFS and OS compared to those who developed a single irAE, although this did not reach statistical significance (p=0.2555, PFS; p=0.0583, OS). Obesity but not age or gender was distinctly associated with irAE development.ConclusionsIn this study, we demonstrated that irAE occurrence was significantly associated with response to anti-PD-1 therapy and improved PFS/OS. Those who developed multiple irAEs had a trend towards improved PFS and OS compared to those who developed only a single irAE. Increased BMI but neither age nor gender were associated with irAE development. Distinct patterns of irAEs observed suggest shared etiopathogenetic mechanisms.

Long-term radiosurgical control of subtotally resected adult pineocytomas

2012 ◽  
Vol 117 (2) ◽  
pp. 212-217 ◽  
Author(s):  
David A. Wilson ◽  
Al-Wala Awad ◽  
David Brachman ◽  
Stephen W. Coons ◽  
Heyoung McBride ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Endoscopic Biopsy ◽  
Definitive Treatment ◽  
Free Survival ◽  
Kaplan Meier ◽  
Radiographic Data

Object The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease. Methods The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival. Results Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13–83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm3. Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p < 0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression. Conclusions Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.

RADT-18. NEOADJUVANT (PRE RADIOTHERAPY) TEMOZOLOMIDE FOLLOWED BY RADIATION THERAPY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi45-vi45
Author(s):  
Chinmaykumar Prajapati ◽  
Maitrik Mehta ◽  
U Suryanarayan Kunikullaya
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Progression Free Survival ◽  
Inclusion Criteria ◽  
Term Survival ◽  
Free Survival ◽  
Adjuvant Temozolomide ◽  
Kaplan Meier ◽  
Extent Of Surgery

Abstract BACKGROUD AND PURPOSE To evaluate the effect of neoadjuvant [pre-radiotherapy(RT)] temozolomide (TMZ) in glioblastoma multiforme (GBM) patients in terms of overall survival(OS) and progression free survival (PFS). MATERIAL AND METHODS Patients with diagnosed GBM are treated with neoadjuvant( pre RT) TMZ followed by concurrent RT-TMZ and adjuvant TMZ. The Kaplan-Meier method is used to estimate OS the differences between groups. RESULTS Twenty five patients are match with inclusion criteria. Age group, Recurvsive partitioning analysis (RPA) class and extent of surgery are found to effect on overall survival but statistically not significant. At end of study, 40 percent patients are alive with 9 months PFS and 11 months OS. CONCLUSION The neo-adjuvant TMZ with concomitant and adjuvant TMZ is feasible and safe which is associated with an encouraging favorable long-term survival with acceptable toxicity.

scholarly journals Yittrium 90 Ibritumomab Tiuxetan (Zevalin®) in the Treatment of Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma; Integrated Analysis of Three Japanese Institution's Experience with Improvement Trend of the Long-Term Responses over a 10 Year Study Period

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Ilseung Choi ◽  
Masaya Okada ◽  
Tomoki Ito
Keyword(s):  
Early Phase ◽  
Myeloid Leukemia ◽  
Late Phase ◽  
Progression Free Survival ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Kaplan Meier

Background This study investigated all cases treated by Yittrium 90 Ibritumomab Tiuxetan (90Y-IT, Zevalin®) for relapsed or refractory indolent B-cell non-Hodgkin lymphoma at the three Japanese institutions between 2008/10/14 and 2018/5/15. 90Y-IT is the only radioimmunoconjugate agent available on the Japanese market since August 2008. J3Zi study (UMIN-CTR: 000037105) created integrated dataset of 90Y-IT treatment, and subjects were requiring at least two years follow-up period. Methods A total of 347 cases were registered and 316 patients of the per-protocol set were analyzed creating the integrated dataset. Overall response rate (ORR) and complete response rate (CR) were evaluated using positron emission tomography (PET, 84%), computed tomography (CT, 8%) or other methods (8%) at 8-12 weeks after 90Y-IT treatment. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The prognostic factors of PFS and OS were analyzed using Cox regression analysis. Results All patients had previously been administered with median of 2 (mean 3.9) chemotherapeutic regimens at a mean age of 65 years. The majority of cases were follicular lymphoma (FL) patients (75%) followed by mucosa-associated lymphoid tissue lymphoma/marginal zone lymphoma (MALT/MZL) patients (13%). The ORR was 89% and CR was 66%. The Kaplan-Meier survival curves of PFS and OS extending over the 10 year study period were shown in Figure 1A. The progression free 2-year cumulative survival rate (PFS 2-years) was 61%. The PFS 2-years of the early phase (2008/10/14-2013/7/9) defined as the cut-off date of the previous report, and the late phase (2013/7/10-2018/5/15) were 51% and 73%, respectively (p&lt;0.0001). The overall 5-year cumulative survival rate (OS 5-years) was 77%. The OS 5-years of the early phase and the late phase were 73% and 83% respectively (p=0.0565). The evident improvement trend of the long-term responses during the 10 year study period was demonstrated (Figure 1B). Among several prognostic factors, treatment response (CR/non-CR), number of prior treatments (≦2/≧3), sIL-2R (≦500/&gt;500 U/ml) and progression of disease within 24 months after the first-line treatment initiation (POD24, no/yes), were the significant factors (univariate analysis, p&lt;0.05) for both PFS and OS. The number of prior treatment and POD24 showed correlation with each other, but also showed a significant different between the early phase and the late phase of the study, thus the factors resulting in the improvement trend shown in figure 1 have to be carefully discussed. In 316 cases, 26 (8.2%) of second primary malignancy (SPM) including 9 (2.8%) haematological malignancy (7 myelodysplastic syndrome, 1 acute myeloid leukemia and 1 chronic myeloid leukemia) were observed and 1 death (treatment related Sepsis) in 15 infection cases recorded. All the long-term follow-up safety reports were consistent with the previous studies of the relapsed/refractory low-grade follicular lymphoma, and there was no obvious trend associated with radioimmunoconjugate therapy. Conclusions The study represents the largest reported cohort for therapeutic use of 90Y-IT in Japan. The improvement trend of the long-term responses (PFS and OS) during the 10 year study period was demonstrated. The response and survival data in this large real-world cohort is superior to the previously published 90Y-IT trial data including the US phase-3 trial conducted 20 years ago. The factors resulting in this improvement trend have to be carefully assessed in attempt to achieve better outcomes for 90Y-IT treatment in future. Figure-1 Legend (A) Overall survival (OS, black line) and progression-free survival (PFS, gray line) with 95% confidence intervals (n=316), Kaplan-Meier method. (B) Improvement trend of the long-term (2-year) treatment responses (PFS and OS) over the 4 periods of 90Y ibritumomab tiuxetan treatment (n=316) dated; 2008/10/14-2011/7/9 (n=91), 2011/7/10-2013/7/9 (n=86), 2013/7/10-2015/7/10 (n=60), 2015/7/10-2018/5/15 (n=79). Disclosures This study was sponsored by Mundipharma. Data management and statistical analysis under the direction of investigators Ilseung Choi, Masaya Okada and Tomoki Ito was provided by L Data Science, Co., Ltd. and was funded by Mundipharma. Figure Disclosures No relevant conflicts of interest to declare.

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