Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature

Author(s):  
Jaclyn J. Renfrow ◽  
Desmond A. Brown ◽  
Michael J. Link ◽  
Nadia N. Laack ◽  
David M. Routman ◽  
...  

<b><i>Introduction:</i></b> Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. <b><i>Methods:</i></b> A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. <b><i>Results:</i></b> Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75–43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16–23.75 months). The median prescription isodose volume was 1.85 cm<sup>3</sup> (IQR, 1.85–7.02 cm<sup>3</sup>); median tumor margin dose was 18 Gy (IQR 14–20 Gy); and median isocenters was 2 (range 1–13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75–53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25–30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. <b><i>Discussion/Conclusion:</i></b> This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1272 ◽  
Author(s):  
Laura Marconato ◽  
Silvia Sabattini ◽  
Giorgia Marisi ◽  
Federica Rossi ◽  
Vito Ferdinando Leone ◽  
...  

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 147-147
Author(s):  
Rui Jin ◽  
Zhaohui Jin ◽  
Sean P. Cleary ◽  
David M. Nagorney ◽  
Rory L. Smoot ◽  
...  

147 Background: Colorectal cancer is one of the leading causes of cancer related deaths with liver being most common site of CRC metastasis. More than 50% of the CRC patients will develop metastatic liver lesion that eventually leads to death in about 70% of them. In this retrospective review we reviewed the outcome of pts who received neoadjuvant chemotherapy followed by resection of liver lesion for metastatic colorectal cancer. Methods: 304 pts who had preoperative chemotherapy were identified from 1045 metastatic colorectal cancer patients who had liver metastasectomy at Mayo Clinic between 1997 and 2018. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: There were 113 (37%) female and 191 (63%) male pts. Median age at primary disease diagnosis was 56.5 yrs. Two hundred forty-nine pts presented with stage IV metastatic colorectal cancer. Primary tumor locations were: 53 right-sided, 117 left-sided and 133 rectum. 152 (50%) pts had extrahepatic metastases. Two pts were found to be MSI-H, 113 MSS, 189 unknown. BRAF mutation was found in 6 patients. RAS mutation was present in 84 patients, with 124 unknown. Pts received chemotherapy for median of 2.82 months. Single agent fluoropyrimidine was administered in 38 (12%) pts and rest receiving chemotherapy doublet or triplet with fluropyrimidine plus oxaliplatin being most common regimen. The median overall survival from primary diagnosis for the entire group was 74.5 months. Median overall survival from liver metastasectomy was 60.0 months. In univariate analysis, metachronous disease, age < 60 yrs, and an absence of extrahepatic lesions led to statistically significant improvement of overall survival from primary diagnosis. Metachronous and extrahepatic lesions remained statistically significant in multivariate analysis. Conclusions: Neoadjuvant chemotherapy followed by liver metastasectomy is beneficial for highly-selected metastatic colorectal cancer pts. Compared to a historical control of 30-36 months, our patient population had a median overall survival of about 5 years from resection.


2021 ◽  
pp. 561-568
Author(s):  
Luke S. McLean ◽  
Wasek Faisal ◽  
Sagun Parakh ◽  
Steven C. Kao ◽  
Craig R. Lewis ◽  
...  

PURPOSE Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non–small-cell lung cancer who developed LMD and were subsequently treated with osimertinib. METHODS We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used. RESULTS Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months). CONCLUSION There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.


Author(s):  
Pedro Valente ◽  
Mónica Farinha ◽  
Manuel Jácome ◽  
Joana Guimarães ◽  
Eurico Monteiro

<p class="abstract"><strong>Background:</strong> Sinonasal tumours with neuroendocrine immunophenotype include olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). These neoplasms usually present in advanced stages and are associated with poor outcome. This study describes the clinical features of these tumours and analyzes treatment outcomes of patients with these malignancies.</p><p class="abstract"><strong>Methods:</strong> Retrospective chart review of all patients with sinonasal tumours diagnosed from 2009 to 2019, in a tertiary cancer centre. Clinical and histopathological prognostic factors were determined by univariate analysis. Overall survival was estimated using Kaplan-Meier method.  </p><p class="abstract"><strong>Results:</strong> A total of 27 patients (77.8% male) with a mean age of 52.0±16.8 years were included in the study. ONB was diagnosed in 9 patients, SNEC in 10 patients and SNUC in 8 patients. TNM stage IV disease was found in 20 patients (74.0%) at presentation. According to staging and treatment results, curative therapy was attempted in 21 patients (77.8%), of whom sixteen (76.2%) received multimodality treatment. Overall mean survival was 49 months and 1-year, 3-years and 5-years overall survival rates were 70.5%, 47.3% and 37.8%, respectively. Patients with SNEC had worse overall survival (p=0.044). Regarding treatment options, patients with SNUC treated with surgery and adjuvant radiation therapy had improved overall survival (p=0.027), as well as patients with SNEC selected for endoscopic resection surgery (p=0.049).</p><p class="abstract"><strong>Conclusions:</strong> Accurate histologic diagnosis, grading, and clinical staging are essential for characterization and treatment selection in this heterogeneous group of sinonasal tumours. Consensus in the management of these tumours is lacking due to their rarity, difficulties in diagnosis and diverse current treatment approaches.</p><p> </p>


2021 ◽  
pp. 107815522110677
Author(s):  
Nadjoua Maouche ◽  
Anandagopal Srinivasan ◽  
Heather Leary ◽  
Freya Collings ◽  
Bing Tseu ◽  
...  

Daratumumab is the first anti-CD38 targeting monoclonal antibody approved as monotherapy in multiply relapsed myeloma patients who progressed following prior treatment with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). We present real world data on the efficacy of single agent daratumumab in a cohort of 55 multiply relapsed patients treated in the UK. The median age was 72 years, the majority (96%) received ≥ 3 previous lines of treatment; 54.5% were PI-refractory, 76.4% were IMiD-refractory and 47.2% were double refractory; 20% of patients had high-risk (HR) disease. The overall response rate was 49%. After a median follow up of 9.2 months, the median progression-free survival (PFS) for the total cohort was 5.1 months. Patients who achieved a partial response or better (≥PR) demonstrated a significantly longer PFS compared to those with <PR; 9.8 versus 2.7 months, p < 0.001. Double-refractory patients had an inferior PFS compared to single-refractory patients; 2.7 versus 7.4 months, p = 0.084. High-risk disease was associated with significantly shorter PFS compared to standard-risk (SR); 2.3 versus 6.7 months, p = 0.001. The median overall survival (OS) was 15.9 months. Despite a relatively short PFS seen in the double-refractory and high-risk patients; a favourable median overall survival of 12.9 months was achieved in these groups. Patients who achieved ≥PR, those with a previous objective response to PIs or IMiDs and those with SR disease, all benefited from a significantly longer OS which was not reached. A clear benefit in survival is encouraging in this setting of unmet clinical need and limited treatment options.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4125-4125
Author(s):  
Ryan A. Wilcox ◽  
Andrew L Feldman ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
Steven Ziesmer ◽  
...  

Abstract Abstract 4125 Background: With the exception of angioimmunoblastic T-cell lymphomas, which are thought to derive from follicular helper T cells, little is known about the cell of origin for the most common peripheral T-cell lymphoma (PTCL), PTCL-unspecified (PTCL-U). Following appropriate antigenic stimulation, naïve CD4+ T helper (TH) cells differentiate into effector cells that secrete TH cytokines under the transcriptional regulation of subset-specific transcription factors. Methods: PTCL-U patients (n=53) from a single institution were retrospectively identified and immunohistochemical analysis of Foxp3, T-bet and GATA-3 expression performed on diagnostic biopsy specimens. Immunohistochemical staining was reviewed in a blinded fashion by a hematopathologist and all specimens with greater than 10% staining were scored as positive. Transcription factor expression was correlated with patient characteristics and clinical outcomes. Results: GATA-3 expression was observed in 22 (42%) patients, T-bet expression in 17 (32%) patients and Foxp3 expression in 4 (7%) patients. In order to determine the prognostic significance of GATA-3 or T-bet expression, overall survival was compared between patients with GATA-3 (or T-bet) positive or negative tumors. The median overall survival (OS) was 2 years (95% confidence interval 0.7–12.8 years) for patients with GATA-3 negative tumors, compared with a median OS of 0.9 years (95% confidence interval 0.5–1.2 years, p=0.02) for GATA-3 positive cases. The median overall survival was 1.6 years (95% confidence interval 1.0–6.8 years) for patients with T-bet negative tumors, compared with a median overall survival of 0.7 years (95% confidence interval 0.3–0.9 years, p=0.005) for T-bet positive cases. As a subset of tumors coexpressed GATA-3 and T-bet, both of which are adverse prognostic factors, we examined survival outcomes between those patients with tumors expressing either GATA-3 or T-bet (n=29) and those with tumors which do not express either transcription factor (n=24). The median OS and PFS observed for patients with positive tumors was 0.7 years (95% confidence interval 0.6–1.1 years) and 0.7 years (95% confidence interval 0.5–0.9 years), respectively. In contrast, patients with GATA-3/T-bet negative tumors experienced markedly superior survival, with a median OS and PFS of 3.8 years (95% confidence interval 1.6–12.9 years, p<0.0001) and 2.0 years (95% confidence interval 1.5–12.8 years, p<0.0001), respectively. Four-year estimates of overall and progression-free survival were less than 10% for patients with GATA-3/T-bet positive tumors, whereas 4-year OS and PFS were 49% and 32%, respectively, for those with negative tumors. Both GATA-3 and T-bet expression were associated with advanced age and tumor stage. Therefore, we analyzed GATA-3/T-bet expression as a prognostic factor for survival on both univariate and multivariate analyses, adjusting for pertinent risk factors, including patient age and tumor stage. On univariate analysis, GATA-3/T-bet expression was associated with inferior overall survival (hazard ratio 4.4, 95% confidence interval 2.1–10.4, p<0.0001). Patient age (>60 years), poor performance status (ECOG performance status >1), and stage III/IV disease were also associated with inferior overall survival on univariate analysis. However, when adjusting for these latter adverse prognostic factors on multivariate analysis, GATA-3/T-bet expression remained an independent predictor of poor overall survival in PTCL-U (adjusted hazard ratio 3.2, 95% confidence interval 1.4–8.5, p=0.008). Similarly, when adjusting only for high-risk features (>2 adverse prognostic factors), as defined by the Prognostic Index in PTCL-U (PIT), GATA-3/T-bet expression remained an independent predictor of inferior overall survival on multivariate analysis (adjusted hazard ratio 4.9, 95% confidence interval 2.2–11.5, p<0.0001). Conclusions: GATA-3 and T-bet expression identify subsets of high-risk PTCL-U patients who may benefit from alternative treatment strategies. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 654-654
Author(s):  
Qiong Yang ◽  
Fangxin Liao ◽  
Shousheng Liu ◽  
Chang Jiang ◽  
Wen-zhuo He ◽  
...  

654 Background: A curative hepatic or pulmonary metastasectomy for colorectal carcer is a generally accepted procedure. However, the value of noncurative locoregional therapy for unresectable metastatic colorectal carcer was not well defined. Methods: Of 1,174 patients with unresectable colorectal cancer from 2003 to 2014 retrospectively reviewed, 62 patients received curative regional treatment, 290 patients received locoregional therapy, and 822 patients received standard chemotherapy. Propensity score matching was used to adjust the balance of baseline data between locoregional therapy arm and chemotherapy arm. Kaplan-Meier survival analyses were based on data after propensity score matching. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. Results: After propensity score matching, 544 patients were included in this study, 272 in locoregional therapy arm and 272 in chemotherapy arm, respectively. Locoregional therapy included metastasectomy, radiofrequency ablation, percutaneous microwave coagulation therapy and radioactive particle implantation. The addition of locoregional therapy to chemotherapy significantly improved the overall survival with median overall survival 38.73 months (95%CI 34.93-42.54 months) in locoregional therapy arm versus 19.8 months (95%CI 18.06-21.54 months) in chemotherapy arm, respectively, p<0.001. 9 factors were associated with overall survival by univariate analysis, which include primary tumor site, initial stage at first diagnosis, pathological grading, target organ of regional treatment, CA199 and LDH at diagnosis of advanced disease, CEA, CA199 and LDH before regional treatment. Furthermore, CEA (>5ng/ml) and LDH (>245U/L) before regional treatment were identified as independent poor prognostic factors by multivariate analysis. Median overall survival according to the presence of 0, 1, or 2 factors was 49.4 months, 35.7 months, and 27 months. Conclusions: Unresectable metastatic colorectal cancer also benefited from locoregional therapy. Two pre-locoregional treatment risk factors could select the patients most likely to benefit from this strategy.


2021 ◽  
pp. 1-11

OBJECTIVE In the era in which more patients with greater numbers of brain metastases (BMs) are being treated with stereotactic radiosurgery (SRS) alone, it is critical to understand how patient, tumor, and treatment factors affect functional status and overall survival (OS). The authors examined the survival outcomes and dosimetry to critical structures in patients treated with Gamma Knife radiosurgery (GKRS) for ≥ 25 metastases in a single session or cumulatively over the course of their disease. METHODS A retrospective analysis was conducted at a single institution. The institution’s prospective Gamma Knife (GK) SRS registry was queried to identify patients treated with GKRS for ≥ 25 cumulative BMs between June 2013 and April 2020. Ninety-five patients were identified, and their data were used for analysis. Treatment plans for dosimetric analysis were available for 89 patients. Patient, tumor, and treatment characteristics were identified, and outcomes and OS were evaluated. RESULTS The authors identified 1132 patients with BMs in their institutional registry. Ninety-five patients were treated for ≥ 25 cumulative metastases, resulting in a total of 3596 tumors treated during 373 separate treatment sessions. The median number of SRS sessions per patient was 3 (range 1–12 SRS sessions), with nearly all patients (n = 93, 98%) having > 1 session. On univariate analysis, factors affecting OS in a statistically significant manner included histology, tumor volume, tumor number, diagnosis-specific graded prognostic assessment (DS-GPA), brain metastasis velocity (BMV), and need for subsequent whole-brain radiation therapy (WBRT). The median of the mean WB dose was 4.07 Gy (range 1.39–10.15 Gy). In the top quartile for both the highest cumulative number and highest cumulative volume of treated metastases, the median of the mean WB dose was 6.14 Gy (range 4.02–10.15 Gy). Seventy-nine patients (83%) had all treated tumors controlled at last follow-up, reflecting the high and durable control rate. Corticosteroids for tumor- or treatment-related effects were prescribed in just over one-quarter of the patients. Of the patients with radiographically proven adverse radiation effects (AREs; 15%), 4 were symptomatic. Four patients required subsequent craniotomy for hemorrhage, progression, or AREs. CONCLUSIONS In selected patients with a large number of cumulative BMs, multiple courses of SRS are feasible and safe. Together with new systemic therapies, the study results demonstrate that the achieved survival rates compare favorably to those of larger contemporary cohorts, while avoiding WBRT in the majority of patients. Therefore, along with the findings of other series, this study supports SRS as a standard practice in selected patients with larger numbers of BMs.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2059-2059 ◽  
Author(s):  
Stephanie E Combs ◽  
Denise Bernhardt ◽  
Sebastian Adeberg ◽  
Klaus K Herfarth ◽  
Andreas Unterberg ◽  
...  

2059 Background: The prospective phase I/II CINDERELLA trial investigates toxicity and effectiveness of a dose escalated reirradiation with carbon ions in patients with recurrent gliomas. Methods: Following a dose escalating protocol, 52 patients with WHO°II-IV gliomas were irradiated with carbon ions with doses of 3 Gy (RBE) in 10 – 16 fractions in 7 dose leels. Median age was 42 years (range: 28 - 69) with 19 female and 33 male participants. Forty-one patients were diagnosed with WHO°III/IV gliomas and 11 patients with WHO°II gliomas. At the time of reirradiation, all patients showed contrast-enhancing recurrences. MRI-based treatment planning encompassed the contrast enhancing lesion (GTV) with additional safety margins of 5 mm (CTV) and 3 mm (PTV). Clinical follow-up visits including contrast-enhanced MRI were scheduled every two months. We used RANO-criteria for diagnosis of progression. Survival rates were analyzed with Kaplan-Meier estimator. Relevant prognostic factors were determined with log rank-test, and toxicity was classified according to CTCAE v4.0. Results: Median time between first irradiation and reirradiation was 9 months (range: 7 – 228). PTV size was 12 – 310 ml. During follow-up ≥°3 toxicities were not observed. Follow-up MRI suggested radiation necrosis in 4 patients. Median overall survival was 352 days and was not influenced by age, gender or radiation dose. A significant trend for improved survival rates was seen in patients with small target volumes (480 days [PTV < 75ml] vs. 322 days [PTV > 75ml], p = 0.06) and initial low grade histology (497 days [WHO °II] vs. 322 days [WHO°III/IV], p = 0.069). During follow-up, 45 patients had local progression, while clinical deterioration was not seen. Median local progression-free survival was 138 days. Twenty-eight patients received chemo-/immunotherapy after reirradiation. Of those, 14 patients were treated with bevacizumab. Progression after reirradiation did not influence overall survival significantly. Conclusions: Carbon ion re-irradiation with 10-16 fractions of 3 Gy for patients with recurrent gliomas is safe; no dose limiting toxicities were observed. Median overall survival with approximately one year is high in comparison to other treatment options. It remains unclear if RANO-criteria is securing the diagnosis of therapy failure after carbon ion reirradiation. Further randomized controlled trials must be awaited to evaluate the effectiveness of reirradiation of carbon ions compared to other treatment options. Clinical trial information: NCT01166308.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14047-e14047
Author(s):  
María Ángeles Vaz Salgado ◽  
Isaac Ceballos Lenza ◽  
Sonia Del Barco Berron ◽  
Oscar Gallego Rubio ◽  
Regina Gironés Sarrió ◽  
...  

e14047 Background: Glioblastoma (GBM) is the most common brain primary tumor. Almost all patients have recurrent disease after initial treatment with surgery, radiotherapy and chemotherapy. After disease recurrence, there is no standardized treatment and reoperation is common but there is no proven benefit in randomized trials. Here we retrospectively review the Spanish national database to identify the frequency of reoperations in recurrent GBM and to analyze the impact of surgery on survival in this setting. Methods: We retrospectively reviewed relapsed GBM patients from the Spanish national database RETSINE (Registro Nacional Español de Tumores del Sistema Nervioso Central) supported by the GEINO group. Kaplan-Meier curves and log rank test were used to compare survival. Results: The number of patients with recurrent GBM analyzed was 538, 40% were women and 60% were men. The MGMT status was: methylated 30.9%, unmethylated 33.8%, unknown 35.3%. A total of 89.9% of the patients received radiotherapy and 88.7% received chemotherapy after initial surgery. The median progression-free survival until first recurrence was 7.63 months (IC95% 6.97-8.29). Median overall survival (OS) from GBM diagnosis was 11.96 months (IC95% 10.69- 23.23). At the time of the first progression, surgery was performed in 75 patients, (13.9%), 18 cases were treated with a second radiotherapy (3.3%), second line CT was administered in 268 patients (49.6%), 221 cases received only chemotherapy (40.9%), 47 cases were treated with both surgery and chemotherapy (8.7%); 28 were treated with surgery without chemotherapy (5.2%), 19 cases had a surgery procedure but we have no data about CT, 223 cases did nor receive CT nor surgery (41%). Median overall survival after relapse was 4.06 months (IC95% 3.25-4.87). For those patients without surgery, median OS after relapse was 3.1 m (IC95% 2.84-3.71) and for patients reoperated, median OS was 12.2 m (IC95% 10.8-13.52) p=0.00 Median overall survival after relapse was 1.7 months (IC95% (IC 1.31-2.08) for patients that did not had CT and 7.03 for those with CT(IC95%5.9-8.16) p=0.00 We also compared the results from different treatment options: median OS was 1.6 m (IC95% 1.11-2.08), for patients without treatment; 6.33 m (IC95% 5.34-7.32) for patients treated with chemotherapy; 12.2 m (IC95%11.05-13.34) for patients treated with surgery and CT;12.1 m(IC95% 4.64-19.55) for patients with surgery. Conclusions: Recurrent glioblastoma is a very aggressive disease. In this retrospective study, patients treated with surgery and surgery and CT could have a clinical benefit in terms of survivalin comparison with those not treated with reoperation. Randomized prospective trials are needed to clarify the role of surgery in recurrent GBM.


Sign in / Sign up

Export Citation Format

Share Document