scholarly journals HOUT-18. TREATMENT STRATEGIES FOR GLIOBLASTOMA IN OLDER PATIENTS: AGE IS JUST A NUMBER

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi115-vi116
Author(s):  
Michael Youssef ◽  
Ethan Ludmir ◽  
Jacob Mandel ◽  
Akash Patel ◽  
Ali Jalali ◽  
...  

Abstract BACKGROUND Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in clinical trials (including EORTC 22981) as well as their historically-poor overall survival. METHODS Retrospective chart review was conducted at a single high-volume cancer center for newly-diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS A total of 158 newly-diagnosed GBM patients aged 65 years and older were identified. 144 patients (91.1%) underwent radiation therapy. One-hundred thirty patient (90.3%) received concurrent temozolomide with radiotherapy. A minority of patients (23%) discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temodar. The median overall survival (OS) time for our cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p=0.002, HR 0.46; 95% CI: 0.63–0.82), completing planned course of radiation (p=0.01, HR 0.29; 95% CI: 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p=0.01, HR 2.62; 95% CI: 1.67–4.12) were associated with improved OS. CONCLUSIONS Our cohort of elderly GBM patients were predominately treated with a standard of care based on EORTC 22981. Despite their age, these patients tolerated treatment well and had a favorable overall survival compared to outcomes reported for patients treated on EORTC 22981. Using age alone as the reason to de-escalate treatment or as an exclusionary criteria in clinical trials should be discouraged.

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.


Author(s):  
David Fortin ◽  
David. R. Macdonald ◽  
J. Gregory Cairncross ◽  
Larry Stitt

Background:We report survival and pretreatment prognostic factors for survival and chemosensitivity in 53 oligodendrogliomas treated with PCV (procarbazine, lomustine and vincristine) chemotherapy.Methods:A total of 53 patients with histologically proven oligodendroglioma, anaplastic oligodendroglioma or oligo-astrocytoma and treated with PCVwere extracted from the London Regional Cancer Center database. A retrospective review was conducted to evaluate overall survival and pretreatment prognostic factors for survival and chemosensitivity.Results:The median survival time from diagnosis was 123.6 months. The overall five- and ten-year survival rates were 72.7% and 52.7% respectively. Age <40, seizure as an initial symptom, absence of cognitive deficit and presence of a homogeneous hypodense lesion without contrast enhancement on the initial pretreatment CT scan were all factors independently associated with favorable outcome. The presence of increased cellularity, pleomorphism, mitosis, vascular proliferation and grading as an anaplastic lesion using these surrogates on pathological assessment, were all associated with an unfavorable outcome in univariable analysis. In multivariable analysis, only the anaplastic grading and presence of increased cellularity were significant determinants of unfavorable survival. The only factor adversely associated with chemosensitivity was the presence of a focal symptom at presentation.Conclusion:Overall survival is significantly longer in oligodendroglial lesions than in fibrillary astrocytic tumors. A two tier grading system using standard morphological features seems accurate in predicting outcome in these patients. The presence of a neoplastic astrocytic component does not seem to impact the outcome. No clinical, radiological or pathological factor could be identified to reliably predict chemotherapy response.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1047
Author(s):  
Justin Z. Amarin ◽  
Razan Mansour ◽  
Sura Al-Ghnimat ◽  
Maysa Al-Hussaini

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Jennifer R. Brown

Abstract Despite the widespread use of highly effective chemoimmunotherapy (CIT), fludarabine-refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical problem associated with poor overall survival (OS). The traditional definition, which includes those patients with no response or relapse within 6 months of fludarabine, is evolving with the recognition that even patients with longer remissions of up to several years after CIT have poor subsequent treatment response and survival. Approved therapeutic options for these patients remain limited, and the goal of therapy for physically fit patients is often to achieve adequate cytoreduction to proceed to allogeneic stem cell transplantation (alloSCT). Fortunately, several novel targeted therapeutics in clinical trials hold promise of significant benefit for this patient population. This review discusses the activity of available and novel therapeutics in fludarabine-refractory or fludarabine-resistant CLL as well as recently updated data on alloSCT in CLL.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6056-6056
Author(s):  
J. K. Keller ◽  
J. Bowman ◽  
J. A. Lee ◽  
M. A. Mathiason ◽  
K. A. Frisby ◽  
...  

6056 Background: Less than 5% of newly diagnosed cancer patients are accrued into clinical trials. In the community setting, the lack of appropriate clinical trials is a major barrier. Our prospective study in 2004 determined that 58% of newly diagnosed adult cancer patients at our community-based cancer center didn’t have a clinical trial available appropriate for their disease stage. Among those with clinical trials, 23% were subsequently found to be ineligible (Go RS, et al. Cancer 2006, in press). However, the availability of clinical trials may vary from year to year. Methods: A retrospective study was conducted to determine what clinical trials were available for newly diagnosed adult cancer patients at our institution from June 1999-July 2004. The study also investigated the proportions of newly diagnosed patients who had a clinical trial available appropriate for type and stage of disease and patients accrued. Results: Over the 5-year period, 207 (82, 87, 99, 102, 117, years 1–5, respectively) trials were available. Most (50.7%) trials were for the following cancers: breast (15.5%), lung (13.5%), head and neck (7.7%), colorectal (7.2%) and lymphoma (6.8%). ECOG (53%), RTOG (26%), and CTSU (9%) provided the majority of the trials. A total of 5,776 new adult cancer patients were seen during this period. Overall, 60% of the patients had a trial available appropriate for type and stage of their cancer, but only 103 (3%) were enrolled. There was a significant upward trend in the proportions of patients with available trials over the years (60.2%, 55.9%, 59.2%, 60.7%, 63.9%, years 1–5, respectively; Mantel-Haenszel P=.008). The proportion of patients with a trial available was highest for prostate (97.3%), lung (90.9%), and breast (73.9%), and lowest for melanoma (17.1%), renal (11.6%), and bladder (7.2%). The majority of patients accrued to trials had the following cancers: breast (32%), lung (17%), lymphoma (9%), colon (7%), and prostate (5%). Conclusions: Nearly half of the newly diagnosed adult patients at our center had no trials available appropriate for type and stage of their cancers. It is likely that if strict clinical trial eligibility criteria were applied, approximately 2/3 of our patients would not be eligible for a clinical trial. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Ishwaria Mohan Subbiah ◽  
Vivek Subbiah ◽  
Ahmed Omar Kaseb ◽  
Filip Janku ◽  
Jennifer J. Wheler ◽  
...  

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease > 4 months. Prognostic factors analyzed include Hg < 10.5 g/dL, elevated CA 19-9 (>47 ng/mL), ECOG PS > 3, LDH > 618 IU/L, albumin < 3.5 g/dL, platelets < 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 414-414
Author(s):  
Kanika Gupta ◽  
Ehab El Bahesh ◽  
Antoine Nafez Finianos ◽  
Brandon Clark ◽  
Samuel Simmens ◽  
...  

414 Background: Bladder cancer is the sixth most common malignancy in the United States. Urothelial carcinoma makes up 90% of bladder cancer histology, which may be pure or mixed. It includes adenocarcinoma (Ad), squamous (SqC), glandular, sarcomatoid (St), micropapillary, small cell (SC) and plasmacytoid variants. Pure non-urothelial cancers have worse overall survival compared to urothelial cancer with mixed histologic features. However, little research has been done to characterize pure non-urothelial histologies, and there are no randomized clinical trials evaluating treatment modalities for non-urothelial cancers. This retrospective study characterizes pure non-urothelial cancers and their treatments. Methods: A retrospective chart review of the last 10 years was performed using data from the George Washington University Cancer Center Tumor Registry Data. Statistical analysis was done using the Fisher’s test and Kaplan-Meier survival curves. Results: Out of 449 consecutive patients with bladder cancers, 19 patients had pure non-urothelial carcinoma (4.2%): 7 SqC, 6 Ad, 3 SC, 2 lymphoma (Ly), and 1 St. SqC and Ad were more likely than SC to be diagnosed at an advanced stage (p = 0.04), with median age of diagnosis at 53.5 years for Ad, 68 years for SC and 69 years for Sq. None of the SC metastasized. Primary treatment for 94% of patients was a surgical intervention (9 TURBT, 2 partial cystectomy, 2 radical cystectomy, and 2 nephroureterectomy); 1 received neoadjuvant therapy. 11 patients received adjuvant chemotherapy – 7 with gemcitabine-based regimens and 10 with platinum-based regimens. While not statistically significant, median overall survival varied – 404 days for Ad, 213 days for SqC, and 1567 days for SC. Conclusions: SC was a more favorable histology when compared to SqC or Ad, presenting at an earlier stage with lower incidence of metastasis that perhaps reflected the improved overall survival. Identifying patients with more aggressive disease earlier allows for the potential role for more aggressive therapies that may result in improved outcomes. While the sample size is small, it identifies characteristics and potential differences between bladder cancer with rare histologies.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Katsuyuki Shirai ◽  
Michael R. Siedow ◽  
Arnab Chakravarti

Malignant gliomas have a poor prognosis despite advances in diagnosis and therapy. Although postoperative temozolomide and radiotherapy improve overall survival in glioblastoma patients, most patients experience a recurrence. The prognosis of recurrent malignant gliomas is dismal, and more effective therapeutic strategies are clearly needed. Antiangiogenesis is currently considered an attractive targeting therapy for malignant gliomas due to its important role in tumor growth. Clinical trials using bevacizumab have been performed for recurrent glioblastoma, and these studies have shown promising response rates along with progression-free survival. Based on the encouraging results, bevacizumab was approved by the FDA for the treatment of recurrent glioblastoma. In addition, bevacizumab has shown to be effective for recurrent anaplastic gliomas. Large phase III studies are currently ongoing to demonstrate the efficacy and safety of the addition of bevacizumab to temozolomide and radiotherapy for newly diagnosed glioblastoma. In contrast, several other antiangiogenic drugs have also been used in clinical trials. However, previous studies have not shown whether antiangiogenesis improves the overall survival of malignant gliomas. Specific severe side effects, difficult assessment of response, and lack of rational predictive markers are challenging problems. Further studies are warranted to establish the optimized antiangiogenesis therapy for malignant gliomas.


2020 ◽  
Author(s):  
MRM Silva ◽  
RC Bonadio ◽  
GDR Matos ◽  
D Toloi ◽  
M Nardo ◽  
...  

AbstractBackgroundStandard treatment for pediatric patients with localized osteosarcoma include high-dose methotrexate (HDMTX) and cure rates greater than 60% are observed. In adult patients, however, the toxicity profile limits the use of HDMTX and it is usually excluded from chemotherapy protocols for this group. We aimed to evaluate the outcomes of adult patients with localized osteosarcoma treated with chemotherapy without methotrexate.MethodsIn this retrospective cohort, we evaluated adult patients with high-grade osteosarcoma who received treatment with chemotherapy without methotrexate in a reference cancer center from 2007 to 2018. Outcomes analyzed were recurrence-free survival (RFS), overall survival (OS), and prognostic factors associated with overall survival.ResultsA total of 48 patients had localized disease and received treatment with chemotherapy without methotrexate. The majority of them received chemotherapy with a combination of cisplatin and doxorubicin (N=42, 87.5%). Median age was 27 years. (range 16.8 – 66.7) With a median follow-up of 29.2 months, median RFS was 29.9 months. Median OS was not reached. 5-year RFS and OS rates were 35.1% (95% CI 20.3 – 50.2%) and 71.6% (95% CI 52.3 – 84.2%), respectively. Patients who received cumulative doses of doxorubicin ≥ 375 mg/m2 had better OS than those who received lower doses (HR 0.26, 95% CI 0.07 – 0.94, P = 0.041). Similarly, patients who received ≥ 6 cycles of neoadjuvant/ adjuvant cisplatin tended to have better OS than those who received < 6 cycles (HR 0.30, 95% CI 0.08 – 1.09, P = 0.069).Nineteen patients received less than 6 cycles of cisplatin and doxorubicin mainly because of grade 3 or 4 toxicities (11), disease progression (6),patient refusal(1), physician choice(1).ConclusionIn our study, adult patients with localized high-grade osteosarcoma who were treated with chemotherapy without methotrexate had unfavorable outcomes. The cumulative doxorubicin dose and the number of cisplatin/doxorubicin cycles were associated with improved OS. The investigation of additional treatment strategies is of utmost importance to improve adult patients outcomes.


Sign in / Sign up

Export Citation Format

Share Document