An institutional evaluation of radiotherapy with concurrent and adjuvant temozolomide exclusively in grade III gliomas

Performance Status ◽

Complete Response ◽

Who Grade ◽

Medical College ◽

Significant Toxicity ◽

Grade 3 ◽

Grade Iii

Background: Gliomas are the most common tumors that develop from glial cells in the brain. As per WHO classification, grade III (high-grade) gliomas are usually treated by surgery followed by radiotherapy. Concurrent and adjuvant chemotherapy with temozolomide (TMZ) is showing new hope in the management.Methods: Prospective study was conducted in 20 WHO grade III glioma patients at GSL medical college and general hospital for a period of 2 years (August 2019 to July 2021) to evaluate the role of concurrent and adjuvant TMZ with radiation in the treatment of grade III gliomas. The primary objectives of the study were to determine toxicity and response rates in our set of patients. The secondary objectives were to determine progression-free survival and overall survival.Results: Majority were males (80%) in the age group of 30 to 49 (75%). 40% of gliomas were in the temporal lobe. Headache was the most presenting symptom (60%) followed by seizures (35%).70 to 80 Karnofsky performance status/ KPS score was seen in 70% of cases. None of the patients in the study had grade 3 or 4 toxicities. 40% had a complete response according to MacDonald’s criteria. At a median follow-up of 10 months, 25% of patients had disease progression and 1yr overall survival was 95%.Conclusions: TMZ combined with radiation was well tolerated in our set of patients with grade III gliomas without any significant toxicity.

Ultrafractionated radiation therapy (3x per day) for glioblastoma: Preliminary results of a phase II study

10.1200/jco.2006.24.18_suppl.1570 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1570-1570

Author(s):

P. D. Beauchesne ◽

L. Taillandier ◽

V. Bernier ◽

M. Djabri ◽

X. Michel ◽

...

Keyword(s):

Radiation Therapy ◽

Phase Ii ◽

High Efficiency ◽

Phase Ii Study ◽

Performance Status ◽

Who Grade ◽

Primary Endpoints ◽

Grade 3

1570 Background: Ultrafractionation radiation therapy consists in irradiating cells or tumors several times daily, delivering low doses at which hyperradiosensitivity occur. We recently reported the high efficiency of ultrafractionation radiotherapy in glioma cell lines and xenografts, and are now conducting a phase II clinical trial to determine the effect of an ultrafractionation regimen for glioblastoma patients. Methods: A prospective, multicenter, phase II study has opened for accrual in September 2003. Patients over 18 years of age who are able to give informed consent and have histologically proven, newly diagnosed and unresectable, supratentorial glioblastoma (WHO grade IV) are eligible. Three doses of 0.75 Gy spaced by at least four hours are delivered daily, five days a week for six consecutive weeks for a total of 67.5 Gy. Conformal irradiation includes the tumor bulk including a margin of 2.5 cm. Tolerance and toxicity are the primary endpoints; survival and progression-free survival are secondary endpoints. Results: To date 25 patients have been enrolled in this study, 19 currently evalualbe: 11 men and 8 women, median age 58 (range 37 to 76), median Karnofsky performance status (80 range from 70 to 100). The median time between histological diagnosis and the start of treatment is 7 weeks. The ultrafractionated radiation therapy has been well tolerated; no acute grade 3 and/or 4 CNS toxicity has been observed. Minor responses at the end of irradiation were seen in 5 patients. Median survival from initial diagnosis was 13.5 months, nine patients remain alive. Conclusions: Ultrafractionated radiation therapy is safe and well tolerated. No acute CNS toxicitiy has been observed. Overall survival of over 13 months for patients without prior debulking surgery compares favorably with other reports. Updated definitive results will be presented. No significant financial relationships to disclose.

PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03765-z ◽

2021 ◽

Author(s):

Jonathan Weller ◽

Sophie Katzendobler ◽

Philipp Karschnia ◽

Stefanie Lietke ◽

Rupert Egensperger ◽

...

Keyword(s):

Stereotactic Biopsy ◽

Tumor Volume ◽

Who Grade ◽

Free Survival ◽

First Relapse ◽

Pcv Chemotherapy ◽

Grade 3 ◽

Histological Progression

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years

Radiation Oncology ◽

10.1186/s13014-019-1389-7 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Makoto Ohno ◽

Yasuji Miyakita ◽

Masamichi Takahashi ◽

Hiroshi Igaki ◽

Yuko Matsushita ◽

...

Keyword(s):

Elderly Patients ◽

Dna Methyltransferase ◽

Performance Status ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Hypofractionated Radiotherapy ◽

Methylguanine Dna Methyltransferase ◽

Grade 3

Abstract Background and purpose The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev). Materials and methods Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%. Results Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%). Conclusion Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.

Phase III study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with metastatic pancreatic adenocarcinoma (mPC): Subgroup analysis of Canadian pts from the MPACT trial.

10.1200/jco.2015.33.3_suppl.439 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 439-439

Author(s):

Mustapha Ali Tehfe ◽

Scot D. Dowden ◽

Hagen F. Kennecke ◽

Robert Hassan El-Maraghi ◽

Bernard Lesperance ◽

...

Keyword(s):

Performance Status ◽

Pancreatic Head ◽

Dose Intensity ◽

Phase Iii ◽

First Line ◽

Common Grade ◽

Grade 3 ◽

Intent To Treat

439 Background: Weekly nab-P + Gem is a new option for first-line treatment (Tx) of mPC. In the MPACT trial, nab-P/Gem demonstrated superior overall survival (OS; primary endpoint) vs Gem alone as first-line Tx of mPC (Table). Here we report a subgroup analyses evaluating the efficacy and safety outcomes with nab-P + Gem vs Gem alone from the Canadian cohort of the MPACT trial. Methods: Previously untreated pts (N = 861) with mPC were randomized 1:1 (stratified by Karnofsky Performance Status [KPS], region, and the presence of liver metastases) to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle or Gem 1000 mg/m2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of each 28-day cycle (cycle ≥ 2). Results: 63 pts from Canada enrolled in the MPACT trial. Baseline pt characteristics were well balanced. Median age was 61 years and KPS was similar for both groups and comparable to the intent-to-treat (ITT) populations. Primary lesion in the pancreatic head was more common among pts in the nab-P + Gem vs Gem arm (55% vs 30%); use of biliary stent was similar (33% nab-P + Gem; 27% Gem). Median OS and progression-free survival (PFS) were longer with nab-P + Gem vs Gem (Table). Median Tx duration was 4.2 mo with nab-P + Gem vs 3.2 mo with Gem. Use of subsequent therapy was 30% in the nab-P + Gem arm vs 43% in the Gem arm. The median relative dose intensity for Gem was similar in each arm (81% nab-P + Gem vs 85% Gem). The most common grade ≥ 3 AEs for nab-P + Gem vs Gem were neutropenia (22% vs 10%), fatigue (34% vs 33%), and neuropathy (25% vs 0%). Conclusions: Canadian pts participating in MPACT were similar to the ITT population and nab-P + Gem was well tolerated and showed improved median OS, PFS, and ORR vs Gem alone, although not statistically significant (likely due to the small number of pts). Clinical trial information: NCT00844649. [Table: see text]

A randomized phase II trial comparing different schedules of nab-paclitaxel (nabP) combined with gemcitabine (GEM) as first line treatment for metastatic pancreatic adenocarcinoma (mPDAC).

10.1200/jco.2017.35.15_suppl.4100 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4100-4100 ◽

Cited By ~ 2

Author(s):

Philippa Corrie ◽

Wendi Qian ◽

Bristi Basu ◽

Juan W. Valle ◽

Stephen Falk ◽

...

Keyword(s):

Cytidine Deaminase ◽

Performance Status ◽

Objective Response ◽

Pancreatic Head ◽

Randomized Phase Ii ◽

Secondary Endpoints ◽

Grade 3 ◽

Age Range

4100 Background: NabP+GEM chemotherapy improves survival compared with GEM monotherapy as treatment for mPDAC. A PDAC mouse model suggested that nabP potentiates GEM activity by reducing cytidine deaminase levels and scheduling may be critical to optimise clinical benefit. Methods: Patients (pts) were randomised to receive standard concomitant (CON) nabP+GEM or sequential (SEQ) administration, with nabP given 24 hours before GEM. After 6 cycles, pts benefiting from treatment could continue the same regimen until disease progression. The primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints included safety, objective response rate (ORR), overall survival (OS) and quality of life (QoL). Serial blood and baseline tumour samples were collected for exploratory biomarkers. Results: Between March 2014 and 2016, 146 pts (71 SEQ, 75 CON) were recruited. Median age (range) was 66 (45-82) years; Karnofsky performance status was 70 (in 12% pts), 80 (27%), 90 (38%) or 100 (24%); 47% had pancreatic head primaries; 84% had liver metastases. Median no. cycles received was 4 SEQ, 3 CON; 51 pts (35%) received ≥6 cycles of treatment (42% SEQ, 28% CON). A 24+2hr interval was achieved in > 90% SEQ admin. Grade ≥3 adverse events experienced by ≥10% pts (SEQ, CON) were neutropaenia (54%, 30%; p = 0.003), febrile neutropaenia (12%, 12%), fatigue (22%, 15%), vomiting (7%, 11%) and anaemia (10%, 5%). G-CSF was administered at local investigator's discretion to 35 pts (23 SEQ, 12 CON; p = 0.015). To date, 112 pts have died. 6 month (m) PFS by SEQ and CON arms were 47% and 33%; median PFS were 5.8 and 4.0m; hazard ratio (HR) = 0.66, 95% CI = 0.46-0.95; 12m OS by SEQ and CON arms were 29% and 26%; median OS were 10.1 and 7.9m; HR = 0.88, 95% CI = 0.61-1.29. ORR was 50% SEQ and 33% CON (p = 0.065). Mean baseline QoL Global health status score was 60.6 SEQ and 63.4 CON. The mean change in QoL score from baseline at 24 weeks was -2.1 SEQ and -12.1 CON. Conclusions: Sequential delivery of nabP combined with GEM trended towards improving all clinically relevant efficacy end points: PFS, OS, and ORR. Translational correlates will be reported in due course. Clinical trial information: ISRCTN71070888.

Modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma.

10.1200/jco.2017.35.4_suppl.484 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 484-484 ◽

Cited By ~ 4

Author(s):

Amit Rauthan ◽

Poonam Patil

Keyword(s):

Biliary Tract ◽

Performance Status ◽

Complete Response ◽

Tertiary Hospital ◽

Efficacy And Safety ◽

Good Performance Status ◽

Pancreatic Cancers ◽

Grade 3 ◽

Dose Modifications

484 Background: The treatment of advanced biliary tract adenocarcinoma is based on chemotherapy with Gemcitabine with Cisplatin or Oxaliplatin in various combinations. After seeing the high efficacy of FOLFIRINOX regimen in advanced pancreatic cancers, we studied the efficacy and safety of a modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma. Methods: We retrospectively reviewed patient with advanced biliary tract adenocarcinoma who were treated with modified FOLFIRINOX regimen from April 2013 to March 2016 in a tertiary hospital. The schedule of modified FOLFIRINOX was - Oxaliplatin 85 mg/m2, Irinotecan 150 mg/ m2, Leucovorin 400 mg/m2, and 5 fluorouracil 2400 mg/m2given as a 46-hour continuous infusion, every 2 weeks. All patients received primary prophylactic growth factors. The objective was to evaluate the efficacy and safety of FOLFIRINOX regimen. Results: 20 patients with untreated advanced biliary tract adenocarcinoma were enrolled. The median age was 55 (range 31 to 66 years). All patients had good performance status. 2 patients had a complete response (10%), 8 patients had a partial response (40%), 5 patients had stable disease (25%) and 5 patients had progression (25%). The median progression free survival was 6 months and the median overall survival was 10 months. The major toxicities were grade 3/4 neutropenia (30%), oral mucositis (20%), fatigue (20%) and neuropathy (10%). Dose reduction was required in 30% patients. Conclusions: A modified FOLFIRINOX regimen is an effective regimen in good performance status patients with advanced biliary tract adenocarcinoma. Dose modifications are required to reduce toxicity of the regimen. It needs to be further studied in a phase 3 study in comparison to Gemcitabine based regimens.

Association of immune-related adverse events (irAEs) with improved clinical outcome in sarcoma patients treated with immune checkpoint blockade (ICB).

10.1200/jco.2020.38.15_suppl.11510 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 11510-11510 ◽

Cited By ~ 1

Author(s):

Evan Rosenbaum ◽

Kenneth Seier ◽

Ciara Marie Kelly ◽

Hannah Kiesler ◽

Moriah Martindale ◽

...

Keyword(s):

Adverse Events ◽

Clinical Benefit ◽

Performance Status ◽

Complete Response ◽

Immune Checkpoint Blockade ◽

Improved Outcomes ◽

Comparison Results ◽

Category Comparison ◽

Grade 3

11510 Background: IrAEs are associated with improved clinical outcomes after treatment with ICB in select epithelial malignancies. We hypothesized that sarcoma patients (pts) treated with ICB who developed an irAE would have improved outcomes compared to pts who had no irAE. Methods: Adverse events (AEs) from 3 sarcoma-specific ICB trials (nivolumab plus NKTR-214, pembrolizumab plus epacadostat, and pembrolizumab plus T-VEC) were reviewed. AEs probably or definitely related to ICB were classified as immune- or non-immune-related by the principal investigator. Endpoints of interest included best overall response (BOR) by RECIST 1.1 (complete response [CR]/partial response [PR]), durable clinical benefit (DCB; CR/PR/stable disease [SD] ≥ 16 weeks), and progression-free survival (PFS). Outcomes were stratified by the presence or absence of ≥ 1 irAE of any grade and by grade 1-2, grade 3-4, or no irAE (three-category comparison). Results: A total of 124 pts received ICB on these studies. Median pt age was 56 (range: 13-90); 53% were male; all but one pt had a performance status of ≤ 1. BOR was PR in 12 pts, SD in 41, and PD in 69. 2 pts were not evaluable. 40 pts (32%) had ≥ 1 irAE of any grade, 6 of whom had a grade 3-4 irAE. The most common irAEs (≥ 5% of pts) were rash (15%), arthralgia (11%), myalgia (9%), pruritis (8%), and hypothyroidism (6%). The proportion of pts with a CR/PR was higher in pts with than without an irAE (18% vs. 6%, respectively; P = 0.058). A significantly higher proportion of pts with an irAE had DCB compared to those without (53% and 29%, respectively; P = 0.017). The median PFS of pts with an irAE was 16.6 months compared to 10.6 in those without (P = 0.013). The proportion of pts with a grade 3-4 irAE and a CR/PR was highest (33%) compared to pts with grade 1-2 (15%) or no irAE (6%) (P = 0.048). More pts with grade 3-4 irAE achieved DCB (67%) than grade 1-2 (50%) or no irAE (29%) (P = 0.027). Median PFS was 22.6, 15, and 10.6 weeks in the grade 3-4, grade 1-2, and no irAE groups, respectively (P = 0.047). Conclusions: Approximately one-third of advanced sarcoma pts with ICB-based immunotherapy developed an irAE. As reported previously in select carcinomas, sarcoma pts with irAEs were more likely to have clinical benefit than those without irAEs. Further research is needed to understand the mechanism behind this association and to validate these findings prospectively.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

10.1200/jco.2020.38.15_suppl.9504 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9504-9504 ◽

Cited By ~ 10

Author(s):

Egbert F. Smit ◽

Kazuhiko Nakagawa ◽

Misako Nagasaka ◽

Enriqueta Felip ◽

Yasushi Goto ◽

...

Keyword(s):

Topoisomerase I ◽

Performance Status ◽

Objective Response ◽

Complete Response ◽

Clinical Activity ◽

Antibody Drug Conjugate ◽

Ecog Performance Status ◽

Platinum Based Chemotherapy ◽

Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Phase III Randomized Controlled Trial Comparing the Survival of Patients With Unresectable Hepatocellular Carcinoma Treated With Nolatrexed or Doxorubicin

10.1200/jco.2006.08.4046 ◽

2007 ◽

Vol 25 (21) ◽

pp. 3069-3075 ◽

Cited By ~ 163

Author(s):

Robert G. Gish ◽

Camillo Porta ◽

Lucian Lazar ◽

Paul Ruff ◽

Ronald Feld ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Controlled Trial ◽

Performance Status ◽

Objective Response ◽

Final Analysis ◽

Complete Response ◽

Phase Iii ◽

Study Objective

PurposeThe study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX).Patients and MethodsPatients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score.ResultsAt the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm.ConclusionNOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

An autopsy case of widespread brain dissemination of glioblastoma unnoticed by magnetic resonance imaging after treatment with bevacizumab

Surgical Neurology International ◽

10.25259/sni-183-2019 ◽

2019 ◽

Vol 10 ◽

pp. 137 ◽

Cited By ~ 2

Author(s):

Ridzky Firmansyah Hardian ◽

Tetsuya Goto ◽

Haruki Kuwabara ◽

Yoshiki Hanaoka ◽

Shota Kobayashi ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Tumor Regression ◽

Performance Status ◽

Malignant Gliomas ◽

Diffuse Astrocytoma ◽

Resonance Imaging ◽

Who Grade

Background: Although glioblastoma has been shown to be able to disseminate widely in the intracranially after treatment with bevacizumab without any significant radiological findings, reports on such cases with subsequent autopsy findings are lacking. Case Description: A 36-year-old man presented with a general seizure and a mass of the right frontal lobe, which was diagnosed as diffuse astrocytoma (WHO Grade II). The patient underwent a total of four surgeries from 2005 to 2017. He showed tumor recurrence, progression, and malignant transformation to glioblastoma (GBM) (WHO Grade IV) despite repeated tumor resections, radiotherapy, and chemotherapies with temozolomide and carmustine wafers. Bevacizumab (10 mg/kg body weight) was started following the fourth surgery. After bevacizumab administration, the patient’s clinical condition improved to a Karnofsky performance status (KPS) score of 50–60, and he was stable for several months before finally deteriorating and passing away. Although sequential magnetic resonance imaging (MRI) showed shrinkage of the lesion and a reduction of edema, an autopsy showed widespread tumor invasion that was not revealed on MRI. Neoplastic foci were identified extensively in the cerebral cortex, basal ganglia, pituitary gland, cerebellum, and brainstem, imposing as gliomatosis cerebri. Conclusion: Imaging follow-up of malignant gliomas needs to be interpreted with caution as marked improvement in radiological response after bevacizumab treatment may not be indicating tumor regression. Despite the notable lack of evidence to increase overall survival in GBM patients with bevacizumab, the increase in progression-free survival and the observed relief of symptoms due to a decrease in edema should be considered relevant for patient management.