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Case Report - (2025) Volume 16, Issue 6

Unusually long survival (over 33 years) observed in 61 high-grade glioma patients treated in phase II studies of Antineoplastons A10 and AS2-1

Stanislaw R. Burzynski1*, Tomasz J. Janicki1, Gregory S. Burzynski1, Radoslaw J. Siwiec2 and Samuel W. Beenken3
 
1The Burzynski Clinic, Houston, Texas, USA
2Lubgen Farma, Poland
3Oncology Writings, Calera, Alabama, USA
 
*Correspondence: Stanislaw R. Burzynski, The Burzynski Clinic, USA, Tel: 713-335-5697, Email:

Received: 11-Nov-2025, Manuscript No. ipjnn-25-15774; Editor assigned: 13-Nov-2025, Pre QC No. P-15774; Reviewed: 27-Nov-2025, QC No. Q-15774; Revised: 04-Dec-2025, Manuscript No. R-15774; Published: 11-Dec-2025

Abstract

Background: High-Grade Gliomas (HGGs) are among the most aggressive and deadly primary brain tumors. Standard treatment includes surgery, external beam radiation and temozolomide, which can cause marked toxicity. Despite intensive therapy, the prognosis remains poor.

Objective: To assess long-term outcomes and safety in non-Glioblastoma (non-GBM) HGG patients treated with Antineoplastons A10 and AS2-1 (ANP) at the Burzynski Clinic (BC) under phase II protocols.

Methods: Sixty-one non-GBM HGG patients received intravenous ANP. Eligibility required Karnofsky/Lansky Performance Scores (KPS/LPS) of at least 60 and a life expectancy of at least 2 months. ANP was administered via a subclavian catheter and automated pump. Maximum tolerated doses of A10 and AS2-1 were achieved. Outcomes included objective response, survival and toxicity

Results: As of October 2025, all 61 patients had survived for at least 5 years, with one patient surpassing 33 years. The criteria of a cure was met when 23 patients survived over 12 years. Ages ranged from 1.08 to 62.66 years (median 35.9). KPS/LPS scores ranged from 40 to 90 (median 60). Four patients experienced six Serious Adverse Events (SAE’s) possibly related to ANP (fever without infection, nausea, dizziness and three cases of somnolence); all recovered fully. In a Kaplan-Meier analysis of 310 non-GBM HGG patients treated at BC, median survival was 1.867 years.

Conclusions: ANP therapy shows significant potential for non-GBM HGG, with many long-term survivors and no observed long-term toxicity. This cohort represents the most extensive documented series of HGG survivors with unusually long-term survivals. Findings support ANP as a viable treatment option.

Keywords

Antineoplastons; Glioma; High-grade glioma; Long-term survival; Phase II studies

Introduction

Arising from glial progenitor cells, gliomas are a diverse group of primary tumors located within the Central Nervous System (CNS) [1]. Mainly affecting older adults, gliomas accounted for 22.9% of all newly diagnosed primary brain and other CNS tumors between 2017 and 2021 in the USA. Among these brain tumors, 14.0% of all tumors and 51.5% of all malignant tumors were Glioblastoma (GBM), a High-Grade Glioma (HGG). In recent years, GBM has caused the deaths of over 7,550 Americans annually [2].

The diagnosis of HGG involves clinical signs and symptoms, imaging studies, histological examination and molecular analysis of tumor tissue. The imaging study of choice is Magnetic Resonance Imaging (MRI) of the brain, which can be performed with or without gadolinium contrast. A brain MRI shows the anatomical relationship between the tumor and surrounding tissue, as well as tumor location, size and the extent of edema and necrosis.

Historically, brain tumor classification has relied on histological features. As a result, classification has been limited by diagnostic discrepancies, variable outcomes and different responses to therapy. However, recent advances in molecular profiling have enabled the integration of both morphological and molecular characteristics of brain tumors [3]. The 2021 World Health Organization (WHO) classification of CNS tumors introduced new types and subtypes often defined by their key molecular features [4]. Additionally, gliomas were categorized by age, with distinctions made between adult and pediatric types [5-7]. Adult-type diffuse HGG was subdivided based on two molecular markers: Isocitrate Dehydrogenase (IDH) and 1p/19q codeletion. Pediatric-type diffuse HGG was subdivided based on tumor location, histone mutations (including H3 K27-altered and H3 G34-mutant) and DNA methylation profiles [5].

Adult-type diffuse gliomas include 1) astrocytoma, IDH-mutant (WHO grades 2-4); 2) oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grades 2-3); and 3) GBM, IDH-wildtype (WHO grade 4). Pediatric-type diffuse high-grade gliomas included 1) diffuse midline glioma, H3 K27-altered (WHO grade 4); 2) diffuse hemispheric glioma, H3 G34-mutant (WHO grade 4); 3) diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (WHO grade 4) and 4) infant-type hemispheric glioma [5].

HGGs are among the most aggressive and deadly types of brain tumors. They present with a wide range of clinical signs and symptoms that significantly reduce patients' Health-Related Quality of Life (HRQoL). These signs and symptoms can vary depending on tumor location and progression. However, common signs and symptoms include severe or chronic headaches, epileptic seizures, muscle weakness, numbness, nausea, vomiting, drowsiness, visual disturbances, concentration problems, memory loss and personality changes [8,9].

HGG is characterized by rapid growth and resistance to conventional therapies, which makes this tumor type a significant challenge in neuro-oncology. The treatment of HGG conventionally consists of a multimodal approach, which includes maximal safe Surgical Resection (SU), adjuvant Radiation Therapy (RT) and concurrent Chemotherapy (CH) with Temozolomide (TMZ) for six weeks, followed by TMZ for an additional six months [10, 11]. However, this approach is not curative. An available clinical trial is the preferred option [12]. The median Overall Survival (OS) for GBM patients receiving conventional multimodal treatment is approximately 13 months, with survival rates of 82% at six months, 55% at 12 months and 19% at 24 months [13]. Patients experience several side effects related to surgery and chemoradiotherapy, including ataxia, motor or language deficits, fatigue, insomnia and malaise. Long-term adverse effects include atrophy of brain tissue and cognitive deficits [14]. These acute and chronic Adverse Effects (AE) significantly decrease the HRQoL of HGG patients.

Recurrence of HGG, defined as tumor regrowth despite treatment, is a very negative prognostic factor [15]. Nearly all patients with HGG experience recurrence within several months and the prognosis is dismal [16]. In cases of GBM, recurrence in all patients is inevitable [17]. There is no standard therapy for recurrent HGG. Generally, the therapeutic strategy is tailored to each patient's specific requirements and guided by recommendations from a multidisciplinary tumor board that considers prior treatment, time to recurrence, performance status, corticosteroid dependence and molecular markers [12,15]. Again, enrollment in a clinical trial is preferred. Conventional therapy options for recurrent HGG include a second surgery, additional RT, additional TMZ or lomustine and bevacizumab [12]. This extra treatment will lead to additional AEs and further reduce patients' HRQoL.

Methods

Antineoplaston research began in 1967, when significant deficiencies were noticed in the peptide content of the serum of patients with cancer compared with healthy people. Initially, Antineoplastons were isolated from the blood and later from urine [18]. Subsequent studies of the isolated Antineoplastons demonstrated that Antineoplaston A10 (Atengenal) and Antineoplaston AS2-1 (Astugenal) were the most promising formulations. The chemical name of Antineoplaston A10 is 3-phenylacetylamino-2,6-piperidinedione. It consists of the cyclic form of L-glutamine connected by a peptide bond to a phenylacetyl residue. The mixture of synthetic Phenylacetyl Glutaminate (PG) and phenylacetyl isogluatminate (isoPG) in a 4:1 ratio, when dissolved in sterile water, constitutes an Antineoplaston A10 intravenous (IV) injection. Further metabolism of Antineoplaston A10 results in Phenylacetate (PN). Both metabolites, PG and PN, have anticancer activity. The mixture of PN and PG in a 4:1 ratio, dissolved in sterile water, constitutes Antineoplaston AS2-1 IV injection [19].

Antineoplastons A10 and AS2-1 (ANP) has been used in several phase II clinical studies [20-68]. Here we present 1) unusually long survival (from more than five years to over 33 years) of 61 HGG patients treated at the Burzynski Clinic (BC), between August 1992 and September 2004, according to phase II protocols of ANP and 2) the lack of long-term adverse sequelae. The eligibility criteria for protocol therapy included a Karnofsky/Lansky Performance Score (KPS/LPS) of 60-100% and a life expectancy of at least 2 months. All patients were treated according to single-arm, phase II studies, which administered ANP by IV injection. Some patients also received oral ANP for maintenance. Gradually increasing doses of IV ANP were administered via a subclavian catheter and infusion pump until the maximum tolerated doses of A10 and AS2-1 were achieved. The outcome criteria were 1) objective response (OR), 2) survival and 3) toxicity. All study patients and/or their legal guardians read, understood and signed an Informed Consent Document before treatment. Disease progression, unacceptable toxicity, physician decision, or patient request resulted in the termination of ANP.

MRI scans of the brain with gadolinium enhancement were used for diagnosis, response evaluation and follow-up of these patients. Brain MRIs were performed serially every 8 weeks during the first 2 years of protocol ANP. Afterward, they were conducted as needed during follow-up. T2-weighted, T2-FLAIR, T1-weighted and contrast-enhanced T1-weighted images were obtained. HGG shows gadolinium enhancement so contrast-enhanced T1-weighted images were used to assess treatment effects [69,70]. Based on the brain MRI, the product of the two largest perpendicular diameters of each measurable (>5mm) and enhancing lesion was calculated. Tumor size was defined as the SUM of these products. The response criteria were as follows: a Complete Response (CR) was indicated by the total disappearance of all enhancing tumors. In contrast, a Partial Response (PR) was indicated by a 50% or greater reduction in the SUM. CR and PR required a confirmatory brain MRI performed at least four weeks after the initial finding. Progressive Disease (PD) was indicated by a 25% or greater increase in the SUM, or the presence of new measurable and enhancing disease. Stable Disease (SD) was defined as the absence of CR, PR, or PD [69,70].

The Phase II studies were conducted in accordance with the U.S. Code of Federal Regulations, Title 21, Parts 11, 50, 56 and 312; the Declaration of Helsinki (1964), including all amendments and revisions; the Good Clinical Practices: Consolidated Guideline (E6), International Conference on Harmonization (ICH) and Guidance for Industry (FDA). By participating in this study protocol, the investigators agreed to provide access to all appropriate documents for monitoring, auditing, Institutional Review Board (IRB) review and review by any authorized regulatory agency.

Results

A total of 310 HGG patients received treatment at the BC between May 1988 and March 2014 as part of Phase II ANP studies. GBM patients were excluded as they were the subjects of another article [66]. Of these patients, 170 were designated as "Special Exceptions" (54.8%) because they did not meet all eligibility criteria, often due to a KPS/LPS of less than 60. These 170 patients were individually approved by the Food and Drug Administration (FDA). Out of 310 HGG patients, 61 survived over 5 years from HGG diagnosis.

Fifty-nine of 310 non-GBM HGG patients (19.0%) were initially diagnosed with low-grade tumors that subsequently transformed into high-grade tumors. In such cases, only the dates for high-grade diagnoses were used to calculate survival. For these 310 patients, Kaplan-Meier survival analysis showed a median OSD of 1.867 years (95% CI 1.555 to 2.133). See Fig. 1., where the “Time” axis is presented in increments of five years and survival extended to over 30 years in our observation.

neurology-neuroscience-kaplan-meier

Figure 1. Kaplan-Meier analysis and survival curve (N=310).

Before being seen at the BC, 18 of 61 long-term survivors underwent SU, followed by RT, and CH; 10 patients had SU and RT; 8 patients had SU only, 5 patients had RT only after initial biopsy; 7 patients had biopsy only; 16 patients had some combination of single SU +/- RT +/- CH. Several patients also had other treatments. Demographic details, prior treatment and overall survival are shown in Tab. 1.

  N=310 (All Patients) N=61 (OSD >5 years)
Sex    
Male 200 39
Female 110 22
Age (at admission at BC)    
Range 0.41-76.66 1.08-62.66
Median 37.8 35.9
Age groups (at admission at BC)    
Below 21 64 10
21+ 246 51
KPS/LPS (at admission at BC)    
Range 30-100 40-90
Median 50 60
Prior Treatment (single treatments/multiple treatments)    
None 3* -
Bx only 46/1 7
Bx, RT 21/1 5/-
Bx, RT, CH 23/12 1/2
Bx, RT, CH, Other 2/4 -/1
Bx, RT, Other 1/- 1/-
Bx, CH 3/1 -/1
Bx, CH, Other 1/1 1/-
SU 34/4 7/1
SU, RT 28/11 9/1
SU, CH 5/2 3/-
SU, CH, Other 1/ - 3/-
SU, RT, CH, 18/47 4/6
SU, RT, CH, Other 5/23 -/8
SU, RT, Other 6/1 -/1
SU, Other 3/- 2/-
RT 2**/ - -
Pathology    
Anaplastic Astrocytoma 189 40
Anaplastic Astrocytoma/BSG 8 -
Anaplastic Astrocytoma/DIPG 22 5
Anaplastic Astrocytoma/Mixed 33 8
Anaplastic Astrocytoma/Mixed/DIPG 1 -
Anaplastic Astrocytoma/Visual Pathway 2 -
Anaplastic Astrocytoma/Spine 2 -
Anaplastic Glioma 1 -
Anaplastic Oligoastrocytoma 2 1
Anaplastic Oligodendroglioma 13 3
Anaplastic Oligodendroglioma/DIPG 1 -
Astrocytoma Fibrillary High Grade 2 -
Astrocytoma Fibrillary High Grade/Spine 1 -
Astrocytoma High Grade/Spine 1 -
Astrocytoma Infiltrating/DIPG 1 1
Glioma High Grade 15 1
Glioma High Grade/Visual Pathway 1 1
Gliomatosis Cerebri 2 -
Oligoastrocytoma High Grade 11 1
Xantoastrocytoma, grade 4 2 -
Overall Survival from diagnosis    
Over 6 months 86.77% NA
Over 5 years 19.68% 100%
Over 12 years 7.41% 37.70%

Tab. 1. Demographics, prior treatment, pathology and OSD.

Fifty-three of the 61 long-term survivors (86.9%) had anaplastic astrocytoma, of which eight were described as "mixed" and five had histological features of diffuse intrinsic pontine glioma. Eight patients had one of five other HGG diagnoses. Pathologists with academic affiliations, including prominent neuropathologists, made the diagnoses. Details of the diagnosis, prior treatment and tumor status at the start of ANP are presented in Tab. 2.

Case Date Pathology Hospital name Prior treatment Tumor characteristic
1 02/15/88 Anaplastic Astrocytoma Cooper Hospital/University Medical Center, Camden, NJ SU Supratentorial; Single lesion; Primary
2 07/29/87 Moderately anaplastic astrocytoma UCSF Medical Center, San Francisco, CA Bx, RT DIPG/Solitary/NE only
3 10/19/87 Anaplastic Astrocytoma National Cancer Institute report SU, RT Supratentorial; Single lesion; Primary
4 04/28/87 Moderately anaplastic astrocytoma UCSF Medical Center, San Francisco, CA SU, RT, CH Supratentorial; Single lesion; Primary
5 04/22/88 Anaplastic Astrocytoma University of Alberta Hospitals, Alberta, Canada SU, RT, CH DIPG/Solitary E+NE
6 09/14/90 Giganto-Cellular Anaplastic Astrocytoma Children's Hospital of Philadelphia, Philadelphia, PA SU, RT Supratentorial; Single lesion; Primary
7 08/28/92 Anaplastic Astrocytoma, Osseous Metaplasia. New York University Medical Center, New York, NY SU, RT, tamoxifen DIPG/Solitary E+NE
8 12/03/1993 Anaplastic Astrocytoma Princess Margaret Hospital for Children, Subiaco, Australia Bx Supratentorial; Single lesion; Primary
01/03/1994 Astrocytoma grade 1-2 Children's Hospital of Philadelphia, Philadelphia, PA
9 1/y/90 Anaplastic Astrocytoma Not available 2SU, 4Bx, RT, 2CH, CT – no data, tamoxifen Supratentorial; Single lesion; Primary
10/25/93 Oligodendroglioma National Institute of Health Medical Center, Bethesda, MD
12/06/1993 Anaplastic Oligodendroglioma National Institute of Health Medical Center, Bethesda, MD
01/25/94 Anaplastic Oligodendroglioma National Institute of Health Medical Center, Bethesda, MD
11/14/94 Oligodendroglioma National Institute of Health Medical Center, Bethesda, MD
03/21/95 Anaplastic Oligodendroglioma National Institute of Health Medical Center, Bethesda, MD
10 12/08/1994 Mixed Glioma grade 3-4 St. Vincent Medical Center, Toledo, OH SU, RT Supratentorial; Single lesion; Primary
11 09/29/94 Anaplastic Oligoastrocytoma The New York Hospital, New York, NY SU, RT Supratentorial; Single lesion; Primary
12 08/30/95 Anaplastic Astrocytoma The Methodist Hospital, Houston, TX Bx, RT Supratentorial; Single lesion; Primary
13 02/26/96 High Grade Glioma The Moses H. Cone Memorial Hospital, Greensboro, NC SU Supratentorial; Single lesion; Primary
03/29/96 Mixed Astrocytoma-Oligodendroglioma Children's Hospital of Philadelphia, Philadelphia, PA
14 02/23/96 Anaplastic Astrocytoma Oregon Health Sciences University, Portland, OR SU Supratentorial; Single lesion; Primary
04/03/1996 Anaplastic Astrocytoma Children's Hospital of Philadelphia, Philadelphia, PA
15 9/y/90 Astrocytoma Infiltrating Medical College of Ohio, Toledo, OH SU, 2Bx, RT, CH Supratentorial; Single lesion; Primary
10/18/95 Astrocytoma Infiltrating Cleveland Clinic, Cleveland, OH
02/06/1996 Astrocytoma infiltrating Cleveland Clinic, Cleveland, OH
16 02/16/96 Astrocytoma, possible anaplastic Air Force USAC Medical Center, Wright Patterson, OH Bx, RT Supratentorial; Multifocal; Primary
03/08/1996 Astrocytoma Infiltrating Air Force USAC Medical Center, Wright Patterson, OH
09/12/1996 Astrocytoma Children's Hospital of Philadelphia, Philadelphia, PA
17 10/06/1989 Moderate anaplastic astrocytoma Huntington Memorial Hospital, Pasadena, CA Bx, RT Supratentorial; Single lesion; Primary
18 09/03/1991 Small cell astrocytoma grade 4 Swedish Medical Center, Englewood, Co 2SU, RT, CH Supratentorial; Multicentric; Primary
09/05/1991 Glioblastoma Multiforme, small cell variant University of Colorado Health Science Center, Aurora, CO
09/09/1991 Small cell malignant astrocytoma Mayo Clinic, Rochester, MN
02/03/1997 High Grade Glioma California Pacific Medical Center, San Francisco, CA
19 12/23/91 Mixed Malignant Glioma. UCSF Medical Center, San Francisco, CA 2SU, RT, CH Supratentorial; Multifocal; Primary
12/15/95 Mixed Malignant Glioma UCSF Medical Center, San Francisco, CA
20 02/24/97 Anaplastic astrocytoma University of Pennsylvania Medical Center, Philadelphia, PA SU Supratentorial; Single lesion; Primary
21 07/18/85 Astrocytoma The Children's Hospital of Philadelphia, Philadelphia, PA SU, Bx, RT, 2CH Supratentorial; Single lesion; Primary
08/10/1992 Anaplastic mixed glioma Zale Lipshy University Hospital, Dallas, TX
03/28/97 Anaplastic astrocytoma The Children's Hospital of Philadelphia, Philadelphia, PA
22 04/23/93 Astrocytoma St. Joseph's Hospital, Houston, TX 2Bx, RT Supratentorial; Single lesion; Primary
05/11/1993 Glioma Infiltrating St. Joseph's Hospital, Houston, TX
07/23/96 Anaplastic Astrocytoma Clinic at the University of Florida, Gainesville, FL
23 12/10/1996 Anaplastic mixed glioma North Shore University Hospital, Manhasset, NY SU, CH Supratentorial; Single lesion; Secondary
04/30/97 High grade glioma/Anaplastic Oligodendroglioma Memorial Hospital for Cancer and Allied Diseases, New York, NY
07/25/97 Anaplastic Astrocytoma North Shore University Hospital, Manhasset, NY
24 4/y/91 Astrocytoma University of Pennsylvania Medical Center, Philadelphia, PA Bx, SU, RT Supratentorial; Multifocal; Secondary
06/02/1997 Anaplastic Astrocytoma University of Pennsylvania Medical Center, Philadelphia, PA
25 04/24/92 Oligoastrocytoma type III Centre Hospitalier Sainte Anne, Paris, France SU, RT Supratentorial; Single lesion; Primary
26 9/y/91 Mixed glioma grade 2/3 New York Medical Center, New York, NY 2SU, RT, CH Supratentorial; Single lesion; Primary
04/27/98 High grade mixed glial-neuronal tumor University Medical Center, New York, NY
27 08/21/98 Astrocytoma Fibrillary, grade 3 Foothills Hospital, Department of Histopathology, Calgary, Alberta, Canada SU Supratentorial; Single lesion; Primary
28 01/06/1989 Anaplastic Astrocytoma UCSF Medical Center, San Francisco, CA Bx, RT, 2CH, Accutane, tamoxifen DIPG/Solitary E+NE
29 4/y/92 Anaplastic Astrocytoma Brookhaven Memorial Hospital Medical Center, Patchogue, NY 3SU, RT, 2CH Supratentorial; Multicentric; Secondary
08/05/1993 Astrocytoma Brookhaven Memorial Hospital Medical Center, Patchogue, NY
08/20/93 Anaplastic Astrocytoma Stoney Brook University Hospital, Stoney Brook, NY
04/14/94 Anaplastic Astrocytoma Brookhaven Memorial Hospital Medical Center, Patchogue, NY
11/09/1998 Anaplastic Astrocytoma Memorial Hospital for Cancer and Allied Diseases, New York, NY
30 12/24/97 Anaplastic Astrocytoma Not available 2SU, RT, 3CH, tamoxifen Supra & Infratentorial; Multicentric; Primary
10/14/98 Anaplastic Astrocytoma UCSF Medical Center, San Francisco, CA
31 05/10/1996 Astrocytoma fibrillary, grade 2 Community Hospitals, Indianapolis, IN Bx Supratentorial; Single lesion; Primary
05/15/96 Astrocytoma Indiana University Medical Center, Indianapolis, IN
07/26/96 Astrocytoma Fibrillary, grade 2 The Johns Hopkins Hospital, Baltimore, MD
32 07/27/98 Anaplastic Astrocytoma Sutter General Hospital, Sacramento, CA Bx, RT, CH Supratentorial; Single lesion; Primary
08/25/98 Anaplastic Astrocytoma Roth Medical Group, Sacramento, CA
33 05/15/00 Anaplastic Astrocytoma Saint John's Health Center, Santa Monica, CA Bx Supratentorial; Multifocal; Primary
34 05/06/1996 Astrocytoma Malignant Not available 2SU Supratentorial; Single lesion; Primary
07/31/00 Anaplastic Astrocytoma University Jagiellonum Collegium Medicum, Krakow, Poland
35 11/07/2000 Astrocytoma Fibrillary /Anaplastic Astrocytoma United Hospital Allina Health System, St. Paul, MN Bx Supratentorial; Multifocal; Primary
36 04/26/00 Glial neoplasia, high grade Beth Israel Medical Center-North Division, New York, NY 2SU, RT Supratentorial; Single lesion; Primary
12/20/00 Anaplastic Astrocytoma Beth Israel Medical Center-North Division, New York, NY
37 05-12-1995 Anaplastic Astrocytoma New York University Medical Center, New York, NY SU, Bx, CH Supratentorial; Single lesion; Primary
01/16/98 Oligoastrocytoma, grade 3 UCSF Medical Center, San Francisco, CA
38 04/30/02 Anaplastic Astrocytoma UCSF Medical Center, San Francisco, CA Bx Supratentorial; Single lesion; Primary
39 11/06/1995 Anaplastic Astrocytoma Armed Forces Institute Of Pathology, Washington, DC SU, RT, CH Supratentorial; Single lesion; Primary
40 07/10/1992 Astrocytoma Infiltrating with pilocytic features grade 2/3 Westchester County Medical Center, Grasslands Reservation Valhalla, NY SU, CH Supratentorial; Single lesion; Primary; Visual Pathway
07/23/92 Juvenile pilocytic astrocytoma Memorial Sloan-Kettering Cancer Center, New York, NY
10/13/92 Anaplastic Astrocytoma Westchester County Medical Center, Grasslands Reservation Valhalla, NY
11/05/1992 Juvenile pilocytic astrocytoma Memorial Sloan-Kettering Cancer Center, New York, NY
07/12/1994 Optic nerve involved by high grade glioma Westchester County Medical Center, Grasslands Reservation Valhalla, NY
41 03/09/1998 Anaplastic Astrocytoma Akron General Medical Center, Akron, OH Bx Supratentorial; Single lesion; Primary
42 03/11/1992 Astrocytoma Hackensack Medical Center, Department of Pathology, Hackensack, NJ SU, alternative therapy Supratentorial; Single lesion; Primary /NE only
02/09/2000 Anaplastic Oligodendroglioma New York Presbyterian Hospital/Columbia Presbyterian Center, New York, NY
03/15/00 Anaplastic Oligodendroglioma Memorial Hospital for Cancer and Allied Diseases, New York, NY
43 08/05/2003 Oligoastrocytoma mixed, grade 3 UCLA Medical Center, Department of Pathology in Los Angeles, CA Bx,2CH Supratentorial; Single lesion; Primary /NE only
44 02/26/03 Anaplastic Astrocytoma Hartford Hospital, Harford, CT Bx, CH, Gleevec Supratentorial; Single lesion; Primary /NE only
45 06/01/1999 Oligoastrocytoma Mixed Robert Wood Johnson University Hospital, New Brunswick, NJ SU, high dose vitamins C and E Supratentorial; Single lesion; Primary
07/28/99 Oligoastrocytoma Mixed, grade 3 Department of Defense, Armed Forces Institute Of Pathology, Washington, DC
09/01/1999 Oligodendroglioma Mayo Clinic, Rochester, MN
09/07/1999 Oligodendroglioma University of Kansas Medical Center, Kansas City
09/21/99 Astrocytoma The Johns Hopkins Hospital, Baltimore, MD
10/07/1999 Glioneuronal tumor with neuropil-like islands Robert Wood Johnson University Hospital, New Brunswick, NJ
46 07/15/83 Astrocytoma Malignant Medical Center Del Oro Hospital, Houston, TX 5SU, Bx, 2RT, 5CH, interferon, Accutane Supratentorial; Multicentric; Primary
03/07/2003 Glioma favor Oligoastrocytoma St. Luke's Baylor Hospital, Houston, TX
11/21/03 Anaplastic mixed glioma St. Luke's Baylor Hospital, Houston, TX
06/28/04 High Grade Glioma M.D. Anderson Cancer Center, Houston, TX
07/05/2004 Anaplastic Astrocytoma M.D. Anderson Cancer Center, Houston, TX
47 07/07/2003 Astrocytoma Fibrillary, grade 3 Mayo Clinic, Rochester, MN 4SU, 2RT, 2CH, LAK cells Supratentorial; Single lesion; Primary
07/08/2003 Anaplastic Astrocytoma Hoag Memorial Hospital Presbyterian, Newport Beach, CA
07/09/2003 Astrocytoma Fibrillary, grade 3 Hoag Memorial Hospital Presbyterian, Newport Beach, CA
03/22/04 Anaplastic Astrocytoma Hoag Memorial Hospital Presbyterian, Newport Beach, CA
48 05/28/96 Astrocytoma, grade 2 with focal grade 3 Santa Barbara Cottage Hospital, Santa Barbara, CA 3SU, Bx, 4RT, 5CH, PB, Accutane, thalidomide Infratentorial; Single lesion; Primary
06/04/1996 Oligodendroglioma Massachusetts General Hospital, Boston, MA
04/02/1998 Oligoastrocytoma, grade 3 UCSF Medical Center, San Francisco, CA
05/02/2001 Glioma infiltrating UCSF Medical Center, San Francisco, CA
02/06/2002 Anaplastic Oligoastrocytoma UCSF Medical Center, San Francisco, CA
03/02/2004 Anaplastic Astrocytoma UCSF Medical Center, San Francisco, CA
49 09/28/04 Anaplastic Astrocytoma Pathology at Massachusetts General Hospital, Boston, MA 3SU, RT, 2CH, Clinical trial CC-8490 Supratentorial; Single lesion; Primary
10/01/2004 Anaplastic Astrocytoma Pathology at Massachusetts General Hospital, Boston, MA
04/25/05 Astrocytoma Not readable
50 7/y/1999 Gemistocytic Astrocytoma Arhus University Hospital, Arhus, Denmark 2SU, RT, CH Supratentorial; Single lesion; Secondary
11/13/01 Anaplastic Astrocytoma
51 08/24/05 Anaplastic Astrocytoma UT Southwestern Medical Center, University Hospitals & Clinics, Zale Lipshy Laboratory, Dallas, TX SU Supratentorial; Single lesion; L-M, Primary
52 10/07/2003 Anaplastic Astrocytoma Cedars-Sinai Medical Center, Los Angeles, CA SU, RT Supratentorial; Single lesion; Primary
53 06/12/2007 Anaplastic Astrocytoma St. Anthony Health Services, Denver, CO SU Supratentorial; Single lesion; Primary
54 10/20/06 Oligoastrocytoma, astrocytic predominant, grade 2 Mayo Clinic, Rochester, MN Bx, RT, 2CH Supratentorial; Single lesion; Primary
12/09/2006 Anaplastic Astrocytoma University of Michigan, Ann Arbor, MI
55 04/06/2010  Astrocytoma Infiltrating Diffuse M.D. Anderson Cancer Center, Houston, TX Bx, RT, anticancer treatment unknown DIPG/Solitary/NE only
56 06/22/07 Anaplastic Astrocytoma Michael Reese Hospital, Chicago, IL SU, RT Supratentorial; Single lesion; Primary
57 02/11/2010 Oligoastrocytoma, grade 2 St. Joseph Hospital and Medical Center, Phoenix, AZ 2SU, Bx, 3RT, CH, bevacizumab Supratentorial; Multicentric; Primary
05/12/2010 Astrocytoma with Gemistocytic features, grade 2 St. Joseph Hospital and Medical Center, Phoenix, AZ
08/24/10 Anaplastic Astrocytoma, gemistocytic St. Joseph Hospital and Medical Center, Phoenix, AZ
58 04/01/2011 Anaplastic Glioma Royal Free Hampstead NHS Trust, London, U.K. SU, RT Supratentorial; Single lesion; Primary
59 04/13/11 Astrocytoma Infiltrating Fleni Hospital Montañeses 2325, C1428, Buenos Aires, Argentina Bx, RT, 2CH DIPG/Single lesion; Primary/NE only
11/08/2011 Astrocytoma Infiltrating M.D. Anderson Cancer Center, Houston, TX
60 01/24/12 Anaplastic Astrocytoma/thalamic UPMC- Presbyterian, Pittsburg, PA Bx Supratentorial; Single lesion; Primary
61 01/05/2006 Anaplastic Oligodendroglioma Barnes-Jewish Hospital Washington University Medical Center, St. Louis, MO 2SU, RT, 2CH, PB, Tarceva, pazopanib, bevacizumab Supratentorial; Single lesion; Primary
08/05/2011 Anaplastic Oligodendroglioma Barnes-Jewish Hospital Washington University Medical Center, St. Louis, MO

Tab. 2. Diagnosis, prior treatment and tumor status at the start of ANP.

At admission to BC, the age of these patients ranged from 1.08 to 62.66 years, with a median age of 35.9 years. There were 22 females and 39 males. KPS/LPS scores ranged from 40 to 90, with a median score of 60. Twenty-five patients (41.0%) were not eligible for protocol ANP but, after FDA approval, were treated as Special Exceptions (SEs) according to protocol.

All ORs were confirmed by prominent neuroradiologists who were not affiliated with BC. ORs consisted of CR in 13 cases, PR in 4 cases, SD in 20 cases and PD in 14 cases. Ten cases were not evaluable. Overall Survival from Diagnosis (OSD) was more than 12 years in 23 patients, more than 20 years in 8 patients and more than 30 years in 2 patients. As of October 2025, 1 patient had an OSD of more than 33 years. Eight patients (13.1%) were alive and doing well at the last follow-up. The best response to ANP, patient status at last follow-up and OSD following ANP for all 61 long-term survivors are described in Tab. 3.

Case Sex Age at admission (years) Protocol Diagnosis at admission KPS/LPS at admission Start Date Days on protocol Best response on treatment Post ANP treatment Cause of death or last contact date OSD years
1 F 13.67 BT-03 Anaplastic Astrocytoma 70 01/19/1989 97 PD None unknown 11.88
2 F 36.41 BT-03 Anaplastic Astrocytoma/DIPG 60 07/12/1988 394 CR None pneumonia 28.60
3 M 30.42 BT-03 Anaplastic Astrocytoma 70 07/08/1988 262 SD None unknown 6.18
4 M 48.42 BT-04 Anaplastic Astrocytoma 70 04/12/1990 654 PR None HGG 9.25
5 M 26.58 BT-03 Anaplastic Astrocytoma/DIPG 40 10/30/1989 113 CR None chronic toxicity from RT 24.76
6 M 9.33 BT-04 Anaplastic Astrocytoma 80 10/08/1990 90 SD SU 5/91 HGG 5.02
7 M 8.25 CAN-01 Anaplastic Astrocytoma/DIPG 60 10/26/1992 2533 (3641 po) CR None unknown 19.92
8 F 12.50 CAN-01 Anaplastic Astrocytoma 60 01/07/1994 1235 (458 po) CR None Alive 12/5/24 31.03 (+)
9 M 27.25 CAN-01 Anaplastic Oligodendroglioma 90 05/30/1995 NE None malignancy 7.55
10 M 32.58 CAN-01 Anaplastic Astrocytoma/Mixed 80 07/26/1995 1639 (876 po) CR None unknown 6.41
11 M 55.25 CAN-01  Anaplastic Astrocytoma/Mixed 70 08/22/1995 433 SD None different malignancy - sinus cancer 17.59
12 M 62.67 CAN-01 Anaplastic Astrocytoma 60 01/31/1996 104 SD None unknown 5.58
13 M 54.33 BT-18 Anaplastic Astrocytoma/Mixed 80 03/27/1996 519 CR RT unknown 14.52
14 F 50.42 BT-08 Anaplastic Astrocytoma 90 04/08/1996 554 (218 po) SD None unknown 7.30
15 M 41.92 BT-15SE Anaplastic Astrocytoma Infiltrating 70 05/02/1996 130 SD None HGG 7.30
16 M 26.58 BT-09 Anaplastic Astrocytoma 80 09/17/1996 1103 PR SU 10/99 HGG 5.21
17 M 44.50 BT-15 Anaplastic Astrocytoma 60 11/15/1996 377 SD None unknown 12.57
18 F 30.67 BT-09 Glioma High Grade 60 02/12/1997 53 PD None HGG 5.59
19 M 38.42 BT-18 Anaplastic Astrocytoma/Mixed 60 02/17/1997 35 PD None HGG 5.68
20 F 29.75 BT-08SE Anaplastic Astrocytoma 90 03/27/1997 134 SD None unknown 5.62
21 M 44.00 BT-15 Anaplastic Astrocytoma 90 04/12/1997 74 PD None HGG 5.10
22 F 45.42 BT-15 Anaplastic Astrocytoma 80 10/14/1998 224 (773 po) CR None unknown 14.96
23 M 26.67 BT-18 Anaplastic Oligodendroglioma 80 06/06/1997 31 PD RT, SU 07/97 Alive 10/10/25 28.83 (+)
24 F 48.83 BT-15SE Anaplastic Astrocytoma 50 03/11/1998 133 NE None HGG 5.49
25 F 40.83 BT-18 Anaplastic Astrocytoma/Mixed 60 06/17/1998 138 PD None unknown 6.66
26 M 35.50 BT-18 Anaplastic Astrocytoma/Mixed 60 06/24/1998 145 PD None HGG 7.18
27 F 17.83 BT-10 Anaplastic Astrocytoma 80 10/20/1998 268 (680 po) SD SU 01/04, RT HGG 10.46
28 M 42.50 BT-11SE Anaplastic Astrocytoma/DIPG 40 03/19/1999 179 PD None HGG 10.88
29 M 41.25 BT-15SE Anaplastic Astrocytoma 40 03/29/1999 85 PD None (shunt) septicemia 7.26
30 F 13.75 BT-22SE Anaplastic Astrocytoma 40 10/01/1999 399 SD None unknown 13.16
31 F 36.92 BT-09SE Anaplastic Astrocytoma 50 10/15/1999 78 (556 po) SD SU 03/02, RT unknown 7.12
32 F 37.25 BT-15 Anaplastic Astrocytoma 60 01/12/2000 184 (763 po) CR None unknown 5.28
33 F 31.92 BT-08 Anaplastic Astrocytoma 60 06/06/2000 56 (454 po) CR None Alive 10/13/25 25.40 (+)
34 M 33.67 BT-09SE Anaplastic Astrocytoma 50 11/09/2000 197 PD RT unknown 5.80
35 M 52.50 BT-08 Anaplastic Astrocytoma 60 02/07/2001 57 NE SU 8/12, RT, 3xCH, OT unknown 17.87
36 M 41.50 BT-15 Anaplastic Astrocytoma 60 02/22/2001 162 PR None HGG 5.04
37 M 35.92 BT-18SE Oligoastrocytoma High Grade 50 02/22/2002 90 PD None HGG 7.05
38 F 3.58 BT-22SE Anaplastic Astrocytoma 50 05/23/2002 621 SD SU 07/04, 2005, RT, CH, OT unknown 18.55
39 M 40.33 BT-15 Anaplastic Astrocytoma 60 01/23/2003 257 (305 po) SD None HGG 10.05
40 M 12.25 BT-23SE Glioma High Grade/Visual Pathway 50 04/09/2003 479 (1983 po) PR None Alive 10/10/25 33.25 (+)
41 F 41.58 BT-09 Anaplastic Astrocytoma 80 05/27/2003 170 PD SU 11/03 unknown 7.33
42 M 43.08 BT-09 Anaplastic Astrocytoma 90 12/03/2003 664 SD SU 10/05 unknown 8.47
43 M 49.25 BT-18 Anaplastic Astrocytoma/Mixed 70 02/10/2004 42 NE 2xRT HGG 8.34
44 F 1.08 BT-06SE Anaplastic Astrocytoma 50 02/26/2004 841 SD SU 03/08, 3xCH, TT unknown 10.98
45 M 33.25 BT-09 Anaplastic Astrocytoma/Mixed 70 04/13/2004 255 SD SU 02/05, RT,CH unknown 15.17
46 M 43.25 BT-15SE Anaplastic Astrocytoma 40 09/22/2004 3 NE None HGG 21.25
47 M 37.00 BT-09SE Anaplastic Astrocytoma 50 02/09/2005 531 (300 po) CR None unknown 14.72
48 M 30.58 BT-15SE Anaplastic Astrocytoma 50 06/15/2005 37 NE TT unknown 10.42
49 M 47.00 BT-15SE Anaplastic Astrocytoma 50 07/01/2005 298 SD None Alive 10/09/25 21.03 (+)
50 M 28.33 BT-15SE Anaplastic Astrocytoma 50 07/07/2005 9 NE None HGG 6.00
51 F 24.42 BT-08SE Anaplastic Astrocytoma 40 10/17/2005 2193 CR None HGG 6.16
52 M 30.58 BT-18 Anaplastic Oligoastrocytoma 70 01/18/2007 84 PD SU 5/07, CH unknown 6.37
53 M 36.25 BT-08 Anaplastic Astrocytoma 80 08/17/2007 427 CR SU 12/08, RT, CH, TT unknown 13.41
54 F 23.25 BT-15 Anaplastic Astrocytoma 80 09/13/2007 474 SD None Alive 10/09/25 18.97 (+)
55 M 27.50 BT-09SE Anaplastic Astrocytoma/DIPG 50 01/06/2011 213 SD None unknown 8.90
56 M 56.00 BT-21SE Anaplastic Astrocytoma 90 06/30/2011 39 NE SU 12/11, 2xOT unknown 5.24
57 M 50.33 BT-15SE Anaplastic Astrocytoma 50 08/31/2011 95 NE TT, CH unknown 6.74
58 F 27.33 BT-09SE Anaplastic Astrocytoma 50 12/14/2011 535 CR None post viral treatment 12.13
59 F 25.67 BT-09SE Astrocytoma Infiltrating/DIPG 90 02/02/2012 506 SD None Alive 09/09/25 14.41 (+)
60 F 20.00 BT-09SE Anaplastic Astrocytoma 90 03/09/2012 52 PD RT, CH, TT Alive 10/23/25 13.75 (+)
61 M 43.50 BT-09SE Anaplastic Oligodendroglioma 90 07/18/2012 9 NE None HGG 6.57

Tab. 3.  Best response to ANP, overall survival from diagnosis and status at last follow-up.

Two representative cases are described:

Case# 1 (Case 8 in Tab. 2. and Tab. 3.)

In November 1993, a 12-year-old Caucasian female, with no prior health issues, was found to have a contrast-enhancing tumor in the left temporal lobe, which crossed the midline and compressed the superior pons. Biopsy revealed pleomorphic tumor cells with mitotic figures. Review of the microscopic sections of tumor tissue by experienced pathologists provided a diagnosis of Anaplastic Astrocytoma (AA). No treatment was started initially, but a brain MRI performed nine weeks later showed tumor progression.

In January 1994, the patient was seen at the BC. Symptoms included headaches, nausea, memory loss, slurred speech and fatigue. She usually experienced four focal seizures per day, some days more, some days less, with occasional grand mal seizures. Physical exam revealed hesitant and slurred speech. LPS was 60. MRI of the brain confirmed a 4.8 cm × 2.1 cm infiltrating, enhancing mass in the left temporal lobe that crossed the midline and compressed the brainstem.

Treatment with IV ANP began on January 7, 1994, per the phase II protocol. Dosages of A10 and AS2-1 were gradually increased until maximum tolerated doses were achieved. Follow-up brain MRIs at 3 and 14 months showed no significant change in tumor size, but by 13 months, all symptoms had been resolved while seizures persisted. Brain MRIs at 23 and 29 months of treatment showed tumor shrinkage by 96% and 98%, respectively, indicating a PR. At 32 months, brain MRI showed no enhancement, indicating achievement of a CR. Persistent seizures were felt to de due to scarring. IV ANP was discontinued at 40 months and oral maintenance ANP was initiated. Brain MRIs at 45, 51 and 55 months revealed a persistent CR. After 56 months of treatment, oral ANP was also discontinued. Three months later, scar tissue in the tumor bed was removed and the seizures ended. Follow-up brain MRIs at 6 and 15 years post-ANP showed no evidence of tumor; the CR was persistent. At the last follow-up in December 2024, the patient was doing well and living a normal life. Her OSD at that time was more than 31 years. There have been no long-term adverse sequelae.

Case #2 (Case 33 in Tab. 2. and Tab. 3.)

In May 2000, a 31-year-old female developed right upper extremity clumsiness and weakness of the right leg. She sought medical attention and was referred to a neurologist. MRI of the brain, performed on May 10, 2000, revealed a 2.0 cm2 mass in the left parietal lobe. Computerized Tomography (CT) scans of the chest, abdomen and pelvis were performed on May 11, 2000 and found to be normal. On May 15, 2000, the patient underwent a stereotactic biopsy of the parietal tumor. Histological examination of tumor tissue slides revealed an AA.

When the patient presented at the BC, she had not had SU, RT, or CH. A baseline MRI of the brain, with gadolinium contrast, performed on June 1, 2000, showed a 2.0 cm2 non-enhancing mass and two smaller enhancing masses (0.02 cm2 and 0.15 cm2) in the left parietal lobe. On June 6, 2000, the patient began IV ANP therapy and the ANP dosages were gradually increased to the maximum tolerated dosages. Throughout her IV ANP therapy, the patient experienced elevations in transaminases, which, on occasion, interrupted her therapy. MRI of the brain on July 3, 2000, one month after initiation of ANP therapy, demonstrated complete resolution of the enhancing disease in the left parietal lobe, indicating the achievement of a CR. However, the 2.0 cm2 non-enhancing tumor persisted. The MRI of the brain, performed on July 31, 2000, demonstrated a persistent CR. On August 1, 2000, IV ANP therapy was terminated, while oral maintenance ANP began on August 4, 2000.

The patient continued taking oral ANP until October 31, 2001, when she elected to stop all ANP therapy. Long-term follow-up brain MRI on February 6, 2017, showed a persistent CR and complete disappearance of the 2.0 cm2 non-enhancing nodule, indicating an enduring CR and complete tumor regression. The patient experienced two serious adverse events possibly related to ANP, both of which were resolved completely.

At the last follow-up in October 2025, she was doing well, had no evidence of tumor recurrence and had an OSD of more than 25 years and five months.

Discussion

An emerging therapeutic approach is Tumor-Treating Fields (TTFields) [71]. These fields are a non-invasive cancer therapy that uses low-intensity, intermediate-frequency, alternating electric fields to disrupt cancer cell division by interfering with mitotic spindle formation and chromosome segregation, resulting in mitotic arrest and apoptosis. Therapy is delivered via transducer arrays placed on the scalp and connected to a portable device [71].

The EF-14 phase III trial evaluated TTFields in combination with maintenance temozolomide and following standard chemoradiotherapy in patients with newly diagnosed GBM. Patients receiving TTFields plus TMZ demonstrated significantly improved progression-free survival (6.7 months vs. 4.0 months) and overall survival (20.9 months vs. 16.0 months) compared to TMZ alone. There was no significant increase in toxicity. Two-year survival rates were also higher in the TTFields arm (43% vs. 30%) [71]. Subsequent analyses have confirmed the findings of the EF-14 trial. TTFields therapy has been correlated with survival benefits and with outcomes similar to those observed in EF-14 [72].

The EF-14 results were published in 2014 and the study design did not fully account for the molecular markers that have become increasingly important for cohort stratification in clinical studies. Because of the diagnostic criteria presented in the 2021 WHO classification of CNS tumors [4,5], challenges to the design of clinical trials for HGG are significant. For example, IDH1/2 mutations define a distinct subset of gliomas with improved survival [73]. Genetic analyses also distinguish primary GBM, characterized by EGFR amplification and PTEN loss, from secondary GBM, arising from lower-grade gliomas with TP53 and IDH mutations [74].

In 2024, Barrera and colleagues reported a retrospective survival analysis of 80 HGG patients who underwent surgical resection and were treated from 2012 to 2015 at the Cancer Institute of the Americas Clinic in Medellin, Colombia [75]. The histological diagnosis was based on the 2007 WHO classification [76], not the diagnostic criteria presented above. Clinical, demographic and lifestyle characteristics were analyzed, along with genetic instability in white blood cells. The Kaplan-Meier analysis indicated an average survival of two years and two months. A Cox proportional hazards model showed that patient age, exposure to polycyclic hydrocarbons at work and the number of sister-chromatid exchanges in lymphocytes at the first sampling were significantly associated with survival in the multivariate analysis.

We report here on a survival analysis of 310 non-GBM HGG patients treated in phase II studies of ANP at BC between May 1988 and March 2014. Survival of more than 5 years up to more than 33 years was observed in 61 patients (19.6%). All these patients were seen after their diagnoses were established at outside academic institutions with prominent neuroradiologists confirming the ORs. The case of one of these patients was reviewed and confirmed by experts from the National Cancer Institute [77].

The mechanism of action of ANP differs from that of RT or CH. The growth of normal cells is controlled by cell cycle progression genes (oncogenes) and by cell cycle arrest genes (tumor suppressor genes). In cancer, alterations in these control genes in malignant cells favor aggressive cell proliferation. Evidence shows that ANP affects more than 535 gene aberrations in the malignant genome and functions as a "molecular switch" that "turns on" tumor-suppressor genes and "turns off" oncogenes [78]. Hence, the antineoplastic action of ANP involves restoration of cell cycle control, induction of programmed cell death and interference with cancer cell metabolism and nuclear transport.

In 1986, we published an article proposing that the neoplastic process is a disease of information processing [79]. The neoplastic process develops according to the "program" encoded in a network of mutated genes [32,79-87]. The technology now utilized can detect the DNA of these mutated genes in blood at concentrations as low as one billionth of a gram/mL [88]. Laboratories, such as Foundation Medicine, Guardant360 and Tempus AI, can provide results within two weeks and many insurance policies in the USA cover the tests.

At the BC, DNA analyses are compared with a list of 535 genomic aberrations compiled from early laboratory data on the effects of ANP on the entire genome of GBM [78] and from clinical data derived from blood and tissue testing of patients treated at the BC [88]. For each patient whose blood was tested, the number of genomic aberrations found to be affected by ANP determined the patient's candidacy for ANP.

We have found the genomic aberrations affected by ANP through our testing of blood samples from patients with over 70 different cancer diagnoses, including brain tumors [89-91]. Our goal is to correlate the ANP-related removal of genomic aberrations from patients’ blood with radiological response and survival. Based on our genomic testing, 114 aberrations significant in driving HGG progression [92] were affected and removed from the patients’ blood by ANP, including 51 aberrations of TP53, 19 of PIK3CA, 11 of NF1, 9 of PTEN, 5 of EGFR, 3 each of CCND1, IDH, and PDGFRA, and 1 each of CCND2, CDK6, CDKN2A, and CDKN2B. Some of these changes may have been influenced by other prescription drugs given to patients with advanced disease. New data will supplement these results once the number of tested genes increases beyond the 600-800 genes currently being tested. Based on this new information, we will include additional targeting agents along with ANP in treatment regimes, likely improving the rate of ORs and length of survival [87].

The survival of 61 evaluable, non-GBM HGG patients patients from 5 years to 33 years and the survival of 23 evaluable patients in this group from 12 years to 33 years, is very unusual. Surviving patients have no adverse long-term sequelae related to ANP and live normal lives, with healthy children. Thirty patients experienced Serious Adverse Events (SAEs) that were unrelated to ANP and all fully recovered. Four patients experienced six SAEs that were possibly related to ANP (fever without infection, nausea, dizziness and somnolence) and all fully recovered, as well. The authors are not aware of similar findings from other clinical studies of HGG.

Based on the OSD data shown above and the lack of consistently corresponding ORs, it is very likely that another ANP mechanism of action contributes to the unusually long survival observed in the 61 HGG patients. Additional publications describing the unusually long survival of patients receiving ANP in phase II studies of GBM, Recurrent Medulloblastoma (RMB) and Diffuse Intrinsic Pontine Glioma (DIPG) have already been published [66-68].

Conclusion

We present here the unusually long OSD seen in 61 non-GBM HGG patients treated in Phase II clinical studies with ANP, a therapy that avoids the long-term sequelae of RT and CH. The survival of 23 HGG patients for more than 12 years implies a cure. Because these studies were performed before current genomic testing techniques were available, these new technologies will permit better clinical trial design, improved cohort stratification and more accurate results.

ANP has proven to be an attractive option for a wide range of patients with persistent, recurrent, disseminated and/or metastatic brain tumors. Multiple Phase II clinical studies of Antineoplaston therapy in various advanced primary brain tumors, conducted under the Burzynski Research Institute's IND # 43,742, have now been completed and numerous articles have been published. The results presented here show that ANP is an effective option for treating HGG without causing long-term toxicity. Our group of HGG patients with exceptionally long-term survival is the largest series of HGG survivors documented in the world literature. Our findings support ANP as a viable treatment choice for these aggressive brain tumors.

Acknowledgement

The authors would like to express their appreciation to Carolyn Powers and Tanya Miller for their involvement.

Conflict of Interest

All the Authors of this paper have declared that there is no conflict of interest.

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