Long-term survival in patients with primary malignant brain tumors after postoperative home hydrogen inhalation: Three case reports

Abstract

BACKGROUND

Primary malignant brain tumors [World Health Organization (WHO) Grades III and IV] have poor prognoses despite standard treatment. We report three cases of such tumors with markedly prolonged overall survival (OS) associated with long-term home hydrogen (H₂) inhalation after conventional therapy.

CASE SUMMARY

Three patients: One with cerebellar medulloblastoma (MB), one with thalamic glioblastoma multiforme (GBM), one with an anaplastic oligoastrocytoma (AOA) evolving from a low-grade glioma, received standard surgery, radiotherapy and/or chemotherapy, followed by daily home inhalation of H₂-oxygen (O₂) gas mixture (66.6% H₂ and 33.4% O₂ at 3 L/minutes) for 4-10 hours/day. Clinical follow-up and serial brain magnetic resonance imaging (MRI) were performed. Case 1 (38-year-old female, cerebellar MB, subtotal approximately 70% resection) achieved OS of 52 months; postoperative MRI showed disappearance of the residual lesion. Case 2 (34-year-old female, thalamic GBM) achieved an OS of 38 months with no evidence of recurrence. Case 3 was a 56-year-old male with AOA WHO Grade III, 1p/19q non-codeleted, evolving from WHO Grade I-II astrocytoma, who achieved an OS of 93 months (80 months from the start of H₂ inhalation). He maintained independent daily living, and MRI showed no obvious residual tumor. All patients regained normal daily activities and social functioning. The Karnofsky Performance Status score improves to 100 in Cases 1 and 2, and > 80 in Case 3.

CONCLUSION

These three cases of malignant brain tumors, with survival times greatly exceeding published norms, were associated with long-term home H₂ inhalation after standard treatment. Given preclinical evidence of H₂’s antioxidant, anti-inflammatory and antitumor properties, these findings warrant further investigation of H₂ inhalation as a rehabilitation-adjunct therapy in patients with malignant brain tumors.

Key Words: Brain tumor; Medulloblastoma; Glioblastoma; Anaplastic oligoastrocytoma; Hydrogen intervention; Survival; Case report

Core Tip: We report three cases of high-grade brain tumors following standard conventional therapy combined with long-term home-based hydrogen inhalation. All patients achieved stable disease and favorable functional recovery. Their overall survival was markedly prolonged, exceeding the standard prognostic expectations. This simple and safe intervention warrants further clinical investigation.

INTRODUCTION

Primary malignant brain tumors are defined as lesions classified as World Health Organization (WHO) Grade III and IV. WHO Grade IV tumors encompass glioblastoma multiforme (GBM) and medulloblastoma (MB), while anaplastic oligodendroglioma and anaplastic oligoastrocytoma (AOA) are classified as WHO Grade III malignant gliomas[1]. The standard therapeutic regimen for these tumors consists of maximal safe neurosurgical resection followed by adjuvant radiotherapy and chemotherapy. Nevertheless, treatment resistance and inevitable tumor recurrence remain formidable clinical challenges; the majority of patients suffer from rapid disease progression and dismal short-term overall survival (OS)[2].

Hydrogen (H₂) is a biologically active gaseous molecule with well-documented antioxidant and anti-inflammatory properties. As early as 1975, Dole et al[3] first reported that hyperbaric H₂ inhalation triggered marked tumor regression in a mouse model of cutaneous squamous cell carcinoma. Subsequent in vitro cellular experiments and in vivo animal studies validated that H₂ exerts inhibitory effects on cancer cell proliferation, invasion, and migration[4,5]. Since 2018, our team has conducted a real-world evidence study focusing on cancer patients receiving long-term home H₂-oxygen (O₂) inhalation as an adjuvant rehabilitation strategy, using commercially available devices (H₂-O₂ Nebulizer, AMS-H-01^®, Shanghai Asclepius; H₂-O₂ Generator^™, Derison, Shanghai, China). Within this cohort, we conducted intensive follow-up and clinical monitoring on three patients with malignant brain tumors: One patient diagnosed with cerebellar MB achieved an OS of 52 months, with postoperative brain magnetic resonance imaging (MRI) demonstrating complete resolution of residual tumor lesions; one patient with thalamic GBM attained OS without any evidence of tumor recurrence. Both patients regained normal daily living and working capacity. The third patient presented with AOA transformed from WHO Grade I-II astrocytoma, with an OS of 93 months since pathological diagnosis. This patient maintains independent daily living, with no visible residual tumor on radiological imaging. The detailed clinical data and outcomes of these three cases are reported as follows.

CASE PRESENTATION

Chief complaints

Case 1: A 38-year-old female patient diagnosed with cerebellar MB received comprehensive treatment for 2 months.

Case 2: A 34-year-old female patient with epithelioid GBM of the right thalamus underwent comprehensive treatment for 4 months.

Case 3: A 56-year-old male patient presented with recurrent brain tumor, accompanied by right limb paralysis and weakness for 3 months.

History of present illness

Case 1: The patient developed dizziness, headache, projectile vomiting, unstable standing, staggering gait, and uncoordinated movements of the left limb, with a Karnofsky Performance Status (KPS) score of 40. At the end of June 2021, the patient underwent near-total (70% resection) of a bilateral cerebellar hemisphere mass at the First Affiliated Hospital of Xi’an Jiaotong University. Postoperative histopathology confirmed a diagnosis of cerebellar MB (WHO Grade IV). The patient subsequently received whole-brain and whole-spine radiotherapy at 1.8 Gy per fraction, for a total of 36 fractions. Her symptoms improved, although headache persisted. No other specific treatments were administered.

Case 2: In June 2022, the patient developed persistent dizziness and headache that did not respond to symptomatic treatment, with a KPS score of 50. Cranial MRI in August 2022 revealed a hypointense lesion in the right thalamus. Later that month, the patient underwent right temporal lobe tumor resection at the West Campus of Huashan Hospital, Fudan University, Shanghai, China. Postoperative histopathology confirmed thalamic epithelioid GBM (WHO Grade IV). The patient received concurrent chemoradiotherapy postoperatively. Radiotherapy was delivered at a total dose of 70 Gy over 44 days, combined with cyclic oral temozolomide (4-week cycles) for a total of 12 cycles, which was completed in October 2023. A follow-up brain MRI performed 3 months after treatment demonstrated patchy T1-weighted imaging (T1WI) hypointensity and mixed fluid-attenuated inversion recovery (FLAIR) signals in the surgical bed, suggestive of either postoperative changes or possible tumor recurrence.

Case 3: A 56-year-old male presented with headache in February 1998. Cranial MRI revealed a space-occupying lesion in the left frontal lobe. He underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences in Beijing, with pathological diagnosis of Grade I-II astrocytoma, followed by adjuvant radiotherapy to a total dose of 54 Gy. After nearly 20 years of asymptomatic survival, he developed headache and vomiting in January 2018. MRI demonstrated tumor recurrence at the original surgical site, measuring 65 mm in diameter. Subtotal (80%) resection was performed at the same hospital, and pathology showed anaplastic AOA with non-codeleted 1p/19q (WHO Grade III). Postoperatively, he received radiotherapy (59.4 Gy in 33 fractions of 1.8 Gy) plus concurrent and adjuvant temozolomide (150 mg/m² daily, 4-week cycles, 12 cycles total).

In November 2018, his neurological status deteriorated abruptly, manifesting as right limb paralysis and weakness, gait disturbance, right facial palsy, headache, insomnia, aphasia, and frequent seizure-like episodes (7-8 times daily, 1-5 minutes each), with a KPS score < 40. MRI identified a residual nodular tumor (approximately 31 mm × 27 mm) at the left frontal resection margin with extensive peritumoral edema. He was then placed on maintenance temozolomide (75 mg/m² daily) combined with bevacizumab (10 mg/kg intravenously every 2 weeks). However, clinical symptoms showed no improvement and progressed further at the 3-month follow-up.

History of past illness

Cases 1 and Case 2: The patients had no significant past medical history, no prior surgical history, and no known chronic medical conditions.

Case 3: The patient had a 5-year history of obstructive sleep apnea hypopnea syndrome, with no prior surgical history and no other known chronic illnesses.

Personal and family history

There was no relevant family history of malignancy or genetic disorders. The patients had no known toxic exposures or relevant personal habits.

Physical examination

Case 1: Vital signs were within the normal range for the patient’s age. An old surgical scar was noted on the right side of the head, with satisfactory healing. No other abnormal physical signs were detected.

Case 2: Vital signs were within the normal range for the patient’s age. An old surgical scar was present on the posterior aspect of the head, with good healing. No abnormal physical signs were found on comprehensive examination.

Case 3: Vital signs were within the normal range for the patient’s age. An old surgical scar was observed on the left side of the head, which had healed well. Muscle strength was grade 1 in the right upper limb and grade 0 in the right lower limb.

Laboratory examinations

Case 1: The resected specimen was routinely stained with hematoxylin and eosin. Microscopically, the tumor cells exhibited a pseudorosette structure, arranged in sheet-like and trabecular patterns (Figure 1). Immunohistochemical staining results showed (Syn⁺), CgA (partially⁺), CD56(⁺), β-catenin (partially⁺), and Ki67 (proliferation index, 70%). Pathological diagnosis: Cerebellar MB (WHO Grade IV).

Figure 1 Pathological image of cerebellar medulloblastoma. A: Hematoxylin and eosin (HE) staining, × 200 magnification; B: HE staining, × 400 magnification (provided by the First Affiliated Hospital of Xi’an Jiaotong University, China).

Case 2: Postoperative pathological examination showed that, under microscopy, the tumor cells had oval nuclei with abundant processes, which were diffusely and densely distributed or arranged around blood vessels. The tumor cells exhibited obvious nuclear atypia, with visible mitotic figures; hemorrhage was present, and occasional small necrotic foci were observed (Figure 2). Immunohistochemical staining results demonstrated positivity for glial fibrillary acidic protein (GFAP), negativity for isocitrate dehydrogenase 1, and positivity for BRAF V600E.

Figure 2 Pathological image of thalamic glioblastoma. A: Hematoxylin and eosin (HE) staining, × 100 magnification; B: HE staining, × 200 magnification (provided by the Pathology Department, West Campus of Huashan Hospital, Fudan University, Shanghai, China).

Imaging examinations

Case 1: Brain MRI on June 8, 2021, revealed patchy slightly hyperintense signals on T1WI and T2-weighted imaging (T2WI) in the cerebellar vermis and bilateral cerebellar hemispheres, with ill-defined boundaries. The cerebellar vermis was displaced downward, compressing the adjacent upper cervical spinal cord, and the fourth ventricle was significantly compressed and narrowed. Contrast-enhanced imaging showed marked heterogeneous enhancement of the lesions in the cerebellar vermis and bilateral cerebellar hemispheres, measuring approximately 58 mm × 37 mm with lobulated morphology. Imaging diagnosis: Space-occupying lesion in the cerebellar vermis and bilateral cerebellar hemispheres, accompanied by secondary cerebellar tonsillar herniation and supratentorial hydrocephalus (Figure 3).

Figure 3 Head magnetic resonance imaging in June 2021 showing space-occupying lesions on T1-weighted imaging in the cerebellar vermis and bilateral cerebellar hemispheres (orange arrows). A: Axial section; B: Sagittal section (provided by Tangdu Hospital, Air Force Medical University, Xi’an, China).

Case 2: Cranial MRI performed in August 2022 showed a hypointense area in the right thalamus on T1WI, along with a patchy, irregular hyperintense area with surrounding edema on T2WI/FLAIR sequences. The lesion measured approximately 30 mm × 25 mm, and MRI findings suggested a thalamic tumor (Figure 4).

Figure 4 Cranial magnetic resonance imaging showing a T1 hypointense area in the right thalamus (orange arrow). A: Axial section; B: Sagittal section [provided by Huashan Hospital (West Campus), affiliated to Fudan University, Shanghai, China].

Case 3: MRI re-evaluation performed in February 2019 showed that the residual tumor in the left frontal lobe had increased in size to 45 mm × 27 mm, compared with approximately 31 mm × 27 mm 3 months prior (Figure 5).

Figure 5 Magnetic resonance imaging before hydrogen inhalation showing an enlarged residual tumor (45 mm × 27 mm) in the left frontal lobe on T1-weighted imaging. A: Axial section; B: Coronal section (provided by Cancer Hospital Affiliated to Sun Yat-sen University, Guangzhou, China).

MULTIDISCIPLINARY EXPERT CONSULTATION

Multidisciplinary expert consultation was conducted within in an interdisciplinary tumorboard.

FINAL DIAGNOSIS

Case 1

Cerebellar MB (WHO Grade IV).

Case 2

Epithelioid GBM of the right thalamus (WHO Grade IV) with BRAF-V600R mutation.

Case 3

AOA of the left frontal lobe (WHO Grade III) with 1p/19q non-codeletion.

TREATMENT

Case 1

The patient began daily home H₂ inhalation (flow rate 3 L/minutes, containing 2 L H₂ and 1 L O₂) at the end of August 2021, with each session lasting 4-6 hours, and this has continued to the present day.

Case 2

Since December 8, 2022, the patient has performed daily home H₂ inhalation (flow rate 3 L/minutes, containing 2 L H₂ and 1 L O₂), with a daily duration of 5-10 hours, which has been maintained to the present.

Case 3

Starting from February 2019, while undergoing the aforementioned treatment, the patient began daily H₂ inhalation (flow rate 3 L/minutes, containing 2 L H₂ and 1 L O₂) for 4-6 hours each day at the rehabilitation center. In November 2019, after 9 months of combined H₂ inhalation therapy, temozolomide and bevacizumab were discontinued, and H₂ inhalation was continued at home to the present day. The patient’s entire treatment course to date is shown in Table 1.

Table 1 Summary of case 3’s clinical course, including patient condition, magnetic-resonance-imaging detected tumor status, relevant treatments, and post-treatment outcomes.

Date	Pre-treatment symptoms and MRI	Therapy	After treatment intervention
1998-02	Headache, dizziness. Brain left-sided space-occupying lesion	Tumor subtotal resection, radio/chemotherapy	Pathology: Confirmed as astrocytoma (WHO I-II)
2018-01	Headache recurrence. Left frontal lobe space-occupying lesion	Second tumor subtotal resection radio/chemotherapy	Pathology: Anaplastic oligoastrocytoma (WHO III)
2018-11	Headache deteriorated, recurrence of tumor at the left frontal lobe surgical margin, 31 mm × 27 mm	Oral temozolomide, and bevacizumab	Headache not improving, sudden right-sided limb paralysis, aphasia, and epileptic seizures
2019-02	Symptoms did not improve, the tumor increased to 45 mm × 27 mm, KPS score 40	The above treatment plus hydrogen inhalation at the rehabilitation center	Symptoms improved a 1 week later, seizures gradually stopping, walk restored, and aphasia improved
2019-11	No headache, MRI showed tumor shrinkage	Stop temozolomide and bevacizumab, hydrogen therapy alone	Symptoms continued to improve
2020-09	Further reduction of the tumor	H2 intervention alone	Symptoms continued to improve
2021-05	Further reduction of the tumor	H2 intervention only	Stable
2023-01	The tumor further shrinks, but fluid accumulation in the ventricles	H2 intervention, 3rd ventriculostomy was given	Stable
2024-07	The tumor is almost invisible on MRI	H2 intervention, at home only	Self-care, KPS score above 80
2025-07	Can take care of oneself in daily life	H2 intervention, at home only	KPS 80 points or above

WHO: World Health Organization; H₂: Hydrogen; KPS: Karnofsky Performance Status; MRI: Magnetic resonance imaging.

OUTCOME AND FOLLOW-UP

Case 1

Two months after H₂ inhalation, the patient had no complaints of discomfort. Subsequent re-examinations revealed no signs of tumor recurrence (Figure 6). Currently, she is in good general condition, has resumed normal work, with a KPS score of 100, and OS has reached 52 months.

Figure 6 Cranial magnetic resonance imaging showed no obvious enhancing abnormal lesions in T1-weighted imaging. A: Axial section in July 2022; B: Sagittal section in July 2022; C: Axial section in November 2024; D: Sagittal section in November 2024 (provided by the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China).

Case 2

Annual MRI follow-up was performed until September 2025, with no signs of tumor recurrence observed (Figure 7). Currently, the patient has no chief complaints of discomfort, is in good general condition, has a KPS score of 100, has returned to normal work, and OS has reached 38 months.

Figure 7 Cranial magnetic resonance imaging performed in November 2022 showed patchy low signals on T1-weighted imaging and mixed signals on fluid-attenuated inversion recovery sequence in the surgical area, suggesting possible postoperative changes or tumor recurrence. A: Follow up cranial magnetic resonance imaging (MRI)-axial section in November 2022; B: Follow up cranial MRI-sagittal section in November 2022; C: Follow up cranial MRI-axial section in December 2023 revealing no obvious enhancing lesions; D: Follow up cranial MRI-sagittal section in December 2023 revealing no obvious enhancing lesions; E: Follow up cranial MRI-axial section in September 2025 revealing no obvious enhancing lesions; F: Follow up cranial MRI-sagittal section in September 2025 revealing no obvious enhancing lesions (provided by the West Campus of Huashan Hospital, affiliated to Fudan University, Shanghai, China).

Case 3

After combining with H₂ inhalation, the patient’s headache and insomnia improved 1 week later. Epileptic seizures decreased and ceased completely after 2 weeks, with no recurrence to date. By 3 weeks, the patient could independently eat with chopsticks, speak phrases of more than three characters, and gradually resume independent walking, with the KPS score increasing to 60. MRI re-examination in November 2019 showed that the lesion in the left frontal lobe was smaller. Subsequently, the patient’s overall condition stabilized and continued to improve. Annual MRI follow-ups revealed a gradual reduction in the residual tumor (Figures 8 and 9), while ventricular cerebrospinal fluid accumulation persisted and showed a tendency to increase. In January 2023, the patient underwent third ventriculostomy combined with choroid plexus cauterization and recovered well postoperatively. As of October 2025, follow-up shows the patient has no subjective complaints such as headache or dizziness, is able to take care of daily life independently, and has a KPS score ≥ 80. Since the pathological diagnosis of AOA, OS has reached 93 months; calculated from the start of H₂ inhalation intervention, OS has reached 80 months.

Figure 8 Changes in the maximum diameter of the tumor observed on magnetic resonance imaging re-examination after the diagnosis of anaplastic oligoastrocytoma. MRI: Magnetic resonance imaging; AOA: Anaplastic oligoastrocytoma; H₂: Hydrogen.

Figure 9 A series of brain magnetic resonance imaging scans after hydrogen intervention showed gradual tumor regression until disappearance. A and B: In November 2019, 9 months after combined hydrogen intervention, T1-weighted magnetic resonance imaging (MRI) revealed a 37 mm × 24 mm tumor in the left frontal lobe (orange arrow), accompanied by mild ventricular dilation and fluid accumulation; C and D: In May 2021, 8 months after hydrogen monotherapy, T1-weighted cranial MRI showed reduced tumor size compared with the previous; E and F: In July 2024, 46 months after hydrogen monotherapy, supratentorial ventricular system hydrocephalus was observed, with no obvious tumor signs on T1-weighted images (A, C, E: Axial section; B, D, F: Coronal section (provided by Cancer Hospital Affiliated to Sun Yat-sen University, Guangzhou, China).

DISCUSSION

According to the WHO classification of primary central nervous system tumors, Grades III and IV are malignant, with Grade IV being the most aggressive (primarily MB and GBM, originating from residual embryonic neural ectoderm and glial cells, respectively). Conventional treatments include surgery combined with radiotherapy and chemotherapy, but long-term survival benefits are limited. Adult MB is rare, with a previous report showing a median progression-free survival of 18.4 months in patients unable to undergo complete surgical resection[6]. For GBM, two large-scale clinical trials (573 patients and 562 patients) reported OS of 9.3 months and 7.6 months, respectively[7,8]; bevacizumab showed no OS benefit in a randomized trial[9]. Thalamic GBM is particularly rare[10], with worse prognosis and no significant association between surgical resection extent, adjuvant chemotherapy and OS in most cases.

Cases 1 and 2 were pathologically confirmed as WHO Grade IV tumors (cerebellar and thalamic, respectively). Both underwent surgery: Case 1 had approximately 70% tumor resection followed only by radiotherapy (no adjuvant chemotherapy), while Case 2 received radiotherapy/chemoradiotherapy. Both received long-term home H₂ inhalation thereafter (no other treatments to date). Case 1 achieved 52 months’ OS with residual tumor disappearance; Case 2 had 38 months’ OS without recurrence. Both had initial KPS ≤ 50 and now have KPS = 100 with normal life and work resumption.

AOA (WHO Grade III) is a glioma composed of oligodendrocyte-like malignant cells, with conventional treatment relying on surgery, radiotherapy and chemotherapy, but drug resistance and recurrence remain major challenges[11]. Most patients have OS < 10 years, and those without 1p/19q co-deletion have worse prognosis[12]. Case 3 was initially diagnosed with benign astrocytoma (WHO Grade I-II), treated with surgery, radiotherapy and chemotherapy, and achieved nearly 20 years of asymptomatic survival before recurrence. Reoperation and pathology confirmed progression to 1p/19q non-co-deleted AOA (WHO Grade III). Despite subsequent radiotherapy and chemotherapy, the disease deteriorated (KPS < 40) with frequent epileptic seizures. After H₂ inhalation, symptoms improved rapidly (seizure cessation, and paralysis recovery), MRI showed gradual residual tumor regression, and eventually tumor disappearance with long-term home H₂ inhalation. The patient now lives independently with KPS > 80.

Animal studies have shown that H₂ inhalation inhibits GBM growth and extends mouse survival, down-regulating stem cell (CD133, Nestin), proliferation (Ki67) and angiogenesis (CD34) markers, up-regulating differentiation marker GFAP, and inhibiting glioma cell migration, invasion and colony formation[13]. Akagi and Baba[14] found that H₂ restores exhausted CD8⁺ T cells (especially PD-1 + Tim³⁺ terminally exhausted subsets). Our previous study[15] in 20 non-small cell lung cancer (NSCLC) patients showed that H₂ reversed exhausted CD8⁺ T cells, enhanced natural killer, CD4⁺, and CD8⁺ T-cell activity, and inhibited T regulatory cell activity, improving overall immune function.

Our clinical observations[16] have shown H₂ efficacy in advanced cancers. A patient with recurrent metastatic gallbladder cancer (only parenteral nutrition + H₂ inhalation) had tumor regression, normalized tumor markers, and 18 months’ survival. Initial tumor enlargement (pseudoprogression, similar to PD-1 antibody therapy[17]) with improved general condition[18] suggested immunomodulation. A patient with NSCLC brain metastasis had progressive brain lesions after conventional treatment, which shrank and disappeared after 1 year of H₂ intervention[19].

The three primary malignant brain tumor patients in this report achieved remarkable outcomes, far exceeding reported OS. Case 3 showed marked improvement after H₂ inhalation, and; Cases 1 and 3 had residual tumor disappearance with H₂ monotherapy. While spontaneous remission (e.g., recurrent GBM remission for more than > 4 months with dexamethasone and antiepileptics[20]) cannot be excluded, H₂ likely contributed. Perioperative H₂ has been reported to reduce glioma postoperative cerebral edema[21], but no studies have addressed its effect on primary malignant brain tumor patient survival.

The three patients had heterogeneous initial treatments but all showed significant improvements after H₂ inhalation, manifesting as prolonged survival, and improved tumor response and quality of life. This suggests that H₂ inhalation may has have potential value for glioma patients, either as a conventional treatment adjuvant or for rehabilitation. Larger, well-designed clinical trials to verify its efficacy and mechanism are urgently needed, with important scientific and clinical significance.

Patient perspective

The patients described the initial period following diagnosis as physically and emotionally challenging, marked by severe neurological symptoms such as headache, dizziness, motor impairment, and, in one case, seizures and paralysis, which significantly limited independence and quality of life. Although standard treatments, including surgery, radiotherapy, and chemotherapy, were necessary, they were often experienced as burdensome and did not fully restore functional capacity. The introduction of long-term home H₂ inhalation was perceived as a simple, non-invasive adjunct that could be conveniently integrated into daily routines, allowing patients to take an active role in their rehabilitation.

Over time, the patients reported gradual but meaningful improvements in their symptoms and overall condition. These included relief of headaches, reduction and cessation of seizures, recovery of mobility and speech, and increasing ability to perform daily activities independently. Some patients were able to return to normal work and social life, reflecting a substantial improvement in quality of life and functional status. The treatment was well tolerated, and patients expressed appreciation for its accessibility and ease of use. At the same time, they recognized that further clinical research is needed to better establish its efficacy and role in the management of malignant brain tumors.

CONCLUSION

We report three cases of WHO Grade III-IV primary brain tumors that achieved unexpectedly prolonged survival following standard therapy combined with long-term home-based H₂ inhalation. All patients attained durable clinical stability, radiological remission or absence of tumor recurrence, and significant functional recovery (KPS ≥ 80-100). Their survival outcomes (38-93 months) substantially exceed the typical prognoses for these malignant brain tumors. The innovative feature of this intervention lies in the sustained, high-dose home administration of H₂-O₂ therapy as a non-invasive adjunct to rehabilitation. These clinical observations, consistent with emerging evidence of H₂’s antioxidative properties and potential antitumor effects, highlight a novel, patient-managed intervention that warrants systematic clinical investigation to validate its efficacy and application value.

ACKNOWLEDGEMENTS

We thank the following experts for their assistance in collecting patients’ medical histories, imaging data, and pathological materials, as well as their participation in the evaluation: Jianguo Shi from Oncology Institute, Tangdu Hospital, Air-force Medical University, Xi’an, Shan’xi Province, China; Yinfeng Zhu from Pathology Department, Huashan Hospital (Baoshan Campus), Fudan University, Shanghai, China; Tong Xiang from Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Youyong Lu from Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China; Qiao Li from Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States; Zhonghai Li from Radiology Department, Guangzhou Fuda Cancer Hospital, Guangzhou, China; Lanyin Ma from International Center of Oncology, Royal Lee Cancer Hospital, Guangzhou, China. We would also like to express our gratitude to the patients who participated in the survey and their families for unreservedly providing information about their diseases and treatment-rehabilitation processes.